Science.gov

Sample records for potential oral markers

  1. Oral keratinocyte stem/progenitor cells: specific markers, molecular signaling pathways and potential uses.

    PubMed

    Calenic, Bogdan; Greabu, Maria; Caruntu, Constantin; Tanase, Cristiana; Battino, Maurizio

    2015-10-01

    Oral keratinocyte stem cells reside in the basal layers of the oral epithelium, representing a minor population of cells with a great potential to self-renew and proliferate over the course of their lifetime. As a result of the potential uses of oral keratinocyte stem cells in regenerative medicine and the key roles they play in tissue homeostasis, inflammatory conditions, wound healing and tumor initiation and progression, intense scientific efforts are currently being undertaken to identify, separate and reprogram these cells. Although currently there is no specific marker that can characterize and isolate oral keratinocyte stem cells, several suggestions have been made. Thus, different stem/progenitor-cell subpopulations have been categorized based on combinations of positive and/or negative membrane-surface markers, which include integrins, clusters of differentiation and cytokeratins. Important advances have also been made in understanding the molecular pathways that govern processes such as self-renewal, differentiation, proliferation, wound healing and programmed cell death. A thorough understanding of stem-cell biology and the molecular players that govern cellular fate is paramount in the quest for using stem-cell-derived therapies in the treatment of various oral pathologies. The current review focuses on recent advances in understanding the molecular signaling pathways coordinating the behavior of these cells and in identifying suitable markers used for their isolation and characterization. Special emphasis will also be placed on the roles played by oral keratinocyte stem and progenitor cells in normal and diseased oral tissues and on their potential uses in the fields of general medicine and dentistry.

  2. Increased nuclear ?-catenin expression in oral potentially malignant lesions: A marker of epithelial dysplasia

    PubMed Central

    Rojas-Alcayaga, Gonzalo; Maturana, Andrea; Aitken, Juan-Pablo; Rojas, Carolina; Ortega, Ana-Verónica

    2015-01-01

    Background Deregulation of ?-catenin is associated with malignant transformation; however, its relationship with potentially malignant and malignant oral processes is not fully understood. The aim of this study was to determine and compare the nuclear ?-catenin expression in oral dysplasia and oral squamous cell carcinoma (OSCC). Material and Methods Cross sectional study. Immunodetection of ?-catenin was performed on 72 samples, with the following distribution: 21 mild dysplasia, 12 moderate dysplasia, severe dysplasia 3, 36 OSCC including 19 well differentiated, 15 moderately differentiated and 2 poorly differentiated. Through microscopic observation the number of positive cells per 1000 epithelial cells was counted. For the statistical analysis, the Kruskal Wallis test was used. Results Nuclear expression of ?-catenin was observed in all samples with severe and moderate dysplasia, with a median of 267.5, in comparison to mild dysplasia whose median was 103.75. Only 10 samples (27.7%) with OSCC showed nuclear expression, with statistically significant differences between groups (p < 0.05). Conclusions Our results are consistent with most of the reports which show increased presence of ?-catenin in severe and moderate dysplasia compared to mild dysplasia; however the expression of nuclear ?-catenin decreased after starting the invasive neoplastic process. This suggests a role for this protein in the progression of dysplasia and early malignant transformation to OSCC. Immunodetection of ?-catenin could be a possible immune marker in the detection of oral dysplasia. Key words:Oral squamous cell carcinoma (OSCC), ?-catenin, oral dysplasia. PMID:26241451

  3. Protein O-fucosyltransferase 1: a potential diagnostic marker and therapeutic target for human oral cancer.

    PubMed

    Yokota, Satoshi; Ogawara, Katsunori; Kimura, Ryota; Shimizu, Fumie; Baba, Takao; Minakawa, Yasuyuki; Higo, Morihiro; Kasamatsu, Atsushi; Endo-Sakamoto, Yosuke; Shiiba, Masashi; Tanzawa, Hideki; Uzawa, Katsuhiro

