Sample records for oral epithelium regenerate

  1. Epithelial–Mesenchymal Interactions as a Working Concept for Oral Mucosa Regeneration

    PubMed Central

    Liu, Jiarong

    2011-01-01

    Oral mucosa consists of two tissue layers, the superficial epithelium and the underlying lamina propria. Together, oral mucosa functions as a barrier against exogenous substances and pathogens. In development, interactions of stem/progenitor cells of the epithelium and mesenchyme are crucial to the morphogenesis of oral mucosa. Previous work in oral mucosa regeneration has yielded important clues for several meritorious proof-of-concept approaches. Tissue engineering offers a broad array of novel tools for oral mucosa regeneration with reduced donor site trauma and accelerated clinical translation. However, the developmental concept of epithelial–mesenchymal interactions (EMIs) is rarely considered in oral mucosa regeneration. EMIs in postnatal oral mucosa regeneration likely will not be a simple recapitulation of prenatal oral mucosa development. Biomaterial scaffolds play an indispensible role for oral mucosa regeneration and should provide a conducive environment for pivotal EMIs. Autocrine and paracrine factors, either exogenously delivered or innately produced, have rarely been and should be harnessed to promote oral mucosa regeneration. This review focuses on a working concept of epithelial and mesenchymal interactions in oral mucosa regeneration. PMID:21062224

  2. Hair cell regeneration in the avian auditory epithelium.

    PubMed

    Stone, Jennifer S; Cotanche, Douglas A

    2007-01-01

    Regeneration of sensory hair cells in the mature avian inner ear was first described just over 20 years ago. Since then, it has been shown that many other non-mammalian species either continually produce new hair cells or regenerate them in response to trauma. However, mammals exhibit limited hair cell regeneration, particularly in the auditory epithelium. In birds and other non-mammals, regenerated hair cells arise from adjacent non-sensory (supporting) cells. Hair cell regeneration was initially described as a proliferative response whereby supporting cells re-enter the mitotic cycle, forming daughter cells that differentiate into either hair cells or supporting cells and thereby restore cytoarchitecture and function in the sensory epithelium. However, further analyses of the avian auditory epithelium (and amphibian vestibular epithelium) revealed a second regenerative mechanism, direct transdifferentiation, during which supporting cells change their gene expression and convert into hair cells without dividing. In the chicken auditory epithelium, these two distinct mechanisms show unique spatial and temporal patterns, suggesting they are differentially regulated. Current efforts are aimed at identifying signals that maintain supporting cells in a quiescent state or direct them to undergo direct transdifferentiation or cell division. Here, we review current knowledge about supporting cell properties and discuss candidate signaling molecules for regulating supporting cell behavior, in quiescence and after damage. While significant advances have been made in understanding regeneration in non-mammals over the last 20 years, we have yet to determine why the mammalian auditory epithelium lacks the ability to regenerate hair cells spontaneously and whether it is even capable of significant regeneration under additional circumstances. The continued study of mechanisms controlling regeneration in the avian auditory epithelium may lead to strategies for inducing

  3. Effect of carbonated drinks on wound healing of oral epithelium

    PubMed Central

    Fahim, Ayesha; Ilyas, Muhammad Sharjeel; Jafari, Fahim Haider; Farzana, Fauzia

    2015-01-01

    Background Carbonated drinks are the second most consumed non-alcoholic beverages in the world after tea. The effects of these drinks on hard tissues and vital organs of the body have been proved beyond doubt. This study, however, explains the effect of these drinks on wound healing of oral epithelium. Methods Thirty-six male Wistar rats were considered for the study. A circular wound of 3.0 mm was created on the buccal mucosa of all animals and they were divided into two groups. Animals in group 1 were fed with chow pellet and water, while those in group 2 were fed with a commercially available carbonated drink instead of water. Six animals from each group were euthanized at 0, 7, and 21 days. Wound site was histologically assessed for differences in thickness and characteristics of the regenerating epithelium between two groups. Results There was a marked difference in the healing pattern between the two groups. Animals in group 1 showed a normal healing pattern at the end of day 21. In the group 2, the regenerated epithelium showed hyperplasia and hyperkeratosis along with acanthosis at the end of the experiment with a subsequent delayed inflammatory reaction at day 21. Conclusion Consumption of carbonated drinks can disrupt oral wound healing. The contents in carbonated drinks have a proinflammatory action on the soft tissue. Results suggest that epithelial changes seen in experimental group 2 could be a result of constant irritation by the acidic and fizzy nature of carbonated drinks. PMID:26937370

  4. Rhinovirus Delays Cell Repolarization in a Model of Injured/Regenerating Human Airway Epithelium

    PubMed Central

    Faris, Andrea N.; Ganesan, Shyamala; Chattoraj, Asamanja; Chattoraj, Sangbrita S.; Comstock, Adam T.; Unger, Benjamin L.; Hershenson, Marc B.

    2016-01-01

    Rhinovirus (RV), which causes exacerbation in patients with chronic airway diseases, readily infects injured airway epithelium and has been reported to delay wound closure. In this study, we examined the effects of RV on cell repolarization and differentiation in a model of injured/regenerating airway epithelium (polarized, undifferentiated cells). RV causes only a transient barrier disruption in a model of normal (mucociliary-differentiated) airway epithelium. However, in the injury/regeneration model, RV prolongs barrier dysfunction and alters the differentiation of cells. The prolonged barrier dysfunction caused by RV was not a result of excessive cell death but was instead associated with epithelial-to-mesenchymal transition (EMT)-like features, such as reduced expression of the apicolateral junction and polarity complex proteins, E-cadherin, occludin, ZO-1, claudins 1 and 4, and Crumbs3 and increased expression of vimentin, a mesenchymal cell marker. The expression of Snail, a transcriptional repressor of tight and adherence junctions, was also up-regulated in RV-infected injured/regenerating airway epithelium, and inhibition of Snail reversed RV-induced EMT-like features. In addition, compared with sham-infected cells, the RV-infected injured/regenerating airway epithelium showed more goblet cells and fewer ciliated cells. Inhibition of epithelial growth factor receptor promoted repolarization of cells by inhibiting Snail and enhancing expression of E-cadherin, occludin, and Crumbs3 proteins, reduced the number of goblet cells, and increased the number of ciliated cells. Together, these results suggest that RV not only disrupts barrier function, but also interferes with normal renewal of injured/regenerating airway epithelium by inducing EMT-like features and subsequent goblet cell hyperplasia. PMID:27119973

  5. Regeneration of tracheal epithelium using mouse induced pluripotent stem cells.

    PubMed

    Ikeda, Masakazu; Imaizumi, Mitsuyoshi; Yoshie, Susumu; Otsuki, Koshi; Miyake, Masao; Hazama, Akihiro; Wada, Ikuo; Omori, Koichi

    2016-01-01

    Conclusion The findings demonstrated the potential use of induced pluripotent stem cells for regeneration of tracheal epithelium. Objective Autologous tissue implantation techniques using skin or cartilage are often applied in cases of tracheal defects with laryngeal inflammatory lesions and malignant tumor invasion. However, these techniques are invasive with an unstable clinical outcome. The purpose of this study was to investigate regeneration in a tracheal defect site of nude rats after implantation of ciliated epithelium that was differentiated from induced pluripotent stem cells. Method Embryoid bodies were formed from mouse induced pluripotent stem cells. They were cultured with growth factors for 5 days, and then cultured at the air-liquid interface. The degree of differentiation achieved prior to implantation was determined by histological findings and the results of real-time polymerase chain reaction. Embryoid bodies including ciliated epithelium were embedded into collagen gel that served as an artificial scaffold, and then implanted into nude rats, creating an 'air-liquid interface model'. Histological evaluation was performed 7 days after implantation. Results The ciliated epithelial structure survived on the lumen side of regenerated tissue. It was demonstrated histologically that the structure was composed of ciliated epithelial cells.

  6. Regeneration of junctional epithelium and its innervation in adult rats: a study using immunocytochemistry for p75 nerve growth factor receptor and calcitonin gene-related peptide.

    PubMed

    Redd, P E; Byers, M R

    1994-05-01

    Junctional epithelium (JE) is a rapidly proliferating tissue that connects the gum to the tooth, that provides a free surface for bidirectional movement of substances between the body and the oral cavity, and that participates in defense against bacterial infection. It is innervated by numerous sensory nerve fibers that are immunoreactive (IR) for neuropeptides such as calcitonin gene-related peptide (CGRP), and for low affinity nerve growth factor receptor (p75-NGFR). Basal epithelial cells of the JE and of adjacent sulcular epithelium also have intense p75-NGFR-IR. In the present study we removed a wedge of the free gingiva and JE from the anterior side of the maxillary first molar of adult rats, and then studied the return of nerve fibers during tissue regeneration from 1-63 days after gingivectomy. The nerve fibers entered the adjacent healing sulcular epithelium before innervating the new JE, in both cases prior to return of epithelial cell p75-NGFR-IR. The regenerating nerve fibers completely bypassed the zone of epithelial down-growth (long junctional epithelium, LJE) that was briefly present along the tooth from 1-3 weeks after injury. The LJE did not have p75-NGFR-IR and was gradually replaced by a modified thicker regenerated junctional epithelium (RJE). The RJE was attached along the injured root surface, had numerous nerves in basal layers, and it had begun to regain p75-NGFR-IR staining of basal epithelial cells by 22 d. Regenerating nerve fibers at 6-10 d had unusually weak CGRP-IR and greatly increased p75-NGFR-IR. Both nerve stains had returned to normal by 3-6 weeks. The intense p75-NGFR-IR of regenerating nerves was found on both axonal and Schwann cell membranes using electron microscopic immunocytochemistry. In both the normal and regenerating JE, nerve fibers were rare in the attachment layers next to the anterior side of the maxillary first molar, compared to well-innervated basal layers. The complete avoidance of LJE by regenerating nerve

  7. Effect of Atmospheric-Pressure Cold Plasma on Pathogenic Oral Biofilms and In Vitro Reconstituted Oral Epithelium.

    PubMed

    Delben, Juliana Aparecida; Zago, Chaiene Evelin; Tyhovych, Natalia; Duarte, Simone; Vergani, Carlos Eduardo

    2016-01-01

    Considering the ability of atmospheric-pressure cold plasma (ACP) to disrupt the biofilm matrix and rupture cell structure, it can be an efficient tool against virulent oral biofilms. However, it is fundamental that ACP does not cause damage to oral tissue. So, this study evaluated (1) the antimicrobial effect of ACP on single- and dual-species biofilms of Candida albicans and Staphylococcus aureus as well as (2) the biological safety of ACP on in vitro reconstituted oral epithelium. Standardized cell suspensions of each microorganism were prepared for biofilm culture on acrylic resin discs at 37°C for 48 hours. The biofilms were submitted to ACP treatment at 10 mm of plasma tip-to-sample distance during 60 seconds. Positive controls were penicillin G and fluconazole for S. aureus and C. albicans, respectively. The biofilms were analyzed through counting of viable colonies, confocal laser scanning microscopy, scanning electron microscopy and fluorescence microscopy for detection of reactive oxygen species. The in vitro reconstituted oral epithelium was submitted to similar ACP treatment and analyzed through histology, cytotoxocity test (LDH release), viability test (MTT assay) and imunnohistochemistry (Ki67 expression). All plasma-treated biofilms presented significant log10 CFU/mL reduction, alteration in microorganism/biofilm morphology, and reduced viability in comparison to negative and positive controls. In addition, fluorescence microscopy revealed presence of reactive oxygen species in all plasma-treated biofilms. Low cytotoxicity and high viability were observed in oral epithelium of negative control and plasma group. Histology showed neither sign of necrosis nor significant alteration in plasma-treated epithelium. Ki67-positive cells revealed maintenance of cell proliferation in plasma-treated epithelium. Atmospheric-pressure cold plasma is a promissing approach to eliminate single- and dual-species biofilms of C. albicans and S. aureus without having

  8. Reactivation of larval keratin gene (krt62.L) in blastema epithelium during Xenopus froglet limb regeneration.

    PubMed

    Satoh, Akira; Mitogawa, Kazumasa; Saito, Nanami; Suzuki, Miyuki; Suzuki, Ken-Ichi T; Ochi, Haruki; Makanae, Aki

    2017-12-15

    Limb regeneration is considered a form of limb redevelopment because of the molecular and morphological similarities. Forming a regeneration blastema is, in essence, creating a developing limb bud in an adult body. This reactivation of a developmental process in a mature body is worth studying. Xenopus laevis has a biphasic life cycle that involves distinct larval and adult stages. These distinct developmental stages are useful for investigating the reactivation of developmental processes in post-metamorphic frogs (froglets). In this study, we focused on the re-expression of a larval gene (krt62.L) during Xenopus froglet limb regeneration. Recently renamed krt62.L, this gene was known as the larval keratin (xlk) gene, which is specific to larval-tadpole stages. During limb regeneration in a froglet, krt62.L was re-expressed in a basal layer of blastema epithelium, where adult-specific keratin (Krt12.6.S) expression was also observable. Nerves produce important regulatory factors for amphibian limb regeneration, and also play a role in blastema formation and maintenance. The effect of nerve function on krt62.L expression could be seen in the maintenance of krt62.L expression, but not in its induction. When an epidermis-stripped limb bud was grafted in a froglet blastema, the grafted limb bud could reach the digit-forming stage. This suggests that krt62.L-positive froglet blastema epithelium is able to support the limb development process. These findings imply that the developmental process is locally reactivated in an postmetamorphic body during limb regeneration. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Gene expression based evidence of innate immune response activation in the epithelium with oral lichen planus

    PubMed Central

    Adami, Guy R.; Yeung, Alexander C.F.; Stucki, Grant; Kolokythas, Antonia; Sroussi, Herve Y.; Cabay, Robert J.; Kuzin, Igor; Schwartz, Joel L.

    2014-01-01

    Objective Oral lichen planus (OLP) is a disease of the oral mucosa of unknown cause producing lesions with an intense band-like inflammatory infiltrate of T cells to the subepithelium and keratinocyte cell death. We performed gene expression analysis of the oral epithelium of lesions in subjects with OLP and its sister disease, oral lichenoid reaction (OLR), in order to better understand the role of the keratinocytes in these diseases. Design Fourteen patients with OLP or OLR were included in the study, along with a control group of 23 subjects with a variety of oral diseases and a normal group of 17 subjects with no clinically visible mucosal abnormalities. Various proteins have been associated with OLP, based on detection of secreted proteins or changes in RNA levels in tissue samples consisting of epithelium, stroma, and immune cells. The mRNA level of twelve of these genes expressed in the epithelium was tested in the three groups. Results Four genes showed increased expression in the epithelium of OLP patients: CD14, CXCL1, IL8, and TLR1, and at least two of these proteins, TLR1 and CXCL1, were expressed at substantial levels in oral keratinocytes. Conclusions Because of the large accumulation of T cells in lesions of OLP it has long been thought to be an adaptive immunity malfunction. We provide evidence that there is increased expression of innate immune genes in the epithelium with this illness, suggesting a role for this process in the disease and a possible target for treatment. PMID:24581860

  10. Quantitative proteomic analysis of microdissected oral epithelium for cancer biomarker discovery.

    PubMed

    Xiao, Hua; Langerman, Alexander; Zhang, Yan; Khalid, Omar; Hu, Shen; Cao, Cheng-Xi; Lingen, Mark W; Wong, David T W

    2015-11-01

    Specific biomarkers are urgently needed for the detection and progression of oral cancer. The objective of this study was to discover cancer biomarkers from oral epithelium through utilizing high throughput quantitative proteomics approaches. Morphologically malignant, epithelial dysplasia, and adjacent normal epithelial tissues were laser capture microdissected (LCM) from 19 patients and used for proteomics analysis. Total proteins from each group were extracted, digested and then labelled with corresponding isobaric tags for relative and absolute quantitation (iTRAQ). Labelled peptides from each sample were combined and analyzed by liquid chromatography-mass spectrometry (LC-MS/MS) for protein identification and quantification. In total, 500 proteins were identified and 425 of them were quantified. When compared with adjacent normal oral epithelium, 17 and 15 proteins were consistently up-regulated or down-regulated in malignant and epithelial dysplasia, respectively. Half of these candidate biomarkers were discovered for oral cancer for the first time. Cornulin was initially confirmed in tissue protein extracts and was further validated in tissue microarray. Its presence in the saliva of oral cancer patients was also explored. Myoglobin and S100A8 were pre-validated by tissue microarray. These data demonstrated that the proteomic biomarkers discovered through this strategy are potential targets for oral cancer detection and salivary diagnostics. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Increased Abundance of M Cells in the Gut Epithelium Dramatically Enhances Oral Prion Disease Susceptibility.

    PubMed

    Donaldson, David S; Sehgal, Anuj; Rios, Daniel; Williams, Ifor R; Mabbott, Neil A

    2016-12-01

    Many natural prion diseases of humans and animals are considered to be acquired through oral consumption of contaminated food or pasture. Determining the route by which prions establish host infection will identify the important factors that influence oral prion disease susceptibility and to which intervention strategies can be developed. After exposure, the early accumulation and replication of prions within small intestinal Peyer's patches is essential for the efficient spread of disease to the brain. To replicate within Peyer's patches, the prions must first cross the gut epithelium. M cells are specialised epithelial cells within the epithelia covering Peyer's patches that transcytose particulate antigens and microorganisms. M cell-development is dependent upon RANKL-RANK-signalling, and mice in which RANK is deleted only in the gut epithelium completely lack M cells. In the specific absence of M cells in these mice, the accumulation of prions within Peyer's patches and the spread of disease to the brain was blocked, demonstrating a critical role for M cells in the initial transfer of prions across the gut epithelium in order to establish host infection. Since pathogens, inflammatory stimuli and aging can modify M cell-density in the gut, these factors may also influence oral prion disease susceptibility. Mice were therefore treated with RANKL to enhance M cell density in the gut. We show that prion uptake from the gut lumen was enhanced in RANKL-treated mice, resulting in shortened survival times and increased disease susceptibility, equivalent to a 10-fold higher infectious titre of prions. Together these data demonstrate that M cells are the critical gatekeepers of oral prion infection, whose density in the gut epithelium directly limits or enhances disease susceptibility. Our data suggest that factors which alter M cell-density in the gut epithelium may be important risk factors which influence host susceptibility to orally acquired prion diseases.

  12. TWIST and p-Akt immunoexpression in normal oral epithelium oral dysplasia and in oral squamous cell carcinoma

    PubMed Central

    Yamamoto, Fernanda-Paula; Corrêa Pontes, Flávia-Sirotheau; Cury, Sérgio-Elias; Fonseca, Felipe-Paiva; Rebelo-Pontes, Hélder; Pinto-Júnior, Décio-dos Santos

    2012-01-01

    Objectives: The aim of this study was to evaluate the immunoexpression of TWIST and p-Akt proteins in oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC), correlating their expressions with the histological features of the lesions. Study design: Immunohistochemical studies were carried out on 10 normal oral epithelium, 30 OL and 20 OSCC formalin-fixed, paraffin-embedded tissue samples. Immunoperoxidase reactions for TWIST and p-Akt proteins were applied on the specimens and the positivity of the reactions was calculated for 1000 epithelial cells. Results: Kruskal-Wallis and Dunn’s post tests revealed a significant difference in TWIST and p-Akt immunoexpression among normal oral mucosa, OL and OSCC. In addition, a significant positive correlation was found between TWIST and p-Akt expressions according to the Pearson’s correlation test. Conclusions: The results obtained in the current study suggest that TWIST and p-Akt may participate of the multi-step process of oral carcinogenesis since its early stages. Key words: Oral cancer, oral leukoplakia, dysplasia, immunohistochemistry. PMID:21743395

  13. Regeneration of Corneal Epithelium With Dental Pulp Stem Cells Using a Contact Lens Delivery System.

    PubMed

    Kushnerev, Evgeny; Shawcross, Susan G; Sothirachagan, Shankari; Carley, Fiona; Brahma, Arun; Yates, Julian M; Hillarby, M Chantal

    2016-10-01

    The corneal epithelium is sloughed off surface of the eye by the action of blinking and is continually replaced by division and maturation of the limbal stem cells (LSCs). In the case of injury or disease, LSCs can be lost or damaged to a point at which the corneal epithelial layer is no longer maintained. leading to LSC deficiencies (LSCDs). When this occurs, the opaque conjunctiva overgrows the anterior surface of the eye, leading to vision impairment or loss. Dental pulp stem cells (DPSCs) are promising candidates as autologous LSC substitutes. In this study, contact lenses (CLs) are used as a novel medical device to deliver DPSCs onto corneal surface to enhance corneal epithelium regeneration. Dental pulp stem cells labeled with green fluorescent Qtracker 525 were seeded onto the pretreated CLs, allowed to adhere, then delivered to debrided human corneas. Expression of KRT3, 12, 13, and 19 was investigated by immunostaining, then standard and confocal microscopy. Dental pulp stem cells were successfully isolated, labeled, and delivered to the corneal surface using CLs. Following removal of CLs, confocal microscopy showed that the DPSCs had migrated onto the cornea. Coexpression of KRT12 and green fluorescent Qtracker 525 confirmed that the DPSCs had transdifferentiated into corneal epithelial progenitors. Delimitation of KRT 19 and green fluorescence provides evidence that Qtracker 525-labeled DPSCs establish a barrier to the invasion of the cornea by conjunctiva. In this study we show that DPSCs, delivered using CLs, can be used to enhance repair and regeneration of the human corneal epithelium.

  14. Epithelial architectural destruction is necessary for bone marrow derived cell contribution to regenerating prostate epithelium.

    PubMed

    Palapattu, Ganesh S; Meeker, Alan; Harris, Timothy; Collector, Michael I; Sharkis, Saul J; DeMarzo, Angelo M; Warlick, Christopher; Drake, Charles G; Nelson, William G

    2006-08-01

    Using various nonphysiological tissue injury/repair models numerous studies have demonstrated the capacity of bone marrow derived cells to contribute to the repopulation of epithelial tissues following damage. To investigate whether this phenomenon might also occur during periods of physiological tissue degeneration/regeneration we compared the ability of bone marrow derived cells to rejuvenate the prostate gland in mice that were castrated and then later treated with dihydrotestosterone vs mice with prostate epithelium that had been damaged by lytic virus infection. Using allogenic bone marrow grafts from female donor transgenic mice expressing green fluorescent protein transplanted into lethally irradiated males we were able to assess the contributions of bone marrow derived cells to recovery of the prostatic epithelium in 2 distinct systems, including 1) surgical castration followed 1 week later by dihydrotestosterone replacement and 2) intraprostatic viral injection. Eight to 10-week-old male C57/Bl6 mice were distributed among bone marrow donor-->recipient/prostate injury groups, including 5 with C57/Bl6-->C57/Bl6/no injury, 3 with green fluorescent protein-->C57/Bl6/no injury, 3 with green fluorescent protein-->C57/Bl6/vehicle injection, 4 with green fluorescent protein-->C57/Bl6/virus injection and 3 each with green fluorescent protein-->C57/Bl6/castration without and with dihydrotestosterone, respectively. Prostate tissues were harvested 3 weeks after dihydrotestosterone replacement or 14 days following intraprostatic viral injection. Prostate tissue immunofluorescence was performed with antibodies against the epithelial marker cytokeratin 5/8, the hematopoietic marker CD45 and green fluorescent protein. Mice that sustained prostate injury from vaccinia virus infection with concomitant severe inflammation and glandular disruption showed evidence of bone marrow derived cell reconstitution of prostate epithelium, that is approximately 4% of all green

  15. Increased Abundance of M Cells in the Gut Epithelium Dramatically Enhances Oral Prion Disease Susceptibility

    PubMed Central

    Sehgal, Anuj; Rios, Daniel

    2016-01-01

    Many natural prion diseases of humans and animals are considered to be acquired through oral consumption of contaminated food or pasture. Determining the route by which prions establish host infection will identify the important factors that influence oral prion disease susceptibility and to which intervention strategies can be developed. After exposure, the early accumulation and replication of prions within small intestinal Peyer’s patches is essential for the efficient spread of disease to the brain. To replicate within Peyer’s patches, the prions must first cross the gut epithelium. M cells are specialised epithelial cells within the epithelia covering Peyer’s patches that transcytose particulate antigens and microorganisms. M cell-development is dependent upon RANKL-RANK-signalling, and mice in which RANK is deleted only in the gut epithelium completely lack M cells. In the specific absence of M cells in these mice, the accumulation of prions within Peyer’s patches and the spread of disease to the brain was blocked, demonstrating a critical role for M cells in the initial transfer of prions across the gut epithelium in order to establish host infection. Since pathogens, inflammatory stimuli and aging can modify M cell-density in the gut, these factors may also influence oral prion disease susceptibility. Mice were therefore treated with RANKL to enhance M cell density in the gut. We show that prion uptake from the gut lumen was enhanced in RANKL-treated mice, resulting in shortened survival times and increased disease susceptibility, equivalent to a 10-fold higher infectious titre of prions. Together these data demonstrate that M cells are the critical gatekeepers of oral prion infection, whose density in the gut epithelium directly limits or enhances disease susceptibility. Our data suggest that factors which alter M cell-density in the gut epithelium may be important risk factors which influence host susceptibility to orally acquired prion diseases

  16. Cigarette Smoke Delays Regeneration of the Olfactory Epithelium in Mice.

    PubMed

    Ueha, Rumi; Ueha, Satoshi; Sakamoto, Takashi; Kanaya, Kaori; Suzukawa, Keigo; Nishijima, Hironobu; Kikuta, Shu; Kondo, Kenji; Matsushima, Kouji; Yamasoba, Tatsuya

    2016-08-01

    The olfactory system is a unique part of the mammalian nervous system due to its capacity for neurogenesis and the replacement of degenerating receptor neurons. Cigarette smoking is a major cause of olfactory dysfunction. However, the mechanisms by which cigarette smoke impairs the regenerative olfactory receptor neurons (ORNs) remain unclear. Here, we investigated the influence of cigarette smoke on ORN regeneration following methimazole-induced ORN injury. Administration of methimazole caused detachment of the olfactory epithelium from the basement membrane and induced olfactory dysfunction, thus enabling us to analyze the process of ORN regeneration. We found that intranasal administration of cigarette smoke solution (CSS) suppressed the recovery of ORNs and olfaction following ORN injury. Defective ORN recovery in CSS-treated mice was not associated with any change in the number of SOX2(+) ORN progenitor cells in the basal layer of the OE, but was associated with impaired recovery of GAP43(+) immature ORNs. In the nasal mucosa, mRNA expression levels of neurotrophic factors such as brain-derived neurotrophic factor, neurotrophin-3, neurotrophin-5, glial cell-derived neurotrophic factor, and insulin-like growth factor-1 (IGF-1) were increased following OE injury, whereas CSS administration decreased the ORN injury-induced IGF-1 expression. Administration of recombinant human IGF-1 prevented the CSS-induced suppression of ORN recovery following injury. These results suggest that CSS impairs regeneration of ORNs by suppressing the development of immature ORNs from ORN progenitors, at least partly by reducing IGF-1 in the nasal mucosa.

  17. Generation of tooth-periodontium complex structures using high-odontogenic potential dental epithelium derived from mouse embryonic stem cells.

    PubMed

    Zhang, Yancong; Li, Yongliang; Shi, Ruirui; Zhang, Siqi; Liu, Hao; Zheng, Yunfei; Li, Yan; Cai, Jinglei; Pei, Duanqing; Wei, Shicheng

    2017-06-08

    A number of studies have shown that tooth-like structures can be regenerated using induced pluripotent stem cells and mouse embryonic stem (mES) cells. However, few studies have reported the regeneration of tooth-periodontium complex structures, which are more suitable for clinical tooth transplantation. We established an optimized approach to induce high-odontogenic potential dental epithelium derived from mES cells by temporally controlling bone morphogenic protein 4 (BMP4) function and regenerated tooth-periodontium complex structures in vivo. First, immunofluorescence and quantitative reverse transcription-polymerase chain reaction were used to identify the watershed of skin and the oral ectoderm. LDN193189 was then used to inhibit the BMP4 receptor around the watershed, followed by the addition of exogenous BMP4 to promote BMP4 function. The generated dental epithelium was confirmed by western blot analysis and immunofluorescence. The generated epithelium was ultimately combined with embryonic day 14.5 mouse mesenchyme and transplanted into the renal capsules of nude mice. After 4 weeks, the tooth-periodontium complex structure was examined by micro-computed tomography (CT) and hematoxylin and eosin (H&E) staining. Our study found that the turning point of oral ectoderm differentiation occurred around day 3 after the embryoid body was transferred to a common culture plate. Ameloblastin-positive dental epithelial cells were detected following the temporal regulation of BMP4. Tooth-periodontium complex structures, which included teeth, a periodontal membrane, and alveolar bone, were formed when this epithelium was combined with mouse dental mesenchyme and transplanted into the renal capsules of nude mice. Micro-CT and H&E staining revealed that the generated tooth-periodontium complex structures shared a similar histological structure with normal mouse teeth. An optimized induction method was established to promote the differentiation of mES cells into dental

  18. The junctional epithelium originates from the odontogenic epithelium of an erupted tooth.

    PubMed

    Yajima-Himuro, Sara; Oshima, Masamitsu; Yamamoto, Gou; Ogawa, Miho; Furuya, Madoka; Tanaka, Junichi; Nishii, Kousuke; Mishima, Kenji; Tachikawa, Tetsuhiko; Tsuji, Takashi; Yamamoto, Matsuo

    2014-05-02

    The junctional epithelium (JE) is an epithelial component that is directly attached to the tooth surface and has a protective function against periodontal diseases. In this study, we determined the origin of the JE using a bioengineered tooth technique. We transplanted the bioengineered tooth germ into the alveolar bone with an epithelial component that expressed green fluorescence protein. The reduced enamel epithelium from the bioengineered tooth fused with the oral epithelium, and the JE was apparently formed around the bioengineered tooth 50 days after transplantation. Importantly, the JE exhibited green fluorescence for at least 140 days after transplantation, suggesting that the JE was not replaced by oral epithelium. Therefore, our results demonstrated that the origin of the JE was the odontogenic epithelium, and odontogenic epithelium-derived JE was maintained for a relatively long period.

  19. Bone morphogenetic protein 4 antagonizes hair cell regeneration in the avian auditory epithelium.

    PubMed

    Lewis, Rebecca M; Keller, Jesse J; Wan, Liangcai; Stone, Jennifer S

    2018-07-01

    Permanent hearing loss is often a result of damage to cochlear hair cells, which mammals are unable to regenerate. Non-mammalian vertebrates such as birds replace damaged hair cells and restore hearing function, but mechanisms controlling regeneration are not understood. The secreted protein bone morphogenetic protein 4 (BMP4) regulates inner ear morphogenesis and hair cell development. To investigate mechanisms controlling hair cell regeneration in birds, we examined expression and function of BMP4 in the auditory epithelia (basilar papillae) of chickens of either sex after hair cell destruction by ototoxic antibiotics. In mature basilar papillae, BMP4 mRNA is highly expressed in hair cells, but not in hair cell progenitors (supporting cells). Supporting cells transcribe genes encoding receptors for BMP4 (BMPR1A, BMPR1B, and BMPR2) and effectors of BMP4 signaling (ID transcription factors). Following hair cell destruction, BMP4 transcripts are lost from the sensory epithelium. Using organotypic cultures, we demonstrate that treatments with BMP4 during hair cell destruction prevent supporting cells from upregulating expression of the pro-hair cell transcription factor ATOH1, entering the cell cycle, and fully transdifferentiating into hair cells, but they do not induce cell death. By contrast, noggin, a BMP4 inhibitor, increases numbers of regenerated hair cells. These findings demonstrate that BMP4 antagonizes hair cell regeneration in the chicken basilar papilla, at least in part by preventing accumulation of ATOH1 in hair cell precursors. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Loss of Aβ-nerve endings associated with the Merkel cell-neurite complex in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis.

    PubMed

    Carrión, Daniela Calderón; Korkmaz, Yüksel; Cho, Britta; Kopp, Marion; Bloch, Wilhelm; Addicks, Klaus; Niedermeier, Wilhelm

    2016-03-30

    The Merkel cell-neurite complex initiates the perception of touch and mediates Aβ slowly adapting type I responses. Lichen planus is a chronic inflammatory autoimmune disease with T-cell-mediated inflammation, whereas hyperkeratosis is characterized with or without epithelial dysplasia in the oral mucosa. To determine the effects of lichen planus and hyperkeratosis on the Merkel cell-neurite complex, healthy oral mucosal epithelium and lesional oral mucosal epithelium of lichen planus and hyperkeratosis patients were stained by immunohistochemistry (the avidin-biotin-peroxidase complex and double immunofluorescence methods) using pan cytokeratin, cytokeratin 20 (K20, a Merkel cell marker), and neurofilament 200 (NF200, a myelinated Aβ- and Aδ-nerve fibre marker) antibodies. NF200-immunoreactive (ir) nerve fibres in healthy tissues and in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis were counted and statistically analysed. In the healthy oral mucosa, K20-positive Merkel cells with and without close association to the intraepithelial NF200-ir nerve fibres were detected. In the lesional oral mucosa of lichen planus and hyperkeratosis patients, extremely rare NF200-ir nerve fibres were detected only in the lamina propria. Compared with healthy tissues, lichen planus and hyperkeratosis tissues had significantly decreased numbers of NF200-ir nerve fibres in the oral mucosal epithelium. Lichen planus and hyperkeratosis were associated with the absence of Aβ-nerve endings in the oral mucosal epithelium. Thus, we conclude that mechanosensation mediated by the Merkel cell-neurite complex in the oral mucosal epithelium is impaired in lichen planus and hyperkeratosis.

  1. Loss of Aβ-nerve endings associated with the Merkel cell-neurite complex in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis

    PubMed Central

    Carrión, Daniela Calderón; Korkmaz, Yüksel; Cho, Britta; Kopp, Marion; Bloch, Wilhelm; Addicks, Klaus; Niedermeier, Wilhelm

    2016-01-01

    The Merkel cell-neurite complex initiates the perception of touch and mediates Aβ slowly adapting type I responses. Lichen planus is a chronic inflammatory autoimmune disease with T-cell-mediated inflammation, whereas hyperkeratosis is characterized with or without epithelial dysplasia in the oral mucosa. To determine the effects of lichen planus and hyperkeratosis on the Merkel cell-neurite complex, healthy oral mucosal epithelium and lesional oral mucosal epithelium of lichen planus and hyperkeratosis patients were stained by immunohistochemistry (the avidin-biotin-peroxidase complex and double immunofluorescence methods) using pan cytokeratin, cytokeratin 20 (K20, a Merkel cell marker), and neurofilament 200 (NF200, a myelinated Aβ- and Aδ-nerve fibre marker) antibodies. NF200-immunoreactive (ir) nerve fibres in healthy tissues and in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis were counted and statistically analysed. In the healthy oral mucosa, K20-positive Merkel cells with and without close association to the intraepithelial NF200-ir nerve fibres were detected. In the lesional oral mucosa of lichen planus and hyperkeratosis patients, extremely rare NF200-ir nerve fibres were detected only in the lamina propria. Compared with healthy tissues, lichen planus and hyperkeratosis tissues had significantly decreased numbers of NF200-ir nerve fibres in the oral mucosal epithelium. Lichen planus and hyperkeratosis were associated with the absence of Aβ-nerve endings in the oral mucosal epithelium. Thus, we conclude that mechanosensation mediated by the Merkel cell-neurite complex in the oral mucosal epithelium is impaired in lichen planus and hyperkeratosis. PMID:27025263

  2. Morphological and functional characteristics of human gingival junctional epithelium.

    PubMed

    Jiang, Qian; Yu, Youcheng; Ruan, Hong; Luo, Yin; Guo, Xuehua

    2014-04-03

    This study aims to observe the morphological characteristics and identify the function characteristics of junctional epithelium (JE) tissues and cultured JE cells. Paraffin sections of human molar or premolar on the gingival buccolingual side were prepared from 6 subjects. HE staining and image analysis were performed to measure and compare the morphological difference among JE, oral gingival epithelium (OGE) and sulcular epithelium (SE). Immunohistochemistry was applied to detect the expression pattern of cytokeratin 5/6, 7, 8/18, 10/13, 16, 17, 19, and 20 in JE, OGE and SE. On the other hand, primary human JE and OGE cells were cultured in vitro. Cell identify was confirmed by histology and immunohistochemistry. In a co-culture model, TEM was used to observe the attachment formation between JE cells and tooth surface. Human JE was a unique tissue which was different from SE and OGE in morphology. Similarly, morphology of JE cells was also particular compared with OGE cells cultured in vitro. In addition, JE cells had a longer incubation period than OGE cells. Different expression of several CKs illustrated JE was in a characteristic of low differentiation and high regeneration. After being co-cultured for 14 d, multiple cell layers, basement membrane-like and hemidesmosome-like structures were appeared at the junction of JE cell membrane and tooth surface. JE is a specially stratified epithelium with low differentiation and high regeneration ability in gingival tissue both in vivo and in vitro. In co-culture model, human JE cells can form basement membrane-like and hemidesmosome-like structures in about 2 weeks.

  3. The junctional epithelium originates from the odontogenic epithelium of an erupted tooth

    PubMed Central

    Yajima-Himuro, Sara; Oshima, Masamitsu; Yamamoto, Gou; Ogawa, Miho; Furuya, Madoka; Tanaka, Junichi; Nishii, Kousuke; Mishima, Kenji; Tachikawa, Tetsuhiko; Tsuji, Takashi; Yamamoto, Matsuo

    2014-01-01

    The junctional epithelium (JE) is an epithelial component that is directly attached to the tooth surface and has a protective function against periodontal diseases. In this study, we determined the origin of the JE using a bioengineered tooth technique. We transplanted the bioengineered tooth germ into the alveolar bone with an epithelial component that expressed green fluorescence protein. The reduced enamel epithelium from the bioengineered tooth fused with the oral epithelium, and the JE was apparently formed around the bioengineered tooth 50 days after transplantation. Importantly, the JE exhibited green fluorescence for at least 140 days after transplantation, suggesting that the JE was not replaced by oral epithelium. Therefore, our results demonstrated that the origin of the JE was the odontogenic epithelium, and odontogenic epithelium-derived JE was maintained for a relatively long period. PMID:24785116

  4. Immunolocalization of osteopontin in dysplasias and squamous cell carcinomas arising from oral epithelium.

    PubMed

    Aravind, Thara; Janardhanan, Mahija; Rakesh, S; Savithri, Vindhya; Unnikrishnan, U G

    2017-01-01

    Early detection of oral squamous cell carcinoma (OSCC) remains one of the most efficient ways to ensure patient survival and improved quality of life. Although specific biomarkers related to OSCC have been investigated, a useful biomarker that assesses the transition potential of potentially malignant lesion to OSCC remains to be found. Osteopontin (OPN) has been recognized as an important factor in tumorigenesis and their expression in OSCC have been investigated earlier. In the present study, evaluation of OPN expression in premalignant and malignant lesions has been carried out to assess their possible role as a biomarker in the early diagnosis and prognosis of OSCC. The objective of this study is to evaluate the role of OPN as a biomarker in the diagnosis and prognosis of OSCC. The study group consisted of archival paraffin-embedded blocks of ten cases each of varying grades of OSCC, oral epithelial dysplasias and epithelial hyperplasias. Sections were subjected to immunohistochemical staining for the biomarker OPN. A positive OPN expression was noticed in epithelial dysplasias and SCC arising from the oral epithelium. A progressive increase in the intensity of staining was seen with increasing grades of dysplasias and a decrease in OPN expression with an increase in grades was observed in OSCC. The expression of OPN in full thickness of epithelium in severe dysplasias, carcinoma in situ, and in the superficial epithelium of OSCC suggest the possibility of considering OPN expression in full epithelial thickness in dysplasias as an indicator for malignant transformation.

  5. Langerhans cells from human oral epithelium are more effective at stimulating allogeneic T cells in vitro than Langerhans cells from skin.

    PubMed

    Hasséus, B; Jontell, M; Bergenholtz, G; Dahlgren, U I

    2004-06-01

    This report is focused on the functional capacity of Langerhans cells (LC) in the epithelium of skin and oral mucosa, which both meet different antigenic challenges. The capacity of LC from human oral and skin epithelium to provide co-stimulatory signals to T cells in vitro was compared. LC in a crude suspension of oral epithelial cells had a significantly enhanced T cell co-stimulatory capacity compared to skin epithelial cells. This applied both to cultures with concanavalin A (con-A)-stimulated syngeneic T cells and to a mixed epithelial cell lymphocyte reaction involving allogeneic T cells. The co-stimulatory capacity of oral and skin epithelial cells was reduced by >70% if monoclonal antibodies against HLA-DR, -DP and -DQ were added to the cultures with allogeneic T cells, indicating the involvement of HLA class II expressing LC. Immunohistochemistry revealed that 6% of the epithelial cells were CD1a + LC in sections from both oral and skin epithelium. Interleukin (IL)-8 production was higher in cultures of oral epithelial cells and con-A stimulated T cells than in corresponding cultures with skin epithelial cells as accessory cells. The results suggest that LC in human oral epithelium are more efficient at stimulating T cells than those of skin.

  6. The chronicles of Porphyromonas gingivalis: the microbium, the human oral epithelium and their interplay

    PubMed Central

    Yilmaz, Özlem

    2009-01-01

    The microbiota of the human oral mucosa consists of a myriad of bacterial species that normally exist in commensal harmony with the host. Porphyromonas gingivalis, an aetiological agent in severe forms of periodontitis (a chronic inflammatory disease), is a prominent component of the oral microbiome and a successful colonizer of the oral epithelium. This Gram-negative anaerobe can also exist within the host epithelium without the existence of overt disease. Gingival epithelial cells, the outer lining of the gingival mucosa, which function as an important part of the innate immune system, are among the first host cells colonized by P. gingivalis. This review describes recent studies implicating the co-existence and intracellular adaptation of the organism in these target host cells. Specifically, recent findings on the putative mechanisms of persistence, intercellular dissemination and opportunism are highlighted. These new findings may also represent an original and valuable model for mechanistic characterization of other successful host-adapted, self-limiting, persistent intracellular bacteria in human epithelial tissues. PMID:18832296

  7. The chronicles of Porphyromonas gingivalis: the microbium, the human oral epithelium and their interplay.

    PubMed

    Yilmaz, Ozlem

    2008-10-01

    The microbiota of the human oral mucosa consists of a myriad of bacterial species that normally exist in commensal harmony with the host. Porphyromonas gingivalis, an aetiological agent in severe forms of periodontitis (a chronic inflammatory disease), is a prominent component of the oral microbiome and a successful colonizer of the oral epithelium. This Gram-negative anaerobe can also exist within the host epithelium without the existence of overt disease. Gingival epithelial cells, the outer lining of the gingival mucosa, which function as an important part of the innate immune system, are among the first host cells colonized by P. gingivalis. This review describes recent studies implicating the co-existence and intracellular adaptation of the organism in these target host cells. Specifically, recent findings on the putative mechanisms of persistence, intercellular dissemination and opportunism are highlighted. These new findings may also represent an original and valuable model for mechanistic characterization of other successful host-adapted, self-limiting, persistent intracellular bacteria in human epithelial tissues.

  8. A Novel Wounding Device Suitable for Quantitative Biochemical Analysis of Wound Healing and Regeneration of Cultured Epithelium

    PubMed Central

    Lan, Rongpei; Geng, Hui; Hwang, Yoon; Mishra, Pramod; Skloss, Wayne L.; Sprague, Eugene A.; Saikumar, Pothana; Venkatachalam, Manjeri

    2010-01-01

    We describe the fabrication and use of an in vitro wounding device that denudes cultured epithelium in patterns designed to leave behind strips or islands of cells sufficiently narrow or small to ensure that all remaining cells become rapidly activated and then migrate, dedifferentiate and proliferate in near synchrony. The design ensures that signals specific to regenerating cells do not become diluted by quiescent differentiated cells that are not affected by wound induced activation. The device consists of a flat circular disk of rubber engraved to produce alternating ridges and grooves in patterns of concentric circles or parallel lines. The disk is mounted at the end of a pneumatically controlled piston assembly. Application of controlled pressure and circular or linear movement of the disk on cultures produced highly reproducible wounding patterns. The near synchronous regenerative activity of cell bands or islands permitted the collection of samples large enough for biochemical studies to sensitively detect alterations involving mRNA for several early response genes and protein phosphorylation in major signaling pathways. The method is versatile, easy to use and reproducible, and should facilitate biochemical, proteomic and genomic studies of wound induced regeneration of cultured epithelium. PMID:20230600

  9. Lineage-negative Progenitors Mobilize to Regenerate Lung Epithelium after Major Injury

    PubMed Central

    Vaughan, Andrew E.; Brumwell, Alexis N.; Xi, Ying; Gotts, Jeffrey; Brownfield, Doug G.; Treutlein, Barbara; Tan, Kevin; Tan, Victor; Liu, Fengchun; Looney, Mark R.; Matthay, Michael; Rock, Jason R.; Chapman, Harold A.

    2014-01-01

    Broadly, tissue regeneration is achieved in two ways: by proliferation of common differentiated cells and/or by deployment of specialized stem/progenitor cells. Which of these pathways applies is both organ and injury-specific1–4. Current paradigms in the lung posit that epithelial repair can be attributed to cells expressing mature lineage markers5–8. In contrast we here define the regenerative role of previously uncharacterized, rare lineage-negative epithelial stem/progenitor (LNEPs) cells present within normal distal lung. Quiescent LNEPs activate a ΔNp63/cytokeratin 5 (Krt5+) remodeling program after influenza or bleomycin injury. Activated cells proliferate and migrate widely to occupy heavily injured areas depleted of mature lineages, whereupon they differentiate toward mature epithelium. Lineage tracing revealed scant contribution of pre-existing mature epithelial cells in such repair, whereas orthotopic transplantation of LNEPs, isolated by a definitive surface profile identified through single cell sequencing, directly demonstrated the proliferative capacity and multipotency of this population. LNEPs require Notch signaling to activate the ΔNp63/Krt5+ program whereas subsequent Notch blockade promotes an alveolar cell fate. Persistent Notch signaling post-injury led to parenchymal micro-honeycombing, indicative of failed regeneration. Lungs from fibrosis patients show analogous honeycomb cysts with evidence of hyperactive Notch signaling. Our findings indicate distinct stem/progenitor cell pools repopulate injured tissue depending on the extent of injury, and the outcomes of regeneration or fibrosis may ride in part on the dynamics of LNEP Notch signaling. PMID:25533958

  10. Neuropilin 1 Receptor Is Up-Regulated in Dysplastic Epithelium and Oral Squamous Cell Carcinoma.

    PubMed

    Shahrabi-Farahani, Shokoufeh; Gallottini, Marina; Martins, Fabiana; Li, Erik; Mudge, Dayna R; Nakayama, Hironao; Hida, Kyoko; Panigrahy, Dipak; D'Amore, Patricia A; Bielenberg, Diane R

    2016-04-01

    Neuropilins are receptors for disparate ligands, including proangiogenic factors such as vascular endothelial growth factor and inhibitory class 3 semaphorin (SEMA3) family members. Differentiated cells in skin epithelium and cutaneous squamous cell carcinoma highly express the neuropilin-1 (NRP1) receptor. We examined the expression of NRP1 in human and mouse oral mucosa. NRP1 was significantly up-regulated in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC). NRP1 receptor localized to the outer suprabasal epithelial layers in normal tongue, an expression pattern similar to the normal skin epidermis. However, dysplastic tongue epithelium and OSCC up-regulated NRP1 in basal and proliferating epithelial layers, a profile unseen in cutaneous squamous cell carcinoma. NRP1 up-regulation is observed in a mouse carcinogen-induced OSCC model and in human tongue OSCC biopsies. Human OSCC cell lines express NRP1 protein in vitro and in mouse tongue xenografts. Sites of capillary infiltration into orthotopic OSCC tumors correlate with high NRP1 expression. HSC3 xenografts, which express the highest NRP1 levels of the cell lines examined, showed massive intratumoral lymphangiogenesis. SEMA3A inhibited OSCC cell migration, suggesting that the NRP1 receptor was bioactive in OSCC. In conclusion, NRP1 is regulated in the oral epithelium and is selectively up-regulated during epithelial dysplasia. NRP1 may function as a reservoir to sequester proangiogenic ligands within the neoplastic compartment, thereby recruiting neovessels toward tumor cells. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  11. Immunolocalization of osteopontin in dysplasias and squamous cell carcinomas arising from oral epithelium

    PubMed Central

    Aravind, Thara; Janardhanan, Mahija; Rakesh, S; Savithri, Vindhya; Unnikrishnan, U G

    2017-01-01

    Background: Early detection of oral squamous cell carcinoma (OSCC) remains one of the most efficient ways to ensure patient survival and improved quality of life. Although specific biomarkers related to OSCC have been investigated, a useful biomarker that assesses the transition potential of potentially malignant lesion to OSCC remains to be found. Osteopontin (OPN) has been recognized as an important factor in tumorigenesis and their expression in OSCC have been investigated earlier. In the present study, evaluation of OPN expression in premalignant and malignant lesions has been carried out to assess their possible role as a biomarker in the early diagnosis and prognosis of OSCC. Objectives: The objective of this study is to evaluate the role of OPN as a biomarker in the diagnosis and prognosis of OSCC. Materials and Methods: The study group consisted of archival paraffin-embedded blocks of ten cases each of varying grades of OSCC, oral epithelial dysplasias and epithelial hyperplasias. Sections were subjected to immunohistochemical staining for the biomarker OPN. Results: A positive OPN expression was noticed in epithelial dysplasias and SCC arising from the oral epithelium. A progressive increase in the intensity of staining was seen with increasing grades of dysplasias and a decrease in OPN expression with an increase in grades was observed in OSCC. Conclusion: The expression of OPN in full thickness of epithelium in severe dysplasias, carcinoma in situ, and in the superficial epithelium of OSCC suggest the possibility of considering OPN expression in full epithelial thickness in dysplasias as an indicator for malignant transformation. PMID:28479681

  12. Origin of Ameloblastoma From Basal Cells of the Oral Epithelium- Establishing the Relation Using Neuroectodermal Markers

    PubMed Central

    Suneela, S; Narayan, T V; Shreedhar, Balasundari; Mohanty, Leeky; Shenoy, Sadhana; Swaminathan, Uma

    2014-01-01

    Background and Objectives: Basal cell layer of the oral epithelium has been rightfully regarded as a potential source of odontogenic tumours and cysts, but, without substantial evidence. Also, whether the basal cell layer retains within it, some properties of ectomesenchyme, which was imbibed during the early embryogenesis and hence its neuroectodermal relation, is not known. Here, an attempt is made to establish the hidden neuroectodermal potential of the oral epithelium, especially the basal layer, by observing the expression of known neuroectodermal markers, NSE (Neuron Specific Enolase), Synaptophysin and CD99. The expression of the same markers has also been studied in Ameloblastoma, connecting it with oral epithelium, in turn establishing basal cell layer as a potential source of Ameloblastoma. Materials and Methods: Sections of formalin fixed, paraffin embedded tissue samples of 20 cases of Ameloblastoma and 10 cases of Normal Retromolar mucosa, were stained immunohistochemically with NSE, Synaptophysin, CD99 and also with CK-19 and evaluated for positive expression. Results: Positive reaction was obtained in all the cases of Ameloblastoma and NRM (Normal Retromolar mucosa) with NSE, all the cases of Ameloblastoma and eight cases of NRM with Synaptophysin and in six cases of Ameloblastoma and NRM with CD99. The staining was diffuse and more marked in case of NSE than Synaptophysin and CD99. CK19 staining done to assure that the tissue antigenicity was maintained was positive in all the samples. Interpretation and Conclusion: A strong relationship between the neuroectoderm, Ameloblastoma and the basal layer of the oral epithelium is established by the study. It favours the hypothesis that the basal cell layer of oral mucosa may be the sought out culprit in most cases of the Ameloblastomas, especially those occurring in the non-tooth bearing area. This would call for the need to incorporate additional therapy in the form of mucosal striping along with the

  13. CD44 variant isoform 9 emerges in response to injury and contributes to the regeneration of the gastric epithelium

    PubMed Central

    Bertaux-Skeirik, Nina; Wunderlich, Mark; Teal, Emma; Chakrabarti, Jayati; Biesiada, Jacek; Mahe, Maxime; Sundaram, Nambirajan; Gabre, Joel; Hawkins, Jennifer; Jian, Gao; Engevik, Amy C.; Yang, Li; Wang, Jiang; Goldenring, James R.; Qualls, Joseph E.; Medvedovic, Mario; Helmrath, Michael A.; Diwan, Tayyab; Mulloy, James C.; Zavros, Yana

    2017-01-01

    The CD44 gene encodes several protein isoforms due to alternative splicing and post translational modifications. Given that CD44 variant isoform 9 (CD44v9) is expressed within Spasmolytic Polypeptide/TFF2-Expressing Metaplasia (SPEM) glands during repair, CD44v9 may be play a functional role during the process of regeneration of the gastric epithelium. Here we hypothesize that CD44v9 marks a regenerative cell lineage responsive to infiltrating macrophages during regeneration of the gastric epithelium. Ulcers were induced in CD44-decient (CD44KO) and C57BL/6 (BL6) mice by a localized application of acetic acid to the serosal surface of the stomach. Gastric organoids expressing CD44v9 were derived from mouse stomachs and transplanted at the ulcer site of CD44KO mice. Ulcers, CD44v9 expression, proliferation and histology were measured 1, 3, 5 and 7-days post-injury. Human-derived gastric organoids were generated from stomach tissue collected from elderly (>55 years) or young (14–20 years) patients. Organoids were transplanted into the stomachs of NOD scid gamma (NSG) mice at the site of injury. Gastric injury was induced in NRG-SGM3 (NRGS) mice harboring human-derived immune cells (hnNRGS) and the immune profile analyzed by CyTOF. CD44v9 expression emerged within regenerating glands the ulcer margin in response to injury. While ulcers in BL6 mice healed within 7-days post-injury, CD44KO mice exhibited loss of repair and epithelial regeneration. Ulcer healing was promoted in CD44KO mice by transplanted CD55v9-expressing gastric organoids. NSG mice exhibited loss of CD44v9 expression and gastric repair. Transplantation of human-derived gastric organoids from young, but not aged stomachs promoted repair in NSG mouse stomachs in response to injury. Finally, compared to NRGS mice, huNRGS animals exhibited reduced ulcer sizes, an infiltration of human CD162+ macrophages and an emergence of CD44v9 expression in SPEM. Thus, during repair of the gastric epithelium CD44v9

  14. Expression pattern of adhesion molecules in junctional epithelium differs from that in other gingival epithelia.

    PubMed

    Hatakeyama, S; Yaegashi, T; Oikawa, Y; Fujiwara, H; Mikami, T; Takeda, Y; Satoh, M

    2006-08-01

    The gingival epithelium is the physiologically important interface between the bacterially colonized gingival sulcus and periodontal soft and mineralized connective tissues, requiring protection from exposure to bacteria and their products. However, of the three epithelia comprising the gingival epithelium, the junctional epithelium has much wider intercellular spaces than the sulcular epithelium and oral gingival epithelium. Hence, the aim of the present study was to characterize the cell adhesion structure in the junctional epithelium compared with the other two epithelia. Gingival epithelia excised at therapeutic flap surgery from patients with periodontitis were examined for expression of adhesion molecules by immunofluorescence. In the oral gingival epithelium and sulcular epithelium, but not in the junctional epithelium, desmoglein 1 and 2 in cell-cell contact sites were more abundant in the upper than the suprabasal layers. E-cadherin, the main transmembranous molecule of adherens junctions, was present in spinous layers of the oral gingival epithelium and sulcular epithelium, but was scarce in the junctional epithelium. In contrast, desmoglein 3 and P-cadherin were present in all layers of the junctional epithelium as well as the oral gingival epithelium and sulcular epithelium. Connexin 43 was clearly localized to spinous layers of the oral gingival epithelium, sulcular epithelium and parts of the junctional epithelium. Claudin-1 and occludin were expressed in the cell membranes of a few superficial layers of the oral gingival epithelium. These findings indicated that the junctional epithelium contains only a few desmosomes, composed of only desmoglein 3; adherens junctions are probably absent because of defective E-cadherin. Thus, the anchoring junctions connecting junctional epithelium cells are lax, causing widened intercellular spaces. In contrast, the oral gingival epithelium, which has a few tight junctions, functions as a barrier.

  15. Diffusion of naltrexone across reconstituted human oral epithelium and histomorphological features.

    PubMed

    Giannola, Libero Italo; De Caro, Viviana; Giandalia, Giulia; Siragusa, Maria Gabriella; Campisi, Giuseppina; Florena, Ada Maria; Ciach, Tomasz

    2007-02-01

    In transbuccal absorption a major limitation could be the low permeability of the mucosa which implies low drug bioavailability. The ability of naltrexone hydrochloride (NLX) to penetrate a resembling histologically human buccal mucosa was assessed and the occurrence of any histomorphological changes observed. We used reconstituted human oral (RHO) non-keratinised epithelium as mucosal section and a Transwell diffusion cells system as bicompartmental model. Buccal permeation was expressed in terms of drug flux (J(s)) and permeability coefficients (K(p)). Data were collected using both artificial and natural human saliva. The main finding was that RHO does not restrain NLX permeation. Drug transport across the epithelium was observed also in presence of various concentrations of penetration enhancers, without any significant differences. On the contrary, the flux throughout the mucosa was extensively affected by iontophoresis. Histologically, no sign of flogosis was observed in any specimen under experiment without iontophoresis, whereas cytoarchitectural changes, up to nuclear pycnosis or cellular swelling, were determined as a consequence of the application of electric fields.

  16. Mast cells distribution and variations in epithelium thickness and basement membrane in oral lichen planus lesion and oral lichenoid reaction

    PubMed Central

    Jahanshahi, Gholamreza; Ghalayani, Parichehr; Maleki, Laleh

    2012-01-01

    Background: Oral lichen planus (OLP) is a chronic mucocutaneous lesion with unknown etiology. Oral lichenoid lesions (OLL) comprise a family of lesions with different etiologies. Both lesions have similar clinical and histopathologic characteristics although their management is different. Differential diagnosis between OLP and OLL has always been a major challenge. Materials and Methods: In this prospective analytical study, the role of mast cells in pathogenesis of these lesions was investigated by evaluation of 52 patients with clinical and histopathological diagnosis of OLP (26 cases) and OLL (26 cases) based on WHO criteria, and by applying a more accessible staining methods, Hematoxylin and Eosin, toluidine blue (histochemistry) and Periodic Acid Schiff staining. In order to distinguish these two lesions, number of mast cells and thickness of epithelium and basement membrane were measured using light microscopy. Data were analyzed by SPSS software using t-test method (P<0.001). Results: No significant difference was observed between the total numbers of mast cells of two groups (P=0.148), but a statistically significant difference was detected between degranulated mast cells in two groups (P<0.001). A significant difference was also observed between the thickness of epithelium in two groups (P<0.001), although no difference was seen between basement membrane thickness in these lesions. Conclusion: Number of degranulated mast cells in reticular layer of corium in lichenoid lesions was more than that of OLP. This implies that despite the increase in number of these cells, in both groups of diseases, the role of these cells has not been the same in pathogenesis of the diseases. Moreover, the epithelium thickness was lower in lesions of OLP compared to lesions of oral lichenoid, so this parameter may be a useful criterion together with other histopathological and clinical finding to discriminate these lesions. However, discrepancy of basement membrane thickness

  17. [Characterization of stem cells derived from the neonatal auditory sensory epithelium].

    PubMed

    Diensthuber, M; Heller, S

    2010-11-01

    In contrast to regenerating hair cell-bearing organs of nonmammalian vertebrates the adult mammalian organ of Corti appears to have lost its ability to maintain stem cells. The result is a lack of regenerative ability and irreversible hearing loss following auditory hair cell death. Unexpectedly, the neonatal auditory sensory epithelium has recently been shown to harbor cells with stem cell features. The origin of these cells within the cochlea's sensory epithelium is unknown. We applied a modified neurosphere assay to identify stem cells within distinct subregions of the neonatal mouse auditory sensory epithelium. Sphere cells were characterized by multiple markers and morphologic techniques. Our data reveal that both the greater and the lesser epithelial ridge contribute to the sphere-forming stem cell population derived from the auditory sensory epithelium. These self-renewing sphere cells express a variety of markers for neural and otic progenitor cells and mature inner ear cell types. Stem cells can be isolated from specific regions of the auditory sensory epithelium. The distinct features of these cells imply a potential application in the development of a cell replacement therapy to regenerate the damaged sensory epithelium.

  18. Progenitor Epithelium

    PubMed Central

    Marty-Santos, Leilani

    2015-01-01

    Insulin-producing β cells within the vertebrate fetal pancreas acquire their fate in a step-wise manner. Whereas the intrinsic factors dictating the transcriptional or epigenetic status of pancreatic lineages have been intensely examined, less is known about cell–cell interactions that might constitute a niche for the developing β cell lineage. It is becoming increasingly clear that understanding and recapitulating these steps may instruct in vitro differentiation of embryonic stem cells and/or therapeutic regeneration. Indeed, directed differentiation techniques have improved since transitioning from 2D to 3D cultures, suggesting that the 3D microenvironment in which β cells are born is critical. However, to date, it remains unknown whether the changing architecture of the pancreatic epithelium impacts the fate of cells therein. An emerging challenge in the field is to elucidate how progenitors are allocated during key events, such as the stratification and subsequent resolution of the pre-pancreatic epithelium, as well as the formation of lumens and branches. Here, we assess the progenitor epithelium and examine how it might influence the emergence of pancreatic multipotent progenitors (MPCs), which give rise to β cells and other pancreatic lineages. PMID:26216134

  19. Ex vivo generation of a functional and regenerative wound epithelium from axolotl (Ambystoma mexicanum) skin.

    PubMed

    Ferris, Donald R; Satoh, Akira; Mandefro, Berhan; Cummings, Gillian M; Gardiner, David M; Rugg, Elizabeth L

    2010-10-01

    Urodele amphibians (salamanders) are unique among adult vertebrates in their ability to regenerate structurally complete and fully functional limbs. Regeneration is a stepwise process that requires interactions between keratinocytes, nerves and fibroblasts. The formation of a wound epithelium covering the amputation site is an early and necessary event in the process but the molecular mechanisms that underlie the role of the wound epithelium in regeneration remain unclear. We have developed an ex vivo model that recapitulates many features of in vivo wound healing. The model comprises a circular explant of axolotl (Ambystoma mexicanum) limb skin with a central circular, full thickness wound. Re-epithelialization of the wound area is rapid (typically <11 h) and is dependent on metalloproteinase activity. The ex vivo wound epithelium is viable, responds to neuronal signals and is able to participate in ectopic blastema formation and limb regeneration. This ex vivo model provides a reproducible and tractable system in which to study the cellular and molecular events that underlie wound healing and regeneration. © 2010 The Authors. Journal compilation © 2010 Japanese Society of Developmental Biologists.

  20. Lens regeneration from the cornea requires suppression of Wnt/β-catenin signaling.

    PubMed

    Hamilton, Paul W; Sun, Yu; Henry, Jonathan J

    2016-04-01

    The frog, Xenopus laevis, possesses a high capacity to regenerate various larval tissues, including the lens, which is capable of complete regeneration from the cornea epithelium. However, the molecular signaling mechanisms of cornea-lens regeneration are not fully understood. Previous work has implicated the involvement of the Wnt signaling pathway, but molecular studies have been very limited. Iris-derived lens regeneration in the newt (Wolffian lens regeneration) has shown a necessity for active Wnt signaling in order to regenerate a new lens. Here we provide evidence that the Wnt signaling pathway plays a different role in the context of cornea-lens regeneration in Xenopus. We examined the expression of frizzled receptors and wnt ligands in the frog cornea epithelium. Numerous frizzled receptors (fzd1, fzd2, fzd3, fzd4, fzd6, fzd7, fzd8, and fzd10) and wnt ligands (wnt2b.a, wnt3a, wnt4, wnt5a, wnt5b, wnt6, wnt7b, wnt10a, wnt11, and wnt11b) are expressed in the cornea epithelium, demonstrating that this tissue is transcribing many of the ligands and receptors of the Wnt signaling pathway. When compared to flank epithelium, which is lens regeneration incompetent, only wnt11 and wnt11b are different (present only in the cornea epithelium), identifying them as potential regulators of cornea-lens regeneration. To detect changes in canonical Wnt/β-catenin signaling occurring within the cornea epithelium, axin2 expression was measured over the course of regeneration. axin2 is a well-established reporter of active Wnt/β-catenin signaling, and its expression shows a significant decrease at 24 h post-lentectomy. This decrease recovers to normal endogenous levels by 48 h. To test whether this signaling decrease was necessary for lens regeneration to occur, regenerating eyes were treated with either 6-bromoindirubin-3'-oxime (BIO) or 1-azakenpaullone - both activators of Wnt signaling - resulting in a significant reduction in the percentage of cases with successful

  1. Identification of Distinct Layers Within the Stratified Squamous Epithelium of the Adult Human True Vocal Fold

    PubMed Central

    Dowdall, Jayme R.; Sadow, Peter M.; Hartnick, Christopher; Vinarsky, Vladimir; Mou, Hongmei; Zhao, Rui; Song, Phillip C.; Franco, Ramon A.; Rajagopal, Jayaraj

    2016-01-01

    Objectives/Hypothesis A precise molecular schema for classifying the different cell types of the normal human vocal fold epithelium is lacking. We hypothesize that the true vocal fold epithelium has a cellular architecture and organization similar to that of other stratified squamous epithelia including the skin, cornea, oral mucosa, and esophagus. In analogy to disorders of the skin and gastrointestinal tract, a molecular definition of the normal cell types within the human vocal fold epithelium and a description of their geometric relationships should serve as a foundation for characterizing cellular changes associated with metaplasia, dysplasia, and cancer. Study Design Qualitative study with adult human larynges. Methods Histologic sections of normal human laryngeal tissue were analyzed for morphology (hematoxylin and eosin) and immunohistochemical protein expression profile, including cytokeratins (CK13 and CK14), cornified envelope proteins (involucrin), basal cells (NGFR/p75), and proliferation markers (Ki67). Results We demonstrated that three distinct cell strata with unique marker profiles are present within the stratified squamous epithelium of the true vocal fold. We used these definitions to establish that cell proliferation is restricted to certain cell types and layers within the epithelium. These distinct cell types are reproducible across five normal adult larynges. Conclusion We have established that three layers of cells are present within the normal adult stratified squamous epithelium of the true vocal fold. Furthermore, replicating cell populations are largely restricted to the parabasal strata within the epithelium. This delineation of distinct cell populations will facilitate future studies of vocal fold regeneration and cancer. Level of Evidence N/A. PMID:25988619

  2. Identification of distinct layers within the stratified squamous epithelium of the adult human true vocal fold.

    PubMed

    Dowdall, Jayme R; Sadow, Peter M; Hartnick, Christopher; Vinarsky, Vladimir; Mou, Hongmei; Zhao, Rui; Song, Phillip C; Franco, Ramon A; Rajagopal, Jayaraj

    2015-09-01

    A precise molecular schema for classifying the different cell types of the normal human vocal fold epithelium is lacking. We hypothesize that the true vocal fold epithelium has a cellular architecture and organization similar to that of other stratified squamous epithelia including the skin, cornea, oral mucosa, and esophagus. In analogy to disorders of the skin and gastrointestinal tract, a molecular definition of the normal cell types within the human vocal fold epithelium and a description of their geometric relationships should serve as a foundation for characterizing cellular changes associated with metaplasia, dysplasia, and cancer. Qualitative study with adult human larynges. Histologic sections of normal human laryngeal tissue were analyzed for morphology (hematoxylin and eosin) and immunohistochemical protein expression profile, including cytokeratins (CK13 and CK14), cornified envelope proteins (involucrin), basal cells (NGFR/p75), and proliferation markers (Ki67). We demonstrated that three distinct cell strata with unique marker profiles are present within the stratified squamous epithelium of the true vocal fold. We used these definitions to establish that cell proliferation is restricted to certain cell types and layers within the epithelium. These distinct cell types are reproducible across five normal adult larynges. We have established that three layers of cells are present within the normal adult stratified squamous epithelium of the true vocal fold. Furthermore, replicating cell populations are largely restricted to the parabasal strata within the epithelium. This delineation of distinct cell populations will facilitate future studies of vocal fold regeneration and cancer. N/A. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

  3. Bone marrow-derived cells contribute to regeneration of injured prostate epithelium and stroma.

    PubMed

    Nakata, Wataru; Nakai, Yasutomo; Yoshida, Takahiro; Sato, Mototaka; Hatano, Koji; Nagahara, Akira; Fujita, Kazutoshi; Uemura, Motohide; Nonomura, Norio

    2015-06-01

    Recent studies have reported that bone marrow-derived cells (BMDCs), which are recruited to sites of tissue injury and inflammation, can differentiate into epithelial cells, such as liver, lung, gastrointestinal tract, and skin cells. We investigated the role of BMDCs in contributing to regeneration of injured prostate epithelium. Using chimera rats that received allogenic bone marrow grafts from green fluorescent protein (GFP) transgenic rats after lethal whole-body irradiation, we investigated the existence of epithelial marker-positive BMDCs in injured prostate tissue caused by transurethral injection of lipopolysaccharide. Prostate tissues were harvested 2 weeks after transurethral lipopolysaccharide injection. Immunofluorescence staining showed that some cells in the stroma co-expressed GFP and pan-cytokeratin, which suggested the existence of epithelial marker-positive BMDCs. To confirm the existence of such cells, we collected bone marrow-derived non-hematopoietic cells (GFP+/CD45- cells) from the prostate by fluorescence-activated cell sorter analysis and analyzed the characteristics of the GFP+/CD45- cells. The number of cells in this population significantly increased from 0.042% to 0.492% compared with normal prostate tissue. We found by immunofluorescent analysis and RT-PCR that GFP+/CD45- cells expressed cytokeratin, which suggested that these cells have some features of epithelial cells. In the prostate obtained from the chimera rats 34 weeks after lipopolysaccharide injection, GFP- and cytokeratin-positive cells were observed in the prostate gland, which suggested that some of the cells in the prostate gland regenerated after prostate inflammation derived from bone marrow. BMDCs might be able to differentiate into prostate epithelial cells after prostatic injury. © 2015 Wiley Periodicals, Inc.

  4. Proteome analysis reveals that de novo regenerated mucosa over fibula flap-reconstructed mandibles resembles mature keratinized oral mucosa.

    PubMed

    Kumar, Vinay V; James, Bonney L; Ruß, Manuela; Mikkat, Stefan; Suresh, Amritha; Kämmerer, Peer W; Glocker, Michael O

    2018-03-01

    The aim of this study was to determine whether intra-oral de novo regenerated mucosa (D) that grew over free fibula flap reconstructed-mandibles resembled the donor tissue i.e. external skin (S) of the lateral leg, or the recipient site tissue, i.e. keratinized oral mucosa (K). Differential proteome analysis was performed with ten tissue samples from each of the three groups: de novo regenerated mucosa (D), external skin (S), and keratinized oral mucosa (K). Expression differences of cornulin and involucrin were validated by Western blot analysis and their spatial distributions in the respective tissues were ascertained by immunohistochemistry. From all three investigated tissue types a total of 1188 proteins were identified, 930 of which were reproducibly and robustly quantified by proteome analysis. The best differentiating proteins were assembled in an oral mucosa proteome signature that encompasses 56 differentially expressed proteins. Principal component analysis of both, the 930 quantifiable proteins and the 56 oral mucosa signature proteins revealed that the de novo regenerated mucosa resembles keratinized oral mucosa much closer than extra-oral skin. Differentially expressed cornification-related proteins comprise proteins from all subclasses of the cornified cell envelope. Prominently expressed in intra-oral mucosa tissues were (i) cornifin-A, cornifin-B, SPRR3, and involucrin from the cornified-cell-envelope precursor group, (ii) S100A9, S100A8 and S100A2 from the S100 group, and (iii) cornulin which belongs to the fused-gene-protein group. According to its proteome signature de novo regenerated mucosa over the free fibula flap not only presents a passive structural surface layer but has adopted active tissue function. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. Distinct mechanisms underlie oral vs aboral regeneration in the cnidarian Hydractinia echinata.

    PubMed

    Bradshaw, Brian; Thompson, Kerry; Frank, Uri

    2015-04-17

    Cnidarians possess remarkable powers of regeneration, but the cellular and molecular mechanisms underlying this capability are unclear. Studying the hydrozoan Hydractinia echinata we show that a burst of stem cell proliferation occurs following decapitation, forming a blastema at the oral pole within 24 hr. This process is necessary for head regeneration. Knocking down Piwi1, Vasa, Pl10 or Ncol1 expressed by blastema cells inhibited regeneration but not blastema formation. EdU pulse-chase experiments and in vivo tracking of individual transgenic Piwi1(+) stem cells showed that the cellular source for blastema formation is migration of stem cells from a remote area. Surprisingly, no blastema developed at the aboral pole after stolon removal. Instead, polyps transformed into stolons and then budded polyps. Hence, distinct mechanisms act to regenerate different body parts in Hydractinia. This model, where stem cell behavior can be monitored in vivo at single cell resolution, offers new insights for regenerative biology.

  6. Changes in the Adult Vertebrate Auditory Sensory Epithelium After Trauma

    PubMed Central

    Oesterle, Elizabeth C.

    2012-01-01

    Auditory hair cells transduce sound vibrations into membrane potential changes, ultimately leading to changes in neuronal firing and sound perception. This review provides an overview of the characteristics and repair capabilities of traumatized auditory sensory epithelium in the adult vertebrate ear. Injured mammalian auditory epithelium repairs itself by forming permanent scars but is unable to regenerate replacement hair cells. In contrast, injured non-mammalian vertebrate ear generates replacement hair cells to restore hearing functions. Non-sensory support cells within the auditory epithelium play key roles in the repair processes. PMID:23178236

  7. Detection of molecular signatures of oral squamous cell carcinoma and normal epithelium - application of a novel methodology for unsupervised segmentation of imaging mass spectrometry data.

    PubMed

    Widlak, Piotr; Mrukwa, Grzegorz; Kalinowska, Magdalena; Pietrowska, Monika; Chekan, Mykola; Wierzgon, Janusz; Gawin, Marta; Drazek, Grzegorz; Polanska, Joanna

    2016-06-01

    Intra-tumor heterogeneity is a vivid problem of molecular oncology that could be addressed by imaging mass spectrometry. Here we aimed to assess molecular heterogeneity of oral squamous cell carcinoma and to detect signatures discriminating normal and cancerous epithelium. Tryptic peptides were analyzed by MALDI-IMS in tissue specimens from five patients with oral cancer. Novel algorithm of IMS data analysis was developed and implemented, which included Gaussian mixture modeling for detection of spectral components and iterative k-means algorithm for unsupervised spectra clustering performed in domain reduced to a subset of the most dispersed components. About 4% of the detected peptides showed significantly different abundances between normal epithelium and tumor, and could be considered as a molecular signature of oral cancer. Moreover, unsupervised clustering revealed two major sub-regions within expert-defined tumor areas. One of them showed molecular similarity with histologically normal epithelium. The other one showed similarity with connective tissue, yet was markedly different from normal epithelium. Pathologist's re-inspection of tissue specimens confirmed distinct features in both tumor sub-regions: foci of actual cancer cells or cancer microenvironment-related cells prevailed in corresponding areas. Hence, molecular differences detected during automated segmentation of IMS data had an apparent reflection in real structures present in tumor. © 2016 The Authors. Proteomics Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Defining a mechanistic link between pigment epithelium-derived factor, docosahexaenoic acid, and corneal nerve regeneration.

    PubMed

    Pham, Thang Luong; He, Jiucheng; Kakazu, Azucena H; Jun, Bokkyoo; Bazan, Nicolas G; Bazan, Haydee E P

    2017-11-10

    The cornea is densely innervated to sustain the integrity of the ocular surface. Corneal nerve damage produced by aging, diabetes, refractive surgeries, and viral or bacterial infections impairs tear production, the blinking reflex, and epithelial wound healing, resulting in loss of transparency and vision. A combination of the known neuroprotective molecule, pigment epithelium-derived factor (PEDF) plus docosahexaenoic acid (DHA), has been shown to stimulate corneal nerve regeneration, but the mechanisms involved are unclear. Here, we sought to define the molecular events of this effect in an in vivo mouse injury model. We first confirmed that PEDF + DHA increased nerve regeneration in the mouse cornea. Treatment with PEDF activates the phospholipase A 2 activity of the PEDF-receptor (PEDF-R) leading to the release of DHA; this free DHA led to enhanced docosanoid synthesis and induction of bdnf, ngf , and the axon growth promoter semaphorin 7a ( sema7a ), and as a consequence, their products appeared in the mouse tears. Surprisingly, corneal injury and treatment with PEDF + DHA induced transcription of neuropeptide y ( npy ), small proline-rich protein 1a ( sprr1a ), and vasoactive intestinal peptide ( vip ) in the trigeminal ganglia (TG). The PEDF-R inhibitor, atglistatin, blocked all of these changes in the cornea and TG. In conclusion, we uncovered here an active cornea-TG axis, driven by PEDF-R activation, that fosters axon outgrowth in the cornea. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. The effects of the stem cell on ciliary regeneration of injured rabbit sinonasal epithelium.

    PubMed

    Kavuzlu, Ali; Tatar, Emel Çadallı; Karagöz, Tuğba; Pınarlı, Ferda Alpaslan; Tatar, İlkan; Bayır, Ömer; Korkmaz, Mehmet Hakan

    2017-08-01

    Defects in mucosal healing after sinonasal surgery cause infection, scar formation causing obstruction, relapse of the disease within a shorter period and revision surgery. The present study aimed to create a functional ciliated epithelium using a stem cell and stem cell sheet of adipose tissue origin and to show such regeneration ultra-structurally on experimentally injured rabbit nasal epithelium. This was an experimental animal study and basic research. A total of 18 white New Zealand rabbits were divided into three groups. The medial wall of the maxillary sinus of the subjects was peeled off bilaterally. No additional procedure was applied to the subjects in Group 1. In Group 2, adipose tissue-derived mesenchymal stem cell was implanted on the wound edges of the subjects. In Group 3, a stem cell sheet of three layers was laid onto the defect area. All subjects were killed after 3 weeks. The presence of the stem cell stained with bromo-deoxyuridine was assessed with a light microscope, whereas cilia density, ciliated orientation and cilia structure were evaluated with a scanning electron microscope. Ciliary densities in Group 2 and Group 3 were statistically superior compared to the control group (p < 0.001, p = 0.007). Cilia morphology in Group 2 and Group 3 was also better than the control group (p < 0.01, p = 0.048). Ciliary orientation in Group 2 was scored highest (p < 0.01). The ratio of BrDu-stained cells was observed to be 27% in Group 3 and 8% in Group 2. Sub-epithelial recovery was observed to be better in Group 3. Adipose tissue-derived mesenchymal stem cell increased the healing of the injured maxillary sinus mucosa of the rabbits in terms of cilia presence, density and morphology regardless of the implementation technique. Level of evidence NA.

  10. Determination of ABO blood grouping from human oral squamous epithelium by the highly sensitive immunohistochemical staining method EnVision+.

    PubMed

    Noda, Hiroshi; Yokota, Makoto; Tatsumi, Shinji; Sugiyama, Shizuyuki

    2002-03-01

    Using the highly sensitive immunohistochemical staining method EnVision+, which employs a dextran polymer reagent for the secondary antibody, the detection of the ABH antigens was attempted in the oral squamous epithelium. This new technique uses monoclonal antibody as a primary antibody and it takes about three hours for staining. The time is much shorter than conventional absorption-elution testing or absorption-inhibition testing for the determination of ABO blood grouping. Secretor saliva samples were stained at strong intensity by the antibody, which corresponded to its blood group and anti-H. On the one hand, nonsecretor saliva samples were stained at strong intensity only by the antibody that corresponded to its blood group, and at weak intensity only by anti-H. Since human oral squamous epithelium antigens were stained specifically by this method, we can examine the ABO blood group of saliva samples and perform cytodiagnosis at the same time. Our research suggested that the EnVision+ Method is a useful technique for ABO blood grouping of saliva in forensic cases.

  11. Response of the flat cochlear epithelium to forced expression of Atoh1.

    PubMed

    Izumikawa, Masahiko; Batts, Shelley A; Miyazawa, Toru; Swiderski, Donald L; Raphael, Yehoash

    2008-06-01

    Following hair cell elimination in severely traumatized cochleae, differentiated supporting cells are often replaced by a simple epithelium with cuboidal or flat appearance. Atoh1 (previously Math1) is a basic helix-loop-helix transcription factor critical to hair cell differentiation during mammalian embryogenesis. Forced expression of Atoh1 in the differentiated supporting cell population can induce transdifferentiation leading to hair cell regeneration. Here, we examined the outcome of adenovirus mediated over-expression of Atoh1 in the non-sensory cells of the flat epithelium. We determined that seven days after unilateral elimination of hair cells with neomycin, differentiated supporting cells are absent, replaced by a flat epithelium. Nerve processes were also missing from the auditory epithelium, with the exception of infrequent looping nerve processes above the habenula perforata. We then inoculated an adenovirus vector with Atoh1 insert into the scala media of the deafened cochlea. The inoculation resulted in upregulation of Atoh1 in the flat epithelium. However, two months after the inoculation, Atoh1-treated ears did not exhibit clear signs of hair cell regeneration. Combined with previous data on induction of supporting cell to hair cell transdifferentiation by forced expression of Atoh1, these results suggest that the presence of differentiated supporting cells in the organ of Corti is necessary for transdifferentiation to occur.

  12. Postnatal epithelium and mesenchyme stem/progenitor cells in bioengineered amelogenesis and dentinogenesis.

    PubMed

    Jiang, Nan; Zhou, Jian; Chen, Mo; Schiff, Michael D; Lee, Chang H; Kong, Kimi; Embree, Mildred C; Zhou, Yanheng; Mao, Jeremy J

    2014-02-01

    Rodent incisors provide a classic model for studying epithelial-mesenchymal interactions in development. However, postnatal stem/progenitor cells in rodent incisors have not been exploited for tooth regeneration. Here, we characterized postnatal rat incisor epithelium and mesenchyme stem/progenitor cells and found that they formed enamel- and dentin-like tissues in vivo. Epithelium and mesenchyme cells were harvested separately from the apical region of postnatal 4-5 day rat incisors. Epithelial and mesenchymal phenotypes were confirmed by immunocytochemistry, CFU assay and/or multi-lineage differentiation. CK14+, Sox2+ and Lgr5+ epithelium stem cells from the cervical loop enhanced amelogenin and ameloblastin expression upon BMP4 or FGF3 stimulation, signifying their differentiation towards ameloblast-like cells, whereas mesenchyme stem/progenitor cells upon BMP4, BMP7 and Wnt3a treatment robustly expressed Dspp, a hallmark of odontoblastic differentiation. We then control-released microencapsulated BMP4, BMP7 and Wnt3a in transplants of epithelium and mesenchyme stem/progenitor cells in the renal capsule of athymic mice in vivo. Enamel and dentin-like tissues were generated in two integrated layers with specific expression of amelogenin and ameloblastin in the newly formed, de novo enamel-like tissue, and DSP in dentin-like tissue. These findings suggest that postnatal epithelium and mesenchyme stem/progenitor cells can be primed towards bioengineered tooth regeneration. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. A transcriptional time-course analysis of oral vs. aboral whole-body regeneration in the Sea anemone Nematostella vectensis.

    PubMed

    Schaffer, Amos A; Bazarsky, Michael; Levy, Karine; Chalifa-Caspi, Vered; Gat, Uri

    2016-09-07

    The ability of regeneration is essential for the homeostasis of all animals as it allows the repair and renewal of tissues and body parts upon normal turnover or injury. The extent of this ability varies greatly in different animals with the sea anemone Nematostella vectensis, a basal cnidarian model animal, displaying remarkable whole-body regeneration competence. In order to study this process in Nematostella we performed an RNA-Seq screen wherein we analyzed and compared the transcriptional response to bisection in the wound-proximal body parts undergoing oral (head) or aboral (tail) regeneration at several time points up to the initial restoration of the basic body shape. The transcriptional profiles of regeneration responsive genes were analyzed so as to define the temporal pattern of differential gene expression associated with the tissue-specific oral and aboral regeneration. The identified genes were characterized according to their GO (gene ontology) assignations revealing groups that were enriched in the regeneration process with particular attention to their affiliation to the major developmental signaling pathways. While some of the genes and gene groups thus analyzed were previously known to be active in regeneration, we have also revealed novel and surprising candidate genes such as cilia-associated genes that likely participate in this important developmental program. This work highlighted the main groups of genes which showed polarization upon regeneration, notably the proteinases, multiple transcription factors and the Wnt pathway genes that were highly represented, all displaying an intricate temporal balance between the two sides. In addition, the evolutionary comparison performed between regeneration in different animal model systems may reveal the basic mechanisms playing a role in this fascinating process.

  14. Alterations in Factors Involved in Differentiation and Barrier Function in the Epithelium in Oral and Genital Lichen Planus.

    PubMed

    Danielsson, Karin; Ebrahimi, Majid; Nylander, Elisabet; Wahlin, Ylva Britt; Nylander, Karin

    2017-02-08

    Lichen planus is a chronic recurrent inflammatory disease affecting both skin and mucosa, mainly in oral and/or genital regions. Keratinocytes go through a well-regulated process of proliferation and differentiation, alterations in which may result in defects in the protective epithelial barrier. Long-term barrier impairment might lead to chronic inflammation. In order to broaden our understanding of the differentiation process in mucosal lichen planus, we mapped the expression of 4 factors known to be involved in differentiation. Biopsies were collected from oral and genital lichen planus lesions and normal controls. Altered expression of all 4 factors in epithelium from lichen planus lesions was found, clearly indicating disturbed epithelial differentiation in lichen planus lesions.

  15. Fingernails Yield Clues to Limb Regeneration

    MedlinePlus

    ... in mice. The findings, published in the journal Nature, could eventually lead to the development of novel ... Nail Epithelium Couples Nail Growth to Digit Regeneration. Nature 2013 Jul 11;499(7457):228-32. doi: ...

  16. A microRNA-mRNA expression network during oral siphon regeneration in Ciona

    PubMed Central

    Spina, Elijah J.; Guzman, Elmer; Zhou, Hongjun; Kosik, Kenneth S.