    2013-12-01

    Protein O-fucosyltransferase 1 (POFUT1) is the enzyme that adds O-fucose through O-glycosidic linkage to conserved serine or threonine residues in the epidermal growth factor-like repeats of a number of cellular surface and secreted proteins. Our previous study using microarray technology showed that significant upregulation of POFUT1 occurs in oral squamous cell carcinoma (OSCC)-derived cell lines compared to human normal oral keratinocytes. The aim of the present study was to examine the status of POFUT1 mRNA and protein expression in OSCC-derived cell lines and human primary OSCCs. POFUT1 mRNA was upregulated significantly (P<0.05 for both comparisons) in five OSCC-derived cell lines and primary OSCCs using quantitative reverse transcriptase-polymerase chain reaction. Immunohistochemistry data indicated that POFUT1 protein expression levels were consistent with mRNA expression status in OSCC-derived cell lines and primary OSCCs. Furthermore, POFUT1 expression status was correlated significantly (P=0.048) with the primary tumor size. The proliferation of POFUT1 knockdown cells was inhibited significantly compared with that of control cells. These results indicated that POFUT1 expression can contribute to cancer progression and that POFUT1 may serve as a diagnostic marker and a therapeutic target for OSCCs.

  4. Determining the potential of desmoglein 3 as a sensitive and specific immunohistochemical marker for the detection of micrometastasis in patients with primary oral squamous cell carcinoma

    PubMed Central

    Spadigam, Anita; Dhupar, Anita

    2016-01-01

    Aim of the study Despite advances in surgical and radiotherapy techniques, the presence of lymph node metastasis drastically decreases the survival rate of patients with primary oral squamous cell carcinoma (OSCC). Thus the accurate pathological staging of the neck is critical. Desmoglein 3 (DSG3), a desmosomal cadherin protein is said to be highly expressed in head and neck squamous cell carcinoma (HNSCC) and in metastatic cervical lymph nodes, but absent in non-invaded nodes. With an aim to improve the sensitivity of tumour cell detection, we investigated the potential of DSG3 as an immunohistochemical marker for the detection of occult lymph node metastasis in patients with primary OSCC. Material and methods Forty-seven lymph node specimens from 10 patients who underwent neck dissection for primary OSCC were immunostained with DSG3. Results The DSG3 positivity was noted in the six positive lymph nodes. However, when using DSG3 as an immunohistochemical marker, no additional micrometastatic deposits were evident in the histologically negative nodes. Interestingly, tumour marker DSG3-positive macrophages could be identified within the subcapsular sinuses, medullary sinuses, and the interfollicular areas. Conclusions Our findings suggest that although DSG3 is overexpressed in HNSCC, it is not specific and may not prove to be a potent immunohistochemical marker to detect micrometastasis. The role of tumour marker-positive macrophages within the lymph nodes needs to be investigated further.

  5. Salivary markers of oxidative stress in oral diseases

    PubMed Central

    Tóthová, L'ubomíra; Kamodyová, Natália; Červenka, Tomáš; Celec, Peter

    2015-01-01

    Saliva is an interesting alternative diagnostic body fluid with several specific advantages over blood. These include non-invasive and easy collection and related possibility to do repeated sampling. One of the obstacles that hinders the wider use of saliva for diagnosis and monitoring of systemic diseases is its composition, which is affected by local oral status. However, this issue makes saliva very interesting for clinical biochemistry of oral diseases. Periodontitis, caries, oral precancerosis, and other local oral pathologies are associated with oxidative stress. Several markers of lipid peroxidation, protein oxidation and DNA damage induced by reactive oxygen species can be measured in saliva. Clinical studies have shown an association with oral pathologies at least for some of the established salivary markers of oxidative stress. This association is currently limited to the population level and none of the widely used markers can be applied for individual diagnostics. Oxidative stress seems to be of local oral origin, but it is currently unclear whether it is caused by an overproduction of reactive oxygen species due to inflammation or by the lack of antioxidants. Interventional studies, both, in experimental animals as well as humans indicate that antioxidant treatment could prevent or slow-down the progress of periodontitis. This makes the potential clinical use of salivary markers of oxidative stress even more attractive. This review summarizes basic information on the most commonly used salivary markers of oxidative damage, antioxidant status, and carbonyl stress and the studies analyzing these markers in patients with caries or periodontitis. PMID:26539412

  6. Urinary marker of oral pregnenolone administration.

    PubMed

    Saudan, Christophe; Desmarchelier, Aurélien; Sottas, Pierre-Edouard; Mangin, Patrice; Saugy, Martial

    2005-03-01

    Pregnenolone (PREG) can potentially be abused by athletes to maintain an equilibration of the steroidal environment after sex steroids administrations. Five men volunteers orally ingested 50 mg PREG to determine optimal urinary markers for detection of this steroid. Our findings show that ingestion of PREG has no significant effects on the testosterone/epitestosterone (T/E) and testosterone/luteinizing hormone (T/LH) ratios, whereas variable changes on the carbon isotopic values of three T metabolites: androsterone, etiocholanolone, 5beta-androstane-3alpha,17beta-diol (5beta-androstanediol) together with 16(5alpha)-androsten-3alpha-ol (androstenol) and 5beta-pregnane-3alpha,20alpha-diol (pregnanediol) have been observed. The difference between the carbon isotopic values (delta13C-values) of androstenol and pregnanediol is potentially the most reliable marker of exogenous PREG administration in males. For all subjects, the differences differ by 3.0 per thousand or more over a period of about 10 h and for both of them the detection window for positivity is extended over 40 h.

  7. Molecular markers in oral lichen planus: A systematic review

    PubMed Central

    Sagari, Shitalkumar; Sanadhya, Sudhanshu; Doddamani, Mallikarjun; Rajput, Rajan

    2016-01-01

    Oral lichen planus (OLP) is a chronic inflammatory mucosal disease that is usually detected in 0.5–2.2% of the human population. Among these, only 0.5–2.9% of the lesions progress to carcinoma. However, there are no prognostic markers available presently to recognize the increased risk in malignant transformation of the lesions. Selected markers for cell proliferation, adhesion, apoptosis and lymphocytic infiltration were analyzed by immunohistochemistry in addition to static cytometry for DNA content. The concept linking OLP and oral squamous cell carcinoma states that chronic inflammation results in crucial DNA damage, which further progresses to development of carcinoma. Even though in the past decade, enormous information has been accumulated on malignant potential of OLP, its transformation still remains unclear. Hence, the purpose of this article was to review cellular and molecular markers to understand the pathogenesis of OLP and its progression toward malignancy. PMID:27194873

  8. Potential Markers in Cardiac Hypertrophy?

    PubMed

    Malinowski, Bartosz; Fulgheri, Gabriele; Wicinski, Michal; Grzesk, Elzbieta; Odrowaz-Sypniewska, Grazyna; Grześk, Grzegorz; Darwish, Nasser

    2012-07-01

    Cardiomyopathies are diagnosed based on medical history of patient (symptoms and family history), physical examination, results of echocardiogram and in some situations additionally ECG or chest-X-ray results. Currently used non-invasive diagnostic methods, could be complemented by biochemical tests. In this review some emerging potential biomarkers such as: osteopontin, ST-2 receptor, osteoprotegerin, neopterin, urocortins, growth differentiation factor 15 and urotensin II are described. In current article human and non human investigations have been reviewed, since rat is most commonly used model in experimental cardiology and gives important foundations to clinical knowledge.

  9. Potentially malignant oral lesions: clinicopathological correlations

    PubMed Central

    Maia, Haline Cunha de Medeiros; Pinto, Najara Alcântara Sampaio; Pereira, Joabe dos Santos; de Medeiros, Ana Miryam Costa; da Silveira, Éricka Janine Dantas; Miguel, Márcia Cristina da Costa

    2016-01-01

    ABSTRACT Objective To determine the incidence of potentially malignant oral lesions, and evaluate and correlate their clinical and pathological aspects. Methods The sample consisted of cases clinically diagnosed as oral leukoplakia, oral erythroplakia, erythroleukoplakia, actinic cheilitis, and oral lichen planus treated at a diagnostic center, between May 2012 and July 2013. Statistical tests were conducted adopting a significance level of 5% (p≤0.05). Results Out of 340 patients, 106 (31.2%) had potentially malignant oral lesions; and 61 of these (17.9%) were submitted to biopsy. Actinic cheilitis was the most frequent lesion (37.5%) and the lower lip was the most affected site (49.6%). Among 106 patients in the sample, 48 (45.3%) reported nicotine consumption, 35 (33%) reported alcohol intake and 34 (32.1%) sun exposure while working. When clinical and histopathological diagnoses were compared, oral erythroplakia and atypical ulcer were the lesions that exhibited greater compatibility (100% each). Conclusion In most cases, clinical and histopathological diagnoses were compatible. An association between the occurrence of erythroplakia, leukoplakia and erythroleukoplakia with smoking was observed. Similarly, an association between actinic cheilitis and sun exposure was noted. Erythroleukoplakia presented the highest malignancy grade in this study. Finally, dental surgeons should draw special attention to diagnosis of potentially malignant oral lesions, choose the best management, and control the lesions to avoid their malignant transformation. PMID:27074232