    2017-01-01

    Here we present a parallel study of mRNA and microRNA expression during oral siphon (OS) regeneration in Ciona robusta, and the derived network of their interactions. In the process of identifying 248 mRNAs and 15 microRNAs as differentially expressed, we also identified 57 novel microRNAs, several of which are among the most highly differentially expressed. Analysis of functional categories identified enriched transcripts related to stress responses and apoptosis at the wound healing stage, signaling pathways including Wnt and TGFβ during early regrowth, and negative regulation of extracellular proteases in late stage regeneration. Consistent with the expression results, we found that inhibition of TGFβ signaling blocked OS regeneration. A correlation network was subsequently inferred for all predicted microRNA-mRNA target pairs expressed during regeneration. Network-based clustering associated transcripts into 22 non-overlapping groups, the functional analysis of which showed enrichment of stress response, signaling pathway and extracellular protease categories that could be related to specific microRNAs. Predicted targets of the miR-9 cluster suggest a role in regulating differentiation and the proliferative state of neural progenitors through regulation of the cytoskeleton and cell cycle. PMID:28432214

  17. Quantification and visualization of injury and regeneration to the ciliated epithelium using quantitative flow imaging and speckle variance optical coherence tomography (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Gamm, Ute A.; Huang, Brendan K.; Mis, Emily K.; Khokha, Mustafa K.; Choma, Michael A.

    2017-04-01

    Mucociliary flow is an important defense mechanism in the lung to remove inhaled pathogens and pollutants. A disruption of ciliary flow can lead to respiratory infections. Even though patients in the intensive care unit (ICU) either have or are very susceptible to respiratory infections, mucociliary flow is not well understood in the ICU setting. We recently demonstrated that hyperoxia, a consequence of administering supplemental oxygen to a patient in respiratory failure, can lead to a significant reduction of cilia-driven fluid flow in mouse trachea. There are other factors that are relevant to ICU medicine that can damage the ciliated tracheal epithelium, including inhalation injury and endotracheal tube placement. In this study we use two animal models, Xenopus embryo and ex vivo mouse trachea, to analyze flow defects in the injured ciliated epithelium. Injury is generated either mechanically with a scalpel or chemically by calcium chloride (CaCl2) shock, which efficiently but reversibly deciliates the embryo skin. In this study we used optical coherence tomography (OCT) and particle tracking velocimetry (PTV) to quantify cilia driven fluid flow over the surface of the Xenopus embryo. We additionally visualized damage to the ciliated epithelium by capturing 3D speckle variance images that highlight beating cilia. Mechanical injury disrupted cilia-driven fluid flow over the injured site, which led to a reduction in cilia-driven fluid flow over the whole surface of the embryo (n=7). The calcium chloride shock protocol proved to be highly effective in deciliating embryos (n=6). 3D speckle variance images visualized a loss of cilia and cilia-driven flow was halted immediately after application. We also applied CaCl2-shock to cultured ex vivo mouse trachea (n=8) and found, similarly to effects in Xenopus embryo, an extensive loss of cilia with resulting cessation of flow. We investigated the regeneration of the ciliated epithelium after an 8 day incubation period

  18. Handheld tunable focus confocal microscope utilizing a double-clad fiber coupler for in vivo imaging of oral epithelium

    NASA Astrophysics Data System (ADS)

    Olsovsky, Cory; Hinsdale, Taylor; Cuenca, Rodrigo; Cheng, Yi-Shing Lisa; Wright, John M.; Rees, Terry D.; Jo, Javier A.; Maitland, Kristen C.

    2017-05-01

    A reflectance confocal endomicroscope with double-clad fiber coupler and electrically tunable focus lens is applied to imaging of the oral mucosa. The instrument is designed to be lightweight and robust for clinical use. The tunable lens allows axial scanning through >250 μm in the epithelium when the probe tip is placed in contact with tissue. Images are acquired at 6.6 frames per second with a field of view diameter up to 850 μm. In vivo imaging of a wide range of normal sites in the oral cavity demonstrates the accessibility of the handheld probe. In vivo imaging of clinical lesions diagnosed as inflammation and dysplasia illustrates the ability of reflectance confocal endomicroscopy to image cellular changes associated with pathology.

  19. Spatially restricted dental regeneration drives pufferfish beak development

    PubMed Central

    Thiery, Alexandre P.; Shono, Takanori; Kurokawa, Daisuke; Britz, Ralf; Johanson, Zerina

    2017-01-01

    Vertebrate dentitions are extraordinarily diverse in both morphology and regenerative capacity. The teleost order Tetraodontiformes exhibits an exceptional array of novel dental morphologies, epitomized by constrained beak-like dentitions in several families, i.e., porcupinefishes, three-toothed pufferfishes, ocean sunfishes, and pufferfishes. Modification of tooth replacement within these groups leads to the progressive accumulation of tooth generations, underlying the structure of their beaks. We focus on the dentition of the pufferfish (Tetraodontidae) because of its distinct dental morphology. This complex dentition develops as a result of (i) a reduction in the number of tooth positions from seven to one per quadrant during the transition from first to second tooth generations and (ii) a dramatic shift in tooth morphogenesis following the development of the first-generation teeth, leading to the elongation of dental units along the jaw. Gene expression and 1,1′-Dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI) lineage tracing reveal a putative dental epithelial progenitor niche, suggesting a highly conserved mechanism for tooth regeneration despite the development of a unique dentition. MicroCT analysis reveals restricted labial openings in the beak, through which the dental epithelium (lamina) invades the cavity of the highly mineralized beak. Reduction in the number of replacement tooth positions coincides with the development of only four labial openings in the pufferfish beak, restricting connection of the oral epithelium to the dental cavity. Our data suggest the spatial restriction of dental regeneration, coupled with the unique extension of the replacement dental units throughout the jaw, are primary contributors to the evolution and development of this unique beak-like dentition. PMID:28507130

  20. Transcription Factors Runx1 to 3 Are Expressed in the Lacrimal Gland Epithelium and Are Involved in Regulation of Gland Morphogenesis and Regeneration

    PubMed Central

    Voronov, Dmitry; Gromova, Anastasia; Liu, Daren; Zoukhri, Driss; Medvinsky, Alexander; Meech, Robyn; Makarenkova, Helen P.

    2013-01-01

    Purpose. Lacrimal gland (LG) morphogenesis and repair are regulated by a complex interplay of intrinsic factors (e.g., transcription factors) and extrinsic signals (e.g., soluble growth/signaling factors). Many of these interconnections remain poorly characterized. Runt-related (Runx) factors belong to a small family of heterodimeric transcription factors known to regulate lineage-specific proliferation and differentiation of stem cells. The purpose of this study was to define the expression pattern and the role of Runx proteins in LG development and regeneration. Methods. Expression of epithelial-restricted transcription factors in murine LG was examined using immunostaining, qRT-PCR, and RT2Profiler PCR microarrays. The role of Runx transcription factors in LG morphogenesis was studied using siRNA and ex vivo LG cultures. Expression of Runx transcription factors during LG regeneration was assessed using in vivo model of LG regeneration. Results. We found that Runx factors are expressed in the epithelial compartment of the LG; in particular, Runx1 was restricted to the epithelium with highest level of expression in ductal and centroacinar cells. Downregulation of Runx1 to 3 expression using Runx-specific siRNAs abolished LG growth and branching and our data suggest that Runx1, 2, and 3 are partially redundant in LG development. In siRNA-treated LG, reduction of branching correlated with reduction of epithelial proliferation, as well as expression of cyclin D1 and the putative epithelial progenitor cell marker cytokeratin-5. Runx1, Runx3, and cytokeratin-5 expression increased significantly in regenerating LG and there was modest increase in Runx2 expression during LG differentiation. Conclusions. Runx1 and 2 are new markers of the LG epithelial lineage and Runx factors are important for normal LG morphogenesis and regeneration. PMID:23532528

  1. A microRNA-mRNA expression network during oral siphon regeneration in Ciona.

    PubMed

    Spina, Elijah J; Guzman, Elmer; Zhou, Hongjun; Kosik, Kenneth S; Smith, William C

    2017-05-15

    Here we present a parallel study of mRNA and microRNA expression during oral siphon (OS) regeneration in Ciona robusta , and the derived network of their interactions. In the process of identifying 248 mRNAs and 15 microRNAs as differentially expressed, we also identified 57 novel microRNAs, several of which are among the most highly differentially expressed. Analysis of functional categories identified enriched transcripts related to stress responses and apoptosis at the wound healing stage, signaling pathways including Wnt and TGFβ during early regrowth, and negative regulation of extracellular proteases in late stage regeneration. Consistent with the expression results, we found that inhibition of TGFβ signaling blocked OS regeneration. A correlation network was subsequently inferred for all predicted microRNA-mRNA target pairs expressed during regeneration. Network-based clustering associated transcripts into 22 non-overlapping groups, the functional analysis of which showed enrichment of stress response, signaling pathway and extracellular protease categories that could be related to specific microRNAs. Predicted targets of the miR-9 cluster suggest a role in regulating differentiation and the proliferative state of neural progenitors through regulation of the cytoskeleton and cell cycle. © 2017. Published by The Company of Biologists Ltd.

  2. Handheld tunable focus confocal microscope utilizing a double-clad fiber coupler for in vivo imaging of oral epithelium

    PubMed Central

    Olsovsky, Cory; Hinsdale, Taylor; Cuenca, Rodrigo; Cheng, Yi-Shing Lisa; Wright, John M.; Rees, Terry D.; Jo, Javier A.; Maitland, Kristen C.

    2017-01-01

    Abstract. A reflectance confocal endomicroscope with double-clad fiber coupler and electrically tunable focus lens is applied to imaging of the oral mucosa. The instrument is designed to be lightweight and robust for clinical use. The tunable lens allows axial scanning through >250  μm in the epithelium when the probe tip is placed in contact with tissue. Images are acquired at 6.6 frames per second with a field of view diameter up to 850  μm. In vivo imaging of a wide range of normal sites in the oral cavity demonstrates the accessibility of the handheld probe. In vivo imaging of clinical lesions diagnosed as inflammation and dysplasia illustrates the ability of reflectance confocal endomicroscopy to image cellular changes associated with pathology. PMID:28541447

  3. Endorsing cellular competitiveness in aberrant epithelium of oral submucous fibrosis progression: neighbourhood analysis of immunohistochemical attributes.

    PubMed

    Anura, Anji; Kazi, Anees; Pal, Mousumi; Paul, Ranjan Rashmi; Sengupta, Sanghamitra; Chatterjee, Jyotirmoy

    2018-04-23

    Epithelial abnormality during the transformation of oral submucous fibrosis (OSF) into oral squamous cell carcinoma has been well studied and documented. However, the differential contribution of atrophy and hyperplasia for malignant potentiality of OSF is yet to be resolved. Existing diagnostic conjectures lack precise diagnostic attributes which may be effectively resolved by substantiation of specific molecular pathology signatures. Present study elucidates existence of cellular competitiveness in OSF conditions using computer-assisted neighbourhood analysis in quantitative immunohistochemistry (IHC) framework. The concept of field cancerization was contributory in finding correspondence among neighbouring cells of epithelial layers with reference to differential expression of cardinal cancer-related genes [c-Myc (oncogene), p53 (tumour suppressor), and HIF-1α (hypoxia regulator)] which are known to be important sensors in recognizing cellular competitive interface. Our analyses indicate that different states of OSF condition may be associated with different forms of competitiveness within epithelial neighbouring cells which might be responsible to shape the present and future of the pre-malignant condition. Analytical findings indicated association of atrophic epithelium with stress-driven competitive environment having low c-Myc, high-p53, and stable HIF-1α (the looser cells) which undergo apoptosis. Whereas, the cells with high c-Myc + (winner cells) give rise to hyperplastic epithelium via possible mutation in p53. The epithelial dysplasia plausibly occurs due to clonal expansion of c-Myc and p53 positive supercompetitor cells. Present study proposes quantitative IHC along with neighbourhood analysis which might help us to dig deeper on to the interaction among epithelial cell population to provide a better understanding of field cancerization and malignant transformation of pre-malignancy.

  4. Quantification and visualization of injury and regeneration in the developing ciliated epithelium using quantitative flow imaging and speckle variance optical coherence tomography (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Gamm, Ute A.; Huang, Brendan K.; Mis, Emily K.; Khokha, Mustafa K.; Choma, Michael A.

    2017-02-01

    investigated the regeneration of the ciliated epithelium after an 8 day incubation period, and found that cilia had regrown and flow was completely restored. In conclusion, OCT is a valuable tool to visualize injury of the ciliated epithelium and to quantify reduction of generated flow. This method allows for systematic investigation of focal and diffuse injury of the ciliated epithelium and the assessment of mechanisms to compensate for loss of flow.

  5. Neurotrophic regulation of epidermal dedifferentiation during wound healing and limb regeneration in the axolotl (Ambystoma mexicanum).

    PubMed

    Satoh, A; Graham, G M C; Bryant, S V; Gardiner, D M

    2008-07-15

    Adult urodeles (salamanders) are unique in their ability to regenerate complex organs perfectly. The recently developed Accessory Limb Model (ALM) in the axolotl provides an opportunity to identify and characterize the essential signaling events that control the early steps in limb regeneration. The ALM demonstrates that limb regeneration progresses in a stepwise fashion that is dependent on signals from the wound epidermis, nerves and dermal fibroblasts from opposite sides of the limb. When all the signals are present, a limb is formed de novo. The ALM thus provides an opportunity to identify and characterize the signaling pathways that control blastema morphogenesis and limb regeneration. In the present study, we have utilized the ALM to identity the buttonhead-like zinc-finger transcription factor, Sp9, as being involved in the formation of the regeneration epithelium. Sp9 expression is induced in basal keratinocytes of the apical blastema epithelium in a pattern that is comparable to its expression in developing limb buds, and it thus is an important marker for dedifferentiation of the epidermis. Induction of Sp9 expression is nerve-dependent, and we have identified KGF as an endogenous nerve factor that induces expression of Sp9 in the regeneration epithelium.

  6. Dkk2/Frzb in the dermal papillae regulates feather regeneration

    PubMed Central

    Chu, Qiqi; Cai, Linyan; Fu, Yu; Chen, Xi; Yan, Zhipeng; Lin, Xiang; Zhou, Guixuan; Han, Hao; Widelitz, Randall B.; Chuong, Cheng-ming; Wu, Wei; Yue, Zhicao

    2015-01-01

    Avian feathers have robust growth and regeneration capability. To evaluate the contribution of signaling molecules and pathways in these processes, we profiled gene expression in the feather follicle using an absolute quantification approach. We identified hundreds of genes that mark specific components of the feather follicle: the dermal papillae (DP) which controls feather regeneration and axis formation, the pulp mesenchyme (Pp) which is derived from DP cells and nourishes the feather follicle, and the ramogenic zone epithelium (Erz) where a feather starts to branch. The feather DP is enriched in BMP/TGF-β signaling molecules and inhibitors for Wnt signaling including Dkk2/Frzb. Wnt ligands are mainly expressed in the feather epithelium and pulp. We find that while Wnt signaling is required for the maintenance of DP marker gene expression and feather regeneration, excessive Wnt signaling delays regeneration and reduces pulp formation. Manipulating Dkk2/Frzb expression by lentiviral-mediated overexpression, shRNA-knockdown, or by antibody neutralization resulted in dual feather axes formation. Our results suggest that the Wnt signaling in the proximal feather follicle is fine-tuned to accommodate feather regeneration and axis formation. PMID:24463139

  7. Regeneration of the gut requires retinoic acid in the budding ascidian Polyandrocarpa misakiensis.

    PubMed

    Kaneko, Nagamoto; Katsuyama, You; Kawamura, Kazuo; Fujiwara, Shigeki

    2010-06-01

    The protochordate ascidian Polyandrocarpa misakiensis has a striking ability to regenerate. When the posterior half of the adult body is amputated, the anterior half completely loses the esophagus, stomach and intestine. These organs are reconstituted in a week. Histological observation revealed that the regeneration involves transdifferentiation of the atrial epithelium near the cut surface. The morphological features of the gut primordium were similar to those observed in the developing bud of this species. Inhibitors of the synthesis of retinoic acid (RA) suppressed the formation of the gut. 13-cis RA rescued the regenerates from the inhibitor-induced hypoplasia. These results suggest that RA is required for the regeneration of the gut. A gene encoding the RA receptor (Pm-RAR) and its target gene, TRAMP, were expressed in and around the regenerating gut. Pm-RAR-specific and TRAMP-specific double-stranded RNA molecules inhibited the regeneration of the gut, indicating that the RA signal is mediated at least in part by Pm-RAR and TRAMP. These results suggested that RA triggers the transdifferentiation of the atrial epithelium into the gut in regenerating animals, as it does during asexual reproduction.

  8. Clinical outcomes after the use of complete autologous oral mucosa equivalents: preliminary cases.

    PubMed

    Peña, Ignacio; Junquera, Luis Manuel; Llorente, Santiago; de Villalaín, Lucas; de Vicente, Juan Carlos; Llames, Sara

    2012-05-01

    Previously, we reported how to obtain complete autologous oral mucosa equivalents (CAOMEs) composed of an autologous plasma scaffold and fibroblasts together with immature keratinocytes able to build an oral epithelium with a structure similar to that of the oral mucosa. In this study, we present the clinical outcomes after applying our CAOMEs as grafts. Four patients who needed a CAOME to restore a defect of oral mucosa were selected. Two of the patients suffered from ankyloglossia, and the other 2 required a restoration of the keratinized gum of the alveolar rim. To assess the outcomes, the scale designed by Ewers et al. was used. Clinical and functional improvements were achieved in the patients with ankyloglossia. In cases of gum restoration, the mucosa was regenerated and a prosthetic restoration with implants was achieved. The results obtained points to the potential use of CAOME in intraoral lining. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. A Curriculum Vitae of Teeth: Evolution, Generation, Regeneration

    PubMed Central

    Koussoulakou, Despina S.; Margaritis, Lukas H.; Koussoulakos, Stauros L.

    2009-01-01

    The ancestor of recent vertebrate teeth was a tooth-like structure on the outer body surface of jawless fishes. Over the course of 500,000,000 years of evolution, many of those structures migrated into the mouth cavity. In addition, the total number of teeth per dentition generally decreased and teeth morphological complexity increased. Teeth form mainly on the jaws within the mouth cavity through mutual, delicate interactions between dental epithelium and oral ectomesenchyme. These interactions involve spatially restricted expression of several, teeth-related genes and the secretion of various transcription and signaling factors. Congenital disturbances in tooth formation, acquired dental diseases and odontogenic tumors affect millions of people and rank human oral pathology as the second most frequent clinical problem. On the basis of substantial experimental evidence and advances in bioengineering, many scientists strongly believe that a deep knowledge of the evolutionary relationships and the cellular and molecular mechanisms regulating the morphogenesis of a given tooth in its natural position, in vivo, will be useful in the near future to prevent and treat teeth pathologies and malformations and for in vitro and in vivo teeth tissue regeneration. PMID:19266065

  10. Platelet-rich plasma (PRP) in dental and oral surgery: from the wound healing to bone regeneration

    PubMed Central

    2013-01-01

    Platelet-rich plasma (PRP) is a new approach to tissue regeneration and it is becoming a valuable adjunct to promote healing in many procedures in dental and oral surgery, especially in aging patients. PRP derives from the centrifugation of the patient's own blood and it contains growth factors that influence wound healing, thereby playing an important role in tissue repairing mechanisms. The use of PRP in surgical practice could have beneficial outcomes, reducing bleeding and enhancing soft tissue healing and bone regeneration. Studies conducted on humans have yielded promising results regarding the application of PRP to many dental and oral surgical procedures (i.e. tooth extractions, periodontal surgery, implant surgery). The use of PRP has also been proposed in the management of bisphosphonate-related osteonecrosis of the jaw (BRONJ) with the aim of enhancing wound healing and bone maturation. The aims of this narrative review are: i) to describe the different uses of PRP in dental surgery (tooth extractions and periodontal surgery) and oral surgery (soft tissues and bone tissue surgery, implant surgery and BRONJ surgery); and ii) to discuss its efficacy, efficiency and risk/benefit ratio. This review suggests that the use of PRP in the alveolar socket after tooth extractions is certainly capable of improving soft tissue healing and positively influencing bone regeneration but the latter effect seems to decrease a few days after the extraction. PRP has produced better results in periodontal therapy in association with other materials than when it is used alone. Promising results have also been obtained in implant surgery, when PRP was used in isolation as a coating material. The combination of necrotic bone curettage and PRP application seem to be encouraging for the treatment of refractory BRONJ, as it has proven successful outcomes with minimal invasivity. Since PRP is free from potential risks for patients, not difficult to obtain and use, it can be employed

  11. Platelet-rich plasma (PRP) in dental and oral surgery: from the wound healing to bone regeneration.

    PubMed

    Albanese, Antonino; Licata, Maria E; Polizzi, Bianca; Campisi, Giuseppina

    2013-06-13

    Platelet-rich plasma (PRP) is a new approach to tissue regeneration and it is becoming a valuable adjunct to promote healing in many procedures in dental and oral surgery, especially in aging patients. PRP derives from the centrifugation of the patient's own blood and it contains growth factors that influence wound healing, thereby playing an important role in tissue repairing mechanisms. The use of PRP in surgical practice could have beneficial outcomes, reducing bleeding and enhancing soft tissue healing and bone regeneration. Studies conducted on humans have yielded promising results regarding the application of PRP to many dental and oral surgical procedures (i.e. tooth extractions, periodontal surgery, implant surgery). The use of PRP has also been proposed in the management of bisphosphonate-related osteonecrosis of the jaw (BRONJ) with the aim of enhancing wound healing and bone maturation. The aims of this narrative review are: i) to describe the different uses of PRP in dental surgery (tooth extractions and periodontal surgery) and oral surgery (soft tissues and bone tissue surgery, implant surgery and BRONJ surgery); and ii) to discuss its efficacy, efficiency and risk/benefit ratio. This review suggests that the use of PRP in the alveolar socket after tooth extractions is certainly capable of improving soft tissue healing and positively influencing bone regeneration but the latter effect seems to decrease a few days after the extraction. PRP has produced better results in periodontal therapy in association with other materials than when it is used alone. Promising results have also been obtained in implant surgery, when PRP was used in isolation as a coating material. The combination of necrotic bone curettage and PRP application seem to be encouraging for the treatment of refractory BRONJ, as it has proven successful outcomes with minimal invasivity. Since PRP is free from potential risks for patients, not difficult to obtain and use, it can be employed

  12. Mex3a marks slow-proliferating multilineage progenitors of the intestinal epithelium

    PubMed Central

    Barriga, Francisco M.; Montagni, Elisa; Mana, Miyeko; Guillaumet-Adkins, Amy; Hernando-Momblona, Xavier; Sevillano, Marta; Rodriguez-Esteban, Gustavo; Mendez-Lago, Maria; Buczacki, Simon J. A.; Gut, Ivo; Gut, Marta; Winton, Douglas J.; Yilmaz, Omer; Stephan-Otto, Camille; Hein, Holger; Batlle, Eduard

    2017-01-01

    SUMMARY The intestinal epithelium is continuously regenerated by highly proliferative Lgr5+ intestinal stem cells (ISCs). The existence of a population of quiescent ISCs has been suggested yet its identity and features remain controversial. Here we describe that the expression of the RNA-binding protein Mex3a labels a subpopulation of Lgr5+ cells that divide less frequently and contribute to regenerate all intestinal lineages with slow kinetics. Single cell transcriptomic analysis revealed two classes of Lgr5-high cells, one of them defined by the Mex3a-expression program and by low levels of proliferation genes. Lineage tracing experiments show that large fraction of Mex3a+ cell population is continuously recalled into the rapidly dividing self-renewing ISC pool in homeostatic conditions. Chemotherapy and radiation target preferentially rapidly dividing Lgr5+ cells but spare the Mex3a-high/Lgr5+ population, which helps sustain the renewal of the intestinal epithelium during treatment. PMID:28285904

  13. Differential Transmission of HIV Traversing Fetal Oral/Intestinal Epithelia and Adult Oral Epithelia

    PubMed Central

    Herrera, Rossana; Veluppillai, Piri; Greenspan, Deborah; Soros, Vanessa; Greene, Warner C.; Levy, Jay A.; Palefsky, Joel M.

    2012-01-01

    While human immunodeficiency virus (HIV) transmission through the adult oral route is rare, mother-to-child transmission (MTCT) through the neonatal/infant oral and/or gastrointestinal route is common. To study the mechanisms of cell-free and cell-associated HIV transmission across adult oral and neonatal/infant oral/intestinal epithelia, we established ex vivo organ tissue model systems of adult and fetal origin. Given the similarity of neonatal and fetal oral epithelia with respect to epithelial stratification and density of HIV-susceptible immune cells, we used fetal oral the epithelium as a model for neonatal/infant oral epithelium. We found that cell-free HIV traversed fetal oral and intestinal epithelia and infected HIV-susceptible CD4+ T lymphocytes, Langerhans/dendritic cells, and macrophages. To study the penetration of cell-associated virus into fetal oral and intestinal epithelia, HIV-infected macrophages and lymphocytes were added to the surfaces of fetal oral and intestinal epithelia. HIV-infected macrophages, but not lymphocytes, transmigrated across fetal oral epithelia. HIV-infected macrophages and, to a lesser extent, lymphocytes transmigrated across fetal intestinal epithelia. In contrast to the fetal oral/intestinal epithelia, cell-free HIV transmigration through adult oral epithelia was inefficient and virions did not infect intraepithelial and subepithelial HIV-susceptible cells. In addition, HIV-infected macrophages and lymphocytes did not transmigrate through intact adult oral epithelia. Transmigration of cell-free and cell-associated HIV across the fetal oral/intestinal mucosal epithelium may serve as an initial mechanism for HIV MTCT. PMID:22205732

  14. Corneal nerve regeneration. Correlation between morphology and restoration of sensitivity.

    PubMed

    de Leeuw, A M; Chan, K Y

    1989-09-01

    Corneal nerve regeneration was determined in albino rabbits after deepithelialization of the cornea using heptanol. Regeneration was monitored up to 10 weeks by measuring corneal tactile sensitivity using an esthesiometer and by examining stromal and intraepithelial nerve patterns following gold chloride impregnation and acetylcholinesterase staining. Tactile sensitivity was much reduced, possibly absent, up to 2 weeks after wounding. From 2.5-4 weeks, sensitivity recovered rapidly to 60% of prewounding levels and remained unchanged thereafter. In control corneas, a distinct orientation of the basoepithelial leashes towards the nasal-most limbus was observed in the central two-thirds of the cornea. Three days after wounding, neurites that were oriented radially towards the wound center extended into the periphery of the wound area from just beyond the wound margin. At 1 week, regenerating axons were present as single neurites and in the form of modified leashes, mainly at the periphery of the wound area but also more towards the center. At 3 weeks, neurites, regenerated leashes and networks of terminals with terminal endings were found throughout the regenerated epithelium. Regional changes in the orientation of the regenerated leashes were observed also. No further change in the intraepithelial nerve pattern was detectable thereafter up to 10 weeks after wounding. It was concluded that partial restoration of tactile sensitivity following deepithelialization of the cornea is a function of the establishment of a near-normal nerve pattern in the regenerated epithelium and is correlated with the subnormal neural density observed in a previous study.

  15. Maintenance of sweat glands by stem cells located in the acral epithelium.

    PubMed

    Ohe, Shuichi; Tanaka, Toshihiro; Yanai, Hirotsugu; Komai, Yoshihiro; Omachi, Taichi; Kanno, Shohei; Tanaka, Kiyomichi; Ishigaki, Kazuhiko; Saiga, Kazuho; Nakamura, Naohiro; Ohsugi, Haruyuki; Tokuyama, Yoko; Atsumi, Naho; Hisha, Hiroko; Yoshida, Naoko; Kumano, Keiki; Yamazaki, Fumikazu; Okamoto, Hiroyuki; Ueno, Hiroo

    2015-10-23

    The skin is responsible for a variety of physiological functions and is critical for wound healing and repair. Therefore, the regenerative capacity of the skin is important. However, stem cells responsible for maintaining the acral epithelium had not previously been identified. In this study, we identified the specific stem cells in the acral epithelium that participate in the long-term maintenance of sweat glands, ducts, and interadnexal epidermis and that facilitate the regeneration of these structures following injury. Lgr6-positive cells and Bmi1-positive cells were found to function as long-term multipotent stem cells that maintained the entire eccrine unit and the interadnexal epidermis. However, while Lgr6-positive cells were rapidly cycled and constantly supplied differentiated cells, Bmi1-positive cells were slow to cycle and occasionally entered the cell cycle under physiological conditions. Upon irradiation-induced injury, Bmi1-positive cells rapidly proliferated and regenerated injured epithelial tissue. Therefore, Bmi1-positive stem cells served as reservoir stem cells. Lgr5-positive cells were rapidly cycled and maintained only sweat glands; therefore, we concluded that these cells functioned as lineage-restricted progenitors. Taken together, our data demonstrated the identification of stem cells that maintained the entire acral epithelium and supported the different roles of three cellular classes. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Assessment of nuclear abnormalities in exfoliated cells from the oral epithelium of mobile phone users.

    PubMed

    Souza, Leonardo da Cunha Menezes; Cerqueira, Eneida de Moraes Marcílio; Meireles, José Roberto Cardoso

    2014-06-01

    Transmission and reception of mobile telephony signals take place through electromagnetic wave radiation, or electromagnetic radiofrequency fields, between the mobile terminal and the radio base station. Based on reports in the literature on adverse effects from exposure to this type of radiation, the objective of this study was to evaluate the genotoxic and cytotoxic potential of such exposure, by means of the micronucleus test on exfoliated cells from the oral epithelium. The sample included 45 individuals distributed in 3 groups according to the amount of time in hours per week (t) spent using mobile phones: group I, t > 5 h; group II, t > 1 h and ≤ 5 h; and group III, t ≤ 1 h. Cells from the oral mucosa were analyzed to assess the numbers of micronuclei, broken egg structures and degenerative nuclear abnormalities indicative of apoptosis (condensed chromatin, karyorrhexis and pyknosis) or necrosis (karyolysis in addition to these changes). The occurrences of micronuclei and degenerative nuclear abnormalities did not differ between the groups, but the number of broken egg (structures that may be associated with gene amplification) was significantly greater in the individuals in group I (p < 0.05).

  17. Maintenance of sweat glands by stem cells located in the acral epithelium

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ohe, Shuichi; Department of Dermatology, Kansai Medical University, Osaka 573-1010; Tanaka, Toshihiro

    The skin is responsible for a variety of physiological functions and is critical for wound healing and repair. Therefore, the regenerative capacity of the skin is important. However, stem cells responsible for maintaining the acral epithelium had not previously been identified. In this study, we identified the specific stem cells in the acral epithelium that participate in the long-term maintenance of sweat glands, ducts, and interadnexal epidermis and that facilitate the regeneration of these structures following injury. Lgr6-positive cells and Bmi1-positive cells were found to function as long-term multipotent stem cells that maintained the entire eccrine unit and the interadnexalmore » epidermis. However, while Lgr6-positive cells were rapidly cycled and constantly supplied differentiated cells, Bmi1-positive cells were slow to cycle and occasionally entered the cell cycle under physiological conditions. Upon irradiation-induced injury, Bmi1-positive cells rapidly proliferated and regenerated injured epithelial tissue. Therefore, Bmi1-positive stem cells served as reservoir stem cells. Lgr5-positive cells were rapidly cycled and maintained only sweat glands; therefore, we concluded that these cells functioned as lineage-restricted progenitors. Taken together, our data demonstrated the identification of stem cells that maintained the entire acral epithelium and supported the different roles of three cellular classes. - Highlights: • The acral epithelium have two types of stem cells. • Lgr6-positive cells are rapid-cycling, short-term stem cells. • Bmi1-positive cells are slow-cycling stem cells that act as reserver stem cells. • Lgr5 may be a useful sweat gland marker in mice.« less

  18. A histopathologic investigation on the effects of electrical stimulation on periodontal tissue regeneration in experimental bony defects in dogs.

    PubMed

    Kaynak, Deniz; Meffert, Roland; Günhan, Meral; Günhan, Omer

    2005-12-01

    One endpoint of periodontal therapy is to regenerate the structure lost due to periodontal disease. In the periodontium, gingival epithelium is regenerated by oral epithelium. Underlying connective tissue, periodontal ligament, bone, and cementum are derived from connective tissue. Primitive connective tissue cells may develop into osteoblasts and cementoblasts, which form bone and cementum. Several procedural advances may support these regenerations; however, the regeneration of alveolar bone does not always occur. Therefore, bone stimulating factors are a main topic for periodontal reconstructive research. The present study was designed to examine histopathologically whether the application of an electrical field could demonstrate enhanced alveolar and cementum regeneration and modify tissue factors. Seven beagle dogs were used for this experiment. Mandibular left and right sides served as control and experimental sides, respectively, and 4-walled intrabony defects were created bilaterally between the third and fourth premolars. The experimental side was treated with a capacitively coupled electrical field (CCEF) (sinusoidal wave, 60 kHz, and 5 V peak-to-peak), applied for 14 hours per day. The following measurements were performed on the microphotographs: 1) the distance from the cemento-enamel junction to the apical notch (CEJ-AN) and from the crest of newly formed bone (alveolar ridge) to the apical notch (AR-AN); 2) the thickness of new cementum in the apical notch region; and 3) the length of junctional epithelium. The following histopathologic parameters were assessed by a semiquantitative subjective method: 1) inflammatory cell infiltration (ICI); 2) cellular activity of the periodontal ligament; 3) number and morphology of osteoclasts; 4) resorption lacunae; and 5) osteoblastic activity. The results showed that the quantity of new bone fill and the mean value of the thickness of the cementum were significantly higher for the experimental side (P < 0

  19. Quantification of oral palatine Langerhans cells in HIV/AIDS associated oral Kaposi sarcoma with and without oral candidiasis.

    PubMed

    Jivan, Vibha; Meer, Shabnum

    2016-01-01

    Langerhans cells (LCs) are effective antigen-presenting cells that function as "custodians" of mucosa, modifying the immune system to pathogen entry, and tolerance to self-antigen and commensal microbes. A reduction in number of LCs in human immunodeficiency virus (HIV)-positive individuals may predispose to local mucosal infections. To quantitatively determine the number of oral mucosal LCs in HIV/acquired immunodeficiency syndrome HIV/acquired immunodeficiency syndrome (AIDS) associated oral Kaposi sarcoma (KS) with/without oral candidiasis (OC) and to define in situ interrelationships between the cells, OC, and HIV infection. Thirty-two periodic acid-Schiff. (PAS) stained histologic sections of palatal HIV/AIDS associated KS with intact oral epithelium were examined for Candida and divided into two groups: . (1) KS coinfected with Candida and. (2) KS noninfected with Candida. Sections were immunohistochemically stained with CD1a. The standard length of surface epithelium was measured and number of positively stained LCs counted per unit length. Control cases included non-Candida infected palatal mucosa overlying pleomorphic adenoma. (PA) and oral mucosa infected with Candida in otherwise healthy individuals. LC number per unit length of surface epithelium was statistically significantly greatest in uninfected PA mucosa and lowest in KS coinfected with Candida (P = 0.0001). A statistically significant difference was also noted between uninfected PA mucosa and non-Candida infected KS (P = 0.0014), in KS coinfected with Candida and non-infected KS (P = 0.0035), between OC and PA (P = 0.0001), and OC and KS coinfected with Candida (P = 0.0247). LC numbers are significantly reduced in oral tissues of HIV/AIDS infected patients by Candida infection when compared to oral tissues without.

  20. Clinical Application of Mesenchymal Stem Cells and Novel Supportive Therapies for Oral Bone Regeneration

    PubMed Central

    O'Valle, Francisco; Lanis, Alejandro; Dohan Ehrenfest, David M.; Wang, Hom-Lay; Galindo-Moreno, Pablo

    2015-01-01

    Bone regeneration is often needed prior to dental implant treatment due to the lack of adequate quantity and quality of the bone after infectious diseases, trauma, tumor, or congenital conditions. In these situations, cell transplantation technologies may help to overcome the limitations of autografts, xenografts, allografts, and alloplastic materials. A database search was conducted to include human clinical trials (randomized or controlled) and case reports/series describing the clinical use of mesenchymal stem cells (MSCs) in the oral cavity for bone regeneration only specifically excluding periodontal regeneration. Additionally, novel advances in related technologies are also described. 190 records were identified. 51 articles were selected for full-text assessment, and only 28 met the inclusion criteria: 9 case series, 10 case reports, and 9 randomized controlled clinical trials. Collectively, they evaluate the use of MSCs in a total of 290 patients in 342 interventions. The current published literature is very diverse in methodology and measurement of outcomes. Moreover, the clinical significance is limited. Therefore, the use of these techniques should be further studied in more challenging clinical scenarios with well-designed and standardized RCTs, potentially in combination with new scaffolding techniques and bioactive molecules to improve the final outcomes. PMID:26064899

  1. Focal Adhesion Kinase Is Required for Intestinal Regeneration and Tumorigenesis Downstream of Wnt/c-Myc Signaling

    PubMed Central

    Ashton, Gabrielle H.; Morton, Jennifer P.; Myant, Kevin; Phesse, Toby J.; Ridgway, Rachel A.; Marsh, Victoria; Wilkins, Julie A.; Athineos, Dimitris; Muncan, Vanesa; Kemp, Richard; Neufeld, Kristi; Clevers, Hans; Brunton, Valerie; Winton, Douglas J.; Wang, Xiaoyan; Sears, Rosalie C.; Clarke, Alan R.; Frame, Margaret C.; Sansom, Owen J.

    2012-01-01

    SUMMARY The intestinal epithelium has a remarkable capacity to regenerate after injury and DNA damage. Here, we show that the integrin effector protein Focal Adhesion Kinase (FAK) is dispensable for normal intestinal homeostasis and DNA damage signaling, but is essential for intestinal regeneration following DNA damage. Given Wnt/c-Myc signaling is activated following intestinal regeneration, we investigated the functional importance of FAK following deletion of the Apc tumor suppressor protein within the intestinal epithelium. Following Apc loss, FAK expression increased in a c-Myc-dependent manner. Codeletion of Apc and Fak strongly reduced proliferation normally induced following Apc loss, and this was associated with reduced levels of phospho-Akt and suppression of intestinal tumorigenesis in Apc heterozygous mice. Thus, FAK is required downstream of Wnt Signaling, for Akt/mTOR activation, intestinal regeneration, and tumorigenesis. Importantly, this work suggests that FAK inhibitors may suppress tumorigenesis in patients at high risk of developing colorectal cancer. PMID:20708588

  2. Analysis of in situ proliferative activity in oral gingival epithelium in patients with xerostomia.

    PubMed

    Celenligil-Nazliel, Haviye; Palali, Ali; Ayhan, Ayşe; Ruacan, Sevket

    2003-02-01

    Sjögren's syndrome is an autoimmune disease characterized by xerostomia and keratoconjunctivitis sicca. The relationship between xero-stomia and proliferative activity in human gingival epithelium is not known. Proliferating cell nuclear antigen (PCNA) is a nuclear protein associated with the cell cycle. Nuclear PCNA immunoreactivity is found in the proliferative compartment of normal tissues. The aims of this study were to evaluate PCNA expression in oral gingival epithelium of healthy and inflamed gingiva obtained from patients with Sjögren's syndrome, and to compare the results to age- and gender-matched subjects with normal salivary function. Eighteen Sjögren's syndrome patients and 28 controls (14 with chronic periodontitis and 14 with no clinical evidence of periodontal disease) were included in the study. Biopsies were obtained from both inflamed and healthy gingiva. The expression of PCNA was evaluated in formalin-fixed, paraffin-embedded gingival samples using an immunoperoxidase technique and PC10 monoclonal antibody to PCNA. PCNA expression was observed both in the basal and suprabasal layers, and was found to be more prominent in the suprabasal layers. Proliferative index (PI) in inflamed gingiva was significantly lower in the Sjögren's syndrome group. However, no significant difference was observed between the study and control groups with respect to PI in healthy gingiva. In both groups, PI was found to be increased due to inflammation. Our data indicate that proliferative activity is observed in the suprabasal layers and, less frequently, in the basal layer. Inflammation caused increased proliferative activity. However, this positive effect of inflammation on epithelial cell proliferation decreased significantly with a lack of saliva. Therefore, it appears that saliva-derived biological mediators may also contribute to increased proliferative activity observed during inflammation.

  3. Examination of the reticular epithelium of the bovine pharyngeal tonsil

    USDA-ARS?s Scientific Manuscript database

    The nasopharyngeal tonsil (adenoid), located at the posterior of the nasopharynx is ideally positioned to sample antigens entering through the nasal cavity or oral cavity. Entering antigens will first contact tonsilar epithelium. To better understand the cellular composition of this important epithe...

  4. Poly(amido amine) dendrimers in oral delivery.

    PubMed

    Yellepeddi, Venkata K; Ghandehari, Hamidreza

    2016-01-01

    Poly(amidoamine) (PAMAM) dendrimers have been extensively investigated for oral delivery applications due to their ability to translocate across the gastrointestinal epithelium. In this Review, we highlight recent advances in the evaluation of PAMAM dendrimers as oral drug delivery carriers. Specifically, toxicity, mechanisms of transepithelial transport, models of the intestinal epithelial barrier including isolated human intestinal tissue model, detection of dendrimers, and surface modification are discussed. We also highlight evaluation of various PAMAM dendrimer-drug conjugates for their ability to transport across gastrointestinal epithelium for improved oral bioavailability. In addition, current challenges and future trends for clinical translation of PAMAM dendrimers as carriers for oral delivery are discussed.

  5. Poly(amido amine) dendrimers in oral delivery

    PubMed Central

    Yellepeddi, Venkata K.; Ghandehari, Hamidreza

    2016-01-01

    ABSTRACT Poly(amidoamine) (PAMAM) dendrimers have been extensively investigated for oral delivery applications due to their ability to translocate across the gastrointestinal epithelium. In this Review, we highlight recent advances in the evaluation of PAMAM dendrimers as oral drug delivery carriers. Specifically, toxicity, mechanisms of transepithelial transport, models of the intestinal epithelial barrier including isolated human intestinal tissue model, detection of dendrimers, and surface modification are discussed. We also highlight evaluation of various PAMAM dendrimer-drug conjugates for their ability to transport across gastrointestinal epithelium for improved oral bioavailability. In addition, current challenges and future trends for clinical translation of PAMAM dendrimers as carriers for oral delivery are discussed. PMID:27358755

  6. Oral Mucosa Harbors a High Frequency of Endothelial Cells: A Novel Postnatal Cell Source for Angiogenic Regeneration.

    PubMed

    Zhou, Jian; Rogers, Jason H; Lee, Scott H; Sun, DongMing; Yao, Hai; Mao, Jeremy J; Kong, Kimi Y

    2017-01-15

    Endothelial progenitor cells/endothelial cells (EPCs/ECs) have great potential to treat pathological conditions such as cardiac infarction, muscle ischemia, and bone fractures, but isolation of EPC/ECs from existing cell sources is challenging due to their low EC frequency. We have isolated endothelial progenitor (EP)-like cells from rat oral mucosa and characterized their yield, immunophenotype, growth, and in vivo angiogenic potential. The frequency of EP-like cells derived from oral mucosa is thousands of folds higher than EPCs derived from donor-match bone marrow samples. EP-like cells from oral mucosa were positive for EC markers CD31, VE-Cadherin, and VEGFR2. Oral mucosa-derived EP-like cells displayed robust uptake of acetylated low-density lipoprotein and formed stable capillary networks in Matrigel. Subcutaneously implanted oral mucosa-derived EP-like cells anastomosed with host blood vessels, implicating their ability to elicit angiogenesis. Similar to endothelial colony-forming cells, EP-like cells from oral mucosa have a significantly higher proliferative rate than human umbilical vein endothelial cells. These findings identify a putative EPC source that is easily accessible in the oral cavity, potentially from discarded tissue specimens, and yet with robust yield and potency for angiogenesis in tissue and organ regeneration.

  7. Oral Mucosa Harbors a High Frequency of Endothelial Cells: A Novel Postnatal Cell Source for Angiogenic Regeneration

    PubMed Central

    Zhou, Jian; Rogers, Jason H.; Lee, Scott H.; Sun, DongMing; Yao, Hai; Mao, Jeremy J.

    2017-01-01

    Endothelial progenitor cells/endothelial cells (EPCs/ECs) have great potential to treat pathological conditions such as cardiac infarction, muscle ischemia, and bone fractures, but isolation of EPC/ECs from existing cell sources is challenging due to their low EC frequency. We have isolated endothelial progenitor (EP)-like cells from rat oral mucosa and characterized their yield, immunophenotype, growth, and in vivo angiogenic potential. The frequency of EP-like cells derived from oral mucosa is thousands of folds higher than EPCs derived from donor-match bone marrow samples. EP-like cells from oral mucosa were positive for EC markers CD31, VE-Cadherin, and VEGFR2. Oral mucosa-derived EP-like cells displayed robust uptake of acetylated low-density lipoprotein and formed stable capillary networks in Matrigel. Subcutaneously implanted oral mucosa-derived EP-like cells anastomosed with host blood vessels, implicating their ability to elicit angiogenesis. Similar to endothelial colony-forming cells, EP-like cells from oral mucosa have a significantly higher proliferative rate than human umbilical vein endothelial cells. These findings identify a putative EPC source that is easily accessible in the oral cavity, potentially from discarded tissue specimens, and yet with robust yield and potency for angiogenesis in tissue and organ regeneration. PMID:27832737

  8. Expression and distribution of the intermediate filament protein nestin and other stem cell related molecules in the human olfactory epithelium.

    PubMed

    Minovi, Amir; Witt, Martin; Prescher, Andreas; Gudziol, Volker; Dazert, Stefan; Hatt, Hanns; Benecke, Heike

    2010-02-01

    The olfactory epithelium (OE) is unique in regenerating throughout life and thus is an attractive target for examining neurogenesis. The nestin protein was shown to be expressed in the OE of rodents and is suggested to be essentially involved in the process of regeneration. Here we report the expression and distribution of nestin in the human OE at RNA and protein level. Moreover, we analysed the expression profiles in dependence on age and olfactory capacity. After sinus surgery, biopsies were taken from the olfactory epithelium of 16 patients aged 20-80 years with documented differences in their olfactory function. Our studies revealed that nestin is constantly detectable in the apical protuberances of sustentacular cells within the human OE of healthy adults. Its expression is not dependent on age, but rather appears to be related to the olfactory function, as a comparison with specimens obtained from patients suffering either from persistent anosmia or hyposmia suggests. Particularly, in the course of dystrophy, often accompanied with impaired olfaction, nestin expression was occasionally decreased. Contrarily, the expression of the p75-NGFR protein, a marker for human OE basal cells, was not altered, indicating that at least in the tested samples olfactory impairment is not connected with abnormalities at the basal cell level. These observations emphasize an essential role of nestin for the process of regeneration, and also highlight this factor as a candidate marker for sustentacular cells in the human olfactory epithelium.

  9. IL-17 and VEGF are necessary for efficient corneal nerve regeneration

    USDA-ARS?s Scientific Manuscript database

    The contribution of acute inflammation to sensory nerve regeneration was investigated in the murine cornea using a model of corneal abrasion that removes the stratified epithelium and subbasal nerve plexus. Abrasion induced accumulation of IL-17(+) CCR6(+) yo T cells, neutrophils, and platelets in t...

  10. Epithelium

    MedlinePlus

    The term "epithelium" refers to layers of cells that line hollow organs and glands. It is also those cells that make ... Kierszenbaum AL, Tres LL. Epithelium. In: Kierszenbaum AL, Tres LL, ... to Pathology . 4th ed. Philadelphia, PA: Elsevier Saunders; ...

  11. Fine structure of the midgut epithelium in the millipede Telodeinopus aoutii (Myriapoda, Diplopoda) with special emphasis on epithelial regeneration.

    PubMed

    Rost-Roszkowska, M M; Kszuk-Jendrysik, M; Marchewka, A; Poprawa, I

    2018-01-01

    The midgut of millipedes is composed of a simple epithelium that rests on a basal lamina, which is surrounded by visceral muscles and hepatic cells. As the material for our studies, we chose Telodeinopus aoutii (Demange, 1971) (Kenyan millipede) (Diplopoda, Spirostreptida), which lives in the rain forests of Central Africa. This commonly reared species is easy to obtain from local breeders and easy to culture in the laboratory. During our studies, we used transmission and scanning electron microscopes and light and fluorescent microscopes. The midgut epithelium of the species examined here shares similarities to the structure of the millipedes analyzed to date. The midgut epithelium is composed of three types of cells-digestive, secretory, and regenerative cells. Evidence of three types of secretion have been observed in the midgut epithelium: merocrine, apocrine, and microapocrine secretion. The regenerative cells of the midgut epithelium in millipedes fulfill the role of midgut stem cells because of their main functions: self-renewal (the ability to divide mitotically and to maintain in an undifferentiated state) and potency (ability to differentiate into digestive cells). We also confirmed that spot desmosomes are common intercellular junctions between the regenerative and digestive cells in millipedes.

  12. Periodontal regeneration in gingival recession defects.

    PubMed

    Trombelli, L

    1999-02-01

    Surgical treatment of gingival recession defects aims at obtaining soft tissue coverage of exposed root surfaces and/or augmentation of gingival tissue dimensions. A variety of protocols have been developed to manage these clinical problems. Since one goal of periodontal therapy is the regeneration of the lost attachment apparatus of the tooth, full restoration of defect should be accomplished following mucogingival procedures. This implies regeneration of all periodontal structures, including formation of new cementum with inserting connective tissue fibers, alveolar bone regeneration and recreation of a functional and aesthetic morphology of the mucogingival complex. Animal and human histological studies have shown that healing at gingiva-root interface following pedicle flaps or free soft tissue grafts generally includes a long junctional epithelium with varying amounts of a new connective tissue attachment in the most apical aspect of the covered root surface. Limited bone regeneration has been observed. Adjunctive use of root conditioning agents and cell excluding, wound-stabilizing devices may amplify regenerative outcomes. Changes in the amount of keratinized tissue, which can significantly affect the aesthetic outcome of treatment, have been shown to depend on the interactions among various tissues involved in the healing process and the selected surgical procedure.

  13. Oral epithelial stem cells – implications in normal development and cancer metastasis

    PubMed Central

    Papagerakis, Silvana; Pannone, Giuseppe; Zheng, Li; About, Imad; Taqi, Nawar; Nguyen, Nghia P.T.; Matossian, Margarite; McAlpin, Blake; Santoro, Angela; McHugh, Jonathan; Prince, Mark E.; Papagerakis, Petros

    2014-01-01

    Oral mucosa is continuously exposed to environmental forces and has to be constantly renewed. Accordingly, the oral mucosa epithelium contains a large reservoir of epithelial stem cells necessary for tissue homeostasis. Despite considerable scientific advances in stem cell behavior in a number of tissues, fewer studies have been devoted to the stem cells in the oral epithelium. Most of oral mucosa stem cells studies are focused on identifying cancer stem cells (CSC) in oral squamous cell carcinomas (OSCCs) among other head and neck cancers. OSCCs are the most prevalent epithelial tumors of the head and neck region, marked by their aggressiveness and invasiveness. Due to their highly tumorigenic properties, it has been suggested that CSC may be the critical population of cancer cells in the development of OSCC metastasis. This review presents a brief overview of epithelium stem cells with implications in oral health, and the clinical implications of the CSC concept in OSCC metastatic dissemination. PMID:24803391

  14. Similar Squamous Cell Carcinoma Epithelium microRNA Expression in Never Smokers and Ever Smokers

    PubMed Central

    Kolokythas, Antonia; Zhou, Yalu; Schwartz, Joel L.; Adami, Guy R.

    2015-01-01

    The incidence of oral tumors in patients who never used mutagenic agents such as tobacco is increasing. In an effort to better understand these tumors we studied microRNA (miRNA) expression in tumor epithelium of never tobacco users, tumor epithelium of ever tobacco users, and nonpathological control oral epithelium. A comparison of levels among 372 miRNAs in 12 never tobacco users with oral squamous cell carcinoma (OSCC) versus 10 healthy controls was made using the reverse transcription quantitative polymerase chain reaction. A similar analysis was done with 8 ever tobacco users with OSCC. These comparisons revealed miR-10b-5p, miR-196a-5p, and miR-31-5p as enriched in the tumor epithelium in OSCC of both never and ever tobacco users. Examination of The Cancer Genome Atlas (TCGA) project miRNA data on 305 OSCCs and 30 controls revealed 100% of those miRNAs enriched in never smoker OSCCs in this patient group were also enriched in ever smoker OSCCs. Nonsupervised clustering of TCGA OSCCs was suggestive of two or four subgroups of tumors based on miRNA levels with limited evidence for differences in tobacco exposure among the groups. Results from both patient groups together stress the importance of miR196a-5p in OSCC malignancy in both never and ever smokers, and emphasize the overall similarity of miRNA expression in OSCCs in these two risk groups. It implies that there may be great similarity in etiology of OSCC in never and ever smokers and that classifying OSCC based on tobacco exposure may not be helpful in the clinic. PMID:26544609

  15. TRPV2 expression in rat oral mucosa.

    PubMed

    Shimohira, Daiji; Kido, Mizuho A; Danjo, Atsushi; Takao, Tomoka; Wang, Bing; Zhang, Jing-Qi; Yamaza, Takayoshi; Masuko, Sadahiko; Goto, Masaaki; Tanaka, Teruo

    2009-10-01

    The oral mucosa is a highly specialised, stratified epithelium that confers protection from infection and physical, chemical and thermal stimuli. The non-keratinised junctional epithelium surrounds each tooth like a collar and is easily attacked by foreign substances from the oral sulcus. We found that TRPV2, a temperature-gated channel, is highly expressed in junctional epithelial cells, but not in oral sulcular epithelial cells or oral epithelial cells. Dual or triple immunolabelling with immunocompetent cell markers also revealed TRPV2 expression in Langerhans cells and in dendritic cells and macrophages. Electron microscopy disclosed TRPV2 immunoreactivity in the unmyelinated and thinly myelinated axons within the connective tissue underlying the epithelium. TRPV2 labelling was also observed in venule endothelial cells. The electron-dense immunoreaction in junctional epithelial cells, macrophages and neural axons occurred on the plasma membrane, on invaginations of the plasma membrane and in vesicular structures. Because TRPV2 has been shown to respond to temperature, hypotonicity and mechanical stimuli, gingival cells expressing TRPV2 may act as sensor cells, detecting changes in the physical and chemical environment, and may play a role in subsequent defence mechanisms.

  16. Spontaneous hair cell regeneration in the mouse utricle following gentamicin ototoxicity.

    PubMed

    Kawamoto, Kohei; Izumikawa, Masahiko; Beyer, Lisa A; Atkin, Graham M; Raphael, Yehoash

    2009-01-01

    Whereas most epithelial tissues turn-over and regenerate after a traumatic lesion, this restorative ability is diminished in the sensory epithelia of the inner ear; it is absent in the cochlea and exists only in a limited capacity in the vestibular epithelium. The extent of regeneration in vestibular hair cells has been characterized for several mammalian species including guinea pig, rat, and chinchilla, but not yet in mouse. As the fundamental model species for investigating hereditary disease, the mouse can be studied using a wide variety of genetic and molecular tools. To design a mouse model for vestibular hair cell regeneration research, an aminoglycoside-induced method of complete hair cell elimination was developed in our lab and applied to the murine utricle. Loss of utricular hair cells was observed using scanning electron microscopy, and corroborated by a loss of fluorescent signal in utricles from transgenic mice with GFP-positive hair cells. Regenerative capability was characterized at several time points up to six months following insult. Using scanning electron microscopy, we observed that as early as two weeks after insult, a few immature hair cells, demonstrating the characteristic immature morphology indicative of regeneration, could be seen in the utricle. As time progressed, larger numbers of immature hair cells could be seen along with some mature cells resembling surface morphology of type II hair cells. By six months post-lesion, numerous regenerated hair cells were present in the utricle, however, neither their number nor their appearance was normal. A BrdU assay suggested that at least some of the regeneration of mouse vestibular hair cells involved mitosis. Our results demonstrate that the vestibular sensory epithelium in mice can spontaneously regenerate, elucidate the time course of this process, and identify involvement of mitosis in some cases. These data establish a road map of the murine vestibular regenerative process, which can be

  17. Olfactory epithelium: Cells, clinical disorders, and insights from an adult stem cell niche

    PubMed Central

    Choi, Rhea

    2018-01-01

    Disorders causing a loss of the sense of smell remain a therapeutic challenge. Basic research has, however, greatly expanded our knowledge of the organization and function of the olfactory system. This review describes advances in our understanding of the cellular components of the peripheral olfactory system, specifically the olfactory epithelium in the nose. The article discusses recent findings regarding the mechanisms involved in regeneration and cellular renewal from basal stem cells in the adult olfactory epithelium, considering the strategies involved in embryonic olfactory development and insights from research on other stem cell niches. In the context of clinical conditions causing anosmia, the current view of adult olfactory neurogenesis, tissue homeostasis, and failures in these processes is considered, along with current and future treatment strategies. Level of Evidence NA PMID:29492466

  18. Oral foregut cyst in a neonate.

    PubMed

    Rosa, Ana Cláudia Garcia; Hiramatsu, Daniel Martins; de Moraes, Fábio Roberto Ruiz; Passador-Santos, Fabrício; de Araújo, Vera Cavalcanti; Soares, Andresa Borges

    2013-11-01

    Oral foregut cysts are congenital choristomas that arise in the oral cavity during embryonic development from remnants of foregut-derived epithelium. This is an unusual report of a neonate with a large congenital sublingual cystic lesion, extending superficially from the left ventral tongue to the anterior floor of the mouth, impeding breast-feeding. The differential diagnosis included dermoid cyst, epidermoid cyst, mucous retention cyst, and oral lymphangioma. The treatment of choice was enucleation under general anesthesia. Histology showed a cystic lesion with a ciliated pseudostratified columnar epithelium with numerous goblet cells. Immunohistochemistry was positive for cytokeratin 7 and thyroid transcription factor 1 and negative for cytokeratin 20, resulting in a final diagnosis of an oral foregut cyst. Three weeks after surgery, the tongue had healed with good mobility, and breast-feeding could be established. No recurrence was present at 6 months of follow-up.

  19. Oral candidosis in relation to oral immunity.

    PubMed

    Feller, L; Khammissa, R A G; Chandran, R; Altini, M; Lemmer, J

    2014-09-01

    Symptomatic oral infection with Candida albicans is characterized by invasion of the oral epithelium by virulent hyphae that cause tissue damage releasing the inflammatory mediators that initiate and sustain local inflammation. Candida albicans triggers pattern-recognition receptors of keratinocytes, macrophages, monocytes and dendritic cells, stimulating the production of IL-1β, IL-6 and IL-23. These cytokines induce the differentiation of Th17 cells and the generation of IL-17- and/or IL-22-mediated antifungal protective immuno-inflammatory responses in infected mucosa. Some immune cells including NKT cells, γδ T cells and lymphoid cells that are innate to the oral mucosa have the capacity to produce large quantities of IL-17 in response to C. albicans, sufficient to mediate effective protective immunity against C. albicans. On the other hand, molecular structures of commensal C. albicans blastoconidia, although detected by pattern-recognition receptors, are avirulent, do not invade the oral epithelium, do not elicit inflammatory responses in a healthy host, but induce regulatory immune responses that maintain tissue tolerance to the commensal fungi. The type, specificity and sensitivity of the protective immune response towards C. albicans is determined by the outcome of the integrated interactions between the intracellular signalling pathways of specific combinations of activated pattern-recognition receptors (TLR2, TLR4, Dectin-1 and Dectin-2). IL-17-mediated protective immune response is essential for oral mucosal immunity to C. albicans infection. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Tissue regeneration in dentistry: Can salamanders provide insight?

    PubMed

    Sader, F; Denis, J-F; Roy, S

    2018-05-01

    The ability to regenerate damaged tissues would be of tremendous benefit for medicine and dentistry. Unfortunately, humans are unable to regenerate tissues such as teeth and fingers or to repair injured spinal cord. With an aging population, health problems are more prominent and dentistry is no exception as loss of bone tissue in the orofacial sphere from periodontal disease is on the rise. Humans can repair oral soft tissues exceptionally well; however, hard tissues, such as bone and teeth, are devoid of the ability to repair well or at all. Fortunately, Mother Nature has solved nearly every problem that we would like to solve for our own benefit and tissue regeneration is no exception. By studying animals that can regenerate, like Axolotls (Mexican salamander), we hope to find ways to stimulate regeneration in humans. We will discuss the role of the transforming growth factor beta cytokines as they are central to wound healing in humans and regeneration in Axolotls. We will also compare wound healing in humans (skin and oral mucosa) to Axolotl skin wound healing and limb regeneration. Finally, we will address the problem of bone regeneration and present results in salamanders which indicate that in order to regenerate bone you need to recruit non-bone cells. Fundamental research, such as the work being performed in animals that can regenerate, offers insight to help understand why some treatments are successful while others fail when it comes to specific tissues such as bones. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Bacterial colonization stimulates a complex physiological response in the immature human intestinal epithelium

    PubMed Central

    Hill, David R; Huang, Sha; Nagy, Melinda S; Yadagiri, Veda K; Fields, Courtney; Mukherjee, Dishari; Bons, Brooke; Dedhia, Priya H; Chin, Alana M; Tsai, Yu-Hwai; Thodla, Shrikar; Schmidt, Thomas M; Walk, Seth

    2017-01-01

    The human gastrointestinal tract is immature at birth, yet must adapt to dramatic changes such as oral nutrition and microbial colonization. The confluence of these factors can lead to severe inflammatory disease in premature infants; however, investigating complex environment-host interactions is difficult due to limited access to immature human tissue. Here, we demonstrate that the epithelium of human pluripotent stem-cell-derived human intestinal organoids is globally similar to the immature human epithelium and we utilize HIOs to investigate complex host-microbe interactions in this naive epithelium. Our findings demonstrate that the immature epithelium is intrinsically capable of establishing a stable host-microbe symbiosis. Microbial colonization leads to complex contact and hypoxia driven responses resulting in increased antimicrobial peptide production, maturation of the mucus layer, and improved barrier function. These studies lay the groundwork for an improved mechanistic understanding of how colonization influences development of the immature human intestine. PMID:29110754

  2. [Experimental studies for the improvement of facial nerve regeneration].

    PubMed

    Guntinas-Lichius, O; Angelov, D N

    2008-02-01

    Using a combination of the following, it is possible to investigate procedures to improve the morphological and functional regeneration of the facial nerve in animal models: 1) retrograde fluorescence tracing to analyse collateral axonal sprouting and the selectivity of reinnervation of the mimic musculature, 2) immunohistochemistry to analyse both the terminal axonal sprouting in the muscles and the axon reaction within the nucleus of the facial nerve, the peripheral nerve, and its environment, and 3) digital motion analysis of the muscles. To obtain good functional facial nerve regeneration, a reduction of terminal sprouting in the mimic musculature seems to be more important than a reduction of collateral sprouting at the lesion site. Promising strategies include acceleration of nerve regeneration, forced induced use of the paralysed face, mechanical stimulation of the face, and transplantation of nerve-growth-promoting olfactory epithelium at the lesion site.

  3. The morphological change of supporting cells in the olfactory epithelium after bulbectomy.

    PubMed

    Makino, Nobuko; Ookawara, Shigeo; Katoh, Kazuo; Ohta, Yasushi; Ichikawa, Masumi; Ichimura, Keiichi

    2009-02-01

    Transmission electron microscopy was used to study the responses of the supporting cells of the olfactory epithelium at 1-5 days after surgical ablation of the olfactory bulb (bulbectomy). In intact olfactory epithelium, lamellar smooth endoplasmic reticulum and rod-shaped mitochondria were distinctly observed in the supporting cells. On the first day after bulbectomy, bending of the microvilli and an increase in the smooth endoplasmic reticulum were observed. Cristae of the mitochondria became obscure, and the density of the mitochondrial matrix decreased. On the second day after bulbectomy, the number of microvilli decreased, broad cytoplasmic projections that contained cytoplasmic organelles protruded into the luminal side, and the mitochondria were swollen. On the fifth day after bulbectomy, microvilli seemed to be normal and some cells had large cytoplasmic projections that protruded toward the lumen of the nasal cavity. Within the cytoplasmic projections of the supporting cells, a large lamellar and reticular-shaped smooth endoplasmic reticulum was evident. Mitochondria exhibited almost normal morphology. The current findings demonstrate that morphological changes occur in the supporting cells after bulbectomy. This new evidence hypothesizes that these changes represent events that contribute to the regeneration of the olfactory epithelium after bulbectomy.

  4. Epithelium-derived Wnt ligands are essential for maintenance of underlying digit bone

    PubMed Central

    Takeo, Makoto; Hale, Christopher S.; Ito, Mayumi

    2018-01-01

    Clinically, many nail disorders accompany bone deformities, but whether the two defects are causally related is under debate. To investigate the potential interactions between the two tissue types, we analyzed epithelial-specific β-catenin deficient mice, in which nail differentiation is abrogated. These mice showed regression of not only the nail plate but also of the underlying digit bone. Characterization of these bone defects revealed active bone resorption, which is suppressed by Wnt activation in osteoblast and osteoclast precursors. Furthermore, we found that Wntless (Wls) expression, essential for Wnt ligand secretion, was lacking in the β-catenin deficient nail epithelium and that genetic deletion of Wls in the nail epithelium led to the lack of Wnt activation in osteoblast and osteoclast precursors and subsequently led to defective regression of the underlying digit bone. Together, these data show epithelial Wnt ligands can ultimately regulate Wnt signaling in osteoblasts and osteoclast precursors, known to regulate bone homeostasis. These results reveal a critical role for the nail epithelium on the digit bone during homeostatic regeneration and show that Wnt/β-catenin signaling is critical for this interaction. PMID:27021406

  5. Epithelium-Derived Wnt Ligands Are Essential for Maintenance of Underlying Digit Bone.

    PubMed

    Takeo, Makoto; Hale, Christopher S; Ito, Mayumi

    2016-07-01

    Clinically, many nail disorders accompany bone deformities, but whether the two defects are causally related is under debate. To investigate the potential interactions between the two tissue types, we analyzed epithelial-specific β-catenin-deficient mice, in which nail differentiation is abrogated. These mice showed regression of not only the nail plate but also of the underlying digit bone. Characterization of these bone defects revealed active bone resorption, which is suppressed by Wnt activation in osteoblast and osteoclast precursors. Furthermore, we found that Wntless expression, essential for Wnt ligand secretion, was lacking in the β-catenin-deficient nail epithelium and that genetic deletion of Wntless (Wls) in the nail epithelium led to the lack of Wnt activation in osteoblast and osteoclast precursors and subsequently led to defective regression of the underlying digit bone. Together, these data show that epithelial Wnt ligands can ultimately regulate Wnt signaling in osteoblast and osteoclast precursors, known to regulate bone homeostasis. These results reveal a critical role for the nail epithelium on the digit bone during homeostatic regeneration and show that Wnt/β-catenin signaling is critical for this interaction. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Expression of nestin and chromogranin in regeneration zones of rat pancreas.

    PubMed

    Ege, Bahadir; Dinc, Tolga; Kayilioglu, Selami Ilgaz; Tezel, Ekmel; Ersoy, Emin

    2017-01-01

    The particular signals that start and orchestrate the regeneration process in pancreas are not well understood yet. We aimed to investigate the expression of nestin and chromogranin A in pancreatic regeneration zones and a secondary objective, we assessed the efficiency of pancreatic duct ligation method in creation of a pancreatic regeneration model in rats. Partial (90%) pancreatectomy and pancreatic duct ligation were performed in Wistar rats, in order to create pancreatic regeneration models. Pancreatic tissues were examined histologically. Expression profiles were investigated by immunohistochemistry for nestin and chromogranin A. Nestin and chromogranin A expressions were observed in regeneration zones. Pancreatic regenerations zones were seen in pancreatic duct ligation group samples as well as partial pancreatectomy group. Nestin was expressed prominently in acinoductular metaplasia cells in regeneration zones. This was best demonstrated in the samples of pancreatic duct ligation group. In the subsequent sections of nestin positive sites, cytoplasmic positivity with chromogranin A was observed. This study confirms that nestin and chromogranin A can be detected in neogenesis-evoked pancreatic tissue, particularly in the acinoductular epithelium. Nestin and chromogranin A may be important markers to identify pancreatic stem cells. Pancreatic duct ligation can be used for creating pancreatic regeneration model in rats. Chromogranin A, Nestin, Pancreas, Regeneration, Stem cells.

  7. Assessment of conjunctival epithelium after severe burns and surgical reconstruction with Tenon plasty by means of a modified impression cytology procedure.

    PubMed

    Reim, M; Becker, J; Genser, C; Salla, S

    1998-07-01

    Tenon plasty has been used to reconstruct the conjunctival surface in severe burns in which ischemic sclera was exposed or undergoing ulceration. A modified impression cytology procedure was applied to investigate the conjunctival epithelium. The quality of the regenerated epithelium on the advanced Tenon sheets was assessed. The 63 conjunctival samples of eye-burn patients were investigated. Among these, 41 patients had very severe bums. Conjunctival samples were collected from 6 weeks after surgery to 5 years after the accident. They were compared with conjunctival epithelia obtained from 53 normal eyes of healthy volunteers. A 25-mm2 Biopore membrane (Millipore Catalogue PICM 01250) was placed on the bulbar conjunctiva surface in the lower temporal quadrant, at a distance of 3-5 mm from the limbus, till it was soaked with fluid. The ablated cell sheets were stained with periodic acid-Schiff (PAS). In all cases, an intact conjunctival epithelium was observed. In healthy eyes, 2,338 epithelial cells/mm2 and 155 goblet cells/ mm2 were found. Eyes after a surgical reconstruction with Tenon plasty resulted only in 1,575 epithelial cells/mm2 and 72 goblet cells/mm2. The differences were highly significant. The ratio of epithelial to goblet cell counts revealed an increase of goblet cells during the postoperative period. Conjunctival epithelium as well as goblet cell densities were reduced after heat, lime, alkali, and acid burns. However, after concrete burns, cell densities were increased. Tenon plasty provided the regeneration of the fully intact conjunctival epithelium. Goblet cells were present from 6 weeks after the surgery on; their number increased gradually. The stimulation of the goblet cell mucous secretion is discussed.

  8. Acute sensitivity of the oral mucosa to oncogenic K-ras

    PubMed Central

    van der Weyden, Louise; Alcolea, Maria P; Jones, Philip H; Rust, Alistair G; Arends, Mark J; Adams, David J

    2011-01-01

    Mouse models of cancer represent powerful tools for analysing the role of genetic alterations in carcinogenesis. Using a mouse model that allows tamoxifen-inducible somatic activation (by Cre-mediated recombination) of oncogenic K-rasG12D in a wide range of tissues, we observed hyperplasia of squamous epithelium located in moist or frequently abraded mucosa, with the most dramatic effects in the oral mucosa. This epithelium showed a sequence of squamous hyperplasia followed by squamous papilloma with dysplasia, in which some areas progressed to early invasive squamous cell carcinoma, within 14 days of widespread oncogenic K-ras activation. The marked proliferative response of the oral mucosa to K-rasG12D was most evident in the basal layers of the squamous epithelium of the outer lip with hair follicles and wet mucosal surface, with these cells staining positively for pAKT and cyclin D1, showing Ras/AKT pathway activation and increased proliferation with Ki-67 and EdU positivity. The stromal cells also showed gene activation by recombination and immunopositivity for pERK indicating K-Ras/ERK pathway activation, but without Ki-67 positivity or increase in stromal proliferation. The oral neoplasms showed changes in the expression pattern of cytokeratins (CK6 and CK13), similar to those observed in human oral tumours. Sporadic activation of the K-rasG12D allele (due to background spontaneous recombination in occasional cells) resulted in the development of benign oral squamous papillomas only showing a mild degree of dysplasia with no invasion. In summary, we show that oral mucosa is acutely sensitive to oncogenic K-ras, as widespread expression of activated K-ras in the murine oral mucosal squamous epithelium and underlying stroma can drive the oral squamous papilloma–carcinoma sequence. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID:21381032

  9. Cellular migration, transition and interaction during regeneration of the sponge Hymeniacidon heliophila.

    PubMed

    Coutinho, Cristiano C; Rosa, Ivone de Andrade; Teixeira, John Douglas de Oliveira; Andrade, Leonardo R; Costa, Manoel Luis; Mermelstein, Claudia

    2017-01-01

    Sponges have a high capacity for regeneration and this process improves biomass production in some species, thus contributing to a solution for the biomass supply problem for biotechnological applications. The aim of this work is to characterize the dynamics of cell behavior during the initial stages of sponge regeneration, using bright-field microscopy, confocal microscopy and SEM. We focused on the first 20 h of regeneration, during which blastema formation and epithelium initialization occur. An innovative sponge organotypic culture of the regenerating internal region is described and investigated by confocal microscopy, cell transplantation and vital staining. Cell-cell interaction and cell density are shown to affect events in morphogenesis such as epithelial/mesenchymal and mesenchymal/epithelial transitions as well as distinct cell movements required for regeneration. Extracellular matrix was organized according to the morphogenetic process observed, with evidence for cell-signaling instructions and remodeling. These data and the method of organotypic culture described here provide support for the development of viable sponge biomass production.

  10. Evaluation of cell proliferation in malignant and potentially malignant oral lesions.

    PubMed

    Madan, Mani; Chandra, Shaleen; Raj, Vineet; Madan, Rohit

    2015-01-01

    To evaluate the cell proliferation rate by the expression of proliferating cell nuclear antigen (PCNA) and argyrophilic nucleolar organizing region (AgNOR) counts and to assess its usefulness as a marker for malignant potential in oral epithelial lesions. The study group included 30 cases of leukoplakia, 15 nondysplastic (NDL), 15 dysplastic (DL), 15 cases of oral squamous cell carcinoma (OSCC) and 5 cases of normal oral mucosa. Formalin fixed paraffin embedded tissues were subjected to immunohistochemical staining for PCNA and AgNOR technique. The PCNA labeling index (LI) and the AgNOR dots were evaluated for the entire sample. ANOVA, Tukey honestly significant difference, Pearson's correlation. In this study, the AgNOR count of OSCC was lower than the DL lesions moreover the AgNOR counts were found to be higher in normal mucosa as compared to the DL and the NDL epithelium. The study results also showed that the mean AgNOR count failed to distinguish between DL and NDL lesions. Overall we observed increased PCNA expression from normal epithelium to NDL to DL lesion. Based on the findings of the present study on oral epithelial precancerous and cancerous lesions we conclude that mean AgNOR count alone cannot be a valuable parameter to distinguish between the normal, NDL, DL epithelium and OSCC but, on the other hand, we found out that PCNA can be a useful biomarker for delineating normal epithelium from DL epithelium and OSCC.

  11. Evolution of the Chordate Regeneration Blastema: Differential Gene Expression and Conserved Role of Notch Signaling During Siphon Regeneration in the Ascidian Ciona

    PubMed Central

    Hamada, Mayuko; Goricki, Spela; Byerly, Mardi S.; Satoh, Noriyuki; Jeffery, William R.

    2015-01-01

    The regeneration of the oral siphon (OS) and other distal structures in the ascidian Ciona intestinalis occurs by epimorphosis involving the formation of a blastema of proliferating cells. Despite the longstanding use of Ciona as a model in molecular developmental biology, regeneration in this system has not been previously explored by molecular analysis. Here we have employed microarray analysis and quantitative real time RT-PCR to identify genes with differential expression profiles during OS regeneration. The majority of differentially expressed genes were downregulated during OS regeneration, suggesting roles in normal growth and homeostasis. However, a subset of differentially expressed genes was upregulated in the regenerating OS, suggesting functional roles during regeneration. Among the upregulated genes were key members of the Notch signaling pathway, including those encoding the delta and jagged ligands, two fringe modulators, and to a lesser extent the notch receptor. In situ hybridization showed a complementary pattern of delta1 and notch gene expression in the blastema of the regenerating OS. Chemical inhibition of the Notch signaling pathway reduced the levels of cell proliferation in the branchial sac, a stem cell niche that contributes progenitor cells to the regenerating OS, and in the OS regeneration blastema, where siphon muscle fibers eventually re-differentiate. Chemical inhibition also prevented the replacement of oral siphon pigment organs, sensory receptors rimming the entrance of the OS, and siphon muscle fibers, but had no effects on the formation of the wound epidermis. Since Notch signaling is involved in the maintenance of proliferative activity in both the Ciona and vertebrate regeneration blastema, the results suggest a conserved evolutionary role of this signaling pathway in chordate regeneration. The genes identified in this investigation provide the foundation for future molecular analysis of OS regeneration. PMID:26206613

  12. The interactions of single-wall carbon nanohorns with polar epithelium.

    PubMed

    Shi, Yujie; Shi, Zujin; Li, Suxin; Zhang, Yuan; He, Bing; Peng, Dong; Tian, Jie; Zhao, Ming; Wang, Xueqing; Zhang, Qiang

    2017-01-01

    Single-wall carbon nanohorns (SWCNHs), which have multitudes of horn interstices, an extensive surface area, and a spherical aggregate structure, offer many advantages over other carbon nanomaterials being used as a drug nanovector. The previous studies on the interaction between SWCNHs and cells have mostly emphasized on cellular uptake and intracellular trafficking, but seldom on epithelial cells. Polar epithelium as a typical biological barrier constitutes the prime obstacle for the transport of therapeutic agents to target site. This work tried to explore the permeability of SWCNHs through polar epithelium and their abilities to modulate transcellular transport, and evaluate the potential of SWCNHs in drug delivery. Madin-Darby canine kidney (MDCK) cell monolayer was used as a polar epithelial cell model, and as-grown SWCNHs, together with oxidized and fluorescein isothiocyanate-conjugated bovine serum albumin-labeled forms, were constructed and comprehensively investigated in vitro and in vivo. Various methods such as transmission electron microscopy and confocal imaging were used to visualize their intracellular uptake and localization, as well as to investigate the potential transcytotic process. The related mechanism was explored by specific inhibitors. Additionally, fast multispectral optoacoustic tomography imaging was used for monitoring the distribution and transport process of SWCNHs in vivo after oral administration in nude mice, as an evidence for their interaction with the intestinal epithelium. The results showed that SWCNHs had a strong bioadhesion property, and parts of them could be uptaken and transcytosed across the MDCK monolayer. Multiple mechanisms were involved in the uptake and transcytosis of SWCNHs with varying degrees. After oral administration, oxidized SWCNHs were distributed in the gastrointestinal tract and retained in the intestine for up to 36 h probably due to their surface adhesion and endocytosis into the intestinal epithelium

  13. CCAAT/Enhancer Binding Protein–α Regulates the Protease/Antiprotease Balance Required for Bronchiolar Epithelium Regeneration

    PubMed Central

    Sato, Atsuyasu; Xu, Yan; Whitsett, Jeffrey A.

    2012-01-01

    Many transcription factors that regulate lung morphogenesis during development are reactivated to mediate repairs of the injured adult lung. We hypothesized that CCAAT/enhancer binding protein–α (C/EBPα), a transcription factor critical for perinatal lung maturation, regulates genes required for the normal repair of the bronchiolar epithelium after injury. Transgenic CebpαΔ/Δ mice, in which Cebpa was conditionally deleted from Clara cells and Type II cells after birth, were used in this study. Airway injury was induced in mice by the intraperitoneal administration of naphthalene to ablate bronchiolar epithelial cells. Although the deletion of C/EBPα did not influence lung structure and function under unstressed conditions, C/EBPα was required for the normal repair of terminal bronchiolar epithelium after naphthalene injury. To identify cellular processes that are influenced by C/EBPα during repair, mRNA microarray was performed on terminal bronchiolar epithelial cells isolated by laser-capture microdissection. Normal repair of the terminal bronchiolar epithelium was highly associated with the mRNAs regulating antiprotease activities, and their induction required C/EBPα. The defective deposition of fibronectin in CebpαΔ/Δ mice was associated with increased protease activity and delayed differentiation of FoxJ1-expressing ciliated cells. The fibronectin and ciliated cells were restored by the intratracheal treatment of CebpαΔ/Δ mice with the serine protease inhibitor. In conclusion, C/EBPα regulates the expression of serine protease inhibitors that are required for the normal increase of fibronectin and the restoration of ciliated cells after injury. Treatment with serine protease inhibitor may aid in the recovery of injured bronchiolar epithelial cells, and prevent common chronic lung diseases. PMID:22652201

  14. Enamel Regeneration - Current Progress and Challenges

    PubMed Central

    Baswaraj; H.K, Navin; K.B, Prasanna

    2014-01-01

    Dental Enamel is the outermost covering of teeth. It is hardest mineralized tissue present in the human body. Enamel faces the challenge of maintaining its integrity in a constant demineralization and remineralization within the oral environment and it is vulnerable to wear, damage, and decay. It cannot regenerate itself, because it is formed by a layer of cells that are lost after the tooth eruption. Conventional treatment relies on synthetic materials to restore lost enamel that cannot mimic natural enamel. With advances in material science and understanding of basic principles of organic matrix mediated mineralization paves a way for formation of synthetic enamel. The knowledge of enamel formation and understanding of protein interactions and their gene products function along with the isolation of postnatal stem cells from various sources in the oral cavity, and the development of smart materials for cell and growth factor delivery, makes possibility for biological based enamel regeneration. This article will review the recent endeavor on biomimetic synthesis and cell based strategies for enamel regeneration. PMID:25386548

  15. Evaluation of cell proliferation in malignant and potentially malignant oral lesions

    PubMed Central

    Madan, Mani; Chandra, Shaleen; Raj, Vineet; Madan, Rohit

    2015-01-01

    Aims: To evaluate the cell proliferation rate by the expression of proliferating cell nuclear antigen (PCNA) and argyrophilic nucleolar organizing region (AgNOR) counts and to assess its usefulness as a marker for malignant potential in oral epithelial lesions. Materials and Methods: The study group included 30 cases of leukoplakia, 15 nondysplastic (NDL), 15 dysplastic (DL), 15 cases of oral squamous cell carcinoma (OSCC) and 5 cases of normal oral mucosa. Formalin fixed paraffin embedded tissues were subjected to immunohistochemical staining for PCNA and AgNOR technique. The PCNA labeling index (LI) and the AgNOR dots were evaluated for the entire sample. Statistical Analysis Used: ANOVA, Tukey honestly significant difference, Pearson's correlation. Results: In this study, the AgNOR count of OSCC was lower than the DL lesions moreover the AgNOR counts were found to be higher in normal mucosa as compared to the DL and the NDL epithelium. The study results also showed that the mean AgNOR count failed to distinguish between DL and NDL lesions. Overall we observed increased PCNA expression from normal epithelium to NDL to DL lesion. Conclusions: Based on the findings of the present study on oral epithelial precancerous and cancerous lesions we conclude that mean AgNOR count alone cannot be a valuable parameter to distinguish between the normal, NDL, DL epithelium and OSCC but, on the other hand, we found out that PCNA can be a useful biomarker for delineating normal epithelium from DL epithelium and OSCC. PMID:26980956

  16. Vitamin D signaling regulates oral keratinocyte proliferation in vitro and in vivo

    PubMed Central

    YUAN, FENG-NING F.; VALIYAPARAMBIL, JAYASANKER; WOODS, MICHAEL C.; TRAN, HUY; PANT, RIMA; ADAMS, JOHN S.; MALLYA, SANJAY M.

    2014-01-01

    The secosteroidal hormone 1,25-dihyroxyvitamin D [1,25(OH)2D3] and its receptor, the vitamin D receptor (VDR), are crucial regulators of epidermal proliferation and differentiation. However, the effects of 1,25(OH)2D3-directed signaling on oral keratinocyte pathophysiology have not been well studied. We examined the role of 1,25(OH)2D3 in regulating proliferation and differentiation in cultured oral keratinocytes and on the oral epithelium in vivo. Using lentiviral-mediated shRNA to silence VDR, we generated an oral keratinocyte cell line with stable knockdown of VDR expression. VDR knockdown significantly enhanced proliferation and disrupted calcium- and 1,25(OH)2D3-induced oral keratinocyte differentiation, emphasizing the anti-proliferative and pro-differentiation effects of 1,25(OH)2D3 in oral keratinocytes. Using vitamin D3-deficient diets, we induced chronic vitamin D deficiency in mice as evidenced by decreased serum 25-hydroxyvitamin D (25OHD) concentrations. The vitamin D-deficient mice manifested increased proliferation of the tongue epithelium, but did not develop any morphological or histological abnormalities in the oral epithelium, suggesting that vitamin D deficiency alone is insufficient to alter oral epithelial homeostasis and provoke carcinogenesis. Immunohistochemical analyses of human and murine oral squamous cell carcinomas showed increased VDR expression. Overall, our results provide strong support for a crucial role for vitamin D signaling in oral keratinocyte pathophysiology. PMID:24626468

  17. Analysis of Cell Turnover in the Bronchiolar Epithelium Through the Normal Aging Process.

    PubMed

    Ortega-Martínez, Marta; Rodríguez-Flores, Laura E; Ancer-Arellano, Adriana; Cerda-Flores, Ricardo M; de-la-Garza-González, Carlos; Ancer-Rodríguez, Jesús; Jaramillo-Rangel, Gilberto

    2016-08-01

    Aging is associated with changes in the lung that leads to a decrease in its function. Alterations in structure and function in the small airways are well recognized in chronic lung diseases. The aim of this study was the assessment of cell turnover in the bronchiolar epithelium of mouse through the normal aging process. Lungs from CD1 mice at the age of 2, 6, 12, 18, or 24 months were fixed in neutral-buffered formalin and paraffin-embedded. Proliferating cell nuclear antigen was examined by immunohistochemistry. Apoptosis was analyzed by in situ end-labeling of fragmented DNA. Epithelial dimensions were analyzed by morphometry. The 2-month-old mice showed significantly higher number of proliferating cells when compared with mice at all other age groups. The number of apoptotic cells in mice at 24 months of age was significantly greater than in mice at all other age groups. Thus, the number of epithelial cells decreased as the age of the subject increased. We also found reductions in both area and height of the bronchiolar epithelium in mice at 18 and 24 months of age. We found a decrease in the total number of epithelial cells in the aged mice, which was accompanied by a thinning of the epithelium. These changes reflect a dysregulated tissue regeneration process in the bronchiolar epithelium that might predispose to respiratory diseases in elderly subjects.