  10. Potential markers of oxidative stress in stroke.

    PubMed

    Cherubini, Antonio; Ruggiero, Carmelinda; Polidori, M Cristina; Mecocci, Patrizia

    2005-10-01

    Free radical production is increased in ischemic and hemorrhagic stroke, leading to oxidative stress that contributes to brain damage. The measurement of oxidative stress in stroke would be extremely important for a better understanding of its pathophysiology and for identifying subgroups of patients that might receive targeted therapeutic intervention. Since direct measurement of free radicals and oxidized molecules in the brain is difficult in humans, several biological substances have been investigated as potential peripheral markers. Among lipid peroxidation products, malondialdehyde, despite its relevant methodological limitations, is correlated with the size of ischemic stroke and clinical outcome, while F2-isoprostanes appear to be promising, but they have not been adequately evaluated. 8-Hydroxy-2-deoxyguanosine has been extensively investigated as markers of oxidative DNA damage but no study has been done in stroke patients. Also enzymatic and nonenzymatic antioxidants have been proposed as indirect markers. Among them ascorbic acid, alpha-tocopherol, uric acid, and superoxide dismutase are related to brain damage and clinical outcome. After a critical evaluation of the literature, we conclude that, while an ideal biomarker is not yet available, the balance between antioxidants and by-products of oxidative stress in the organism might be the best approach for the evaluation of oxidative stress in stroke patients.

  11. Leptin receptor expression and Gln223Arg polymorphism as prognostic markers in oral and oropharyngeal cancer.

    PubMed

    Rodrigues, P R S; Maia, L L; Santos, M; Peterle, G T; Alves, L U; Takamori, J T; Souza, R P; Barbosa, W M; Mercante, A M C; Nunes, F D; Carvalho, M B; Tajara, E H; Louro, I D; Silva-Conforti, A M A

    2015-11-25

    The leptin gene product is released into the blood stream, passes through the blood-brain barrier, and finds the leptin receptor (LEPR) in the central nervous system. This hormone regulates food intake, hematopoiesis, inflammation, immunity, differentiation, and cell proliferation. The LEPR Gln223Arg polymorphism has been reported to alter receptor function and expression, both of which have been related with prognostics in several tumor types. Furthermore, several studies have shown a relationship between the Gln223Arg polymorphism and tumor development, and its role in oral and oropharyngeal squamous cell carcinoma is now well understood. In this study, 315 DNA samples were used for LEPR Gln223Arg genotyping and 87 primary oral and oropharyngeal squamous cell carcinomas were used for immunohistochemical expression analysis, such that a relationship between these and tumor development and prognosis could be established. Homozygous LEPR Arg223 was found to be associated with a 2-fold reduction in oral and oropharyngeal cancer risk. In contrast, the presence of the Arg223 allele in tumors was associated with worse disease-free and disease-specific survival. Low LEPR expression was found to be an independent risk factor, increasing the risk for lymph node metastasis 4-fold. In conclusion, the Gln223Arg polymorphism and LEPR expression might be valuable markers for oral and oropharyngeal cancer, suggesting that LEPR might serve as a potential target for future therapies.

  12. hTR RNA component as a marker of cellular proliferation in oral lichen planus.

    PubMed

    Flatharta, Cathal O; Flint, Stephen; Toner, Mary; Mabruk, Mohamed

    2008-01-01

    Previously, we have shown that the telomerase RNA component hTR is highly expressed in the epithelium of non-dysplastic Oral Lichen Planus (OLP) lesions (11). We concluded that it is possible that this high expression might be related to the increased cellular proliferation seen in OLP rather than being an indicator of potential malignant transformation. In the present study, and in order to confirm our finding in the previous study that hTR might be a marker for cellular proliferation in OLP, we analysed OLP biopsies known to be positive for RNA component of Telomerase (hTR) for the expression of Ki-67 as a marker for cellular proliferation. Fourteen OLP tissue biopsies known to be positive for telomerase RNA component hTR, were investigated using an immunohistochemical approach to determine the rate of cellular proliferation in OLP, looking at the expression of Ki-67 protein as a marker for cellular proliferation. A statistically significant increase was found between Ki-67 expression in OLP in comparison to normal control buccal mucosa samples. The expression of hTR component in OLP might thus be a marker for cellular proliferation.