  18. Histology, Immunohistochemistry and Ultrastructure of the Bovine Palatine Tonsil with Special Emphasis on Reticular Epithelium

    USDA-ARS?s Scientific Manuscript database

    The paired palatine tonsils are located at the junction of the nasopharynx and oropharynx; ideally positioned to sample antigens entering through either the nasal cavity or oral cavity. Entering antigens will first contact tonsilar epithelium. To better understand the cellular and functional composi...

  19. A Consistent Orally-Infected Hamster Model for Enterovirus A71 Encephalomyelitis Demonstrates Squamous Lesions in the Paws, Skin and Oral Cavity Reminiscent of Hand-Foot-and-Mouth Disease.

    PubMed

    Phyu, Win Kyaw; Ong, Kien Chai; Wong, Kum Thong

    2016-01-01

    Enterovirus A71 (EV-A71) causes self-limiting, hand-foot-and-mouth disease (HFMD) that may rarely be complicated by encephalomyelitis. Person-to-person transmission is usually by fecal-oral or oral-oral routes. To study viral replication sites in the oral cavity and other tissues, and to gain further insights into virus shedding and neuropathogenesis, we developed a consistent, orally-infected, 2-week-old hamster model of HFMD and EV-A71 encephalomyelitis. Tissues from orally-infected, 2-week-old hamsters were studied by light microscopy, immunohistochemistry and in situ hybridization to detect viral antigens and RNA, respectively, and by virus titration. Hamsters developed the disease and died after 4-8 days post infection; LD50 was 25 CCID50. Macroscopic cutaneous lesions around the oral cavity and paws were observed. Squamous epithelium in the lip, oral cavity, paw, skin, and esophagus, showed multiple small inflammatory foci around squamous cells that demonstrated viral antigens/RNA. Neurons (brainstem, spinal cord, sensory ganglia), acinar cells (salivary gland, lacrimal gland), lymphoid cells (lymph node, spleen), and muscle fibres (skeletal, cardiac and smooth muscles), liver and gastric epithelium also showed varying amounts of viral antigens/RNA. Intestinal epithelium, Peyer's patches, thymus, pancreas, lung and kidney were negative. Virus was isolated from oral washes, feces, brain, spinal cord, skeletal muscle, serum, and other tissues. Our animal model should be useful to study squamous epitheliotropism, neuropathogenesis, oral/fecal shedding in EV-A71 infection, person-to-person transmission, and to test anti-viral drugs and vaccines.

  20. A Consistent Orally-Infected Hamster Model for Enterovirus A71 Encephalomyelitis Demonstrates Squamous Lesions in the Paws, Skin and Oral Cavity Reminiscent of Hand-Foot-and-Mouth Disease

    PubMed Central

    Phyu, Win Kyaw; Ong, Kien Chai; Wong, Kum Thong

    2016-01-01

    Enterovirus A71 (EV-A71) causes self-limiting, hand-foot-and-mouth disease (HFMD) that may rarely be complicated by encephalomyelitis. Person-to-person transmission is usually by fecal-oral or oral-oral routes. To study viral replication sites in the oral cavity and other tissues, and to gain further insights into virus shedding and neuropathogenesis, we developed a consistent, orally-infected, 2-week-old hamster model of HFMD and EV-A71 encephalomyelitis. Tissues from orally-infected, 2-week-old hamsters were studied by light microscopy, immunohistochemistry and in situ hybridization to detect viral antigens and RNA, respectively, and by virus titration. Hamsters developed the disease and died after 4–8 days post infection; LD50 was 25 CCID50. Macroscopic cutaneous lesions around the oral cavity and paws were observed. Squamous epithelium in the lip, oral cavity, paw, skin, and esophagus, showed multiple small inflammatory foci around squamous cells that demonstrated viral antigens/RNA. Neurons (brainstem, spinal cord, sensory ganglia), acinar cells (salivary gland, lacrimal gland), lymphoid cells (lymph node, spleen), and muscle fibres (skeletal, cardiac and smooth muscles), liver and gastric epithelium also showed varying amounts of viral antigens/RNA. Intestinal epithelium, Peyer’s patches, thymus, pancreas, lung and kidney were negative. Virus was isolated from oral washes, feces, brain, spinal cord, skeletal muscle, serum, and other tissues. Our animal model should be useful to study squamous epitheliotropism, neuropathogenesis, oral/fecal shedding in EV-A71 infection, person-to-person transmission, and to test anti-viral drugs and vaccines. PMID:26815859

  1. Sclerostin-neutralizing Antibody Enhances Bone Regeneration around Oral Implants.

    PubMed

    Yu, Shan Huey; Hao, Jie; Fretwurst, Tobias; Liu, Min; Kostenuik, Paul; Giannobile, William V; Jin, Qiming

    2018-06-19

    Dental implants have been an important option for the replacement of missing teeth. A major clinical challenge is how best to accelerate bone regeneration and reduce the healing time for functional restoration after implant placement. Monoclonal antibody against sclerostin (Scl-Ab) has been shown to enhance alveolar bone formation and fracture repair. The aim of this study was to investigate the effects of systemic administration of Scl-Ab on dental implant osseointegration and bone regeneration in an experimental alveolar ridge tooth extraction model. To investigate the effects of Scl-Ab on bone regeneration and dental implant osseointegration, an experimental alveolar bone osteotomy rat model was adopted. One month after the extraction of maxillary right first molars, osteotomy defects were created at the coronal aspect of each of the extraction sites, and 1x2 mm custom titanium implants were pressed-fitted into the osteotomies. Coincident with initial implant placement, Scl-Ab or vehicle was administered subcutaneously twice weekly at a dose of 25 mg/kg for 10-28 days and compared to a vehicle control. Rats were sacrificed 10, 14 and 28d after surgery, and maxillae were harvested and analyzed by micro-computed tomography (microCT), histology and histomorphometry. MicroCT analysis demonstrated that maxillary bone volume fraction was approximately 2 to 2.5-fold greater in Scl-Ab treated animals as compared to vehicle alone at days 14 and 28. Consistent with those findings, 2-D bone fill percentage within the coronal osteotomy sites were highest in Scl-Ab treatment groups at 28d. In addition, bone-implant contact at 28d was approximately 2-fold greater in the Scl-Ab group compared to vehicle controls. These results indicate that systemic Scl-Ab administration enhances osseointegration and bone regeneration around dental implants. This approach offers potential as a treatment modality for patients with low bone mass or bone defects to achieve more predictable bone

  2. The Favorable Effect of Mesenchymal Stem Cell Treatment on the Antioxidant Protective Mechanism in the Corneal Epithelium and Renewal of Corneal Optical Properties Changed after Alkali Burns.

    PubMed

    Cejka, Cestmir; Holan, Vladimir; Trosan, Peter; Zajicova, Alena; Javorkova, Eliska; Cejkova, Jitka

    2016-01-01

    The aim of this study was to examine whether mesenchymal stem cells (MSCs) and/or corneal limbal epithelial stem cells (LSCs) influence restoration of an antioxidant protective mechanism in the corneal epithelium and renewal of corneal optical properties changed after alkali burns. The injured rabbit corneas (with 0.25 N NaOH) were untreated or treated with nanofiber scaffolds free of stem cells, with nanofiber scaffolds seeded with bone marrow MSCs (BM-MSCs), with adipose tissue MSCs (Ad-MSCs), or with LSCs. On day 15 following the injury, after BM-MSCs or LSCs nanofiber treatment (less after Ad-MSCs treatment) the expression of antioxidant enzymes was restored in the regenerated corneal epithelium and the expressions of matrix metalloproteinase 9 (MMP9), inducible nitric oxide synthase (iNOS), α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), and vascular endothelial factor (VEGF) were low. The central corneal thickness (taken as an index of corneal hydration) increased after the injury and returned to levels before the injury. In injured untreated corneas the epithelium was absent and numerous cells revealed the expressions of iNOS, MMP9, α-SMA, TGF-β1, and VEGF. In conclusion, stem cell treatment accelerated regeneration of the corneal epithelium, restored the antioxidant protective mechanism, and renewed corneal optical properties.

  3. Macrophage/epithelium cross-talk regulates cell cycle progression and migration in pancreatic progenitors.

    PubMed

    Mussar, Kristin; Tucker, Andrew; McLennan, Linsey; Gearhart, Addie; Jimenez-Caliani, Antonio J; Cirulli, Vincenzo; Crisa, Laura

    2014-01-01

    Macrophages populate the mesenchymal compartment of all organs during embryogenesis and have been shown to support tissue organogenesis and regeneration by regulating remodeling of the extracellular microenvironment. Whether this mesenchymal component can also dictate select developmental decisions in epithelia is unknown. Here, using the embryonic pancreatic epithelium as model system, we show that macrophages drive the epithelium to execute two developmentally important choices, i.e. the exit from cell cycle and the acquisition of a migratory phenotype. We demonstrate that these developmental decisions are effectively imparted by macrophages activated toward an M2 fetal-like functional state, and involve modulation of the adhesion receptor NCAM and an uncommon "paired-less" isoform of the transcription factor PAX6 in the epithelium. Over-expression of this PAX6 variant in pancreatic epithelia controls both cell motility and cell cycle progression in a gene-dosage dependent fashion. Importantly, induction of these phenotypes in embryonic pancreatic transplants by M2 macrophages in vivo is associated with an increased frequency of endocrine-committed cells emerging from ductal progenitor pools. These results identify M2 macrophages as key effectors capable of coordinating epithelial cell cycle withdrawal and cell migration, two events critical to pancreatic progenitors' delamination and progression toward their differentiated fates.

  4. Lgr5 Identifies Progenitor Cells Capable of Taste Bud Regeneration after Injury.

    PubMed

    Takeda, Norifumi; Jain, Rajan; Li, Deqiang; Li, Li; Lu, Min Min; Epstein, Jonathan A

    2013-01-01

    Taste buds are composed of a variety of taste receptor cell types that develop from tongue epithelium and are regularly replenished under normal homeostatic conditions as well as after injury. The characteristics of cells that give rise to regenerating taste buds are poorly understood. Recent studies have suggested that Lgr5 (leucine-rich repeat-containing G-protein coupled receptor 5) identifies taste bud stem cells that contribute to homeostatic regeneration in adult circumvallate and foliate taste papillae, which are located in the posterior region of the tongue. Taste papillae in the adult anterior region of the tongue do not express Lgr5. Here, we confirm and extend these studies by demonstrating that Lgr5 cells give rise to both anterior and posterior taste buds during development, and are capable of regenerating posterior taste buds after injury induced by glossopharyngeal nerve transection.

  5. Neuregulin-1 signaling is essential for nerve-dependent axolotl limb regeneration.

    PubMed

    Farkas, Johanna E; Freitas, Polina D; Bryant, Donald M; Whited, Jessica L; Monaghan, James R

    2016-08-01

    The Mexican axolotl (Ambystoma mexicanum) is capable of fully regenerating amputated limbs, but denervation of the limb inhibits the formation of the post-injury proliferative mass called the blastema. The molecular basis behind this phenomenon remains poorly understood, but previous studies have suggested that nerves support regeneration via the secretion of essential growth-promoting factors. An essential nerve-derived factor must be found in the blastema, capable of rescuing regeneration in denervated limbs, and its inhibition must prevent regeneration. Here, we show that the neuronally secreted protein Neuregulin-1 (NRG1) fulfills all these criteria in the axolotl. Immunohistochemistry and in situ hybridization of NRG1 and its active receptor ErbB2 revealed that they are expressed in regenerating blastemas but lost upon denervation. NRG1 was localized to the wound epithelium prior to blastema formation and was later strongly expressed in proliferating blastemal cells. Supplementation by implantation of NRG1-soaked beads rescued regeneration to digits in denervated limbs, and pharmacological inhibition of NRG1 signaling reduced cell proliferation, blocked blastema formation and induced aberrant collagen deposition in fully innervated limbs. Taken together, our results show that nerve-dependent NRG1/ErbB2 signaling promotes blastemal proliferation in the regenerating limb and may play an essential role in blastema formation, thus providing insight into the longstanding question of why nerves are required for axolotl limb regeneration. © 2016. Published by The Company of Biologists Ltd.

  6. Long-lived keratin 15+ esophageal progenitor cells contribute to homeostasis and regeneration

    PubMed Central

    Giroux, Véronique; Lento, Ashley A.; Islam, Mirazul; Pitarresi, Jason R.; Kharbanda, Akriti; Hamilton, Kathryn E.; Whelan, Kelly A.; Long, Apple; Rhoades, Ben; Tang, Qiaosi; Nakagawa, Hiroshi; Lengner, Christopher J.; Bass, Adam J.; Wileyto, E. Paul; Klein-Szanto, Andres J.; Wang, Timothy C.; Rustgi, Anil K.

    2017-01-01

    The esophageal lumen is lined by a stratified squamous epithelium comprised of proliferative basal cells that differentiate while migrating toward the luminal surface and eventually desquamate. Rapid epithelial renewal occurs, but the specific cell of origin that supports this high proliferative demand remains unknown. Herein, we have described a long-lived progenitor cell population in the mouse esophageal epithelium that is characterized by expression of keratin 15 (Krt15). Genetic in vivo lineage tracing revealed that the Krt15 promoter marks a long-lived basal cell population able to self-renew, proliferate, and generate differentiated cells, consistent with a progenitor/stem cell population. Transcriptional profiling demonstrated that Krt15+ basal cells are molecularly distinct from Krt15– basal cells. Depletion of Krt15-derived cells resulted in decreased proliferation, thereby leading to atrophy of the esophageal epithelium. Further, Krt15+ cells were radioresistant and contributed to esophageal epithelial regeneration following radiation-induced injury. These results establish the presence of a long-lived and indispensable Krt15+ progenitor cell population that provides additional perspective on esophageal epithelial biology and the widely prevalent diseases that afflict this epithelium. PMID:28481227

  7. Peripheral Exophytic Oral Lesions: A Clinical Decision Tree

    PubMed Central

    Safi, Yaser; Jafari, Soudeh

    2017-01-01

    Diagnosis of peripheral oral exophytic lesions might be quite challenging. This review article aimed to introduce a decision tree for oral exophytic lesions according to their clinical features. General search engines and specialized databases including PubMed, PubMed Central, Medline Plus, EBSCO, Science Direct, Scopus, Embase, and authenticated textbooks were used to find relevant topics by means of keywords such as “oral soft tissue lesion,” “oral tumor like lesion,” “oral mucosal enlargement,” and “oral exophytic lesion.” Related English-language articles published since 1988 to 2016 in both medical and dental journals were appraised. Upon compilation of data, peripheral oral exophytic lesions were categorized into two major groups according to their surface texture: smooth (mesenchymal or nonsquamous epithelium-originated) and rough (squamous epithelium-originated). Lesions with smooth surface were also categorized into three subgroups according to their general frequency: reactive hyperplastic lesions/inflammatory hyperplasia, salivary gland lesions (nonneoplastic and neoplastic), and mesenchymal lesions (benign and malignant neoplasms). In addition, lesions with rough surface were summarized in six more common lesions. In total, 29 entities were organized in the form of a decision tree in order to help clinicians establish a logical diagnosis by a stepwise progression method. PMID:28757870

  8. Vasopressin regulates the growth of the biliary epithelium in polycystic liver disease

    PubMed Central

    Mancinelli, Romina; Franchitto, Antonio; Glaser, Shannon; Vetuschi, Antonella; Venter, Julie; Sferra, Roberta; Pannarale, Luigi; Olivero, Francesca; Carpino, Guido; Alpini, Gianfranco; Onori, Paolo; Gaudio, Eugenio

    2017-01-01

    The neurohypophysial hormone arginine vasopressin (AVP) acts by three distinct receptor subtypes: V1a, V1b, and V2. In the liver, AVP is involved in ureogenesis, glycogenolysis, neoglucogenesis and regeneration. No data exist about the presence of AVP in the biliary epithelium. Cholangiocytes are the target cells in a number of animal models of cholestasis, including bile duct ligation (BDL), and in several human pathologies, such as polycystic liver disease characterized by the presence of cysts that bud from the biliary epithelium. In vivo, liver fragments from normal and BDL mice and rats as well as liver samples from normal and ADPKD patients were collected to evaluate: (i) intrahepatic bile duct mass by immunohistochemistry for cytokeratin-19; and (ii) expression of V1a, V1b and V2 by immunohistochemistry, immunofluorescence and real-time PCR. In vitro, small and large mouse cholangiocytes, H69 (non-malignant human cholangiocytes) and LCDE (human cholangiocytes from the cystic epithelium) were stimulated with vasopressin in the absence/presence of AVP antagonists such as OPC-31260 and Tolvaptan, before assessing cellular growth by MTT assay and cAMP levels. Cholangiocytes express V2 receptor that was upregulated following BDL and in ADPKD liver samples. Administration of AVP increased proliferation and cAMP levels of small cholangiocytes and LCDE cells. We found no effect in the proliferation of large mouse cholangiocytes and H69 cells. Increases were blocked by preincubation with the AVP antagonists. These results showed that AVP and its receptors may be important in the modulation of the proliferation rate of the biliary epithelium. PMID:27571215

  9. Vasopressin regulates the growth of the biliary epithelium in polycystic liver disease.

    PubMed

    Mancinelli, Romina; Franchitto, Antonio; Glaser, Shannon; Vetuschi, Antonella; Venter, Julie; Sferra, Roberta; Pannarale, Luigi; Olivero, Francesca; Carpino, Guido; Alpini, Gianfranco; Onori, Paolo; Gaudio, Eugenio

    2016-11-01

    The neurohypophysial hormone arginine vasopressin (AVP) acts by three distinct receptor subtypes: V1a, V1b, and V2. In the liver, AVP is involved in ureogenesis, glycogenolysis, neoglucogenesis and regeneration. No data exist about the presence of AVP in the biliary epithelium. Cholangiocytes are the target cells in a number of animal models of cholestasis, including bile duct ligation (BDL), and in several human pathologies, such as polycystic liver disease characterized by the presence of cysts that bud from the biliary epithelium. In vivo, liver fragments from normal and BDL mice and rats as well as liver samples from normal and ADPKD patients were collected to evaluate: (i) intrahepatic bile duct mass by immunohistochemistry for cytokeratin-19; and (ii) expression of V1a, V1b and V2 by immunohistochemistry, immunofluorescence and real-time PCR. In vitro, small and large mouse cholangiocytes, H69 (non-malignant human cholangiocytes) and LCDE (human cholangiocytes from the cystic epithelium) were stimulated with vasopressin in the absence/presence of AVP antagonists such as OPC-31260 and Tolvaptan, before assessing cellular growth by MTT assay and cAMP levels. Cholangiocytes express V2 receptor that was upregulated following BDL and in ADPKD liver samples. Administration of AVP increased proliferation and cAMP levels of small cholangiocytes and LCDE cells. We found no effect in the proliferation of large mouse cholangiocytes and H69 cells. Increases were blocked by preincubation with the AVP antagonists. These results showed that AVP and its receptors may be important in the modulation of the proliferation rate of the biliary epithelium.

  10. Neurotrophic regulation of fibroblast dedifferentiation during limb skeletal regeneration in the axolotl (Ambystoma mexicanum).

    PubMed

    Satoh, Akira; Cummings, Gillian M C; Bryant, Susan V; Gardiner, David M

    2010-01-15

    The ability of animals to repair tissue damage is widespread and impressive. Among tissues, the repair and remodeling of bone occurs during growth and in response to injury; however, loss of bone above a threshold amount is not regenerated, resulting in a "critical-size defect" (CSD). The development of therapies to replace or regenerate a CSD is a major focus of research in regenerative medicine and tissue engineering. Adult urodeles (salamanders) are unique in their ability to regenerate complex tissues perfectly, yet like mammals do not regenerate a CSD. We report on an experimental model for the regeneration of a CSD in the axolotl (the Excisional Regeneration Model) that allows for the identification of signals to induce fibroblast dedifferentiation and skeletal regeneration. This regenerative response is mediated in part by BMP signaling, as is the case in mammals; however, a complete regenerative response requires the induction of a population of undifferentiated, regeneration-competent cells. These cells can be induced by signaling from limb amputation to generate blastema cells that can be grafted to the wound, as well as by signaling from a nerve and a wound epithelium to induce blastema cells from fibroblasts within the wound environment. Copyright 2009 Elsevier Inc. All rights reserved.

  11. The Effect of Plasma Exposure on Tail Regeneration of Tadpoles Xenopus Laevis

    NASA Astrophysics Data System (ADS)

    June, Joyce; Rivie, Adonis; Ezuduemoih, Raphael; Menon, Jaishri; Martus, Kevin

    2014-03-01

    Wound healing requires a balanced combination of nutrients and growth factors for healing and tissue regeneration. The effect of plasma exposure on tail regeneration of tadpoles, Xenopus laevis is investigated. The exposure of the wound to the helium plasma immediately followed the amputation of 40% of the tail. Amputation of the tail initiates regeneration of spinal cord, muscle, notochord, skin and connective tissues. By 24 h, the wound was covered by wound epithelium and blastema was formed by day 5. There was increased angiogenesis in plasma exposed tail regenerate compared to the control following 5 d post amputation. Observed was an increase in NO production in the regenerate of plasma exposed tadpoles was derived from increased activity of nNOS and iNOS. Western blot analysis for vascular endothelial growth factor showed stronger bands for the protein in amputated tadpoles of both the groups. Analysis of the composition and characteristics of the plasma using optical emission spectroscopy indicates excited state species consisting of N2, N2+,and OH is present in the plasma. This study was supported, in part, by the NSF Grant 1040108.

  12. Lesion of the Olfactory Epithelium Accelerates Prion Neuroinvasion and Disease Onset when Prion Replication Is Restricted to Neurons

    PubMed Central

    Crowell, Jenna; Wiley, James A.; Bessen, Richard A.

    2015-01-01

    Natural prion diseases of ruminants are moderately contagious and while the gastrointestinal tract is the primary site of prion agent entry, other mucosae may be entry sites in a subset of infections. In the current study we examined prion neuroinvasion and disease induction following disruption of the olfactory epithelium in the nasal mucosa since this site contains environmentally exposed olfactory sensory neurons that project directly into the central nervous system. Here we provide evidence for accelerated prion neuroinvasion and clinical onset from the olfactory mucosa after disruption and regeneration of the olfactory epithelium and when prion replication is restricted to neurons. In transgenic mice with neuron restricted replication of prions, there was a reduction in survival when the olfactory epithelium was disrupted prior to intranasal inoculation and there was >25% decrease in the prion incubation period. In a second model, the neurotropic DY strain of transmissible mink encephalopathy was not pathogenic in hamsters by the nasal route, but 50% of animals exhibited brain infection and/or disease when the olfactory epithelium was disrupted prior to intranasal inoculation. A time course analysis of prion deposition in the brain following loss of the olfactory epithelium in models of neuron-restricted prion replication suggests that neuroinvasion from the olfactory mucosa is via the olfactory nerve or brain stem associated cranial nerves. We propose that induction of neurogenesis after damage to the olfactory epithelium can lead to prion infection of immature olfactory sensory neurons and accelerate prion spread to the brain. PMID:25822718

  13. Risk factors and etiopathogenesis of potentially premalignant oral epithelial lesions.

    PubMed

    Porter, Stephen; Gueiros, Luiz Alcino; Leão, Jair Carneiro; Fedele, Stefano

    2018-06-01

    Potentially malignant oral mucosal disease has some ability to give rise to malignancy of the oral epithelium, that is, oral squamous cell carcinoma (OSCC). The present article provides a succinct review of the possible or probable causes of potentially premalignant oral epithelial lesions. There is a focus upon studies that examined the causes or etiologic associations with clinically likely or histopathologically detectable oral epithelial dysplasia. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Prognostic Potential of N-Cadherin in Oral Squamous Cell Carcinoma via Immunohistochemical Methods.

    PubMed

    Chandolia, Betina; Rajliwal, Jai Parkash; Bajpai, Manas; Arora, Manika

    2017-08-01

    To assess the prognostic potential for N-cadherin in oral squamous cell carcinoma and oral epithelial dysplasia. Across-sectional study, analytical study. Maharishi Markandeshwar College of Dental Science Research (MMCDSR), Ambala, India, from 2011 to 2014. Immunohistochemistry was used to observe the N-cadherin expression in 100 cases having epithelium with normal oral mucosa, oral epithelial dysplastic lesions and oral squamous cell carcinoma (OSCC). For statistical significance, SPSS 13.0 was used to calculate the data by Mann-Whitney and Kruskal-Wallis tests. In OSCC, N-cadherin expression was more evident than in oral epithelial dysplasia followed by the normal oral epithelium that did not show any dysplastic changes (p=0.001). Conversely, N-cadherin expression was not significant among the histological grade of OSCC. N-cadherin can be used as a potential biomarker for early diagnosis of OSCC. However, the N-cadherin expression did not show any correlation with the histological grade of OSCC.

  15. E-cigarettes and flavorings induce inflammatory and pro-senescence responses in oral epithelial cells and periodontal fibroblasts.

    PubMed

    Sundar, Isaac K; Javed, Fawad; Romanos, Georgios E; Rahman, Irfan

    2016-11-22

    Electronic-cigarettes (e-cigs) represent a significant and increasing proportion of tobacco product consumption, which may pose an oral health concern. Oxidative/carbonyl stress via protein carbonylation is an important factor in causing inflammation and DNA damage. This results in stress-induced premature senescence (a state of irreversible growth arrest which re-enforces chronic inflammation) in gingival epithelium, which may contribute to the pathogenesis of oral diseases. We show that e-cigs with flavorings cause increased oxidative/carbonyl stress and inflammatory cytokine release in human periodontal ligament fibroblasts, Human Gingival Epithelium Progenitors pooled (HGEPp), and epigingival 3D epithelium. We further show increased levels of prostaglandin-E2 and cycloxygenase-2 are associated with upregulation of the receptor for advanced glycation end products (RAGE) by e-cig exposure-mediated carbonyl stress in gingival epithelium/tissue. Further, e-cigs cause increased oxidative/carbonyl and inflammatory responses, and DNA damage along with histone deacetylase 2 (HDAC2) reduction via RAGE-dependent mechanisms in gingival epithelium. A greater response is elicited by flavored e-cigs. Increased oxidative stress, pro-inflammatory and pro-senescence responses (DNA damage and HDAC2 reduction) can result in dysregulated repair due to proinflammatory and pro-senescence responses in periodontal cells. These data highlight the pathologic role of e-cig aerosol and its flavoring to cells and tissues of the oral cavity in compromised oral health.

  16. MOR23 promotes muscle regeneration and regulates cell adhesion and migration

    PubMed Central

    Griffin, Christine A.; Kafadar, Kimberly A.; Pavlath, Grace K.

    2009-01-01

    Summary Odorant receptors (ORs) in the olfactory epithelium bind to volatile small molecules leading to the perception of smell. ORs are expressed in many tissues but their functions are largely unknown. We show multiple ORs display distinct mRNA expression patterns during myogenesis in vitro and muscle regeneration in vivo. Mouse OR23 (MOR23) expression is induced during muscle regeneration when muscle cells are extensively fusing and plays a key role in regulating migration and adhesion of muscle cells in vitro, two processes common during tissue repair. A soluble ligand for MOR23 is secreted by muscle cells in vitro and muscle tissue in vivo. MOR23 is necessary for proper skeletal muscle regeneration as loss of MOR23 leads to increased myofiber branching, commonly associated with muscular dystrophy. Together these data identify a functional role for an OR outside of the nose and suggest a larger role for ORs during tissue repair. PMID:19922870

  17. Ascl1 (Mash1) Knockout Perturbs Differentiation of Nonneuronal Cells in Olfactory Epithelium

    PubMed Central

    Jang, Woochan; Wildner, Hendrik; Schwob, James E.

    2012-01-01

    The embryonic olfactory epithelium (OE) generates only a very few olfactory sensory neurons when the basic helix-loop-helix transcription factor, ASCL1 (previously known as MASH1) is eliminated by gene mutation. We have closely examined the structure and composition of the OE of knockout mice and found that the absence of neurons dramatically affects the differentiation of multiple other epithelial cell types as well. The most prominent effect is observed within the two known populations of stem and progenitor cells of the epithelium. The emergence of horizontal basal cells, a multipotent progenitor population in the adult epithelium, is anomalous in the Ascl1 knockout mice. The differentiation of globose basal cells, another multipotent progenitor population in the adult OE, is also aberrant. All of the persisting globose basal cells are marked by SOX2 expression, suggesting a prominent role for SOX2 in progenitors upstream of Ascl1. However, NOTCH1-expressing basal cells are absent from the knockout; since NOTCH1 signaling normally acts to suppress Ascl1 via HES1 and drives sustentacular (Sus) cell differentiation during adult epithelial regeneration, its absence suggests reciprocity between neurogenesis and the differentiation of Sus cells. Indeed, the Sus cells of the mutant mice express a markedly lower level of HES1, strengthening that notion of reciprocity. Duct/gland development appears normal. Finally, the expression of cKIT by basal cells is also undetectable, except in those small patches where neurogenesis escapes the effects of Ascl1 knockout and neurons are born. Thus, persistent neurogenic failure distorts the differentiation of multiple other cell types in the olfactory epithelium. PMID:23284756

  18. Effects of artificial tracheal fixation on tracheal epithelial regeneration and prevention of tracheal stenosis.

    PubMed

    Nakaegawa, Yuta; Nakamura, Ryosuke; Tada, Yasuhiro; Suzuki, Ryo; Takezawa, Toshiaki; Nakamura, Tatsuo; Omori, Koichi

    2017-06-01

    Tight fixation of the artificial trachea is important for epithelialization and tracheal stenosis. The authors have developed an artificial trachea and have used it for tracheal reconstruction. Although various studies on tracheal reconstruction have been conducted, no studies have examined the effect of artificial tracheal fixation on tracheal stenosis and regeneration. Therefore, the purpose of the present study was to evaluate the effect of artificial tracheal fixation. Preliminary animal experiment. Artificial tracheae were implanted into rabbits with partial tracheal defects. Tracheal stenosis and regeneration of the tracheal epithelium on the artificial tracheae were evaluated by endoscopic examination, scanning electron microscopic analysis, and histological examination. The artificial tracheae fixed to the tracheal defects were classified into three groups (0-point, 4-point, and 8-point) by the number of fixation points. At 14 and 28 days post-implantation, the luminal surface of the implantation area was mostly covered with epithelium in all fixation groups. However, a small amount of granulation tissue was observed in the 0-point fixation group at 14 days post-implantation. Moreover, tracheal stenosis did not occur in the 8-point fixation group, but stenosis was detected in the other groups.

  19. Melanin: the biophysiology of oral melanocytes and physiological oral pigmentation

    PubMed Central

    2014-01-01

    The presence of melanocytes in the oral epithelium is a well-established fact, but their physiological functions are not well defined. Melanin provides protection from environmental stressors such as ultraviolet radiation and reactive oxygen species; and melanocytes function as stress-sensors having the capacity both to react to and to produce a variety of microenvironmental cytokines and growth factors, modulating immune, inflammatory and antibacterial responses. Melanocytes also act as neuroendocrine cells producing local neurotransmitters including acetylcholine, catecholamines and opioids, and hormones of the melanocortin system such as proopiomelanocortin, adrenocorticotropic hormone and α-melanocyte stimulating hormone, that participate in intracellular and in intercellular signalling pathways, thus contributing to tissue homeostasis. There is a wide range of normal variation in melanin pigmentation of the oral mucosa. In general, darker skinned persons more frequently have oral melanin pigmentation than light-skinned persons. Variations in oral physiological pigmentation are genetically determined unless associated with some underlying disease. In this article, we discuss some aspects of the biophysiology of oral melanocytes, of the functions of melanin, and of physiological oral pigmentation. PMID:24661309

  20. Noninvasive molecular screening for oral precancer in Fanconi anemia patients.

    PubMed

    Smetsers, Stephanie E; Velleuer, Eunike; Dietrich, Ralf; Wu, Thijs; Brink, Arjen; Buijze, Marijke; Deeg, Dorly J H; Soulier, Jean; Leemans, C René; Braakhuis, Boudewijn J M; Brakenhoff, Ruud H

    2015-11-01

    LOH at chromosome arms 3p, 9p, 11q, and 17p are well-established oncogenetic aberrations in oral precancerous lesions and promising biomarkers to monitor the development of oral cancer. Noninvasive LOH screening of brushed oral cells is a preferable method for precancer detection in patients at increased risk for head and neck squamous cell carcinoma (HNSCC), such as patients with Fanconi anemia. We determined the prevalence of LOH in brushed samples of the oral epithelium of 141 patients with Fanconi anemia and 144 aged subjects, and studied the association between LOH and HNSCC. LOH was present in 14 (9.9%) nontransplanted patients with Fanconi anemia, whereas LOH was not detected in a low-risk group (n = 50, >58 years, nonsmoking/nonalcohol history) and a group with somewhat increased HNSCC risk (n = 94, >58 years, heavy smoking/excessive alcohol use); Fisher exact test, P = 0.023 and P = 0.001, respectively. Most frequent genetic alteration was LOH at 9p. Age was a significant predictor of LOH (OR, 1.13, P = 0.001). Five patients with Fanconi anemia developed HNSCC during the study at a median age of 39.6 years (range, 24.8-53.7). LOH was significantly associated with HNSCC (Fisher exact test, P = 0.000). Unexpectedly, the LOH assay could not be used for transplanted patients with Fanconi anemia because donor DNA in brushed oral epithelium, most likely from donor leukocytes present in the oral cavity, disturbed the analysis. Noninvasive screening using a LOH assay on brushed samples of the oral epithelium has a promising outlook in patients with Fanconi anemia. However, assays need to be adapted in case of stem cell transplantation, because of contaminating donor DNA. ©2015 American Association for Cancer Research.

  1. Gene-expression analysis of hair cell regeneration in the zebrafish lateral line

    PubMed Central

    Jiang, Linjia; Romero-Carvajal, Andres; Haug, Jeff S.; Seidel, Christopher W.; Piotrowski, Tatjana

    2014-01-01

    Deafness caused by the terminal loss of inner ear hair cells is one of the most common sensory diseases. However, nonmammalian animals (e.g., birds, amphibians, and fish) regenerate damaged hair cells. To understand better the reasons underpinning such disparities in regeneration among vertebrates, we set out to define at high resolution the changes in gene expression associated with the regeneration of hair cells in the zebrafish lateral line. We performed RNA-Seq analyses on regenerating support cells purified by FACS. The resulting expression data were subjected to pathway enrichment analyses, and the differentially expressed genes were validated in vivo via whole-mount in situ hybridizations. We discovered that cell cycle regulators are expressed hours before the activation of Wnt/β-catenin signaling following hair cell death. We propose that Wnt/β-catenin signaling is not involved in regulating the onset of proliferation but governs proliferation at later stages of regeneration. In addition, and in marked contrast to mammals, our data clearly indicate that the Notch pathway is significantly down-regulated shortly after injury, thus uncovering a key difference between the zebrafish and mammalian responses to hair cell injury. Taken together, our findings lay the foundation for identifying differences in signaling pathway regulation that could be exploited as potential therapeutic targets to promote either sensory epithelium or hair cell regeneration in mammals. PMID:24706903

  2. Anti-inflammatory and protective effects of 2-methacryloyloxyethyl phosphorylcholine polymer on oral epithelial cells.

    PubMed

    Yumoto, Hiromichi; Hirota, Katsuhiko; Hirao, Kouji; Miyazaki, Tsuyoshi; Yamamoto, Nobuyuki; Miyamoto, Koji; Murakami, Keiji; Fujiwara, Natsumi; Matsuo, Takashi; Miyake, Yoichiro

    2015-02-01

    Periodontitis is a chronic inflammatory disease initiated by a microbial biofilm formed in the periodontal pocket. Gingival epithelium plays important roles as the first physical barrier to bacterial invasion and in orchestrating the innate immune reaction via toll-like receptors (TLRs), which recognize various bacterial products, and maintaining its function. Newly developed oral care products to inhibit bacterial adherence, subsequent inflammatory reaction and protect the gingival epithelium are expected. We previously reported that 2-methacryloyloxyethyl phosphorylcholine (MPC)-polymer coating decreased bacterial adhesion to human oral keratinocytes, RT-7, and mouth-rinsing with MPC-polymer inhibited the increase of oral bacteria. In this study, regarding the possibility of MPC-polymer application for preventing the adherence of periodontal pathogen, subsequent inflammatory reaction and protection of gingival epithelium, we examined the effects of MPC-polymer on the adherence of Porphyromonas gingivalis, major periodontitis-related pathogen, and TLR2 ligand to RT-7 and subsequent interleukin (IL)-8 production. MPC-polymer treatment significantly reduced P. gingivalis adherence by 44% and TLR2-mediated IL-8 production by blocking the binding of its specific-ligand in a concentration-dependent manner. Furthermore, MPC-polymer pretreatment protected RT-7 from injury by chemical irritants, cetylpyridinium chloride. These findings suggest that MPC-polymer is potentially useful for oral care to prevent oral infection and to maintain oral epithelial function. © 2014 Wiley Periodicals, Inc.

  3. Stem/progenitor cells derived from the cochlear sensory epithelium give rise to spheres with distinct morphologies and features.

    PubMed

    Diensthuber, Marc; Oshima, Kazuo; Heller, Stefan

    2009-06-01

    Nonmammalian vertebrates regenerate lost sensory hair cells by means of asymmetric division of supporting cells. Inner ear or lateral line supporting cells in birds, amphibians, and fish consequently serve as bona fide stem cells resulting in high regenerative capacity of hair cell-bearing organs. Hair cell regeneration does not happen in the mammalian cochlea, but cells with proliferative capacity can be isolated from the neonatal cochlea. These cells have the ability to form clonal floating colonies, so-called spheres, when cultured in nonadherent conditions. We noticed that the sphere population derived from mouse cochlear sensory epithelium cells was heterogeneous, consisting of morphologically distinct sphere types, hereby classified as solid, transitional, and hollow. Cochlear sensory epithelium-derived stem/progenitor cells initially give rise to small solid spheres, which subsequently transition into hollow spheres, a change that is accompanied by epithelial differentiation of the majority of sphere cells. Only solid spheres, and to a lesser extent, transitional spheres, appeared to harbor self-renewing stem cells, whereas hollow spheres could not be consistently propagated. Solid spheres contained significantly more rapidly cycling Pax-2-expressing presumptive otic progenitor cells than hollow spheres. Islet-1, which becomes upregulated in nascent sensory patches, was also more abundant in solid than in hollow spheres. Likewise, hair cell-like cells, characterized by the expression of multiple hair cell markers, differentiated in significantly higher numbers in cell populations derived from solid spheres. We conclude that cochlear sensory epithelium cell populations initially give rise to small solid spheres that have self-renewing capacity before they subsequently convert into hollow spheres, a process that is accompanied by loss of stemness and reduced ability to spontaneously give rise to hair cell-like cells. Solid spheres might, therefore, represent

  4. Distribution and time course of hair cell regeneration in the pigeon utricle

    NASA Technical Reports Server (NTRS)

    Dye, B. J.; Frank, T. C.; Newlands, S. D.; Dickman, J. D.

    1999-01-01

    Vestibular and cochlear regeneration following ototoxic insult from aminoglycoside antibiotics has been well documented, particularly in birds. In the present study, intraotic application of a 2 mg streptomycin paste was used to achieve complete vestibular hair cell destruction in pigeons (Columba livia) while preserving regenerative ability. Scanning electron microscopy was used to quantify hair cell density longitudinally during regeneration in three different utricular macula locations, including the striola, central and peripheral regions. The utricular epithelium was void of stereocilia (indicating hair cell loss) at 4 days after intraotic treatment with streptomycin. At 2 weeks the stereocilia began to appear randomly and mostly in an immature form. However, when present most kinocilia were polarized toward the developing striola. Initially, regeneration occurred more rapidly in the central and peripheral regions of the utricle as compared to the striola. As regeneration proceeded from 2 to 12 weeks, hair cell density in the striola region equaled the density noted in the central and peripheral regions. At 24 weeks, hair cell density of the central and peripheral regions was equal to normal values, however the striola region had a slightly greater hair cell density than that observed for normal animals.

  5. BDNF is required for taste axon regeneration following unilateral chorda tympani nerve section.

    PubMed

    Meng, Lingbin; Huang, Tao; Sun, Chengsan; Hill, David L; Krimm, Robin

    2017-07-01

    Taste nerves readily regenerate to reinnervate denervated taste buds; however, factors required for regeneration have not yet been identified. When the chorda tympani nerve is sectioned, expression of brain-derived neurotrophic factor (BDNF) remains high in the geniculate ganglion and lingual epithelium, despite the loss of taste buds. These observations suggest that BDNF is present in the taste system after nerve section and may support taste nerve regeneration. To test this hypothesis, we inducibly deleted Bdnf during adulthood in mice. Shortly after Bdnf gene recombination, the chorda tympani nerve was unilaterally sectioned causing a loss of both taste buds and neurons, irrespective of BDNF levels. Eight weeks after nerve section, however, regeneration was differentially affected by Bdnf deletion. In control mice, there was regeneration of the chorda tympani nerve and taste buds reappeared with innervation. In contrast, few taste buds were reinnervated in mice lacking normal Bdnf expression such that taste bud number remained low. In all genotypes, taste buds that were reinnervated were normal-sized, but non-innervated taste buds remained small and atrophic. On the side of the tongue contralateral to the nerve section, taste buds for some genotypes became larger and all taste buds remained innervated. Our findings suggest that BDNF is required for nerve regeneration following gustatory nerve section. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Guided bone regeneration using individualized ceramic sheets.

    PubMed

    Malmström, J; Anderud, J; Abrahamsson, P; Wälivaara, D-Å; Isaksson, S G; Adolfsson, E

    2016-10-01

    Guided bone regeneration (GBR) describes the use of membranes to regenerate bony defects. A membrane for GBR needs to be biocompatible, cell-occlusive, non-toxic, and mouldable, and possess space-maintaining properties including stability. The purpose of this pilot study was to describe a new method of GBR using individualized ceramic sheets to perfect bone regeneration prior to implant placement; bone regeneration was assessed using traditional histology and three-dimensional (3D) volumetric changes in the bone and soft tissue. Three patients were included. After full-thickness flap reflection, the individualized ceramic sheets were fixed. The sites were left to heal for 7 months. All patients were evaluated preoperatively and at 7 months postoperative using cone beam computed tomography and 3D optical equipment. Samples of the regenerated bone and soft tissue were collected and analyzed. The bone regenerated in the entire interior volume of all sheets. Bone biopsies revealed newly formed trabecular bone with a lamellar structure. Soft tissue biopsies showed connective tissue with no signs of an inflammatory response. This was considered to be newly formed periosteum. Thus ceramic individualized sheets can be used to regenerate large volumes of bone in both vertical and horizontal directions independent of the bone defect and with good biological acceptance of the material. Copyright © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  7. Guided Bone Regeneration in Long-Bone Defects with a Structural Hydroxyapatite Graft and Collagen Membrane

    DTIC Science & Technology

    2013-01-01

    Praetorius, F. Guided tissue regeneration using de- gradable and nondegradable membranes in rabbit tibia. Clin Oral Implants Res 4, 172, 1993. 8. Queiroz... Regeneration of periodontal tissues : combinations of barrier membranes and grafting materials–biological foundation and preclinical evi- dence: a...structural graft provides benefits for bone tissue regeneration in terms of early interfacial integration. Introduction The treatment of large-bone defects

  8. LYSOSOMAL FRACTIONS FROM TRANSITIONAL EPITHELIUM

    PubMed Central

    Kanczak, Norbert M.; Krall, Joseph I.; Hayes, E. Russell; Elliott, Willard B.

    1965-01-01

    Histochemical data suggested that the so called lipoid granules of transitional epithelium in some species are equivalent to lysosomes. Scrapings of bovine and canine transitional epithelium were subjected to differential centrifugation to confirm this identification biochemically. Fractions of rat liver, the classic source of lysosomes, were also prepared by the same methods to compare with the fractions obtained from urinary epithelium. In contrast to rat liver, uroepithelial fractions with a high relative specific activity for hydrolases were sedimented before the heavy mitochondria. Microscopically, these fractions contained the highest proportion of lipoid granules. The size and sedimentation characteristics of lysosomes from transitional epithelium more closely resembled those of lysosomes derived from rat kidney than those isolated from liver. PMID:14326111

  9. [The stimulation of pulmonary epithelial regeneration and of the clearance function of the mucociliary apparatus by using bemetil].

    PubMed

    Kobylianskiĭ, V I

    1995-01-01

    A method of stimulation of the bronchial epithelium regeneration and mucociliary apparatus function is described. The effect is achieved with the help of bemithyl, an agent of the actoprotector group. In combination with immunocorrection, this effect is potentiated. The method is quite simple and may be extensively used in experimental investigations and clinical practice.

  10. Congenital choristomas of the oral cavity in children.

    PubMed

    Chai, Raymond L; Ozolek, John A; Branstetter, Barton F; Mehta, Deepak K; Simons, Jeffrey P

    2011-10-01

    To review our institutional experience with oral cavity choristomas in children. Retrospective case series and medical record review. Medical records including clinic notes, operative reports, radiologic studies, and pathology specimens were reviewed. All imaging studies and pathology material were reviewed by a head and neck radiologist and pediatric pathologist, respectively. Sixteen patients (10 males and 6 females) with congenital oral cavity choristomas were identified. Mean age at diagnosis was 1.8 months. Location of the lesions included tongue (n = 9) and floor of mouth (n = 7). Preoperative imaging included magnetic resonance imaging (n = 6), computed tomography (n = 5), plain radiography (n = 1), and no imaging (n = 4). Radiographically, the lesions were consistently lobular with well-defined margins, but other imaging features often mimicked other masses that can arise in the tongue and floor of mouth. Symptoms were present in five of 16 patients and included difficulty feeding, swelling with upper respiratory infection, and partial airway obstruction. Complete surgical excision was performed in 15 of 16 patients; mean age at the time of surgery was 12.7 months. One patient underwent marsupialization. No complications were noted perioperatively. No recurrences of choristoma were seen. On histologic examination, the predominant component was cystic with cyst linings of respiratory epithelium (n = 5), gastric (foveolar) epithelium (n = 1), or both (n = 10). This study supports surgical excision as an effective intervention for children with oral cavity choristomas. Because the etiology of these cysts is unknown and diagnostic terminology is widely variable, we propose a more descriptive diagnosis based on the histology (i.e., lingual choristoma [or lingual developmental cyst] with respiratory epithelium or lingual choristoma [or lingual developmental cyst] with gastric epithelium). Copyright © 2011 The American Laryngological, Rhinological, and Otological

  11. [Regeneration of the ciliary beat of human ciliated cells].

    PubMed

    Wolf, G; Koidl, B; Pelzmann, B

    1991-10-01

    The influence of an isotonic, alkaline saline solution (diluted "Emser Sole" or brine from the spa of Bad Ems) on the ciliary beat of isolated cultured human ciliated cells of the upper respiratory tract was investigated. The ciliary beat was observed via an inverted phase contrast microscope (Zeiss Axiomat IDPC) and measured microphotometrically under physiological conditions and after the damaging influence of 1% propanal solution. Under physiological conditions the saline solution had a positive, although statistically not significant influence on the frequency of the ciliary beat. After damage of the cultivated cells by 1% propanal solution, the saline solution had a significant better influence on the regeneration of the cultured cells than a physiological sodium chloride solution. It is concluded that diluted brine from Bad Ems has a positive effect on the ciliary beat of the respiratory epithelium and accelerates its regeneration after damage by viral and bacterial infections, surgery or inhaled noxae.

  12. A loss of profilin-1 in late-stage oral squamous cell carcinoma.

    PubMed

    Adami, Guy R; O'Callaghan, Thomas N; Kolokythas, Antonia; Cabay, Robert J; Zhou, Yalu; Schwartz, Joel L

    2017-08-01

    The genes for PFN1 and TMSB4 are both highly expressed in oral tissue and both encode actin monomer binding proteins thought to play a role in cell motility and possibly other crucial parts of tumor progression. Oral brush cytology of epithelium from oral squamous cell carcinoma (OSCC) was used to measure PFN1 and TMSB4 mRNA in OSCC, while immunohistochemical analysis of tissue was used to check protein levels. High but variable expression of mRNAs encoding these two proteins was observed suggesting they may contribute to tumor characteristics in a subset of OSCCs. Both proteins were highly expressed in normal appearing basal epithelium, in the cytoplasm, and perinuclear area, while expression was minimal in upper epithelial layers. In OSCCs, expression of these proteins varied. In tumors classified as later stage, based on size and/or lymph node involvement, PFN1 levels were lower in tumor epithelium. A control gene, KRT13, showed expression in normal differentiated basal and suprabasal oral mucosa epithelial cells and as reported was lost in OSCC cells. Loss of PFN1 in tumor cells has been associated with lymph node invasion and metastasis in other tumor types, strengthening the argument that the protein has the potential to be a tumor suppressor in late-stage OSCC. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Cap-n-Collar Promotes Tissue Regeneration by Regulating ROS and JNK Signaling in the Drosophila melanogaster Wing Imaginal Disc.

    PubMed

    Brock, Amanda R; Seto, Mabel; Smith-Bolton, Rachel K

    2017-07-01

    Regeneration is a complex process that requires an organism to recognize and repair tissue damage, as well as grow and pattern new tissue. Here, we describe a genetic screen to identify novel regulators of regeneration. We ablated the Drosophila melanogaster larval wing primordium by inducing apoptosis in a spatially and temporally controlled manner and allowed the tissue to regenerate and repattern. To identify genes that regulate regeneration, we carried out a dominant-modifier screen by assessing the amount and quality of regeneration in adult wings heterozygous for isogenic deficiencies. We have identified 31 regions on the right arm of the third chromosome that modify the regenerative response. Interestingly, we observed several distinct phenotypes: mutants that regenerated poorly, mutants that regenerated faster or better than wild-type, and mutants that regenerated imperfectly and had patterning defects. We mapped one deficiency region to cap-n-collar ( cnc ), the Drosophila Nrf2 ortholog, which is required for regeneration. Cnc regulates reactive oxygen species levels in the regenerating epithelium, and affects c-Jun N-terminal protein kinase (JNK) signaling, growth, debris localization, and pupariation timing. Here, we present the results of our screen and propose a model wherein Cnc regulates regeneration by maintaining an optimal level of reactive oxygen species to promote JNK signaling. Copyright © 2017 by the Genetics Society of America.

  14. Human Histologic Repair and Regeneration After Biologic Preparation of Diseased Root Surfaces,

    DTIC Science & Technology

    1983-12-01

    Continue on reverse side if neceesar and Identify by block number) Periodontal disease Tooth roots Connective tissue regeneration 20 ABSTRACT (Continue on... regeneration of periodontal attachment loss, due to inflammatory periodontal disease (1). Most procedures for new attachment achieve a new dentogingival...good appearance for a lifetime. Oral hygiene is the most important factor in the prevention and treatment of inflammatory periodontal diseases

  15. Ovarian surface epithelium at the junction area contains a cancer-prone stem cell niche.

    PubMed

    Flesken-Nikitin, Andrea; Hwang, Chang-Il; Cheng, Chieh-Yang; Michurina, Tatyana V; Enikolopov, Grigori; Nikitin, Alexander Yu

    2013-03-14

    Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer deaths among women in the United States, but its pathogenesis is poorly understood. Some epithelial cancers are known to occur in transitional zones between two types of epithelium, whereas others have been shown to originate in epithelial tissue stem cells. The stem cell niche of the ovarian surface epithelium (OSE), which is ruptured and regenerates during ovulation, has not yet been defined unequivocally. Here we identify the hilum region of the mouse ovary, the transitional (or junction) area between the OSE, mesothelium and tubal (oviductal) epithelium, as a previously unrecognized stem cell niche of the OSE. We find that cells of the hilum OSE are cycling slowly and express stem and/or progenitor cell markers ALDH1, LGR5, LEF1, CD133 and CK6B. These cells display long-term stem cell properties ex vivo and in vivo, as shown by our serial sphere generation and long-term lineage-tracing assays. Importantly, the hilum cells show increased transformation potential after inactivation of tumour suppressor genes Trp53 and Rb1, whose pathways are altered frequently in the most aggressive and common type of human EOC, high-grade serous adenocarcinoma. Our study supports experimentally the idea that susceptibility of transitional zones to malignant transformation may be explained by the presence of stem cell niches in those areas. Identification of a stem cell niche for the OSE may have important implications for understanding EOC pathogenesis.

  16. Differential Expression of Unconventional Myosins in Apoptotic and Regenerating Chick Hair Cells Confirms Two Regeneration Mechanisms

    PubMed Central

    DUNCAN, LUKE J.; MANGIARDI, DOMINIC A.; MATSUI, JONATHAN I.; ANDERSON, JULIA K.; McLAUGHLIN-WILLIAMSON, KATE; COTANCHE, DOUGLAS A.

    2008-01-01

    Hair cells of the inner ear are damaged by intense noise, aging, and aminoglycoside antibiotics. Gentamicin causes oxidative damage to hair cells, inducing apoptosis. In mammals, hair cell loss results in a permanent deficit in hearing and balance. In contrast, avians can regenerate lost hair cells to restore auditory and vestibular function. This study examined the changes of myosin VI and myosin VIIa, two unconventional myosins that are critical for normal hair cell formation and function, during hair cell death and regeneration. During the late stages of apoptosis, damaged hair cells are ejected from the sensory epithelium. There was a 4–5-fold increase in the labeling intensity of both myosins and a redistribution of myosin VI into the stereocilia bundle, concurrent with ejection. Two separate mechanisms were observed during hair cell regeneration. Proliferating supporting cells began DNA synthesis 60 hours after gentamicin treatment and peaked at 72 hours postgentamicin treatment. Some of these mitotically produced cells began to differentiate into hair cells at 108 hours after gentamicin (36 hours after bromodeoxyuridine (BrdU) administration), as demonstrated by the colabeling of myosin VI and BrdU. Myosin VIIa was not expressed in the new hair cells until 120 hours after gentamicin. Moreover, a population of supporting cells expressed myosin VI at 78 hours after gentamicin treatment and myosin VIIa at 90 hours. These cells did not label for BrdU and differentiated far too early to be of mitotic origin, suggesting they arose by direct transdifferentiation of supporting cells into hair cells. PMID:17048225

  17. Spinal cord regeneration in Xenopus tadpoles proceeds through activation of Sox2-positive cells

    PubMed Central

    2012-01-01

    Background In contrast to mammals, amphibians, such as adult urodeles (for example, newts) and anuran larvae (for example, Xenopus) can regenerate their spinal cord after injury. However, the cellular and molecular mechanisms involved in this process are still poorly understood. Results Here, we report that tail amputation results in a global increase of Sox2 levels and proliferation of Sox2+ cells. Overexpression of a dominant negative form of Sox2 diminished proliferation of spinal cord resident cells affecting tail regeneration after amputation, suggesting that spinal cord regeneration is crucial for the whole process. After spinal cord transection, Sox2+ cells are found in the ablation gap forming aggregates. Furthermore, Sox2 levels correlated with regenerative capabilities during metamorphosis, observing a decrease in Sox2 levels at non-regenerative stages. Conclusions Sox2+ cells contribute to the regeneration of spinal cord after tail amputation and transection. Sox2 levels decreases during metamorphosis concomitantly with the lost of regenerative capabilities. Our results lead to a working hypothesis in which spinal cord damage activates proliferation and/or migration of Sox2+ cells, thus allowing regeneration of the spinal cord after tail amputation or reconstitution of the ependymal epithelium after spinal cord transection. PMID:22537391

  18. Chemosensory brush cells of the trachea. A stable population in a dynamic epithelium.

    PubMed

    Saunders, Cecil J; Reynolds, Susan D; Finger, Thomas E

    2013-08-01

    Tracheal brush cells (BCs) are specialized epithelial chemosensors that use the canonical taste transduction cascade to detect irritants. To test whether BCs are replaced at the same rate as other cells in the surrounding epithelium of adult mice, we used 5-bromo-2'-deoxyuridine (BrdU) to label dividing cells. Although scattered BrdU-labeled epithelial cells are present 5-20 days after BrdU, no BCs are labeled. These data indicate that BCs comprise a relatively static population. To determine how BCs are generated during development, we injected 5-day-old mice with BrdU and found labeled BCs and non-BC epithelial cells 5 days after BrdU. During the next 60 days, the percentage of labeled BCs increased, whereas the percentage of other labeled cell types decreased. These data suggest that BCs are generated from non-BC progenitor cells during postnatal tracheal growth. To test whether the adult epithelium retains the capacity to generate BCs, tracheal epithelial cells were recovered from adult mice and grown in an air-liquid interface (ALI) culture. After transition to differentiation conditions, BCs are detected, and comprise 1% of the total cell population by Day 14. BrdU added to cultures before the differentiation of BCs was chased into BCs, indicating that the increase in BC density is attributable to the proliferation of a non-BC progenitor. We conclude that: (1) BCs are normally a static population in adult mice; (2) BC progenitors proliferate and differentiate during neonatal development; and (3) BCs can be regenerated from a proliferative population resident in adult epithelium.

  19. Ovarian surface epithelium at the junction area contains cancer-prone stem cell niche

    PubMed Central

    Flesken-Nikitin, Andrea; Hwang, Chang-Il; Cheng, Chieh-Yang; Michurina, Tatyana V.; Enikolopov, Grigori; Nikitin, Alexander Yu.

    2014-01-01

    Epithelial ovarian cancer (EOC) is the fifth-leading cause of cancer death among women in the United States, but its pathogenesis is poorly understood 1-3. Some epithelial cancers are known to occur in transitional zones between two types of epithelium, while others have been shown to originate in epithelial tissue stem cells 4-6. The stem cell niche of the ovarian surface epithelium (OSE), which is ruptured and regenerates during ovulation, has not yet been unequivocally defined. Here we identify the hilum region of the mouse ovary, the transitional/junction area between OSE, mesothelium and tubal (oviductal) epithelium as a previously unrecognized stem cell niche of the OSE. We find that cells of the hilum OSE are slowly-cycling and express stem/progenitor cell markers ALDH1, Lgr5, Lef1, CD133, and CK6b. These cells display long-term stem cell properties ex vivo and in vivo, as shown by our serial sphere generation and by long-term lineage tracing assays. Importantly, the hilum cells exhibit increased transformation potential after inactivation of tumour suppressor genes Trp53 and Rb1, whose pathways are frequently altered in the most aggressive and common type of human EOC, high-grade serous adenocarcinoma 7,8. Our study experimentally supports the notion that susceptibility of transitional zones to malignant transformation may be explained by the presence of stem cell niches in those areas. Identification of a stem cell niche for the OSE may have important implications for understanding EOC pathogenesis. PMID:23467088

  20. Constitutively active mutation of ACVR1 in oral epithelium causes submucous cleft palate in mice.

    PubMed

    Noda, Kazuo; Mishina, Yuji; Komatsu, Yoshihiro

    2016-07-15

    Cleft palate is among the most common human birth defects. Submucous cleft palate (SMCP) is a subgroup of cleft palate, which may be as common as overt cleft palate. Despite the high frequency of SMCP in humans, only recently have several animal models of SMCP begun to provide insight into the mechanisms by which SMCP develops. In this study, we show that enhanced BMP signaling through constitutively active ACVR1 in palatal epithelium causes submucous cleft palate in mice. In these mutant mice, the fusion of both palatal mesenchyme in hard palate, and muscles in soft palate were hampered by epithelial tissue. During palatal fusion, enhanced SMAD-dependent BMP signaling impaired cell death and altered cell proliferation rate in medial edge epithelium (MEE), and resulted in MEE persistence. At the molecular level, downregulation of ΔNp63, which is crucial for normal palatal fusion, in MEE cells was impaired, leading to a reduction in caspase-3 activation. Our study provides a new insight into the etiology of SMCP caused by augmented BMP signaling. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Oral exposure to polystyrene nanoparticles affects iron absorption

    NASA Astrophysics Data System (ADS)

    Mahler, Gretchen J.; Esch, Mandy B.; Tako, Elad; Southard, Teresa L.; Archer, Shivaun D.; Glahn, Raymond P.; Shuler, Michael L.

    2012-04-01

    The use of engineered nanoparticles in food and pharmaceuticals is expected to increase, but the impact of chronic oral exposure to nanoparticles on human health remains unknown. Here, we show that chronic and acute oral exposure to polystyrene nanoparticles can influence iron uptake and iron transport in an in vitro model of the intestinal epithelium and an in vivo chicken intestinal loop model. Intestinal cells that are exposed to high doses of nanoparticles showed increased iron transport due to nanoparticle disruption of the cell membrane. Chickens acutely exposed to carboxylated particles (50 nm in diameter) had a lower iron absorption than unexposed or chronically exposed birds. Chronic exposure caused remodelling of the intestinal villi, which increased the surface area available for iron absorption. The agreement between the in vitro and in vivo results suggests that our in vitro intestinal epithelium model is potentially useful for toxicology studies.

  2. Usefulness of myofascial flap without skin in contemporary oral and maxillofacial reconstruction.

    PubMed

    Wada, Takeshi; Nakatani, Ken; Hiraishi, Yukihiro; Negoro, Kenji; Iwagami, Yoshinobu; Fujita, Shigeyuki

    2011-06-01

    Pedicle myofascial graft should be considered in contemporary oral and maxillofacial reconstruction for the following reasons: 1) the pedicle myofascial unit is reliable and easily handled; 2) on the grafted myofascia in the oral cavity, the mucosa regenerates naturally with regard to suppleness and surface characteristics; and 3) vascularized myofascial coverage of tissues or materials is useful in some clinical situations. The purpose of this retrospective study was to evaluate the usefulness of this graft material. Using myofascial flaps from the pectoralis major muscle in 15 patients and from the platysma muscle in 11 patients, several types of reconstructive procedures were conducted in the Department of Oral and Maxillofacial Surgery, Wakayama Medical University. Myofascial tissue was used to cover the surgical defect and for regeneration of oral mucosa (24 patients), to prevent exposure of the mandibular reconstruction plate (4 patients), for prevention of wound breakdown and secondary infection in the oral cavity (2 patients), for vascularized coverage of free grafted autologous bone (2 patients), and for protection of large vessels after radical neck dissection (9 patients). Although partial flap necrosis or wound dehiscence was noticed in 3 patients with a platysma-myofascial graft, the healing process of all patients was favorable and required no additional operations. This procedure is most suitable for the reconstruction of small to medium-sized soft tissue defects in the oral cavity, because it induces the formation of nearly normal mucosa through epithelial regeneration without clear scar formation. Myofascial flap is a useful option in certain oral and maxillofacial reconstruction cases in which mucosal regeneration and/or vascularized soft tissue coverage are required. Copyright © 2011 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  3. The anatomy and histology of caudal autotomy and regeneration in lizards.

    PubMed

    Gilbert, Emily A B; Payne, Samantha L; Vickaryous, Matthew K

    2013-01-01

    Abstract Caudal autotomy-the ability to self-detach the tail-is a dramatic adaptation common to many structural-grade lizards. For most species, tail loss is followed by the equally dramatic phenomenon of tail regeneration. Here we review the anatomy and histology of caudal autotomy and regeneration in lizards, drawing heavily from research published over the past 2 decades. The autotomous tail is characterized by various structural adaptations, which act to minimize blood loss and trauma to adjacent tissues. The early phase of wound healing involves a leukocytic response but limited inflammation. Reepithelialization via a specialized wound epithelium is not only critical for scar-free healing but also necessary for subsequent tissue patterning and regenerative outgrowth. Regeneration begins with the formation of the blastema, a mass of proliferating mesenchymal-like cells. As the blastema expands, it is invaded by blood vessels and the spinal cord. Whereas the replacement tail outwardly resembles the original appendage, it differs in several notable respects, including the tissue composition and organization of the skeleton, muscular system, and spinal cord. Increasingly, the lizard tail is being recognized among biomedical scientists as an important model for the study of wound healing and multitissue restoration.

  4. Cell-based regenerative approaches to the treatment of oral soft tissue defects.

    PubMed

    Bates, Damien; Kampa, Peggy

    2013-01-01

    Oral soft tissue plays an important role in the structure and function of the oral cavity by protecting against exogenous substances, pathogens, and mechanical stresses. Repair of oral soft tissue defects that arise as a result of disease, trauma, or congenital abnormalities is often accomplished via transplantation or transfer of autologous mucosal tissue. However, this method of treatment can be complicated by the relatively small amount of autologous mucosal tissue that is available, as well as by the morbidity that may be associated with the donor site and patient reluctance to have oral (eg, palatal) surgery. To circumvent these problems, clinicians have turned to the fields of tissue engineering and regenerative medicine to develop acellular and cellular strategies for regenerating oral soft tissue. This review focuses on the efficacy and safety of cell-based investigational approaches to the regeneration of oral soft tissue.

  5. Transcriptome analysis of the planarian eye identifies ovo as a specific regulator of eye regeneration.

    PubMed

    Lapan, Sylvain W; Reddien, Peter W

    2012-08-30

    Among the millions of invertebrate species with visual systems, the genetic basis of eye development and function is well understood only in Drosophila melanogaster. We describe an eye transcriptome for the planarian Schmidtea mediterranea. Planarian photoreceptors expressed orthologs of genes required for phototransduction and microvillus structure in Drosophila and vertebrates, and optic pigment cells expressed solute transporters and melanin synthesis enzymes similar to those active in the vertebrate retinal pigment epithelium. Orthologs of several planarian eye genes, such as bestrophin-1 and Usher syndrome genes, cause eye defects in mammals when perturbed and were not previously described to have roles in invertebrate eyes. Five previously undescribed planarian eye transcription factors were required for normal eye formation during head regeneration. In particular, a conserved, transcription-factor-encoding ovo gene was expressed from the earliest stages of eye regeneration and was required for regeneration of all cell types of the eye. Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Transcriptome analysis of the planarian eye identifies ovo as a specific regulator of eye regeneration

    PubMed Central

    Lapan, Sylvain W.; Reddien, Peter W.

    2013-01-01

    Summary Among the millions of invertebrate species with visual systems, the genetic basis of eye development and function is well understood only in Drosophila melanogaster. We describe an eye transcriptome for the planarian Schmidtea mediterranea. Planarian photoreceptors expressed orthologs of genes required for phototransduction and microvillus structure in Drosophila and vertebrates, and optic pigment cells expressed solute transporters and melanin synthesis enzymes similar to those active in the vertebrate retinal pigment epithelium. Orthologs of several planarian eye genes, such as bestrophin-1 and Usher syndrome genes, cause eye defects in mammals when perturbed and were not previously described to have roles in invertebrate eyes. Five previously undescribed planarian eye transcription factors were required for normal eye formation during head regeneration. In particular, a conserved, transcription factor-encoding ovo gene was expressed from the earliest stages of eye regeneration and was required for regeneration of all cell types of the eye. PMID:22884275

  7. Serous goblet cells: the protein secreting cells in the oral cavity of a catfish, Rita rita (Hamilton, 1822) (Bagridae, Siluriformes).

    PubMed

    Yashpal, Madhu; Mittal, Ajay Kumar

    2014-02-01

    Serous goblet cells in the oral epithelium of Rita rita are characterized by the presence of distinct eosinophilic granules occupying large parts of the cytoplasm. In R. rita, a range of histochemical results reveal that these cells are involved in proteinaceous secretions, and thus likely contribute to various functions analogous to those of mammalian saliva. The secretions of these cells have also been associated with specific functions and are discussed in relation to their physiological importance with special reference to their roles in lubrication, alteration in viscosity, various functions of mucus such as handling, maneuvering and driving of food items toward the esophagus, maintaining taste sensitivity and protection of the oral epithelium. In addition, the serous goblet cells may also be considered as the primary defensive cell of the oral epithelium of R. rita. The results significantly add to very limited set of literature on the serous goblet cells and provide noteworthy information on the mucous secretions in the oral cavity of fish. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. A Comparative Immunohistochemical Study of Anal Canal Epithelium in Humans and Swine, Focusing on the Anal Transitional Zone Epithelium and the Anal Glands.

    PubMed

    Muranaka, Futoshi; Nakajima, Tomoyuki; Iwaya, Mai; Ishii, Keiko; Higuchi, Kayoko; Ogiwara, Naoko; Miyagawa, Shinichi; Ota, Hiroyoshi

    2018-05-01

    To better understand the cellular origins and differentiation of anal canal epithelial neoplasms, the immunohistochemical profiles of the anal canal epithelium in humans and swine were evaluated. Formalin-fixed tissue sections were immunostained for mucin (MUC: MUC2, MUC5AC, MUC5B), desmoglein 3 (DGS3), p63, CDX2, SOX2, and α-smooth muscle actin (α-SMA). The anal transitional zone (ATZ) epithelium covered the anal sinus and consisted of a stratified epithelium with mucous cells interspersed within the surface lining. Anal glands opened into the anal sinus. Ducts and acini of intraepithelial or periepithelial mucous type were the main structures of human anal glands, whereas those of swine were compound tubuloacinar mixed glands. Distal to the ATZ epithelium, non-keratinized stratified squamous epithelium merged with the keratinized stratified squamous epithelium of the perianal skin. MUC5AC expression predominated over MUC5B expression in the ATZ epithelium, while MUC5B expression was higher in the anal glands. SOX2 was positive in the ATZ epithelium, anal glands, and squamous epithelium except in the perianal skin. In humans, DGS3 was expressed in the ATZ epithelium, anal gland ducts, and squamous epithelium. p63 was detected in the ATZ epithelium, anal glands, and squamous epithelium. Myoepithelial cells positive for α-SMA and p63 were present in the anal glands of swine. Colorectal columnar cells were MUC5B + /MUC2 + /CDX2 + /MUC5AC - /SOX2 - . The ATZ epithelium seems to be a distinctive epithelium, with morphological and functional features allowing smooth defecation. The MUC5AC + /SOX2 + /MUC2 - /CDX2 - profile of the ATZ epithelium and anal glands is a useful feature for diagnosing adenocarcinoma arising from these regions. Anat Rec, 301:796-805, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  9. Interspecies variations in oral epithelial cytokeratin expression

    PubMed Central

    BARRETT, A. W.; SELVARAJAH, S.; FRANEY, S.; WILLS, K.-A.; BERKOVITZ, B. K. B.

    1998-01-01

    The aim of this study was to determine the degree to which the epidermis and oral epithelium of species other than man express cytokeratin (CK) intermediate filaments, which are markers of epithelial differentiation. Fixed, wax-embedded samples of skin, buccal mucosa and gingiva from rhesus monkey, marmoset, cow, sheep, pig, ferret, hamster, axolotl and trout were tested for CK expression using a panel of antihuman CK antibodies and an immunoperoxidase procedure. Human skin and oral mucosa were also stained to act as positive control. The results showed that antihuman CK antibodies stained animal tissues, but the patterns of staining were not always identical to the established human CK profile. Of particular interest was the expression of CK18, typically only detected in ‘simple’ epithelium in man, in bovine, ferret and hamster stratified epithelium from different sites. However, there was evidence of variable anti-CK antibody cross-reactivity, both as a result of intrinsic variations in CK polypeptide structure and as artifacts of fixation. We conclude that some CK are conserved between species, but that biological variables, for example local functional requirements, and technical factors affect the results. These considerations need to be borne in mind in animal studies of epithelial differentiation employing CK immunohistochemistry. Biochemical characterisation is ultimately necessary to determine specific differences between human and animal CK. PMID:9827634

  10. Bioengineering in the oral cavity: our experience

    PubMed Central

    Catalfamo, L; Belli, E; Nava, C; Mici, E; Calvo, A; D’Alessandro, B; De Ponte, FS

    2013-01-01

    Background To date, there are no studies reported in the literature on the possible use of bovine collagen, oxidized regenerated cellulose, or synthetic hyaluronic acid medications in the oral cavity. The aim of this paper is to report the use of bovine collagen, oxidized regenerated cellulose, and synthetic hyaluronic acid medications to improve wound healing in the oral cavity by stimulating granulomatous tissue. Methods From 2007 to 2011, 80 patients (median age 67 years) suffering from oral mucosal lesions participated in this double-blind study. The patients were divided into two groups, each consisting of 40 patients. One group received conventional medications, while the other group of patients were treated with the advanced medications. Results Advanced medications allowed re-epithelialization of the wound margin in 2–20 days, whereas patients receiving conventional medication showed a median healing duration of 45 days. Conclusion The results of this study demonstrate that treating oral mucosal wounds with advanced medication has an advantage with regard to wound healing time, allowing patients to have a rapid, functional, and esthetic recovery. PMID:24143092

  11. Microscopic anatomy of the digestive system in normal and regenerating specimens of the brittlestar Amphipholis kochii.

    PubMed

    Frolova, Lidia T; Dolmatov, Igor Yu

    2010-06-01

    The morphology and regeneration of the digestive system of the ophiuroid Amphipholis kochii were investigated. The epithelia of the esophagus and stomach of A. kochii were composed of typical enterocytes and mucous cells. The digestive epithelium of the stomach contained two types of granular secretory cells. After autotomy of the disk, the animals retained the esophagus and a small part of the stomach. The dedifferentiation of enterocytes and mucous cells began on the first day after autotomy. On day 3 the cells formed an anlage of stomach around the mouth opening. Later, the stomach anlage grew as a result of cell proliferation. The opening on the aboral side of the body was closed by day 7. By this time differentiating cells were already observed in the stomach lining. The stomach mesothelium was formed by peritoneocytes and myoepithelial cells, which migrated from other coelomic epithelia of the body. Our study showed that the formation of the digestive system in A. kochii during regeneration depended on cells from the esophagus and the stomach remnant. Both enterocytes and mucous cells were able to dedifferentiate, migrate, and proliferate to give rise to the luminal epithelium. The basic mechanism of stomach formation was epithelial morphogenesis.

  12. The Microbial Challenge to Pulp Regeneration

    PubMed Central

    Fouad, A.F.

    2011-01-01

    Pulp regeneration is considered in cases where the dental pulp has been destroyed because of microbial irritation. Diverse oral and food-borne micro-organisms are able to invade the pulp space, form biofilm on canal walls, and infiltrate dentinal tubules. Prior to pulp regeneration procedures, the pulp space and dentinal walls need to be sufficiently disinfected to allow for and promote regeneration. The necessary level of disinfection is likely higher than that accepted for traditional endodontic therapy, because in traditional techniques the mere lowering of bacterial loads and prevention of bacterial access to periapical tissues is conducive to healing. Moreover, several of the non-specific antimicrobials used in traditional endodontic therapy may cause significant changes in remaining dentin that interfere with its inherent potential to mediate regeneration. Non-specific antimicrobials also suppress all microbial taxa, which may allow residual virulent micro-organisms to preferentially repopulate the pulp space. Therefore, it is important for endodontic pathogens to be studied by molecular methods that allow for a broad depth of coverage. It is then essential to determine the most effective protocols to disinfect the pulp space, with minimal disruption of remaining dentin. These protocols include the topical use of effective antibiotics, including newer agents that have demonstrated efficacy against endodontic pathogens. PMID:21677080

  13. Raman mapping of oral buccal mucosa: a spectral histopathology approach

    NASA Astrophysics Data System (ADS)

    Behl, Isha; Kukreja, Lekha; Deshmukh, Atul; Singh, S. P.; Mamgain, Hitesh; Hole, Arti R.; Krishna, C. Murali

    2014-12-01

    Oral cancer is one of the most common cancers worldwide. One-fifth of the world's oral cancer subjects are from India and other South Asian countries. The present Raman mapping study was carried out to understand biochemical variations in normal and malignant oral buccal mucosa. Data were acquired using WITec alpha 300R instrument from 10 normal and 10 tumors unstained tissue sections. Raman maps of normal sections could resolve the layers of epithelium, i.e. basal, intermediate, and superficial. Inflammatory, tumor, and stromal regions are distinctly depicted on Raman maps of tumor sections. Mean and difference spectra of basal and inflammatory cells suggest abundance of DNA and carotenoids features. Strong cytochrome bands are observed in intermediate layers of normal and stromal regions of tumor. Epithelium and stromal regions of normal cells are classified by principal component analysis. Classification among cellular components of normal and tumor sections is also observed. Thus, the findings of the study further support the applicability of Raman mapping for providing molecular level insights in normal and malignant conditions.

  14. Retinoid signaling in progenitors controls specification and regeneration of the urothelium.

    PubMed

    Gandhi, Devangini; Molotkov, Andrei; Batourina, Ekatherina; Schneider, Kerry; Dan, Hanbin; Reiley, Maia; Laufer, Ed; Metzger, Daniel; Liang, Fengxia; Liao, Yi; Sun, Tung-Tien; Aronow, Bruce; Rosen, Roni; Mauney, Josh; Adam, Rosalyn; Rosselot, Carolina; Van Batavia, Jason; McMahon, Andrew; McMahon, Jill; Guo, Jin-Jin; Mendelsohn, Cathy

    2013-09-16

    The urothelium is a multilayered epithelium that serves as a barrier between the urinary tract and blood, preventing the exchange of water and toxic substances. It consists of superficial cells specialized for synthesis and transport of uroplakins that assemble into a tough apical plaque, one or more layers of intermediate cells, and keratin 5-expressing basal cells (K5-BCs), which are considered to be progenitors in the urothelium and other specialized epithelia. Fate mapping, however, reveals that intermediate cells rather than K5-BCs are progenitors in the adult regenerating urothelium, that P cells, a transient population, are progenitors in the embryo, and that retinoids are critical in P cells and intermediate cells, respectively, for their specification during development and regeneration. These observations have important implications for tissue engineering and repair and, ultimately, may lead to treatments that prevent loss of the urothelial barrier, a major cause of voiding dysfunction and bladder pain syndrome. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Challenges and opportunities for tissue-engineering polarized epithelium.

    PubMed

    Paz, Ana C; Soleas, John; Poon, James C H; Trieu, Dennis; Waddell, Thomas K; McGuigan, Alison P

    2014-02-01

    The epithelium is one of the most important tissue types in the body and the specific organization of the epithelial cells in these tissues is important for achieving appropriate function. Since many tissues contain an epithelial component, engineering functional epithelium and understanding the factors that control epithelial maturation and organization are important for generating whole artificial organ replacements. Furthermore, disruption of the cellular organization leads to tissue malfunction and disease; therefore, engineered epithelium could provide a valuable in vitro model to study disease phenotypes. Despite the importance of epithelial tissues, a surprisingly limited amount of effort has been focused on organizing epithelial cells into artificial polarized epithelium with an appropriate structure that resembles that seen in vivo. In this review, we provide an overview of epithelial tissue organization and highlight the importance of cell polarization to achieve appropriate epithelium function. We next describe the in vitro models that exist to create polarized epithelium and summarize attempts to engineer artificial epithelium for clinical use. Finally, we highlight the opportunities that exist to translate strategies from tissue engineering other tissues to generate polarized epithelium with a functional structure.

  16. Inhibition of 4NQO-Induced Oral Carcinogenesis by Dietary Oyster Shell Calcium

    PubMed Central

    Chen, Ying; Jiang, Yi; Liao, Liyan; Zhu, Xiaoxin; Tang, Shengan; Yang, Qing; Sun, Lihua; Li, Yujie; Gao, Shuangrong; Xie, Zhongjian

    2015-01-01

    Oyster has gained much attention recently for its anticancer activity but it is unclear whether calcium, the major antitumor ingredient in oyster shell, is responsible for the anticarcinogenic role of the oyster. To address this issue, C57BL/6 mice were fed with the carcinogen 4-nitroquinoline-1-oxide (4NQO, 50 µg/mL) and normal diet or a diet containing oyster powder, oyster calcium, or calcium depleted oyster powder. The tongue tissue specimens isolated from these mice were histologically evaluated for hyperplasia, dysplasia, and papillary lesions, and then analyzed for proliferation and differentiation markers by immunohistochemistry. The results showed that mice on the diet containing oyster calcium significantly reduced rates of tumors in the tongue and proliferation and enhanced differentiation in the oral epithelium compared with the diet containing calcium depleted oyster powder. These results suggest that calcium in oyster plays a critical role in suppressing formation of oral squamous cell carcinoma and proliferation and promoting differentiation of the oral epithelium. PMID:26293805

  17. A dielectrophoretic method of discrimination between normal oral epithelium, and oral and oropharyngeal cancer in a clinical setting.

    PubMed

    Graham, K A; Mulhall, H J; Labeed, F H; Lewis, M P; Hoettges, K F; Kalavrezos, N; McCaul, J; Liew, C; Porter, S; Fedele, S; Hughes, M P

    2015-08-07

    Despite the accessibility of the oral cavity to clinical examination, delays in diagnosis of oral and oropharyngeal carcinoma (OOPC) are observed in a large majority of patients, with negative impact on prognosis. Diagnostic aids might help detection and improve early diagnosis, but there remains little robust evidence supporting the use of any particular diagnostic technology at the moment. The aim of the present feasibility first-in-human study was to evaluate the preliminary diagnostic validity of a novel technology platform based on dielectrophoresis (DEP). DEP does not require labeling with antibodies or stains and it is an ideal tool for rapid analysis of cell properties. Cells from OOPC/dysplasia tissue and healthy oral mucosa were collected from 57 study participants via minimally-invasive brush biopsies and tested with a prototype DEP platform using median membrane midpoint frequency as main analysis parameter. Results indicate that the current DEP platform can discriminate between brush biopsy samples from cancerous and healthy oral tissue with a diagnostic sensitivity of 81.6% and a specificity of 81.0%. The present ex vivo results support the potential application of DEP testing for identification of OOPC. This result indicates that DEP has the potential to be developed into a low-cost, rapid platform as an assistive tool for the early identification of oral cancer in primary care; given the rapid, minimally-invasive and non-expensive nature of the test, dielectric characterization represents a promising platform for cost-effective early cancer detection.

  18. Transcytosis of F4 fimbriae by villous and dome epithelia in F4-receptor positive pigs supports importance of receptor-dependent endocytosis in oral immunization strategies.

    PubMed

    Snoeck, Veerle; Van den Broeck, Wim; De Colvenaer, Veerle; Verdonck, Frank; Goddeeris, Bruno; Cox, Eric

    2008-07-15

    Very few antigens have been described that induce an intestinal immunity when given orally. Our laboratory demonstrated that oral administration of isolated F4 (K88) fimbriae of Escherichia coli to F4-receptor positive (F4R(+)) pigs induces protective mucosal immunity against challenge infection. However, presence of F4-receptors (F4R) on villous enterocytes is a prerequisite for inducing the immune response, as no F4-specific antibody-secreting cells (ASC) can be induced in F4R(-) pigs. In this study, the in vivo binding of isolated F4 fimbriae (F4) to the gut epithelium was examined in F4R(+) and F4R(-) pigs. It was further investigated whether binding of F4 to the F4R results in endocytosis in and translocation across the gut epithelium using microscopy. F4 did not adhere to the intestinal epithelium of F4R(-) pigs, whereas it strongly adhered to the villous epithelium and the follicle-associated epithelium (FAE) of the jejunum and ileum of F4R(+) pigs. Following binding to F4R, F4 was endocytosed by villous enterocytes, follicle-associated enterocytes and M cells. Transcytosis of F4 across the epithelium resulted in the appearance of F4 in the lamina propria and dome region of the jejunal and ileal PP. This is the first study showing transcytosis of fimbriae across the gut epithelium. This receptor-dependent transcytosis can explain the success of F4 fimbriae as oral immunogen for inducing protective immunity in F4R(+) pigs strengthening the importance of receptor-dependent endocytosis and translocation in oral vaccine strategies. Further identification of the receptor responsible for this transport is in progress.

  19. Detection and typing of human papillomaviruses (HPV) in malignant, dysplastic, nondysplastic and normal oral epithelium by nested polymerase chain reaction, immunohistochemistry and transitional electron microscopy in patients of northern Greece.

    PubMed

    Blioumi, E; Chatzidimitriou, D; Pazartzi, Ch; Katopodi, Th; Tzimagiorgis, G; Emmanouil-Nikoloussi, E-N; Markopoulos, A; Kalekou, C; Lazaridis, N; Diza, E; Antoniades, D

    2014-09-01

    To evaluate the role of HPV in oral carcinogenesis, we examined the prevalence of HPV in malignant, potentially malignant and normal oral epithelium and studied the relation of HPV prevalence with other factors obtained from the patient's records. Our material consisted of 291 tissue specimens from 258 individuals. From every individual formalin fixed and paraffin embedded tissues were examined by nested Polymerase Chain Reaction (NPCR) for the detection of HPV DNA and by immunohistochemistry (IHC) for the in situ detection of HPV L1 protein. Positive PCR products were sequenced in order to type HPVs. Also 33 fresh tissues were obtained, fixed and used to detect HPV particles by transitional electron microscopy (TEM). HPV was detected in 32.9% of the tissue specimens by NPCR, in 4.7% by immunohistochemistry and in 28.1% by TEM. In detail, by nested PCR HPV L1 DNA was detected in 40% of normal tissues, 40% of fibromas, 35.8% of non-dysplastic leukoplakias, 31.6% of dysplastic leukoplakias and 22.2% of oral squamous cell carcinomas. The HPV viral load of 96.5% of the samples was very low (1 viral copy per 10(2)-10(4) cells). HPV16 prevails in all histological groups in 89-100%. We conclude that HPV does not seem, from the specific sample examined, to play a substantial role in oral carcinogenesis. However, it cannot be excluded that HPV could be involved in oral carcinogenesis only in cases with high viral load or at early stages of carcinogenesis possibly through the hit-and-run mechanism. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Olfactory epithelium changes in germfree mice

    PubMed Central

    François, Adrien; Grebert, Denise; Rhimi, Moez; Mariadassou, Mahendra; Naudon, Laurent; Rabot, Sylvie; Meunier, Nicolas

    2016-01-01

    Intestinal epithelium development is dramatically impaired in germfree rodents, but the consequences of the absence of microbiota have been overlooked in other epithelia. In the present study, we present the first description of the bacterial communities associated with the olfactory epithelium and explored differences in olfactory epithelium characteristics between germfree and conventional, specific pathogen-free, mice. While the anatomy of the olfactory epithelium was not significantly different, we observed a thinner olfactory cilia layer along with a decreased cellular turn-over in germfree mice. Using electro-olfactogram, we recorded the responses of olfactory sensitive neuronal populations to various odorant stimulations. We observed a global increase in the amplitude of responses to odorants in germfree mice as well as altered responses kinetics. These changes were associated with a decreased transcription of most olfactory transduction actors and of olfactory xenobiotic metabolising enzymes. Overall, we present here the first evidence that the microbiota modulates the physiology of olfactory epithelium. As olfaction is a major sensory modality for most animal species, the microbiota may have an important impact on animal physiology and behaviour through olfaction alteration. PMID:27089944

  1. Characterization of oral immune cells in birch pollen-allergic patients: impact of the oral allergy syndrome and sublingual allergen immunotherapy on antigen-presenting cells.

    PubMed

    Mascarell, L; Rak, S; Worm, M; Melac, M; Soulie, S; Lescaille, G; Lemoine, F; Jospin, F; Paul, S; Caplier, L; Hasséus, B; Björhn, C; Zeldin, R K; Baron-Bodo, V; Moingeon, P

    2015-04-01

    A detailed characterization of human oral immune cells is needed to better understand local mechanisms associated with allergen capture following oral exposure. Oral immune cells were characterized by immunohistology and immunofluorescence in biopsies obtained from three healthy individuals and 23 birch pollen-allergic patients with/without oral allergy syndrome (OAS), at baseline and after 5 months of sublingual allergen immunotherapy (AIT). Similar cell subsets (i.e., dendritic cells, mast cells, and T lymphocytes) were detected in oral tissues from healthy and birch pollen-allergic individuals. CD207+ Langerhans cells (LCs) and CD11c+ myeloid dendritic cells (DCs) were found in both the epithelium and the papillary layer of the Lamina propria (LP), whereas CD68+ macrophages, CD117+ mast cells, and CD4+ /CD8+ T cells were rather located in both the papillary and reticular layers of the LP. Patterns of oral immune cells were identical in patients with/without OAS, except lower numbers of CD207+ LCs found in oral tissues from patients with OAS, when compared to OAS- patients (P < 0.05). A 5-month sublingual AIT had a limited impact on oral immune cells, with only a significant increase in IgE+ cells in patients from the active group. Colocalization experiments confirmed that such IgE-expressing cells mostly encompass CD68+ macrophages located in the LP, and to a lesser extent CD207+ LCs in the epithelium. Two cell subsets contribute to antigen/allergen uptake in human oral tissues, including (i) CD207+ LCs possibly involved in the physiopathology of OAS and (ii) CD68+ macrophages likely critical in allergen capture via IgE-facilitated mechanisms during sublingual AIT. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Detection of human papillomavirus and Epstein-Barr virus DNA sequences in oral mucosa of HIV-infected patients by the polymerase chain reaction.

    PubMed Central

    Snijders, P. J.; Schulten, E. A.; Mullink, H.; ten Kate, R. W.; Jiwa, M.; van der Waal, I.; Meijer, C. J.; Walboomers, J. M.

    1990-01-01

    The presence of human papillomavirus (HPV) and Epstein-Barr virus (EBV) was analyzed in 21 oral biopsy specimens of HIV-infected patients using the polymerase chain reaction (PCR) method. Biopsies were categorized as hairy leukoplakia (HL) (n = 12), candidiasis (n = 3), oral warts (n = 2), and clinically normal epithelium (n = 4). For HPV detection a modified general primer-mediated PCR method (GP-PCR), which detects a broad spectrum of HPV genotypes at sub-picogram levels, was used. Human papillomavirus DNA was only found in two oral warts and was identified as HPV type 32. Epstein-Barr virus DNA was detected in 16 biopsy specimens, including the 12 HLs, 2 cases of candidiasis, and 2 samples of normal epithelium. Epstein-Barr virus positivity in HL could be confirmed by Southern blot analysis and DNA in situ hybridization using biotinylated DNA probes (bio-DISH). Epstein-Barr virus bio-DISH was also positive in one sample of normal epithelium from a patient with HL. The results indicate that HL is strongly associated with EBV and not with any of the common HPV types that react with general HPV primers in the PCR. However the detection of EBV in normal oral epithelium by PCR and bio-DISH suggests that the presence of this virus is not exclusively related to HL. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:2169191

  3. Cytokeratin expression in mouse lacrimal gland germ epithelium.

    PubMed

    Hirayama, Masatoshi; Liu, Ying; Kawakita, Tetsuya; Shimmura, Shigeto; Tsubota, Kazuo

    2016-05-01

    The lacrimal gland secretes tear fluids that protect the ocular surface epithelium, and its dysfunction leads to dry eye disease (DED). The functional restoration of the lacrimal gland by engraftment of a bioengineered lacrimal gland using lacrimal gland germ epithelial cells has been proposed to cure DED in mice. Here, we investigate the expression profile of cytokeratins in the lacrimal gland germ epithelium to clarify their unique characteristics. We performed quantitative polymerase chain reaction (Q-PCR) and immunohistochemistry (IHC) analysis to clarify the expression profile of cytokeratin in the lacrimal gland germ epithelium. The mRNA expression of keratin (KRT) 5, KRT8, KRT14, KRT15, and KRT18 in the lacrimal gland germ epithelium was increased compared with that in mouse embryonic stem cells and the lacrimal gland germ mesenchyme, as analyzed by Q-PCR. The expression level of KRT15 increased in the transition from stem cells to lacrimal gland germ epithelium, then decreased as the lacrimal gland matured. IHC revealed that the expression set of these cytokeratins in the lacrimal gland germ epithelium was different from that in the adult lacrimal gland. The expression of KRT15 was observed in the lacrimal gland germ epithelium, and it segmentalized into some of the basal cells in the intercanulated duct in mature gland. We determined the expression profile of cytokeratins in the lacrimal gland epithelium, and identified KRT15 as a candidate unique cellular marker for the lacrimal gland germ epithelium. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. The stat3/socs3a pathway is a key regulator of hair cell regeneration in zebrafish. [corrected].

    PubMed

    Liang, Jin; Wang, Dongmei; Renaud, Gabriel; Wolfsberg, Tyra G; Wilson, Alexander F; Burgess, Shawn M

    2012-08-01

    All nonmammalian vertebrates studied can regenerate inner ear mechanosensory receptors (i.e., hair cells) (Corwin and Cotanche, 1988; Lombarte et al., 1993; Baird et al., 1996), but mammals possess only a very limited capacity for regeneration after birth (Roberson and Rubel, 1994). As a result, mammals experience permanent deficiencies in hearing and balance once their inner ear hair cells are lost. The mechanisms of hair cell regeneration are poorly understood. Because the inner ear sensory epithelium is highly conserved in all vertebrates (Fritzsch et al., 2007), we chose to study hair cell regeneration mechanism in adult zebrafish, hoping the results would be transferrable to inducing hair cell regeneration in mammals. We defined the comprehensive network of genes involved in hair cell regeneration in the inner ear of adult zebrafish with the powerful transcriptional profiling technique digital gene expression, which leverages the power of next-generation sequencing ('t Hoen et al., 2008). We also identified a key pathway, stat3/socs3, and demonstrated its role in promoting hair cell regeneration through stem cell activation, cell division, and differentiation. In addition, transient pharmacological inhibition of stat3 signaling accelerated hair cell regeneration without overproducing cells. Taking other published datasets into account (Sano et al., 1999; Schebesta et al., 2006; Dierssen et al., 2008; Riehle et al., 2008; Zhu et al., 2008; Qin et al., 2009), we propose that the stat3/socs3 pathway is a key response in all tissue regeneration and thus an important therapeutic target for a broad application in tissue repair and injury healing.

  5. Cytokeratin expression in pseudoepitheliomatous hyperplasia of oral paracoccidioidomycosis.

    PubMed

    Kaminagakura, E; Bonan, P R F; Lopes, M A; Almeida, O P; Scully, C

    2006-08-01

    Paracoccidioidomycosis (Pmycosis) is one the most prevalent deep systemic mycoses in Latin America. It is characterized by granulomatous inflammation and pseudoepitheliomatous hyperplasia. Cytokeratins (CKs) are a group of intermediate filaments of epithelial cells and their expression varies according to the epithelium type, differentiation and pathological processes. This study describes cytokeratin expression as examined by immunohistochemistry, in 28 cases of oral Pmycosis involving the buccal mucosa, lip, gingiva and hard palate. Expression of CKs in the basal layer of the epithelium in pseudoepitheliomatous hyperplasia of Pmycosis was similar to that in normal oral mucosa (NOM), but in Pmycosis CK1 and CK10 were not expressed in the spinous and superficial layers of the lip, gingiva or hard palate, and, in the spinous and superficial layers of the lip and buccal mucosa, CK14 was positive in contrast to NOM where it was negative. In Pmycosis, CK6 was more frequently expressed in the spinous layer of the lip, gingiva and hard palate, but nevertheless CK16 expression was decreased in the spinous and superficial layers of the gingiva and hard palate. We conclude that pseudoepitheliomatous hyperplasia in oral Pmycosis shows a different pattern of CK expression, particularly CKs 1, 10 and 14, compared with NOM.

  6. Maintained expression of the planar cell polarity molecule Vangl2 and reformation of hair cell orientation in the regenerating inner ear.

    PubMed

    Warchol, Mark E; Montcouquiol, Mireille

    2010-09-01

    The avian inner ear possesses a remarkable ability to regenerate sensory hair cells after ototoxic injury. Regenerated hair cells possess phenotypes and innervation that are similar to those found in the undamaged ear, but little is known about the signaling pathways that guide hair cell differentiation during the regenerative process. The aim of the present study was to examine the factors that specify the orientation of hair cell stereocilia bundles during regeneration. Using organ cultures of the chick utricle, we show that hair cells are properly oriented after having regenerated entirely in vitro and that orientation is not affected by surgical removal of the striolar reversal zone. These results suggest that the orientation of regenerating stereocilia is not guided by the release of a diffusible morphogen from the striolar reversal zone but is specified locally within the regenerating sensory organ. In order to determine the nature of the reorientation cues, we examined the expression patterns of the core planar cell polarity molecule Vangl2 in the normal and regenerating utricle. We found that Vangl2 is asymmetrically expressed on cells within the sensory epithelium and that this expression pattern is maintained after ototoxic injury and throughout regeneration. Notably, treatment with a small molecule inhibitor of c-Jun-N-terminal kinase disrupted the orientation of regenerated hair cells. Both of these results are consistent with the hypothesis that noncanonical Wnt signaling guides hair cell orientation during regeneration.

  7. Functional recovery of anterior semicircular canal afferents following hair cell regeneration in birds

    NASA Technical Reports Server (NTRS)

    Boyle, Richard; Highstein, Stephen M.; Carey, John P.; Xu, Jinping

    2002-01-01

    Streptomycin sulfate (1.2 g/kg i.m.) was administered for 5 consecutive days to 5-7-day-old white Leghorn chicks; this causes damage to semicircular canal hair cells that ultimately regenerate to reform the sensory epithelium. During the recovery period, electrophysiological recordings were taken sequentially from anterior semicircular canal primary afferents using an indentation stimulus of the canal that has been shown to mimic rotational stimulation. Chicks were assigned to an early (14-18 days; n = 8), intermediate (28-34 days; n = 5), and late (38-58 days; n = 4) period based on days after treatment. Seven untreated chicks, 15-67 days old, provided control data. An absence of background and indent-induced discharge was the prominent feature of afferents in the early period: only "silent" afferents were encountered in 5/8 experiments. In several of these chicks, fascicles of afferent fibers were seen extending up to the epithelium that was void of hair cells, and intra- and extracellular biocytin labeling revealed afferent processes penetrating into the supporting cell layer of the crista. In 3/8 chicks 74 afferents could be characterized, and they significantly differed from controls (n = 130) by having a lower discharge rate and a negligible response to canal stimulation. In the intermediate period there was considerable variability in discharge properties of 121 afferents, but as a whole the number of "silent" fibers in the canal nerve diminished, the background rate increased, and a response to canal stimulation detected. Individually biocytin-labeled afferents had normal-appearing terminal specializations in the sensory epithelium by 28 days poststreptomycin. In the late period, afferents (n = 58) remained significantly different from controls in background discharge properties and response gain. The evidence suggests that a considerable amount of variability exists between chicks in the return of vestibular afferent function following ototoxic injury and

  8. The Reaction and Regeneration of Cementum in Various Pathological Conditions : (Section of Odontology).

    PubMed

    Stones, H H

    1934-04-01

    (1) The reaction of cementum and its adjoining tissues to induced pathological conditions associated with the gingival sulcus is described.(2) After subjecting the sulcus to interference, its histological appearance is compared with that of definite parodontal disease.(3) Various methods were adopted for these experiments, which were performed on monkeys.(4) Artificial pockets were produced by detaching the subgingival epithelium and underlying connective tissue from the cementum. (a) Cementum is easily removed accidentally, when scraping monkeys' teeth. (b) Reattachment of connective tissues to cementum is effected, but is usually incomplete. (c) Epithelium always firmly reunites with cementum. (d) The artificial sulcus which is usually deeper than normal does not show, microscopically, the same pathological changes as in parodontal disease.(5) In other experiments, in addition to deepening the sulcus, the cementum lining the pockets was also removed, leaving denuded dentine in contact with the connective tissue. A similar condition was achieved by another method in which a dental bur was inserted between two teeth below the gum margin. (a) The gingival epithelium is capable of forming a weak attachment to the dentine, though this does not usually occur. It always proliferates down and unites with the nearest layer of cementum. It seems to have a peculiar affinity for this tissue. (b) Underlying connective tissue does not usually unite with the dentine. When this happens it is effected by the regeneration of cementum, this new tissue being lined by new cementoblasts. (c) The width of the periodontal membrane, which was increased by the experiment, is reduced to a more normal level by deposition of new alveolar bone, and to a lesser extent by regeneration of cementum. (d) In this series of experiments the artificial pocket is permanent and somewhat resembles that of parodontal disease. This is probably due, not so much to the injury, but to its effects creating a

  9. Utilizing collagen membranes for guided tissue regeneration-based root coverage.

    PubMed

    Wang, Hom-Lay; Modarressi, Marmar; Fu, Jia-Hui

    2012-06-01

    Gingival recession is a common clinical problem that can result in hypersensitivity, pain, root caries and esthetic concerns. Conventional soft tissue procedures for root coverage require an additional surgical site, thereby causing additional trauma and donor site morbidity. In addition, the grafted tissues heal by repair, with formation of long junctional epithelium with some connective tissue attachment. Guided tissue regeneration-based root coverage was thus developed in an attempt to overcome these limitations while providing comparable clinical results. This paper addresses the biologic foundation of guided tissue regeneration-based root coverage, and describes the indications and contraindications for this technique, as well as the factors that influence outcomes. The step-by-step clinical techniques utilizing collagen membranes are also described. In comparison with conventional soft tissue procedures, the benefits of guided tissue regeneration-based root coverage procedures include new attachment formation, elimination of donor site morbidity, less chair-time, and unlimited availability and uniform thickness of the product. Collagen membranes, in particular, benefit from product biocompatibility with the host, while promoting chemotaxis, hemostasis, and exchange of gas and nutrients. Such characteristics lead to better wound healing by promoting primary wound coverage, angiogenesis, space creation and maintenance, and clot stability. In conclusion, collagen membranes are a reliable alternative for use in root coverage procedures. © 2012 John Wiley & Sons A/S.

  10. Oral squamous papilloma occurring on the palate with review of literature.

    PubMed

    Nayak, Anjali; Nayak, Meghanand T

    2016-11-01

    Squamous papillomas are common lesions occurring on skin, oral and nasal mucosa and male and female genital organs. Oral squamous cell papilloma (OSP) is a benign proliferation of the stratified squamous epithelium and is generally believed to be caused by Human Papilloma Viruses (HPV). It constitutes around 2.5% of all oral verruco-papillary lesions. We here, report a case of palatal OSP occurring in a 55-year-old male. The aetiological, clinical, diagnostic and treatment aspects of OSP are discussed here. © 2016 Old City Publishing, Inc.

  11. Lung development: orchestrating the generation and regeneration of a complex organ

    PubMed Central

    Herriges, Michael; Morrisey, Edward E.

    2014-01-01

    The respiratory system, which consists of the lungs, trachea and associated vasculature, is essential for terrestrial life. In recent years, extensive progress has been made in defining the temporal progression of lung development, and this has led to exciting discoveries, including the derivation of lung epithelium from pluripotent stem cells and the discovery of developmental pathways that are targets for new therapeutics. These discoveries have also provided new insights into the regenerative capacity of the respiratory system. This Review highlights recent advances in our understanding of lung development and regeneration, which will hopefully lead to better insights into both congenital and acquired lung diseases. PMID:24449833

  12. Scar-free wound healing and regeneration following tail loss in the leopard gecko, Eublepharis macularius.

    PubMed

    Delorme, Stephanie Lynn; Lungu, Ilinca Mihaela; Vickaryous, Matthew Kenneth

    2012-10-01

    Many lizards are able to undergo scar-free wound healing and regeneration following loss of the tail. In most instances, lizard tail loss is facilitated by autotomy, an evolved mechanism that permits the tail to be self-detached at pre-existing fracture planes. However, it has also been reported that the tail can regenerate following surgical amputation outside the fracture plane. In this study, we used the leopard gecko, Eublepharis macularius, to investigate and compare wound healing and regeneration following autotomy at a fracture plane and amputation outside the fracture plane. Both forms of tail loss undergo a nearly identical sequence of events leading to scar-free wound healing and regeneration. Early wound healing is characterized by transient myofibroblasts and the formation of a highly proliferative wound epithelium immunoreactive for the wound keratin marker WE6. The new tail forms from what is commonly referred to as a blastema, a mass of proliferating mesenchymal-like cells. Blastema cells express the protease matrix metalloproteinase-9. Apoptosis (demonstrated by activated caspase 3 immunostaining) is largely restricted to isolated cells of the original and regenerating tail tissues, although cell death also occurs within dermal structures at the original-regenerated tissue interface and among clusters of newly formed myocytes. Furthermore, the autotomized tail is unique in demonstrating apoptosis among cells adjacent to the fracture planes. Unlike mammals, transforming growth factor-β3 is not involved in wound healing. We demonstrate that scar-free wound healing and regeneration are intrinsic properties of the tail, unrelated to the location or mode of tail detachment. Copyright © 2012 Wiley Periodicals, Inc.

  13. Oral lichen planus: An update on pathogenesis and treatment

    PubMed Central

    Lavanya, N; Jayanthi, P; Rao, Umadevi K; Ranganathan, K

    2011-01-01

    Oral lichen planus (OLP) is a chronic inflammatory disease that affects the mucus membrane of the oral cavity. It is a T-cell mediated autoimmune disease in which the cytotoxic CD8+ T cells trigger apoptosis of the basal cells of the oral epithelium. Several antigen-specific and nonspecific inflammatory mechanisms have been put forward to explain the accumulation and homing of CD8+ T cells subepithelially and the subsequent keratinocyte apoptosis. A wide spectrum of treatment modalities is available, from topical corticosteroids to laser ablation of the lesion. In this review, we discuss the various concepts in the pathogenesis and current treatment modalities of OLP. PMID:22529568

  14. An ancient dental gene set governs development and continuous regeneration of teeth in sharks.

    PubMed

    Rasch, Liam J; Martin, Kyle J; Cooper, Rory L; Metscher, Brian D; Underwood, Charlie J; Fraser, Gareth J

    2016-07-15

    The evolution of oral teeth is considered a major contributor to the overall success of jawed vertebrates. This is especially apparent in cartilaginous fishes including sharks and rays, which develop elaborate arrays of highly specialized teeth, organized in rows and retain the capacity for life-long regeneration. Perpetual regeneration of oral teeth has been either lost or highly reduced in many other lineages including important developmental model species, so cartilaginous fishes are uniquely suited for deep comparative analyses of tooth development and regeneration. Additionally, sharks and rays can offer crucial insights into the characters of the dentition in the ancestor of all jawed vertebrates. Despite this, tooth development and regeneration in chondrichthyans is poorly understood and remains virtually uncharacterized from a developmental genetic standpoint. Using the emerging chondrichthyan model, the catshark (Scyliorhinus spp.), we characterized the expression of genes homologous to those known to be expressed during stages of early dental competence, tooth initiation, morphogenesis, and regeneration in bony vertebrates. We have found that expression patterns of several genes from Hh, Wnt/β-catenin, Bmp and Fgf signalling pathways indicate deep conservation over ~450 million years of tooth development and regeneration. We describe how these genes participate in the initial emergence of the shark dentition and how they are redeployed during regeneration of successive tooth generations. We suggest that at the dawn of the vertebrate lineage, teeth (i) were most likely continuously regenerative structures, and (ii) utilised a core set of genes from members of key developmental signalling pathways that were instrumental in creating a dental legacy redeployed throughout vertebrate evolution. These data lay the foundation for further experimental investigations utilizing the unique regenerative capacity of chondrichthyan models to answer evolutionary

  15. Clinical and biochemical studies support smokeless tobacco’s carcinogenic potential in the human oral cavity

    PubMed Central

    Mallery, Susan R.; Tong, Meng; Michaels, Gregory C.; Kiyani, Amber R.; Hecht, Stephen S.

    2014-01-01

    In 2007, International Agency for Cancer Research presented compelling evidence that linked smokeless tobacco use to the development of human oral cancer. While these findings imply vigorous local carcinogen metabolism, little is known regarding levels and distribution of Phase I, II and drug egress enzymes in human oral mucosa. In the study presented here, we integrated clinical data, imaging and histopathologic analyses of an oral squamous cell carcinoma that arose at the site of smokeless tobacco quid placement in a patient. Immunoblot and immunohistochemical (IHC) analyses were employed to identify tumor and normal human oral mucosal smokeless tobacco-associated metabolic activation and detoxification enzymes. Human oral epithelium contains every known Phase I enzyme associated with nitrosamine oxidative bioactivation with ~2 fold inter-donor differences in protein levels. Previous studies have confirmed ~3.5 fold inter-donor variations in intraepithelial Phase II enzymes. Unlike the superficially located enzymes in non-replicating esophageal surface epithelium, IHC studies confirmed oral mucosal nitrosamine metabolizing enzymes reside in the basilar and suprabasilar region which notably is the site of ongoing keratinocyte DNA replication. Clearly, variations in product composition, nitrosamine metabolism and exposure duration will modulate clinical outcomes. The data presented here form a coherent picture consistent with the abundant experimental data that links tobacco-specific nitrosamines to human oral cancer. PMID:24265177

  16. The effect of hypergravity on the lens, cornea and tail regeneration in Urodela

    NASA Astrophysics Data System (ADS)

    Grigoryan, E. N.; Dvorochkin, N.; Poplinskaya, V. A.; Yousuf, R.; Radugina, E. A.; Almeida, E. A.

    2017-09-01

    In previous experiments onboard Russian Bion/Foton satellites it was found that exposure to microgravity causes changes in eye lens regeneration of Urodela. The changes included higher rate of regeneration, increased cell proliferation in lens anlage, and synchronization of lens restoration. Similar changes were observed regarding tail regeneration. Recently, investigations were performed to find out whether exposure to hypergravity could also alter lens, cornea and tail regeneration in the newt P. waltl. Nine days prior to exposure the left lens was surgically removed through corneal incision and distal 1/3 of the tail was amputated, thus initiating regeneration. The experimental animals were allowed to recover for 9 days at 1 g and then exposed to 2 g for 12 days in an 8 ft diameter centrifuge at NASA Ames Research Center. The experimental animals were divided into 1 g controls, 2 g centrifugation animals, basal controls, and aquarium controls. Lens and corneal regeneration appeared to be inhibited in 2 g group compared to 1 g animals. In all 1 g controls, lens regeneration reached stages VII-IX in a synchronous fashion and corneal regeneration was nearly complete. In the 2 g newts, neural retinal detachment from the pigmented epithelium was seen in most operated eyes. It was also observed in the non-operated (right) eyes of the animals exposed to 2 g. The level of retinal detachment varied and could have been caused by hypergravity-induced high intraocular pressure. Regeneration (when it could be assessed) proceeded asynchronously, reaching stages from II to IX. Corneal restoration was also noticeably delayed and corneal morphology changed. Cell proliferation was measured using BrdU; the results were not comparable to the 1 g data because of retinal detachment. Previous investigations demonstrated that lens regeneration was controlled by the neural retina; therefore, lower regeneration rate at 2 g was, at least in part, associated with retinal detachment. FGF2

  17. Functional salivary gland regeneration by transplantation of a bioengineered organ germ

    PubMed Central

    Ogawa, Miho; Oshima, Masamitsu; Imamura, Aya; Sekine, Yurie; Ishida, Kentaro; Yamashita, Kentaro; Nakajima, Kei; Hirayama, Masatoshi; Tachikawa, Tetsuhiko; Tsuji, Takashi

    2013-01-01

    Salivary gland hypofunction, also known as xerostomia, occurs as a result of radiation therapy for head cancer, Sjögren’s syndrome or aging, and can cause a variety of critical oral health issues, including dental decay, bacterial infection, mastication dysfunction, swallowing dysfunction and reduced quality of life. Here we demonstrate the full functional regeneration of a salivary gland that reproduces the morphogenesis induced by reciprocal epithelial and mesenchymal interactions through the orthotopic transplantation of a bioengineered salivary gland germ as a regenerative organ replacement therapy. The bioengineered germ develops into a mature gland through acinar formations with a myoepithelium and innervation. The bioengineered submandibular gland produces saliva in response to the administration of pilocarpine and gustatory stimulation by citrate, protects against oral bacterial infection and restores normal swallowing in a salivary gland-defective mouse model. This study thus provides a proof-of-concept for bioengineered salivary gland regeneration as a potential treatment of xerostomia. PMID:24084982

  18. Cyclosporine a inhibits apoptosis of rat gingival epithelium.

    PubMed

    Ma, Su; Liu, Peihong; Li, Yanwu; Hou, Lin; Chen, Li; Qin, Chunlin

    2014-08-01

    The use of cyclosporine A (CsA) induces hyperplasia of the gingival epithelium in a site-specific response manner, but the molecular mechanism via which the lesion occurs is unclear. The present research aims to investigate the site-specific effect of CsA on the apoptosis of gingival epithelium associated with gingival hyperplasia. Forty Wistar rats were divided into CsA-treated and non-treated groups. Paraffin-embedded sections of mandibular first molars were selected for hematoxylin and eosin staining, immunohistochemistry analyses of bcl-2 and caspase-3, and the staining of terminal deoxynucleotidyl transfer-mediated dUTP nick-end labeling (TUNEL). The area of the whole gingival epithelium and the length of rete pegs were measured, and the number of bcl-2- and caspase-3-positive cells in the longest rete peg were counted. The analysis of variance for factorial designs and Fisher least significant difference test for post hoc analysis were used to determine the significance levels. In CsA-treated rats, bcl-2 expression was significantly upregulated, whereas caspase-3 expression was downregulated, along with a reduced number of TUNEL-positive cells. The site-specific distribution of bcl-2 was consistent with the site-specific hyperplasia of the gingival epithelium in CsA-treated rats. CsA inhibited gingival epithelial apoptosis via the mitochondrial pathway and common pathway. The antiapoptotic protein bcl-2 might play a critical role in the pathogenesis of the site-specific hyperplasia of gingival epithelium induced by CsA. There were mechanistic differences in the regulation of apoptosis for cells in the attached gingival epithelium, free gingival epithelium, and junctional epithelium.

  19. Secreted Oral Epithelial Cell Membrane Vesicles Induce Epstein-Barr Virus Reactivation in Latently Infected B Cells

    PubMed Central

    Lin, Zhen; Swan, Kenneth; Zhang, Xin; Cao, Subing; Brett, Zoe; Drury, Stacy; Fewell, Claire; Puetter, Adriane; Wang, Xia; Ferris, MaryBeth; Sullivan, Deborah E.; Li, Li

    2016-01-01

    ABSTRACT In the oral epithelium, peripheral stores of Epstein-Barr virus (EBV) are transmitted from infiltrating B cells to epithelial cells. Once the virus is transmitted to epithelial cells, the highly permissive nature of this cell type for lytic replication allows virus amplification and exchange to other hosts. Since the initial transfer of EBV from B cells to epithelial cells requires transitioning of the B-cell to a state that induces virus reactivation, we hypothesized that there might be epithelium-specific signals that allow the infiltrating B cells to sense the appropriate environment to initiate reactivation and begin this exchange process. We previously found that the epithelium-specific miR-200 family of microRNAs promotes EBV lytic replication. Here we show that there are high levels of miR-200 family members in oral and tonsillar epithelia and in saliva. Analysis of cultured oral epithelial cells (OKF6) showed that they actively secrete membrane vesicles (exosomes) that are enriched with miR-200 family members. Coculturing of EBV-positive B cells with OKF6 cells induced viral reactivation. Further, treatment of EBV-positive B cells with OKF6 cell-derived membrane vesicles promoted reactivation. Using a cell system that does not naturally express miR-200 family members, we found that enforced expression of a miR-200 family member produced membrane vesicles that were able to induce the lytic cascade in EBV-positive B cells. We propose that membrane vesicles secreted by oral and tonsillar epithelial cells may serve as a tissue-specific environmental cue that initiates reactivation in B cells, promoting the transfer of virus from peripheral B-cell stores to the oral epithelium to facilitate virus amplification and exchange to other hosts. IMPORTANCE Epstein-Barr virus (EBV) is an important human pathogen that is causally associated with several lymphomas and carcinomas. The switch from latency to the lytic cycle is critical for successful host infection

  20. Corneal epithelium and UV-protection of the eye.

    PubMed

    Ringvold, A

    1998-04-01

    To study UV-absorption and UV-induced fluorescence in the bovine corneal epithelium. Spectrophotometry and spectrofluorimetry. The corneal epithelium absorbs UV-B radiation mainly owing to its content of protein, RNA, and ascorbate. Some of the absorbed energy is transformed to the less biotoxic UV-A radiation by fluorescence. RNA and ascorbate reduce tissue fluorescence. The corneal epithelium acts as a UV-filter, protecting internal eye structures through three different mechanisms: (1) Absorption of UV-B roughly below 310 nm wavelength. (2) Fluorescence-mediated ray transformation to longer wavelengths. (3) Fluorescence reduction. The extremely high ascorbate concentration in the corneal epithelium has a key role in two of these processes.

  1. Regulatory aspects in the pharmaceutical development of nanoparticle drug delivery systems designed to cross the intestinal epithelium and M-cells.

    PubMed

    Hussain, Nasir

    2016-11-30

    This article reviews the field of oral uptake of nanoparticles across the gastrointestinal epithelium for the period 2006-2016. Analysis is conducted from the viewpoint of i) M-cell genetics and model development, ii) drug targeting to Peyer's patches and M-cells, and iii) physicochemical interactions of nanoparticles in the intestinal milieu. In light of these recent developments, regulatory considerations in the development of orally-absorbable nanoparticle drug products are discussed and focused on Module 3.2.P sub-sections of the Common Technical Document. Particular attention is paid to novel excipients, ligands and the non-standard method of manufacture. The novelty of this drug delivery system demands not only a multi-disciplinary scientific and regulatory approach but also a risk-adjusted consideration for a system defined by both processes and specifications. Given the current state of scientific development in the field it is suggested (in the author's personal opinion) that the design of nanoparticulate drug delivery systems should be kept as simple as possible (from a regulatory and manufacturing perspective) and to target the entire gastrointestinal epithelium. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

  2. THE PERMEABILITY OF RAT TRANSITIONAL EPITHELIUM

    PubMed Central

    Hicks, R. M.

    1966-01-01

    Permeability barriers must exist in transitional epithelium to prevent the free flow of water from underlying blood capillaries through the epithelium into the hypertonic urine, and such a barrier has now been demonstrated in isolated bladders. This barrier is passive in function and can be destroyed by damaging the luminal surface of the transitional epithelium with sodium hydroxide and 8 M urea solutions, by digesting it with trypsin, lecithinase C, and lecithinase D, or by treating it with lipid solvents such as Triton x 100 and saponin. From this it is concluded that the barrier depends on the integrity of lipoprotein cell membranes. The barrier function is also destroyed by sodium thioglycollate solutions, and electron microscope investigations show that sodium thioglycollate damages the thick asymmetric membrane which limits the luminal face of the superficial squamous cell. Cytochemical staining shows the epithelium to contain disulfide and thiol groups and to have a concentration of these groups at the luminal margin of the superficial cells. It thus appears that the permeability barrier also depends on the presence of disulfide bridges in the epithelium, and it is presumed that these links are located in keratin. Because of the effect of thioglycollates, both on the barrier function and on the morphology of the membrane, it is suggested that keratin may be incorporated in the thick barrier membrane. It is proposed that the cells lining the urinary bladder and ureters should be regarded as a keratinizing epitheluim. PMID:5901498

  3. The epithelial-mesenchymal interactions: insights into physiological and pathological aspects of oral tissues.

    PubMed

    Santosh, Arvind Babu Rajendra; Jones, Thaon Jon

    2014-03-17

    In the human biological system, the individual cells divide and form tissues and organs. These tissues are hetero-cellular. Basically any tissue consists of an epithelium and the connective tissue. The latter contains mainly mesenchymally-derived tissues with a diversified cell population. The cell continues to grow and differentiate in a pre-programmed manner using a messenger system. The epithelium and the mesenchymal portion of each tissue have two different origins and perform specific functions, but there is a well-defined interaction mechanism, which mediates between them. Epithelial mesenchymal interactions (EMIs) are part of this mechanism, which can be regarded as a biological conversation between epithelial and mesenchymal cell populations involved in the cellular differentiation of one or both cell populations. EMIs represent a process that is essential for cell growth, cell differentiation and cell multiplication. EMIs are associated with normal physiological processes in the oral cavity, such as odontogenesis, dentino-enamel junction formation, salivary gland development, palatogenesis, and also pathological processes, such as oral cancer. This paper focuses the role EMIs in odontogenesis, salivary gland development, palatogenesis and oral cancer.

  4. Corneal epithelium, visual acuity, and laser refractive keratectomy

    NASA Astrophysics Data System (ADS)

    Simon, Gabriel; Parel, Jean-Marie A.; Kervick, Gerard N.; Rol, Pascal O.; Hanna, Khalil; Thompson, Keith P.

    1991-06-01

    Photorefractive keratectomy (PRK) using an argon fluoride excimer laser for photoablation of the cornea shows potential for the precise correction of refractive errors in patients. Usually, the epithelium is mechanically removed, and Bowman's layer and stromal tissue are photoablated to precomputed depths and shapes that are based on known ablation rates for these tissues. After four day's time, the epithelium has regrown. Assuming the epithelium to be preoperatively uniform in thickness across the central optical zone, and assuming that it regrows to the same thickness, a theoretical precision of +/- 0.05 diopters is achievable with PRK. Keratometric measurements of the epithelium and of Bowman's layer were made at the 2.0 and 3.6 mm optical zones on 10 fresh cadaver eyes (<21 hours postmortem). In the eyes studied, the epithelium thickness was found to vary across the central optical zone, accounting for the measured refractive differences of 0.5 to 1.8 diopters. Bowman's layer was found to be more prolated than the epithelial surface (ratios: 1.005 compared to 1.033). In addition, the surface of Bowman's layer had a larger degree of astigmatism. Other studies have shown that the epithelium regrowth is a function of the newly exposed corneal topography as the wing cells compensate for irregularities in Bowman's surface. As the preoperative topography of the epithelium cannot be used as a reference surface when computing photoablation depth, intraoperative keratometry of Bowman's surface becomes a necessity in PRK.

  5. Exophytic oral verrucous hyperplasia: a new entity.

    PubMed

    Patil, Shankargouda; Warnakulasuriya, Saman; Raj, Thirumal; Sanketh, D S; Rao, Roopa S

    2016-11-01

    Exophytic oral verrucous hyperplasia (OVH) is a new entity described by an expert working group from South Asia. First reported in Taiwan, there are no reports so far from an Indian population. The aim was to use the microscopic features described by the expert group to differentiate OVH from other oral verruco-papillary lesions in an Indian archive. In a retrospective multicentre study, using pathology archives, 188 verruco-papillary lesions were retrieved from pathology archives. A proforma listing histopathological criteria for OVH based on published guidelines (Annals of Dentistry, University of Malaya, 2013) was used. Patients' demographic and clinical data were transcribed from patient charts. The Pearson chi-square test was used to determine associations between clinical and histopathological features. Of 188 oral verruco-papillary lesions that were evaluated, based on microscopic features the cases were reclassified as OVH (57), verrucous carcinoma (VC) (84), oral squamous cell carcinoma (16), and other verruco-papillary lesions (31). Both OVH (70%) and VC (60%) showed male predominance and commonly affected buccal mucosa (OVH 74% and VC 57%). Absence of downward growth of the hyperplastic epithelium into lamina propria when compared with the level of the basement membrane of the adjacent normal epithelium was a distinct feature in OVH. Keratin plugging, epithelial dysplasia and subepithelial lymphocytic infiltration were found to be significantly different (P < 0.05) in OVH versus VC. The sample size of other verruco-papillary lesions was insufficient for statistical comparison. Apart from the absence of an endophytic growth pattern in OVH, we noted the presence of dysplasia in OVH. This significant observation does institute a debate as to whether this enigmatic lesion could possibly be a precedent of oral squamous or verrucous carcinoma. We propose OVH is a distinct entity in our Indian population and should be considered in the classification of oral

  6. Sub-Periosteal Dissection with Denture-Guided Epithelial Regeneration: A Novel Method for Peri-Implant Soft Tissue Management in Reconstructed Mandibles.

    PubMed

    Kumar, Vinay V; Jacob, P C; Kuriakose, Moni A

    2016-12-01

    In patients with reconstructed mandibles using free fibula flaps, management of soft tissues around implants supporting dental rehabilitation, is often a clinical problem. The aim of this paper is to describe a new technique, namely "Sub-periosteal dissection and denture-guided epithelial regeneration (SD-DGER)", as a method of peri-implant soft tissue management in these patients. The technique consists of performing a subperiosteal dissection with creation of buccal and lingual flaps. These flaps form the buccal and lingual vestibule. Implants are placed and an interim denture is immediately loaded onto the implants to guide the regenerated epithelium. A keratinized mucosal layer is formed on the bare fibula bone in six months time. This technique was successful in producing fixed keratinized epithelial tissue around implants in patients with mandibles reconstructed using the free fibula flap in patients who did not undergo radiotherapy. The sub-periosteal dissection with denture guided epithelial regeneration is a predictable form of peri-implant soft tissue management in selected patients with reconstructed jaws.

  7. Prevalence of ciliated epithelium in apical periodontitis lesions.

    PubMed

    Ricucci, Domenico; Loghin, Simona; Siqueira, José F; Abdelsayed, Rafik A

    2014-04-01

    This article reports on the morphologic features and the frequency of ciliated epithelium in apical cysts and discusses its origin. The study material consisted of 167 human apical periodontitis lesions obtained consecutively from patients presenting for treatment during a period of 12 years in a dental practice operated by one of the authors. All of the lesions were obtained still attached to the root apices of teeth with untreated (93 lesions) or treated canals (74 lesions). The former were obtained by extraction and the latter by extraction or apical surgery. Specimens were processed for histopathologic and histobacteriologic analyses. Lesions were classified, and the type of epithelium, if present, was recorded. Of the lesions analyzed, 49 (29%) were diagnosed as cysts. Of these, 26 (53%) were found in untreated teeth, and 23 (47%) related to root canal-treated teeth. Ciliated columnar epithelium was observed partially or completely lining the cyst wall in 4 cysts, and all of them occurred in untreated maxillary molars. Three of these lesions were categorized as pocket cysts, and the other was a true cyst. Ciliated columnar epithelium-lined cysts corresponded to approximately 2% of the apical periodontitis lesions and 8% of the cysts of endodontic origin in the population studied. This epithelium is highly likely to have a sinus origin in the majority of cases. However, the possibility of prosoplasia or upgraded differentiation into ciliated epithelium from the typical cystic lining squamous epithelium may also be considered. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  8. Transport mechanism of lipid covered saquinavir pure drug nanoparticles in intestinal epithelium.

    PubMed

    Xia, Dengning; He, Yuan; Li, Qiuxia; Hu, Cunde; Huang, Wei; Zhang, Yunhai; Wan, Feng; Wang, Chi; Gan, Yong

    2018-01-10

    Pure drug nanoparticles (NPs) represent a promising formulation for improved drug solubility and controlled dissolution velocity. However, limited absorption by the intestinal epithelium remains challenge to their clinical application, and little is known about how these NPs within the cells are transported. To improve cellular uptake and transport of pure nanodrug in cells, here, a lipid covered saquinavir (SQV) pure drug NP (Lipo@nanodrug) was designed by modifying a pure SQV NP (nanodrug) with a phospholipid bilayer. We studied their endocytosis, intracellular trafficking mechanism using Caco-2 cell model. Uptake of Lipo@nanodrug by Caco-2 cells was 1.91-fold greater than that of pure nanodrug via processes involving cell lipid raft. The transcellular transport of Lipo@nanodrug across Caco-2 monolayers was 3.75-fold and 1.92-fold higher than that of coarse crystals and pure nanodrug, respectively. Within cells, Lipo@nanodrug was mainly localized in the endoplasmic reticulum and Golgi apparatus, leading to transcytosis of Lipo@nanodrug across intestinal epithelial cells, whereas pure nanodrug tended to be retained and to dissolve in cell and removed by P-gp-mediated efflux. In rats, the oral bioavailability of the model drug SQV after Lipo@nanodrug administration was 4.29-fold and 1.77-fold greater than after coarse crystal and pure nanodrug administration, respectively. In conclusion, addition of a phospholipid bilayer to pure drug NP increased their cellular uptake and altered their intracellular processing, helping to improve drug transport across intestinal epithelium. To our knowledge, this is the first presentation of the novel phospholipid bilayer covered SQV pure drug NP design, and a mechanistic study on intracellular trafficking in in vitro cell models has been described. The findings provide a new platform for oral delivery of poorly water-soluble drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Sonic Hedgehog Initiates Cochlear Hair Cell Regeneration through Downregulation of Retinoblastoma Protein

    PubMed Central

    Lu, Na; Chen, Yan; Wang, Zhengmin; Chen, Guoling; Lin, Qin; Chen, Zheng-Yi; Li, Huawei

    2013-01-01

    Cell cycle re-entry by cochlear supporting cells and/or hair cells is considered one of the best approaches for restoring hearing loss as a result of hair cell damage. To identify mechanisms that can be modulated to initiate cell cycle re-entry and hair cell regeneration, we studied the effect of activating the sonic hedgehog (Shh) pathway. We show that Shh signaling in postnatal rat cochleae damaged by neomycin leads to renewed proliferation of supporting cells and hair cells. Further, proliferating supporting cells are likely to transdifferentiate into hair cells. Shh treatment leads to inhibition of retinoblastoma protein (pRb) by increasing phosphorylated pRb and reducing retinoblastoma gene transcription. This results in upregulation of cyclins B1, D2, and D3, and CDK1. These results suggest that Shh signaling induces cell cycle re-entry in cochlear sensory epithelium and the production of new hair cells, in part by attenuating pRb function. This study provides an additional route to modulate pRb function with important implications in mammalian hair cell regeneration. PMID:23211596

  10. Model of in vitro healing to test the influence of dedifferentiated Crithmum maritimum cells on dermal repair and epidermal regeneration.

    PubMed

    Lequeux, C; Lhoste, A; Rovere, M R; Montastier, C; Damour, O

    2011-01-01

    The aim was to test the influence of dedifferentiated Crithmum maritimum cells (dCMC), totipotent vegetal stem cells, on epidermal regeneration in perfect homeostasis using a skin equivalent (SE) model. SE are prepared by seeding fibroblasts on a collagen-glycosaminoglycan-chitosan dermal substrate (DS) epidermalized by keratinocytes 3 weeks later. The originality of this present study lies in the systemic administration of dCMC from the moment when fibroblasts are seeded in the DS right through to the reconstruction of the SE. The thickness of the epidermis as well as the number of proliferating cells expressing Ki-67 and layers expressing terminal differentiation marker (filaggrin) were compared in the dCMC-treated SE versus an untreated control group. dCMC accelerated the complete regeneration and differentiation of the epidermis compared to the negative control (35 days instead of 42 days). Histology showed a multilayered, thick and differentiated epithelium after 35 days of culture. The basal and suprabasal layers had increased 4.88 ± 0.41 times versus the negative control (Mann-Whitney U test: p < 0.001). This result was attributed to the greater proliferation of basal cells because the cell numbers expressing the Ki-67 proliferation marker had increased significantly compared to the negative control (Mann-Whitney U test: p < 0.001). Moreover, dCMC allowed the differentiated epithelium to recover because only treated SE expressed the terminal differentiation marker filaggrin. Our data show that dCMC enhance epidermal cell grafts by stimulating their regeneration and differentiation in perfect homeostasis. They allow the epidermis to recover its structure for protective functions faster than the negative control. Copyright © 2010 S. Karger AG, Basel.

  11. Transport across the choroid plexus epithelium.

    PubMed

    Praetorius, Jeppe; Damkier, Helle Hasager

    2017-06-01

    The choroid plexus epithelium is a secretory epithelium par excellence. However, this is perhaps not the most prominent reason for the massive interest in this modest-sized tissue residing inside the brain ventricles. Most likely, the dominant reason for extensive studies of the choroid plexus is the identification of this epithelium as the source of the majority of intraventricular cerebrospinal fluid. This finding has direct relevance for studies of diseases and conditions with deranged central fluid volume or ionic balance. While the concept is supported by the vast majority of the literature, the implication of the choroid plexus in secretion of the cerebrospinal fluid was recently challenged once again. Three newer and promising areas of current choroid plexus-related investigations are as follows: 1 ) the choroid plexus epithelium as the source of mediators necessary for central nervous system development, 2 ) the choroid plexus as a route for microorganisms and immune cells into the central nervous system, and 3 ) the choroid plexus as a potential route for drug delivery into the central nervous system, bypassing the blood-brain barrier. Thus, the purpose of this review is to highlight current active areas of research in the choroid plexus physiology and a few matters of continuous controversy. Copyright © 2017 the American Physiological Society.

  12. Intra-oral Sebaceous Gland Tumours in Two Dogs.

    PubMed

    Go, D-M; Lee, S-H; Woo, S-H; Kim, D-Y

    2017-11-01

    A 12-year-old female miniature schnauzer and a 12-year-old neutered female cocker spaniel each had a grey-yellow nodular lesion arising from the gingiva. Microscopical examination showed that both nodules were composed of varied proportions of sebocytes and basal-type reserve cells with few ducts lined by stratified squamous epithelium. Based on the histopathological findings, the cases were diagnosed as sebaceous adenoma and sebaceous epithelioma, respectively. In man, the occurrence of sebaceous neoplasms in the oral cavity has been reported to some extent, but these lesions are very rare in animals. To the best of our knowledge, this is the first report of intra-oral sebaceous neoplasms in dogs. Intra-oral sebaceous epithelioma has never been reported in animals. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Increase of poorly proliferated p63+ /Ki67+ basal cells forming multiple layers in the aberrant remodeled epithelium in nasal polyps.

    PubMed

    Zhao, L; Li, Y Y; Li, C W; Chao, S S; Liu, J; Nam, H N; Dung, N T N; Shi, L; Wang, D Y

    2017-06-01

    Aberrant epithelial remodeling with the ectopic expression of p63 (basal cell markers) is an important pathologic phenomenon seen in chronically inflamed airway epithelium such as in nasal polyps (NPs). Biopsies were obtained from 55 NP patients and 18 healthy controls (inferior turbinate). Among NP patients, 15 were treated with oral and nasal steroids, so that two sets of NP biopsies were taken before and after the treatments. p63, Ki67, type IV β-tubulin, and cell cycle markers were investigated in these specimens. The number of p63 + cells is significantly higher in both hyperplastic (1.53-fold, P < 0.0001) and squamous metaplastic (2.02-fold, P < 0.0001) epithelium from NPs than from healthy controls. There are three types of proliferative basal cells (p63 + /Ki67 + ) which are in different phases of the cell cycle, such as G1 phase (type I cells), S to G2 phase (type II cells), and mitosis (type III cells). Of importance, some type I cells may arrest after proliferation although they may still be p63 + /Ki67 + . In healthy epithelium, the ratio of the type I and II cells is almost 50:50. However, less type II cells are found in hyperplastic epithelium (34.85%, P = 0.012) and in squamous metaplastic epithelium (30.77%, P = 0.02) together with the presence of type III cells (3.45%, P = 0.01). These findings were not changed after steroid treatments. An increase of poorly proliferated basal cells forming multiple layers, which may stain for basal cell markers but does not form a proper epidermal barrier, is an important histopathologic phenomenon in aberrant remodeled epithelium of NPs. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Functional recovery of odor representations in regenerated sensory inputs to the olfactory bulb

    PubMed Central

    Cheung, Man C.; Jang, Woochan; Schwob, James E.; Wachowiak, Matt

    2014-01-01

    The olfactory system has a unique capacity for recovery from peripheral damage. After injury to the olfactory epithelium (OE), olfactory sensory neurons (OSNs) regenerate and re-converge on target glomeruli of the olfactory bulb (OB). Thus far, this process has been described anatomically for only a few defined populations of OSNs. Here we characterize this regeneration at a functional level by assessing how odor representations carried by OSN inputs to the OB recover after massive loss and regeneration of the sensory neuron population. We used chronic imaging of mice expressing synaptopHluorin in OSNs to monitor odor representations in the dorsal OB before lesion by the olfactotoxin methyl bromide and after a 12 week recovery period. Methyl bromide eliminated functional inputs to the OB, and these inputs recovered to near-normal levels of response magnitude within 12 weeks. We also found that the functional topography of odor representations recovered after lesion, with odorants evoking OSN input to glomerular foci within the same functional domains as before lesion. At a finer spatial scale, however, we found evidence for mistargeting of regenerated OSN axons onto OB targets, with odorants evoking synaptopHluorin signals in small foci that did not conform to a typical glomerular structure but whose distribution was nonetheless odorant-specific. These results indicate that OSNs have a robust ability to reestablish functional inputs to the OB and that the mechanisms underlying the topography of bulbar reinnervation during development persist in the adult and allow primary sensory representations to be largely restored after massive sensory neuron loss. PMID:24431990

  15. Objectivity in the classification of tumours of the nasal epithelium

    PubMed Central

    Michaels, L.; Hyams, V. J.

    1975-01-01

    A survey of tumours derived from each of the four cell types of nasal epithelium is presented. Criticism is levelled at the adoption of additional terms for tissue types such as lympho-epithelium and transitional cell epithelium and tumours said to be derived from them. Electron microscopy is of assistance in classification particularly in the detection of evidence of keratin synthesis. The proposed classification of tumours of the nasal epithelium is: (1) Pseudostratified columnar epithelium: (a) papillary adenoma, (b) papillary carcinoma. (2) Squamous epithelium: (a) everted squamous papilloma, (b) inverted papilloma, (c) squamous carcinoma of any grade of differentiation from well differentiated to undifferentiated. (3) Melanocyte: malignant melanoma. (4) Olfactory neuroepithelium: olfactory neuroblastoma. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7Fig. 8Fig. 9Fig. 10Fig. 11Fig. 12Fig. 13Fig. 14Fig. 15Fig. 16Fig. 17Fig. 18Fig. 19Fig. 21Fig. 20 PMID:1197175

  16. Oral Insulin Delivery: How Far Are We?

    PubMed Central

    Fonte, Pedro; Araújo, Francisca; Reis, Salette; Sarmento, Bruno

    2013-01-01

    Oral delivery of insulin may significantly improve the quality of life of diabetes patients who routinely receive insulin by the subcutaneous route. In fact, compared with this administration route, oral delivery of insulin in diabetes treatment offers many advantages: higher patient compliance, rapid hepatic insulinization, and avoidance of peripheral hyperinsulinemia and other adverse effects such as possible hypoglycemia and weight gain. However, the oral delivery of insulin remains a challenge because its oral absorption is limited. The main barriers faced by insulin in the gastrointestinal tract are degradation by proteolytic enzymes and lack of transport across the intestinal epithelium. Several strategies to deliver insulin orally have been proposed, but without much clinical or commercial success. Protein encapsulation into nanoparticles is regarded as a promising alternative to administer insulin orally because they have the ability to promote insulin paracellular or transcellular transport across the intestinal mucosa. In this review, different delivery systems intended to increase the oral bioavailability of insulin will be discussed, with a special focus on nanoparticulate carrier systems, as well as the efforts that pharmaceutical companies are making to bring to the market the first oral delivery system of insulin. The toxicological and safety data of delivery systems, the clinical value and progress of oral insulin delivery, and the future prospects in this research field will be also scrutinized. PMID:23567010

  17. Developmental origin of the posterior pigmented epithelium of iris.

    PubMed

    Wang, Xiaobing; Xiong, Kai; Lu, Lei; Gu, Dandan; Wang, Songtao; Chen, Jing; Xiao, Honglei; Zhou, Guomin

    2015-03-01

    Iris epithelium is a double-layered pigmented cuboidal epithelium. According to the current model, the neural retina and the posterior iris pigment epithelium (IPE) are derived from the inner wall of the optic cup, while the retinal pigment epithelium (RPE) and the anterior IPE are derived from the outer wall of the optic cup during development. Our current study shows evidence, contradicting this model of fetal iris development. We demonstrate that human fetal iris expression patterns of Otx2 and Mitf transcription factors are similar, while the expressions of Otx2 and Sox2 are complementary. Furthermore, IPE and RPE exhibit identical morphologic development during the early embryonic period. Our results suggest that the outer layer of the optic cup forms two layers of the iris epithelium, and the posterior IPE is the inward-curling anterior rim of the outer layer of the optic cup. These findings provide a reasonable explanation of how IPE cells can be used as an appropriate substitute for RPE cells.

  18. Matrices and scaffolds for drug delivery in dental, oral and craniofacial tissue engineering☆

    PubMed Central

    Moioli, Eduardo K.; Clark, Paul A.; Xin, Xuejun; Lal, Shan; Mao, Jeremy J.

    2010-01-01

    Current treatments for diseases and trauma of dental, oral and craniofacial (DOC) structures rely on durable materials such as amalgam and synthetic materials, or autologous tissue grafts. A paradigm shift has taken place to utilize tissue engineering and drug delivery approaches towards the regeneration of these structures. Several prototypes of DOC structures have been regenerated such as temporomandibular joint (TMJ) condyle, cranial sutures, tooth structures and periodontium components. However, many challenges remain when taking in consideration the high demand for esthetics of DOC structures, the complex environment and yet minimal scar formation in the oral cavity, and the need for accommodating multiple tissue phenotypes. This review highlights recent advances in the regeneration of DOC structures, including the tooth, periodontium, TMJ, cranial sutures and implant dentistry, with specific emphasis on controlled release of signaling cues for stem cells, biomaterial matrices and scaffolds, and integrated tissue engineering approaches. PMID:17499385

  19. Epithelium percentage estimation facilitates epithelial quantitative protein measurement in tissue specimens.

    PubMed

    Chen, Jing; Toghi Eshghi, Shadi; Bova, George Steven; Li, Qing Kay; Li, Xingde; Zhang, Hui

    2013-12-01

    The rapid advancement of high-throughput tools for quantitative measurement of proteins has demonstrated the potential for the identification of proteins associated with cancer. However, the quantitative results on cancer tissue specimens are usually confounded by tissue heterogeneity, e.g. regions with cancer usually have significantly higher epithelium content yet lower stromal content. It is therefore necessary to develop a tool to facilitate the interpretation of the results of protein measurements in tissue specimens. Epithelial cell adhesion molecule (EpCAM) and cathepsin L (CTSL) are two epithelial proteins whose expressions in normal and tumorous prostate tissues were confirmed by measuring staining intensity with immunohistochemical staining (IHC). The expressions of these proteins were measured by ELISA in protein extracts from OCT embedded frozen prostate tissues. To eliminate the influence of tissue heterogeneity on epithelial protein quantification measured by ELISA, a color-based segmentation method was developed in-house for estimation of epithelium content using H&E histology slides from the same prostate tissues and the estimated epithelium percentage was used to normalize the ELISA results. The epithelium contents of the same slides were also estimated by a pathologist and used to normalize the ELISA results. The computer based results were compared with the pathologist's reading. We found that both EpCAM and CTSL levels, measured by ELISA assays itself, were greatly affected by epithelium content in the tissue specimens. Without adjusting for epithelium percentage, both EpCAM and CTSL levels appeared significantly higher in tumor tissues than normal tissues with a p value less than 0.001. However, after normalization by the epithelium percentage, ELISA measurements of both EpCAM and CTSL were in agreement with IHC staining results, showing a significant increase only in EpCAM with no difference in CTSL expression in cancer tissues. These results

  20. Endocrine cells in ectocervical epithelium. An immunohistochemical and ultrastructural analysis.

    PubMed

    Fetissof, F; Arbeille, B; Boivin, F; Sam-Giao, M; Henrion, C; Lansac, J

    1987-01-01

    A systematic study of endocrine cells in the ectocervix was carried out using histochemical, immunohistochemical and ultrastructural techniques. Serotonin and calcitonin immunoreactive cells were demonstrated in this site. Serotonin and calcitonin immunoreactivities were coexpressed in the same endocrine cell. These distinctive cells were encountered in two main morphological varieties of ectocervical epithelium. Normal-appearing stratified squamous epithelium contained only very rare serotonin and calcitonin cells. In contrast, endocrine cells were fairly abundant in a specific epithelium termed "transitional-like". This type of epithelium was not only confined to the transformation zone but could also extend onto the portio as far as the vaginal cut margin. In some cases, transitional-like epithelium bore morphological resemblance to urothelium. In other cases, it could be regarded as basal cell hyperplasia or immature squamous metaplasia. Of interest, serotonin and calcitonin cells have been well-documented as normal inhabitants of some other non-squamous epithelia, such as urothelium or pseudostratified columnar epithelium. Therefore, it is suggested that certain ectocervical epithelia show some similarities to urothelium, in respect of their morphological appearance and endocrine profile. Further investigations using more objective and specific markers of urothelial cells are needed to assess the exact degree of homology connecting all these types of epithelium.

  1. Morphological studies of the developing human esophageal epithelium.

    PubMed

    Ménard, D

    1995-06-15

    This article focusses on the structural development of human esophageal ciliated epithelium. A combination of transmission electron microscopic (TEM), scanning electron microscopic (SEM), radioautographic, and light microscopic (LM) analyses were carried out using intact fetal tissues between 8 and 20 weeks of gestation as well as cultured esophageal explants. Up to the age of 10 weeks, the stratified esophageal epithelium consisted of two longitudinal primary folds. The surface cells were undifferentiated and contained large glycogen aggregates. Between 11 and 16 weeks, the primary folds (now up to four) had developed secondary folds. The thickness of the epithelium drastically increased (123%) in concomittance with a differentiation of surface columnar ciliated cells. These highly specialized surface cells exhibited junctional complexes and well-developed organelles with numerous microvilli interspersed among the cilia. Transverse sections revealed the internal structure of the cilia with a consistent pattern of nine doublet microtubules surrounding a central pair of single microtubules. Freeze-fracture studies illustrated the presence of a ciliary necklace composed of 6 ring-like rows of intramembranous particles. They also revealed the structure of ciliary cell tight junctions consisting of up to nine anastomosing strands (P-face) or complementary grooves (E-face). Ultrastructural studies (LM, TEM, SEM) of the esophageal squamous epithelium obtained after 15 days of culture showed that the newly formed epithelium was similar to adult human epithelium. Finally LM and SEM observations established that the esophagogastric junction was not yet well delineated, consisting of a transitional area composed of a mixture of esophageal ciliated cells and gastric columnar mucous cells.

  2. Establishment of a Novel Lingual Organoid Culture System: Generation of Organoids Having Mature Keratinized Epithelium from Adult Epithelial Stem Cells

    NASA Astrophysics Data System (ADS)

    Hisha, Hiroko; Tanaka, Toshihiro; Kanno, Shohei; Tokuyama, Yoko; Komai, Yoshihiro; Ohe, Shuichi; Yanai, Hirotsugu; Omachi, Taichi; Ueno, Hiroo

    2013-11-01

    Despite the strong need for the establishment of a lingual epithelial cell culture system, a simple and convenient culture method has not yet been established. Here, we report the establishment of a novel lingual epithelium organoid culture system using a three-dimensional matrix and growth factors. Histological analyses showed that the generated organoids had both a stratified squamous epithelial cell layer and a stratum corneum. Very recently, we showed via a multicolor lineage tracing method that Bmi1-positive stem cells exist at the base of the epithelial basal layer in the interpapillary pit. Using our new culture system, we found that organoids could be generated by single Bmi1-positive stem cells and that in the established organoids, multiple Bmi1-positive stem cells were generated at the outermost layer. Moreover, we observed that organoids harvested at an early point in culture could be engrafted and maturate in the tongue of recipient mice and that the organoids generated from carcinogen-treated mice had an abnormal morphology. Thus, this culture system presents valuable settings for studying not only the regulatory mechanisms of lingual epithelium but also lingual regeneration and carcinogenesis.

  3. Ultrastructural study on the embryonic development of the orthokeratinized epithelium and its cornified layer (lingual nail) on the ventral surface of the lingual apex in the domestic duck (Anas platyrhynchos f. domestica).

    PubMed

    Skieresz-Szewczyk, Kinga; Jackowiak, Hanna; Ratajczak, Marlena

    2018-02-01

    The lingual nail as the cornified layer of the orthokeratinized epithelium in birds is responsible for the collection of solid food by pecking. The aim of the present study is to determine the manner of orthokeratinized epithelium development and assess the degree of readiness of the epithelium to fulfill its mechanical function at hatching. Three developmental phases are distinguished, i.e. embryonic, transformation and pre-hatching stage. In the embryonic stage lasting until day 13 of incubation the epithelium is composed of several layers of undifferentiated cells. During the transformation stage, from day 14 to 20 of incubation, the epithelium becomes differentiated to form three layers. A characteristic feature is the formation of osmophilic granules in the superficial layer, referred to as periderm granules. Until the pre-hatching stage the fibrous cytoskeleton of epithelial cells and an impermeable epithelial barrier are gradually developed. In the pre-hatching stage, a cornified lingual nail is formed, while the periderm is exfoliated. At hatching the orthokeratinized epithelium and lingual nail are fully developed and ready to perform feeding activities. The presence of periderm, similarly as in the epidermis, indicates the ectodermal derivation of the oral cavity epithelium. Moreover, occurrence of osmophilic granules may be considered as evidence for the phylogenetic affinity of birds and reptiles. Copyright © 2018 Elsevier GmbH. All rights reserved.

  4. Oral Chlamydia trachomatis in Patients with Established Periodontitis

    PubMed Central

    Reed, Susan G.; Lopatin, Dennis E.; Foxman, Betsy; Burt, Brian A.

    2009-01-01

    Periodontitis is considered a consequence of a pathogenic microbial infection at the periodontal site and host susceptibility factors. Periodontal research supports the association of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, and Bacteroides forsythus, and periodontitis; however causality has not been demonstrated. In pursuit of the etiology of periodontitis, we hypothesized that the intracellular bacteria, Chlamydia trachomatis, may play a role. As a first step, a cross-sectional study of dental school clinic patients with established periodontitis were assessed for the presence of C. trachomatis in the oral cavity, and in particular from the lining epithelium of periodontal sites. C. trachomatis was detected using a direct fluorescent monoclonal antibody (DFA) in oral specimens from 7% (6/87) of the patients. Four patients tested positive in specimens from the lining epithelium of diseased periodontal sites, one patient tested positive in healthy periodontal sites, and one patient tested positive in the general mucosal specimen. In conclusion, this study provides preliminary evidence of C. trachomatis in the periodontal sites. Planned studies include the use of a more precise periodontal epithelial cell collection device, the newer nucleic acid amplification techniques to detect C. trachomatis, and additional populations to determine the association of C. trachomatis and periodontitis. PMID:11218493

  5. Cellular and nerve regeneration within a biosynthetic extracellular matrix for corneal transplantation

    NASA Astrophysics Data System (ADS)

    Li, Fengfu; Carlsson, David; Lohmann, Chris; Suuronen, Erik; Vascotto, Sandy; Kobuch, Karin; Sheardown, Heather; Munger, Rejean; Nakamura, Masatsugu; Griffith, May

    2003-12-01

    Our objective was to determine whether key properties of extracellular matrix (ECM) macromolecules can be replicated within tissue-engineered biosynthetic matrices to influence cellular properties and behavior. To achieve this, hydrated collagen and N-isopropylacrylamide copolymer-based ECMs were fabricated and tested on a corneal model. The structural and immunological simplicity of the cornea and importance of its extensive innervation for optimal functioning makes it an ideal test model. In addition, corneal failure is a clinically significant problem. Matrices were therefore designed to have the optical clarity and the proper dimensions, curvature, and biomechanical properties for use as corneal tissue replacements in transplantation. In vitro studies demonstrated that grafting of the laminin adhesion pentapeptide motif, YIGSR, to the hydrogels promoted epithelial stratification and neurite in-growth. Implants into pigs' corneas demonstrated successful in vivo regeneration of host corneal epithelium, stroma, and nerves. In particular, functional nerves were observed to rapidly regenerate in implants. By comparison, nerve regeneration in allograft controls was too slow to be observed during the experimental period, consistent with the behavior of human cornea transplants. Other corneal substitutes have been produced and tested, but here we report an implantable matrix that performs as a physiologically functional tissue substitute and not simply as a prosthetic device. These biosynthetic ECM replacements should have applicability to many areas of tissue engineering and regenerative medicine, especially where nerve function is required. regenerative medicine | tissue engineering | cornea | implantation | innervation

  6. Expression patterns of epiplakin1 in pancreas, pancreatic cancer and regenerating pancreas.

    PubMed

    Yoshida, Tetsu; Shiraki, Nobuaki; Baba, Hideo; Goto, Mizuki; Fujiwara, Sakuhei; Kume, Kazuhiko; Kume, Shoen

    2008-07-01

    Epiplakin1 (Eppk1) is a plakin family gene with its function remains largely unknown, although the plakin genes are known to function in interconnecting cytoskeletal filaments and anchoring them at plasma membrane-associated adhesive junction. Here we analyzed the expression patterns of Eppk1 in the developing and adult pancreas in the mice. In the embryonic pancreas, Eppk1+/Pdx1+ and Eppk1+/Sox9+ pancreatic progenitor cells were observed in early pancreatic epithelium. Since Pdx1 expression overlapped with that of Sox9 at this stage, these multipotent progenitor cells are Eppk1+/Pdx1+/Sox9+ cells. Then Eppk1 expression becomes confined to Ngn3+ or Sox9+ endocrine progenitor cells, and p48+ exocrine progenitor cells, and then restricted to the duct cells and a cells at birth. In the adult pancreas, Eppk1 is expressed in centroacinar cells (CACs) and in duct cells. Eppk1 is observed in pancreatic intraepithelial neoplasia (PanIN), previously identified as pancreatic ductal adenocarcinoma (PDAC) precursor lesions. In addition, the expansion of Eppk1-positive cells occurs in a caerulein-induced acute pancreatitis, an acinar cell regeneration model. Furthermore, in the partial pancreatectomy (Px) regeneration model using mice, Eppk1 is expressed in "ducts in foci", a tubular structure transiently induced. These results suggest that Eppk1 serves as a useful marker for detecting pancreatic progenitor cells in developing and regenerating pancreas.

  7. Approaches for Enhancing Oral Bioavailability of Peptides and Proteins

    PubMed Central

    Renukuntla, Jwala; Vadlapudi, Aswani Dutt; Patel, Ashaben; Boddu, Sai HS.; Mitra, Ashim K

    2013-01-01

    Oral delivery of peptide and protein drugs faces immense challenge partially due to the gastrointestinal (GI) environment. In spite of considerable efforts by industrial and academic laboratories, no major breakthrough in the effective oral delivery of polypeptides and proteins has been accomplished. Upon oral administration, gastrointestinal epithelium acts as a physical and biochemical barrier for absorption of proteins resulting in low bioavailability (typically less than 1–2%). An ideal oral drug delivery system should be capable of a) maintaining the integrity of protein molecules until it reaches the site of absorption, b) releasing the drug at the target absorption site, where the delivery system appends to that site by virtue of specific interaction, and c) retaining inside the gastrointestinal tract irrespective of its transitory constraints. Various technologies have been explored to overcome the problems associated with the oral delivery of macromolecules such as insulin, gonadotropin-releasing hormones, calcitonin, human growth factor, vaccines, enkephalins, and interferons, all of which met with limited success. This review article intends to summarize the physiological barriers to oral delivery of peptides and proteins and novel pharmaceutical approaches to circumvent these barriers and enhance oral bioavailability of these macromolecules. PMID:23428883

  8. Unusual epithelium in a subpubic sinus.

    PubMed

    Chao, Hong-Ming; Chuang, Chia-Jueng; Chen, Ke-Chi; Chu, Chih-Chun; Chou, Jung-Mao

    2002-09-01

    A 5-year-old male presented with the history of whitish discharge from a midline sinus opening just above the pubis for 2 months. Attempted radiography of the sinus revealed a blind fistula and voiding cystourethrography was normal. The fistula was excised deep to the subpubic space without any evidence of connection to the lower urinary tract. Pathologic evaluation of the lesion revealed a ciliated-columnar lining with stratified-squamous and transitional epithelium. To our knowledge, a subpubic sinus with this unique presentation of epithelium has not been reported previously.

  9. Epigenetic Disregulation in Oral Cancer

    PubMed Central

    Mascolo, Massimo; Siano, Maria; Ilardi, Gennaro; Russo, Daniela; Merolla, Francesco; De Rosa, Gaetano; Staibano, Stefania

    2012-01-01

    Squamous cell carcinoma of the oral region (OSCC) is one of the most common and highly aggressive malignancies worldwide, despite the fact that significant results have been achieved during the last decades in its detection, prevention and treatment. Although many efforts have been made to define the molecular signatures that identify the clinical outcome of oral cancers, OSCC still lacks reliable prognostic molecular markers. Scientific evidence indicates that transition from normal epithelium to pre-malignancy, and finally to oral carcinoma, depends on the accumulation of genetic and epigenetic alterations in a multistep process. Unlike genetic alterations, epigenetic changes are heritable and potentially reversible. The most common examples of such changes are DNA methylation, histone modification, and small non-coding RNAs. Although several epigenetic changes have been currently linked to OSCC initiation and progression, they have been only partially characterized. Over the last decade, it has been demonstrated that especially aberrant DNA methylation plays a critical role in oral cancer. The major goal of the present paper is to review the recent literature about the epigenetic modifications contribution in early and later phases of OSCC malignant transformation; in particular we point out the current evidence of epigenetic marks as novel markers for early diagnosis and prognosis as well as potential therapeutic targets in oral cancer. PMID:22408457

  10. ADAM10 and γ-secretase regulate sensory regeneration in the avian vestibular organs.

    PubMed

    Warchol, Mark E; Stone, Jennifer; Barton, Matthew; Ku, Jeffrey; Veile, Rose; Daudet, Nicolas; Lovett, Michael

    2017-08-01

    The loss of sensory hair cells from the inner ear is a leading cause of hearing and balance disorders. The mammalian ear has a very limited ability to replace lost hair cells, but the inner ears of non-mammalian vertebrates can spontaneously regenerate hair cells after injury. Prior studies have shown that replacement hair cells are derived from epithelial supporting cells and that the differentiation of new hair cells is regulated by the Notch signaling pathway. The present study examined molecular influences on regeneration in the avian utricle, which has a particularly robust regenerative ability. Chicken utricles were placed in organotypic culture and hair cells were lesioned by application of the ototoxic antibiotic streptomycin. Cultures were then allowed to regenerate in vitro for seven days. Some specimens were treated with small molecule inhibitors of γ-secretase or ADAM10, proteases which are essential for transmission of Notch signaling. As expected, treatment with both inhibitors led to increased numbers of replacement hair cells. However, we also found that inhibition of both proteases resulted in increased regenerative proliferation. Subsequent experiments showed that inhibition of γ-secretase or ADAM10 could also trigger proliferation in undamaged utricles. To better understand these phenomena, we used RNA-Seq profiling to characterize changes in gene expression following γ-secretase inhibition. We observed expression patterns that were consistent with Notch pathway inhibition, but we also found that the utricular sensory epithelium contains numerous γ-secretase substrates that might regulate cell cycle entry and possibly supporting cell-to-hair cell conversion. Together, our data suggest multiple roles for γ-secretase and ADAM10 in vestibular hair cell regeneration. Copyright © 2017. Published by Elsevier Inc.

  11. Boron microlocalization in oral mucosal tissue: implications for boron neutron capture therapy

    PubMed Central

    Morris, G M; Smith, D R; Patel, H; Chandra, S; Morrison, G H; Hopewell, J W; Rezvani, M; Micca, P L; Coderre, J A

    2000-01-01

    Clinical studies of the treatment of glioma and cutaneous melanoma using boron neutron capture therapy (BNCT) are currently taking place in the USA, Europe and Japan. New BNCT clinical facilities are under construction in Finland, Sweden, England and California. The observation of transient acute effects in the oral mucosa of a number of glioma patients involved in the American clinical trials, suggests that radiation damage of the oral mucosa could be a potential complication in future BNCT clinical protocols, involving higher doses and larger irradiation field sizes. The present investigation is the first to use a high resolution surface analytical technique to relate the microdistribution of boron-10 (10B) in the oral mucosa to the biological effectiveness of the 10B(n,α)7Li neutron capture reaction in this tissue. The two boron delivery agents used clinically in Europe/Japan and the USA, borocaptate sodium (BSH) and p-boronophenylalanine (BPA), respectively, were evaluated using a rat ventral tongue model. 10B concentrations in various regions of the tongue mucosa were estimated using ion microscopy. In the epithelium, levels of 10B were appreciably lower after the administration of BSH than was the case after BPA. The epithelium:blood 10B partition ratios were 0.2:1 and 1:1 for BSH and BPA respectively. The 10B content of the lamina propria was higher than that measured in the epithelium for both BSH and BPA. The difference was most marked for BSH, where 10B levels were a factor of six higher in the lamina propria than in the epithelium. The concentration of 10B was also measured in blood vessel walls where relatively low levels of accumulation of BSH, as compared with BPA, was demonstrated in blood vessel endothelial cells and muscle. Vessel wall:blood 10B partition ratios were 0.3:1 and 0.9:1 for BSH and BPA respectively. Evaluation of tongue mucosal response (ulceration) to BNC irradiation indicated a considerably reduced radiation sensitivity using BSH as

  12. Coelomic epithelium-derived cells in visceral morphogenesis.

    PubMed

    Ariza, Laura; Carmona, Rita; Cañete, Ana; Cano, Elena; Muñoz-Chápuli, Ramón

    2016-03-01

    Coelomic cavities of vertebrates are lined by a mesothelium which develops from the lateral plate mesoderm. During development, the coelomic epithelium is a highly active cell layer, which locally is able to supply mesenchymal cells that contribute to the mesodermal elements of many organs and provide signals which are necessary for their development. The relevance of this process of mesenchymal cell supply to the developing organs is becoming clearer because genetic lineage tracing techniques have been developed in recent years. Body wall, heart, liver, lungs, gonads, and gastrointestinal tract are populated by cells derived from the coelomic epithelium which contribute to their connective and vascular tissues, and sometimes to specialized cell types such as the stellate cells of the liver, the Cajal interstitial cells of the gut or the Sertoli cells of the testicle. In this review we collect information about the contribution of coelomic epithelium derived cells to visceral development, their developmental fates and signaling functions. The common features displayed by all these processes suggest that the epithelial-mesenchymal transition of the embryonic coelomic epithelium is an underestimated but key event of vertebrate development, and probably it is shared by all the coelomate metazoans. © 2015 Wiley Periodicals, Inc.

  13. Use of Mesothelial Cells and Biological Matrices for Tissue Engineering of Simple Epithelium Surrogates.

    PubMed

    Lachaud, Christian Claude; Rodriguez-Campins, Berta; Hmadcha, Abdelkrim; Soria, Bernat

    2015-01-01

    Tissue-engineering technologies have progressed rapidly through last decades resulting in the manufacture of quite complex bioartificial tissues with potential use for human organ and tissue regeneration. The manufacture of avascular monolayered tissues such as simple squamous epithelia was initiated a few decades ago and is attracting increasing interest. Their relative morphostructural simplicity makes of their biomimetization a goal, which is currently accessible. The mesothelium is a simple squamous epithelium in nature and is the monolayered tissue lining the walls of large celomic cavities (peritoneal, pericardial, and pleural) and internal organs housed inside. Interestingly, mesothelial cells can be harvested in clinically relevant numbers from several anatomical sources and not less important, they also display high transdifferentiation capacities and are low immunogenic characteristics, which endow these cells with therapeutic interest. Their combination with a suitable scaffold (biocompatible, degradable, and non-immunogenic) may allow the manufacture of tailored serosal membranes biomimetics with potential spanning a wide range of therapeutic applications, principally for the regeneration of simple squamous-like epithelia such as the visceral and parietal mesothelium vascular endothelium and corneal endothelium among others. Herein, we review recent research progresses in mesothelial cells biology and their clinical sources. We make a particular emphasis on reviewing the different types of biological scaffolds suitable for the manufacture of serosal mesothelial membranes biomimetics. Finally, we also review progresses made in mesothelial cells-based therapeutic applications and propose some possible future directions.

  14. Use of Mesothelial Cells and Biological Matrices for Tissue Engineering of Simple Epithelium Surrogates

    PubMed Central

    Lachaud, Christian Claude; Rodriguez-Campins, Berta; Hmadcha, Abdelkrim; Soria, Bernat

    2015-01-01

    Tissue-engineering technologies have progressed rapidly through last decades resulting in the manufacture of quite complex bioartificial tissues with potential use for human organ and tissue regeneration. The manufacture of avascular monolayered tissues such as simple squamous epithelia was initiated a few decades ago and is attracting increasing interest. Their relative morphostructural simplicity makes of their biomimetization a goal, which is currently accessible. The mesothelium is a simple squamous epithelium in nature and is the monolayered tissue lining the walls of large celomic cavities (peritoneal, pericardial, and pleural) and internal organs housed inside. Interestingly, mesothelial cells can be harvested in clinically relevant numbers from several anatomical sources and not less important, they also display high transdifferentiation capacities and are low immunogenic characteristics, which endow these cells with therapeutic interest. Their combination with a suitable scaffold (biocompatible, degradable, and non-immunogenic) may allow the manufacture of tailored serosal membranes biomimetics with potential spanning a wide range of therapeutic applications, principally for the regeneration of simple squamous-like epithelia such as the visceral and parietal mesothelium vascular endothelium and corneal endothelium among others. Herein, we review recent research progresses in mesothelial cells biology and their clinical sources. We make a particular emphasis on reviewing the different types of biological scaffolds suitable for the manufacture of serosal mesothelial membranes biomimetics. Finally, we also review progresses made in mesothelial cells-based therapeutic applications and propose some possible future directions. PMID:26347862

  15. Noninvasive imaging of oral mucosae with optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Lee, Cheng-Yu; Chen, Wei-Chuan; Tsai, Meng-Tsan

    2017-04-01

    In this study, a swept-source optical coherence tomography (OCT) system is developed for in vivo visualization of structural and vascular morphology oral mucosa. For simplification of optical probe fabrication, probe weight, and system setup, the body of the scanning probe is fabricated by a 3D printer to fix the optical components and the mechanical scanning device, and a partially reflective slide is attached at the output end of probe to achieve a common-path configuration. Aside from providing the ability of 3D structural imaging with the developed system, 3D vascular images of oral mucosa can be simultaneously obtained. Then, different locations of oral mucosa are scanned with common-path OCT. The results show that epithelium and lamina propria layers as well as fungiform papilla can be identified and microvascular images can be acquired. With the proposed probe, the system cost and volume can be greatly reduced. Experimental results indicate that such common-path OCT system could be further implemented for oral cancer diagnosis.

  16. Dynamics of Bovine Sperm Interaction with Epithelium Differ Between Oviductal Isthmus and Ampulla.

    PubMed

    Ardon, Florencia; Markello, Ross D; Hu, Lian; Deutsch, Zarah I; Tung, Chih-Kuan; Wu, Mingming; Suarez, Susan S

    2016-10-01

    In mammals, many sperm that reach the oviduct are held in a reservoir by binding to epithelium. To leave the reservoir, sperm detach from the epithelium; however, they may bind and detach again as they ascend into the ampulla toward oocytes. In order to elucidate the nature of binding interactions along the oviduct, we compared the effects of bursts of strong fluid flow (as would be caused by oviductal contractions), heparin, and hyperactivation on detachment of bovine sperm bound in vitro to epithelium on intact folds of isthmic and ampullar mucosa. Intact folds of oviductal mucosa were used to represent the strong attachments of epithelial cells to each other and to underlying connective tissue that exist in vivo. Effects of heparin on binding were tested because heparin binds to the Binder of SPerm (BSP) proteins that attach sperm to oviductal epithelium. Sperm bound by their heads to beating cilia on both isthmic and ampullar epithelia and could not be detached by strong bursts of fluid flow. Addition of heparin immediately detached sperm from isthmic epithelium but not ampullar epithelium. Addition of 4-aminopyridine immediately stimulated hyperactivation of sperm but did not detach them from isthmic or ampullar epithelium unless added with heparin. These observations indicate that the nature of binding of sperm to ampullar epithelium differs from that of binding to isthmic epithelium; specifically, sperm bound to isthmic epithelium can be detached by heparin alone, while sperm bound to ampullar epithelium requires both heparin and hyperactivation to detach from the epithelium. © 2016 by the Society for the Study of Reproduction, Inc.

  17. Laser treatment of an oral squamous papilloma in a pediatric patient: a case report.

    PubMed

    Misir, Ahmet Ferhat; Demiriz, Levent; Barut, Figen

    2013-01-01

    Oral squamous papilloma is a benign proliferation of the stratified squamous epithelium, which results in a papillary or verrucous exophytic mass induced by human papilloma virus (HPV). These oral mucosa lesions are most often asymptomatic and have small progression. Laser assisted surgery is common nowadays with several advantages including successful hemostasis, devoid of sutures, wound sterilization and minimal post-operative pain and edema. The aim of this report is to present the oral squamous papilloma in a pediatric patient and its treatment with soft tissue laser. The lesion was excised with diode laser and the healing was uneventful in follow-up visit after one year. Oral squamous papillomas can be found in child's oral cavity and laser dentistry can be used by dental clinicians to treat these kinds of oral lesions and should be considered as an alternative to conventional surgery.

  18. Does Guided Bone Regeneration Prevent Unfavorable Bone Shapes in Distraction Gap?

    PubMed

    Demetoglu, Umut; Alkan, Alper; Kiliç, Erdem; Ozturk, Mustafa; Bilge, Suheyb

    2018-03-01

    Complications related to distraction osteogenesis can cause degradation of newly regenerated bone. Additionally, an unfavorable shape of the regenerated bone at the distraction gap can reduce the quantity of regenerated bone. The aim of the present study was to report on the prevention of unfavorable shapes of regenerated bone using guided bone regeneration during distraction. Bilateral alveolar distraction was performed in 10 beagle dog mandibles. One side of the mandible formed the experimental group and the other side served as the control group. In the experimental group, guided bone regeneration was performed simultaneously with distraction osteogenesis. In the control group, only alveolar distraction was applied. At the end of a 1-week latent period, all mandibles were distracted 10 mm (1 mm/day). After the distraction period, 3 months were allowed for consolidation. After consolidation, all the dogs were euthanized, and the shape of the regenerated bone was determined to be either favorable or unfavorable. Densitometric evaluation and area measurements were performed using computed tomography scans. Statistical evaluation was performed using the independent t test, with a significance level of P < .05. In the experimental group, no unfavorable bone shape developed in the distraction gap, and the new bone had a surface and volume similar to those of the segments. In contrast, in the control group, 4 mandibles had an unfavorable bone shape in the distraction gap and 4 showed favorable bone healing with no defect. The surface area of the regenerating bone in the experimental group was significantly greater than that in the control group. Also, the surface area differed significantly between the experimental and control groups (P < .05). However, the densitometric values did not differ between the 2 groups (P < .05). Concomitant use of guided bone regeneration with distraction osteogenesis could be an optimal method for generating a favorable bone shape

  19. Oral Delivery of Protein Drugs Bioencapsulated in Plant Cells.

    PubMed

    Kwon, Kwang-Chul; Daniell, Henry

    2016-08-01

    Plants cells are now approved by the FDA for cost-effective production of protein drugs (PDs) in large-scale current Good Manufacturing Practice (cGMP) hydroponic growth facilities. In lyophilized plant cells, PDs are stable at ambient temperature for several years, maintaining their folding and efficacy. Upon oral delivery, PDs bioencapsulated in plant cells are protected in the stomach from acids and enzymes but are subsequently released into the gut lumen by microbes that digest the plant cell wall. The large mucosal area of the human intestine offers an ideal system for oral drug delivery. When tags (receptor-binding proteins or cell-penetrating peptides) are fused to PDs, they efficiently cross the intestinal epithelium and are delivered to the circulatory or immune system. Unique tags to deliver PDs to human immune or nonimmune cells have been developed recently. After crossing the epithelium, ubiquitous proteases cleave off tags at engineered sites. PDs are also delivered to the brain or retina by crossing the blood-brain or retinal barriers. This review highlights recent advances in PD delivery to treat Alzheimer's disease, diabetes, hypertension, Gaucher's or ocular diseases, as well as the development of affordable drugs by eliminating prohibitively expensive purification, cold chain and sterile delivery.

  20. Expressions of TRPVs in the cholesteatoma epithelium.

    PubMed

    Do, Ba Hung; Koizumi, Hiroki; Ohbuchi, Toyoaki; Kawaguchi, Rintaro; Suzuki, Hideaki

    2017-10-01

    We have recently proposed a hypothesis that acid leakage through the cholesteatoma epithelium mediates bone resorption in middle ear cholesteatoma. In the present study, we investigated the expressions of transient receptor potential vanilloid (TRPV) channels, which have been shown to play roles in the regulation of epidermal barrier function, in the cholesteatoma epithelium in comparison with the normal skin. Cholesteatoma epithelium and postauricular skin were collected from 17 patients with primary acquired middle ear cholesteatoma who underwent tympanomastoidectomy. Expressions of TRPV1, TRPV3, TRPV4, and TRPV6 were explored by fluorescence immunohistochemistry and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). TRPV1, TRPV3, TRPV4, and TRPV6 mRNAs were all detected by qRT-PCR both in the skin and cholesteatoma tissue. Immunohistochemical staining showed that TRPV1 and TRPV3 were positive in the viable cell layers of the epidermis of the skin, and only TRPV3 was positive in those of the cholesteatoma epithelium. The immunoreactivity for TRPV3 was significantly weaker in cholesteatoma than in the skin. The lower expression of TRPV3 in cholesteatoma may be one of the mechanisms underlying the increased permeability of this tissue. On the other hand, TRPV1, TRPV4, and TRPV6 are unlikely to be involved in the regulation of epithelial permeability in cholesteatoma.

  1. Neutral endopeptidase regulates neurogenic inflammatory responses induced by stimulation of human oral keratinocytes with bacterial lipopolysaccharide and nicotine.

    PubMed

    Nakata, Motoki; Awano, Shuji; Kinoshita, Naomasa; Yoshida, Akihiro; Ansai, Toshihiro

    2013-10-01

    Neutral endopeptidase (NEP) is present on various epithelial cells and inactivates numerous physiologically active peptides. Neutral endopeptidase may regulate proinflammatory signals in oral mucosal epithelium. However, the function of NEP in oral mucosal epithelium is unknown. The present study investigated the action of NEP upon proinflammatory signals on human oral keratinocytes and the influence of endothelin-converting enzyme (ECE)-1, an enzyme similar to NEP, on the functions of NEP. Oral keratinocytes were cultured in medium containing inflammatory inducers [lipopolysaccharide (LPS) and nicotine], NEP inhibitors, and ECE-1/NEP inhibitors, either alone or in combination. The concentrations of substance P (SP) and interleukin-1β (IL-1β) were measured in the supernatant. Additionally, the concentrations of SP and IL-1β were measured in the supernatant of cells incubated with LPS or nicotine after transfection with NEP small interfering RNA (siRNA). The concentrations of SP and IL-1β were significantly increased in cells incubated with NEP inhibitors and, to a lesser extent, in cells incubated with ECE-1/NEP inhibitors, compared with controls (cells incubated with LPS or nicotine alone). The concentrations of SP and IL-1β in cells transfected with NEP siRNA were significantly augmented compared with controls. In conclusion, the present study demonstrated that NEP down-regulated the levels of SP and IL-1β produced from human oral keratinocytes, although ECE-1 may be partly related to the down-regulation. © 2013 Eur J Oral Sci.

  2. Meckel's diverticulum and ectopic epithelium: Evaluation of a complex relationship.

    PubMed

    Burjonrappa, Sathyaprasad; Khaing, Phue

    2014-04-01

    Meckel's diverticulum is the most common congenital anomaly of the gastrointestinal tract. Currently, for any incidentally discovered Meckel's diverticulum, the management approach is based on weighing the statistical odds of future complications against the risks of a diverticulectomy. The temporal relationship between age at Meckel's diverticulectomy and the presence of ectopic epithelium was evaluated in our series. A meta-analysis of all reported recent literature on this condition was subsequently performed to evaluate the strength of the relationship between ectopic epithelium and symptomatic Meckel's diverticulum. There was a paucity of ectopic epithelium in Meckel's diverticulectomy specimens in infants operated on at less than 1 year of age. Having two or more ectopic epithelia in a diverticulum does not appear to carry an additive risk for complications. The meta-analysis confirmed that ectopic epithelium was the most significant factor that influenced surgical intervention in all series of Meckel's diverticulum. The relationship between ectopic epithelium and the development of symptomatic Meckel's diverticulum is complex. Further understanding of the development of ectopic rests in the diverticulum will facilitate elucidating the pathophysiology in symptomatic cases.

  3. Tubularized urethral replacement with unseeded matrices: what is the maximum distance for normal tissue regeneration?

    PubMed

    Dorin, Ryan P; Pohl, Hans G; De Filippo, Roger E; Yoo, James J; Atala, Anthony

    2008-08-01

    Complete urethral replacement using unseeded matrices has been proposed as a possible therapy in cases of congenital or acquired anomalies producing significant defects. Tissue regeneration involves fibrin deposition, re-epithelialization, and remodeling that are limited by the size of the defect. Scar formation occurs because of an inability of native cells to regenerate over the defect before fibrosis takes place. We investigated the maximum potential distance of normal native tissue regeneration over a range of distances using acellular matrices for tubular grafts as an experimental model. Tubularized urethroplasties were performed in 12 male rabbits using acellular matrices of bladder submucosa at varying lengths (0.5, 1, 2, and 3 cm). Serial urethrography was performed at 1, 3, and 4 weeks. Animals were sacrificed at 1, 3, and 4 weeks and the grafts harvested. Urothelial and smooth muscle cell regeneration was documented histologically with H&E and Masson's trichrome stains. Urethrograms demonstrated normal urethral calibers in the 0.5 cm group at all time points. The evolution of a stricture was demonstrated in the 1, 2, and 3 cm grafts by 4 weeks. Histologically all grafts demonstrated ingrowth of urothelial cells from the anastomotic sites at 1 week. By 4 weeks, the 0.5 cm grafts had a normal transitional layer of epithelium surrounded by a layer of muscle within the wall of the urethral lumen. The 1, 2, and 3 cm grafts showed ingrowth and normal cellular regeneration only at the anastomotic edges with increased collagen deposition and fibrosis toward the center by 2 weeks, and dense fibrin deposition throughout the grafts by 4 weeks. The maximum defect distance suitable for normal tissue formation using acellular grafts that rely on the native cells for tissue regeneration appears to be 0.5 cm. The indications for the use of acellular matrices in tubularized grafts may therefore be limited by the size of the defect to be repaired.

  4. Regeneration of the digestive system in the crinoid Himerometra robustipinna occurs by transdifferentiation of neurosecretory-like cells

    PubMed Central

    Kalacheva, Nadezhda V.; Eliseikina, Marina G.; Frolova, Lidia T.

    2017-01-01

    The structure and regeneration of the digestive system in the crinoid Himerometra robustipinna (Carpenter, 1881) were studied. The gut comprises a spiral tube forming radial lateral processes, which gives it a five-lobed shape. The digestive tube consists of three segments: esophagus, intestine, and rectum. The epithelia of these segments have different cell compositions. Regeneration of the gut after autotomy of the visceral mass progresses very rapidly. Within 6 h after autotomy, an aggregation consisting of amoebocytes, coelomic epithelial cells and juxtaligamental cells (neurosecretory neurons) forms on the inner surface of the skeletal calyx. At 12 h post-autotomy, transdifferentiation of the juxtaligamental cells starts. At 24 h post-autotomy these cells undergo a mesenchymal-epithelial-like transition, resulting in the formation of the luminal epithelium of the gut. Specialization of the intestinal epithelial cells begins on day 2 post-autotomy. At this stage animals acquire the mouth and anal opening. On day 4 post-autotomy the height of both the enterocytes and the visceral mass gradually increases. Proliferation does not play any noticeable role in gut regeneration. The immersion of animals in a 10−7 M solution of colchicine neither stopped formation of the lost structures nor caused accumulation of mitoses in tissues. Weakly EdU-labeled nuclei were observed in the gut only on day 2 post-autotomy and were not detected at later regeneration stages. Single mitotically dividing cells were recorded during the same period. It is concluded that juxtaligamental cells play a major role in gut regeneration in H. robustipinna. The main mechanisms of morphogenesis are cell migration and transdifferentiation. PMID:28753616

  5. Regeneration of the digestive system in the crinoid Himerometra robustipinna occurs by transdifferentiation of neurosecretory-like cells.

    PubMed

    Kalacheva, Nadezhda V; Eliseikina, Marina G; Frolova, Lidia T; Dolmatov, Igor Yu

    2017-01-01

    The structure and regeneration of the digestive system in the crinoid Himerometra robustipinna (Carpenter, 1881) were studied. The gut comprises a spiral tube forming radial lateral processes, which gives it a five-lobed shape. The digestive tube consists of three segments: esophagus, intestine, and rectum. The epithelia of these segments have different cell compositions. Regeneration of the gut after autotomy of the visceral mass progresses very rapidly. Within 6 h after autotomy, an aggregation consisting of amoebocytes, coelomic epithelial cells and juxtaligamental cells (neurosecretory neurons) forms on the inner surface of the skeletal calyx. At 12 h post-autotomy, transdifferentiation of the juxtaligamental cells starts. At 24 h post-autotomy these cells undergo a mesenchymal-epithelial-like transition, resulting in the formation of the luminal epithelium of the gut. Specialization of the intestinal epithelial cells begins on day 2 post-autotomy. At this stage animals acquire the mouth and anal opening. On day 4 post-autotomy the height of both the enterocytes and the visceral mass gradually increases. Proliferation does not play any noticeable role in gut regeneration. The immersion of animals in a 10-7 M solution of colchicine neither stopped formation of the lost structures nor caused accumulation of mitoses in tissues. Weakly EdU-labeled nuclei were observed in the gut only on day 2 post-autotomy and were not detected at later regeneration stages. Single mitotically dividing cells were recorded during the same period. It is concluded that juxtaligamental cells play a major role in gut regeneration in H. robustipinna. The main mechanisms of morphogenesis are cell migration and transdifferentiation.

  6. Raman spectroscopy of normal oral buccal mucosa tissues: study on intact and incised biopsies

    NASA Astrophysics Data System (ADS)

    Deshmukh, Atul; Singh, S. P.; Chaturvedi, Pankaj; Krishna, C. Murali

    2011-12-01

    Oral squamous cell carcinoma is one of among the top 10 malignancies. Optical spectroscopy, including Raman, is being actively pursued as alternative/adjunct for cancer diagnosis. Earlier studies have demonstrated the feasibility of classifying normal, premalignant, and malignant oral ex vivo tissues. Spectral features showed predominance of lipids and proteins in normal and cancer conditions, respectively, which were attributed to membrane lipids and surface proteins. In view of recent developments in deep tissue Raman spectroscopy, we have recorded Raman spectra from superior and inferior surfaces of 10 normal oral tissues on intact, as well as incised, biopsies after separation of epithelium from connective tissue. Spectral variations and similarities among different groups were explored by unsupervised (principal component analysis) and supervised (linear discriminant analysis, factorial discriminant analysis) methodologies. Clusters of spectra from superior and inferior surfaces of intact tissues show a high overlap; whereas spectra from separated epithelium and connective tissue sections yielded clear clusters, though they also overlap on clusters of intact tissues. Spectra of all four groups of normal tissues gave exclusive clusters when tested against malignant spectra. Thus, this study demonstrates that spectra recorded from the superior surface of an intact tissue may have contributions from deeper layers but has no bearing from the classification of a malignant tissues point of view.

  7. Urinary proteomic profiling reveals diclofenac-induced renal injury and hepatic regeneration in mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Swelm, Rachel P.L. van; Laarakkers, Coby M.M.; Pertijs, Jeanne C.L.M.

    Diclofenac (DF) is a widely used non-steroidal anti-inflammatory drug for the treatment of rheumatic disorders, but is often associated with liver injury. We applied urinary proteomic profiling using MALDI-TOF MS to identify biomarkers for DF-induced hepatotoxicity in mice. Female CH3/HeOUJIco mice were treated with 75 mg/kg bw DF by oral gavage and 24 h urine was collected. Proteins identified in urine of DF-treated mice included epidermal growth factor, transthyretin, kallikrein, clusterin, fatty acid binding protein 1 and urokinase, which are related to liver regeneration but also to kidney injury. Both organs showed enhanced levels of oxidative stress (TBARS, p regeneration. In conclusion, urinary proteome analysis revealed that DF treatment in mice induced kidney and liver injury. Within 24 h, however, the liver was able to recover by activating tissue regeneration processes. Hence, the proteins found in urine of DF-treated mice represent kidney damage rather than hepatic injury. - Highlights: • The urinary proteome shows biological processes involved in adverse drug reactions. • Urine proteins of DF-treated mice relate to kidney injury rather than liver injury. • Liver regeneration, not liver injury, is apparent 24h after oral DF administration. • Pretreatment with LPS does not enhance DF-induced liver injury in mice.« less

  8. Characterization of inflammatory cells in oral paracoccidioidomycosis.

    PubMed

    Kaminagakura, E; Bonan, P R F; Jorge, J; Almeida, O P; Scully, C

    2007-07-01

    Paracoccidioidomycosis (Pmycosis) is one of the most common deep mycoses in many regions of Latin America, particularly in Brazil. Microscopically, it shows granulomatous inflammatory reaction with giant cells, macrophages, lymphocytes, plasma cells, polymorphonuclear neutrophilic leukocytes, and eosinophils. The purpose of this study was to assess the distribution of inflammatory cells in oral Pmycosis. Fifteen cases of oral Pmycosis were studied by immunohistochemistry for the presence of macrophages, CD4(+) and CD8(+) lymphocytes, CD20(+), CD15(+), and S100(+) cells. Macrophages were the main cells in well-organized granulomas and non-granulomatous areas. The CD4 phenotype was predominant in well-organized granulomas and a balance between CD4(+) and CD8(+) cells was observed in non-granulomatous areas. Dendritic, S100(+) cells were found mainly in the epithelium, in subepithelial connective tissue, and at the periphery of organized granulomas. CD15(+) cells were concentrated mainly in areas of intraepithelial microabscess and ulceration. Macrophages and T cells are the predominant cells in oral Pmycosis. Well-organized granulomas contain fewer yeast particles, indicating a more effective host immune response. Better understanding of the histopathological changes in oral Pmycosis might help determine treatment, severity and systemic involvement of the disease.

  9. Morphology of the epithelium of the lower rectum and the anal canal in the adult human.

    PubMed

    Tanaka, Eiichi; Noguchi, Tsuyoshi; Nagai, Kaoruko; Akashi, Yuichi; Kawahara, Katsunobu; Shimada, Tatsuo

    2012-06-01

    The anal canal is an important body part clinically. However, there is no agreement about the epithelium of the anal canal, the anal transitional zone (ATZ) epithelium in particular. The aim of this study is to clarify the structure of the epithelium of the human lower rectum and anal canal. Intact rectum and anus obtained from patients who underwent surgery for rectal carcinoma were examined by light and scanning electron microscopy (LM and SEM). By LM, three types of epithelium were observed in the anal canal: simple columnar epithelium, stratified squamous epithelium, and stratified columnar epithelium. The lower rectum was composed of simple columnar epithelium. SEM findings showed stratified squamous epithelium that consisted of squamous cells with microridges, changing to simple columnar epithelium consisting of columnar cells with short microvilli at the anorectal line. LM and SEM observations in a one-to-one ratio revealed that the area of stratified columnar epithelium based on LM corresponded to the anal crypt and sinus. In conclusion, the epithelium of the human anal canal was fundamentally composed of simple columnar epithelium and stratified squamous epithelium. We found no evidence of the ATZ.

  10. Evaluation of Guided Bone Regeneration around Oral Implants over Different Healing Times Using Two Different Bovine Bone Materials: A Randomized, Controlled Clinical and Histological Investigation.

    PubMed

    Kohal, Ralf Joachim; Straub, Lisa Marie; Wolkewitz, Martin; Bächle, Maria; Patzelt, Sebastian Berthold Maximilian

    2015-10-01

    To evaluate the potential of two bone substitute materials and the influence of different healing periods in guided bone regeneration therapy of osseous defects around implants. Twenty-four edentulous patients received implants in the region of the lost lower incisors. Around two standardized osseous defects were created, treated either with a 50:50 mixture of PepGen P-15® and OsteoGraf®/N-700 (test group) or with BioOss® (control group), and covered with titanium membranes. After healing periods of 2, 4, 6, or 9 months, the implants were removed together with the surrounding bone and subsequently prepared for histological evaluations. Defect depths in both groups showed a clinical reduction after intervention. The histologically measured distance from the implant shoulder to the first point of bone-implant contact (BIC) after treatment did not differ between the two groups. The healing time influenced the level of the first point of BIC, with a longer healing period producing a more coronal first point of BIC. A greater percentage BIC and a higher fraction of mineralized bone were found in the pristine bone area compared with the augmented defect area. It can be concluded that in the treatment of osseous defects around oral implants, both materials were equally effective bone substitute materials when used in combination with guided bone regeneration. © 2014 Wiley Periodicals, Inc.

  11. Dynamics of Bovine Sperm Interaction with Epithelium Differ Between Oviductal Isthmus and Ampulla1

    PubMed Central

    Ardon, Florencia; Markello, Ross D.; Hu, Lian; Deutsch, Zarah I.; Tung, Chih-Kuan; Wu, Mingming; Suarez, Susan S.

    2016-01-01

    In mammals, many sperm that reach the oviduct are held in a reservoir by binding to epithelium. To leave the reservoir, sperm detach from the epithelium; however, they may bind and detach again as they ascend into the ampulla toward oocytes. In order to elucidate the nature of binding interactions along the oviduct, we compared the effects of bursts of strong fluid flow (as would be caused by oviductal contractions), heparin, and hyperactivation on detachment of bovine sperm bound in vitro to epithelium on intact folds of isthmic and ampullar mucosa. Intact folds of oviductal mucosa were used to represent the strong attachments of epithelial cells to each other and to underlying connective tissue that exist in vivo. Effects of heparin on binding were tested because heparin binds to the Binder of SPerm (BSP) proteins that attach sperm to oviductal epithelium. Sperm bound by their heads to beating cilia on both isthmic and ampullar epithelia and could not be detached by strong bursts of fluid flow. Addition of heparin immediately detached sperm from isthmic epithelium but not ampullar epithelium. Addition of 4-aminopyridine immediately stimulated hyperactivation of sperm but did not detach them from isthmic or ampullar epithelium unless added with heparin. These observations indicate that the nature of binding of sperm to ampullar epithelium differs from that of binding to isthmic epithelium; specifically, sperm bound to isthmic epithelium can be detached by heparin alone, while sperm bound to ampullar epithelium requires both heparin and hyperactivation to detach from the epithelium. PMID:27605344

  12. Raman microspectroscopic study of oral buccal mucosa

    NASA Astrophysics Data System (ADS)

    Behl, Isha; Mamgain, Hitesh; Deshmukh, Atul; Kukreja, Lekha; Hole, Arti R.; Krishna, C. Murali

    2014-03-01

    Oral cancer is the most common cancer among Indian males, with 5-year- survival-rates of less than 50%. Efficacy of Raman spectroscopic methods in non-invasive and objective diagnosis of oral cancers and confounding factors has already been demonstrated. The present Raman microspectroscopic study was undertaken for in-depth and site-specific analysis of normal and tumor tissues. 10 normal and 10 tumors unstained sections from 20 tissues were accrued. Raman data of 160 x 60 μm and 140 x 140 μm in normal and tumor sections, respectively, were acquired using WITec alpha 300R equipped with 532 nm laser, 50X objective and 600 gr/mm grating. Spectral data were corrected for CCDresponse, background. First-derivitized and vector-normalized data were then subjected to K-mean cluster analysis to generate Raman maps and correlated with their respective histopathology. In normal sections, stratification among epithelial layers i.e. basal, intermediate, superficial was observed. Tumor, stromal and inflammatory regions were identified in case of tumor section. Extracted spectra of the pathologically annotated regions were subjected to Principal component analysis. Findings suggest that all three layers of normal epithelium can be differentiated against tumor cells. In epithelium, basal and superficial layers can be separated while intermediate layer show misclassifications. In tumors, discrimination of inflammatory regions from tumor cells and tumor-stroma regions were observed. Finding of the study indicate Raman mapping can lead to molecular level insights of normal and pathological states.

  13. Assessing regeneration potential

    Treesearch

    Ivan L. Sander

    1989-01-01

    When a regeneration harvest cut is planned for even-aged stands or it is time to make another cut in uneven-aged stands, the first thing to do is assess the regeneration potential. Regeneration potential is the likelihood of being successful in reproducing desired species. You need an assessment to be reasonably sure that regeneration and management objectives can be...

  14. Reconstituted human gingival epithelium: nonsubmerged in vitro model.

    PubMed

    Delcourt-Huard, A; Corlu, A; Joffre, A; Magloire, H; Bonnaure-Mallet, M

    1997-01-01

    Many studies have shown that human gingival keratinocytes grown in submerged culture fail to attain optimal differentiation. This study reports an in vitro culture system for oral gingival epithelial cells, in which they are grown at the air-liquid interface, on polycarbonate inserts, in the presence of an NIH-3T3 feeder layer. This model was compared with two submerged culture methods for gingival keratinocytes, on type 1 collagen gel and on an NIH-3T3 feeder layer. Transmission electron microscopy showed an advanced level of stratification (over six layers of cells) for cultures grown at the air-liquid interface. Immunofluorescence and electrophoretic patterns showed the presence of cytokeratins 10 and 11 in cytoskeletal protein extracts of these cultured keratinocytes. In this air-liquid interface culture model, in the presence of NIH-3T3 feeder cells, keratinocytes can achieve an advanced level of stratification and differentiation and a resemblance to in vivo gingiva. The obtention of a highly differentiated epithelium will permit in vitro pharmacological studies and studies on the biocompatability of certain alloys with the superficial periodontium; it will also provide grafts for patients undergoing periodontal surgery.

  15. Meckel's diverticulum and ectopic epithelium: Evaluation of a complex relationship

    PubMed Central

    Burjonrappa, Sathyaprasad; Khaing, Phue

    2014-01-01

    Introduction: Meckel's diverticulum is the most common congenital anomaly of the gastrointestinal tract. Currently, for any incidentally discovered Meckel's diverticulum, the management approach is based on weighing the statistical odds of future complications against the risks of a diverticulectomy. Materials and Methods: The temporal relationship between age at Meckel's diverticulectomy and the presence of ectopic epithelium was evaluated in our series. A meta-analysis of all reported recent literature on this condition was subsequently performed to evaluate the strength of the relationship between ectopic epithelium and symptomatic Meckel's diverticulum. Results: There was a paucity of ectopic epithelium in Meckel's diverticulectomy specimens in infants operated on at less than 1 year of age. Having two or more ectopic epithelia in a diverticulum does not appear to carry an additive risk for complications. The meta-analysis confirmed that ectopic epithelium was the most significant factor that influenced surgical intervention in all series of Meckel's diverticulum. Conclusion: The relationship between ectopic epithelium and the development of symptomatic Meckel's diverticulum is complex. Further understanding of the development of ectopic rests in the diverticulum will facilitate elucidating the pathophysiology in symptomatic cases. PMID:24741211

  16. The cancer paradigms of mammalian regeneration: can mammals regenerate as amphibians?

    PubMed

    Sarig, Rachel; Tzahor, Eldad

    2017-04-01

    Regeneration in mammals is restricted to distinct tissues and occurs mainly by expansion and maturation of resident stem cells. During regeneration, even subtle mutations in the proliferating cells may cause a detrimental effect by eliciting abnormal differentiation or malignant transformation. Indeed, cancer in mammals has been shown to arise through deregulation of stem cells maturation, which often leads to a differentiation block and cell transformation. In contrast, lower organisms such as amphibians retain a remarkable regenerative capacity in various organs, which occurs via de- and re-differentiation of mature cells. Interestingly, regenerating amphibian cells are highly resistant to oncogenic transformation. Therapeutic approaches to improve mammalian regeneration mainly include stem-cell transplantations; but, these have proved unsuccessful in non-regenerating organs such as the heart. A recently developed approach is to induce de-differentiation of mature cardiomyocytes using factors that trigger their re-entry into the cell cycle. This novel approach raises numerous questions regarding the balance between transformation and regeneration induced by de-differentiation of mature mammalian somatic cells. Can this balance be controlled artificially? Do de-differentiated cells acquire the protection mechanisms seen in regenerating cells of lower organisms? Is this model unique to the cardiac tissue, which rarely develops tumors? This review describes regeneration processes in both mammals and lower organisms and, particularly, the ability of regenerating cells to avoid transformation. By comparing the characteristics of mammalian embryonic and somatic cells, we discuss therapeutic strategies of using various cell populations for regeneration. Finally, we describe a novel cardiac regeneration approach and its implications for regenerative medicine. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email

  17. The ureteric bud epithelium: morphogenesis and roles in metanephric kidney patterning.

    PubMed

    Nagalakshmi, Vidya K; Yu, Jing

    2015-03-01

    The mammalian metanephric kidney is composed of two epithelial components, the collecting duct system and the nephron epithelium, that differentiate from two different tissues -the ureteric bud epithelium and the nephron progenitors, respectively-of intermediate mesoderm origin. The collecting duct system is generated through reiterative ureteric bud branching morphogenesis, whereas the nephron epithelium is formed in a process termed nephrogenesis, which is initiated with the mesenchymal-epithelial transition of the nephron progenitors. Ureteric bud branching morphogenesis is regulated by nephron progenitors, and in return, the ureteric bud epithelium regulates nephrogenesis. The metanephric kidney is physiologically divided along the corticomedullary axis into subcompartments that are enriched with specific segments of these two epithelial structures. Here, we provide an overview of the major molecular and cellular processes underlying the morphogenesis and patterning of the ureteric bud epithelium and its roles in the cortico-medullary patterning of the metanephric kidney. © 2015 Wiley Periodicals, Inc.

  18. Adenosine uptake by the isolated epithelium of guine pig jejunum.

    PubMed

    Kolassa, N; Stengg, R; Turnheim, K

    1977-10-01

    The uptake of [8-14C]adenosine by the isolated epithelium of guinea pig jejunum was faster than that of inosine, hypoxanthine, or adenine. The initial velocity of adenosine uptake from both the luminal and the antiluminal side of the epithelium exhibited saturation kinetics. The apparent Km, V, and passive permeability of luminal adenosine uptake were all lower than the corresponding values of antiluminal uptake. p-Nitrobenzyl-thioguanosine inhibited adenosine uptake from both the luminal and the antiluminal side, whilst hexobendine decreased the uptake only from the antiluminal side of the epithelium. The results suggest that adenosine enters the intestinal epithelium by a carrier-mediated process in addition to passive diffusion. The antiluminal transport system for adenosine seems similar to that of other tissues with respect to hexobendine inhibition; the luminal transport mechanism, however, exhibits different properties, being insensitive to hexobendine.

  19. FSP1+ fibroblast subpopulation is essential for the maintenance and regeneration of medullary thymic epithelial cells

    PubMed Central

    Sun, Lina; Sun, Chenming; Liang, Zhanfeng; Li, Hongran; Chen, Lin; Luo, Haiying; Zhang, Hongmei; Ding, Pengbo; Sun, Xiaoning; Qin, Zhihai; Zhao, Yong

    2015-01-01

    Thymic epithelial cells (TECs) form a 3-dimentional network supporting thymocyte development and maturation. Besides epithelium and thymocytes, heterogeneous fibroblasts are essential components in maintaining thymic microenvironments. However, thymic fibroblast characteristics, development and function remain to be determined. We herein found that thymic non-hematopoietic CD45-FSP1+ cells represent a unique Fibroblast specific protein 1 (FSP1)—fibroblast-derived cell subset. Deletion of these cells in FSP1-TK transgenic mice caused thymus atrophy due to the loss of TECs, especially mature medullary TECs (MHCIIhigh, CD80+ and Aire+). In a cyclophosphamide-induced thymus injury and regeneration model, lack of non-hematopoietic CD45-FSP1+ fibroblast subpopulation significantly delayed thymus regeneration. In fact, thymic FSP1+ fibroblasts released more IL-6, FGF7 and FSP1 in the culture medium than their FSP1- counterparts. Further experiments showed that the FSP1 protein could directly enhance the proliferation and maturation of TECs in the in vitro culture systems. FSP1 knockout mice had significantly smaller thymus size and less TECs than their control. Collectively, our studies reveal that thymic CD45-FSP1+ cells are a subpopulation of fibroblasts, which is crucial for the maintenance and regeneration of TECs especially medullary TECs through providing IL-6, FGF7 and FSP1. PMID:26445893

  20. Feasibility of speckle variance OCT for imaging cutaneous microvasculature regeneration during healing of wounds in diabetic mice

    NASA Astrophysics Data System (ADS)

    Sharma, P.; Kumawat, J.; Kumar, S.; Sahu, K.; Verma, Y.; Gupta, P. K.; Rao, K. D.

    2018-02-01

    We report on a study to assess the feasibility of a swept source-based speckle variance optical coherence tomography setup for monitoring cutaneous microvasculature. Punch wounds created in the ear pinnae of diabetic mice were monitored at different times post wounding to assess the structural and vascular changes. It was observed that the epithelium thickness increases post wounding and continues to be thick even after healing. Also, the wound size assessed by vascular images is larger than the physical wound size. The results show that the developed speckle variance optical coherence tomography system can be used to monitor vascular regeneration during wound healing in diabetic mice.

  1. Oral Toxicity and Intestinal Transport Mechanism of Colloidal Gold Nanoparticle-Treated Red Ginseng

    PubMed Central

    Bae, Song-Hwa; Yu, Jin; Go, Mi-Ran; Kim, Hyun-Jin; Hwang, Yun-Gu; Choi, Soo-Jin

    2016-01-01

    (1) Background: Application of nanotechnology or nanomaterials in agricultural food crops has attracted increasing attention with regard to improving crop production, quality, and nutrient utilization. Gold nanoparticles (Au-NPs) have been reported to enhance seed yield, germination rate, and anti-oxidant potential in food crops, raising concerns about their toxicity potential. In this study, we evaluated the oral toxicity of red ginseng exposed to colloidal Au-NPs during cultivation (G-red ginseng) in rats and their intestinal transport mechanism. (2) Methods: 14-day repeated oral administration of G-red ginseng extract to rats was performed, and body weight, hematological, serum biochemical, and histopathological values were analyzed. An in vitro model of human intestinal follicle-associated epithelium (FAE) and an intestinal epithelial monolayer system were used for intestinal transport mechanistic study. (3) Results: No remarkable oral toxicity of G-red ginseng extract in rats was found, and Au-NPs did not accumulate in any organ, although Au-NP transfer to G-red ginseng and some increased saponin levels were confirmed. Au-NPs were transcytozed by microfold (M) cells, but not by a paracellular pathway in the intestinal epithelium. (4) Conclusion: These findings suggest great potential of Au-NPs for agricultural food crops at safe levels. Further study is required to elucidate the functional effects of Au-NPs on ginseng and long-term toxicity. PMID:28335336

  2. Azithromycin ameliorates airway remodeling via inhibiting airway epithelium apoptosis.

    PubMed

    Liu, Yuanqi; Pu, Yue; Li, Diandian; Zhou, Liming; Wan, Lihong

    2017-02-01

    Azithromycin can benefit treating allergic airway inflammation and remodeling. In the present study, we hypothesized that azithromycin alleviated airway epithelium injury through inhibiting airway epithelium apoptosis via down regulation of caspase-3 and Bax/Bcl2 ratio in vivo and in vitro. Ovalbumin induced rat asthma model and TGF-β1-induced BEAS-2B cell apoptosis model were established, respectively. In vivo experiments, airway epithelium was stained with hematoxylin and eosin (HE) and periodic acid-Schiff (PAS) to histologically evaluate the airway inflammation and remodeling. Airway epithelium apoptotic index (AI) was further analyzed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), while expression of apoptosis related gene (Bax, Bcl2, Caspase-3) in lungs were measured by qRT-PCR and western blotting, respectively. In vitro experiments, apoptosis were evaluated by Flow cytometry (FCM) and TUNEL. Above apoptosis related gene were also measured by qRT-PCR and western blotting. Compared with the OVA group, azithromycin significantly reduced the inflammation score, peribronchial smooth muscle layer thickness, epithelial thickening and goblet cell metaplasia (P<0.05), and effectively suppressed AI of airway epithelium (P<0.05). Moreover, the increasing mRNA and protein expressions of Caspase-3 and Bax/Bcl-2 ratio in lung tissue were all significantly decreased in azithromycin-treated rats (P<0.05). In vitro, azithromycin significantly suppressed TGF-β1-induced BEAS-2B cells apoptosis (P<0.05) and reversed TGF-β1 elevated Caspase-3 mRNA level and Bax/Bcl-2 ratio (P<0.05). Azithromycin is an attractive treatment option for reducing airway epithelial cell apoptosis by improving the imbalance of Bax/Bcl-2 ratio and inhibiting Caspase-3 level in airway epithelium. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Development of the ovarian follicular epithelium.

    PubMed

    Rodgers, R J; Lavranos, T C; van Wezel, I L; Irving-Rodgers, H F

    1999-05-25

    A lot is known about the endocrine control of the development of ovarian follicles, but a key question now facing researchers is which molecular and cellular processes take part in control of follicular growth and development. The growth and development of ovarian follicles occurs postnatally and throughout adult life. In this review, we focus on the follicular epithelium (membrana granulosa) and its basal lamina. We discuss a model of how granulosa cells arise from a population of stem cells and then enter different lineages before differentiation. The structure of the epithelium at the antral stage of development is presented, and the effects that follicle growth has on the behavior of the granulosa cells are discussed. Finally, we discuss the evidence that during follicle development the follicular basal lamina changes in composition. This would be expected if the behavior of the granulosa cells changes, or if the permeability of the basal lamina changes. It will be evident that the follicular epithelium has similarities to other epithelia in the body, but that it is more dynamic, as gross changes occur during the course of follicle development. This basic information will be important for the development of future reproductive technologies in both humans and animals, and possibly for understanding polycystic ovarian syndrome in women.

  4. Oral Lichen Planus: An Update on Etiology, Pathogenesis, Clinical Presentation, Diagnosis and Management

    PubMed Central

    Gupta, Sonia; Jawanda, Manveen Kaur

    2015-01-01

    The mouth is a mirror of health or disease, a sentinel or early warning system. The oral cavity might well be thought as a window to the body because oral manifestations accompany many systemic diseases. In many instances, oral involvement precedes the appearance of other symptoms or lesions at other locations. Oral lichen planus (OLP) is a chronic mucocutaneous disorder of stratified squamous epithelium of uncertain etiology that affects oral and genital mucous membranes, skin, nails, and scalp. LP is estimated to affect 0.5% to 2.0% of the general population. This disease has most often been reported in middle-aged patients with 30-60 years of age and is more common in females than in males. The disease seems to be mediated by an antigen-specific mechanism, activating cytotoxic T cells, and non-specific mechanisms like mast cell degranulation and matrix metalloproteinase activation. A proper understanding of the pathogenesis, clinical presentation, diagnosis of the disease becomes important for providing the right treatment. This article discusses the prevalence, etiology, clinical features, oral manifestations, diagnosis, complications and treatment of oral LP. PMID:26120146

  5. A single nucleotide polymorphism associated with isolated cleft lip and palate, thyroid cancer and hypothyroidism alters the activity of an oral epithelium and thyroid enhancer near FOXE1

    PubMed Central

    Lidral, Andrew C.; Liu, Huan; Bullard, Steven A.; Bonde, Greg; Machida, Junichiro; Visel, Axel; Uribe, Lina M. Moreno; Li, Xiao; Amendt, Brad; Cornell, Robert A.

    2015-01-01

    Three common diseases, isolated cleft lip and cleft palate (CLP), hypothyroidism and thyroid cancer all map to the FOXE1 locus, but causative variants have yet to be identified. In patients with CLP, the frequency of coding mutations in FOXE1 fails to account for the risk attributable to this locus, suggesting that the common risk alleles reside in nearby regulatory elements. Using a combination of zebrafish and mouse transgenesis, we screened 15 conserved non-coding sequences for enhancer activity, identifying three that regulate expression in a tissue specific pattern consistent with endogenous foxe1 expression. These three, located −82.4, −67.7 and +22.6 kb from the FOXE1 start codon, are all active in the oral epithelium or branchial arches. The −67.7 and +22.6 kb elements are also active in the developing heart, and the −67.7 kb element uniquely directs expression in the developing thyroid. Within the −67.7 kb element is the SNP rs7850258 that is associated with all three diseases. Quantitative reporter assays in oral epithelial and thyroid cell lines show that the rs7850258 allele (G) associated with CLP and hypothyroidism has significantly greater enhancer activity than the allele associated with thyroid cancer (A). Moreover, consistent with predicted transcription factor binding differences, the −67.7 kb element containing rs7850258 allele G is significantly more responsive to both MYC and ARNT than allele A. By demonstrating that this common non-coding variant alters FOXE1 expression, we have identified at least in part the functional basis for the genetic risk of these seemingly disparate disorders. PMID:25652407

  6. Mechanical Barriers Restrict Invasion of Herpes Simplex Virus 1 into Human Oral Mucosa

    PubMed Central

    Thier, Katharina; Petermann, Philipp; Rahn, Elena; Rothamel, Daniel; Bloch, Wilhelm

    2017-01-01

    ABSTRACT Oral mucosa is one of the main target tissues of the human pathogen herpes simplex virus 1 (HSV-1). How the virus overcomes the protective epithelial barriers and penetrates the tissue to reach its receptors and initiate infection is still unclear. Here, we established an ex vivo infection assay with human oral mucosa that allows viral entry studies in a natural target tissue. The focus was on the susceptibility of keratinocytes in the epithelium and the characterization of cellular receptors that mediate viral entry. Upon ex vivo infection of gingiva or vestibular mucosa, we observed that intact human mucosa samples were protected from viral invasion. In contrast, the basal layer of the oral epithelium was efficiently invaded once the connective tissue and the basement membrane were removed. Later during infection, HSV-1 spread from basal keratinocytes to upper layers, demonstrating the susceptibility of the stratified squamous epithelium to HSV-1. The analysis of potential receptors revealed nectin-1 on most mucosal keratinocytes, whereas herpesvirus entry mediator (HVEM) was found only on a subpopulation of cells, suggesting that nectin-1 acts as primary receptor for HSV-1 in human oral mucosa. To mimic the supposed entry route of HSV-1 via microlesions in vivo, we mechanically wounded the mucosa prior to infection. While we observed a limited number of infected keratinocytes in some wounded mucosa samples, other samples showed no infected cells. Thus, we conclude that mechanical wounding of mucosa is insufficient for the virus to efficiently overcome epithelial barriers and to make entry-mediating receptors accessible. IMPORTANCE To invade the target tissue of its human host during primary infection, herpes simplex virus (HSV) must overcome the epithelial barriers of mucosa, skin, or cornea. For most viruses, the mechanisms underlying the invasion into the target tissues of their host organism are still open. Here, we established an ex vivo infection

  7. Mechanical Barriers Restrict Invasion of Herpes Simplex Virus 1 into Human Oral Mucosa.

    PubMed

    Thier, Katharina; Petermann, Philipp; Rahn, Elena; Rothamel, Daniel; Bloch, Wilhelm; Knebel-Mörsdorf, Dagmar

    2017-11-15

    Oral mucosa is one of the main target tissues of the human pathogen herpes simplex virus 1 (HSV-1). How the virus overcomes the protective epithelial barriers and penetrates the tissue to reach its receptors and initiate infection is still unclear. Here, we established an ex vivo infection assay with human oral mucosa that allows viral entry studies in a natural target tissue. The focus was on the susceptibility of keratinocytes in the epithelium and the characterization of cellular receptors that mediate viral entry. Upon ex vivo infection of gingiva or vestibular mucosa, we observed that intact human mucosa samples were protected from viral invasion. In contrast, the basal layer of the oral epithelium was efficiently invaded once the connective tissue and the basement membrane were removed. Later during infection, HSV-1 spread from basal keratinocytes to upper layers, demonstrating the susceptibility of the stratified squamous epithelium to HSV-1. The analysis of potential receptors revealed nectin-1 on most mucosal keratinocytes, whereas herpesvirus entry mediator (HVEM) was found only on a subpopulation of cells, suggesting that nectin-1 acts as primary receptor for HSV-1 in human oral mucosa. To mimic the supposed entry route of HSV-1 via microlesions in vivo , we mechanically wounded the mucosa prior to infection. While we observed a limited number of infected keratinocytes in some wounded mucosa samples, other samples showed no infected cells. Thus, we conclude that mechanical wounding of mucosa is insufficient for the virus to efficiently overcome epithelial barriers and to make entry-mediating receptors accessible. IMPORTANCE To invade the target tissue of its human host during primary infection, herpes simplex virus (HSV) must overcome the epithelial barriers of mucosa, skin, or cornea. For most viruses, the mechanisms underlying the invasion into the target tissues of their host organism are still open. Here, we established an ex vivo infection model of

  8. Regeneration

    Treesearch

    George A. Schier; Wayne D. Shepperd; John R. Jones

    1985-01-01

    There are basically two approaches to regenerating aspen stands-sexual reproduction using seed, or vegetative regeneration by root suckering. In the West, root suckering is the most practical method. The advantage of having an existing, well established root system capable of producing numerous root suckers easily outweighs natural or artificial reforestation in the...

  9. Transplantation of mature adipocyte-derived dedifferentiated fat cells into three-wall defects in the rat periodontium induces tissue regeneration.

    PubMed

    Suzuki, Daigo; Akita, Daisuke; Tsurumachi, Niina; Kano, Koichiro; Yamanaka, Katsuyuki; Kaneko, Tadashi; Kawano, Eisuke; Iguchi, Shinya; Toriumi, Taku; Arai, Yoshinori; Matsumoto, Taro; Sato, Shuichi; Honda, Masaki

    2017-01-01

    The transplantation of dedifferentiated fat (DFAT) cells in combination with poly(d,l-lactic-co-glycolic acid) (PLGA) scaffolds has previously been proven as an effective approach in promoting periodontal tissue regeneration in a rat fenestration defect model. The aim of this study was to assess the regenerative potential of DFAT cells in a rat model of three-wall periodontal bone defect. Three-wall bone defects were created bilaterally on the mesial side of rat maxillary first molars and were either left untreated or treated by implantation of PLGA scaffolds with DFAT cells or PLGA alone. Four weeks after surgery, the tissues were processed for micro-computed tomography (micro-CT) and histomorphometric examination. Micro-CT revealed that the PLGA/DFAT group had significantly higher rates of bone regeneration than the other groups, while histomorphometric analysis showed that the PLGA/DFAT group had significantly higher densities of collagen fiber bundles in acellular and cellular cementum than the PLGA group. Moreover, the results indicate that the placement of the PLGA scaffold prevented the downgrowth of the junctional epithelium. These findings suggest that DFAT cells contribute to tissue regeneration in three-wall periodontal defects, while PLGA provides space necessary for periodontal tissue restoration.

  10. Bone Repair Cells for Craniofacial Regeneration

    PubMed Central

    Pagni, G; Kaigler, D; Rasperini, G; Avila-Ortiz, G; Bartel, R; Giannobile, WV

    2012-01-01

    Reconstruction of complex craniofacial deformities is a clinical challenge in situations of injury, congenital defects or disease. The use of cell-based therapies represents one of the most advanced methods for enhancing the regenerative response for craniofacial wound healing. Both Somatic and Stem Cells have been adopted in the treatment of complex osseous defects and advances have been made in finding the most adequate scaffold for the delivery of cell therapies in human regenerative medicine. As an example of such approaches for clinical application for craniofacial regeneration, Ixmyelocel-T or bone repair cells are a source of bone marrow derived stem and progenitor cells. They are produced through the use of single pass perfusion bioreactors for CD90+ mesenchymal stem cells and CD14+ monocyte/macrophage progenitor cells. The application of ixmyelocel-T has shown potential in the regeneration of muscular, vascular, nervous and osseous tissue. The purpose of this manuscript is to highlight cell therapies used to repair bony and soft tissue defects in the oral and craniofacial complex. The field at this point remains at an early stage, however this review will provide insights into the progress being made using cell therapies for eventual development into clinical practice. PMID:22433781

  11. Desulfurization sorbent regeneration

    DOEpatents

    Jalan, V.M.; Frost, D.G.

    1982-07-07

    A spent solid sorbent resulting from the removal of hydrogen sulfide from a fuel gas flow is regenerated with a steam-air mixture. The mixture of steam and air may also include additional nitrogen or carbon dioxide. The gas mixture contacts the spent sorbent containing metal sulfide at a temperature above 500/sup 0/C to regenerate the sulfide to metal oxide or carbonate. Various metal species including the period four transition metals and the lanthanides are suitable sorbents that may be regenerated by this method. In addition, the introduction of carbon dioxide gas permits carbonates such as those of strontium, barium and calcium to be regenerated. The steam permits regeneration of spent sorbent without formation of metal sulfate. Moreover, the regeneration will proceed with low oxygen concentrations and will occur without the increase in temperature to minimize the risk of sintering and densification of the sorbent. This method may be used for high-temperature fuel cells.

  12. Hair organ regeneration via the bioengineered hair follicular unit transplantation

    PubMed Central

    Asakawa, Kyosuke; Toyoshima, Koh-ei; Ishibashi, Naoko; Tobe, Hirofumi; Iwadate, Ayako; Kanayama, Tatsuya; Hasegawa, Tomoko; Nakao, Kazuhisa; Toki, Hiroshi; Noguchi, Shotaro; Ogawa, Miho; Sato, Akio; Tsuji, Takashi

    2012-01-01

    Organ regenerative therapy aims to reproduce fully functional organs to replace organs that have been lost or damaged as a result of disease, injury, or aging. For the fully functional regeneration of ectodermal organs, a concept has been proposed in which a bioengineered organ is developed by reproducing the embryonic processes of organogenesis. Here, we show that a bioengineered hair follicle germ, which was reconstituted with embryonic skin-derived epithelial and mesenchymal cells and ectopically transplanted, was able to develop histologically correct hair follicles. The bioengineered hair follicles properly connected to the host skin epithelium by intracutaneous transplantation and reproduced the stem cell niche and hair cycles. The bioengineered hair follicles also autonomously connected with nerves and the arrector pili muscle at the permanent region and exhibited piloerection ability. Our findings indicate that the bioengineered hair follicles could restore physiological hair functions and could be applicable to surgical treatments for alopecia. PMID:22645640

  13. [Simulation of corneal epithelial injuries by mechanical and corrosive damage : Influence of fetal bovine serum and dexpanthenol on epithelial regeneration in a cell culture model].

    PubMed

    Hahne, M; Reichl, S

    2010-06-01

    The present study describes simulation of corneal epithelial injury and its regeneration using an in-vitro model of immortalized human corneal epithelial cells (HCE-T) growing as monolayer cultures. The epithelial model was damaged using defined strengths by mechanical injury or partial damage using chemical detergents (SDS and acidified medium) and subsequently the epithelium was further cultivated using serum-containing and serum-free medium supplemented with varying concentrations of calcium pantothenat. After mechanical injury wound healing was evaluated using a photomicroscope over a period of up to 48 h whereas after chemical injury a cell viability assay was used to detect the course of ATP levels in the cell layers as an indicator for the metabolic activity. Depending on the kind of injury pantothenat showed a regeneration enhancing effect in the concentration range from 0.001% to 0.01%. However, a concentration of 0.1% pantothenat appeared to be regeneration inhibiting. The combination of pantothenat and serum was more beneficial for wound healing than pantothenat alone, whereas serum partly levelled the effect of pantothenat. The described model allowed simulation of corneal epithelial injury and its regeneration, whereby the influence of the serum content and the kind of injury could be determined.

  14. Perspectives on human regeneration.

    PubMed

    Stark, James F

    2018-06-12

    Regeneration is a concept that has fascinated humans for centuries. Whether we have been trying to bring things back to life, extract additional resources from the world, or remodel our living spaces-domestic and urban-it is often presented as an unproblematic force for good. But what exactly does it mean to regenerate a body, mind or space? This paper, which introduces a collection of contributions on the theme of human regeneration, explores the limits and possibilities of regeneration as a conceptual tool for understanding the biological realm. What does it mean to be regenerated? How can a scholarly focus on this concept enrich our histories of bodies, ageing, disability and science, technology and medicine? As a secondary goal, I identify two distinct aspects of regeneration-'hard' and 'soft' regeneration-which concern the medical and social elements of regeneration respectively. By recognising that everything from cosmetics and fictions to prosthetics and organs grown in vitro display a combination of 'hard' and 'soft' elements, we are better placed to understand that the biological and social must be considered in consort for us to fully appreciate the meanings and practices that underpin multiple forms of human regeneration.

  15. Oral administration of aflatoxin G₁ induces chronic alveolar inflammation associated with lung tumorigenesis.

    PubMed

    Liu, Chunping; Shen, Haitao; Yi, Li; Shao, Peilu; Soulika, Athena M; Meng, Xinxing; Xing, Lingxiao; Yan, Xia; Zhang, Xianghong

    2015-02-03

    Our previous studies showed oral gavage of aflatoxin G₁ (AFG₁) induced lung adenocarcinoma in NIH mice. We recently found that a single intratracheal administration of AFG₁ caused chronic inflammatory changes in rat alveolar septum. Here, we examine whether oral gavage of AFG₁ induces chronic lung inflammation and how it contributes to carcinogenesis. We evaluated chronic lung inflammatory responses in Balb/c mice after oral gavage of AFG₁ for 1, 3 and 6 months. Inflammatory responses were heightened in the lung alveolar septum, 3 and 6 months after AFG₁ treatment, evidenced by increased macrophages and lymphocytes infiltration, up-regulation of NF-κB and p-STAT3, and cytokines production. High expression levels of superoxide dismutase (SOD-2) and hemoxygenase-1 (HO-1), two established markers of oxidative stress, were detected in alveolar epithelium of AFG₁-treated mice. Promoted alveolar type II cell (AT-II) proliferation in alveolar epithelium and angiogenesis, as well as increased COX-2 expression were also observed in lung tissues of AFG₁-treated mice. Furthermore, we prolonged survival of the mice in the above model for another 6 months to examine the contribution of AFG₁-induced chronic inflammation to lung tumorigenesis. Twelve months later, we observed that AFG₁ induced alveolar epithelial hyperplasia and adenocarcinoma in Balb/c mice. Up-regulation of NF-κB, p-STAT3, and COX-2 was also induced in lung adenocarcinoma, thus establishing a link between AFG₁-induced chronic inflammation and lung tumorigenesis. This is the first study to show that oral administration of AFG₁ could induce chronic lung inflammation, which may provide a pro-tumor microenvironment to contribute to lung tumorigenesis. Copyright © 2014. Published by Elsevier Ireland Ltd.

  16. Regenerable Iodine Water-Disinfection System

    NASA Technical Reports Server (NTRS)

    Sauer, Richard L.; Colombo, Gerald V.; Jolly, Clifford D.

    1994-01-01

    Iodinated resin bed for disinfecting water regenerated to extend its useful life. Water flows through regeneration bed of crystalline iodine during regeneration. At other times, flow diverted around regeneration bed. Although regeneration cycle was manually controlled in demonstration, readily automated to start and stop according to signals and stop according to signals from concentration sensors. Further benefit of regeneration is that regeneration bed provides highly concentrated biocide source (200 mg/L) when needed. Concentrated biocide used to superiodinate system after contamination from routine maintenance or unexpected introduction of large concentration of microbes.

  17. Healing of human intrabony defects following regenerative periodontal therapy with a bovine-derived xenograft and guided tissue regeneration.

    PubMed

    Sculean, A; Stavropoulos, A; Windisch, P; Keglevich, T; Karring, T; Gera, I

    2004-06-01

    The purpose of the present study was to histologically evaluate the healing of human intrabony defects following treatment with either a bovine-derived xenograft (BDX) and guided tissue regeneration (GTR) [BDX + GTR] or a bovine-derived xenograft mixed with collagen (BDX Coll) and GTR [BDX Coll + GTR]. Eight patients with chronic periodontitis and each with one very deep intrabony defect around a tooth scheduled for extraction were treated with either a combination of BDX + GTR (five patients) or with BDX Coll + GTR (three patients). The postoperative healing was uneventful in all eight cases. After a healing period of 6 months, the teeth or roots were extracted together with some of their surrounding soft and hard tissues and subsequently fixed in 10% buffered formalin. Following decalcification in EDTA, the specimens were embedded in paraffin and 8-microm histological sections were cut in the mesio-distal direction, parallel to the long axes of the teeth. The sections were alternatively stained with hematoxylin and eosin, van Giesson's connective tissue stain or with the Ladevig's connective tissue staining method and examined under the light microscope. Generally, formation of new cementum with inserting collagen fibers was found in seven out of the eight treated cases, whereas in the remaining case (treated with BDX + GTR) the healing was characterized by formation of a long junctional epithelium along the debrided root surface and no formation of cementum or bone. In the specimens demonstrating periodontal regeneration the new cementum was always of a cellular type. In most cases, the graft particles were surrounded by bone. In some areas, the bone tissue around the graft particles was connected by perpendicularly inserting collagen fibers to the newly formed cementum on the root surface. The epithelium downgrowth stopped always at the most coronal part of the newly formed cementum. No remnants of the membrane material were observed in any of the biopsies

  18. Regenerable Iodine Water-Disinfection System

    NASA Technical Reports Server (NTRS)

    Sauer, Richard L.; Colombo, Gerald V.; Jolly, Clifford D.

    1994-01-01

    Iodinated resin bed for disinfecting water regenerated to extend useful life. Water flows through regeneration bed of crystalline iodine during regeneration. At other times, flow diverted around regeneration bed. Although regeneration cycle manually controlled readily automated to start and stop according to signals from concentration sensors. Further benefit of regeneration is bed provides highly concentrated biocide source when needed. Concentrated biocide used to superiodinate system after contamination from routine maintenance or unexpected introduction of large concentration of microbes.

  19. How good is the neosquamous epithelium?

    PubMed

    Orlando, Roy C

    2014-01-01

    Endoscopic radiofrequency ablation of dysplastic Barrett's esophagus (BE) combined with proton pump inhibitor therapy is commonly utilized for preventing progression of dysplastic BE to esophageal adenocarcinoma. Fundamental to the success of this and all ablative approaches is the healing of the ablated areas of BE with a stratified squamous epithelium referred to as 'neosquamous epithelium' (NSE). Although NSE appears 'normal' endoscopically, the reemergence of BE over time in the previously ablated segments raises the question of the health and integrity of NSE. The health of NSE was recently investigated in endoscopic biopsies in vitro in a group of patients after ablation while on proton pump inhibitors. Biopsies of NSE were compared to upper squamous epithelium (USE) from the same patients morphologically (light microscopy) and with respect to barrier function by measuring electrical resistance and fluorescein flux in mini-Ussing chambers. Compared to USE, NSE exhibited dilated intercellular spaces and inflammation and defective barrier function by low electrical resistance and high fluorescein flux. Moreover, NSE exhibited downregulation of claudin-4, a highly expressed protein in squamous tight junctions. NSE has defective barrier function in part due to downregulation of claudin-4. Since downregulation of claudin-4 increases paracellular permeability to cations, e.g. hydrogen ions, NSE is more vulnerable to attack and damage by acidic and weakly acidic refluxates--a phenomenon that may contribute in part to the reemergence of BE. 2014 S. Karger AG, Basel.

  20. pH-Responsive carriers for oral drug delivery: challenges and opportunities of current platforms.

    PubMed

    Liu, Lin; Yao, WenDong; Rao, YueFeng; Lu, XiaoYang; Gao, JianQing

    2017-11-01

    Oral administration is a desirable alternative of parenteral administration due to the convenience and increased compliance to patients, especially for chronic diseases that require frequent administration. The oral drug delivery is a dynamic research field despite the numerous challenges limiting their effective delivery, such as enzyme degradation, hydrolysis and low permeability of intestinal epithelium in the gastrointestinal (GI) tract. pH-Responsive carriers offer excellent potential as oral therapeutic systems due to enhancing the stability of drug delivery in stomach and achieving controlled release in intestines. This review provides a wide perspective on current status of pH-responsive oral drug delivery systems prepared mainly with organic polymers or inorganic materials, including the strategies used to overcome GI barriers, the challenges in their development and future prospects, with focus on technology trends to improve the bioavailability of orally delivered drugs, the mechanisms of drug release from pH-responsive oral formulations, and their application for drug delivery, such as protein and peptide therapeutics, vaccination, inflammatory bowel disease (IBD) and bacterial infections.

  1. Common cellular events occur during wound healing and organ regeneration in the sea cucumber Holothuria glaberrima.

    PubMed

    San Miguel-Ruiz, José E; García-Arrarás, José E

    2007-10-18

    All animals possess some type of tissue repair mechanism. In some species, the capacity to repair tissues is limited to the healing of wounds. Other species, such as echinoderms, posses a striking repair capability that can include the replacement of entire organs. It has been reported that some mechanisms, namely extracellular matrix remodeling, appear to occur in most repair processes. However, it remains unclear to what extent the process of organ regeneration, particularly in animals where loss and regeneration of complex structures is a programmed natural event, is similar to wound healing. We have now used the sea cucumber Holothuria glaberrima to address this question. Animals were lesioned by making a 3-5 mm transverse incision between one of the longitudinal muscle pairs along the bodywall. Lesioned tissues included muscle, nerve, water canal and dermis. Animals were allowed to heal for up to four weeks (2, 6, 12, 20, and 28 days post-injury) before sacrificed. Tissues were sectioned in a cryostat and changes in cellular and tissue elements during repair were evaluated using classical dyes, immmuohistochemistry and phalloidin labeling. In addition, the temporal and spatial distribution of cell proliferation in the animals was assayed using BrdU incorporation. We found that cellular events associated with wound healing in H. glaberrima correspond to those previously shown to occur during intestinal regeneration. These include: (1) an increase in the number of spherule-containing cells, (2) remodeling of the extracellular matrix, (3) formation of spindle-like structures that signal dedifferentiation of muscle cells in the area flanking the lesion site and (4) intense cellular division occurring mainly in the coelomic epithelium after the first week of regeneration. Our data indicate that H. glaberrima employs analogous cellular mechanisms during wound healing and organ regeneration. Thus, it is possible that regenerative limitations in some organisms are due

  2. Immunohistochemical expression of basement membrane proteins of verrucous carcinoma of the oral mucosa.

    PubMed

    Arduino, Paolo G; Carrozzo, Marco; Pagano, Marco; Broccoletti, Roberto; Scully, Crispian; Gandolfo, Sergio

    2010-06-01

    Squamous cell carcinoma (SCC) of the oral cavity is an extremely invasive tumour of stratified squamous epithelium that spreads throughout degradation of the basement membrane (BM) and extra-cellular matrix. Oral verrucous carcinoma (VC) is a rare low-grade variant of oral SCC that penetrates into the subepithelial connective tissue. It also has a different clinical behaviour from classical oral SCC. We investigated the immunohistochemical expression of laminin, laminin-5, collagen IV and fibronectin in VC, severe epithelial dysplasia (SED) and SCC in order to analyse if the pattern of these molecules expression contributes to the differences in the biological behaviour of these diseases. The staining pattern of laminin was less intensive in SCC compared with SED and VC, and collagen IV expression was increased in VC compared with SED. Discontinuities of laminin, collagen IV and fibronectin were more evident in SED than in VC. This study indicates that VC has a biological behaviour different from SED or SCC, observable by immunohistochemistry in the BM zone.

  3. Chromosomal Damage and Apoptosis in Exfoliated Buccal Cells from Individuals with Oral Cancer

    PubMed Central

    Dórea, Lavínia Tércia Magalhães; Meireles, José Roberto Cardoso; Lessa, Júlia Paula Ramos; Oliveira, Márcio Campos; de Bragança Pereira, Carlos Alberto; Polpo de Campos, Adriano; Cerqueira, Eneida de Moraes Macílio

    2012-01-01

    This study aimed to investigate cytological abnormalities indicative of chromosome damage (micronuclei) and apoptosis (karyorrhexis, pyknosis, and condensed chromatin) in exfoliated cells from the buccal mucosa of patients with oral cancer and control subjects. The sample included twenty individuals with oral cancer and forty individuals with normal buccal mucosa. Material was collected from the cheek epithelium in areas with lesions and areas without abnormalities. A minimum of one thousand cells was analyzed. Micronuclei were found significantly more frequently in cells collected from lesions than in cells from normal areas, independent of the presence/absence of cancer (P < 0.0001). They were also significantly more frequent in smokers and in mouthwash users (P < 0.0001). Apoptosis occurred significantly less frequently in individuals with oral cancer (P < 0.0001). These results show that oral cancer is associated with higher frequency of chromosomal damage and suggest that apoptosis is compromised in the buccal cells of individuals with this kind of neoplasia. PMID:22315605

  4. Retinoid-signaling in progenitors controls specification and regeneration of the urothelium

    PubMed Central

    Reiley, Maia; Laufer, Ed; Metzger, Daniel; Liang, Fengxia; Liao, Yi; Sun, Tung-Tien; Aronow, Bruce; Rosen, Roni; Mauney, Josh; Adam, Rosalyn; Rosselot, Carolina; Van Batavia, Jason; McMahon, Andrew; McMahon, Jill; Guo, Jin-Jin; Mendelsohn, Cathy

    2013-01-01

    The urothelium is a stratified epithelium that prevents exchange of water and toxic substances between the urinary tract and blood. It is composed of Keratin-5-expressing-basal-cells (K5-BCs), intermediate cells and superficial cells specialized for synthesis and transport of uroplakins that assemble into the apical barrier. K5-BCs are considered to be a progenitor cell type in the urothelium and other stratified epithelia. Fate mapping studies however, reveal that P-cells, a transient population, are urothelial progenitors in the embryo, intermediate cells are superficial cell progenitors in the adult regenerating urothelium, and K5-BCs are a distinct lineage. Our studies indicate that retinoids, potent regulators of ES cells and other progenitors, are also required in P-cells and intermediate cells for their specification. These observations have important implications for tissue engineering and repair, and ultimately, may lead to treatments that prevent loss of the urothelial barrier, a major cause of voiding dysfunction and bladder pain syndrome. PMID:23993789

  5. Histomorphometric analysis of nuclear and cellular volumetric alterations in oral lichen planus, lichenoid lesions and normal oral mucosa using image analysis software.

    PubMed

    Venkatesiah, Sowmya S; Kale, Alka D; Hallikeremath, Seema R; Kotrashetti, Vijayalakshmi S

    2013-01-01

    Lichen planus is a chronic inflammatory mucocutaneous disease that clinically and histologically resembles lichenoid lesions, although the latter has a different etiology. Though criteria have been suggested for differentiating oral lichen planus from lichenoid lesions, confusion still prevails. To study the cellular and nuclear volumetric features in the epithelium of normal mucosa, lichen planus, and lichenoid lesions to determine variations if any. A retrospective study was done on 25 histologically diagnosed cases each of oral lichen planus, oral lichenoid lesions, and normal oral mucosa. Cellular and nuclear morphometric measurements were assessed on hematoxylin and eosin sections using image analysis software. Analysis of variance test (ANOVA) and Tukey's post-hoc test. The basal cells of oral lichen planus showed a significant increase in the mean nuclear and cellular areas, and in nuclear volume; there was a significant decrease in the nuclear-cytoplasmic ratio as compared to normal mucosa. The suprabasal cells showed a significant increase in nuclear and cellular areas, nuclear diameter, and nuclear and cellular volumes as compared to normal mucosa. The basal cells of oral lichenoid lesions showed significant difference in the mean cellular area and the mean nuclear-cytoplasmic ratio as compared to normal mucosa, whereas the suprabasal cells differed significantly from normal mucosa in the mean nuclear area and the nuclear and cellular volumes. Morphometry can differentiate lesions of oral lichen planus and oral lichenoid lesions from normal oral mucosa. Thus, morphometry may serve to discriminate between normal and premalignant lichen planus and lichenoid lesions. These lesions might have a high risk for malignant transformation and may behave in a similar manner with respect to malignant transformation.

  6. Ceramic regenerator program

    NASA Technical Reports Server (NTRS)

    Franklin, Jerrold E.

    1991-01-01

    The feasibility of fabricating an Air Turbo Ramjet (ATR) regenerator containing intricate hydraulic passages from a ceramic material in order to allow operation with high temperature combustion gas and to reduce weight as compared with metallic materials was demonstrated. Platelet technology, ceramic tape casting, and multilayer ceramic packaging techniques were used in this fabrication of subscale silicon nitride components. Proof-of-concept demonstrations were performed to simulate a methane cooled regenerator for an ATR engine. The regenerator vane was designed to operate at realistic service conditions, i.e., 600 psi in a 3500 R (3040 F), 500 fps combustion gas environment. A total of six regenerators were fabricated and tested. The regenerators were shown to be able to withstand internal pressurization to 1575 psi. They were subjected to testing in 500 fps, 3560 R (3100 F) air/propane combustion products and were operated satisfactorily for an excess of 100 hr and 40 thermal cycles which exceeded 2460 R (2000 F).

  7. Regeneration methods

    Treesearch

    James P. Barnett; James B. Baker

    1991-01-01

    Southern pines can be regenerated naturally, by clearcutting, seedtree, shelterwood, or selection reproduction culling methods, or artificially, by direct seeding or by planting either container or bareroot seedlings. All regeneration methods have inherent advantages: and disadvantages; thus, land managers must consider many factors before deciding on a specific method...

  8. Differential induction of four msx homeobox genes during fin development and regeneration in zebrafish.

    PubMed

    Akimenko, M A; Johnson, S L; Westerfield, M; Ekker, M

    1995-02-01

    To study the genetic regulation of growth control and pattern formation during fin development and regeneration, we have analysed the expression of four homeobox genes, msxA, msxB, msxC and msxD in zebrafish fins. The median fin fold, which gives rise to the unpaired fins, expresses these four msx genes during development. Transcripts of the genes are also present in cells of the presumptive pectoral fin buds. The most distal cells, the apical ectodermal ridge of the paired fins and the cleft and flanking cells of the median fin fold express all these msx genes with the exception of msxC. Mesenchymal cells underlying the most distal cells express all four genes. Expression of the msx genes in the fin fold and fin buds is transient and, by 3 days after fertilization, msx expression in the median fin fold falls below levels detectable by in situ hybridization. Although the fins of adult zebrafish normally have levels of msx transcripts undetectable by in situ hybridization, expression of all four genes is strongly reinduced during regeneration of both paired and unpaired fins. Induction of msx gene expression in regenerating caudal fins occurs as early as 30 hours postamputation. As the blastema forms, the levels of expression increase and reach a maximum between the third and fifth days. Then, msx expression progressively declines and disappears by day 12 when the caudal fin has grown back to its normal size. In the regenerating fin, the blastema cells that develop at the tip of each fin ray express msxB and msxC. Cells of the overlying epithelium express msxA and msxD, but do not express msxB or msxC. Amputations at various levels along the proximodistal axis of the fin suggest that msxB expression depends upon the position of the blastema, with cells of the rapidly proliferating proximal blastema expressing higher levels than the cells of the less rapidly proliferating distal blastema. Expression of msxC and msxD is independent of the position of the blastema cell

  9. Mental Regeneration.

    ERIC Educational Resources Information Center

    Langer, Jonas

    Techniques for developing the potential of culturally deprived people cannot be developed without more knowledge of the basic mechanisms of mental change. Psysiological generation and regeneration are both apparently governed by the same set of mechanisms. Regeneration is possible only when a part of the damaged structure is left, and these…

  10. The differentiation profile of the epithelium of the human lip.

    PubMed

    Barrett, A W; Morgan, M; Nwaeze, G; Kramer, G; Berkovitz, B K B

    2005-04-01

    The aim of this study was to analyse the immunohistochemical differentiation profile of the stratified squamous epithelium of the adult human lip. Full-thickness lower lips taken from 31 cadavers were analysed. Sections were stained with haematoxylin and eosin, periodic acid-Schiff (PAS), cytokeratins (CK), loricrin, involucrin, profilaggrin and filaggrin. The stratified squamous epithelium covering the lip could be divided into: (i) appendage-bearing, orthokeratinised epidermis; (ii) orthokeratinised vermilion which had a more prominent rete pattern than the epidermis; (iii) parakeratinised, PAS-positive intermediate zone; and (iv) non- or parakeratinised labial mucosal epithelium. Epithelial thickness increased gradually from the skin to the mucosal aspect. The CK pattern changed across the intermediate zone, with gradual loss of CK 1 and 10 from the skin, and CK 4, 13 and 19 from the mucosal, aspect. CK 5 and 14 were consistently expressed basally, and variably expressed suprabasally. Apart from labelling Merkel cells, CK 8, 18 and 20 were negative. Involucrin, which was present at all sites, was restricted to the stratum granulosum in skin, but extended into the stratum spinosum, and gradually into parabasal keratinocytes, across the vermilion and mucosa. Loricrin, profilaggrin and filaggrin were present in the stratum granulosum of orthokeratinised sites, but expression was abruptly lost at the junction between the vermilion and the intermediate zone. In conclusion, the phenotype of the stratified squamous epithelium covering the lip changes at, or across, the intermediate zone of the adult vermilion. It is possible that changes in the composition of the stratified squamous epithelium affect the colour of the vermilion.

  11. Models for oral uptake of nanoparticles in consumer products

    PubMed Central

    Fröhlich, Eleonore; Roblegg, Eva

    2012-01-01

    Presently, many consumer products contain nano-sized materials (NMs) to improve material properties, product quality and ease of use. NMs in food additives and in cosmetic articles (e.g., tooth paste) may be taken up by the oral route. As adverse effects of environmental nanoparticles, like ultrafine particles, have been reported, consumers worry about potential risks when using products containing NMs. The review focuses on metal and metal oxide NMs as common additives in tooth paste and in food industry and exposure by the oral route. Testing of NMs for oral exposure is very complex because differences in the diet, in mucus secretion and composition, in pH, in gastrointestinal transit time and in gastrointestinal flora influence NM uptake. Acellular (mucus, saliva) and epithelial layer of the orogastrointestinal barrier are described. Expected exposure doses, interaction of the NMs with mucus and permeation through the epithelium as well as in vivo data are mentioned. The role of in vitro models for the study of parameters relevant for ingested NMs is discussed. PMID:22120540

  12. EMERGING MICROTECHNOLOGIES FOR THE DEVELOPMENT OF ORAL DRUG DELIVERY DEVICES

    PubMed Central

    Chirra, Hariharasudhan D.; Desai, Tejal A.

    2012-01-01

    The development of oral drug delivery platforms for administering therapeutics in a safe and effective manner across the gastrointestinal epithelium is of much importance. A variety of delivery systems such as enterically coated tablets, capsules, particles, and liposomes have been developed to improve oral bioavailability of drugs. However, orally administered drugs suffer from poor localization and therapeutic efficacy due to various physiological conditions such as low pH, and high shear intestinal fluid flow. Novel platforms combining controlled release, improved adhesion, tissue penetration, and selective intestinal targeting may overcome these issues and potentially diminish the toxicity and high frequency of administration associated with conventional oral delivery. Microfabrication along with appropriate surface chemistry, provide a means to fabricate these platforms en masse with flexibility in tailoring the shape, size, reservoir volume, and surface characteristics of microdevices. Moreover, the same technology can be used to include integrated circuit technology and sensors for designing sophisticated autonomous drug delivery devices that promise to significantly improve point of care diagnostic and therapeutic medical applications. This review sheds light on some of the fabrication techniques and addresses a few of the microfabricated devices that can be effectively used for controlled oral drug delivery applications. PMID:22981755

  13. Oral metastasis from primary transitional cell carcinoma of the renal pelvis: report of a case.

    PubMed

    Zhang, Y; Gu, Z-Y; Tian, Z; Yang, C; Cai, X-Y

    2010-07-01

    Transitional cell carcinoma of the renal pelvis is initially a slow growing tumor arising from the transitional epithelium of the mucous membrane of the renal pelvis. Recurrences occur in two forms: superficial bladder cancer and distant metastases. The common metastasis is in the lung, liver, brain and bone. Oral metastasis is seldom reported. The authors report an unusual case of transitional cell carcinoma of the renal pelvis metastasized to the oral cavity and lung simultaneously in a 74-year-old man, which occurred 1 year after a left nephroureterectomy. The patient underwent six courses of chemotherapy (gemcitabine, oxaliplatin, fluorouracil and nedaplatin), and received radiotherapy for the oral lesion. The symptoms were alleviated, but the tumor recurred in the oral cavity 2 years later. Brain and liver metastases were confirmed by CT. Repeated radiotherapy for oral metastasis was performed, but the patient died 4 years after the initial nephroureterectomy due to multiple metastases. Copyright 2010 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  14. A study of the uptake and biodistribution of nano-titanium dioxide using in vitro and in vivo models of oral intake

    NASA Astrophysics Data System (ADS)

    MacNicoll, Alan; Kelly, Mick; Aksoy, Hatice; Kramer, Evelien; Bouwmeester, Hans; Chaudhry, Qasim

    2015-02-01

    Certain food additives may contain a sizeable fraction of particles in the nanoscale. However, little is known about the fate, behaviour and toxicological effects of orally-ingested nanoparticles. This study investigated the uptake and biodistribution of nano- and larger-sized titanium dioxide (TiO2) using an in vitro model of gut epithelium and in vivo in rat. The results of the in vivo study showed that oral administration of 5 mg/kg body weight of TiO2 nano- or larger particles did not lead to any significant translocation of TiO2 (measured as titanium) either to blood, urine or to various organs in rat at any of the time intervals studied over a 96 h post-administration period. Different methods used for dispersing particles did not affect the uptake, and orally administered TiO2 was found excreted in the faeces over a period of time. The in vitro study provided further evidence for the lack of translocation of TiO2 across the gut epithelium model. The overall evidence from both in vivo and in vitro studies did not support that oral ingestion of nano- or larger particles of TiO2 via food would result in any significant internal exposure of the consumer to the nanoparticles. The dietary TiO2 nanoparticles are likely to be excreted in the faeces.

  15. Hexavalent Chromium Is Carcinogenic to F344/N Rats and B6C3F1 Mice after Chronic Oral Exposure

    PubMed Central

    Stout, Matthew D.; Herbert, Ronald A.; Kissling, Grace E.; Collins, Bradley J.; Travlos, Gregory S.; Witt, Kristine L.; Melnick, Ronald L.; Abdo, Kamal M.; Malarkey, David E.; Hooth, Michelle J.

    2009-01-01

    Background Hexavalent chromium [Cr(VI)] is a human carcinogen after inhalation exposure. Humans also ingest Cr(VI) from contaminated drinking water and soil; however, limited data exist on the oral toxicity and carcinogenicity of Cr(VI). Objective We characterized the chronic oral toxicity and carcinogenicity of Cr(VI) in rodents. Methods The National Toxicology Program (NTP) conducted 2-year drinking water studies of Cr(VI) (as sodium dichromate dihydrate) in male and female F344/N rats and B6C3F1 mice. Results Cr(VI) exposure resulted in increased incidences of rare neoplasms of the squamous epithelium that lines the oral cavity (oral mucosa and tongue) in male and female rats, and of the epithelium lining the small intestine in male and female mice. Cr(VI) exposure did not affect survival but resulted in reduced mean body weights and water consumption, due at least in part to poor palatability of the dosed water. Cr(VI) exposure resulted in transient microcytic hypochromic anemia in rats and microcytosis in mice. Nonneoplastic lesions included diffuse epithelial hyperplasia in the duodenum and jejunum of mice and histiocytic cell infiltration in the duodenum, liver, and mesenteric and pancreatic lymph nodes of rats and mice. Conclusions Cr(VI) was carcinogenic after administration in drinking water to male and female rats and mice. PMID:19479012

  16. Perspectives on human regeneration

    PubMed Central

    Stark, James F.

    2018-01-01

    Regeneration is a concept that has fascinated humans for centuries. Whether we have been trying to bring things back to life, extract additional resources from the world, or remodel our living spaces—domestic and urban—it is often presented as an unproblematic force for good. But what exactly does it mean to regenerate a body, mind or space? This paper, which introduces a collection of contributions on the theme of human regeneration, explores the limits and possibilities of regeneration as a conceptual tool for understanding the biological realm. What does it mean to be regenerated? How can a scholarly focus on this concept enrich our histories of bodies, ageing, disability and science, technology and medicine? As a secondary goal, I identify two distinct aspects of regeneration—'hard' and 'soft' regeneration—which concern the medical and social elements of regeneration respectively. By recognising that everything from cosmetics and fictions to prosthetics and organs grown in vitro display a combination of 'hard' and 'soft' elements, we are better placed to understand that the biological and social must be considered in consort for us to fully appreciate the meanings and practices that underpin multiple forms of human regeneration. PMID:29910957

  17. Potential of insulin nanoparticle formulations for oral delivery and diabetes treatment.

    PubMed

    Wong, Chun Y; Al-Salami, Hani; Dass, Crispin R

    2017-10-28

    Nanoparticles have demonstrated significant advancements in potential oral delivery of insulin. In this publication, we review the current status of polymeric, inorganic and solid-lipid nanoparticles designed for oral administration of insulin. Firstly, the structure and physiological function of insulin are examined. Then, the efficiency and shortcomings of insulin nanoparticle are discussed. These include the susceptibility to digestive enzyme degradation, instability in the acidic pH environment, poor mucus diffusion and inadequate permeation through the gastrointestinal epithelium. In order to optimise the nanocarriers, the following considerations, including polymer nature, surface charge, size, polydispersity index and morphology of nanoparticles, have to be taken into account. Some novel designs such as chitosan-based glucose-responsive nanoparticles, layer by layer technique-based nanoparticles and zwitterion nanoparticles are being adopted to overcome the physiological challenges. The review ends with some future directions and challenges to be addressed for the success of oral delivery of insulin-loaded nanoparticle formulation. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Morphology and distribution of taste papillae and oral denticles in the developing oropharyngeal cavity of the bamboo shark, Chiloscyllium punctatum.

    PubMed

    Atkinson, Carla J L; Martin, Kyle J; Fraser, Gareth J; Collin, Shaun P

    2016-12-15

    Gustation in sharks is not well understood, especially within species that ingest food items using suction. This study examines the morphological and immunohistochemical characterisation of taste papillae and oral denticles in the oropharynx of the brown-banded bamboo shark Chiloscyllium punctatum and compares their distribution during development. Taste papillae of C. punctatum are located throughout the oropharyngeal region and are most concentrated on the oral valves (2125-3483 per cm 2 in embryos; 89-111 per cm 2 in mature adults) close to the tooth territories. Papillae appearance is comparable at all stages of development, with the exception of the embryos (unhatched specimens), where no microvilli are present. Oral valve papillae are comparable in structure to Type I taste buds of teleost fishes, whereas those of the rest of the oropharyngeal region are comparable to Type II. Both types of papillae show immunofluorescence for a number of markers of taste buds, including β-Catenin and Sox2. Taste papillae densities are highest in embryos with 420-941 per cm 2 compared to 8-29 per cm 2 in mature adults. The total number of papillae remains around 1900 for all stages of development. However, the papillae increase in diameter from 72±1 μm (mean±s.e.m.) in embryos to 310±7 μm in mature individuals. Microvilli protrude in multiple patches at the apical tip of the papilla covering ∼0.5% of the papillar surface area. We further document the relationship between taste papillae and the closely associated oral denticles within the shark orophayngeal cavity. Oral denticles first break through the epithelium in the antero-central region of the dorsal oral cavity, shortly after the emergence of teeth, around time of hatching. Denticles are located throughout the oropharyngeal epithelium of both immature and mature stages, with the highest concentrations in the antero-dorsal oral cavity and the central regions of the pharynx. These denticle-rich areas of the

  19. Alternative cells for regeneration.

    PubMed

    Slack, Jonathan M W

    2012-04-17

    Normally, in fish fin regeneration, bone regenerates from bone. But what happens when there is no bone? Singh et al. (2012) show in this issue of Developmental Cell that the bony rays still regenerate from an alternative cell source. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. NORMAL GENE EXPRESSION IN MALE F344 RAT NASAL TRANSITIONAL/RESPIRATORY EPITHELIUM

    EPA Science Inventory

    Abstract

    The nasal epithelium is an important target site for chemically-induced toxicity and carcinogenicity in rodents. Gene expression profiles were determined in order to provide normal baseline data for nasal transitional/respiratory epithelium from healthy rats. Ce...

  1. Optimization for zeolite regeneration and nitrogen removal performance of a hypochlorite-chloride regenerant.

    PubMed

    Zhang, Wei; Zhou, Zhen; An, Ying; Du, Silu; Ruan, Danian; Zhao, Chengyue; Ren, Ning; Tian, Xiaoce

    2017-07-01

    Simultaneous zeolites regeneration and nitrogen removal were investigated by using a mixed solution of NaClO and NaCl (NaClO-NaCl solution), and effects of the regenerant on ammonium removal performance and textural properties of zeolites were analyzed by long-term adsorption and regeneration operations. Mixed NaClO-NaCl solution removed more NH 4 + exchanged on zeolites and converted more of them to nitrogen than using NaClO or NaCl solution alone. Response surface methodological analysis indicated that molar ratio of hypochlorite and nitrogen (ClO - /N), NaCl concentration and pH value all had significant effects on zeolites regeneration and NH 4 + conversion to nitrogen, and the optimum condition was obtained at ClO - /N of 1.75, NaCl concentration of 20 g/L and pH of 10.0. Zeolites regenerated by mixed NaClO-NaCl solution showed higher ammonium adsorption rate and lower capacity than unused zeolites. Zeolites and the regeneration solution were both effective even after 20 cycles of use. Composition and morphological analysis revealed that the main mineral species and surface morphology of zeolites before and after NaClO-NaCl regeneration were unchanged. Textural analysis indicated that NaClO-NaCl regeneration leads to an increased surface area of zeolites, especially the microporosity. The results indicated that NaClO-NaCl regeneration is an attractive method to achieve sustainable removal of nitrogen from wastewater through zeolite. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Gastric Helicobacter Infection Inhibits Development of Oral Tolerance to Food Antigens in Mice

    PubMed Central

    Matysiak-Budnik, Tamara; van Niel, Guillaume; Mégraud, Francis; Mayo, Kathryn; Bevilacqua, Claudia; Gaboriau-Routhiau, Valérie; Moreau, Marie-Christiane; Heyman, Martine

    2003-01-01

    The increase in the transcellular passage of intact antigens across the digestive epithelium infected with Helicobacter pylori may interfere with the regulation of mucosal immune responses. The aim of this work was to study the capacity of Helicobacter infection to inhibit the development of oral tolerance or to promote allergic sensitization and the capacity of a gastro-protective agent, rebamipide, to interfere with these processes in mice. Oral tolerance to ovalbumin (OVA) was studied in 48 C3H/He 4-week-old mice divided into four groups: (i) OVA-sensitized mice; (ii) OVA-“tolerized” mice (that is, mice that were rendered immunologically tolerant); (iii) H. felis-infected, OVA-tolerized mice; (iv) and H. felis-infected, OVA-tolerized, rebamipide-treated mice. Oral sensitization to hen egg lysozyme (HEL) was studied in 48 mice divided into four groups: (i) controls; (ii) HEL-sensitized mice; (iii) H. felis-infected, HEL-sensitized mice; and (iv) H. felis-infected, HEL-sensitized, rebamipide-treated mice. Specific anti-OVA or anti-HEL immunoglobulin E (IgE) and IgG1/IgG2a serum titers were measured by enzyme-linked immunosorbent assay. Additionally, the capacity of rebamipide to interfere with antigen presentation and T-cell activation in vitro, as well as absorption of rebamipide across the epithelial monolayer, was tested. H. felis infection led to the inhibition of oral tolerance to OVA, but rebamipide prevented this inhibitive effect of H. felis. H. felis infection did not enhance the sensitization to HEL, but rebamipide inhibited the development of this sensitization. Moreover, rebamipide inhibited in a dose-dependent manner antigen presentation and T-cell activation in vitro and was shown to be able to cross the epithelium at a concentration capable of inducing this inhibitory effect. We conclude that H. felis can inhibit the development of oral tolerance to OVA in mice and that this inhibition is prevented by rebamipide. PMID:12933867

  3. Solitary chemoreceptor cell proliferation in adult nasal epithelium.

    PubMed

    Gulbransen, Brian D; Finger, Thomas E

    2005-03-01

    Nasal trigeminal chemosensitivity in mice and rats is mediated in part by solitary chemoreceptor cells (SCCs) in the nasal epithelium (Finger et al., 2003). Many nasal SCCs express the G-protein alpha-gustducin as well as other elements of the bitter-taste signaling cascade including phospholipase Cbeta2, TRPM5 and T2R bitter-taste receptors. While some populations of sensory cells are replaced throughout life (taste and olfaction), others are not (hair cells and carotid body chemoreceptors). These experiments were designed to test whether new SCCs are generated within the epithelium of adult mice. Wild type C57/B6 mice were injected with the thymidine analog 5-bromo-2'-deoxyuridine (BrdU) to label dividing cells. At various times after injection (1-40 days), the mice were perfused with 4% paraformaldehyde and prepared for dual-label immunocytochemistry. Double labeled cells were detected as early as 3 days post BrdU injection and remained for as long as 12 days post-injection suggesting that SCCs do undergo turnover like the surrounding nasal epithelium. No BrdU labeled cells were detected after 24 days suggesting relatively rapid replacement of the SCCs.

  4. Solitary Chemoreceptor Cell Proliferation in Adult Nasal Epithelium

    PubMed Central

    Gulbransen, Brian D.; Finger, Thomas E.

    2008-01-01

    Nasal trigeminal chemosensitivity in mice and rats is mediated in part by solitary chemoreceptor cells (SCCs) in the nasal epithelium (Finger et al., 2003). Many nasal SCCs express the G-protein α-gustducin as well as other elements of the bitter-taste signaling cascade including phospholipase Cβ2, TRPM5 and T2R bitter-taste receptors. While some populations of sensory cells are replaced throughout life (taste and olfaction), others are not (hair cells and carotid body chemoreceptors). These experiments were designed to test whether new SCCs are generated within the epithelium of adult mice. Wild type C57/B6 mice were injected with the thymidine analog 5-bromo-2'-deoxyuridine (BrdU) to label dividing cells. At various times after injection (1-40 days), the mice were perfused with 4% paraformaldehyde and prepared for dual-label immunocytochemistry. Double labeled cells were detected as early as 3 days post BrdU injection and remained for as long as 12 days post-injection suggesting that SCCs do undergo turnover like the surrounding nasal epithelium. No BrdU labeled cells were detected after 24 days suggesting relatively rapid replacement of the SCCs. PMID:16374713

  5. Expression patterns of tight junction components induced by CD24 in an oral epithelial cell-culture model correlated to affected periodontal tissues.

    PubMed

    Ye, P; Yu, H; Simonian, M; Hunter, N

    2014-04-01

    Previously we demonstrated uniformly strong expression of CD24 in the epithelial attachment to the tooth and in the migrating epithelium of the periodontitis lesion. Titers of serum antibodies autoreactive with CD24 peptide correlated with reduced severity of periodontal disease. Ligation of CD24 expressed by oral epithelial cells induced formation of tight junctions that limited paracellular diffusion. In this study, we aimed to reveal that the lack of uniform expression of tight junction components in the pocket epithelium of periodontitis lesions is likely to contribute to increased paracellular permeability to bacterial products. This is proposed as a potential driver of the immunopathology of periodontitis. An epithelial culture model with close correspondence for expression patterns for tight junction components in periodontal epithelia was used. Immunohistochemical staining and confocal laser scanning microscopy were used to analyse patterns of expression of gingival epithelial tight junction components. The minimally inflamed gingival attachment was characterized by uniformly strong staining at cell contacts for the tight junction components zona occludens-1, zona occludens-2, occludin, junction adhesion molecule-A, claudin-4 and claudin-15. In contrast, the pocket epithelium of the periodontal lesion showed scattered, uneven staining for these components. This pattern correlated closely with that of unstimulated oral epithelial cells in culture. Following ligation of CD24 expressed by these cells, the pattern of tight junction component expression of the minimally inflamed gingival attachment developed rapidly. There was evidence for non-uniform and focal expression only of tight junction components in the pocket epithelium. In the cell-culture model, ligation of CD24 induced a tight junction expression profile equivalent to that observed for the minimally inflamed gingival attachment. Ligation of CD24 expressed by gingival epithelial cells by lectin

  6. Hair cell regeneration in the chick inner ear following acoustic trauma: ultrastructural and immunohistochemical studies.

    PubMed

    Umemoto, M; Sakagami, M; Fukazawa, K; Ashida, K; Kubo, T; Senda, T; Yoneda, Y

    1995-09-01

    The regeneration of hair cells in the chick inner ear following acoustic trauma was examined using transmission electron microscopy. In addition, the localization of proliferation cell nuclear antigen (PCNA) and basic fibroblast growth factor (b-FGF) was demonstrated immunohistochemically. The auditory sensory epithelium of the normal chick consists of short and tall hair cells and supporting cells. Immediately after noise exposure to a 1500-Hz pure tone at a sound pressure level of 120 decibels for 48 h, all the short hair cells disappeared in the middle region of the auditory epithelium. Twelve hours to 1 day after exposure, mitotic cells, binucleate cells and PCNA-positive supporting cells were observed, and b-FGF immunoreactivity was shown in the supporting cells and glial cells near the habenula perforata. Spindle-shaped hair cells with immature stereocilia and a kinocilium appeared 3 days after exposure; these cells had synaptic connections with the newly developed nerve endings. The spindle-shaped hair cell is considered to be a transitional cell in the lineage of the supporting cell to the mature short hair cell. These results indicate that, after acoustic trauma, the supporting cells divide and differentiate into new short hair cells via spindle-shaped hair cells. Furthermore, it is suggested that b-FGF is related to the proliferation of the supporting cells and the extension of the nerve fibers.

  7. Abnormal Ion Permeation through Cystic Fibrosis Respiratory Epithelium

    NASA Astrophysics Data System (ADS)

    Knowles, M. R.; Stutts, M. J.; Spock, A.; Fischer, N.; Gatzy, J. T.; Boucher, R. C.

    1983-09-01

    The epithelium of nasal tissue excised from subjects with cystic fibrosis exhibited higher voltage and lower conductance than tissue from control subjects. Basal sodium ion absorption by cystic fibrosis and normal nasal epithelia equaled the short-circuit current and was amiloride-sensitive. Amiloride induced chloride ion secretion in normal but not cystic fibrosis tissue and consequently was more effective in inhibiting the short-circuit current in cystic fibrosis epithelia. Chloride ion-free solution induced a smaller hyperpolarization of cystic fibrosis tissue. The increased voltage and amiloride efficacy in cystic fibrosis reflect absorption of sodium ions across an epithelium that is relatively impermeable to chloride ions.

  8. Principles of natural regeneration

    Treesearch

    1989-01-01

    To maximize chances of successful regeneration, carefully consider the following regeneration principles. Harvesting alone does not guarantee that the desired species will be established. The conditions required for the initial establishment and early growth of the desired species largely determine what regeneration method you should use and any supplemental treatments...

  9. Repair of tracheal epithelium by basal cells after chlorine-induced injury

    PubMed Central

    2012-01-01

    Background Chlorine is a widely used toxic compound that is considered a chemical threat agent. Chlorine inhalation injures airway epithelial cells, leading to pulmonary abnormalities. Efficient repair of injured epithelium is necessary to restore normal lung structure and function. The objective of the current study was to characterize repair of the tracheal epithelium after acute chlorine injury. Methods C57BL/6 mice were exposed to chlorine and injected with 5-ethynyl-2′-deoxyuridine (EdU) to label proliferating cells prior to sacrifice and collection of tracheas on days 2, 4, 7, and 10 after exposure. Airway repair and restoration of a differentiated epithelium were examined by co-localization of EdU labeling with markers for the three major tracheal epithelial cell types [keratin 5 (K5) and keratin 14 (K14) for basal cells, Clara cell secretory protein (CCSP) for Clara cells, and acetylated tubulin (AcTub) for ciliated cells]. Morphometric analysis was used to measure proliferation and restoration of a pseudostratified epithelium. Results Epithelial repair was fastest and most extensive in proximal trachea compared with middle and distal trachea. In unexposed mice, cell proliferation was minimal, all basal cells expressed K5, and K14-expressing basal cells were absent from most sections. Chlorine exposure resulted in the sloughing of Clara and ciliated cells from the tracheal epithelium. Two to four days after chlorine exposure, cell proliferation occurred in K5- and K14-expressing basal cells, and the number of K14 cells was dramatically increased. In the period of peak cell proliferation, few if any ciliated or Clara cells were detected in repairing trachea. Expression of ciliated and Clara cell markers was detected at later times (days 7–10), but cell proliferation was not detected in areas in which these differentiated markers were re-expressed. Fibrotic lesions were observed at days 7–10 primarily in distal trachea. Conclusion The data are

  10. Seminal epithelium in prostate biopsy can mimic malignant and premalignant prostatic lesions.

    PubMed

    Arista-Nasr, J; Trolle-Silva, A; Aguilar-Ayala, E; Martínez-Benítez, B

    2016-01-01

    In most prostate biopsies, the seminal epithelium is easily recognised because it meets characteristic histological criteria. However, some biopsies can mimic malignant or premalignant prostatic lesions. The aims of this study were to analyse the histological appearance of the biopsies that mimic adenocarcinomas or preneoplastic prostatic lesions, discuss the differential diagnosis and determine the frequency of seminal epithelia in prostate biopsies. We consecutively reviewed 500 prostate puncture biopsies obtained using the sextant method and selected those cases in which we observed seminal vesicle or ejaculatory duct epithelium. In the biopsies in which the seminal epithelium resembled malignant or premalignant lesions, immunohistochemical studies were conducted that included prostate-specific antigen and MUC6. The most important clinical data were recorded. Thirty-six (7.2%) biopsies showed seminal epithelium, and 7 of them (1.4%) resembled various prostate lesions, including high-grade prostatic intraepithelial neoplasia, atypical acinar proliferations, adenocarcinomas with papillary patterns and poorly differentiated carcinoma. The seminal epithelium resembled prostate lesions when the lipofuscin deposit, the perinuclear vacuoles or the nuclear pseudoinclusions were inconspicuous or missing. Five of the 7 biopsies showed mild to moderate cellular atypia with small and hyperchromatic nuclei, and only 2 showed cellular pleomorphism. The patients were alive and asymptomatic after an average of 6 years of progression. The seminal epithelium resembles prostatic intraepithelial neoplasia, atypical acinar proliferations and various types of prostatic adenocarcinomas in approximately 1.4% of prostate biopsies. Copyright © 2015 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. Sonic hedgehog initiates cochlear hair cell regeneration through downregulation of retinoblastoma protein

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lu, Na; Department of Otolaryngology and Program in Neuroscience, Harvard Medical School and Eaton Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston, MA 02114; Chen, Yan

    Highlights: Black-Right-Pointing-Pointer Shh activation in neonatal cochleae enhances sensory cell proliferation. Black-Right-Pointing-Pointer Proliferating supporting cells can transdifferentiate into hair cells. Black-Right-Pointing-Pointer Shh promotes proliferation by transiently modulating pRb activity. Black-Right-Pointing-Pointer Shh inhibits pRb by inhibiting transcription and increasing phosphorylation of pRb. -- Abstract: Cell cycle re-entry by cochlear supporting cells and/or hair cells is considered one of the best approaches for restoring hearing loss as a result of hair cell damage. To identify mechanisms that can be modulated to initiate cell cycle re-entry and hair cell regeneration, we studied the effect of activating the sonic hedgehog (Shh) pathway. We showmore » that Shh signaling in postnatal rat cochleae damaged by neomycin leads to renewed proliferation of supporting cells and hair cells. Further, proliferating supporting cells are likely to transdifferentiate into hair cells. Shh treatment leads to inhibition of retinoblastoma protein (pRb) by increasing phosphorylated pRb and reducing retinoblastoma gene transcription. This results in upregulation of cyclins B1, D2, and D3, and CDK1. These results suggest that Shh signaling induces cell cycle re-entry in cochlear sensory epithelium and the production of new hair cells, in part by attenuating pRb function. This study provides an additional route to modulate pRb function with important implications in mammalian hair cell regeneration.« less

  12. Retinal pigment epithelium changes in Kartagener syndrome.

    PubMed

    Garcia, Maria D; Ventura, Camila V; Dias, João R; Chang, Ta Chen P; Berrocal, Audina M

    2018-06-01

    We present the first case in the literature of a patient with Kartagener syndrome and ocular findings of nonexudative age-related macular degeneration. A 55-year-old woman with Kartagener syndrome and chronic angle closure glaucoma presented for evaluation of the retina. Optos ultra-widefield imaging of the fundus showed glaucomatous cupping, drusen, and retinal pigment epithelium changes within the macular region. Humphrey visual field testing confirmed glaucomatous changes. Drusenoid pigment epithelial detachments were observed bilaterally with optical coherence tomography. We hypothesize that in addition to the lungs, spermatozoa and the Fallopian tubes, the retinal pigment epithelium may also be affected by ciliary dysfunction in individuals with Kartagener syndrome. Given recent advances in our knowledge of retinal ciliopathies, further studies are needed to understand how ciliary dysfunction affects the retina in Kartagener syndrome.

  13. Axon Regeneration in C. elegans: worming our way to mechanisms of axon regeneration

    PubMed Central

    Byrne, Alexandra B.; Hammarlund, Marc

    2016-01-01

    How axons repair themselves after injury is a fundamental question in neurobiology. With its conserved genome, relatively simple nervous system, and transparent body, C. elegans has recently emerged as a productive model to uncover the cellular mechanisms that regulate and execute axon regeneration. In this review, we discuss the strengths and weaknesses of the C. elegans model of regeneration. We explore the technical advances that enable the use of C. elegans for in vivo regeneration studies, review findings in C. elegans that have contributed to our understanding of the regeneration response across species, discuss the potential of C. elegans research to provide insight into mechanisms that function in the injured mammalian nervous system, and present potential future directions of axon regeneration research using C. elegans. PMID:27569538

  14. Neural crest contribution to lingual mesenchyme, epithelium and developing taste papillae and taste buds.

    PubMed

    Liu, Hong-Xiang; Komatsu, Yoshihiro; Mishina, Yuji; Mistretta, Charlotte M

    2012-08-15

    The epithelium of mammalian tongue hosts most of the taste buds that transduce gustatory stimuli into neural signals. In the field of taste biology, taste bud cells have been described as arising from "local epithelium", in distinction from many other receptor organs that are derived from neurogenic ectoderm including neural crest (NC). In fact, contribution of NC to both epithelium and mesenchyme in the developing tongue is not fully understood. In the present study we used two independent, well-characterized mouse lines, Wnt1-Cre and P0-Cre that express Cre recombinase in a NC-specific manner, in combination with two Cre reporter mouse lines, R26R and ZEG, and demonstrate a contribution of NC-derived cells to both tongue mesenchyme and epithelium including taste papillae and taste buds. In tongue mesenchyme, distribution of NC-derived cells is in close association with taste papillae. In tongue epithelium, labeled cells are observed in an initial scattered distribution and progress to a clustered pattern between papillae, and within papillae and early taste buds. This provides evidence for a contribution of NC to lingual epithelium. Together with previous reports for the origin of taste bud cells from local epithelium in postnatal mouse, we propose that NC cells migrate into and reside in the epithelium of the tongue primordium at an early embryonic stage, acquire epithelial cell phenotypes, and undergo cell proliferation and differentiation that is involved in the development of taste papillae and taste buds. Our findings lead to a new concept about derivation of taste bud cells that include a NC origin. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Ultrastructure of free-ending nerve fibres in oesophageal epithelium.

    PubMed Central

    Robles-Chillida, E M; Rodrigo, J; Mayo, I; Arnedo, A; Gómez, A

    1981-01-01

    For the first time, at the ultrastructural level, the existence of free-ending, intraepithelial nerve fibres has been demonstrated in the oesophagus wall of adult cats and monkeys. Their form, the way they penetrate the epithelium, their location within the epithelium and their relationships with neighbouring cells have been established. A sensory function is suggested for this type of ending. Images Figs. 1-4 Figs. 5-6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Figs. 14-15 Figs. 16-17 PMID:7333951

  16. Evaluation of Cameroonian plants towards experimental bone regeneration.

    PubMed

    Ngueguim, Florence Tsofack; Khan, Mohd Parvez; Donfack, Jean Hubert; Siddiqui, Jawed Akhtar; Tewari, Deepshikha; Nagar, Geet K; Tiwari, Satish C; Theophile, Dimo; Maurya, Rakesh; Chattopadhyay, Naibedya

    2012-05-07

    Elephantopus mollis, Spilanthes africana, Urena lobata, Momordica multiflora, Asystasia gangetica and Brillantaisia ovariensis are used in Cameroonian traditional medicine for the treatment of bone diseases and fracture repair. The aim of this study was to evaluate the effect of ethanolic extracts of six Cameroonian medicinal plants on bone regeneration following bone and marrow injury. Ethanol extract of Cameroonian medicinal plants were administered (each extract at 250, 500 and 750mg/kg doses) orally to adult female Sprague-Dawley rats having a drill hole injury (0.8mm) in the femur diaphysis. Vehicle (gum-acacia in distilled water) was given to the control group. After 12 days of treatment, animals were euthanized and femur bones collected. Confocal microscopy of fractured bone was performed to evaluate bone regeneration (calcein labeling). Only active plant extracts were used for further experiments. Thus, callus was analyzed by microcomputed tomography. Osteogenic effects of the extracts were evaluated by assessing mineralized nodules formation of bone marrow stromal cells and osteoblast recruitment at drill hole site by immunohistochemistry. Ethanolic extract of the leaves and twigs of Elephantopus mollis (EM) and whole plant of Spilanthes africana (SA) dose-dependently stimulated bone regeneration at the drill hole site. EM at 250 and 750mg/kg doses and SA at 750mg/kg dose significantly increased mineral deposition compared to controls. Both extracts at 500 and 750mg/kg doses improved microarchitecture of the regenerating bone evident from increased bone volume fraction, trabecular thickness, trabecular number, and decreased trabecular separation and structure model index. EM and SA extracts increased the formation of mineralized nodules from the bone marrow stromal cells. In addition, EM and SA extracts increased osteoblast recruitment at the drill hole site evident from increased Runx-2 positive cells following their treatments compared to control

  17. Cochlear hair cell regeneration after noise-induced hearing loss: does regeneration follow development?

    PubMed Central

    Zheng, Fei; Zuo, Jian

    2017-01-01

    Noise-induced hearing loss (NIHL) affects a large number of military personnel and civilians. Regenerating inner-ear cochlear hair cells (HCs) is a promising strategy to restore hearing after NIHL. In this review, we first summarize recent transcriptome profile analysis of zebrafish lateral lines and chick utricles where spontaneous HC regeneration occurs after HC damage. We then discuss recent studies in other mammalian regenerative systems such as pancreas, heart and central nervous system. Both spontaneous and forced HC regeneration occurs in mammalian cochleae in vivo involving proliferation and direct lineage conversion. However, both processes are inefficient and incomplete, and decline with age. For direct lineage conversion in vivo in cochleae and in other systems, further improvement requires multiple factors, including transcription, epigenetic and trophic factors, with appropriate stoichiometry in appropriate architectural niche. Increasing evidence from other systems indicates that the molecular paths of direct lineage conversion may be different from those of normal developmental lineages. We therefore hypothesize that HC regeneration does not have to follow HC development and that epigenetic memory of supporting cells influences the HC regeneration, which may be a key to successful cochlear HC regeneration. Finally, we discuss recent efforts in viral gene therapy and drug discovery for HC regeneration. We hope that combination therapy targeting multiple factors and epigenetic signaling pathways will provide promising avenues for HC regeneration in humans with NIHL and other types of hearing loss. PMID:28034617

  18. Vegetative regeneration

    Treesearch

    George A. Schier; John R. Jones; Robert P. Winokur

    1985-01-01

    Aspen is noted for its ability to regenerate vegetatively by adventitious shoots or suckers that arise on its long lateral roots. It also produces sprouts from stumps and root collars; but they are not common. In a survey of regeneration after clearcutting mature aspen in Utah. Baker (1918b) found that 92% of the shoots originated from roots, 7% from root collars, and...

  19. Harvest survivability of oak advanced regeneration

    Treesearch

    Jeff Stringer

    2005-01-01

    Natural regeneration of oak requires the occurrence of advance regeneration and/or stems capable of stump sprouting. These stems must be present before harvest and adequate numbers must survive harvest for oaks to successfully regenerate. Regeneration predictions are based on pre-harvest advance regeneration inventories. However, the use of these inventories does not...

  20. Immunohistochemical expression of Notch signaling in the lining epithelium of periapical cysts.

    PubMed

    Meliou, Eleni; Kerezoudis, Nikolaos; Tosios, Konstantinos; Lafkas, Daniel; Kiaris, Hippokratis

    2011-02-01

    In this study we evaluated the immunohistochemical expression of the receptors Notch 1 and Notch 2, the ligand Delta 1, and the transcription factors HES 1 and HES 5 in the epithelium of well-defined periapical cysts. Immunohistochemistry was carried out on 55 formalin-fixed and paraffin-embedded, well-defined periapical cysts with minimum inflammation, obtained from the archival tissue database of the Department of Oral Pathology and Surgery. Western blotting was performed to evaluate the specificity of the anti-Notch antibody and the expression of Notch signaling in 5 fresh-frozen periapical cysts. The levels of staining intensity were estimated by the performance of a semiautomated image analysis system. Descriptive statistic of mean values obtained by computerized image analysis method was performed. Immunostaining reaction of all Notch signaling components was observed in the cytoplasm and/or the cytoplasmic membrane in the majority of epithelial cells of periapical cysts. Nuclear staining was observed occasionally in all cases. Notch 2 showed strong staining in 52.83% of the cases, followed by Notch 1 (35.85%), HES 1 and HES 5 moderate staining in 72.73% and 57.69% of the cases, respectively, and Delta 1 weak staining in 58.33% of the cases. No statistical correlation was found between the antibodies and the sex or the age of the study group. Notch is an evolutionarily conserved signaling mechanism that regulates cell fate decisions during development and postnatal life in organisms as diverse as worms, flies, and humans. The present observations indicate that Notch pathway is active downstream in the lining epithelium of periapical cysts, suggesting an involvement of this pathway in periapical cyst growth and expansion. Copyright © 2011 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  1. A hierarchical Bayesian model for understanding the spatiotemporal dynamics of the intestinal epithelium

    PubMed Central

    Parker, Aimée; Pin, Carmen; Carding, Simon R.; Watson, Alastair J. M.; Byrne, Helen M.

    2017-01-01

    Our work addresses two key challenges, one biological and one methodological. First, we aim to understand how proliferation and cell migration rates in the intestinal epithelium are related under healthy, damaged (Ara-C treated) and recovering conditions, and how these relations can be used to identify mechanisms of repair and regeneration. We analyse new data, presented in more detail in a companion paper, in which BrdU/IdU cell-labelling experiments were performed under these respective conditions. Second, in considering how to more rigorously process these data and interpret them using mathematical models, we use a probabilistic, hierarchical approach. This provides a best-practice approach for systematically modelling and understanding the uncertainties that can otherwise undermine the generation of reliable conclusions—uncertainties in experimental measurement and treatment, difficult-to-compare mathematical models of underlying mechanisms, and unknown or unobserved parameters. Both spatially discrete and continuous mechanistic models are considered and related via hierarchical conditional probability assumptions. We perform model checks on both in-sample and out-of-sample datasets and use them to show how to test possible model improvements and assess the robustness of our conclusions. We conclude, for the present set of experiments, that a primarily proliferation-driven model suffices to predict labelled cell dynamics over most time-scales. PMID:28753601

  2. A hierarchical Bayesian model for understanding the spatiotemporal dynamics of the intestinal epithelium.

    PubMed

    Maclaren, Oliver J; Parker, Aimée; Pin, Carmen; Carding, Simon R; Watson, Alastair J M; Fletcher, Alexander G; Byrne, Helen M; Maini, Philip K

    2017-07-01

    Our work addresses two key challenges, one biological and one methodological. First, we aim to understand how proliferation and cell migration rates in the intestinal epithelium are related under healthy, damaged (Ara-C treated) and recovering conditions, and how these relations can be used to identify mechanisms of repair and regeneration. We analyse new data, presented in more detail in a companion paper, in which BrdU/IdU cell-labelling experiments were performed under these respective conditions. Second, in considering how to more rigorously process these data and interpret them using mathematical models, we use a probabilistic, hierarchical approach. This provides a best-practice approach for systematically modelling and understanding the uncertainties that can otherwise undermine the generation of reliable conclusions-uncertainties in experimental measurement and treatment, difficult-to-compare mathematical models of underlying mechanisms, and unknown or unobserved parameters. Both spatially discrete and continuous mechanistic models are considered and related via hierarchical conditional probability assumptions. We perform model checks on both in-sample and out-of-sample datasets and use them to show how to test possible model improvements and assess the robustness of our conclusions. We conclude, for the present set of experiments, that a primarily proliferation-driven model suffices to predict labelled cell dynamics over most time-scales.

  3. Carbon Sorption Cryogenic Regenerator

    NASA Technical Reports Server (NTRS)

    Jones, Jack A.; Petrick, S. Walter; Britcliffe, Michael J.

    1989-01-01

    Liquid-helium refrigerator includes regenerator filled with carbon sorbent made from Saran polyvinylidene chloride. Material results in lower operating temperatures and longer times between maintenance than comparable refrigerators containing other regenerators. Sorbent material machined to various configurations to fit inside cylindrical regenerator can. Configuration chosen with regard to heat capacity, pressure drop, and rate of sorption.

  4. Active magnetic regenerator

    DOEpatents

    Barclay, John A.; Steyert, William A.

    1982-01-01

    The disclosure is directed to an active magnetic regenerator apparatus and method. Brayton, Stirling, Ericsson, and Carnot cycles and the like may be utilized in an active magnetic regenerator to provide efficient refrigeration over relatively large temperature ranges.

  5. Integrin Beta 1 Suppresses Multilayering of a Simple Epithelium

    PubMed Central

    Chen, Jichao; Krasnow, Mark A.

    2012-01-01

    Epithelia are classified as either simple, a single cell layer thick, or stratified (multilayered). Stratified epithelia arise from simple epithelia during development, and transcription factor p63 functions as a key positive regulator of epidermal stratification. Here we show that deletion of integrin beta 1 (Itgb1) in the developing mouse airway epithelium abrogates airway branching and converts this monolayer epithelium into a multilayer epithelium with more than 10 extra layers. Mutant lung epithelial cells change mitotic spindle orientation to seed outer layers, and cells in different layers become molecularly and functionally distinct, hallmarks of normal stratification. However, mutant lung epithelial cells do not activate p63 and do not switch to the stratified keratin profile of epidermal cells. These data, together with previous data implicating Itgb1 in regulation of epidermal stratification, suggest that the simple-versus-stratified developmental decision may involve not only stratification inducers like p63 but suppressors like Itgb1 that prevent simple epithelia from inappropriately activating key steps in the stratification program. PMID:23285215

  6. PEGylated PLGA-based nanoparticles targeting M cells for oral vaccination.

    PubMed

    Garinot, Marie; Fiévez, Virginie; Pourcelle, Vincent; Stoffelbach, François; des Rieux, Anne; Plapied, Laurence; Theate, Ivan; Freichels, Hélène; Jérôme, Christine; Marchand-Brynaert, Jacqueline; Schneider, Yves-Jacques; Préat, Véronique

    2007-07-31

    To improve the efficiency of orally delivered vaccines, PEGylated PLGA-based nanoparticles displaying RGD molecules at their surface were designed to target human M cells. RGD grafting was performed by an original method called "photografting" which covalently linked RGD peptides mainly on the PEG moiety of the PCL-PEG, included in the formulation. First, three non-targeted formulations with size and zeta potential adapted to M cell uptake and stable in gastro-intestinal fluids, were developed. Their transport by an in vitro model of the human Follicle associated epithelium (co-cultures) was largely increased as compared to mono-cultures (Caco-2 cells). RGD-labelling of nanoparticles significantly increased their transport by co-cultures, due to interactions between the RGD ligand and the beta(1) intregrins detected at the apical surface of co-cultures. In vivo studies demonstrated that RGD-labelled nanoparticles particularly concentrated in M cells. Finally, ovalbumin-loaded nanoparticles were orally administrated to mice and induced an IgG response, attesting antigen ability to elicit an immune response after oral delivery.

  7. The physiological basics of the olfactory neuro-epithelium.

    PubMed

    Watelet, J B; Katotomichelakis, M; Eloy, P; Danielidis, V

    2009-01-01

    All living organisms can detect and identify chemical substances in their environment. The olfactory epithelium is covered by a mucus layer which is essential for the function of the olfactory neurons that are directly connected to the brain through the cribriform plate. However, little is known about the composition of this mucus in humans and its significance for the diagnosis of olfactory disorders. The olfactory epithelium consists of four primary cell types, including the olfactory receptor cells essential for odour transduction. This review examines the anatomical, histological and physiological fundamentals of olfactory mucosa. Particular attention is paid to the biochemical environment of the olfactory mucosa that regulates both peri-receptor events and several protective functions.

  8. Supercritical fluid regeneration of adsorbents

    NASA Astrophysics Data System (ADS)

    Defilippi, R. P.; Robey, R. J.

    1983-05-01

    The results of a program to perform studies supercritical (fluid) carbon dioxide (SCF CO2) regeneration of adsorbents, using samples of industrial wastewaters from manufacturing pesticides and synthetic solution, and to estimate the economics of the specific wastewater treatment regenerations, based on test data are given. Processing costs for regenerating granular activated carbon GAC) for treating industrial wastewaters depend on stream properties and regeneration throughput.

  9. Neural Regeneration in Caenorhabditis elegans

    PubMed Central

    El Bejjani, Rachid; Hammarlund, Marc

    2013-01-01

    Axon regeneration is a medically relevant process that can repair damaged neurons. This review describes current progress in understanding axon regeneration in the model organism Caenorhabditis elegans. Factors that regulate axon regeneration in C. elegans have broadly similar roles in vertebrate neurons. This means that using C. elegans as a tool to leverage discovery is a legitimate strategy for identifying conserved mechanisms of axon regeneration. PMID:22974301

  10. Nucleolar Organizer Regions in Oral Squamous Cell Carcinoma

    PubMed Central

    Moradzadeh Khiavi, Monir; Vosoughhosseini, Sepideh; Halimi, Monire; Mahmoudi, Seyyed Mostafa; Yarahmadi, Asghar

    2012-01-01

    Background and aims Several diagnostic methods are being employed to detect benign and malignant lesions, one of which is silver nitrate staining for organizer regions. The number of nucleolar organizing regions (NORs) can be used to show the degree of cell activity or metabolism in pathologic lesions. This study was designed to evaluate NORs as determi-nants of precancerous and squamous cell carcinoma. Materials and methods A silver colloid technique was applied on paraffin sections of 40 cases of oral squamous cell carcinoma and 25 cases of precancerous lesions; 15 specimens of normal epithelium were selected for the control group. After staining with silver nitrate, argyrophilic nucleolar organizer regions (AgNORs) were counted in 100 epithelial cells in three groups with the use of an oil immersion and ×1000 objective lens. One-way ANOVA and a post hoc Tukey test were used for statistical analysis. Results The mean numbers and standard deviations of AgNORs were 1.58 ± 0.76 in normal epithelium, 2.1 ± 1.05 in pre-cancerous lesions and 2.43 ±1.33 in squamous cell carcinoma (SCC). There were statistically significant differences in Ag-NORs numbers between the groups (P<0.001) and significant differences in precancerous lesions between dysplastic and non-dysplastic epithelia (P<0.001). The mean AgNORs count per nucleus increased from healthy epithelium to precancer-ous lesion to SCC. Conclusion This study suggests that the silver staining technique for the detection of NORs (AgNOR) can be used to distinguish precancerous lesions and benign and malignant lesions. PMID:22991629

  11. Barrier properties of cultured retinal pigment epithelium.

    PubMed

    Rizzolo, Lawrence J

    2014-09-01

    The principal function of an epithelium is to form a dynamic barrier that regulates movement between body compartments. Each epithelium is specialized with barrier functions that are specific for the tissues it serves. The apical surface commonly faces a lumen, but the retinal pigment epithelium (RPE) appears to be unique by a facing solid tissue, the sensory retina. Nonetheless, there exists a thin (subretinal) space that can become fluid filled during pathology. RPE separates the subretinal space from the blood supply of the outer retina, thereby forming the outer blood-retinal barrier. The intricate interaction between the RPE and sensory retina presents challenges for learning how accurately culture models reflect native behavior. The challenge is heightened by findings that detail the variation of RPE barrier proteins both among species and at different stages of the life cycle. Among the striking differences is the expression of claudin family members. Claudins are the tight junction proteins that regulate ion diffusion across the spaces that lie between the cells of a monolayer. Claudin expression by RPE varies with species and life-stage, which implies functional differences among commonly used animal models. Investigators have turned to transcriptomics to supplement functional studies when comparing native and cultured tissue. The most detailed studies of the outer blood-retinal barrier have focused on human RPE with transcriptome and functional studies reported for human fetal, adult, and stem-cell derived RPE. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Amyloid β1-43 Accumulates in the Lens Epithelium of Cortical Opacification in Japanese Patients.

    PubMed

    Nagai, Noriaki; Mano, Yu; Otake, Hiroko; Shibata, Teppei; Kubo, Eri; Sasaki, Hiroshi

    2017-06-01

    We investigated the accumulation of amyloid β (Aβ1-40, Aβ1-42, Aβ1-43) in the lens epithelium of patients with opacification of five different types (cortical cataract [COR]; nuclear cataract [NUC]; posterior subcapsular cataract [PSC]; retrodots [RD]; and water clefts [WC]). Samples were collected from Japanese patients taken during cataract surgery; Aβ levels and mRNA expression were determined by ELISA and a real-time RT-PCR method, respectively. Levels of Aβ1-40 and Aβ1-42 in the lens epithelium of patients with COR, NUC, PSC, RD, and WC showed no significant differences in comparison with transparent lens epithelium. Levels of Aβ1-43 in the lens epithelium of patients with PSC and WC were not detected, and NUC and RD were slightly elevated. In contrast to the results in these cataract types, high Aβ1-43 levels were observed in the lens epithelium of patients with COR, and a close relationship was observed between Aβ1-43 levels and the degree of lens opacification (R = 0.8229, n = 6). The levels of Aβ1-43 were also higher in the lens epithelium of patients with mixed-cataract showing cortical opacification, and the Aβ1-43 levels in the lens epithelium of mixed-cataract patients with cortical opacification was significantly higher than in that of mixed-cataract patients without cortical opacification. In addition, the level of an amyloid precursor protein mRNA in the lens epithelium of mixed-cataract patients with cortical opacification was significantly higher than in transparent lens and mixed-cataract patients without cortical opacification. We found high levels of Aβ1-43 accumulation in the lens epithelium of Japanese patients with cortical opacification.

  13. Strategies to Improve Regeneration of the Soft Palate Muscles After Cleft Palate Repair

    PubMed Central

    Carvajal Monroy, Paola L.; Grefte, Sander; Kuijpers-Jagtman, Anne Marie; Wagener, Frank A.D.T.G.

    2012-01-01

    Children with a cleft in the soft palate have difficulties with speech, swallowing, and sucking. These patients are unable to separate the nasal from the oral cavity leading to air loss during speech. Although surgical repair ameliorates soft palate function by joining the clefted muscles of the soft palate, optimal function is often not achieved. The regeneration of muscles in the soft palate after surgery is hampered because of (1) their low intrinsic regenerative capacity, (2) the muscle properties related to clefting, and (3) the development of fibrosis. Adjuvant strategies based on tissue engineering may improve the outcome after surgery by approaching these specific issues. Therefore, this review will discuss myogenesis in the noncleft and cleft palate, the characteristics of soft palate muscles, and the process of muscle regeneration. Finally, novel therapeutic strategies based on tissue engineering to improve soft palate function after surgical repair are presented. PMID:22697475

  14. Strategies to improve regeneration of the soft palate muscles after cleft palate repair.

    PubMed

    Carvajal Monroy, Paola L; Grefte, Sander; Kuijpers-Jagtman, Anne Marie; Wagener, Frank A D T G; Von den Hoff, Johannes W

    2012-12-01

    Children with a cleft in the soft palate have difficulties with speech, swallowing, and sucking. These patients are unable to separate the nasal from the oral cavity leading to air loss during speech. Although surgical repair ameliorates soft palate function by joining the clefted muscles of the soft palate, optimal function is often not achieved. The regeneration of muscles in the soft palate after surgery is hampered because of (1) their low intrinsic regenerative capacity, (2) the muscle properties related to clefting, and (3) the development of fibrosis. Adjuvant strategies based on tissue engineering may improve the outcome after surgery by approaching these specific issues. Therefore, this review will discuss myogenesis in the noncleft and cleft palate, the characteristics of soft palate muscles, and the process of muscle regeneration. Finally, novel therapeutic strategies based on tissue engineering to improve soft palate function after surgical repair are presented.

  15. Olfactory epithelium influences the orientation of mitral cell dendrites during development.

    PubMed

    López-Mascaraque, Laura; García, Concepción; Blanchart, Albert; De Carlos, Juan A

    2005-02-01

    We have established previously that, although the olfactory epithelium is absent in the homozygous Pax-6 mutant mouse, an olfactory bulb-like structure (OBLS) does develop. Moreover, this OBLS contains cells that correspond to mitral cells, the primary projection neurons in the olfactory bulb. The current study aimed to address whether the dendrites of mitral cells in the olfactory bulb or in the OBLS mitral-like cells, exhibit a change in orientation in the presence of the olfactory epithelium. The underlying hypothesis is that the olfactory epithelium imparts a trophic signal on mitral and mitral-like cell that influences the growth of their primary dendrites, orientating them toward the surface of the olfactory bulb. Hence, we cultured hemibrains from wild-type and Pax 6 mutant mice from two different embryonic stages (embryonic days 14 and 15) either alone or in coculture with normal olfactory epithelial explants or control tissue (cerebellum). Our results indicate that the final dendritic orientation of mitral and mitral-like cells is directly influenced both by age and indeed by the presence of the olfactory epithelium. Copyright 2004 Wiley-Liss, Inc.

  16. deltaNp63 Has a Role in Maintaining Epithelial Integrity in Airway Epithelium

    PubMed Central

    Arason, Ari Jon; Jonsdottir, Hulda R.; Halldorsson, Skarphedinn; Benediktsdottir, Berglind Eva; Bergthorsson, Jon Thor; Ingthorsson, Saevar; Baldursson, Olafur; Sinha, Satrajit; Gudjonsson, Thorarinn; Magnusson, Magnus K.

    2014-01-01

    The upper airways are lined with a pseudostratified bronchial epithelium that forms a barrier against unwanted substances in breathing air. The transcription factor p63, which is important for stratification of skin epithelium, has been shown to be expressed in basal cells of the lungs and its ΔN isoform is recognized as a key player in squamous cell lung cancer. However, the role of p63 in formation and maintenance of bronchial epithelia is largely unknown. The objective of the current study was to determine the expression pattern of the ΔN and TA isoforms of p63 and the role of p63 in the development and maintenance of pseudostratified lung epithelium in situ and in culture. We used a human bronchial epithelial cell line with basal cell characteristics (VA10) to model bronchial epithelium in an air-liquid interface culture (ALI) and performed a lentiviral-based silencing of p63 to characterize the functional and phenotypic consequences of p63 loss. We demonstrate that ΔNp63 is the major isoform in the human lung and its expression was exclusively found in the basal cells lining the basement membrane of the bronchial epithelium. Knockdown of p63 affected proliferation and migration of VA10 cells and facilitated cellular senescence. Expression of p63 is critical for epithelial repair as demonstrated by wound healing assays. Importantly, generation of pseudostratified VA10 epithelium in the ALI setup depended on p63 expression and goblet cell differentiation, which can be induced by IL-13 stimulation, was abolished by the p63 knockdown. After knockdown of p63 in primary bronchial epithelial cells they did not proliferate and showed marked senescence. We conclude that these results strongly implicate p63 in the formation and maintenance of differentiated pseudostratified bronchial epithelium. PMID:24533135

  17. deltaNp63 has a role in maintaining epithelial integrity in airway epithelium.

    PubMed

    Arason, Ari Jon; Jonsdottir, Hulda R; Halldorsson, Skarphedinn; Benediktsdottir, Berglind Eva; Bergthorsson, Jon Thor; Ingthorsson, Saevar; Baldursson, Olafur; Sinha, Satrajit; Gudjonsson, Thorarinn; Magnusson, Magnus K

    2014-01-01

    The upper airways are lined with a pseudostratified bronchial epithelium that forms a barrier against unwanted substances in breathing air. The transcription factor p63, which is important for stratification of skin epithelium, has been shown to be expressed in basal cells of the lungs and its ΔN isoform is recognized as a key player in squamous cell lung cancer. However, the role of p63 in formation and maintenance of bronchial epithelia is largely unknown. The objective of the current study was to determine the expression pattern of the ΔN and TA isoforms of p63 and the role of p63 in the development and maintenance of pseudostratified lung epithelium in situ and in culture. We used a human bronchial epithelial cell line with basal cell characteristics (VA10) to model bronchial epithelium in an air-liquid interface culture (ALI) and performed a lentiviral-based silencing of p63 to characterize the functional and phenotypic consequences of p63 loss. We demonstrate that ΔNp63 is the major isoform in the human lung and its expression was exclusively found in the basal cells lining the basement membrane of the bronchial epithelium. Knockdown of p63 affected proliferation and migration of VA10 cells and facilitated cellular senescence. Expression of p63 is critical for epithelial repair as demonstrated by wound healing assays. Importantly, generation of pseudostratified VA10 epithelium in the ALI setup depended on p63 expression and goblet cell differentiation, which can be induced by IL-13 stimulation, was abolished by the p63 knockdown. After knockdown of p63 in primary bronchial epithelial cells they did not proliferate and showed marked senescence. We conclude that these results strongly implicate p63 in the formation and maintenance of differentiated pseudostratified bronchial epithelium.

  18. Usefulness of GATA-3 as a marker of seminal epithelium in prostate biopsies.

    PubMed

    Ortiz-Rey, J A; Chantada-de la Fuente, D; Peteiro-Cancelo, M Á; Gómez-de María, C; San Miguel-Fraile, M P

    2017-11-01

    The incidental presence of seminal vesicle epithelium in prostate needle biopsies is generally recognisable through routine microscopy. However, the biopsy can sometimes be erroneously interpreted as malignant due to its architectural and cytological characteristics, and immunohistochemistry can be useful for correctly identifying the biopsy. Our objective was to analyse the potential usefulness of GATA-3 as a marker of seminal epithelium. Through immunohistochemistry with a monoclonal anti-GATA-3 antibody (clone L50-823), we studied seminal vesicle sections from 20 prostatectomy specimens, 12 prostate needle biopsies that contained seminal vesicle tissue and 68 prostate biopsies without seminal vesicle epithelium, 36 of which showed adenocarcinoma. Staining for GATA-3 was intense in the 20 seminal vesicles of the prostatectomy specimens and in the 12 prostate needle biopsies that contained seminal epithelium. In the 60 biopsies without a seminal vesicle, GATA-3 was positive in the prostate basal cells and even in the secretory cells (57 cases), although with less intensity in 55 of the cases. One of the 36 prostatic adenocarcinomas tested positive for GATA-3. The intense immunohistochemical expression of GATA-3 in the seminal vesicle epithelium can help identify the epithelium in prostate biopsies. This marker is also positive in the basal cells of healthy prostates and, with less intensity, in the secretory cells. Positivity, weak or moderate, is observed on rare occasions in prostatic adenocarcinomas. Copyright © 2017 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. Tissue engineering: state of the art in oral rehabilitation

    PubMed Central

    SCHELLER, E. L.; KREBSBACH, P. H.; KOHN, D. H.

    2009-01-01

    SUMMARY More than 85% of the global population requires repair or replacement of a craniofacial structure. These defects range from simple tooth decay to radical oncologic craniofacial resection. Regeneration of oral and craniofacial tissues presents a formidable challenge that requires synthesis of basic science, clinical science and engineering technology. Identification of appropriate scaffolds, cell sources and spatial and temporal signals (the tissue engineering triad) is necessary to optimize development of a single tissue, hybrid organ or interface. Furthermore, combining the understanding of the interactions between molecules of the extracellular matrix and attached cells with an understanding of the gene expression needed to induce differentiation and tissue growth will provide the design basis for translating basic science into rationally developed components of this tissue engineering triad. Dental tissue engineers are interested in regeneration of teeth, oral mucosa, salivary glands, bone and periodontium. Many of these oral structures are hybrid tissues. For example, engineering the periodontium requires growth of alveolar bone, cementum and the periodontal ligament. Recapitulation of biological development of hybrid tissues and interfaces presents a challenge that exceeds that of engineering just a single tissue. Advances made in dental interface engineering will allow these tissues to serve as model systems for engineering other tissues or organs of the body. This review will begin by covering basic tissue engineering principles and strategic design of functional biomaterials. We will then explore the impact of biomaterials design on the status of craniofacial tissue engineering and current challenges and opportunities in dental tissue engineering. PMID:19228277

  20. Tissue engineering: state of the art in oral rehabilitation.

    PubMed

    Scheller, E L; Krebsbach, P H; Kohn, D H

    2009-05-01

    More than 85% of the global population requires repair or replacement of a craniofacial structure. These defects range from simple tooth decay to radical oncologic craniofacial resection. Regeneration of oral and craniofacial tissues presents a formidable challenge that requires synthesis of basic science, clinical science and engineering technology. Identification of appropriate scaffolds, cell sources and spatial and temporal signals (the tissue engineering triad) is necessary to optimize development of a single tissue, hybrid organ or interface. Furthermore, combining the understanding of the interactions between molecules of the extracellular matrix and attached cells with an understanding of the gene expression needed to induce differentiation and tissue growth will provide the design basis for translating basic science into rationally developed components of this tissue engineering triad. Dental tissue engineers are interested in regeneration of teeth, oral mucosa, salivary glands, bone and periodontium. Many of these oral structures are hybrid tissues. For example, engineering the periodontium requires growth of alveolar bone, cementum and the periodontal ligament. Recapitulation of biological development of hybrid tissues and interfaces presents a challenge that exceeds that of engineering just a single tissue. Advances made in dental interface engineering will allow these tissues to serve as model systems for engineering other tissues or organs of the body. This review will begin by covering basic tissue engineering principles and strategic design of functional biomaterials. We will then explore the impact of biomaterials design on the status of craniofacial tissue engineering and current challenges and opportunities in dental tissue engineering.

  1. Claudin-8d is a cortisol-responsive barrier protein in the gill epithelium of trout.

    PubMed

    Kolosov, Dennis; Kelly, Scott P

    2017-10-01

    The influence of claudin (Cldn) 8 tight junction (TJ) proteins on cortisol-mediated alterations in gill epithelium permeability was examined using a primary cultured trout gill epithelium model. Genes encoding three Cldn-8 proteins ( cldn-8b, -8c and -8d ) have been identified in trout and all are expressed in the model gill epithelium. Cortisol treatment 'tightened' the gill epithelium, as indicated by increased transepithelial resistance (TER) and reduced paracellular [ 3 H]polyethylene glycol (MW 400 Da; PEG-400) flux. This occurred in association with elevated cldn-8d mRNA abundance, but no alterations in cldn-8b and -8c mRNA abundance were observed. Transcriptional knockdown (KD) of cldn-8d inhibited a cortisol-induced increase in Cldn-8d abundance and reduced the 'epithelium tightening' effect of cortisol in association with increased paracellular PEG-400 flux. Under simulated in vivo conditions (i.e. apical freshwater), cldn-8d KD hindered a cortisol-mediated reduction in basolateral to apical Na + and Cl - flux (i.e. reduced the ability of cortisol to mitigate ion loss). However, cldn-8d KD did not abolish the tightening effect of cortisol on the gill epithelium. This is likely due, in part, to the effect of cortisol on genes encoding other TJ proteins, which in some cases appeared to exhibit a compensatory response. Data support the idea that Cldn-8d is a barrier protein of the gill epithelium TJ that contributes significantly to corticosteroid-mediated alterations in gill epithelium permeability. © 2017 Society for Endocrinology.

  2. Quantum Dot Distribution in the Olfactory Epithelium After Nasal Delivery

    NASA Astrophysics Data System (ADS)

    Garzotto, D.; De Marchis, S.

    2010-10-01

    Nanoparticles are used in a wide range of human applications from industrial to bio-medical fields. However, the unique characteristics of nanoparticles, such as the small size, large surface area per mass and high reactivity raises great concern on the adverse effects of these particles on ecological systems and human health. There are several pioneer studies reporting translocation of inhaled particulates to the brain through a potential neuronal uptake mediated by the olfactory nerve (1, 2, 3). However, no direct evidences have been presented up to now on the pathway followed by the nanoparticles from the nose to the brain. In addition to a neuronal pathway, nanoparticles could gain access to the central nervous system through extracellular pathways (perineuronal, perivascular and cerebrospinal fluid paths). In the present study we investigate the localization of intranasally delivered fluorescent nanoparticles in the olfactory epithelium. To this purpose we used quantum dots (QDs), a model of innovative fluorescent semiconductor nanocrystals commonly used in cell and animal biology (4). Intranasal treatments with QDs were performed acutely on adult CD1 mice. The olfactory epithelium was collected and analysed by confocal microscopy at different survival time after treatment. Data obtained indicate that the neuronal components of the olfactory epithelium are not preferentially involved in QDs uptake, thus suggesting nanoparticles can cross the olfactory epithelium through extracellular pathways.

  3. Apico-basal forces exerted by apoptotic cells drive epithelium folding.

    PubMed

    Monier, Bruno; Gettings, Melanie; Gay, Guillaume; Mangeat, Thomas; Schott, Sonia; Guarner, Ana; Suzanne, Magali

    2015-02-12

    Epithelium folding is a basic morphogenetic event that is essential in transforming simple two-dimensional epithelial sheets into three-dimensional structures in both vertebrates and invertebrates. Folding has been shown to rely on apical constriction. The resulting cell-shape changes depend either on adherens junction basal shift or on a redistribution of myosin II, which could be driven by mechanical signals. Yet the initial cellular mechanisms that trigger and coordinate cell remodelling remain largely unknown. Here we unravel the active role of apoptotic cells in initiating morphogenesis, thus revealing a novel mechanism of epithelium folding. We show that, in a live developing tissue, apoptotic cells exert a transient pulling force upon the apical surface of the epithelium through a highly dynamic apico-basal myosin II cable. The apoptotic cells then induce a non-autonomous increase in tissue tension together with cortical myosin II apical stabilization in the surrounding tissue, eventually resulting in epithelium folding. Together our results, supported by a theoretical biophysical three-dimensional model, identify an apoptotic myosin-II-dependent signal as the initial signal leading to cell reorganization and tissue folding. This work further reveals that, far from being passively eliminated as generally assumed (for example, during digit individualization), apoptotic cells actively influence their surroundings and trigger tissue remodelling through regulation of tissue tension.

  4. Epithelium-Innate Immune Cell Axis in Mucosal Responses to SIV

    PubMed Central

    Shang, L.; Duan, L.; Perkey, K. E.; Wietgrefe, S.; Zupancic, M.; Smith, A. J.; Southern, P. J.; Johnson, R. P.; Haase, A. T.

    2016-01-01

    In the SIV-rhesus macaque model of HIV-1 transmission to women, one hallmark of the mucosal response to exposure to high doses of SIV is CD4 T cell recruitment that fuels local virus expansion in early infection. In this study, we systematically analyzed the cellular events and chemoattractant profiles in cervical tissues that precede CD4 T cell recruitment. We show that vaginal exposure to the SIV inoculum rapidly induces chemokine expression in cervical epithelium including CCL3, CCL20, and CXCL8. The chemokine expression is associated with early recruitment of macrophages and plasmacytoid dendritic cells that are co-clustered underneath the cervical epithelium. Production of chemokines CCL3 and CXCL8 by these cells in turn generates a chemokine gradient that is spatially correlated with the recruitment of CD4 T cells. We further show that the protection of SIVmac239Δnef vaccination against vaginal challenge is correlated with the absence of this epithelium-innate immune cell-CD4 T cell axis response in the cervical mucosa. Our results reveal a critical role for cervical epithelium in initiating early mucosal responses to vaginal infection, highlight an important role for macrophages in target cell recruitment and provide further evidence of a paradoxical dampening effect of a protective vaccine on these early mucosal responses. PMID:27435105

  5. Epithelium-innate immune cell axis in mucosal responses to SIV.

    PubMed

    Shang, L; Duan, L; Perkey, K E; Wietgrefe, S; Zupancic, M; Smith, A J; Southern, P J; Johnson, R P; Haase, A T

    2017-03-01

    In the SIV (simian immunodeficiency virus)-rhesus macaque model of HIV-1 (human immunodeficiency virus type I) transmission to women, one hallmark of the mucosal response to exposure to high doses of SIV is CD4 T-cell recruitment that fuels local virus expansion in early infection. In this study, we systematically analyzed the cellular events and chemoattractant profiles in cervical tissues that precede CD4 T-cell recruitment. We show that vaginal exposure to the SIV inoculum rapidly induces chemokine expression in cervical epithelium including CCL3, CCL20, and CXCL8. The chemokine expression is associated with early recruitment of macrophages and plasmacytoid dendritic cells that are co-clustered underneath the cervical epithelium. Production of chemokines CCL3 and CXCL8 by these cells in turn generates a chemokine gradient that is spatially correlated with the recruitment of CD4 T cells. We further show that the protection of SIVmac239Δnef vaccination against vaginal challenge is correlated with the absence of this epithelium-innate immune cell-CD4 T-cell axis response in the cervical mucosa. Our results reveal a critical role for cervical epithelium in initiating early mucosal responses to vaginal infection, highlight an important role for macrophages in target cell recruitment, and provide further evidence of a paradoxical dampening effect of a protective vaccine on these early mucosal responses.

  6. Weak Evidence of Regeneration Habitat but Strong Evidence of Regeneration Niche for a Leguminous Shrub

    PubMed Central

    Delerue, Florian; Gonzalez, Maya; Michalet, Richard; Pellerin, Sylvain; Augusto, Laurent

    2015-01-01

    The identification of an ecological niche specific to the regeneration phase has mobilised significant attention. However, the importance of the regeneration niche concept remains unclear. Our main objective was to study the existence of such a regeneration niche for a leguminous shrub, Ulex europaeus. This study was carried out in southwest France in the context of water and nutrient stresses (mainly phosphorus limitation) due to the presence of nutrient-poor sandy soils. We analysed the regeneration of the species from the germination of seeds and emergence of new seedlings until the seedlings reached young shrub size. Our design included a P fertilisation treatment. We also investigated microsite characteristics (micro-topography and vegetation development) as they can interact with meteorological conditions and determine water availability for seeds and seedlings. We found that P availability controlled seedling growth and the time necessary to reach young shrub size. Water availability appeared to impact the species germination and seedlings survival. We also found that P and water availability depended on the interactions between microsite characteristics and climatic variations. Finally we found evidence that P and water availability are important ecological factors shaping the regeneration niche of the species, but we found weak evidence that any microsite would be appropriate for the regeneration of the species in the long term. Future studies regarding regeneration niches need to distinguish more clearly the ecological factors important for regeneration (the regeneration niche per se) and the physical world where the seedlings appear and develop (the regeneration habitat). PMID:26098877

  7. Msx2 Prevents Stratified Squamous Epithelium Formation in the Enamel Organ.

    PubMed

    Nakatomi, M; Ida-Yonemochi, H; Nakatomi, C; Saito, K; Kenmotsu, S; Maas, R L; Ohshima, H

    2018-06-01

    Tooth enamel is manufactured by the inner enamel epithelium of the multilayered enamel organ. Msx2 loss-of-function mutation in a mouse model causes an abnormal accumulation of epithelial cells in the enamel organ, but the underlying mechanism by which Msx2 regulates amelogenesis is poorly understood. We therefore performed detailed histological and molecular analyses of Msx2 null mice. Msx2 null ameloblasts and stratum intermedium (SI) cells differentiated normally in the early stages of amelogenesis. However, during subsequent developmental stages, the outer enamel epithelium (OEE) became highly proliferative and transformed into a keratinized stratified squamous epithelium that ectopically expressed stratified squamous epithelium markers, including Heat shock protein 25, Loricrin, and Keratin 10. Moreover, expression of hair follicle-specific keratin genes such as Keratin 26 and Keratin 73 was upregulated in the enamel organ of Msx2 mutants. With the accumulation of keratin in the stellate reticulum (SR) region and subsequent odontogenic cyst formation, SI cells gradually lost the ability to differentiate, and the expression of Sox2 and Notch1 was downregulated, leading to ameloblast depolarization. As a consequence, the organization of the Msx2 mutant enamel organ became disturbed and enamel failed to form in the normal location. Instead, there was ectopic mineralization that likely occurred within the SR. In summary, we show that during amelogenesis, Msx2 executes a bipartite function, repressing the transformation of OEE into a keratinized stratified squamous epithelium while simultaneously promoting the development of a properly differentiated enamel organ competent for enamel formation.

  8. Phagocytosis of Giardia muris by macrophages in Peyer's patch epithelium in mice.

    PubMed

    Owen, R L; Allen, C L; Stevens, D P

    1981-08-01

    No mechanism for the initiation of immunological clearance of Giardia from the mammalian intestinal tract has been identified. In normal and nude mice experimentally infected with G. muris, we examined antigen-sampling epithelium over Peyer's patch follicles by electron microscopy for evidence of interaction between G. muris and lymphoid cells. Invading G. muris were found in the epithelium near dying or desquamating columnar cells. Macrophages beneath the basal lamina extended pseudopods into the epithelium, trapping invading G. muris and enclosing them in phagolysosomes. In normal mice, which clear G. muris in 4 to 6 weeks, macrophages containing digested G. muris were surrounded by rosettes of lymphoblasts in the epithelium. In nude mice deficient in lymphocytes, there was apparent hyperplasia of macrophages, which filled the follicle domes, resulting in more frequent entrapment of G. muris but no contact between macrophages and lymphoblasts in the epithelium. In nude mice, which require 6 months to control G. muris infection, lymphoblast contact with macrophages containing distinctive microtubular remnants of G. muris was only identified in the follicle dome. This close physical association of lymphoblasts and macrophages containing G. muris remnants suggests that this macrophage activity represents intraepithelial antigen processing as well as a defense against the effects of the uncontrolled entrance of microorganisms and other antigenic particles into Peyer's patch lymphoid follicles.

  9. Morphological alterations of periodontal pocket epithelium following Nd:YAG laser irradiation.

    PubMed

    Ting, Chun-Chan; Fukuda, Mitsuo; Watanabe, Tomohisa; Sanaoka, Atsushi; Mitani, Akio; Noguchi, Toshihide

    2014-12-01

    The purpose of this in vivo study was to examine morphologic alterations in the periodontal pocket epithelium with presence or absence of clinical inflammation following the use of the Neodymium: Yttrium-Aluminum-Garnet (Nd:YAG) laser irradiation. Subgingival Nd:YAG laser irradiation has been proposed as an alternative technique for treatment of chronic periodontitis. Several published studies have reported the clinical outcomes of such treatment. Twenty patients, diagnosed with moderate chronic periodontitis, were selected for the study. A total of 32 sites was identified and divided into a control (n=18) and laser-treated test groups (n=14). Probing depth (PD) and bleeding on probing (BOP) were recorded for all sites. Test sites were irradiated with an Nd:YAG laser using parameters of 2 W, 200 mJ pulse energy, and 10 pps delivered through a 320 μm diameter tip. Total laser treatment time ranged from 1 to 2 min. Following treatment, all specimens were harvested via biopsy and processed for scanning electron microscopy (SEM) and histologic examination. Control group specimens, depending upon initial PD, exhibited either a relatively smooth and intact epithelium with little desquamation (PD≤3 mm), or increasing degrees of epithelial desquamation and leukocytic infiltration at a PD of ≥4 mm. In the laser-treated test group, the specimens with PD≤3 mm that were BOP negative (-) exhibited a thin layer of epithelium that was disrupted. In the specimens with initial PD of ≥4 mm, complete removal of the epithelium whose extent and degree were increasing, was observed in the inflamed portion, while epithelium remained in the uninflamed portion. The SEM and histologic findings demonstrated the feasibility of ablating pocket epithelium with an Nd:YAG laser irradiation using parameters of 2 W of power (200 mJ, 10 pps). Furthermore, the presence or absence of clinical inflammation appeared to have an impact on the degree of laser

  10. Biomaterial Selection for Tooth Regeneration

    PubMed Central

    Yuan, Zhenglin; Nie, Hemin; Wang, Shuang; Lee, Chang Hun; Li, Ang; Fu, Susan Y.; Zhou, Hong

    2011-01-01

    Biomaterials are native or synthetic polymers that act as carriers for drug delivery or scaffolds for tissue regeneration. When implanted in vivo, biomaterials should be nontoxic and exert intended functions. For tooth regeneration, biomaterials have primarily served as a scaffold for (1) transplanted stem cells and/or (2) recruitment of endogenous stem cells. This article critically synthesizes our knowledge of biomaterial use in tooth regeneration, including the selection of native and/or synthetic polymers, three-dimensional scaffold fabrication, stem cell transplantation, and stem cell homing. A tooth is a complex biological organ. Tooth loss represents the most common organ failure. Tooth regeneration encompasses not only regrowth of an entire tooth as an organ, but also biological restoration of individual components of the tooth including enamel, dentin, cementum, or dental pulp. Regeneration of tooth root represents perhaps more near-term opportunities than the regeneration of the whole tooth. In the adult, a tooth owes its biological vitality, arguably more, to the root than the crown. Biomaterials are indispensible for the regeneration of tooth root, tooth crown, dental pulp, or an entire tooth. PMID:21699433

  11. Transmigration of macrophages across the choroid plexus epithelium in response to the feline immunodeficiency virus

    PubMed Central

    Meeker, Rick B.; Bragg, D. C.; Poulton, Winona; Hudson, Lola

    2013-01-01

    Although lentiviruses such as human, feline and simian immunodeficiency viruses (HIV, FIV, SIV) rapidly gain access to cerebrospinal fluid (CSF), the mechanisms that control this entry are not well understood. One possibility is that the virus may be carried into the brain by immune cells that traffic across the blood–CSF barrier in the choroid plexus. Since few studies have directly examined macrophage trafficking across the blood–CSF barrier, we established transwell and explant cultures of feline choroid plexus epithelium and measured trafficking in the presence or absence of FIV. Macrophages in co-culture with the epithelium showed significant proliferation and robust trafficking that was dependent on the presence of epithelium. Macrophage migration to the apical surface of the epithelium was particularly robust in the choroid plexus explants where 3-fold increases were seen over the first 24 h. Addition of FIV to the cultures greatly increased the number of surface macrophages without influencing replication. The epithelium in the transwell cultures was also permissive to PBMC trafficking, which increased from 17 to 26% of total cells after exposure to FIV. Thus, the choroid plexus epithelium supports trafficking of both macrophages and PBMCs. FIV significantly enhanced translocation of macrophages and T cells indicating that the choroid plexus epithelium is likely to be an active site of immune cell trafficking in response to infection. PMID:22281685

  12. Sox9 regulates cell proliferation and is required for Paneth cell differentiation in the intestinal epithelium

    PubMed Central

    Bastide, Pauline; Darido, Charbel; Pannequin, Julie; Kist, Ralf; Robine, Sylvie; Marty-Double, Christiane; Bibeau, Frédéric; Scherer, Gerd; Joubert, Dominique; Hollande, Frédéric; Blache, Philippe; Jay, Philippe

    2007-01-01

    The HMG-box transcription factor Sox9 is expressed in the intestinal epithelium, specifically, in stem/progenitor cells and in Paneth cells. Sox9 expression requires an active β-catenin–Tcf complex, the transcriptional effector of the Wnt pathway. This pathway is critical for numerous aspects of the intestinal epithelium physiopathology, but processes that specify the cell response to such multipotential signals still remain to be identified. We inactivated the Sox9 gene in the intestinal epithelium to analyze its physiological function. Sox9 inactivation affected differentiation throughout the intestinal epithelium, with a disappearance of Paneth cells and a decrease of the goblet cell lineage. Additionally, the morphology of the colon epithelium was severely altered. We detected general hyperplasia and local crypt dysplasia in the intestine, and Wnt pathway target genes were up-regulated. These results highlight the central position of Sox9 as both a transcriptional target and a regulator of the Wnt pathway in the regulation of intestinal epithelium homeostasis. PMID:17698607

  13. Macrophage depletion impairs skeletal muscle regeneration: The roles of regulatory factors for muscle regeneration.

    PubMed

    Liu, Xiaoguang; Liu, Yu; Zhao, Linlin; Zeng, Zhigang; Xiao, Weihua; Chen, Peijie

    2017-03-01

    Though macrophages are essential for skeletal muscle regeneration, which is a complex process, the roles and mechanisms of the macrophages in the process of muscle regeneration are still not fully understood. The objective of this study is to explore the roles of macrophages and the mechanisms involved in the regeneration of injured skeletal muscle. One hundred and twelve C57BL/6 mice were randomly divided into muscle contusion and macrophages depleted groups. Their gastrocnemius muscles were harvested at the time points of 12 h, 1, 3, 5, 7, 14 d post-injury. The changes in skeletal muscle morphology were assessed by hematoxylin and eosin (HE) stain. The gene expression was analyzed by real-time polymerase chain reaction. The data showed that CL-liposomes treatment did affect the expression of myogenic regulatory factors (MyoD, myogenin) after injury. In addition, CL-liposomes treatment decreased the expression of regulatory factors of muscle regeneration (HGF, uPA, COX-2, IGF-1, MGF, FGF6) and increased the expression of inflammatory cytokines (TGF-β1, TNF-α, IL-1β, RANTES) in the late stage of regeneration. Moreover, there were significant correlations between macrophages and some regulatory factors (such as HGF, uPA) for muscle regeneration. These results suggested that macrophages depletion impairs skeletal muscle regeneration and that the regulatory factors for muscle regeneration may play important roles in this process. © 2017 International Federation for Cell Biology.

  14. Bacteriome and mycobiome associations in oral tongue cancer.

    PubMed

    Mukherjee, Pranab K; Wang, Hannah; Retuerto, Mauricio; Zhang, Huan; Burkey, Brian; Ghannoum, Mahmoud A; Eng, Charis

    2017-11-14

    Squamous cell carcinoma of the oral (mobile) tongue (OMTC), a non-human papilloma virus-associated oral cancer, is rapidly increasing without clear etiology. Poor oral hygiene has been associated with oral cancers, suggesting that oral bacteriome (bacterial community) and mycobiome (fungal community) could play a role. While the bacteriome is increasingly recognized as an active participant in health, the role of the mycobiome has not been studied in OMTC. Tissue DNA was extracted from 39 paired tumor and adjacent normal tissues from patients with OMTC. Microbiome profiling, principal coordinate, and dissimilarity index analyses showed bacterial diversity and richness, and fungal richness, were significantly reduced in tumor tissue (TT) compared to their matched non-tumor tissues (NTT, P <0.006). Firmicutes was the most abundant bacterial phylum, which was significantly increased in TT compared to NTT (48% vs. 40%, respectively; P =0.004). Abundance of Bacteroidetes and Fusobacteria were significantly decreased in TT compared to matched NTT ( P ≤0.003 for both). Abundance of 22 bacterial and 7 fungal genera was significantly different between the TT and NTT, including Streptococcus , which was the most abundant and significantly increased in the tumor group (34% vs. 22%, P <0.001). Abundance of fungal genus Aspergillus in TT correlated negatively with bacteria ( Actinomyces, Prevotella , Streptococcus) , but positively with Aggregatibacter . Patients with high T-stage disease had lower mean differences between TT and NTT compared with patients with low T-stage disease (0.07 vs. 0.21, P =0.04). Our results demonstrate differences in bacteriome and mycobiome between OMTC and their matched normal oral epithelium, and their association with T-stage.

  15. Polymeric nanocarriers for transport modulation across the pulmonary epithelium: dendrimers, polymeric nanoparticles, and their nanoblends.

    PubMed

    Bharatwaj, Balaji; Dimovski, Radovan; Conti, Denise S; da Rocha, Sandro R P

    2014-05-01

    The purpose of this study was to (a) Determine the cellular transport and uptake of amine-terminated generation 3 (G3) poly(amido amine) (PAMAM) dendrimers across an in vitro model of the pulmonary epithelium, and the ability to modulate their transport by forming nanoblends of the dendrimers with biodegradable solid polymeric nanoparticles (NPs) and (b) to formulate dendrimer nanocarriers in portable oral inhalation devices and evaluate their aerosol characteristics. To that end, fluorescein isothiocyanate (FITC)-labeled G3 PAMAM dendrimer nanocarriers (DNCs) were synthesized, and also encapsulated within poly lactide-co-glycolide nanoparticles (NPs). Transport and uptake of both DNCs encapsulated within NPs (nanoblends) and unencapsulated DNCs were tracked across polarized monolayers of airway epithelial cells, Calu-3. DNCs were also formulated as core-shell microparticles in pressurized metered-dose inhalers (pMDIs) and their aerodynamic properties evaluated by Andersen cascade impaction. The apparent permeability of DNCs across the airway epithelial model was similar to that of a paracellular marker of comparable molar mass--order of 10(-7) cm s(-1). The transport and cellular internalization of the DNCs can be modulated by formulating them as nanoblends. The transport of the DNCs across the lung epithelium was completely suppressed within the time of the experiment (5 h) when formulated as blends. The encapsulation also prevents saturation of the cellular internalization profile. Nanoblending may be a potential strategy to modulate the rate of transport and cellular uptake of DNCs, and thus be used as a design strategy to achieve enhanced local or systemic drug delivery.

  16. Nanocomposites for bone tissue regeneration.

    PubMed

    Sahoo, Nanda Gopal; Pan, Yong Zheng; Li, Lin; He, Chao Bin

    2013-04-01

    Natural bone tissue possesses a nanocomposite structure that provides appropriate physical and biological properties. For bone tissue regeneration, it is crucial for the biomaterial to mimic living bone tissue. Since no single type of material is able to mimic the composition, structure and properties of native bone, nanocomposites are the best choice for bone tissue regeneration as they can provide the appropriate matrix environment, integrate desirable biological properties, and provide controlled, sequential delivery of multiple growth factors for the different stages of bone tissue regeneration. This article reviews the composition, structure and properties of advanced nanocomposites for bone tissue regeneration. It covers aspects of interest such as the biomimetic synthesis of bone-like nanocomposites, guided bone regeneration from inert biomaterials and bioactive nanocomposites, and nanocomposite scaffolds for bone tissue regeneration. The design, fabrication, and in vitro and in vivo characterization of such nanocomposites are reviewed.

  17. Topical administration of orbital fat-derived stem cells promotes corneal tissue regeneration.

    PubMed

    Lin, Ko-Jo; Loi, Mei-Xue; Lien, Gi-Shih; Cheng, Chieh-Feng; Pao, Hsiang-Yin; Chang, Yun-Chuang; Ji, Andrea Tung-Qian; Ho, Jennifer Hui-Chun

    2013-06-14

    topical administration of OFSCs was superior to that of the IL injection. OFSCs from the IL injection clustered in the limbal area and central corneal epithelium, which was associated with a persistent corneal haze. Topical OFSC administration is a simple, non-surgical route for stem cell delivery to promote corneal tissue regeneration through ameliorating acute inflammation and corneal epithelial differentiation. The limbal area serves as a niche for OFSCs differentiating into corneal epithelial cells in the first week, while the stroma is a potential site for anti-inflammation of OFSCs. Inhibition of corneal inflammation is related to corneal transparency.

  18. Topical administration of orbital fat-derived stem cells promotes corneal tissue regeneration

    PubMed Central

    2013-01-01

    therapeutic effect of the topical administration of OFSCs was superior to that of the IL injection. OFSCs from the IL injection clustered in the limbal area and central corneal epithelium, which was associated with a persistent corneal haze. Conclusions Topical OFSC administration is a simple, non-surgical route for stem cell delivery to promote corneal tissue regeneration through ameliorating acute inflammation and corneal epithelial differentiation. The limbal area serves as a niche for OFSCs differentiating into corneal epithelial cells in the first week, while the stroma is a potential site for anti-inflammation of OFSCs. Inhibition of corneal inflammation is related to corneal transparency. PMID:23769140

  19. mTOR signaling promotes stem cell activation via counterbalancing BMP-mediated suppression during hair regeneration.

    PubMed

    Deng, Zhili; Lei, Xiaohua; Zhang, Xudong; Zhang, Huishan; Liu, Shuang; Chen, Qi; Hu, Huimin; Wang, Xinyue; Ning, Lina; Cao, Yujing; Zhao, Tongbiao; Zhou, Jiaxi; Chen, Ting; Duan, Enkui

    2015-02-01

    Hair follicles (HFs) undergo cycles of degeneration (catagen), rest (telogen), and regeneration (anagen) phases. Anagen begins when the hair follicle stem cells (HFSCs) obtain sufficient activation cues to overcome suppressive signals, mainly the BMP pathway, from their niche cells. Here, we unveil that mTOR complex 1 (mTORC1) signaling is activated in HFSCs, which coincides with the HFSC activation at the telogen-to-anagen transition. By using both an inducible conditional gene targeting strategy and a pharmacological inhibition method to ablate or inhibit mTOR signaling in adult skin epithelium before anagen initiation, we demonstrate that HFs that cannot respond to mTOR signaling display significantly delayed HFSC activation and extended telogen. Unexpectedly, BMP signaling activity is dramatically prolonged in mTOR signaling-deficient HFs. Through both gain- and loss-of-function studies in vitro, we show that mTORC1 signaling negatively affects BMP signaling, which serves as a main mechanism whereby mTORC1 signaling facilitates HFSC activation. Indeed, in vivo suppression of BMP by its antagonist Noggin rescues the HFSC activation defect in mTORC1-null skin. Our findings reveal a critical role for mTOR signaling in regulating stem cell activation through counterbalancing BMP-mediated repression during hair regeneration. © The Author (2015). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.

  20. Cellular internalization and transport of biodegradable polyester dendrimers on a model of the pulmonary epithelium and their formulation in pressurized metered-dose inhalers.

    PubMed

    Heyder, Rodrigo S; Zhong, Qian; Bazito, Reinaldo C; da Rocha, Sandro R P

    2017-03-30

    The purpose of this study was to evaluate the effect of generation and surface PEGylation of degradable polyester-based dendrimers nanocarriers on their interactions with an in vitro model of the pulmonary epithelium as well as to assess the ability to formulate such carriers in propellant-based, portable oral-inhalation devices to determine their potential for local and systemic delivery of drugs to and through the lungs. Hydroxyl (-OH) terminated polyester dendrimers of generation 3 and 4 (G3, and G4) were synthesized using a divergent approach. G4 was surface-modified with PEG (1,000Da). All dendrimers and their building blocks were determined to be highly compatible with the model pulmonary epithelium, with toxicity profiles much more favorable than non-degradable polyamidoamine dendrimers (PAMAM). The transport of the species from the apical to basolateral side across polarized Calu-3 monolayers showed to be generation and surface-chemistry (PEGylation) dependent. The extent of the transport is modulated by their interaction with the polarized epithelium and their transient opening of the tight junctions. G3 was the one most efficiently internalized by the epithelium, and had a small impact on the integrity of the monolayer. On the other hand, the PEGylated G4 was the one least internalized by the polarized epithelium, and at the same time had a more pronounced transient impact on the cellular junctions, resulting in more efficient transport across the cell monolayer. PEGylation of the dendrimer surface played other roles as well. PEGylation modulated the degradation profile of the dendrimer, slowing the process in a step-wise fashion - first the PEG layer is shed and then the dendrimer starts degrading. PEGylation also helped increase the solvation of the nanocarriers by the hydrofluoroalkane propellant used in pressurized metered-dose inhalers, resulting in formulations with excellent dispersibility and aerosol quality (deep lung deposition of 88

  1. Progress of Oral Insulin and Related Drug Delivery Systems and their Pharmacokinetics.

    PubMed

    Chen, Jingjing; Liu, Rui; Liu, Changxiao; Jin, Xin; Zhang, Qinghua; Wang, Jialu; Zhao, Fang; Wang, Ze; Qiu, Haiyan; Li, Yazhuo; Yi, Xiulin

    2018-05-22

    As society has developed and living standards have improved, diabetes has become a severe public health issue. Insulin plays a crucial role in managing hyperglycemia caused by type I diabetes and particular type II diabetes. Many researchers are seeking alternative, more acceptable methods of insulin delivery, such as oral insulin. An oral formulation has become a new goal for insulin delivery in recent years. The PubMed and CNKI databases were searched for "oral insulin, " "drug delivery systems, " and "pharmacokinetics, " and 85 relevant articles were selected from the results as material for this review. These papers were authoritative and had a higher number of citations. Oral insulin would be highly advantageous but is poorly absorbed. The main reason for low absorptivity is the hydrolysis of insulin by enzymes in the gastrointestinal tract. Lack of active transport vectors that pass through the intestinal epithelium is also a non-negligible problem. Additional issues need to be considered to facilitate appropriate research, such as long-term efficacy and safety, clinical data, and toxicological characteristics. This review summarized recent advances in oral insulin and the pharmacokinetic profile of the suitable delivery system, providing valuable reference material for future research. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. Neural crest contribution to lingual mesenchyme, epithelium and developing taste papillae and taste buds

    PubMed Central

    Liu, Hong-Xiang; Komatsu, Yoshihiro; Mishina, Yuji; Mistretta, Charlotte M.

    2012-01-01

    The epithelium of mammalian tongue hosts most of the taste buds that transduce gustatory stimuli into neural signals. In the field of taste biology, taste bud cells have been described as arising from “local epithelium”, in distinction from many other receptor organs that are derived from neurogenic ectoderm including neural crest (NC). In fact, contribution of NC to both epithelium and mesenchyme in the developing tongue is not fully understood. In the present study we used two independent, well-characterized mouse lines, Wnt1-Cre and P0-Cre that express Cre recombinase in a NC-specific manner, in combination with two Cre reporter mouse lines, R26R and ZEG, and demonstrate a contribution of NC-derived cells to both tongue mesenchyme and epithelium including taste papillae and taste buds. In tongue mesenchyme, distribution of NC-derived cells is in close association with taste papillae. In tongue epithelium, labeled cells are observed in an initial scattered distribution and progress to a clustered pattern between papillae, and within papillae and early taste buds. This provides evidence for a contribution of NC to lingual epithelium. Together with previous reports for the origin of taste bud cells from local epithelium in postnatal mouse, we propose that NC cells migrate into and reside in the epithelium of the tongue primordium at an early embryonic stage, acquire epithelial cell phenotypes, and undergo cell proliferation and differentiation that is involved in the development of taste papillae and taste buds. Our findings lead to a new concept about derivation of taste bud cells that include a NC origin. PMID:22659543

  3. Detection of Helicobacter pylori in Oral Lesions

    PubMed Central

    Irani, Soussan; Monsef Esfahani, Alireza; Bidari Zerehpoush, Farahnaz

    2013-01-01

    Background and aims. Helicobacter pylori is a microaerophilic gram-negative spiral organism. It is recognized as the etiologic factor for peptic ulcers, gastric adenocarcinoma and gastric lymphoma. Recently, it has been isolated from dental plaque and the dorsum of the tongue. This study was designed to assess the association between H. pylori and oral lesions such as ulcerative/inflammatory lesions, squamous cell carcinoma (SCC) and primary lymphoma. Materials and methods. A total of 228 biopsies diagnosed as oral ulcerative/inflammatory lesions, oral squamous cell carcinoma (OSCC) and oral primary lymphoma were selected from the archives of the Pathology Department. Thirty-two samples that were diagnosed as being without any pathological changes were selected as the control group. All the paraffin blocks were cut for hematoxylin and eosin staining to confirm the diagnoses and then the samples were prepared for immunohistochemistry staining. Data were collected and analyzed. Results. Chi-squared test showed significant differences between the frequency of H. pylori positivity in normal tissue and the lesions were examined (P=0.000). In addition, there was a statistically significant difference between the lesions examined (P=0.042). Chi-squared test showed significant differences between H. pylori positivity and different tissue types except inside the muscle layer as follows: in epithelium and in lamina propria (P=0.000), inside the blood vessels (P=0.003), inside the salivary gland duct (P=0.036), and muscle layer (P=0.122). Conclusion. There might be a relation between the presence of H. pylori and oral lesions. Therefore, early detection and eradication of H. pylori in high-risk patients are suggested. PMID:24578822

  4. Conditional Ablation of Retinol Dehydrogenase 10 in the Retinal Pigmented Epithelium Causes Delayed Dark Adaption in Mice*

    PubMed Central

    Sahu, Bhubanananda; Sun, Wenyu; Perusek, Lindsay; Parmar, Vipulkumar; Le, Yun-Zheng; Griswold, Michael D.; Palczewski, Krzysztof; Maeda, Akiko

    2015-01-01

    Regeneration of the visual chromophore, 11-cis-retinal, is a crucial step in the visual cycle required to sustain vision. This cycle consists of sequential biochemical reactions that occur in photoreceptor cells and the retinal pigmented epithelium (RPE). Oxidation of 11-cis-retinol to 11-cis-retinal is accomplished by a family of enzymes termed 11-cis-retinol dehydrogenases, including RDH5 and RDH11. Double deletion of Rdh5 and Rdh11 does not limit the production of 11-cis-retinal in mice. Here we describe a third retinol dehydrogenase in the RPE, RDH10, which can produce 11-cis-retinal. Mice with a conditional knock-out of Rdh10 in RPE cells (Rdh10 cKO) displayed delayed 11-cis-retinal regeneration and dark adaption after bright light illumination. Retinal function measured by electroretinogram after light exposure was also delayed in Rdh10 cKO mice as compared with controls. Double deletion of Rdh5 and Rdh10 (cDKO) in mice caused elevated 11/13-cis-retinyl ester content also seen in Rdh5−/−Rdh11−/− mice as compared with Rdh5−/− mice. Normal retinal morphology was observed in 6-month-old Rdh10 cKO and cDKO mice, suggesting that loss of Rdh10 in the RPE does not negatively affect the health of the retina. Compensatory expression of other retinol dehydrogenases was observed in both Rdh5−/− and Rdh10 cKO mice. These results indicate that RDH10 acts in cooperation with other RDH isoforms to produce the 11-cis-retinal chromophore needed for vision. PMID:26391396

  5. Automated selection of the most epithelium-rich areas in gynecologic tumor sections.

    PubMed

    Schipper, N W; Baak, J P; Smeulders, A W

    1991-12-01

    The paper describes an image analysis technique for automated selection of the epithelium-rich areas in standard paraffin tissue sections of ovarian and endometrial premalignancies and malignancies. Two staining procedures were evaluated, Feulgen (pararosanilin) and CAM 5.2, demonstrating the presence of cytokeratin 8 and 18; both were counterstained with naphthol yellow. The technique is based on the corresponding image processing method of automated estimation of the percentage of epithelium in interactively selected microscope fields. With the technique, one image is recorded with a filter to demonstrate where epithelium and stroma lie. This filter is chosen according to the type of staining: it is yellow (lambda = 552 nm) for Feulgen and blue (lambda = 470 nm) for anticytokeratin CAM 5.2. When stroma cannot be distinguished from lumina with the green filter or from epithelium with the blue filter, a second image is recorded from the same microscope field, with a blue filter (lambda = 420 nm) for Feulgen and a yellow filter (lambda = 576 nm) for anticytokeratin CAM 5.2. Discrimination between epithelium and stroma is based on the image contrast range and the packing of nuclei in the yellow image and on the automated classification of the gray value histogram peaks in the blue image. For Feulgen stain the method was evaluated on 30 ovarian tumors of the common epithelial types (8 borderline tumors and 22 carcinomas with various degrees of differentiation) and 30 endometrial carcinomas of different grades.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. The oral and craniofacial relevance of chemically modified RNA therapeutics.

    PubMed

    Elangovan, Satheesh; Kormann, Michael S D; Khorsand, Behnoush; Salem, Aliasger K

    2016-01-01

    Several tissue engineering strategies in the form of protein therapy, gene therapy, cell therapy, and their combinations are currently being explored for oral and craniofacial regeneration and repair. Though each of these approaches has advantages, they all have common inherent drawbacks of being expensive and raising safety concerns. Using RNA (encoding therapeutic protein) has several advantages that have the potential to overcome these limitations. Chemically modifying the RNA improves its stability and mitigates immunogenicity allowing for the potential of RNA to become an alternative to protein and gene based therapies. This brief review article focuses on the potential of RNA therapeutics in the treatment of disorders in the oral and craniofacial regions.

  7. The Oral and Craniofacial Relevance of Chemically Modified RNA Therapeutics

    PubMed Central

    Kormann, Michael S.D.; Khorsand, Behnoush

    2016-01-01

    Several tissue engineering strategies in the form of protein therapy, gene therapy, cell therapy and its combinations are currently being explored for oral and cranio-facial regeneration and repair. Though each of these approaches has advantages, they all have common inherent drawbacks of being expensive and raising safety concerns. Using RNA (encoding therapeutic protein) has several advantages that have the potential to overcome these limitations. Chemically modifying the RNA improves its stability and mitigates immunogenicity allowing for the potential of RNA to become an alternative to protein and gene based therapies. This brief review article focuses on the potential of RNA therapeutics in the treatment of disorders in the oral and craniofacial regions. PMID:26896600

  8. Proteomic profiling of fetal esophageal epithelium, esophageal cancer, and tumor-adjacent esophageal epithelium and immunohistochemical characterization of a representative differential protein, PRX6

    PubMed Central

    Guo, Jun-Hui; Xing, Guo-Lan; Fang, Xin-Hui; Wu, Hui-Fang; Zhang, Bo; Yu, Jin-Zhong; Fan, Zong-Min; Wang, Li-Dong

    2017-01-01

    AIM To understand the molecular mechanism of esophageal cancer development and provide molecular markers for screening high-risk populations and early diagnosis. METHODS Two-dimensional electrophoresis combined with mass spectrometry were adopted to screen differentially expressed proteins in nine cases of fetal esophageal epithelium, eight cases of esophageal cancer, and eight cases of tumor-adjacent normal esophageal epithelium collected from fetuses of different gestational age, or esophageal cancer patients from a high-risk area of esophageal cancer in China. Immunohistochemistry (avidin-biotin-horseradish peroxidase complex method) was used to detect the expression of peroxiredoxin (PRX)6 in 91 cases of esophageal cancer, tumor-adjacent normal esophageal tissue, basal cell hyperplasia, dysplasia, and carcinoma in situ, as well as 65 cases of esophageal epithelium from fetuses at a gestational age of 3-9 mo. RESULTS After peptide mass fingerprint analysis and search of protein databases, 21 differential proteins were identified; some of which represent a protein isoform. Varying degrees of expression of PRX6 protein, which was localized mainly in the cytoplasm, were detected in adult and fetal normal esophageal tissues, precancerous lesions, and esophageal cancer. With the progression of esophageal lesions, PRX6 protein expression showed a declining trend (P < 0.05). In fetal epithelium from fetuses at gestational age 3-6 mo, PRX6 protein expression showed a declining trend with age (P < 0.05). PRX6 protein expression was significantly higher in well-differentiated esophageal cancer tissues than in poorly differentiated esophageal cancer tissues (P < 0.05). CONCLUSION Development and progression of esophageal cancer result from interactions of genetic changes (accumulation or superposition). PRX6 protein is associated with fetal esophageal development and cancer differentiation. PMID:28293090

  9. Proteomic profiling of fetal esophageal epithelium, esophageal cancer, and tumor-adjacent esophageal epithelium and immunohistochemical characterization of a representative differential protein, PRX6.

    PubMed

    Guo, Jun-Hui; Xing, Guo-Lan; Fang, Xin-Hui; Wu, Hui-Fang; Zhang, Bo; Yu, Jin-Zhong; Fan, Zong-Min; Wang, Li-Dong

    2017-02-28

    To understand the molecular mechanism of esophageal cancer development and provide molecular markers for screening high-risk populations and early diagnosis. Two-dimensional electrophoresis combined with mass spectrometry were adopted to screen differentially expressed proteins in nine cases of fetal esophageal epithelium, eight cases of esophageal cancer, and eight cases of tumor-adjacent normal esophageal epithelium collected from fetuses of different gestational age, or esophageal cancer patients from a high-risk area of esophageal cancer in China. Immunohistochemistry (avidin-biotin-horseradish peroxidase complex method) was used to detect the expression of peroxiredoxin (PRX)6 in 91 cases of esophageal cancer, tumor-adjacent normal esophageal tissue, basal cell hyperplasia, dysplasia, and carcinoma in situ , as well as 65 cases of esophageal epithelium from fetuses at a gestational age of 3-9 mo. After peptide mass fingerprint analysis and search of protein databases, 21 differential proteins were identified; some of which represent a protein isoform. Varying degrees of expression of PRX6 protein, which was localized mainly in the cytoplasm, were detected in adult and fetal normal esophageal tissues, precancerous lesions, and esophageal cancer. With the progression of esophageal lesions, PRX6 protein expression showed a declining trend ( P < 0.05). In fetal epithelium from fetuses at gestational age 3-6 mo, PRX6 protein expression showed a declining trend with age ( P < 0.05). PRX6 protein expression was significantly higher in well-differentiated esophageal cancer tissues than in poorly differentiated esophageal cancer tissues ( P < 0.05). Development and progression of esophageal cancer result from interactions of genetic changes (accumulation or superposition). PRX6 protein is associated with fetal esophageal development and cancer differentiation.

  10. Chemical genetics and regeneration.

    PubMed

    Sengupta, Sumitra; Zhang, Liyun; Mumm, Jeff S

    2015-01-01

    Regeneration involves interactions between multiple signaling pathways acting in a spatially and temporally complex manner. As signaling pathways are highly conserved, understanding how regeneration is controlled in animal models exhibiting robust regenerative capacities should aid efforts to stimulate repair in humans. One way to discover molecular regulators of regeneration is to alter gene/protein function and quantify effect(s) on the regenerative process: dedifferentiation/reprograming, stem/progenitor proliferation, migration/remodeling, progenitor cell differentiation and resolution. A powerful approach for applying this strategy to regenerative biology is chemical genetics, the use of small-molecule modulators of specific targets or signaling pathways. Here, we review advances that have been made using chemical genetics for hypothesis-focused and discovery-driven studies aimed at furthering understanding of how regeneration is controlled.

  11. Potential, Current, and Ionic Fluxes across the Isolated Retinal Pigment Epithelium and Choroid

    PubMed Central

    Lasansky, Arnaldo; de Fisch, Felisa W.

    1966-01-01

    A flux chamber was utilized for in vitro studies of a membrane formed by the retinal pigment epithelium and choroid of the eye of the toad (Bufo arenarum and Bufo marinus). A transmembrane potential of 20 to 30 mv was found, the pigment epithelium surface positive with respect to the choroidal surface. Unidirectional fluxes of chloride, sodium, potassium, and calcium were determined in the absence of an electrochemical potential difference. A net transfer of chloride from pigment epithelium to choroid accounted for a major fraction of the mean short-circuit current. A small net flux of sodium from choroid to pigment epithelium was detected in Bufo marinus. In both species of toads, however, about one-third of the mean short-circuit current remained unaccounted for. Manometric determinations of bicarbonate suggested an uptake of this ion at the epithelial surface of the membrane but did not provide evidence of a relationship between this process and the short-circuit current. PMID:5961357

  12. Ion transport by primary cultures of canine tracheal epithelium: methodology, morphology, and electrophysiology.

    PubMed

    Welsh, M J

    1985-01-01

    Canine tracheal epithelial cells were isolated by enzymatic and mechanical dispersion and cultured on permeable supports. The cells formed confluent monolayers and retained most of the morphologic characteristics of the intact epithelium, including apical microvilli, apical tight junctions, and a moderately interdigitated lateral intercellular space. The cells also retained the functional properties of the epithelium. The monolayer responded to addition of isoproterenol with the characteristic changes in cellular electrical properties expected for stimulation of C1 secretion: isoproterenol increased transepithelial voltage, depolarized apical membrane voltage, and decreased both transepithelial resistance and the ratio of apical-to-basolateral membrane resistance. Examination of the cellular response to ion substitutions and inhibitors of C1 secretion indicate that the cultured monolayers retain the same cellular mechanisms of ion transport as the intact epithelium. Thus, primary cultures of tracheal epithelium may provide a useful preparation for future studies of the mechanism and regulation of C1 secretion by airway epithelia.

  13. Differential transmission of the molecular signature of RBSP3, LIMD1 and CDC25A in basal/ parabasal versus spinous of normal epithelium during head and neck tumorigenesis: A mechanistic study.

    PubMed

    Sarkar, Shreya; Alam, Neyaz; Mandal, Syam Sundar; Chatterjee, Kabita; Ghosh, Supratim; Roychoudhury, Susanta; Panda, Chinmay Kumar

    2018-01-01

    Head and neck squamous cell carcinoma (HNSCC) is a global disease and mortality burden, necessitating the elucidation of its molecular progression for effective disease management. The study aims to understand the molecular profile of three candidate cell cycle regulatory genes, RBSP3, LIMD1 and CDC25A in the basal/ parabasal versus spinous layer of normal oral epithelium and during head and neck tumorigenesis. Immunohistochemical expression and promoter methylation was used to determine the molecular signature in normal oral epithelium. The mechanism of alteration transmission of this profile during tumorigenesis was then explored through additional deletion and mutation in HPV/ tobacco etiological groups, followed byclinico-pathological correlation. In basal/parabasal layer, the molecular signature of the genes was low protein expression/ high promoter methylation of RBSP3, high expression/ low methylation of LIMD1 and high expression of CDC25A. Dysplastic epithelium maintained the signature of RBSP3 through high methylation/ additional deletion with loss of the signatures of LIMD1 and CDC25A via deletion/ additional methylation. Similarly, maintenance and / or loss of signature in invasive tumors was by recurrent deletion/ methylation. Thus, differential patterns of alteration of the genes might be pre-requisite for the development of dysplastic and invasive lesions. Etiological factors played a key role in promoting genetic alterations and determining prognosis. Tobacco negative HNSCC patients had significantly lower alterations of LIMD1 and CDC25A, along with better survival among tobacco negative/ HPV positive patients. Our data suggests the necessity for perturbation of normal molecular profile of RBSP3, LIMD1 and CDC25A in conjunction with etiological factors for head and neck tumorigenesis, implying their diagnostic and prognostic significance.

  14. Tbx1 regulates oral epithelial adhesion and palatal development

    PubMed Central

    Funato, Noriko; Nakamura, Masataka; Richardson, James A.; Srivastava, Deepak; Yanagisawa, Hiromi

    2012-01-01

    Cleft palate, the most frequent congenital craniofacial birth defect, is a multifactorial condition induced by the interaction of genetic and environmental factors. In addition to complete cleft palate, a large number of human cases involve soft palate cleft and submucosal cleft palate. However, the etiology of these forms of cleft palate has not been well understood. T-box transcriptional factor (Tbx) family of transcriptional factors has distinct roles in a wide range of embryonic differentiation or response pathways. Here, we show that genetic disruption of Tbx1, a major candidate gene for the human congenital disorder 22q11.2 deletion syndrome (Velo-cardio-facial/DiGeorge syndrome), led to abnormal epithelial adhesion between the palate and mandible in mouse, resulting in various forms of cleft palate similar to human conditions. We found that hyperproliferative epithelium failed to undergo complete differentiation in Tbx1-null mice (Tbx1−/−). Inactivation of Tbx1 specifically in the keratinocyte lineage (Tbx1KCKO) resulted in an incomplete cleft palate confined to the anterior region of the palate. Interestingly, Tbx1 overexpression resulted in decreased cell growth and promoted cell-cycle arrest in MCF7 epithelial cells. These findings suggest that Tbx1 regulates the balance between proliferation and differentiation of keratinocytes and is essential for palatal fusion and oral mucosal differentiation. The impaired adhesion separation of the oral epithelium together with compromised palatal mesenchymal growth is an underlying cause for various forms of cleft palate phenotypes in Tbx1−/− mice. Our present study reveals new pathogenesis of incomplete and submucous cleft palate during mammalian palatogenesis. PMID:22371266

  15. Macrophages are required for dendritic cell uptake of respiratory syncytial virus from an infected epithelium.

    PubMed

    Ugonna, Kelechi; Bingle, Colin D; Plant, Karen; Wilson, Kirsty; Everard, Mark L

    2014-01-01

    We have previously shown that the respiratory syncytial virus [RSV] can productively infect monocyte derived dendritic cells [MoDC] and remain dormant within the same cells for prolonged periods. It is therefore possible that infected dendritic cells act as a reservoir within the airways of individuals between annual epidemics. In the present study we explored the possibility that sub-epithelial DCs can be infected with RSV from differentiated bronchial epithelium and that in turn RSV from DCs can infect the epithelium. A dual co-culture model was established in which a differentiated primary airway epithelium on an Air Liquid Interface (ALI) was cultured on a transwell insert and MoDCs were subsequently added to the basolateral membrane of the insert. Further experiments were undertaken using a triple co-culture model in which in which macrophages were added to the apical surface of the differentiated epithelium. A modified RSV [rr-RSV] expressing a red fluorescent protein marker of replication was used to infect either the MoDCs or the differentiated epithelium and infection of the reciprocal cell type was assessed using confocal microscopy. Our data shows that primary epithelium became infected when rr-RSV infected MoDCs were introduced onto the basal surface of the transwell insert. MoDCs located beneath the epithelium did not become infected with virus from infected epithelial cells in the dual co-culture model. However when macrophages were present on the apical surface of the primary epithelium infection of the basal MoDCs occurred. Our data suggests that RSV infected dendritic cells readily transmit infection to epithelial cells even when they are located beneath the basal layer. However macrophages appear to be necessary for the transmission of infection from epithelial cells to basal dendritic cells.

  16. Clinicopathologic assessment of Candida colonization of oral leukoplakia.

    PubMed

    Sarkar, Reena; Rathod, G P

    2014-01-01

    Leukoplakia is the most common premalignant lesion of the oral mucosa. We studied the colonization of Candida in oral leukoplakia using direct microscopy, culture and histopathology to determine if there is a statistical correlation between Candida invasion and the clinical appearance and presence of epithelial dysplasia in leukoplakia. Samples were collected from 40 patients with oral leukoplakia and 21 controls. The swabs collected were used to inoculate Sabouraud's dextrose agar slant and for direct microscopy with Gram's stain. Culture growths were subjected to germ tube and corn meal agar tests to differentiate between Candida albicans and non-albicans groups. Biopsies were also done in all patients for histopathological confirmation; Gomori's methanamine silver stain was used to identify fungal invasion of lesional epithelium. Nineteen cases of leukoplakia showed Candida on direct smears, compared to 3 controls. Eighteen cases and one control showed growth of Candida on culture. Non-homogenous leukoplakia showed a higher positivity rate on microscopy and culture than homogenous lesions. All these correlations were statistically significant. Forty percent of leukoplakia cases were simultaneously positive for Candida on direct microscopy, culture and histopathologic evaluation. No significant difference was found between non-dysplastic and distinctly dysplastic lesions with respect to Candida detection on microscopy or culture.

  17. A Review of the Aetiopathogenesis and Clinical and Histopathological Features of Oral Mucosal Melanoma.

    PubMed

    Feller, Liviu; Khammissa, Razia A G; Lemmer, Johan

    2017-01-01

    Oral mucosal melanoma is an uncommon, usually heavily melanin-pigmented, but occasionally amelanotic aggressive tumour with a poor prognosis. Despite radical surgery, radiotherapy, or chemotherapy, local recurrence and distant metastasis are frequent. Microscopical examination is essential for diagnosis, and routine histological staining must be supplemented by immunohistochemical studies. The aetiology is unknown, the pathogenesis is poorly understood, and the 5-year survival rate rarely exceeds 30%. In most cases, oral mucosal melanoma arises from epithelial melanocytes in the basal layer of the epithelium and less frequently from immature melanocytes arrested in the lamina propria. In both cases the melanocytes undergo malignant transformation, invade deeper tissues, and metastasize to regional lymph nodes and to distant sites. Very rarely metastasis from skin melanoma may give rise to oral mucosal melanoma that may be mistaken for primary oral mucosal melanoma. The pathogenesis of oral mucosal melanoma is complex involving multiple interactions between cytogenetic factors including dysregulation of the cKit signalling pathways, cell cycle, apoptosis, and cell-to-cell interactions on the one hand and melanin itself, melanin intermediates, and local microenvironmental agents regulating melanogenesis on the other hand. The detailed mechanisms that initiate the malignant transformation of oral melanocytes and thereafter sustain and promote the process of melanomagenesis are unknown.

  18. A Review of the Aetiopathogenesis and Clinical and Histopathological Features of Oral Mucosal Melanoma

    PubMed Central

    Lemmer, Johan

    2017-01-01

    Oral mucosal melanoma is an uncommon, usually heavily melanin-pigmented, but occasionally amelanotic aggressive tumour with a poor prognosis. Despite radical surgery, radiotherapy, or chemotherapy, local recurrence and distant metastasis are frequent. Microscopical examination is essential for diagnosis, and routine histological staining must be supplemented by immunohistochemical studies. The aetiology is unknown, the pathogenesis is poorly understood, and the 5-year survival rate rarely exceeds 30%. In most cases, oral mucosal melanoma arises from epithelial melanocytes in the basal layer of the epithelium and less frequently from immature melanocytes arrested in the lamina propria. In both cases the melanocytes undergo malignant transformation, invade deeper tissues, and metastasize to regional lymph nodes and to distant sites. Very rarely metastasis from skin melanoma may give rise to oral mucosal melanoma that may be mistaken for primary oral mucosal melanoma. The pathogenesis of oral mucosal melanoma is complex involving multiple interactions between cytogenetic factors including dysregulation of the cKit signalling pathways, cell cycle, apoptosis, and cell-to-cell interactions on the one hand and melanin itself, melanin intermediates, and local microenvironmental agents regulating melanogenesis on the other hand. The detailed mechanisms that initiate the malignant transformation of oral melanocytes and thereafter sustain and promote the process of melanomagenesis are unknown. PMID:28638859

  19. Upland Oak Regeneration and Management

    Treesearch

    David L. Loftis

    2004-01-01

    In oak-dominated plant communities and in other communities where oaks are important, the keys to natural regeneration of upland oak components are (1) to ensure presence of competitive regeneration sources, and (2) to provide timely, sufficient release of these sources. Regeneration sources vary significantly among different types of plant communities and disturbance...

  20. Epigenetic influences on sensory regeneration: histone deacetylases regulate supporting cell proliferation in the avian utricle.

    PubMed

    Slattery, Eric L; Speck, Judith D; Warchol, Mark E

    2009-09-01

    The sensory hair cells of the cochlea and vestibular organs are essential for normal hearing and balance function. The mammalian ear possesses a very limited ability to regenerate hair cells and their loss can lead to permanent sensory impairment. In contrast, hair cells in the avian ear are quickly regenerated after acoustic trauma or ototoxic injury. The very different regenerative abilities of the avian vs. mammalian ear can be attributed to differences in injury-evoked expression of genes that either promote or inhibit the production of new hair cells. Gene expression is regulated both by the binding of cis-regulatory molecules to promoter regions as well as through structural modifications of chromatin (e.g., methylation and acetylation). This study examined effects of histone deacetylases (HDACs), whose main function is to modify histone acetylation, on the regulation of regenerative proliferation in the chick utricle. Cultures of regenerating utricles and dissociated cells from the utricular sensory epithelia were treated with the HDAC inhibitors valproic acid, trichostatin A, sodium butyrate, and MS-275. All of these molecules prevent the enzymatic removal of acetyl groups from histones, thus maintaining nuclear chromatin in a "relaxed" (open) configuration. Treatment with all inhibitors resulted in comparable decreases in supporting cell proliferation. We also observed that treatment with the HDAC1-, 2-, and 3-specific inhibitor MS-275 was sufficient to reduce proliferation and that two class I HDACs--HDAC1 and HDAC2--were expressed in the sensory epithelium of the utricle. These results suggest that inhibition of specific type I HDACs is sufficient to prevent cell cycle entry in supporting cells. Notably, treatment with HDAC inhibitors did not affect the differentiation of replacement hair cells. We conclude that histone deacetylation is a positive regulator of regenerative proliferation but is not critical for avian hair cell differentiation.

  1. Inhibiting poly(ADP-ribosylation) improves axon regeneration.

    PubMed

    Byrne, Alexandra B; McWhirter, Rebecca D; Sekine, Yuichi; Strittmatter, Stephen M; Miller, David M; Hammarlund, Marc

    2016-10-04

    The ability of a neuron to regenerate its axon after injury depends in part on its intrinsic regenerative potential. Here, we identify novel intrinsic regulators of axon regeneration: poly(ADP-ribose) glycohodrolases (PARGs) and poly(ADP-ribose) polymerases (PARPs). PARGs, which remove poly(ADP-ribose) from proteins, act in injured C. elegans GABA motor neurons to enhance axon regeneration. PARG expression is regulated by DLK signaling, and PARGs mediate DLK function in enhancing axon regeneration. Conversely, PARPs, which add poly(ADP-ribose) to proteins, inhibit axon regeneration of both C. elegans GABA neurons and mammalian cortical neurons. Furthermore, chemical PARP inhibitors improve axon regeneration when administered after injury. Our results indicate that regulation of poly(ADP-ribose) levels is a critical function of the DLK regeneration pathway, that poly-(ADP ribosylation) inhibits axon regeneration across species, and that chemical inhibition of PARPs can elicit axon regeneration.

  2. cAMP Stimulates Transepithelial Short-Circuit Current and Fluid Transport Across Porcine Ciliary Epithelium.

    PubMed

    Cheng, Angela King-Wah; Civan, Mortimer M; To, Chi-Ho; Do, Chi-Wai

    2016-12-01

    To investigate the effects of cAMP on transepithelial electrical parameters and fluid transport across porcine ciliary epithelium. Transepithelial electrical parameters were determined by mounting freshly isolated porcine ciliary epithelium in a modified Ussing chamber. Similarly, fluid movement across intact ciliary body was measured with a custom-made fluid flow chamber. Addition of 1, 10, and 100 μM 8-Br-cAMP (cAMP) to the aqueous side (nonpigmented ciliary epithelium, NPE) induced a sustained increase in short-circuit current (Isc). Addition of niflumic acid (NFA) to the aqueous surface effectively blocked the cAMP-induced Isc stimulation. The administration of cAMP to the stromal side (pigmented ciliary epithelium, PE) triggered a significant stimulation of Isc only at 100 μM. No additive effect was observed with bilateral application of cAMP. Likewise, forskolin caused a significant stimulation of Isc when applied to the aqueous side. Concomitantly, cAMP and forskolin increased fluid transport across porcine ciliary epithelium, and this stimulation was effectively inhibited by aqueous NFA. Depleting Cl- in the bathing solution abolished the baseline Isc and inhibited the subsequent stimulation by cAMP. Pretreatment with protein kinase A (PKA) blockers (H89/KT5720) significantly inhibited the cAMP- and forskolin-induced Isc responses. Our results suggest that cAMP triggers a sustained stimulation of Cl- and fluid transport across porcine ciliary epithelium; Cl- channels in the NPE cells are potentially a cellular site for this PKA-sensitive cAMP-mediated response.

  3. Ciliated cells of pseudostratified airway epithelium do not become mucous cells after ovalbumin challenge.

    PubMed

    Pardo-Saganta, Ana; Law, Brandon M; Gonzalez-Celeiro, Meryem; Vinarsky, Vladimir; Rajagopal, Jayaraj

    2013-03-01

    Mucous cell metaplasia is a hallmark of airway diseases, such as asthma and chronic obstructive pulmonary disease. The majority of human airway epithelium is pseudostratified, but the cell of origin of mucous cells has not been definitively established in this type of airway epithelium. There is evidence that ciliated, club cell (Clara), and basal cells can all give rise to mucus-producing cells in different contexts. Because pseudostratified airway epithelium contains distinct progenitor cells from simple columnar airway epithelium, the lineage relationships of progenitor cells to mucous cells may be different in these two epithelial types. We therefore performed lineage tracing of the ciliated cells of the murine basal cell-containing airway epithelium in conjunction with the ovalbumin (OVA)-induced murine model of allergic lung disease. We genetically labeled ciliated cells with enhanced Yellow Fluorescent Protein (eYFP) before the allergen challenge, and followed the fate of these cells to determine whether they gave rise to newly formed mucous cells. Although ciliated cells increased in number after the OVA challenge, the newly formed mucous cells were not labeled with the eYFP lineage tag. Even small numbers of labeled mucous cells could not be detected, implying that ciliated cells make virtually no contribution to the new goblet cell pool. This demonstrates that, after OVA challenge, new mucous cells do not originate from ciliated cells in a pseudostratified basal cell-containing airway epithelium.

  4. Regenerating an Arsenic Removal Iron-Based Adsorptive ...

    EPA Pesticide Factsheets

    The replacement of exhausted, adsorptive media used to remove arsenic from drinking water accounts for approximately 80% of the total operational and maintenance (O/M) costs of this commonly used small system technology. The results of three, full scale system studies of an on-site media regeneration process (Part 1) showed it to be effective in stripping arsenic and other contaminants from the exhausted media. Part 2, of this two part paper, presents information on the performance of the regenerated media to remove arsenic through multiple regeneration cycles (3) and the approximate cost savings of regeneration over media replacement. The results of the studies indicate that regenerated media is very effective in removing arsenic and the regeneration cost is substantially less than the media replacement cost. On site regeneration, therefore, provides small systems with alternative to media replacement when removing arsenic from drinking water using adsorptive media technology. Part 2 of a two part paper on the performance of the regenerated media to remove arsenic through multiple regeneration cycles (3) and the approximate cost savings of regeneration over media replacement.

  5. Zebrafish heart regeneration: 15 years of discoveries

    PubMed Central

    González‐Rosa, Juan Manuel; Burns, Caroline E.

    2017-01-01

    Abstract Cardiovascular disease is the leading cause of death worldwide. Compared to other organs such as the liver, the adult human heart lacks the capacity to regenerate on a macroscopic scale after injury. As a result, myocardial infarctions are responsible for approximately half of all cardiovascular related deaths. In contrast, the zebrafish heart regenerates efficiently upon injury through robust myocardial proliferation. Therefore, deciphering the mechanisms that underlie the zebrafish heart's endogenous regenerative capacity represents an exciting avenue to identify novel therapeutic strategies for inducing regeneration of the human heart. This review provides a historical overview of adult zebrafish heart regeneration. We summarize 15 years of research, with a special focus on recent developments from this fascinating field. We discuss experimental findings that address fundamental questions of regeneration research. What is the origin of regenerated muscle? How is regeneration controlled from a genetic and molecular perspective? How do different cell types interact to achieve organ regeneration? Understanding natural models of heart regeneration will bring us closer to answering the ultimate question: how can we stimulate myocardial regeneration in humans? PMID:28979788

  6. Expression of E-cadherin and vimentin in oral squamous cell carcinoma

    PubMed Central

    Zhou, Jingping; Tao, Detao; Xu, Qing; Gao, Zhenlin; Tang, Daofang

    2015-01-01

    The aim of the study is to determine the levels of E-cadherin, vimentin expression in tumor tissues from patients with oral squamous cell carcinoma (OSCC), and the relationship between the expression of E-cadherin, vimentin and epithelial-mesenchymal transition, in order to explore its values for predicting the invasion and metastasis of oral squamous cell carcinoma, short survival of patients in many types of cancer. E-cadherin and vimentin expression of 10 benign and 42 OSCC tumor tissues was examined by immunohistochemical staining. E-cadherin is positively expressed in normal oral mucosa epithelium, but vimentin expression is not found in normal oral mucosa epithelia; the E-cadherin and vimentin were expressed in 26 of 42 (61.9%) and 16 of 42 (38.1%), respectively. No statistically difference was found for E-cadherin and vimentin expression in patients with different age, gender and tumor location, E-cadherin and vimentin expression was significantly associated with lymph node metastasis and tissue location (P < 0.05); E-cadherin expression was also significantly associated with tumor stage (P < 0.05); there are significantly difference between infiltrative margin and central area in patients with oral squamous cell carcinoma for E-cadherin and vimentin positive expression (P < 0.05). E-cadherin and vimentin positive expression was associated with tumor metastasis of oral squamous cell carcinoma. Our study preliminarily confirmed that EMT phenomenon is existed during the development of oral squamous cell carcinoma. Co-evaluation of E-cadherin and vimentin might be a valuable tool for predicting OSCC patient outcome. PMID:26045832

  7. Reflectance confocal microscopy of oral epithelial tissue using an electrically tunable lens

    NASA Astrophysics Data System (ADS)

    Jabbour, Joey M.; Malik, Bilal H.; Cuenca, Rodrigo; Cheng, Shuna; Jo, Javier A.; Cheng, Yi-Shing L.; Wright, John M.; Maitland, Kristen C.

    2014-02-01

    We present the use of a commercially available electrically tunable lens to achieve axial scanning in a reflectance confocal microscope. Over a 255 μm axial scan range, the lateral and axial resolutions varied from 1-2 μm and 4-14 μm, respectively, dependent on the variable focal length of the tunable lens. Confocal imaging was performed on normal human biopsies from the oral cavity ex vivo. Sub-cellular morphologic features were seen throughout the depth of the epithelium while axially scanning using the focus tunable lens.

  8. Peripheral Nerve Regeneration Following Crush Injury to Rat Peroneal Nerve by Aqueous Extract of Medicinal Mushroom Hericium erinaceus (Bull.: Fr) Pers. (Aphyllophoromycetideae)

    PubMed Central

    Wong, Kah-Hui; Naidu, Murali; David, Pamela; Abdulla, Mahmood Ameen; Abdullah, Noorlidah; Kuppusamy, Umah Rani; Sabaratnam, Vikineswary

    2011-01-01

    Nerve crush injury is a well-established axonotmetic model in experimental regeneration studies to investigate the impact of various pharmacological treatments. Hericium erinaceus is a temperate mushroom but is now being cultivated in tropical Malaysia. In this study, we investigated the activity of aqueous extract of H. erinaceus fresh fruiting bodies in promoting functional recovery following an axonotmetic peroneal nerve injury in adult female Sprague-Dawley rats by daily oral administration. The aim was to investigate the possible use of this mushroom in the treatment of injured nerve. Functional recovery was assessed in behavioral experiment by walking track analysis. Peroneal functional index (PFI) was determined before surgery and after surgery as rats showed signs of recovery. Histological examinations were performed on peroneal nerve by immunofluorescence staining and neuromuscular junction by combined silver-cholinesterase stain. Analysis of PFI indicated that return of hind limb function occurred earlier in rats of aqueous extract or mecobalamin (positive control) group compared to negative control group. Regeneration of axons and reinnervation of motor endplates in extensor digitorum longus muscle in rats of aqueous extract or mecobalamin group developed better than in negative control group. These data suggest that daily oral administration of aqueous extract of H. erinaceus fresh fruiting bodies could promote the regeneration of injured rat peroneal nerve in the early stage of recovery. PMID:21941586

  9. Inhibiting poly(ADP-ribosylation) improves axon regeneration

    PubMed Central

    Byrne, Alexandra B; McWhirter, Rebecca D; Sekine, Yuichi; Strittmatter, Stephen M; Miller, David M; Hammarlund, Marc

    2016-01-01

    The ability of a neuron to regenerate its axon after injury depends in part on its intrinsic regenerative potential. Here, we identify novel intrinsic regulators of axon regeneration: poly(ADP-ribose) glycohodrolases (PARGs) and poly(ADP-ribose) polymerases (PARPs). PARGs, which remove poly(ADP-ribose) from proteins, act in injured C. elegans GABA motor neurons to enhance axon regeneration. PARG expression is regulated by DLK signaling, and PARGs mediate DLK function in enhancing axon regeneration. Conversely, PARPs, which add poly(ADP-ribose) to proteins, inhibit axon regeneration of both C. elegans GABA neurons and mammalian cortical neurons. Furthermore, chemical PARP inhibitors improve axon regeneration when administered after injury. Our results indicate that regulation of poly(ADP-ribose) levels is a critical function of the DLK regeneration pathway, that poly-(ADP ribosylation) inhibits axon regeneration across species, and that chemical inhibition of PARPs can elicit axon regeneration. DOI: http://dx.doi.org/10.7554/eLife.12734.001 PMID:27697151

  10. Natural Regeneration of Longleaf Pine

    Treesearch

    William D. Boyer

    1979-01-01

    Natural regeneration is now a reliable alternative for existing longleaf pine forests. The shelterwood system, or modifications of it, has been used experimentally to regenerate longleaf pine for over 20 years, and regional tests have confirmed its value for a wide range of site conditions. Natural regeneration, because of its low cost when compared to other...

  11. Excipient foods: designing food matrices that improve the oral bioavailability of pharmaceuticals and nutraceuticals.

    PubMed

    McClements, David Julian; Xiao, Hang

    2014-07-25

    The oral bioavailability of many lipophilic bioactive agents (pharmaceuticals and nutraceuticals) is limited due to various physicochemical and physiological processes: poor release from food or drug matrices; low solubility in gastrointestinal fluids; metabolism or chemical transformation within the gastrointestinal tract; low epithelium cell permeability. The bioavailability of these agents can be improved by specifically designing food matrices that control their release, solubilization, transport, metabolism, and absorption within the gastrointestinal tract. This article discusses the impact of food composition and structure on oral bioavailability, and how this knowledge can be used to design excipient foods for improving the oral bioavailability of lipophilic bioactives. Excipient foods contain ingredients or structures that may have no bioactivity themselves, but that are able to promote the bioactivity of co-ingested bioactives. These bioactives may be lipophilic drugs in pharmaceutical preparations (such as capsules, pills, or syrups) or nutraceuticals present within food matrices (such as natural or processed foods and beverages).

  12. Serum levels of pigment epithelium-derived factor (PEDF) are positively associated with acanthosis nigricans in obese adolescents.

    PubMed

    Galhardo, J; Hunt, L P; Shield, J P H

    2012-07-01

    Circulating pigment epithelium-derived factor, or serine protease inhibitor F1, is upregulated during adipogenesis, contributing to obesity-induced insulin resistance. Furthermore, pigment epithelium-derived factor is abundant in stage I melanosomes and has been reported to increase pigment granules and the appearance of mature melanosomes in retinal pigment epithelium. As acanthosis nigricans is a well-recognized clinical marker of insulin resistance, we hypothesized that increased pigment epithelium-derived factor might be associated with the generation of acanthosis nigricans. Acanthosis nigricans, anthropometric measurements, circulating total PEDF and metabolic profiles were assessed in 28 obese adolescents in a hospital-based obesity clinic. Subjects with acanthosis nigricans (n = 10) showed greater plasma levels of pigment epithelium-derived factor (PEDF) than those without [geometric mean 23.55 (range 15.2-40.2) vs. 9.01 (range 5.5-18.7) μg/ml; P < 0.001]. Although pigment epithelium-derived factor was positively correlated with the homeostasis model assessment for insulin resistance (HOMA-IR) (r = 0.779, P < 0.001; 95% CI 0.573-0.892), as previously reported, for the same degree of insulin resistance, those with acanthosis nigricans exhibited a 2.1-fold (95%CI 2.0-2.3) higher level of pigment epithelium-derived factor. While acanthosis nigricans is undoubtedly associated with insulin resistance, its appearance is not ubiquitous in patients at any given level of HOMA-IR. The higher levels of pigment epithelium-derived factor in those with acanthosis nigricans compared with those without, with similar levels of resistance, suggest that pigment epithelium-derived factor levels are associated with acanthosis nigricans. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

  13. Antimicrobial activity and regulation of CXCL9 and CXCL10 in oral keratinocytes.

    PubMed

    Marshall, Alison; Celentano, Antonio; Cirillo, Nicola; Mignogna, Michele D; McCullough, Michael; Porter, Stephen

    2016-10-01

    Chemokine (C-X-C motif) ligand (CXCL)9 and CXCL10 are dysregulated in oral inflammatory conditions, and it is not known if these chemokines target microorganisms that form oral biofilm. The aim of this study was to investigate the antimicrobial activity of CXCL9 and CXCL10 on oral microflora and their expression profiles in oral keratinocytes following exposure to inflammatory and infectious stimuli. Streptococcus sanguinis was used as a model and Escherichia coli as a positive control. The antimicrobial effect of CXCL9/CXCL10 was tested using a radial diffusion assay. mRNA transcripts were isolated from lipopolysaccharide (LPS)-treated and untreated (control) oral keratinocyte cell lines at 2-, 4-, 6-, and 8-h time-points of culture. The CXCL9/10 expression profile in the presence or absence of interferon-γ (IFN-γ) was assessed using semiquantitative PCR. Although both chemokines demonstrated antimicrobial activity, CXCL9 was the most effective chemokine against both S. sanguinis and E coli. mRNA for CXCL10 was expressed in control cells and its production was enhanced at all time-points following stimulation with LPS. Conversely, CXCL9 mRNA was not expressed in control or LPS-stimulated cells. Finally, stimulation with IFN-γ enhanced basal expression of both CXCL9 and CXCL10 in oral keratinocytes. Chemokines derived from oral epithelium, particularly CXCL9, demonstrate antimicrobial properties. Bacterial and inflammatory-stimulated up-regulation of CXCL9/10 could represent a key element in oral bacterial colonization homeostasis and host-defense mechanisms. © 2016 Eur J Oral Sci.

  14. Toxic corneal epitheliopathy after intravitreal methotrexate and its treatment with oral folic acid.

    PubMed

    Gorovoy, Ian; Prechanond, Tidarat; Abia, Maravillas; Afshar, Armin R; Stewart, Jay M

    2013-08-01

    To determine whether oral folic acid can ameliorate an iatrogenic, visually significant corneal epitheliopathy, which commonly occurs with intravitreal injections of methotrexate for the treatment of intraocular lymphoma. We report 2 cases of visually significant corneal epitheliopathy occurring after intravitreal injections of methotrexate for intraocular lymphoma. The first patient did not receive any treatment for the corneal disease, and the second patient with bilateral intraocular lymphoma received 1 mg of oral folic acid daily, a commonly used dosage for patients on systemic methotrexate. In the first patient without treatment, there was a complete regression of the corneal epithelial disease only when the frequency of intravitreal methotrexate was reduced from weekly to monthly as per a commonly used dosage regimen for methotrexate. In the second patient, the corneal disease improved 80% within 1 week of initiating oral folic acid for her eye already experiencing severe epitheliopathy during her weekly dosing regimen of methotrexate and also had significantly decreased epithelial disease in her second eye that started weekly intravitreal methotrexate several weeks after beginning oral folic acid. Currently, oral folic acid supplements are recommended for patients using systemic methotrexate to minimize drug toxicity. We suggest a similar use in patients undergoing intravitreal methotrexate injections to decrease toxic effects on the corneal epithelium.

  15. Comparative analysis of the oral mucosae from rodents and non-rodents: Application to the nonclinical evaluation of sublingual immunotherapy products

    PubMed Central

    Thirion-Delalande, Catherine; Gervais, Frédéric; Fisch, Cécile; Cuiné, Jean; Baron-Bodo, Véronique; Moingeon, Philippe

    2017-01-01

    Background A comparative characterization of the oral mucosa in various animals is needed to identify the best animal model(s) for nonclinical evaluation of sublingual immunotherapy products. With this aim, we studied the histological characteristics and immune cell infiltrates of oral mucosae from common animal species. Methods Three oral regions (i.e. ventral surface of the tongue, mouth floor and cheek) obtained from eight animal species, including rodents (i.e. mice, rats, hamsters, guinea pigs) and non-rodents (i.e. rabbits, dogs, minipigs and monkeys) were characterized by histology and immunohistology in comparison with a human tongue. Results Rodents exhibit a thin keratinized epithelium with low epithelial extensions, whereas non-rodents, most particularly minipigs and monkeys, display a non-keratinized epithelium with larger rete ridges, similarly to humans. Glycogen-rich cells in the superficial epithelial layers are observed in samples from both minipigs, monkeys and humans. Comparable immune subpopulations detected in the 3 oral regions from rodent and non-rodent species include MHC-II+ antigen presenting cells, mostly CD163+ macrophages, located in the lamina propria (LP) and muscle tissue in the vicinity of resident CD3+CD4+ T cells. Limited numbers of mast cells are also detected in the LP and muscle tissue from all species. Conclusion The oral mucosae of minipigs and monkeys are closest to that of humans, and the immune networks are quite similar between all rodents and non-rodents. Taking into account the ethical and logistical difficulties of performing research in the latter species, rodents and especially mice, should preferentially be used for pharmacodynamics/efficacy studies. Our data also support the use of minipigs to perform biodistribution and safety studies of sublingual immunotherapy products. PMID:28886055

  16. Keratinocyte growth factor is a growth factor for mammary epithelium in vivo. The mammary epithelium of lactating rats is resistant to the proliferative action of keratinocyte growth factor.

    PubMed Central

    Ulich, T. R.; Yi, E. S.; Cardiff, R.; Yin, S.; Bikhazi, N.; Biltz, R.; Morris, C. F.; Pierce, G. F.

    1994-01-01

    Keratinocyte growth factor (KGF) is a member of the fibroblast growth factor (FGF) family. KGF is secreted by stromal cells and affects epithelial but not mesenchymal cell proliferation. KGF injected intravenously was found to cause dramatic proliferation of mammary epithelium in the mammary glands of rats. KGF causes ductal neogenesis and intraductal epithelial hyperplasia but not lobular differentiation in nulliparous female rats. KGF causes ductal and lobular epithelial hyperplasia in male rats. KGF causes proliferation of ductal and acinar cells in the mammary glands of pregnant rats. On the other hand, the ductal epithelium of lactating postpartum rats is resistant to the proliferative action of KGF. The mammary glands of lactating rats did not express less KGF receptor mRNA than the glands of pregnant rats, suggesting that the resistance of the ductal epithelium to KGF during lactation is not related to KGF receptor mRNA down-regulation. The mammary glands of both pregnant and postpartum lactating rats express KGF mRNA with more KGF present in the glands of lactating rats. In conclusion, the KGF and KGF receptor genes are expressed in rat mammary glands and recombinant KGF is a potent growth factor for mammary epithelium. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:8178937

  17. The blastema and epimorphic regeneration in mammals.

    PubMed

    Seifert, Ashley W; Muneoka, Ken

    2018-01-15

    Studying regeneration in animals where and when it occurs is inherently interesting and a challenging research topic within developmental biology. Historically, vertebrate regeneration has been investigated in animals that display enhanced regenerative abilities and we have learned much from studying organ regeneration in amphibians and fish. From an applied perspective, while regeneration biologists will undoubtedly continue to study poikilothermic animals (i.e., amphibians and fish), studies focused on homeotherms (i.e., mammals and birds) are also necessary to advance regeneration biology. Emerging mammalian models of epimorphic regeneration are poised to help link regenerative biology and regenerative medicine. The regenerating rodent digit tip, which parallels human fingertip regeneration, and the regeneration of large circular defects through the ear pinna in spiny mice and rabbits, provide tractable, experimental systems where complex tissue structures are regrown through blastema formation and morphogenesis. Using these models as examples, we detail similarities and differences between the mammalian blastema and its classical counterpart to arrive at a broad working definition of a vertebrate regeneration blastema. This comparison leads us to conclude that regenerative failure is not related to the availability of regeneration-competent progenitor cells, but is most likely a function of the cellular response to the microenvironment that forms following traumatic injury. Recent studies demonstrating that targeted modification of this microenvironment can restrict or enhance regenerative capabilities in mammals helps provide a roadmap for eventually pushing the limits of human regeneration. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Membranes for periodontal regeneration: From commercially available to spatially designed and functionally graded materials

    NASA Astrophysics Data System (ADS)

    Bottino, Marco Cicero

    The aging of the global population will lead to a considerable increase in the number of surgical and restorative procedures related to oral rehabilitation or periodontal regeneration. Periodontitis is one of the most aggressive pathologies that concern the integrity of the periodontal system that can lead to the destruction of the periodontium. Guided tissue and guided bone regeneration (GTR/GBR) have been used for the repair and regeneration of periodontal tissues by utilizing an occlusive membrane. The goal of this dissertation is to advance the knowledge in the area of periodontal regeneration by investigating the properties of a commercially available freeze-dried collagen-based graft (AlloDermRTM) and by designing/fabricating a functionally graded membrane (FGM) via multilayer electrospinning. The effects of different rehydration times and of a simultaneous rehydration/crosslinking procedure on the biomechanical properties and matrix stability of the commercially available membrane were investigated. The results revealed that there are significant changes on the biomechanical properties of the graft as rehydration time increases. Moreover, it was demonstrated that the simultaneous rehydration/crosslinking protocol has a synergistic effect in terms of enhancing biomechanical properties. A FGM consisting of a core-layer (CL) and two functional surface-layers (SL) was fabricated via sequential electrospinning. Hydroxyapatite nanoparticles (n-HAp) were incorporated to enhance bone formation (SL facing bone defect), and metronidazole benzoate (MET) was added to prevent bacterial colonization (SL facing the epithelial tissue). Degradation studies performed on both the CL and the FGM confirmed that the design holds promise in terms of providing the required mechanical stability to avoid membrane collapse and, therefore, enhance bone regeneration. Finally, it was demonstrated that MET incorporation into the SL that would face epithelial tissue is effective in

  19. Comparison of NaCl-induced response across the tongue epithelium to that across other epithelia in the frog.

    PubMed

    Soeda, H; Sakudo, F

    1990-01-01

    Electrical properties of the frog tongue epithelium were compared to those of skin and bladder, which have active sodium transport. During perfusion with Ringer solution, the potential difference across the tongue epithelium was negligible, unlike those of the skin and bladder. NaCl stimulation of the tongue epithelium produced a response with a polarity opposite to that of the skin and bladder. The response profile of the tongue epithelium except for the polarity resembled that of other tissues. In conclusion, the NaCl response of the tongue epithelium is independent of active sodium transport and instead occurs by passive transport, which may influence taste reception.

  20. Engineering Functional Epithelium for Regenerative Medicine and In Vitro Organ Models: A Review

    PubMed Central

    Vrana, Nihal E.; Lavalle, Philippe; Dokmeci, Mehmet R.; Dehghani, Fariba; Ghaemmaghami, Amir M.

    2013-01-01

    Recent advances in the fields of microfabrication, biomaterials, and tissue engineering have provided new opportunities for developing biomimetic and functional tissues with potential applications in disease modeling, drug discovery, and replacing damaged tissues. An intact epithelium plays an indispensable role in the functionality of several organs such as the trachea, esophagus, and cornea. Furthermore, the integrity of the epithelial barrier and its degree of differentiation would define the level of success in tissue engineering of other organs such as the bladder and the skin. In this review, we focus on the challenges and requirements associated with engineering of epithelial layers in different tissues. Functional epithelial layers can be achieved by methods such as cell sheets, cell homing, and in situ epithelialization. However, for organs composed of several tissues, other important factors such as (1) in vivo epithelial cell migration, (2) multicell-type differentiation within the epithelium, and (3) epithelial cell interactions with the underlying mesenchymal cells should also be considered. Recent successful clinical trials in tissue engineering of the trachea have highlighted the importance of a functional epithelium for long-term success and survival of tissue replacements. Hence, using the trachea as a model tissue in clinical use, we describe the optimal structure of an artificial epithelium as well as challenges of obtaining a fully functional epithelium in macroscale. One of the possible remedies to address such challenges is the use of bottom-up fabrication methods to obtain a functional epithelium. Modular approaches for the generation of functional epithelial layers are reviewed and other emerging applications of microscale epithelial tissue models for studying epithelial/mesenchymal interactions in healthy and diseased (e.g., cancer) tissues are described. These models can elucidate the epithelial/mesenchymal tissue interactions at the

  1. Engineering functional epithelium for regenerative medicine and in vitro organ models: a review.

    PubMed

    Vrana, Nihal E; Lavalle, Philippe; Dokmeci, Mehmet R; Dehghani, Fariba; Ghaemmaghami, Amir M; Khademhosseini, Ali

    2013-12-01

    Recent advances in the fields of microfabrication, biomaterials, and tissue engineering have provided new opportunities for developing biomimetic and functional tissues with potential applications in disease modeling, drug discovery, and replacing damaged tissues. An intact epithelium plays an indispensable role in the functionality of several organs such as the trachea, esophagus, and cornea. Furthermore, the integrity of the epithelial barrier and its degree of differentiation would define the level of success in tissue engineering of other organs such as the bladder and the skin. In this review, we focus on the challenges and requirements associated with engineering of epithelial layers in different tissues. Functional epithelial layers can be achieved by methods such as cell sheets, cell homing, and in situ epithelialization. However, for organs composed of several tissues, other important factors such as (1) in vivo epithelial cell migration, (2) multicell-type differentiation within the epithelium, and (3) epithelial cell interactions with the underlying mesenchymal cells should also be considered. Recent successful clinical trials in tissue engineering of the trachea have highlighted the importance of a functional epithelium for long-term success and survival of tissue replacements. Hence, using the trachea as a model tissue in clinical use, we describe the optimal structure of an artificial epithelium as well as challenges of obtaining a fully functional epithelium in macroscale. One of the possible remedies to address such challenges is the use of bottom-up fabrication methods to obtain a functional epithelium. Modular approaches for the generation of functional epithelial layers are reviewed and other emerging applications of microscale epithelial tissue models for studying epithelial/mesenchymal interactions in healthy and diseased (e.g., cancer) tissues are described. These models can elucidate the epithelial/mesenchymal tissue interactions at the

  2. Noninvasive structural and microvascular anatomy of oral mucosae using handheld optical coherence tomography

    PubMed Central

    Tsai, Meng-Tsan; Chen, Yingdan; Lee, Cheng-Yu; Huang, Bo-Huei; Trung, Nguyen Hoang; Lee, Ya-Ju; Wang, Yen-Li

    2017-01-01

    In this study, we demonstrated the feasibility of using a handheld optical coherence tomography (OCT) for in vivo visualizations of the microstructural and microvascular features of various oral mucosal types. To scan arbitrary locations of the oral mucosa, a scanning probe was developed, composed of a probe body fabricated by a 3D printer, miniaturized two-axis galvanometer, relay lenses, and reflective prism. With a 3D printing technique, the probe weight and the system volume were greatly reduced, enabling the effective improvement of imaging artifacts from unconscious motion and system complexity. Additionally, in our design, the distal end of the probe can be switched to fit various oral conditions, and the optical parameters of the probe, such as the transverse resolution, working distance, and probe length can be easily varied. The results showed that the epithelium and lamina propria layers, as well as the fungiform papilla and salivary gland, were differentiated. Moreover, various microcirculation features at different mucosal sites were identified that are potentially effective indicators for the diagnosis of premalignant lesions. The demonstrated results indicate that the developed OCT system is a promising tool for noninvasive imaging of oral mucosae. PMID:29188097

  3. 450 nm diode laser: A new help in oral surgery.

    PubMed

    Fornaini, Carlo; Rocca, Jean-Paul; Merigo, Elisabetta

    2016-09-16

    To describe the performance of 450 nm diode laser in oral surgery procedures. The case described consisted of the removal of a lower lip fibroma through a blue diode laser (λ = 450 nm). The efficacy of this device, even at very low power (1W, CW), allows us to obtain very high intra and postoperative comfort for the patient, even with just topical anaesthesia and without needing suture. The healing process was completed in one week and, during the follow-up, the patient did not report any problems, pain or discomfort even without the consumption of any kind of drugs, such as painkillers and antibiotics. The histological examination performed by the pathologist showed a large area of fibrous connective tissue with some portions of epithelium-connective detachments and a regular incision with very scanty areas of carbonization. The 450 nm diode laser proved of being very efficient in the oral soft tissue surgical procedures, with no side effects for the patients.

  4. Early bioelectric activities mediate redox-modulated regeneration

    PubMed Central

    Ferreira, Fernando; Luxardi, Guillaume; Reid, Brian

    2016-01-01

    Reactive oxygen species (ROS) and electric currents modulate regeneration; however, the interplay between biochemical and biophysical signals during regeneration remains poorly understood. We investigate the interactions between redox and bioelectric activities during tail regeneration in Xenopus laevis tadpoles. We show that inhibition of NADPH oxidase-mediated production of ROS, or scavenging or blocking their diffusion into cells, impairs regeneration and consistently regulates the dynamics of membrane potential, transepithelial potential (TEP) and electric current densities (JI) during regeneration. Depletion of ROS mimics the altered TEP and JI observed in the non-regenerative refractory period. Short-term application of hydrogen peroxide (H2O2) rescues (from depleted ROS) and induces (from the refractory period) regeneration, TEP increase and JI reversal. H2O2 is therefore necessary for and sufficient to induce regeneration and to regulate TEP and JI. Epistasis assays show that voltage-gated Na+ channels act downstream of H2O2 to modulate regeneration. Altogether, these results suggest a novel mechanism for regeneration via redox-bioelectric orchestration. PMID:27827821

  5. Early bioelectric activities mediate redox-modulated regeneration.

    PubMed

    Ferreira, Fernando; Luxardi, Guillaume; Reid, Brian; Zhao, Min

    2016-12-15

    Reactive oxygen species (ROS) and electric currents modulate regeneration; however, the interplay between biochemical and biophysical signals during regeneration remains poorly understood. We investigate the interactions between redox and bioelectric activities during tail regeneration in Xenopus laevis tadpoles. We show that inhibition of NADPH oxidase-mediated production of ROS, or scavenging or blocking their diffusion into cells, impairs regeneration and consistently regulates the dynamics of membrane potential, transepithelial potential (TEP) and electric current densities (J I ) during regeneration. Depletion of ROS mimics the altered TEP and J I observed in the non-regenerative refractory period. Short-term application of hydrogen peroxide (H 2 O 2 ) rescues (from depleted ROS) and induces (from the refractory period) regeneration, TEP increase and J I reversal. H 2 O 2 is therefore necessary for and sufficient to induce regeneration and to regulate TEP and J I Epistasis assays show that voltage-gated Na + channels act downstream of H 2 O 2 to modulate regeneration. Altogether, these results suggest a novel mechanism for regeneration via redox-bioelectric orchestration. © 2016. Published by The Company of Biologists Ltd.

  6. STUDIES OF NORMAL GENE EXPRESSION IN THE RAT NASAL EPITHELIUM USNG CDNA ARRAY TECHNOLOGY

    EPA Science Inventory


    Studies of Normal Gene Expression in the Rat Nasal Epithelium Using cDNA Array

    The nasal epithelium is an important target site for chemically-induced toxicity and carcinogenicity .Gene expression data are being used increasingly for studies of such conditions. In or...

  7. Regeneration mechanisms in Syllidae (Annelida)

    PubMed Central

    Ribeiro, Rannyele P.

    2018-01-01

    Abstract Syllidae is one of the most species‐rich groups within Annelida, with a wide variety of reproductive modes and different regenerative processes. Syllids have striking ability to regenerate their body anteriorly and posteriorly, which in many species is redeployed during sexual (schizogamy) and asexual (fission) reproduction. This review summarizes the available data on regeneration in syllids, covering descriptions of regenerative mechanisms in different species as well as regeneration in relation to reproductive modes. Our survey shows that posterior regeneration is widely distributed in syllids, whereas anterior regeneration is limited in most of the species, excepting those reproducing by fission. The latter reproductive mode is well known for a few species belonging to Autolytinae, Eusyllinae, and Syllinae. Patterns of fission areas have been studied in these animals. Deviations of the regular regeneration pattern or aberrant forms such as bifurcated animals or individuals with multiple heads have been reported for several species. Some of these aberrations show a deviation of the bilateral symmetry and antero‐posterior axis, which, interestingly, can also be observed in the regular branching body pattern of some species of syllids. PMID:29721325

  8. Acoustic field modulation in regenerators

    NASA Astrophysics Data System (ADS)

    Hu, J. Y.; Wang, W.; Luo, E. C.; Chen, Y. Y.

    2016-12-01

    The regenerator is a key component that transfers energy between heat and work. The conversion efficiency is significantly influenced by the acoustic field in the regenerator. Much effort has been spent to quantitatively determine this influence, but few comprehensive experimental verifications have been performed because of difficulties in modulating and measuring the acoustic field. In this paper, a method requiring two compressors is introduced and theoretically investigated that achieves acoustic field modulation in the regenerator. One compressor outputs the acoustic power for the regenerator; the other acts as a phase shifter. A RC load dissipates the acoustic power out of both the regenerator and the latter compressor. The acoustic field can be modulated by adjusting the current in the two compressors and opening the RC load. The acoustic field is measured with pressure sensors instead of flow-field imaging equipment, thereby greatly simplifying the experiment.

  9. Synthetic Phage for Tissue Regeneration

    PubMed Central

    Merzlyak, Anna; Lee, Seung-Wuk

    2014-01-01

    Controlling structural organization and signaling motif display is of great importance to design the functional tissue regenerating materials. Synthetic phage, genetically engineered M13 bacteriophage has been recently introduced as novel tissue regeneration materials to display a high density of cell-signaling peptides on their major coat proteins for tissue regeneration purposes. Structural advantages of their long-rod shape and monodispersity can be taken together to construct nanofibrous scaffolds which support cell proliferation and differentiation as well as direct orientation of their growth in two or three dimensions. This review demonstrated how functional synthetic phage is designed and subsequently utilized for tissue regeneration that offers potential cell therapy. PMID:24991085

  10. Cell Migration During Heart Regeneration in Zebrafish

    PubMed Central

    Tahara, Naoyuki; Brush, Michael; Kawakami, Yasuhiko

    2018-01-01

    Zebrafish possess the remarkable ability to regenerate injured hearts as adults, which contrasts the very limited ability in mammals. Although very limited, mammalian hearts do in fact have measurable levels of cardiomyocyte regeneration. Therefore, elucidating mechanisms of zebrafish heart regeneration would provide information of naturally occurring regeneration to potentially apply to mammalian studies, in addition to addressing this biologically interesting phenomenon in itself. Studies over the past 13 years have identified processes and mechanisms of heart regeneration in zebrafish. After heart injury, preexisting cardiomyocytes dedifferentiate, enter the cell cycle, and repair the injured myocardium. This process requires interaction with epicardial cells, endocardial cells, and vascular endothelial cells. Epicardial cells envelope the heart, while endocardial cells make up the inner lining of the heart. They provide paracrine signals to cardiomyocytes to regenerate the injured myocardium, which is vascularized during heart regeneration. In addition, accumulating results suggest that local migration of these major cardiac cell types have roles in heart regeneration. In this review, we summarize the characteristics of various heart injury methods used in the research community and regeneration of the major cardiac cell types. Then, we discuss local migration of these cardiac cell types and immune cells during heart regeneration. PMID:27085002

  11. New approaches to increase intestinal length: Methods used for intestinal regeneration and bioengineering

    PubMed Central

    Shirafkan, Ali; Montalbano, Mauro; McGuire, Joshua; Rastellini, Cristiana; Cicalese, Luca

    2016-01-01

    Inadequate absorptive surface area poses a great challenge to the patients suffering a variety of intestinal diseases causing short bowel syndrome. To date, these patients are managed with total parenteral nutrition or intestinal transplantation. However, these carry significant morbidity and mortality. Currently, by emergence of tissue engineering, anticipations to utilize an alternative method to increase the intestinal absorptive surface area are increasing. In this paper, we will review the improvements made over time in attempting elongating the intestine with surgical techniques as well as using intestinal bioengineering. Performing sequential intestinal lengthening was the preliminary method applied in humans. However, these methods did not reach widespread use and has limited outcome. Subsequent experimental methods were developed utilizing scaffolds to regenerate intestinal tissue and organoids unit from the intestinal epithelium. Stem cells also have been studied and applied in all types of tissue engineering. Biomaterials were utilized as a structural support for naive cells to produce bio-engineered tissue that can achieve a near-normal anatomical structure. A promising novel approach is the elongation of the intestine with an acellular biologic scaffold to generate a neo-formed intestinal tissue that showed, for the first time, evidence of absorption in vivo. In the large intestine, studies are more focused on regeneration and engineering of sphincters and will be briefly reviewed. From the review of the existing literature, it can be concluded that significant progress has been achieved in these experimental methods but that these now need to be fully translated into a pre-clinical and clinical experimentation to become a future viable therapeutic option. PMID:27011901

  12. Axon Regeneration in C. elegans

    PubMed Central

    Hammarlund, Marc; Jin, Yishi

    2014-01-01

    Single axon transection by laser surgery has made C. elegans a new model for axon regeneration. Multiple conserved molecular signaling modules have been discovered through powerful genetic screening. in vivo imaging with single cell and axon resolution has revealed unprecedented cellular dynamics in regenerating axons. Information from C. elegans has greatly expanded our knowledge of the molecular and cellular mechanisms of axon regeneration. PMID:24794753

  13. Role of nanoparticle size, shape and surface chemistry in oral drug delivery.

    PubMed

    Banerjee, Amrita; Qi, Jianping; Gogoi, Rohan; Wong, Jessica; Mitragotri, Samir

    2016-09-28

    Nanoparticles find intriguing applications in oral drug delivery since they present a large surface area for interactions with the gastrointestinal tract and can be modified in various ways to address the barriers associated with oral delivery. The size, shape and surface chemistry of nanoparticles can greatly impact cellular uptake and efficacy of the treatment. However, the interplay between particle size, shape and surface chemistry has not been well investigated especially for oral drug delivery. To this end, we prepared sphere-, rod- and disc-shaped nanoparticles and conjugated them with targeting ligands to study the influence of size, shape and surface chemistry on their uptake and transport across intestinal cells. A triple co-culture model of intestinal cells was utilized to more closely mimic the intestinal epithelium. Results demonstrated higher cellular uptake of rod-shaped nanoparticles in the co-culture compared to spheres regardless of the presence of active targeting moieties. Transport of nanorods across the intestinal co-culture was also significantly higher than spheres. The findings indicate that nanoparticle-mediated oral drug delivery can be potentially improved with departure from spherical shape which has been traditionally utilized for the design of nanoparticles. We believe that understanding the role of nanoparticle geometry in intestinal uptake and transport will bring forth a paradigm shift in nanoparticle engineering for oral delivery and non-spherical nanoparticles should be further investigated and considered for oral delivery of therapeutic drugs and diagnostic materials. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. The genetic and epigenetic landscapes of the epithelium in asthma.

    PubMed

    Moheimani, Fatemeh; Hsu, Alan C-Y; Reid, Andrew T; Williams, Teresa; Kicic, Anthony; Stick, Stephen M; Hansbro, Philip M; Wark, Peter A B; Knight, Darryl A

    2016-09-22

    Asthma is a global health problem with increasing prevalence. The airway epithelium is the initial barrier against inhaled noxious agents or aeroallergens. In asthma, the airway epithelium suffers from structural and functional abnormalities and as such, is more susceptible to normally innocuous environmental stimuli. The epithelial structural and functional impairments are now recognised as a significant contributing factor to asthma pathogenesis. Both genetic and environmental risk factors play important roles in the development of asthma with an increasing number of genes associated with asthma susceptibility being expressed in airway epithelium. Epigenetic factors that regulate airway epithelial structure and function are also an attractive area for assessment of susceptibility to asthma. In this review we provide a comprehensive discussion on genetic factors; from using linkage designs and candidate gene association studies to genome-wide association studies and whole genome sequencing, and epigenetic factors; DNA methylation, histone modifications, and non-coding RNAs (especially microRNAs), in airway epithelial cells that are functionally associated with asthma pathogenesis. Our aims were to introduce potential predictors or therapeutic targets for asthma in airway epithelium. Overall, we found very small overlap in asthma susceptibility genes identified with different technologies. Some potential biomarkers are IRAKM, PCDH1, ORMDL3/GSDMB, IL-33, CDHR3 and CST1 in airway epithelial cells. Recent studies on epigenetic regulatory factors have further provided novel insights to the field, particularly their effect on regulation of some of the asthma susceptibility genes (e.g. methylation of ADAM33). Among the epigenetic regulatory mechanisms, microRNA networks have been shown to regulate a major portion of post-transcriptional gene regulation. Particularly, miR-19a may have some therapeutic potential.

  15. Expression of heat shock protein in the atrophic corneal epithelium of the Royal College of Surgeons dystrophic rat.

    PubMed

    Yamaguchi, K; Yamaguchi, K; Sheedlo, H J; Turner, J E

    1991-03-01

    We report atrophic changes in the corneal epithelium of Royal College of Surgeons (RCS) dystrophic rats. The thickness of the corneal epithelium of 180-day-old RCS dystrophic rats was significantly decreased compared to that of 26-day-old RCS dystrophic and age-matched Sprague-Dawley (SD) rats. Immunostaining for (Na+ + K+) ATPase in the corneal epithelium of 180-day-old RCS dystrophic rats was dramatically reduced when compared to that of 26-day-old RCS dystrophic and age-matched SD rats. In contrast, heat shock protein immunostaining in the corneal epithelium was dense in all of the basal cells, wing cells, and superficial cells of 180-day-old RCS dystrophic rats but was minimally observed in some of the basal cells and in fewer wing and superficial cells of the corneal epithelium of 26-day-old RCS dystrophic and age-matched SD rats. We speculate that toxic products from the degenerating rod outer segments in the course of retinal dystrophy may affect the corneal epithelium, resulting in its atrophy. It is also possible that heat shock proteins appear in the atrophic corneal epithelium due to its degenerative condition.

  16. Impact and mechanistic role of oral contraceptive pills on the number and epithelial type of ovarian cortical inclusion cysts; a clinicopathology and immunohistochemical study.

    PubMed

    DastranjTabrizi, Ali; MostafaGharabaghi, Parvin; SheikhzadehHesari, Farzam; Sadeghi, Liela; Zamanvandi, Sharareh; Sarbakhsh, Parvin; Ghojazadeh, Morteza

    2016-03-22

    Ovarian epithelial cancers are among the most lethal women's cancers. There is no doubt about the preventive role of oral contraceptive pills (OCPs) in development of ovarian cancers. But, there are limited numbers of studies to address the effect of these agents on the number of cortical inclusion cysts (CICs), their epithelial type and suppression of the metaplastic phenomenon by these pills. The aim of this study was to clarify the role of these agents in the prevention of these cyst formation and tubal metaplasia and also examine the mesenchymal-epithelial transition theory in this context by immunohistochemical methods. The representative section(s) of ovarian cortex from a total number of 201 consecutive total abdominal hysterectomy with bilateral or unilateral salpingo-oophorectomy specimens were examined for mean number of CICs and their epithelial type between two groups of the patients. Group A included the patients who were on oral contraceptive pills for more than 5 years. All of the subjects with other contraceptive methods or a history of less than 5 years contraceptive pills usage were stratified in group B. Sections from 20 cases in which more than five inclusion cysts were found, were selected for IHC staining with calretinine and PAX8 as markers for mesothelium and mullerian epithelium respectively. The mean age of the patients was 51.67 years with no significant differences between two groups. The mean number of cysts were 1.27 and 3.23 in group A and B respectively (P =0.0001). Similarly the mean number of CICs, lined by tubal epithelium, was significantly different between two groups (0.65 vs 2.65, P =0.0001). In IHC staining 123 out of 150 CICs (82 %) were PAX+ while only 7 CICs (4.8 %) showed positive reaction for calretinin irrespective of type of epithelium. Our findings showed that the use of OCP for more than five years in women, significantly prevents development of cortical inclusion cysts in the ovaries which lined by tubal

  17. Regenerating Fish Optic Nerves and a Regeneration-Like Response in Injured Optic Nerves of Adult Rabbits

    NASA Astrophysics Data System (ADS)

    Schwartz, M.; Belkin, M.; Harel, A.; Solomon, A.; Lavie, V.; Hadani, M.; Rachailovich, I.; Stein-Izsak, C.

    1985-05-01

    Regeneration of fish optic nerve (representing regenerative central nervous system) was accompanied by increased activity of regeneration-triggering factors produced by nonneuronal cells. A graft of regenerating fish optic nerve, or a ``wrap-around'' implant containing medium conditioned by it, induced a response associated with regeneration in injured optic nerves of adult rabbits (representing a nonregenerative central nervous system). This response was manifested by an increase of general protein synthesis and of selective polypeptides in the retinas and by the ability of the retina to sprout in culture.

  18. Mechanisms of urodele limb regeneration

    PubMed Central

    2017-01-01

    Abstract This review explores the historical and current state of our knowledge about urodele limb regeneration. Topics discussed are (1) blastema formation by the proteolytic histolysis of limb tissues to release resident stem cells and mononucleate cells that undergo dedifferentiation, cell cycle entry and accumulation under the apical epidermal cap. (2) The origin, phenotypic memory, and positional memory of blastema cells. (3) The role played by macrophages in the early events of regeneration. (4) The role of neural and AEC factors and interaction between blastema cells in mitosis and distalization. (5) Models of pattern formation based on the results of axial reversal experiments, experiments on the regeneration of half and double half limbs, and experiments using retinoic acid to alter positional identity of blastema cells. (6) Possible mechanisms of distalization during normal and intercalary regeneration. (7) Is pattern formation is a self‐organizing property of the blastema or dictated by chemical signals from adjacent tissues? (8) What is the future for regenerating a human limb? PMID:29299322

  19. Simultaneous Sinus Lifting and Alveolar Distraction of a Severely Atrophic Posterior Maxilla for Oral Rehabilitation with Dental Implants

    PubMed Central

    Kanno, Takahiro; Mitsugi, Masaharu; Paeng, Jun-Young; Sukegawa, Shintaro; Furuki, Yoshihiko; Ohwada, Hiroyuki; Nariai, Yoshiki; Ishibashi, Hiroaki; Katsuyama, Hideaki; Sekine, Joji

    2012-01-01

    We retrospectively reviewed a new preimplantation regenerative augmentation technique for a severely atrophic posterior maxilla using sinus lifting with simultaneous alveolar distraction, together with long-term oral rehabilitation with implants. We also analyzed the regenerated bone histomorphologically. This study included 25 maxillary sinus sites in 17 patients. The technique consisted of alveolar osteotomy combined with simultaneous sinus lifting. After sufficient sinus lifting, a track-type vertical alveolar distractor was placed. Following a latent period, patient self-distraction was started. After the required augmentation was achieved, the distractor was left in place to allow consolidation. The distractor was then removed, and osseointegrated implants (average of 3.2 implants per sinus site, 80 implants) were placed. Bone for histomorphometric analysis was sampled from six patients and compared with samples collected after sinus lifting alone as controls (n = 4). A sufficient alveolus was regenerated, and all patients achieved stable oral rehabilitation. The implant survival rate was 96.3% (77/80) after an average postloading followup of 47.5 months. Good bone regeneration was observed in a morphological study, with no significant difference in the rate of bone formation compared with control samples. This new regenerative technique could be a useful option for a severely atrophic maxilla requiring implant rehabilitation. PMID:22792105

  20. "Snowmelt Sign" and "Corkscrew Microvessels" Predicting Epithelium Regeneration After Acute Rejection of Small-Bowel Transplantation: A Case Report.

    PubMed

    Chung, C-S; Lee, T-H; Chiu, C-T; Chen, Y

    2017-12-01

    Intestinal failure characterized by inadequate maintenance of nutrition via normal intestinal function comprises a group of disorders with many different causes. If parenteral nutrition dependency develops, which is associated with higher mortality and complications, it is considered for intestine transplantation. However, the graft failure rate is not low, and acute cellular rejection is one of the most important reasons for graft failure. As a result, early identification of rejection and timely modification of anti-rejection medications have been considered to be associated with better graft and patient survival rates. The diagnostic gold standard for rejection is mainly based on histology, but hours of delay by pathology may occur. Some researchers investigated the association of endoscopic images with graft rejection to provide timely diagnosis. In this study, we present the first case report with characteristic features under magnifying endoscopy with a narrow-band imaging system to predict epithelial regeneration and improvement of graft rejection in a patient with small-bowel transplantation. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Guide to Regeneration of Bottomland Hardwoods

    Treesearch

    Martha R. McKevlin

    1992-01-01

    This guide will help landowners, consulting foresters, and public service foresters regenerate bottomland hardwoods. It discusses (1) interpretation of site characteristics, (2) selection of species, and (3) selection of regeneration methods. A dichotomous key for selection of appropriate regeneration methods under various conditions is presented.

  2. Axonal regeneration in zebrafish spinal cord

    PubMed Central

    Hui, Subhra Prakash

    2018-01-01

    Abstract In the present review we discuss two interrelated events—axonal damage and repair—known to occur after spinal cord injury (SCI) in the zebrafish. Adult zebrafish are capable of regenerating axonal tracts and can restore full functionality after SCI. Unlike fish, axon regeneration in the adult mammalian central nervous system is extremely limited. As a consequence of an injury there is very little repair of disengaged axons and therefore functional deficit persists after SCI in adult mammals. In contrast, peripheral nervous system axons readily regenerate following injury and hence allow functional recovery both in mammals and fish. A better mechanistic understanding of these three scenarios could provide a more comprehensive insight into the success or failure of axonal regeneration after SCI. This review summarizes the present understanding of the cellular and molecular basis of axonal regeneration, in both the peripheral nervous system and the central nervous system, and large scale gene expression analysis is used to focus on different events during regeneration. The discovery and identification of genes involved in zebrafish spinal cord regeneration and subsequent functional experimentation will provide more insight into the endogenous mechanism of myelination and remyelination. Furthermore, precise knowledge of the mechanism underlying the extraordinary axonal regeneration process in zebrafish will also allow us to unravel the potential therapeutic strategies to be implemented for enhancing regrowth and remyelination of axons in mammals. PMID:29721326

  3. Hyperinnervation improves Xenopus laevis limb regeneration.

    PubMed

    Mitogawa, Kazumasa; Makanae, Aki; Satoh, Akira

    2018-01-15

    Xenopus laevis (an anuran amphibian) shows limb regeneration ability between that of urodele amphibians and that of amniotes. Xenopus frogs can initiate limb regeneration but fail to form patterned limbs. Regenerated limbs mainly consist of cone-shaped cartilage without any joints or branches. These pattern defects are thought to be caused by loss of proper expressions of patterning-related genes. This study shows that hyperinnervation surgery resulted in the induction of a branching regenerate. The hyperinnervated blastema allows the identification and functional analysis of the molecules controlling this patterning of limb regeneration. This paper focuses on the nerve affects to improve Xenopus limb patterning ability during regeneration. The nerve molecules, which regulate limb patterning, were also investigated. Blastemas grown in a hyperinnervated forelimb upregulate limb patterning-related genes (shh, lmx1b, and hoxa13). Nerves projecting their axons to limbs express some growth factors (bmp7, fgf2, fgf8, and shh). Inputs of these factors to a blastema upregulated some limb patterning-related genes and resulted in changes in the cartilage patterns in the regenerates. These results indicate that additional nerve factors enhance Xenopus limb patterning-related gene expressions and limb regeneration ability, and that bmp, fgf, and shh are candidate nerve substitute factors. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Axonal regeneration in zebrafish spinal cord.

    PubMed

    Ghosh, Sukla; Hui, Subhra Prakash

    2018-03-01

    In the present review we discuss two interrelated events-axonal damage and repair-known to occur after spinal cord injury (SCI) in the zebrafish. Adult zebrafish are capable of regenerating axonal tracts and can restore full functionality after SCI. Unlike fish, axon regeneration in the adult mammalian central nervous system is extremely limited. As a consequence of an injury there is very little repair of disengaged axons and therefore functional deficit persists after SCI in adult mammals. In contrast, peripheral nervous system axons readily regenerate following injury and hence allow functional recovery both in mammals and fish. A better mechanistic understanding of these three scenarios could provide a more comprehensive insight into the success or failure of axonal regeneration after SCI. This review summarizes the present understanding of the cellular and molecular basis of axonal regeneration, in both the peripheral nervous system and the central nervous system, and large scale gene expression analysis is used to focus on different events during regeneration. The discovery and identification of genes involved in zebrafish spinal cord regeneration and subsequent functional experimentation will provide more insight into the endogenous mechanism of myelination and remyelination. Furthermore, precise knowledge of the mechanism underlying the extraordinary axonal regeneration process in zebrafish will also allow us to unravel the potential therapeutic strategies to be implemented for enhancing regrowth and remyelination of axons in mammals.

  5. Frequency of Candidiasis and Colonization of Candida albicans in Relation to Oral Contraceptive Pills.

    PubMed

    Aminzadeh, Atousa; Sabeti Sanat, Ali; Nik Akhtar, Saeed

    2016-10-01

    Candidiasis, the infection caused by Candida albicans , is one of the most common infections of the oral cavity in humans. Candidiasis causes irritation and is known for its carcinogenic effects. Thus, it is important to recognize the predisposing factors for this opportunistic infection. Several previous studies have demonstrated an increased frequency of vaginal candidiasis in relation to oral contraceptive consumption. Only a few studies on the relation between oral contraceptives and oral candidiasis have been previously conducted. This study aims to evaluate the possible relation between oral contraceptive pills and oral candidiasis. This analytic, case-control study included 40 non-pregnant women divided into two groups: 20 who used oral contraceptive pills and 20 who did not. The groups were matched according to age, oral health, and past and present medical history. Samples were collected from the tongue's dorsum using a cotton swab and inoculated on CHROMagar culture plates. The frequency of positive cultures and the number of Candida colonies were compared between the two groups using independent t-tests and Mann-Whitney statistical tests with SPSS18 software. The frequency of positive cultures of Candida albicans was higher (P value = 0.03) for the case group. Also, the number of C. albicans and C. krusei was significantly higher for the case group compared to the control group (P value = 0.04, P value = 0.03). The results of the present study demonstrate that oral contraceptives containing estradiol can lead to Candida colonization in the oral cavity. It is recommended that further studies comparing the influence of oral contraceptives on Candida's adherence to the epithelium is highly recommended.

  6. Cellular chloride and bicarbonate retention alters intracellular pH regulation in Cftr KO crypt epithelium

    PubMed Central

    Walker, Nancy M.; Liu, Jinghua; Stein, Sydney R.; Stefanski, Casey D.; Strubberg, Ashlee M.

    2015-01-01

    Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR), an anion channel providing a major pathway for Cl− and HCO3− efflux across the apical membrane of the epithelium. In the intestine, CF manifests as obstructive syndromes, dysbiosis, inflammation, and an increased risk for gastrointestinal cancer. Cftr knockout (KO) mice recapitulate CF intestinal disease, including intestinal hyperproliferation. Previous studies using Cftr KO intestinal organoids (enteroids) indicate that crypt epithelium maintains an alkaline intracellular pH (pHi). We hypothesized that Cftr has a cell-autonomous role in downregulating pHi that is incompletely compensated by acid-base regulation in its absence. Here, 2′,7′-bis(2-carboxyethyl)-5(6)-carboxyfluorescein microfluorimetry of enteroids showed that Cftr KO crypt epithelium sustains an alkaline pHi and resistance to cell acidification relative to wild-type. Quantitative real-time PCR revealed that Cftr KO enteroids exhibit downregulated transcription of base (HCO3−)-loading proteins and upregulation of the basolateral membrane HCO3−-unloader anion exchanger 2 (Ae2). Although Cftr KO crypt epithelium had increased Ae2 expression and Ae2-mediated Cl−/HCO3− exchange with maximized gradients, it also had increased intracellular Cl− concentration relative to wild-type. Pharmacological reduction of intracellular Cl− concentration in Cftr KO crypt epithelium normalized pHi, which was largely Ae2-dependent. We conclude that Cftr KO crypt epithelium maintains an alkaline pHi as a consequence of losing both Cl− and HCO3− efflux, which impairs pHi regulation by Ae2. Retention of Cl− and an alkaline pHi in crypt epithelium may alter several cellular processes in the proliferative compartment of Cftr KO intestine. PMID:26542396

  7. Anterior lens epithelium in cataract patients with retinitis pigmentosa - scanning and transmission electron microscopy study.

    PubMed

    Andjelic, Sofija; Drašlar, Kazimir; Hvala, Anastazija; Hawlina, Marko

    2017-05-01

    In retinitis pigmentosa (RP) patients, relatively minor lens opacity in central part of posterior pole of the lens may cause disproportionate functional symptoms requiring cataract operation. To investigate the possible structural reasons for this opacity development, we studied the structure of the lens epithelium of patients with RP. The anterior lens capsule (aLC: basement membrane and associated lens epithelial cells, LECs) was obtained from cataract surgery and prepared for scanning and transmission electron microscopy (SEM and TEM). Both SEM and TEM show a number of abnormal features in the anterior lens epithelium of cataract patients with RP. The abnormalities appear mainly as holes, thinning and degradation of the epithelium, with the dimensions from <1 μm to more than 50 μm. Other types of holes in size up to 20 μm were seen that may be formed by gradual stretching of the lens epithelium. Another type of abnormalities was cracks that were seen between adjacent LECs, with dimensions 0.1-2 μm × up to 10 μm. Abnormal structural features were observed in the anterior lens epithelium that may cause water influx into the lens. This may lead to clouding along the water clefts leading towards the posterior pole in the RP cataractous lens. We suggest that the lens epithelium has a role in the development of the cataract in patients with RP. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  8. Laser-induced regeneration of cartilage

    NASA Astrophysics Data System (ADS)

    Sobol, Emil; Shekhter, Anatoly; Guller, Anna; Baum, Olga; Baskov, Andrey

    2011-08-01

    Laser radiation provides a means to control the fields of temperature and thermo mechanical stress, mass transfer, and modification of fine structure of the cartilage matrix. The aim of this outlook paper is to review physical and biological aspects of laser-induced regeneration of cartilage and to discuss the possibilities and prospects of its clinical applications. The problems and the pathways of tissue regeneration, the types and features of cartilage will be introduced first. Then we will review various actual and prospective approaches for cartilage repair; consider possible mechanisms of laser-induced regeneration. Finally, we present the results in laser regeneration of joints and spine disks cartilages and discuss some future applications of lasers in regenerative medicine.

  9. Cell migration during heart regeneration in zebrafish.

    PubMed

    Tahara, Naoyuki; Brush, Michael; Kawakami, Yasuhiko

    2016-07-01

    Zebrafish possess the remarkable ability to regenerate injured hearts as adults, which contrasts the very limited ability in mammals. Although very limited, mammalian hearts do in fact have measurable levels of cardiomyocyte regeneration. Therefore, elucidating mechanisms of zebrafish heart regeneration would provide information of naturally occurring regeneration to potentially apply to mammalian studies, in addition to addressing this biologically interesting phenomenon in itself. Studies over the past 13 years have identified processes and mechanisms of heart regeneration in zebrafish. After heart injury, pre-existing cardiomyocytes dedifferentiate, enter the cell cycle, and repair the injured myocardium. This process requires interaction with epicardial cells, endocardial cells, and vascular endothelial cells. Epicardial cells envelope the heart, while endocardial cells make up the inner lining of the heart. They provide paracrine signals to cardiomyocytes to regenerate the injured myocardium, which is vascularized during heart regeneration. In addition, accumulating results suggest that local migration of these major cardiac cell types have roles in heart regeneration. In this review, we summarize the characteristics of various heart injury methods used in the research community and regeneration of the major cardiac cell types. Then, we discuss local migration of these cardiac cell types and immune cells during heart regeneration. Developmental Dynamics 245:774-787, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. Claudin-31 contributes to corticosteroid-induced alterations in the barrier properties of the gill epithelium.

    PubMed

    Kolosov, Dennis; Donini, Andrew; Kelly, Scott P

    2017-01-05

    The contribution of Claudin-31 (Cldn-31) to corticosteroid-induced tightening of the trout gill epithelium was examined using a primary cultured model preparation. Cldn-31 is a ∼23 kDa protein that localizes to the periphery of gill epithelial cells and diffusely in select gill cells that are Na + -K + -ATPase-immunoreactive. Transcriptional knockdown (KD) of cldn-31 reduced Cldn-31 abundance and increased epithelium permeability. Under simulated in vivo conditions (apical freshwater), cldn-31 KD increased net ion flux rates (≡ efflux). Cortisol treatment increased Cldn-31 abundance and decreased epithelium permeability. This tightening effect was diminished, but not eliminated, by cldn-31 KD, most likely due to other cortisol-sensitive TJ proteins that were transcriptionally unperturbed or enhanced in cortisol-treated cldn-31 KD preparations. However, cldn-31 KD abolished a cortisol-induced increase in Cldn-8d abundance, which may contribute to compromised cldn-31 KD epithelium permeability. Data suggest an important barrier function for Cldn-31 and an integral role for Cldn-31 in corticosteroid-induced gill epithelium tightening. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Effect of ground skidding on oak advance regeneration

    Treesearch

    Jeffrey W. Stringer

    2006-01-01

    Vigorous advance regeneration is required to naturally regenerate oaks. However, a reduction in the number of advance regeneration stems from harvesting activities could be an important factor in determining successful oak regeneration. This study assessed the harvest survivability of advance regeneration of oak (Quercus spp.) and co-occurring...

  12. Megalin and cubilin in the human gallbladder epithelium.

    PubMed

    Tsaroucha, Alexandra K; Chatzaki, Ekaterini; Lambropoulou, Maria; Despoudi, Kaliopi; Laftsidis, Prodromos; Charsou, Chara; Polychronidis, Alexandros; Papadopoulos, Nikolaos; Simopoulos, Constantinos E

    2008-09-01

    Although the role of cholesterol absorption by the gallbladder epithelium in gallstone formation is well established, the exact process is poorly understood. Potential candidates for regulation of transepithelial cholesterol transport are suggested to be two large membrane multiple ligand receptors, megalin and cubilin. We studied the expression of these two proteins in both acalculous and calculous human gallbladder epithelia. Adult human gallbladder tissues were received from 21 patients (9 men, 12 women) who had undergone cholecystectomy. The patients were divided into two groups: group A (calculous gallbladder group; 5 men, 6 women; mean age 64.4 +/- 11.1 years) with cholelithiasis, and group B (acalculous gallbladder group; 4 men, 6 women; mean age 55.3 +/- 16.1 years). In the gallbladder tissues megalin and cubilin expression was studied by immunohistochemistry and conventional RT-PCR, and gene expression levels were estimated by real-time RT-PCR. Both megalin and cubilin gene transcripts were found in total RNA preparations from acalculous gallbladder. In contrast, in preparations from calculous gallbladder, none or only one of the proteins was detected. Immunoreactive proteins were detected in the simple columnar acalculous gallbladder epithelium but not in the calculous gallbladder epithelium. Our results show different expression patterns of the two proteins in calculous gallbladders and acalculous gallbladders. In the latter both proteins are expressed, suggesting an association with gallstone formation and implying a putative role of the two proteins in cholesterol endocytosis. In other words, the presence of both proteins may be essential for the prevention of stone formation.

  13. Zebrafish fin and heart: what's special about regeneration?

    PubMed

    Sehring, Ivonne M; Jahn, Christopher; Weidinger, Gilbert

    2016-10-01

    Many organs regenerate well in adult zebrafish, but most research has been directed toward fin and heart regeneration. Cells have been found to remain generally lineage-restricted during regeneration, and proliferative regenerative progenitors can be formed by dedifferentiation from differentiated cells. Recent studies begin to shed light on the molecular underpinnings of differences between development and regeneration. Retinoic acid, BMP and NF-κB signaling are emerging as regulators of cellular dedifferentiation. Reactive oxygen species promote regeneration, and the dynamics of ROS signaling might help explain differences between wound healing and regeneration. Finally, the heart has been added to those organs that require a nerve supply to regenerate, and a trade-off between regeneration and tumor suppression has been proposed to help explain why mammals regenerate poorly. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Claudin expression in follicle-associated epithelium of rat Peyer's patches defines a major restriction of the paracellular pathway.

    PubMed

    Markov, A G; Falchuk, E L; Kruglova, N M; Radloff, J; Amasheh, S

    2016-01-01

    Members of the tight junction protein family of claudins have been demonstrated to specifically determine paracellular permeability of the intestinal epithelium. In small intestinal mucosa, which is generally considered to be a leaky epithelium, Peyer's patches are a primary part of the immune system. The aim of this study was to analyse the tight junctional barrier of follicle-associated epithelium covering Peyer's patches (lymphoid follicles). Employing small intestinal tissue specimens of male Wistar rats, electrophysiological analyses including the Ussing chamber technique, marker flux measurements and one-path impedance spectroscopy were performed. Morphometry of HE-stained tissue sections was taken into account. Claudin expression and localization was analysed by immunoblotting and confocal laser scanning immunofluorescence microscopy. Almost twofold higher parameters of epithelial and transepithelial tissue resistance and a markedly lower permeability for the paracellular permeability markers 4 and 20 kDa FITC-dextran were detected in follicle-associated epithelium compared to neighbouring villous epithelium. Analysis of claudin expression and localization revealed a stronger expression of major sealing proteins in follicle-associated epithelium, including claudin-1, claudin-4, claudin-5 and claudin-8. Therefore, the specific expression and localization of claudins is in accordance with barrier properties of follicle-associated epithelium vs. neighbouring villous epithelium. We demonstrate that follicle-associated epithelium is specialized to ensure maximum restriction of the epithelial paracellular pathway in Peyer's patches by selective sealing of tight junctions. This results in an exclusive transcellular pathway of epithelial cells as the limiting and mandatory route for a controlled presentation of antigens to the underlying lymphocytes under physiological conditions. © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  15. A quantitative metabolomics peek into planarian regeneration.

    PubMed

    Natarajan, Nivedita; Ramakrishnan, Padma; Lakshmanan, Vairavan; Palakodeti, Dasaradhi; Rangiah, Kannan

    2015-05-21

    The fresh water planarian species Schmidtea mediterranea is an emerging stem cell model because of its capability to regenerate a whole animal from a small piece of tissue. It is one of the best model systems to address the basic mechanisms essential for regeneration. Here, we are interested in studying the roles of various amines, thiols and nucleotides in planarian regeneration, stem cell function and growth. We developed mass spectrometry based quantitative methods and validated the differential enrichment of 35 amines, 7 thiol metabolites and 4 nucleotides from both intact and regenerating planarians. Among the amines, alanine in sexual and asparagine in asexual are the highest (>1000 ng/mg) in the intact planarians. The levels of thiols such as cysteine and GSH are 651 and 1107 ng mg(-1) in planarians. Among the nucleotides, the level of cGMP is the lowest (0.03 ng mg(-1)) and the level of AMP is the highest (187 ng mg(-1)) in both of the planarian strains. We also noticed increasing levels of amines in both anterior and posterior regenerating planarians. The blastema from day 3 regenerating planarians also showed higher amounts of many amines. Interestingly, the thiol (cysteine and GSH) levels are well maintained during planarian regeneration. This suggests an inherent and effective mechanism to control induced oxidative stress because of the robust regeneration and stem cell proliferation. Like in intact planarians, the level of cGMP is also very low in regenerating planarians. Surprisingly, the levels of amines and thiols in head regenerating blastemas are ∼3 times higher compared to those for tail regenerating blastemas. Thus our results strongly indicate the potential roles of amines, thiols and nucleotides in planarian regeneration.

  16. The Effect of Corneal Epithelium on Corneal Curvature in Patients with Keratoconus.

    PubMed

    Akcay, Emine Kalkan; Uysal, Betul Seher; Sarac, Ozge; Ugurlu, Nagehan; Yulek, Fatma; Cagil, Nurullah; Aslan, Nabi

    2015-01-01

    To investigate the effects of corneal epithelium on corneal curvature in patients with keratoconus. This is a prospective, nonrandomized study. Fifty-nine eyes of 47 patients diagnosed as keratoconus and for whom corneal collagen crosslinking (CXL) was recruited in this study. This study is a single-center clinical trial. Pregnancy, lactation, connective tissue disease, corneal thickness below 350 μm, severe dry eyes, or scar of corneal surgery were exclusion criteria. Before and during CXL procedure after removing the corneal epithelium, maximum values of corneal apical curvature, simulated keratometry 1 (Sim-K1), simulated keratometry 2 (Sim-K2), temporal and inferior curvature values, all of which are 1.5 mm from the corneal center, were calculated. These values before and after removal of epithelium were compared statistically. Mean age of patients was 23.30 ± 5.5 (12-38) years. Twenty-eight (59%) were male while 19 (41%) were female. Mean values measured before and after removing the corneal epithelium were: apical curvature; 59.19 ± 7.2 (47.06-82.40) diopter (D) and 61.70 ± 8.8 (49.19-92.66) D (p = 0.001), SimK1; 47.57 ± 4.3 (39.14-64.57) D and 48.23 ± 4.3 (41.89-66.70) D (p = 0.001), SimK2; 52.04 ± 5.3 (43.56-69.34) D and 53.34 ± 5.6 (43.73-70.89) D (p = 0.001), inferior curvature; 53,85 ± 5.2 (43.47-76.56) D and 55.05 ± 5.8 (44.56-81.93) D (p = 0.002), temporal curvature 49.49 ± 5.1 (41.50-71.03) D and 51.53 ± 5.4 (41.58-73.34) D (p = 0.001), respectively. In keratoconus patients during CXL treatment, after removing the corneal epithelium, more steepness is detected in the curvature of the steeper area of the cornea. When evaluating patients with keratoconus, the masking effect of corneal epithelium on values of curvature should be taken into consideration.

  17. Multi-resolution cell orientation congruence descriptors for epithelium segmentation in endometrial histology images.

    PubMed

    Li, Guannan; Raza, Shan E Ahmed; Rajpoot, Nasir M

    2017-04-01

    It has been recently shown that recurrent miscarriage can be caused by abnormally high ratio of number of uterine natural killer (UNK) cells to the number of stromal cells in human female uterus lining. Due to high workload, the counting of UNK and stromal cells needs to be automated using computer algorithms. However, stromal cells are very similar in appearance to epithelial cells which must be excluded in the counting process. To exclude the epithelial cells from the counting process it is necessary to identify epithelial regions. There are two types of epithelial layers that can be encountered in the endometrium: luminal epithelium and glandular epithelium. To the best of our knowledge, there is no existing method that addresses the segmentation of both types of epithelium simultaneously in endometrial histology images. In this paper, we propose a multi-resolution Cell Orientation Congruence (COCo) descriptor which exploits the fact that neighbouring epithelial cells exhibit similarity in terms of their orientations. Our experimental results show that the proposed descriptors yield accurate results in simultaneously segmenting both luminal and glandular epithelium. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Oak regeneration why big is better

    Treesearch

    Paul P. Kormanik; Shi-Jean S. Sung; T.L. Kormanik; Stanley J. Zarnoch

    1995-01-01

    It is generally accepted that large preharvest advanced oak regeneration is required for maintaining a significant oak component in future stands. However, developing advanced oak regeneration on productive sites has been difficult because stand prescriptions encouraging oak regeneration are the same conditions that favor development of potentially faster growing...

  19. Trends in tissue repair and regeneration.

    PubMed

    Galliot, Brigitte; Crescenzi, Marco; Jacinto, Antonio; Tajbakhsh, Shahragim

    2017-02-01

    The 6th EMBO conference on the Molecular and Cellular Basis of Regeneration and Tissue Repair took place in Paestum (Italy) on the 17th-21st September, 2016. The 160 scientists who attended discussed the importance of cellular and tissue plasticity, biophysical aspects of regeneration, the diverse roles of injury-induced immune responses, strategies to reactivate regeneration in mammals, links between regeneration and ageing, and the impact of non-mammalian models on regenerative medicine. © 2017. Published by The Company of Biologists Ltd.

  20. Method And Apparatus For Regenerating Nox Adsorbers

    DOEpatents

    Driscoll, J. Joshua; Endicott, Dennis L.; Faulkner, Stephen A.; Verkiel, Maarten

    2006-03-28

    Methods and apparatuses for regenerating a NOx adsorber coupled with an exhaust of an engine. An actuator drives a throttle valve to a first position when regeneration of the NOx adsorber is desired. The first position is a position that causes the regeneration of the NOx adsorber. An actuator drives the throttle valve to a second position while regeneration of the NOx adsorber is still desired. The second position being a position that is more open than the first position and operable to regenerate a NOx adsorber.

  1. Angiogenesis is inhibitory for mammalian digit regeneration

    PubMed Central

    Yu, Ling; Yan, Mingquan; Simkin, Jennifer; Ketcham, Paulina D.; Leininger, Eric; Han, Manjong

    2014-01-01

    Abstract The regenerating mouse digit tip is a unique model for investigating blastema formation and epimorphic regeneration in mammals. The blastema is characteristically avascular and we previously reported that blastema expression of a known anti‐angiogenic factor gene, Pedf, correlated with a successful regenerative response (Yu, L., Han, M., Yan, M., Lee, E. C., Lee, J. & Muneoka, K. (2010). BMP signaling induces digit regeneration in neonatal mice. Development, 137, 551–559). Here we show that during regeneration Vegfa transcripts are not detected in the blastema but are expressed at the onset of differentiation. Treating the amputation wound with vascular endothelial growth factor enhances angiogenesis but inhibits regeneration. We next tested bone morphogenetic protein 9 (BMP9), another known mediator of angiogenesis, and found that BMP9 is also a potent inhibitor of digit tip regeneration. BMP9 induces Vegfa expression in the digit stump suggesting that regenerative failure is mediated by enhanced angiogenesis. Finally, we show that BMP9 inhibition of regeneration is completely rescued by treatment with pigment epithelium‐derived factor. These studies show that precocious angiogenesis is inhibitory for regeneration, and provide compelling evidence that the regulation of angiogenesis is a critical factor in designing therapies aimed at stimulating mammalian regeneration. PMID:27499862

  2. Regeneration-associated genes on optic nerve regeneration in fish retina.

    PubMed

    Ogai, Kazuhiro; Nishitani, Maki; Kuwana, Ayaka; Mawatari, Kazuhiro; Koriyama, Yoshiki; Sugitani, Kayo; Nakashima, Hiroshi; Kato, Satoru

    2014-01-01

    It has been well documented that fish central nervous system, including retina and optic nerve, can regenerate and recover its function after nerve injury. Within a few decades, a number of regeneration-associated genes (RAGs) have been identified in fish retina following optic nerve injury (ONI). RAGs can be classified into two groups: cell survival- and axonal outgrowth-related genes. In fish retina after ONI, cell survival-related genes were upregulated in 1-6 days after ONI, which corresponds to the preparation stage for cell survival and axonal sprouting. Subsequently, axonal outgrowth-related genes were upregulated in 1-6 weeks after ONI, which corresponds to the axonal regrowth stage. Recently, we've found a novel type of RAGs, dedifferentiation-related genes, that are upregulated in overlapping time between cell survival and axonal regrowth (3-10 days after ONI). In this chapter we summarize these three types of RAGs that promote optic nerve regeneration in the fish retina after ONI.

  3. Antimicrobial Barrier of an in vitro Oral Epithelial Model

    PubMed Central

    Kimball, Janet R.; Nittayananta, Wipawee; Klausner, Mitchell; Chung, Whasun O.; Dale, Beverly A.

    2008-01-01

    Objective Oral epithelia function as a microbial barrier and are actively involved in recognizing and responding to bacteria. Our goal was to examine a tissue engineered model of buccal epithelium for its response to oral bacteria and proinflammatory cytokines and compare the tissue responses with those of a submerged monolayer cell culture. Design The tissue model was characterized for keratin and β-defensin expression. Altered expression of β-defensins was evaluated by RT-PCR after exposure of the apical surface to oral bacteria and after exposure to TNF-α in the medium. These were compared to the response in traditional submerged oral epithelial cell culture. Results The buccal model showed expression of differentiation specific keratin 13, hBD1 and hBD3 in the upper half of the tissue; hBD2 was not detected. hBD1 mRNA was constitutively expressed, while hBD2 mRNA increased 2-fold after exposure of the apical surface to three oral bacteria tested and hBD3 mRNA increased in response to the non-pathogenic bacteria tested. In contrast, hBD2 mRNA increased 3–600 fold in response to bacteria in submerged cell culture. HBD2 mRNA increased over 100 fold in response to TNF-α in the tissue model and 50 fold in submerged cell culture. Thus, the tissue model is capable of upregulating hBD2, however, the minimal response to bacteria suggests that the tissue has an effective antimicrobial barrier due to its morphology, differentiation, and defensin expression. Conclusions The oral mucosal model is differentiated, expresses hBD1 and hBD3, and has an intact surface with a functional antimicrobial barrier. PMID:16815238

  4. Polymeric Micro- and Nanofabricatced Devices for Oral Drug Delivery

    NASA Astrophysics Data System (ADS)

    Fox, Cade Brylee

    While oral drug administration is by far the most preferred route, it is accompanied by many barriers that limit drug uptake such as the low pH of the stomach, metabolic and proteolytic enzymes, and limited permeability of the intestinal epithelium. As a result, many drugs ranging from small molecules to biological therapeutics have limited oral bioavailability, precluding them from oral administration. To address this issue, microfabrication has been applied to create planar, asymmetric devices capable of binding to the lining of the gastrointestinal tract and releasing drug at high concentrations, thereby increasing oral drug uptake. While the efficacy of these devices has been validated in vitro and in vivo, modifying their surfaces with nanoscale features has potential to refine their properties for enhanced drug delivery. This dissertation first presents an approach to fabricate polymeric microdevices coated with nanowires in a rapid, high throughput manner. The nanowires demonstrate rapid drug localization onto the surface of these devices via capillary action and increased adhesion to epithelial tissue, suggesting that this fabrication technique can be used to create devices with enhanced properties for oral drug delivery. Also presented are microdevices sealed with nanostraw membranes. The nanostraw membranes provide sustained drug release by limiting drug efflux from the devices, prevent drug degradation by limiting influx of outside biomolecules, and enhance device bioadhesion by penetrating into the mucus layer of the intestinal lining. Finally, an approach that dramatically increases the capacity and efficiency of drug loading into microdevices over previous methods is presented. A picoliter-volume printer is used to print drug directly into device reservoirs in an automated fashion. The technologies presented here expand the capabilities of microdevices for oral drug delivery by incorporating nanoscale structures that enhance device bioadhesion

  5. Resolvin D1 promotes corneal epithelial wound healing and restoration of mechanical sensation in diabetic mice.

    PubMed

    Zhang, Zhenzhen; Hu, Xiaoli; Qi, Xia; Di, Guohu; Zhang, Yangyang; Wang, Qian; Zhou, Qingjun

    2018-01-01

    To investigate the effect and mechanism of proresolving lipid mediator resolvin D1 (RvD1) on the corneal epithelium and the restoration of mechanical sensation in diabetic mice. Type 1 diabetes was induced in mice with intraperitoneal streptozocin injections. The healthy and diabetic mice underwent removal of the central corneal epithelium, and then 100 ng/ml RvD1 or its formyl peptide receptor 2 (FPR2) antagonist WRW4 was used to treat the diabetic mice. Regeneration of the corneal epithelium and nerves was observed with sodium fluorescein staining and whole-mount anti-β3-tubulin fluorescence staining. The inflammatory response level was measured with hematoxylin and eosin staining (inflammatory cell infiltration), enzyme-linked immunosorbent assay (tumor necrosis factor alpha and interleukin-1 beta content), myeloperoxidase activity, and fluorescence staining (macrophage content). The reactive oxygen species (ROS) and glutathione (GSH) levels were examined with incubation with fluorescent probes, and oxidative stress-related protein expression levels were evaluated with fluorescence staining and western blotting. Topical application of RvD1 promoted regeneration of the corneal epithelium in diabetic mice, accompanied by the reactivation of signaling and inflammation resolution related to regeneration of the epithelium. Furthermore, RvD1 directly attenuated the accumulation of ROS and nicotinamide adenine dinucleotide phosphate oxidase 2/4 expression, while RvD1 enhanced GSH synthesis and reactivated the Nrf2-ARE signaling pathway that was impaired in the corneal epithelium in the diabetic mice. More interestingly, topical application of RvD1 promoted regeneration of corneal nerves and completely restored impaired mechanical sensitivity of the cornea in diabetic mice. In addition, the promotion of corneal epithelial wound healing by RvD1 in diabetic mice was abolished by its FPR2 antagonist WRW4. Topical application of RvD1 promotes corneal epithelial wound

  6. Dynamic relationship of the epithelium and mesenchyme during salivary gland initiation: the role of Fgf10

    PubMed Central

    Wells, Kirsty L.; Gaete, Marcia; Matalova, Eva; Deutsch, Danny; Rice, David; Tucker, Abigail S.

    2013-01-01

    Summary Salivary glands provide an excellent model for the study of epithelial–mesenchymal interactions. We have looked at the interactions involved in the early initiation and development of murine salivary glands using classic recombination experiments and knockout mice. We show that salivary gland epithelium, at thickening and initial bud stages, is able to direct salivary gland development in non-gland pharyngeal arch mesenchyme at early stages. The early salivary gland epithelium is therefore able to induce gland development in non-gland tissue. This ability later shifts to the mesenchyme, with non-gland epithelium, such as from the limb bud, able to form a branching gland when combined with pseudoglandular stage gland mesenchyme. This shift appears to involve Fgf signalling, with signals from the epithelium inducing Fgf10 in the mesenchyme. Fgf10 then signals back to the epithelium to direct gland down-growth and bud development. These experiments highlight the importance of epithelial–mesenchymal signalling in gland initiation, controlling where, when and how many salivary glands form. PMID:24167707

  7. Self-regenerating column chromatography

    DOEpatents

    Park, Woo K.

    1995-05-30

    The present invention provides a process for treating both cations and anions by using a self-regenerating, multi-ionic exchange resin column system which requires no separate regeneration steps. The process involves alternating ion-exchange chromatography for cations and anions in a multi-ionic exchange column packed with a mixture of cation and anion exchange resins. The multi-ionic mixed-charge resin column works as a multi-function column, capable of independently processing either cationic or anionic exchange, or simultaneously processing both cationic and anionic exchanges. The major advantage offered by the alternating multi-function ion exchange process is the self-regeneration of the resins.

  8. Different alpha crystallin expression in human age-related and congenital cataract lens epithelium.

    PubMed

    Yang, Jing; Zhou, Sheng; Guo, Minfei; Li, Yuting; Gu, Jianjun

    2016-05-28

    The purpose of this study was to investigate the different expressions of αA-crystallin and αB-crystallin in human lens epithelium of age-related and congenital cataracts. The central part of the human anterior lens capsule approximately 5 mm in diameter together with the adhering epithelial cells, were harvested and processed within 6 hours after cataract surgery from age-related and congenital cataract patients or from normal eyes of fresh cadavers. The mRNA and soluble protein levels of αA-crystallin and αB-crystallin in the human lens epithelium were detected by real-time PCR and western blots, respectively. The mRNA and soluble protein expressions of αA-crystallin and αB-crystallin in the lens epithelium were both reduced in age-related and congenital cataract groups when compared with the normal control group. However, the degree of α-crystallin loss in the lens epithelium was highly correlated with different cataract types. The α-crystallin expression of the lens epithelium was greatly reduced in the congenital cataract group but only moderately decreased in the age-related cataract group. The reduction of αA-crystallin soluble protein levels in the congenital cataract group was approximately 2.4 fold decrease compared with that of the age-related cataract group, while an mRNA fold change of 1.67 decrease was observed for the age-related cataract group. Similarly, the reduction of soluble protein levels of αB-crystallin in the congenital cataract group was approximately a 1.57 fold change compared with that of the age-related cataract group. A 1.75 fold change for mRNA levels compared with that of the age-related cataract group was observed. The results suggest that the differential loss of α-crystallin in the human lens epithelium could be associated with the different mechanisms of cataractogenesis in age-related versus congenital cataracts, subsequently resulting in different clinical presentations.

  9. Vascular Endothelial Growth Factor and Angiopoietin are Required for Prostate Regeneration.

    PubMed Central

    Wang, Gui-min; Kovalenko, Bruce; Huang, Yili; Moscatelli, David

    2007-01-01

    BACKGROUND The regulation of the prostate size by androgens may be partly the result of androgen effects on the prostatic vasculature. We examined the effect of changes in androgen levels on the expression of a variety of angiogenic factors in the mouse prostate and determined if vascular endothelial growth factor (VEGF)-A and the angiopoietins are involved in the vascular response to androgens. METHODS Expression of angiogenic factors in prostate was quantitated using real-time PCR at different times after castration and after administration of testosterone to castrated mice. Angiopoietins were localized in prostate by immunohistochemistry and in situ hybridization. The roles of VEGF and the angiopoietins in regeneration of the prostate were examined in mice inoculated with cells expressing soluble VEGF receptor-2 or soluble Tie-2. RESULTS Castration resulted in a decrease in VEGF-A, VEGF-B, VEGF-C, placenta growth factor, FGF-2, and FGF-8 expression after one day. In contrast, VEGF-D mRNA levels increased. No changes in angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), hepatocyte growth factor, VEGF receptor-1, VEGF receptor-2 or tie-2 mRNA levels were observed. Administration of testosterone to castrated mice had the opposite effect on expression of these angiogenic factors. Ang-2 was expressed predominately in prostate epithelial cells whereas Ang-1 was expressed in epithelium and smooth muscle. Inoculation of mice with cells expressing soluble VEGF receptor-2 or Tie-2 blocked the increase in vascular density normally observed after administration of testosterone to castrated mice. The soluble receptors also blocked the increase in prostate weight and proliferation of prostatic epithelial cells. CONCLUSION VEGF-A and angiopoietins are required for the vascular response to androgens and for the ability of the prostate to regenerate in response to androgens. PMID:17221843

  10. The effects of changes of water balance on the renal pelvic epithelium of the rat.

    PubMed

    Khorshid, M R; Moffat, D B

    1975-01-01

    The effects of changes of water balance on the renal pelvic epithelium of the rat. The fine structure of the various epithelia which line the renal pelvis was investigated in five hydropenic rats and five rats undergoing a water diuresis. In the former, the thin epithelium which covers the outer medulla showed dilated intercellular spaces and an increased number of cytoplasmic vacuoles whereas the intercellular spaces were tightly closed and there were few vacuoles in the diuretic rats. It was considered that these changes indicate an exchange of water and solute between pelvic urine and the outer since medulla they are similar to those occurring in epithelia elsewhere which are engaged in transport of salt or water. Similar but less marked changes were found in the papillary epithelium. Changes in the transitional epithelium were similar to those which have previously been described elsewhere in the urinary tract.

  11. Xenogeneic Acellular Conjunctiva Matrix as a Scaffold of Tissue-Engineered Corneal Epithelium

    PubMed Central

    Zhao, Haifeng; Qu, Mingli; Wang, Yao; Wang, Zhenyu; Shi, Weiyun

    2014-01-01

    Amniotic membrane-based tissue-engineered corneal epithelium has been widely used in the reconstruction of the ocular surface. However, it often degrades too early to ensure the success of the transplanted corneal epithelium when treating patients with severe ocular surface disorders. In the present study, we investigated the preparation of xenogeneic acellular conjunctiva matrix (aCM) and evaluated its efficacy and safety as a scaffold of tissue-engineered corneal epithelium. Native porcine conjunctiva was decellularized with 0.1% sodium dodecyl sulfate (SDS) for 12 h at 37°C and sterilized via γ-irradiation. Compared with native conjunctiva, more than 92% of the DNA was removed, and more than 90% of the extracellular matrix components (glycosaminoglycan and collagen) remained after the decellularization treatment. Compared with denuded amniotic membrane (dAM), the aCM possessed favorable optical transmittance, tensile strength, stability and biocompatibility as well as stronger resistance to degradation both in vitro and in vivo. The corneal epithelial cells seeded on aCM formed a multilayered epithelial structure and endured longer than did those on dAM. The aCM-based tissue-engineered corneal epithelium was more effective in the reconstruction of the ocular surface in rabbits with limbal stem cell deficiency. These findings support the application of xenogeneic acellular conjunctiva matrix as a scaffold for reconstructing the ocular surface. PMID:25375996

  12. Spatiotemporal expression of Ezh2 in the developing mouse cochlear sensory epithelium.

    PubMed

    Chen, Yan; Li, Wenyan; Li, Wen; Chai, Renjie; Li, Huawei

    2016-09-01

    The enhancer of zeste 2 polycomb repressive complex 2 subunit (Ezh2) is a histone-lysine Nmethyltransferase enzyme that participates in DNA methylation. Ezh2 has also been reported to play crucial roles in stem cell proliferation and differentiation. However, the detailed expression profile of Ezh2 during mouse cochlear development has not been investigated. Here, we examined the spatiotemporal expression of Ezh2 in the cochlea during embryonic and postnatal development. Ezh2 expression began to be observed in the whole otocyst nuclei at embryonic day 9.5 (E9.5). At E12.5, Ezh2 was expressed in the nuclei of the cochlear prosensory epithelium. At E13.5 and E15.5, Ezh2 was expressed from the apical to the basal turns in the nuclei of the differentiating cochlear epithelium. At postnatal day (P) 0 and 7, the Ezh2 expression was located in the nuclei of the cochlear epithelium in all three turns and could be clearly seen in outer and inner hair cells, supporting cells, the stria vascularis, and spiral ganglion cells. Ezh2 continued to be expressed in the cochlear epithelium of adult mice. Our results provide the basic Ezh2 expression pattern and might be useful for further investigating the detailed role of Ezh2 during cochlear development.

  13. Epoxyeicosanoids promote organ and tissue regeneration.

    PubMed

    Panigrahy, Dipak; Kalish, Brian T; Huang, Sui; Bielenberg, Diane R; Le, Hau D; Yang, Jun; Edin, Matthew L; Lee, Craig R; Benny, Ofra; Mudge, Dayna K; Butterfield, Catherine E; Mammoto, Akiko; Mammoto, Tadanori; Inceoglu, Bora; Jenkins, Roger L; Simpson, Mary A; Akino, Tomoshige; Lih, Fred B; Tomer, Kenneth B; Ingber, Donald E; Hammock, Bruce D; Falck, John R; Manthati, Vijaya L; Kaipainen, Arja; D'Amore, Patricia A; Puder, Mark; Zeldin, Darryl C; Kieran, Mark W

    2013-08-13

    Epoxyeicosatrienoic acids (EETs), lipid mediators produced by cytochrome P450 epoxygenases, regulate inflammation, angiogenesis, and vascular tone. Despite pleiotropic effects on cells, the role of these epoxyeicosanoids in normal organ and tissue regeneration remains unknown. EETs are produced predominantly in the endothelium. Normal organ and tissue regeneration require an active paracrine role of the microvascular endothelium, which in turn depends on angiogenic growth factors. Thus, we hypothesize that endothelial cells stimulate organ and tissue regeneration via production of bioactive EETs. To determine whether endothelial-derived EETs affect physiologic tissue growth in vivo, we used genetic and pharmacological tools to manipulate endogenous EET levels. We show that endothelial-derived EETs play a critical role in accelerating tissue growth in vivo, including liver regeneration, kidney compensatory growth, lung compensatory growth, wound healing, corneal neovascularization, and retinal vascularization. Administration of synthetic EETs recapitulated these results, whereas lowering EET levels, either genetically or pharmacologically, delayed tissue regeneration, demonstrating that pharmacological modulation of EETs can affect normal organ and tissue growth. We also show that soluble epoxide hydrolase inhibitors, which elevate endogenous EET levels, promote liver and lung regeneration. Thus, our observations indicate a central role for EETs in organ and tissue regeneration and their contribution to tissue homeostasis.

  14. Ozone-Induced Injury and Oxidative Stress in Bronchiolar Epithelium Are Associated with Altered Pulmonary Mechanics

    PubMed Central

    Sunil, Vasanthi R.

    2013-01-01

    In these studies, we analyzed the effects of ozone on bronchiolar epithelium. Exposure of rats to ozone (2 ppm, 3h) resulted in rapid (within 3h) and persistent (up to 72h) histological changes in the bronchiolar epithelium, including hypercellularity, loss of cilia, and necrotizing bronchiolitis. Perivascular edema and vascular congestion were also evident, along with a decrease in Clara cell secretory protein in bronchoalveolar lavage, which was maximal 24h post-exposure. Ozone also induced the appearance of 8-hydroxy-2′-deoxyguanosine, Ym1, and heme oxygenase-1 in the bronchiolar epithelium. This was associated with increased expression of cleaved caspase-9 and beclin-1, indicating initiation of apoptosis and autophagy. A rapid and persistent increase in galectin-3, a regulator of epithelial cell apoptosis, was also observed. Following ozone exposure (3–24h), increased expression of cyclooxygenase-2, inducible nitric oxide synthase, and arginase-1 was noted in bronchiolar epithelium. Ozone-induced injury and oxidative stress in bronchiolar epithelium were linked to methacholine-induced alterations in pulmonary mechanics. Thus, significant increases in lung resistance and elastance, along with decreases in lung compliance and end tidal volume, were observed at higher doses of methacholine. This indicates that ozone causes an increase in effective stiffness of the lung as a consequence of changes in the conducting airways. Collectively, these studies demonstrate that bronchiolar epithelium is highly susceptible to injury and oxidative stress induced by acute exposure to ozone; moreover, this is accompanied by altered lung functioning. PMID:23492811

  15. In-vivo nonlinear optical microscopy (NLOM) of epithelial-connective tissue interface (ECTI) reveals quantitative measures of neoplasia in hamster oral mucosa.

    PubMed

    Pal, Rahul; Yang, Jinping; Ortiz, Daniel; Qiu, Suimin; Resto, Vicente; McCammon, Susan; Vargas, Gracie

    2015-01-01

    The epithelial-connective tissue interface (ECTI) plays an integral role in epithelial neoplasia, including oral squamous cell carcinoma (OSCC). This interface undergoes significant alterations due to hyperproliferating epithelium that supports the transformation of normal epithelium to precancers and cancer. We present a method based on nonlinear optical microscopy to directly assess the ECTI and quantify dysplastic alterations using a hamster model for oral carcinogenesis. Neoplastic and non-neoplastic normal mucosa were imaged in-vivo by both multiphoton autofluorescence microscopy (MPAM) and second harmonic generation microscopy (SHGM) to obtain cross-sectional reconstructions of the oral epithelium and lamina propria. Imaged sites were biopsied and processed for histopathological grading and measurement of ECTI parameters. An ECTI shape parameter was calculated based on deviation from the linear geometry (ΔLinearity) seen in normal mucosa was measured using MPAM-SHGM and histology. The ECTI was readily visible in MPAM-SHGM and quantitative shape analysis showed ECTI deformation in dysplasia but not in normal mucosa. ΔLinearity was significantly (p < 0.01) higher in dysplasia (0.41±0.24) than normal (0.11±0.04) as measured in MPAM-SHGM and results were confirmed in histology which showed similar trends in ΔLinearity. Increase in ΔLinearity was also statistically significant for different grades of dysplasia. In-vivo ΔLinearity measurement alone from microscopy discriminated dysplasia from normal tissue with 87.9% sensitivity and 97.6% specificity, while calculations from histology provided 96.4% sensitivity and 85.7% specificity. Among other quantifiable architectural changes, a progressive statistically significant increase in epithelial thickness was seen with increasing grade of dysplasia. MPAM-SHGM provides new noninvasive ways for direct characterization of ECTI which may be used in preclinical studies to investigate the role of this interface in

  16. The immunohistochemical detection of involucrin in denture induced fibrous inflammatory hyperplasia of oral mucous membrane.

    PubMed

    Thomas, G A

    1991-01-01

    Involucrin is a major structural protein specific to the cross-linked cell envelope found in the stratum corneum of stratified squamous epithelium. This protein is considered to be an excellent immunohistochemical marker of normal squamous differentiation. Detection of variations to the patterns of immunostaining for involucrin may also be of value in the differential diagnosis between benign and malignant lesions. Previous studies of involucrin expression in oral mucosa have failed to clarify the effect of chronic inflammatory change upon the patterns of immunoreactivity. This study investigated involucrin staining patterns in fibrous inflammatory hyperplasia of oral mucous membrane (FIH). The results suggest that in FIH an altered pattern of involucrin immunostain occurs in areas of severe inflammatory change. This may reflect changes to the pattern of squamous differentiation in this tissue.

  17. Nerves Regulate Cardiomyocyte Proliferation and Heart Regeneration.

    PubMed

    Mahmoud, Ahmed I; O'Meara, Caitlin C; Gemberling, Matthew; Zhao, Long; Bryant, Donald M; Zheng, Ruimao; Gannon, Joseph B; Cai, Lei; Choi, Wen-Yee; Egnaczyk, Gregory F; Burns, Caroline E; Burns, C Geoffrey; MacRae, Calum A; Poss, Kenneth D; Lee, Richard T

    2015-08-24

    Some organisms, such as adult zebrafish and newborn mice, have the capacity to regenerate heart tissue following injury. Unraveling the mechanisms of heart regeneration is fundamental to understanding why regeneration fails in adult humans. Numerous studies have revealed that nerves are crucial for organ regeneration, thus we aimed to determine whether nerves guide heart regeneration. Here, we show using transgenic zebrafish that inhibition of cardiac innervation leads to reduction of myocyte proliferation following injury. Specifically, pharmacological inhibition of cholinergic nerve function reduces cardiomyocyte proliferation in the injured hearts of both zebrafish and neonatal mice. Direct mechanical denervation impairs heart regeneration in neonatal mice, which was rescued by the administration of neuregulin 1 (NRG1) and nerve growth factor (NGF) recombinant proteins. Transcriptional analysis of mechanically denervated hearts revealed a blunted inflammatory and immune response following injury. These findings demonstrate that nerve function is required for both zebrafish and mouse heart regeneration. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Regeneration of tert-butylhydroquinone by tea polyphenols.

    PubMed

    Guo, Yafang; Guo, Yahui; Xie, Yunfei; Cheng, Yuliang; Qian, He; Yao, Weirong

    2017-05-01

    To study the antioxidant capacity (AC) regeneration of tert-butylhydroquinone (TBHQ) by tea polyphenols (TPs), a separable system has been designed for its evaluation. The AC values of three natural food matrices (liquorice, oat, and ginger) and TBHQ regenerated by TPs were all higher than their controls, and similar to the initial values (p<0.05). The average regeneration efficiency (RE) value was 1.49 for these three natural food matrices, and 0.82 for TBHQ. Electron paramagnetic resonance spectroscopy analysis has revealed the synergistic effect of TBHQ and TPs, which arose from the regeneration of TBHQ by TPs. The RE value of TBHQ regeneration by TPs embedded in a gelatine membrane was 0.51. The results demonstrated that TPs showed a capacity for regenerating TBHQ, indicating a potential application in regenerative packaging, whereby one antioxidant would be added to the food matrix, with another one as the regenerator incorporated into the packaging material. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Induction of heat shock protein 70 in rat olfactory epithelium by toxic chemicals: in vitro and in vivo studies.

    PubMed

    Simpson, S A; Alexander, D J; Reed, C J

    2005-04-01

    We have previously developed a rat nasal explant system for investigating upper respiratory tract toxicity, and the aims of this study were to determine whether heat shock protein (HSP) 70 is induced in this model following exposure to carbon tetrachloride (CCl4), dimethyl adipate (DMA), methyl iodide (CH3I) or paracetamol, and whether HSP70 can also be induced in the nasal cavity in vivo. Intracellular ATP was significantly depleted in ethmoturbinates incubated for 4 h with the toxins (0-100 mM; EC50 concentrations: CCl4 32 mM, DMA 3 mM, CH3I 1.5 mM, paracetamol 70 mM), but there was little induction of HSP70. Turbinates were then incubated for 1 h with CCl4 (5 mM), DMA (1.5 mM), CH3I (0.57 mM) or paracetamol (30 mM) and allowed to recover for up to 24 h. Treatment with CCl4, DMA or paracetamol resulted in 250-300% induction of HSP70. Male rats were administered a single oral dose of CCl4 (1600 mg/kg) and killed 16 h later. Degenerative lesions (epithelial undulation and hydropic vacuolation) were evident in the olfactory epithelium, and immunohistochemical analysis of HSP70 revealed increased staining in, or proximate to, areas of damage. Thus, HSP70 can be induced in the olfactory epithelium both in vitro and in vivo.

  20. A current overview of materials and strategies for potential use in maxillofacial tissue regeneration.

    PubMed

    Jazayeri, Hossein E; Tahriri, Mohammadreza; Razavi, Mehdi; Khoshroo, Kimia; Fahimipour, Farahnaz; Dashtimoghadam, Erfan; Almeida, Luis; Tayebi, Lobat

    2017-01-01

    Tissue regeneration is rapidly evolving to treat anomalies in the entire human body. The production of biodegradable, customizable scaffolds to achieve this clinical aim is dependent on the interdisciplinary collaboration among clinicians, bioengineers and materials scientists. While bone grafts and varying reconstructive procedures have been traditionally used for maxillofacial defects, the goal of this review is to provide insight on all materials involved in the progressing utilization of the tissue engineering approach to yield successful treatment outcomes for both hard and soft tissues. In vitro and in vivo studies that have demonstrated the restoration of bone and cartilage tissue with different scaffold material types, stem cells and growth factors show promise in regenerative treatment interventions for maxillofacial defects. The repair of the temporomandibular joint (TMJ) disc and mandibular bone were discussed extensively in the report, supported by evidence of regeneration of the same tissue types in different medical capacities. Furthermore, in addition to the thorough explanation of polymeric, ceramic, and composite scaffolds, this review includes the application of biodegradable metallic scaffolds for regeneration of hard tissue. The purpose of compiling all the relevant information in this review is to lay the foundation for future investigation in materials used in scaffold synthesis in the realm of oral and maxillofacial surgery. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Animal regeneration: ancestral character or evolutionary novelty?

    PubMed

    Slack, Jonathan Mw

    2017-09-01

    An old question about regeneration is whether it is an ancestral character which is a general property of living matter, or whether it represents a set of specific adaptations to the different circumstances faced by different types of animal. In this review, some recent results on regeneration are assessed to see if they can throw any new light on this question. Evidence in favour of an ancestral character comes from the role of Wnt and bone morphogenetic protein signalling in controlling the pattern of whole-body regeneration in acoels, which are a basal group of bilaterian animals. On the other hand, there is some evidence for adaptive acquisition or maintenance of the regeneration of appendages based on the occurrence of severe non-lethal predation, the existence of some novel genes in regenerating organisms, and differences at the molecular level between apparently similar forms of regeneration. It is tentatively concluded that whole-body regeneration is an ancestral character although has been lost from most animal lineages. Appendage regeneration is more likely to represent a derived character resulting from many specific adaptations. © 2017 The Author.

  2. Chemopreventive effect of fermented brown rice and rice bran on 4-nitroquinoline 1-oxide-induced oral carcinogenesis in rats.

    PubMed

    Long, Nguyen Khanh; Makita, Hiroki; Yamashita, Tomomi; Toida, Makoto; Kato, Keizo; Hatakeyama, Daijiro; Shibata, Toshiyuki

    2007-04-01

    The preventive effects of the dietary administration of brown rice and rice bran fermented with Aspergillus oryzae (FBRA) on oral carcinogenesis induced by 4-nitroquinoline 1-oxide (4-NQO) were investigated in male F344 rats. At 7 weeks of age, the animals were given 20 ppm 4-NQO in their drinking water for 8 weeks to induce tongue neoplasms. Groups of rats were fed diets containing 5 or 10% FBRA during the initiation or postinitiation phases of the 4-NQO-induced oral carcinogenesis. The other groups consisted of rats fed 10% FBRA or untreated rats. At the termination of the study (week 32), the incidences, multiplicities of tongue lesions (pre-neoplasms and neoplasms) and the cell proliferation activity estimated by the 5-bromodeoxyuridine (BrdU)-labeling index were compared among the groups. Feeding of 5% FBRA during the initiation phase significantly decreased the incidence (68.2 vs 36.8%; p<0.05) and multiplicity (1.05+/-0.84 vs 0.37+/-0.50; p<0.005) of the tongue carcinoma. When feeding of 10% FBRA occurred after the 4-NQO exposure, the multiplicity of tongue carcinoma was also reduced (1.05+/-0.84 vs 0.52+/-0.60; p<0.05). In addition, the dietary administration of FBRA at both doses significantly decreased the BrdU-labeling index in the oral squamous epithelium (p<0.05). Although a dose-dependent response was not observed, FBRA is effective in suppressing the development of 4-NQO-induced oral carcinogenesis by its concurrent exposure to the carcinogen. The inhibitory effect could be related to the suppression of the hyperproliferation of cells in the tongue epithelium and the radical scavenging activity of FBRA.

  3. Return of Function after Hair Cell Regeneration

    PubMed Central

    Ryals, Brenda M.; Dent, Micheal L.; Dooling, Robert J.

    2012-01-01

    The ultimate goal of hair cell regeneration is to restore functional hearing. Because birds begin perceiving and producing song early in life, they provide a propitious model for studying not only whether regeneration of lost hair cells can return auditory sensitivity but also whether this regenerated periphery can restore complex auditory perception and production. They are the only animal where hair cell regeneration occurs naturally after hair cell loss and where the ability to correctly perceive and produce complex acoustic signals is critical to procreation and survival. The purpose of this review article is to survey the most recent literature on behavioral measures of auditory functional return in adult birds after hair cell regeneration. The first portion of the review summarizes the effect of ototoxic drug induced hair cell loss and regeneration on hearing loss and recovery for pure tones. The second portion reviews studies of complex, species-specific vocalization discrimination and recognition after hair cell regeneration. Finally, we discuss the relevance of temporary hearing loss and recovery through hair cell regeneration on complex call and song production. Hearing sensitivity is restored, except for the highest frequencies, after hair cell regeneration in birds, but there are enduring changes to complex auditory perception. These changes do not appear to provide any obstacle to future auditory or vocal learning. PMID:23202051

  4. Biomechanical and Histopathologic Effects of Pulsed-Light Accelerated Epithelium-On/-Off Corneal Collagen Cross-Linking.

    PubMed

    Zhang, Xiaoyu; Sun, Ling; Shen, Yang; Tian, Mi; Zhao, Jing; Zhao, Yu; Li, Meiyan; Zhou, Xingtao

    2017-07-01

    This study aimed to compare the biomechanical and histopathologic effects of transepithelial and accelerated epithelium-off pulsed-light accelerated corneal collagen cross-linking (CXL). A total of 24 New Zealand rabbits were analyzed after sham operation (control) or transepithelial or epithelium-off operation (45 mW/cm for both). The transepithelial group was treated with pulsed-light ultraviolet A for 5 minutes 20 seconds, and the epithelium-off group was treated for 90 seconds. Biomechanical testing, including ultimate stress, Young modulus, and the physiological modulus, was analyzed. Histological changes were evaluated by light microscopy and transmission electron microscopy. The stress-strain curve was nonlinear in both accelerated transepithelial and epithelium-off CXL groups. The stress and elastic moduli were all significantly higher in both experimental groups compared with the control group (P < 0.05), whereas there were no significant differences between the 2 treatment groups (P > 0.05). Six months after the operation, hematoxylin and eosin staining and transmission electron microscopy showed that the subcutaneous collagen fibers were arranged in a regular pattern, and the fiber density was higher in the experimental groups. Both transepithelial and accelerated epithelium-off CXL produced biomechanical and histopathologic improvements, which were not significantly different between the 2 pulsed-light accelerated CXL treatments.

  5. Tonsil Epithelial Factors May Influence Oropharyngeal Human Immunodeficiency Virus Transmission

    PubMed Central

    Moutsopoulos, Niki M.; Nares, Salvador; Nikitakis, Nikolaos; Rangel, Zoila; Wen, Jie; Munson, Peter; Sauk, John; Wahl, Sharon M.

    2007-01-01

    Tonsil epithelium has been implicated in human immunodeficiency virus (HIV) pathogenesis, but its role in oral transmission remains controversial. To study characteristics of this tissue, which may influence susceptibility or resistance to HIV, we performed microarray analysis of the tonsil epithelium. Our data revealed that genes related to immune functions such as antibody production and antigen processing were increasingly expressed in tonsil compared with the epithelium of another oropharyngeal site, the gingival epithelium. Importantly, tonsil epithelium highly expressed genes associated with HIV entrapment and/or transmission, including the HIV co-receptor CXCR4 and the potential HIV-binding molecules FcRγIII, complement receptor 2, and various complement components. Immunohistochemical staining confirmed the increased presence of CXCR4 in the tonsil epithelium compared with multiple oral epithelial sites, particularly in basal and parabasal layers. This increased expression of molecules involved in viral recognition, binding, and entry may favor virus-epithelium interactions in an environment with reduced innate antiviral mechanisms. Specifically, secretory leukocyte protease inhibitor, an innate molecule with anti-HIV activity, was minimal in the tonsil epithelium, in contrast to oral mucosa. Collectively, our data suggest that increased expression of molecules associated with HIV binding and entry coupled with decreased innate antiviral factors may render the tonsil a potential site for oral transmission. PMID:17620369

  6. Small Interfering RNA Pathway Modulates Initial Viral Infection in Midgut Epithelium of Insect after Ingestion of Virus.

    PubMed

    Lan, Hanhong; Chen, Hongyan; Liu, Yuyan; Jiang, Chaoyang; Mao, Qianzhuo; Jia, Dongsheng; Chen, Qian; Wei, Taiyun

    2016-01-15

    Numerous viruses are transmitted in a persistent manner by insect vectors. Persistent viruses establish their initial infection in the midgut epithelium, from where they disseminate to the midgut visceral muscles. Although propagation of viruses in insect vectors can be controlled by the small interfering RNA (siRNA) antiviral pathway, whether the siRNA pathway can control viral dissemination from the midgut epithelium is unknown. Infection by a rice virus (Southern rice black streaked dwarf virus [SRBSDV]) of its incompetent vector (the small brown planthopper [SBPH]) is restricted to the midgut epithelium. Here, we show that the siRNA pathway is triggered by SRBSDV infection in continuously cultured cells derived from the SBPH and in the midgut of the intact insect. Knockdown of the expression of the core component Dicer-2 of the siRNA pathway by RNA interference strongly increased the ability of SRBSDV to propagate in continuously cultured SBPH cells and in the midgut epithelium, allowing viral titers in the midgut epithelium to reach the threshold (1.99 × 10(9) copies of the SRBSDV P10 gene/μg of midgut RNA) needed for viral dissemination into the SBPH midgut muscles. Our results thus represent the first elucidation of the threshold for viral dissemination from the insect midgut epithelium. Silencing of Dicer-2 further facilitated the transmission of SRBSDV into rice plants by SBPHs. Taken together, our results reveal the new finding that the siRNA pathway can control the initial infection of the insect midgut epithelium by a virus, which finally affects the competence of the virus's vector. Many viral pathogens that cause significant global health and agricultural problems are transmitted via insect vectors. The first bottleneck in viral infection, the midgut epithelium, is a principal determinant of the ability of an insect species to transmit a virus. Southern rice black streaked dwarf virus (SRBSDV) is restricted exclusively to the midgut epithelium of an

  7. Small Interfering RNA Pathway Modulates Initial Viral Infection in Midgut Epithelium of Insect after Ingestion of Virus

    PubMed Central

    Lan, Hanhong; Chen, Hongyan; Liu, Yuyan; Jiang, Chaoyang; Mao, Qianzhuo; Jia, Dongsheng; Chen, Qian

    2015-01-01

    ABSTRACT Numerous viruses are transmitted in a persistent manner by insect vectors. Persistent viruses establish their initial infection in the midgut epithelium, from where they disseminate to the midgut visceral muscles. Although propagation of viruses in insect vectors can be controlled by the small interfering RNA (siRNA) antiviral pathway, whether the siRNA pathway can control viral dissemination from the midgut epithelium is unknown. Infection by a rice virus (Southern rice black streaked dwarf virus [SRBSDV]) of its incompetent vector (the small brown planthopper [SBPH]) is restricted to the midgut epithelium. Here, we show that the siRNA pathway is triggered by SRBSDV infection in continuously cultured cells derived from the SBPH and in the midgut of the intact insect. Knockdown of the expression of the core component Dicer-2 of the siRNA pathway by RNA interference strongly increased the ability of SRBSDV to propagate in continuously cultured SBPH cells and in the midgut epithelium, allowing viral titers in the midgut epithelium to reach the threshold (1.99 × 109 copies of the SRBSDV P10 gene/μg of midgut RNA) needed for viral dissemination into the SBPH midgut muscles. Our results thus represent the first elucidation of the threshold for viral dissemination from the insect midgut epithelium. Silencing of Dicer-2 further facilitated the transmission of SRBSDV into rice plants by SBPHs. Taken together, our results reveal the new finding that the siRNA pathway can control the initial infection of the insect midgut epithelium by a virus, which finally affects the competence of the virus's vector. IMPORTANCE Many viral pathogens that cause significant global health and agricultural problems are transmitted via insect vectors. The first bottleneck in viral infection, the midgut epithelium, is a principal determinant of the ability of an insect species to transmit a virus. Southern rice black streaked dwarf virus (SRBSDV) is restricted exclusively to the

  8. Cryogenic regenerator including sarancarbon heat conduction matrix

    NASA Technical Reports Server (NTRS)

    Jones, Jack A. (Inventor); Petrick, S. Walter (Inventor); Britcliffe, Michael J. (Inventor)

    1989-01-01

    A saran carbon matrix is employed to conduct heat through the heat storing volume of a cryogenic regenerator. When helium is adsorbed into the saran carbon matrix, the combination exhibits a volumetric specific heat much higher than previously used lead balls. A helium adsorbed saran regenerator should allow much lower refrigerator temperatures than those practically obtainable with lead based regenerators for regenerator type refrigeration systems.

  9. Familial grouped pigmentation of the retinal pigment epithelium.

    PubMed Central

    de Jong, P T; Delleman, J W

    1988-01-01

    Grouped pigmentation of the retinal pigment epithelium was found in a father and his son. They had a normal resting potential on the electro-oculogram, but the son had a lower normal light rise. We believe this is the first description of familial grouped pigmentation. Images PMID:3390419

  10. The regenerative medicine in oral and maxillofacial surgery: the most important innovations in the clinical application of mesenchymal stem cells.

    PubMed

    Tatullo, Marco; Marrelli, Massimo; Paduano, Francesco

    2015-01-01

    Regenerative medicine is an emerging field of biotechnology that combines various aspects of medicine, cell and molecular biology, materials science and bioengineering in order to regenerate, repair or replace tissues. The oral surgery and maxillofacial surgery have a role in the treatment of traumatic or degenerative diseases that lead to a tissue loss: frequently, to rehabilitate these minuses, you should use techniques that have been improved over time. Since 1990, we started with the use of growth factors and platelet concentrates in oral and maxillofacial surgery; in the following period we start to use biomaterials, as well as several type of scaffolds and autologous tissues. The frontier of regenerative medicine nowadays is represented by the mesenchymal stem cells (MSCs): overcoming the ethical problems thanks to the use of mesenchymal stem cells from adult patient, and with the increasingly sophisticated technology to support their manipulation, MSCs are undoubtedly the future of medicine regenerative and they are showing perspectives unimaginable just a few years ago. Most recent studies are aimed to tissues regeneration using MSCs taken from sites that are even more accessible and rich in stem cells: the oral cavity turned out to be an important source of MSCs with the advantage to be easily accessible to the surgeon, thus avoiding to increase the morbidity of the patient. The future is the regeneration of whole organs or biological systems consisting of many different tissues, starting from an initial stem cell line, perhaps using innovative scaffolds together with the nano-engineering of biological tissues.

  11. Effect of coffee drinking on cell proliferation in rat urinary bladder epithelium.

    PubMed

    Lina, B A; Rutten, A A; Woutersen, R A

    1993-12-01

    A possible effect of freshly brewed drip coffee on urinary bladder carcinogenesis was investigated in male Wistar rats using cell proliferation in urinary bladder epithelium as the indicator of tumour promotion. Male rats were given either undiluted coffee brew (100% coffee), coffee diluted 10 times (10% coffee) or tap water (controls), as their only source of drinking fluid for 2 or 6 wk. Uracil, known to induce cell proliferation in urinary bladder epithelium, was included in the study as a positive control. In rats receiving 100% coffee, body weights, liquid intake and urinary volume were decreased. Neither histopathological examination of urinary bladder tissue nor the bromodeoxyuridine labelling index revealed biologically significant differences between rats receiving coffee and the tap water controls. Uracil increased the labelling index and induced hyperplasia of the urinary bladder epithelium, as expected. It was concluded that these results produced no evidence that drinking coffee predisposes to tumour development in the urinary bladder.

  12. Sox2+ progenitors in sharks link taste development with the evolution of regenerative teeth from denticles

    PubMed Central

    Martin, Kyle J.; Rasch, Liam J.; Cooper, Rory L.; Johanson, Zerina; Fraser, Gareth J.

    2016-01-01

    Teeth and denticles belong to a specialized class of mineralizing epithelial appendages called odontodes. Although homology of oral teeth in jawed vertebrates is well supported, the evolutionary origin of teeth and their relationship with other odontode types is less clear. We compared the cellular and molecular mechanisms directing development of teeth and skin denticles in sharks, where both odontode types are retained. We show that teeth and denticles are deeply homologous developmental modules with equivalent underlying odontode gene regulatory networks (GRNs). Notably, the expression of the epithelial progenitor and stem cell marker sex-determining region Y-related box 2 (sox2) was tooth-specific and this correlates with notable differences in odontode regenerative ability. Whereas shark teeth retain the ancestral gnathostome character of continuous successional regeneration, new denticles arise only asynchronously with growth or after wounding. Sox2+ putative stem cells associated with the shark dental lamina (DL) emerge from a field of epithelial progenitors shared with anteriormost taste buds, before establishing within slow-cycling cell niches at the (i) superficial taste/tooth junction (T/TJ), and (ii) deep successional lamina (SL) where tooth regeneration initiates. Furthermore, during regeneration, cells from the superficial T/TJ migrate into the SL and contribute to new teeth, demonstrating persistent contribution of taste-associated progenitors to tooth regeneration in vivo. This data suggests a trajectory for tooth evolution involving cooption of the odontode GRN from nonregenerating denticles by sox2+ progenitors native to the oral taste epithelium, facilitating the evolution of a novel regenerative module of odontodes in the mouth of early jawed vertebrates: the teeth. PMID:27930309

  13. The cellular basis for animal regeneration

    PubMed Central

    Tanaka, Elly; Reddien, Peter W.

    2011-01-01

    The ability of animals to regenerate missing parts is a dramatic and poorly understood aspect of biology. The sources of new cells for these regenerative phenomena have been sought for decades. Recent advances involving cell fate tracking in complex tissues have shed new light on the cellular underpinnings of regeneration in Hydra, planarians, zebrafish, Xenopus, and Axolotl. Planarians accomplish regeneration with use of adult pluripotent stem cells, whereas several vertebrates utilize a collection of lineage-restricted progenitors from different tissues. Together, an array of cellular strategies—from pluripotent stem cells to tissue-specific stem cells and dedifferentiation—are utilized for regeneration. PMID:21763617

  14. Metabolomic Analyses of Blood Plasma after Oral Administration of D-Glucosamine Hydrochloride to Dogs

    PubMed Central

    Osaki, Tomohiro; Azuma, Kazuo; Kurozumi, Seiji; Takamori, Yoshimori; Tsuka, Takeshi; Imagawa, Tomohiro; Okamoto, Yoshiharu; Minami, Saburo

    2012-01-01

    D-Glucosamine hydrochloride (GlcN∙HCl) is an endogenous amino monosaccharide synthesized from glucose that is useful in the treatment of joint diseases in both humans and animals. The aim of this study was to examine amino acid metabolism in dogs after oral administration of GlcN∙HCl. Accelerated fumarate respiration and elevated plasma levels of lactic acid and alanine were observed after administration. These results suggest that oral administration of GlcN∙HCl induces anaerobic respiration and starvation in cells, and we hypothesize that these conditions promote cartilage regeneration. Further studies are required to evaluate the expression of transforming growth factor-beta (TGF-β). PMID:23015778

  15. Guided tissue regeneration with heterologous materials in primary subtalar arthrodesis: a case report.

    PubMed

    Frangez, Igor; Kasnik, Tea; Cimerman, Matej; Smrke, Dragica Maja

    2016-05-03

    Calcaneal fractures are relatively rare and difficult to treat. Treatment options vary based on the type of fracture and the surgeon's experiences. In recent years, surgical procedures have increasingly been used due to the better long-term results. We present a case where guided tissue regeneration was performed in a calcaneal fracture that needed primary subtalar arthrodesis. We used the principles of guided tissue regeneration from oral surgery to perform primary subtalar arthrodesis and minimize the risk of non-union. We used a heterologous collagen membrane, which acts as a mechanical barrier and protects the bone graft from the invasion of unwanted cells that could lead to non-union. The collagenous membrane also has osteoconductive properties and is therefore able to increase the osteoblast proliferation rate. A 62-year-old Caucasian woman sustained multiple fractures of her lower limbs and spine after a fall from a ladder. Her left calcaneus had a comminuted multifragmental fracture (Sanders type IV) with severe destruction of the cartilage of her subtalar joint and depression of the Böhler's angle. Therefore, we performed primary arthrodesis of her subtalar joint with elevation of the Böhler's angle using a 7.3 mm titanium screw, a heterologous cortico-cancellous collagenated pre-hydrated bone mix, a heterologous cancellous collagenated bone wedge, and a heterologous collagen membrane (Tecnoss®, Italy). The graft was fully incorporated 12 weeks after the procedure and a year and a half later our patient walks without limping. We present a new use of guided tissue regeneration with heterologous materials that can be used to treat extensive bone defects after bone injuries. We believe that guided tissue regeneration using heterologous materials, including a heterologous collagen membrane that presents a mechanical barrier between soft tissues and bone as well as a stimulative component that enhances bone formation, could be more often used in bone surgery.

  16. Patterned substrates and methods for nerve regeneration

    DOEpatents

    Mallapragada, Surya K.; Heath, Carole; Shanks, Howard; Miller, Cheryl A.; Jeftinija, Srdija

    2004-01-13

    Micropatterned substrates and methods for fabrication of artificial nerve regeneration conduits and methods for regenerating nerves are provided. Guidance compounds or cells are seeded in grooves formed on the patterned substrate. The substrates may also be provided with electrodes to provide electrical guidance cues to the regenerating nerve. The micropatterned substrates give physical, chemical, cellular and/or electrical guidance cues to promote nerve regeneration at the cellular level.

  17. Smokeless tobacco (paan and gutkha) consumption, prevalence, and contribution to oral cancer

    PubMed Central

    2017-01-01

    Smokeless tobacco consumption, which is widespread throughout the world, leads to oral submucous fibrosis (OSMF), which is a long-lasting and devastating condition of the oral cavity with the potential for malignancy. In this review, we mainly focus on the consumption of smokeless tobacco, such as paan and gutkha, and the role of these substances in the induction of OSMF and ultimately oral cancer. The list of articles to be examined was established using citation discovery tools provided by PubMed, Scopus, and Google Scholar. The continuous chewing of paan and swallowing of gutkha trigger progressive fibrosis in submucosal tissue. Generally, OSMF occurs due to multiple risk factors, especially smokeless tobacco and its components, such as betel quid, areca nuts, and slaked lime, which are used in paan and gutkha. The incidence of oral cancer is higher in women than in men in South Asian countries. Human oral epithelium cells experience carcinogenic and genotoxic effects from the slaked lime present in the betel quid, with or without areca nut. Products such as 3-(methylnitrosamino)-proprionitrile, nitrosamines, and nicotine initiate the production of reactive oxygen species in smokeless tobacco, eventually leading to fibroblast, DNA, and RNA damage with carcinogenic effects in the mouth of tobacco consumers. The metabolic activation of nitrosamine in tobacco by cytochrome P450 enzymes may lead to the formation of N-nitrosonornicotine, a major carcinogen, and micronuclei, which are an indicator of genotoxicity. These effects lead to further DNA damage and, eventually, oral cancer. PMID:28292008

  18. Inflammation and immunity in organ regeneration.

    PubMed

    Mescher, Anthony L; Neff, Anton W; King, Michael W

    2017-01-01

    The ability of vertebrates to regenerate amputated appendages is increasingly well-understood at the cellular level. Cells mediating an innate immune response and inflammation in the injured tissues are a prominent feature of the limb prior to formation of a regeneration blastema, with macrophage activity necessary for blastema growth and successful development of the new limb. Studies involving either anti-inflammatory or pro-inflammatory agents suggest that the local inflammation produced by injury and its timely resolution are both important for regeneration, with blastema patterning inhibited in the presence of unresolved inflammation. Various experiments with Xenopus larvae at stages where regenerative competence is declining show improved digit formation after treatment with certain immunosuppressive, anti-inflammatory, or antioxidant agents. Similar work with the larval Xenopus tail has implicated adaptive immunity with regenerative competence and suggests a requirement for regulatory T cells in regeneration, which also occurs in many systems of tissue regeneration. Recent analyses of the human nail organ indicate a capacity for local immune tolerance, suggesting roles for adaptive immunity in the capacity for mammalian appendage regeneration. New information and better understanding regarding the neuroendocrine-immune axis in the response to stressors, including amputation, suggest additional approaches useful for investigating effects of the immune system during repair and regeneration. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Development of zinc-plated regenerator material

    NASA Astrophysics Data System (ADS)

    Y Xu, M.; Morie, T.; Tsuchiya, A.

    2017-12-01

    An effective way to improve the efficiency of a cryocooler is to improve the efficiency of the regenerator. In general, the heat capacity of materials decreases as temperature decreases. Thus, when temperature is below 40 K, lead or bismuth spheres are often used as regenerator materials. However, the pressure drop in a sphere regenerator is much larger than that in a screen regenerator. To overcome this dilemma, Xu et al. reported that cooling performance at the temperature of less than 40 K was improved when using tin-plated screens at the cold end of the regenerator. However, the reliability of tin at low temperatures is still not verified fully because of its phase transition from a normal β phase to an abnormal α phase, which may result in a significant reduction of the mechanical strength. In this paper, a zinc-plated screen is proposed as another potential alternative. A comparison test was performed with a two-stage GM cryocooler by replacing part of the first stage regenerator material, phosphorus bronze screens, with zinc-plated screens. Compared to a regenerator filled with bronze screens, the cooling capacity of the first stage increased by about 11% at 40 K and 60% at 30 K with these zinc-plated screens. The detailed experimental results are reported in this paper.

  20. Novel multiplexed low coherence interferometry endoscopic probe for analyzing the cervical epithelium in vivo (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Ho, Derek; Chu, Kengyeh K.; Crose, Michael; Desoto, Michael; Peters, Jennifer J.; Murtha, Amy P.; Wax, Adam

    2017-02-01

    The cervix is primarily composed of two types of epithelium: stratified squamous ectocervix and simple columnar endocervix. In between these two layers lies a metaplastic squamocolumnar junction commonly referred to as the transformation zone (T-zone). During puberty, the cervical epithelium undergoes dynamic changes including cervical ectropion and increased area and rates of metaplasia. Although these metaplastic changes have been linked to higher incidence of cervical cancer among young women, research in this field has been limited to surface analysis using computerized planimetry of colopophotographs. Here, we present a novel multiplexed low coherence interferometry (mLCI) system for interrogating the cervical epithelium. The system is comprised of 6 parallel Mach-Zehnder interferometers in a time-multiplexed configuration that increases throughput by 6-fold to realize a combined 36-channel acquisition. A custom designed endoscopic handheld probe is used to collect sparsely sampled, depth-resolved scattering intensity profiles (A-scans) from a large field of view (25 x 25 mm) on the cervical epithelium in vivo. The instrument incorporates white light imaging through a plastic fiber bundle to co-register the mLCI A-scans to colpophotographs which are analyzed by a clinician to manually segment the cervical epithelium. Our preliminary data shows significant differences in characteristic A-scans from endocervical and ectocervical epithelium. These results demonstrate the feasibility of using mLCI as both a research tool for studying the relationship between cervical ectopy and cancer as well as a clinical instrument for identifying the at-risk T-zone on the cervix in vivo as a means to improve biopsy targeting. Further analysis will be performed to develop an algorithm for distinguishing the mLCI A-scans of endocervical, ectocervical, and metaplastic epithelium in real time.

  1. [Study on different responses of rats' small intestine mucous membrane and bladder transitional epithelium in the same carcinogenic urine environment].

    PubMed

    Wu, B; Pan, C; Song, G

    2001-10-25

    To preliminarily verify the tentative idea of replacement of bladder transitional epithelium with small intestine mucous membrane to prevent recurrence of carcinoma of bladder. A certain segment of small intestine was transplanted to the urinary bladder of the same body in 17 rats. Then N-butyl-N-(4-hydroxy-butyl) nitrosamine (BBN) was used to induce carcinoma of bladder. BBN was used to 11 control rats that did not undergo operation. Bladder carcinoma failed to be found in the transplanted small intestine mucous membrane in all experimental rats except one. After stimulation of BBN, carcinoma of urinary bladder occurred in all rats' bladder transitional epithelium. 1) The carcinogenic substances in the urine of rats suffering from BBN-induced bladder carcinoma are carcinogenic only to bladder transitional epithelium and have no effect on small intestine epithelium. 2) Bladder transitional epithelium may be more sensitive to the urine carcinogenic substances and easier to be cancerized than small intestine epithelium. 3) The tentative idea of substitution of small intestine mucous membrane for bladder transitional epithelium to prevent the recurrence of bladder carcinoma is worth further studying.

  2. In situ hybridization analysis of human papillomavirus DNA in oral mucosal lesions.

    PubMed

    Zeuss, M S; Miller, C S; White, D K

    1991-06-01

    Commercial biotinylated DNA probes specific for human papillomavirus (HPV) types 6 and 11; 16 and 18; and 31, 33, and 35 were used for in situ hybridization analysis of 105 oral mucosal specimens from 5 cases of verruca vulgaris, 15 cases of condyloma acuminatum, 30 cases of squamous papilloma, 20 cases of hyperkeratosis/acanthosis, 15 cases of epithelial dysplasia, 5 cases of carcinoma in situ, and 15 cases of squamous cell carcinoma. Positive hybridization signals were found in 26 specimens (24.8%). Only HPV-6/11 was detected. HPV DNA occurred significantly more often (p less than 0.005, chi-square analysis) in condyloma acuminatum (100%) and verruca vulgaris (100%) than squamous papilloma (13.3%), hyperkeratotic/acanthotic lesions (10%), and malignant and premalignant lesions (0%). The tongue (19.1%) and labial epithelium (17.1%) were infected most frequently. Nuclear reaction products indicating HPV infection were associated primarily with koilocytes. These results demonstrate the usefulness of commercial biotinylated probes for HPV DNA analysis in routine paraffin-embedded lesion specimens. They confirm HPV involvement in benign lesions of the oral mucosa but fail to associate HPV infection with oral cancer and precancer.

  3. Regenerating an Arsenic Removal Iron-Based Adsorptive ...

    EPA Pesticide Factsheets

    Adsorptive media technology is a frequently used method of removing arsenic by small water systems because of its simplicity and efficiency. Current practice is to replace the media when it no longer reduces arsenic below the USEPA drinking water maximum contaminant level (MCL) of 10 µg/L. Media replacement typically accounts for approximately 80% of the total operational and maintenance (O/M) costs. This cost can be substantial and cost prohibitive for many small systems. One potential option to reduce the cost is on-site regeneration and reuse of the media. To evaluate the regeneration option, three consecutive regeneration studies were conducted on a full scale 295 gpm arsenic removal adsorptive media system. This paper, of a two part series, describes the regeneration process and its effectiveness to strip the arsenic and other contaminants from an exhausted media. The results of the regeneration studies found that a three step regeneration process of media backwash, caustic regeneration and acid neutralization/conditioning is very effective for stripping arsenic and other contaminants from the exhaustive media of a full scale arsenic removal system This paper, of a two part series, describes the regeneration process and its effectiveness to strip the arsenic and other contaminants from an exhausted media

  4. Effects of the Loss of Conjunctival Muc16 on Corneal Epithelium and Stroma in Mice

    PubMed Central

    Shirai, Kumi; Okada, Yuka; Cheon, Dong-Joo; Miyajima, Masayasu; Behringer, Richard R.; Yamanaka, Osamu; Saika, Shizuya

    2014-01-01

    Purpose. To examine the role of conjunctival Muc16 in the homeostasis of the ocular surface epithelium and stroma using Muc16-null knockout (KO) mice. Methods. We used KO mice (n = 58) and C57/BL6 (WT) mice (n = 58). Histology and immunohistochemistry were employed to analyze the phenotypes in the ocular surface epithelium. The expression of phospho-Stat3, AP-1 components, interleukin 6 (IL-6), and tumor necrosis factor-α (TNFα) in the cornea and conjunctiva was examined. The shape of the nuclei of corneal epithelial cells was examined to evaluate intraepithelial cell differentiation. Epithelial cell proliferation was studied using bromo-deoxyuridine labeling. Finally, the wound healing of a round defect (2-mm diameter) in the corneal epithelium was measured. The keratocyte phenotype and macrophage invasion in the stroma were evaluated after epithelial repair. Results. The loss of Muc16 activated Stat3 signal, affected JunB signal, and upregulated the expression of IL-6 in the conjunctiva. Basal-like cells were observed in the suprabasal layer of the corneal epithelium with an increase in proliferation. The loss of Muc16 accelerated the wound healing of the corneal epithelium. The incidence of myofibroblast appearance and macrophage invasion were more marked in KO stroma than in WT stroma after epithelial repair. Conclusions. The loss of Muc16 in the conjunctiva affected the homeostasis of the corneal epithelium and stroma. The mechanism might include the upregulation of the inflammatory signaling cascade (i.e., Stat3 signal, and IL-6 expression in the KO conjunctiva). Current data provides insight into the research of the pathophysiology of dry eye syndrome. PMID:24812549

  5. [Guided bone regeneration: general survey].

    PubMed

    Cosyn, Jan; De Bruyn, Hugo

    2009-01-01

    The principle of 'guided bone regeneration' was first described in 1988 on the basis of animal-experimental data. Six weeks after transmandibular defects had been created and protected by non-resorbable teflonmembranes, complete bone regeneration was found. The technique was based on the selective repopulation of the wound: every infiltration of cells outside the neighbouring bone tissue was prevented by the application of the membrane. Additional animal experiments showed that guided bone regeneration was a viable treatment option for local bone defects surrounding dental implants. Clinical practice, however, showed that premature membrane exposure was a common complication, which was responsible for a tremendous reduction in regenerated bone volume. In addition, a second surgical intervention was always necessary to remove the membrane. As a result, resorbable alternatives were developed. Since these are less rigid, bone fillers are usually used simultaneously. These comprise autogenous bone chips and bone substitutes from allogenic or xenogenic origine. Also alloplastic materials could be used for this purpose. Based on their characteristics this article provides an overview of the biomaterials that could be considered for guided bone regeneration. Specific attention goes to their application in clinical practice.

  6. Hindlimb suspension reduces muscle regeneration

    NASA Technical Reports Server (NTRS)

    Mozdziak, P. E.; Truong, Q.; Macius, A.; Schultz, E.

    1998-01-01

    Exposure of juvenile skeletal muscle to a weightless environment reduces growth and satellite cell mitotic activity. However, the effect of a weightless environment on the satellite cell population during muscle repair remains unknown. Muscle injury was induced in rat soleus muscles using the myotoxic snake venom, notexin. Rats were placed into hindlimb-suspended or weightbearing groups for 10 days following injury. Cellular proliferation during regeneration was evaluated using 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry and image analysis. Hindlimb suspension reduced (P < 0.05) regenerated muscle mass, regenerated myofiber diameter, uninjured muscle mass, and uninjured myofiber diameter compared to weightbearing rats. Hindlimb suspension reduced (P < 0.05) BrdU labeling in uninjured soleus muscles compared to weight-bearing muscles. However, hindlimb suspension did not abolish muscle regeneration because myofibers formed in the injured soleus muscles of hindlimb-suspended rats, and BrdU labeling was equivalent (P > 0.10) on myofiber segments isolated from the soleus muscles of hindlimb-suspended and weightbearing rats following injury. Thus, hindlimb suspension (weightlessness) does not suppress satellite cell mitotic activity in regenerating muscles before myofiber formation, but reduces growth of the newly formed myofibers.

  7. Peptide-Based Materials for Cartilage Tissue Regeneration.

    PubMed

    Hastar, Nurcan; Arslan, Elif; Guler, Mustafa O; Tekinay, Ayse B

    2017-01-01

    Cartilaginous tissue requires structural and metabolic support after traumatic or chronic injuries because of its limited capacity for regeneration. However, current techniques for cartilage regeneration are either invasive or ineffective for long-term repair. Developing alternative approaches to regenerate cartilage tissue is needed. Therefore, versatile scaffolds formed by biomaterials are promising tools for cartilage regeneration. Bioactive scaffolds further enhance the utility in a broad range of applications including the treatment of major cartilage defects. This chapter provides an overview of cartilage tissue, tissue defects, and the methods used for regeneration, with emphasis on peptide scaffold materials that can be used to supplement or replace current medical treatment options.

  8. Single-Cell RNA Sequencing of the Bronchial Epithelium in Smokers With Lung Cancer

    DTIC Science & Technology

    2015-07-01

    AWARD NUMBER: W81XWH-14-1-0234 TITLE: Single-Cell RNA Sequencing of the Bronchial Epithelium in Smokers With Lung Cancer PRINCIPAL INVESTIGATOR...TITLE AND SUBTITLE Single-Cell RNA Sequencing of the Bronchial Epithelium in Smokers With Lung Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH...single cell RNA sequencing on airway epithelial cells obtained from smokers with and without lung cancer to identify cell-type dependent gene expression

  9. [Alterations in the metabolism of cornmeal epithelium during medium-term storage (author's transl)].

    PubMed

    Schmidt-Martens, F W; Hennighausen, U; Wirz, K; Teping, C

    1977-08-08

    Freshly prepared bovine corneas were stored in medium TC 199 with penicillin and fetal calf serum at +4 degrees C over a storage period of 168h. Every 24h, the levels of glucose, lactate, and pyruvate in the corneal epithelium were estimated. Also the glucose levels in the corneal epithelium and stroma were compared at the same time intervals. Furthermore, alterations in the enzyme pattern of the epithelial cells during storage were observed.

  10. WIND1 Promotes Shoot Regeneration through Transcriptional Activation of ENHANCER OF SHOOT REGENERATION1 in Arabidopsis[OPEN

    PubMed Central

    Ohnuma, Mariko; Kurata, Tetsuya; Nakata, Masaru; Ohme-Takagi, Masaru

    2017-01-01

    Many plant species display remarkable developmental plasticity and regenerate new organs after injury. Local signals produced by wounding are thought to trigger organ regeneration but molecular mechanisms underlying this control remain largely unknown. We previously identified an AP2/ERF transcription factor WOUND INDUCED DEDIFFERENTIATION1 (WIND1) as a central regulator of wound-induced cellular reprogramming in plants. In this study, we demonstrate that WIND1 promotes callus formation and shoot regeneration by upregulating the expression of the ENHANCER OF SHOOT REGENERATION1 (ESR1) gene, which encodes another AP2/ERF transcription factor in Arabidopsis thaliana. The esr1 mutants are defective in callus formation and shoot regeneration; conversely, its overexpression promotes both of these processes, indicating that ESR1 functions as a critical driver of cellular reprogramming. Our data show that WIND1 directly binds the vascular system-specific and wound-responsive cis-element-like motifs within the ESR1 promoter and activates its expression. The expression of ESR1 is strongly reduced in WIND1-SRDX dominant repressors, and ectopic overexpression of ESR1 bypasses defects in callus formation and shoot regeneration in WIND1-SRDX plants, supporting the notion that ESR1 acts downstream of WIND1. Together, our findings uncover a key molecular pathway that links wound signaling to shoot regeneration in plants. PMID:28011694

  11. Evaluation of advanced regenerator systems

    NASA Technical Reports Server (NTRS)

    Cook, J. A.; Fucinari, C. A.; Lingscheit, J. N.; Rahnke, C. J.

    1978-01-01

    The major considerations are discussed which will affect the selection of a ceramic regenerative heat exchanger for an improved 100 HP automotive gas turbine engine. The regenerator considered for this application is about 36cm in diameter. Regenerator comparisons are made on the basis of material, method of fabrication, cost, and performance. A regenerator inlet temperature of 1000 C is assumed for performance comparisons, and laboratory test results are discussed for material comparisons at 1100 and 1200 C. Engine test results using the Ford 707 industrial gas turbine engine are also discussed.

  12. Epithelio-mesenchymal transitional attributes in oral sub-mucous fibrosis.

    PubMed

    Das, Raunak Kumar; Anura, Anji; Pal, Mousumi; Bag, Swarnendu; Majumdar, Subhadipa; Barui, Ananya; Chakraborty, Chandan; Ray, Ajoy Kumar; Sengupta, Sanghamitra; Paul, Ranjan Rashmi; Chatterjee, Jyotirmoy

    2013-12-01

    Evaluating molecular attributes in association with its epithelial and sub-epithelial changes of oral sub-mucous fibrosis is meaningful in exploring the plausibility of an epithelio-mesenchymal transition (EMT) and malignant potentiality of this pathosis. In this study histopathological and histochemical attributes for basement membrane and connective tissue in biopsies of oral sub-mucous fibrosis (n = 55) and normal oral mucosa (n = 16) were assessed and expressions of p63, E-cadherin, β-catenin, N-cadherin and TWIST were analyzed immunohistochemically. The p63 and its isoforms (TA and ∆N), PARD3, E-cadherin and β-catenin were also assessed transcriptomically by q-PCR and EMT players like TWIST1, ZEB1, MMP9 and micro-RNA 205 were searched in gene expression microarrays. Oral epithelium demonstrating impairment in progressive maturation in oral sub-mucous fibrosis concomitantly experienced an increase in basement membrane thickness and collagen deposition along with alteration in target molecular expressions. In comparison to non-dysplastic conditions dysplastic stages exhibited significant increase in p63 and p63∆N expressions whereas, E-cadherin and β-catenin exhibited loss from the membrane with concurrent increase in cytoplasm. Further the N-cadherin and TWIST were gained remarkably along with the appearance of nuclear accumulation features of β-catenin. The microarray search had noticed the up-regulation of TWIST1, ZEB1 and MMP9 along with down regulation of micro-RNA 205. The simultaneous increase in basement membrane thickness and sub-epithelial collagen deposition were the plausible indicators for increased matrix stiffness with expected impact on oral epithelial functional homoeostasis. This was corroborated with the increase in expressions of epithelial master regulator p63 and its oncogenic isoform (∆N) along with membranous loss of E-cadherin (EMT hallmark) and its associate β-catein and gain of mesenchymal markers like N-cadherin and TWIST

  13. Induction of Subacute Ruminal Acidosis Affects the Ruminal Microbiome and Epithelium

    PubMed Central

    McCann, Joshua C.; Luan, Shaoyu; Cardoso, Felipe C.; Derakhshani, Hooman; Khafipour, Ehsan; Loor, Juan J.

    2016-01-01

    Subacute ruminal acidosis (SARA) negatively impacts the dairy industry by decreasing dry matter intake, milk production, profitability, and increasing culling rate and death loss. Six ruminally cannulated, lactating Holstein cows were used in a replicated incomplete Latin square design to determine the effects of SARA induction on the ruminal microbiome and epithelium. Experimental periods were 10 days with days 1–3 for ad libitum intake of control diet, followed by 50% feed restriction on day 4, and ad libitum access on day 5 to the basal diet or the basal diet with an additional 10% of a 50:50 wheat/barley pellet. Based on subsequent ruminal pH, cows were grouped (SARA grouping; SG) as Non-SARA or SARA based on time <5.6 pH (0 and 3.4 h, respectively). Ruminal samples were collected on days 1 and 6 of each period prior to feeding and separated into liquid and solid fractions. Microbial DNA was extracted for bacterial analysis using 16S rRNA gene paired-end sequencing on the MiSeq Illumina platform and quantitative PCR (qPCR). Ruminal epithelium biopsies were taken on days 1 and 6 before feeding. Quantitative RT-PCR was used to determine gene expression in rumen epithelium. Bray–Curtis similarity indicated samples within the liquid fraction separated by day and coincided with an increased relative abundance of genera Prevotella, Ruminococcus, Streptococcus, and Lactobacillus on day 6 (P < 0.06). Although Firmicutes was the predominant phyla in the solid fraction, a SG × day interaction (P < 0.01) indicated a decrease on day 6 for SARA cows. In contrast, phylum Bacteroidetes increased on day 6 (P < 0.01) for SARA cows driven by greater genera Prevotella and YRC22 (P < 0.01). Streptococcus bovis and Succinivibrio dextrinosolvens populations tended to increase on day 6 but were not affected by SG. In ruminal epithelium, CLDN1 and CLDN4 expression increased on day 6 (P < 0.03) 24 h after SARA induction and a tendency for a SG × day interaction (P < 0.10) was

  14. A review of adipocyte lineage cells and dermal papilla cells in hair follicle regeneration

    PubMed Central

    Zhang, Peipei; Kling, Russell E; Ravuri, Sudheer K; Kokai, Lauren E; Rubin, J Peter; Chai, Jia-ke

    2014-01-01

    Alopecia is an exceedingly prevalent problem effecting men and women of all ages. The standard of care for alopecia involves either transplanting existing hair follicles to bald areas or attempting to stimulate existing follicles with topical and/or oral medication. Yet, these treatment options are fraught with problems of cost, side effects, and, most importantly, inadequate long-term hair coverage. Innovative cell-based therapies have focused on the dermal papilla cell as a way to grow new hair in previously bald areas. However, despite this attention, many obstacles exist, including retention of dermal papilla inducing ability and maintenance of dermal papilla productivity after several passages of culture. The use of adipocyte lineage cells, including adipose-derived stem cells, has shown promise as a cell-based solution to regulate hair regeneration and may help in maintaining or increasing dermal papilla cells inducing hair ability. In this review, we highlight recent advances in the understanding of the cellular contribution and regulation of dermal papilla cells and summarize adipocyte lineage cells in hair regeneration. PMID:25383178

  15. Effects of vitamin D receptor knockout on cornea epithelium gap junctions.

    PubMed

    Lu, Xiaowen; Watsky, Mitchell A

    2014-05-06

    Gap junctions are present in all corneal cell types and have been shown to have a critical role in cell phenotype determination. Vitamin D has been shown to influence cell differentiation, and recent work demonstrates the presence of vitamin D in the ocular anterior segment. This study measured and compared gap junction diffusion coefficients among different cornea epithelium phenotypes and in keratocytes using a noninvasive technique, fluorescence recovery after photobleaching (FRAP), and examined the influence of vitamin D receptor (VDR) knockout on epithelial gap junction communication in intact corneas. Previous gap junction studies in cornea epithelium and keratocytes were performed using cultured cells or ex vivo invasive techniques. These invasive techniques were unable to measure diffusion coefficients and likely were disruptive to normal cell physiology. Corneas from VDR knockout and control mice were stained with 5(6)-carboxyfluorescein diacetate (CFDA). Gap junction diffusion coefficients of the corneal epithelium phenotypes and of keratocytes, residing in intact corneas, were detected using FRAP. Diffusion coefficients equaled 18.7, 9.8, 5.6, and 4.2 μm(2)/s for superficial squamous cells, middle wing cells, basal cells, and keratocytes, respectively. Corneal thickness, superficial cell size, and the superficial squamous cell diffusion coefficient of 10-week-old VDR knockout mice were significantly lower than those of control mice (P < 0.01). The superficial cell diffusion coefficient of heterozygous mice was significantly lower than control mice (P < 0.05). Our results demonstrate differences in gap junction dye spread among the epithelial cell phenotypes, mirroring the epithelial developmental axis. The VDR knockout influences previously unreported cell-to-cell communication in superficial epithelium.

  16. [Muscle regeneration in mdx mouse, and a trial of normal myoblast transfer into regenerating dystrophic muscle].

    PubMed

    Takemitsu, M; Arahata, K; Nonaka, I

    1990-10-01

    The most ideal therapeutic trial on Duchenne muscular dystrophy (DMD) is a transfer of normal myoblasts into dystrophic muscle which has been attempted on animal models in several institutes. In the process of muscle regeneration, the transferred normal myoblasts are expected to incorporate into the regenerating fibers in host dystrophic mouse. To know the capacity of muscle regeneration in dystrophic muscle, we compared the regenerating process of the normal muscle with that of the dystrophic muscle after myonecrosis induced by 0.25% bupivacaine hydrochloride (BPVC) chronologically. In the present study, C57BL/10ScSn-mdx (mdx) mouse was used as an animal model of DMD and C57BL/10ScSn (B10) mouse as a control. There was no definite difference in the behavior of muscle fiber regeneration between normal and dystrophic muscles. The dystrophic muscle regenerated rapidly at the similar tempo to the normal as to their size and fiber type differentiation. The variation in fiber size diameter of dystrophic muscle, however, was more obvious than that of normal. To promote successful myoblast transfer from B10 mouse into dystrophic mdx mouse at higher ratio, cultured normal myoblasts were transferred into the regenerating dystrophic muscle on the first and the second day after myonecrosis induced by BPVC. Two weeks after the myoblast injection, the muscles were examined with immunohistochemical stain using anti dystrophin antibody. Although dystrophin-positive fibers appeared in dystrophic muscle, the positive fibers were unexpectedly small in number (3.86 +/- 1.50%).(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Hair cell regeneration

    PubMed Central

    Edge, Albert SB; Chen, Zheng-Yi

    2017-01-01

    The mammalian inner ear largely lacks the capacity to regenerate hair cells, the sensory cells required for hearing and balance. Recent studies in both lower vertebrates and mammals have uncovered genes and pathways important in hair cell development and have suggested ways that the sensory epithelia could be manipulated to achieve hair cell regeneration. These approaches include the use of inner ear stem cells, transdifferentiation of nonsensory cells, and induction of a proliferative response in the cells that can become hair cells. PMID:18929656

  18. Surgical treatment in combined hamartoma of the retina and retinal pigment epithelium.

    PubMed

    Sánchez-Vicente, J L; Rueda-Rueda, T; Llerena-Manzorro, L; Molina-Socola, F E; Contreras-Díaz, M; Szewc, M; Vital-Berral, C; Alfaro-Juárez, A; Medina-Tapia, A; López-Herrero, F; González-García, L; Muñoz-Morales, A

    2017-03-01

    The case is presented of a 39 year-old man with a combined hamartoma of the retina and retinal pigment epithelium, who experienced progressive visual loss and worsening of metamorphopsia. The patient underwent vitrectomy and epiretinal component peeling, with improvement in visual acuity, metamorphopsia, and retinal architecture, assessed by optical coherence tomography. Selected patients with combined hamartomas of the retina and retinal pigment epithelium may benefit from surgical management. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. Platelet-Rich Fibrin Promotes Periodontal Regeneration and Enhances Alveolar Bone Augmentation

    PubMed Central

    Li, Qi; Pan, Shuang; Dangaria, Smit J.; Gopinathan, Gokul; Kolokythas, Antonia; Chu, Shunli; Geng, Yajun; Zhou, Yanmin; Luan, Xianghong

    2013-01-01

    In the present study we have determined the suitability of platelet-rich fibrin (PRF) as a complex scaffold for periodontal tissue regeneration. Replacing PRF with its major component fibrin increased mineralization in alveolar bone progenitors when compared to periodontal progenitors, suggesting that fibrin played a substantial role in PRF-induced osteogenic lineage differentiation. Moreover, there was a 3.6-fold increase in the early osteoblast transcription factor RUNX2 and a 3.1-fold reduction of the mineralization inhibitor MGP as a result of PRF application in alveolar bone progenitors, a trend not observed in periodontal progenitors. Subcutaneous implantation studies revealed that PRF readily integrated with surrounding tissues and was partially replaced with collagen fibers 2 weeks after implantation. Finally, clinical pilot studies in human patients documented an approximately 5 mm elevation of alveolar bone height in tandem with oral mucosal wound healing. Together, these studies suggest that PRF enhances osteogenic lineage differentiation of alveolar bone progenitors more than of periodontal progenitors by augmenting osteoblast differentiation, RUNX2 expression, and mineralized nodule formation via its principal component fibrin. They also document that PRF functions as a complex regenerative scaffold promoting both tissue-specific alveolar bone augmentation and surrounding periodontal soft tissue regeneration via progenitor-specific mechanisms. PMID:23586051

  20. Platelet-rich fibrin promotes periodontal regeneration and enhances alveolar bone augmentation.

    PubMed

    Li, Qi; Pan, Shuang; Dangaria, Smit J; Gopinathan, Gokul; Kolokythas, Antonia; Chu, Shunli; Geng, Yajun; Zhou, Yanmin; Luan, Xianghong

    2013-01-01

    In the present study we have determined the suitability of platelet-rich fibrin (PRF) as a complex scaffold for periodontal tissue regeneration. Replacing PRF with its major component fibrin increased mineralization in alveolar bone progenitors when compared to periodontal progenitors, suggesting that fibrin played a substantial role in PRF-induced osteogenic lineage differentiation. Moreover, there was a 3.6-fold increase in the early osteoblast transcription factor RUNX2 and a 3.1-fold reduction of the mineralization inhibitor MGP as a result of PRF application in alveolar bone progenitors, a trend not observed in periodontal progenitors. Subcutaneous implantation studies revealed that PRF readily integrated with surrounding tissues and was partially replaced with collagen fibers 2 weeks after implantation. Finally, clinical pilot studies in human patients documented an approximately 5 mm elevation of alveolar bone height in tandem with oral mucosal wound healing. Together, these studies suggest that PRF enhances osteogenic lineage differentiation of alveolar bone progenitors more than of periodontal progenitors by augmenting osteoblast differentiation, RUNX2 expression, and mineralized nodule formation via its principal component fibrin. They also document that PRF functions as a complex regenerative scaffold promoting both tissue-specific alveolar bone augmentation and surrounding periodontal soft tissue regeneration via progenitor-specific mechanisms.