  13. Keratins 17 and 19 expression as prognostic markers in oral squamous cell carcinoma.

    PubMed

    Coelho, B A; Peterle, G T; Santos, M; Agostini, L P; Maia, L L; Stur, E; Silva, C V M; Mendes, S O; Almança, C C J; Freitas, F V; Borçoi, A R; Archanjo, A B; Mercante, A M C; Nunes, F D; Carvalho, M B; Tajara, E H; Louro, I D; Silva-Conforti, A M A

    2015-11-25

    Five-year survival rates for oral squamous cell carcinoma (OSCC) are 30% and the mortality rate is 50%. Immunohistochemistry panels are used to evaluate proliferation, vascularization, apoptosis, HPV infection, and keratin expression, which are important markers of malignant progression. Keratins are a family of intermediate filaments predominantly expressed in epithelial cells and have an essential role in mechanical support and cytoskeleton formation, which is essential for the structural integrity and stability of the cell. In this study, we analyzed the expressions of keratins 17 and 19 (K17 and K19) by immunohistochemistry in tumoral and non-tumoral tissues from patients with OSCC. The results show that expression of these keratins is higher in tumor tissues compared to non-tumor tissues. Positive K17 expression correlates with lymph node metastasis and multivariate analysis confirmed this relationship, revealing a 6-fold increase in lymph node metastasis when K17 is expressed. We observed a correlation between K17 expression with disease-free survival and disease-specific death in patients who received surgery and radiotherapy. Multivariate analysis revealed that low expression of K17 was an independent marker for early disease relapse and disease-specific death in patients treated with surgery and radiotherapy, with an approximately 4-fold increased risk when compared to high K17 expression. Our results suggest a potential role for K17 and K19 expression profiles as tumor prognostic markers in OSCC patients.

  14. Differences in the expression of five senescence markers in oral cancer, oral leukoplakia and control samples in humans

    PubMed Central

    BASCONES-MARTÍNEZ, ANTONIO; LÓPEZ-DURÁN, MERCEDES; CANO-SÁNCHEZ, JORGE; SÁNCHEZ-VERDE, LYDIA; DÍEZ-RODRÍGUEZ, ANA; AGUIRRE-ECHEBARRÍA, PABLO; ÁLVAREZ-FERNÁNDEZ, EMILIO; GONZÁLEZ-MOLES, MIGUEL ANGEL; BASCONES-ILUNDAIN, JAIME; MUZIO, LORENZO LO; CAMPO-TRAPERO, JULIÁN

    2012-01-01

    Oncogene-induced senescence (OIS) may be a response to oncogenic activation, acting as a natural barrier against carcinogenesis at a premalignant stage. Thus, numerous cells in premalignant lesions enter senescence, but none or few in malignant tumours. This event could be due to the loss of senescence pathway effectors, including p16 (INK4a)-pRb or ARF-p53. The aim of this study was to characterize and compare the expression of certain senescent markers between oral precancer and cancer tissue samples. The expression of cyclin D1, Rb, maspin, p53 and mouse double minute 2 (MDM2) was analyzed in 20 paraffin-embedded tissue samples of normal oral mucosa (NOM), 14 samples of oral leukoplakia without dysplasia (OLD−), 11 samples of leukoplakia with dysplasia (OLD+) and 15 samples of oral squamous cell carcinoma (OSCC) by immunohistochemistry in tissue arrays. The expression of p16-pRb pathway markers, cyclin D1, maspin and Rb, was more frequent in OLD+ samples than in OSCC samples, although a statistical significance was only observed for maspin (P=0.036). Cyclin D1 expression was also significantly more frequent in OLD− samples vs. NOM samples. For the ARF-p53 pathway, the expression of p53 and MDM2 was significantly more frequent in the OLD− samples compared to in the NOM ones. These findings may indicate a role for cellular senescence in oral carcinogenesis, considering maspin as a reliable senescence marker and prognostic factor in oral premalignant lesions. PMID:22783442

  15. Assessment of angiogenic markers in oral hemangiomas and pyogenic granulomas.

    PubMed

    Freitas, Tarsila M C; Miguel, Márcia C C; Silveira, Ericka J D; Freitas, Roseana A; Galvão, Hébel C

    2005-08-01

    The purpose of this research was to evaluate the immunohistochemical expression of the vascular endothelial growth factor (VEGF-C1) and measuring the angiogenic activity by the staining for von Willebrand factor (vWF) and CD31 in oral pyogenic granulomas and hemangiomas. The results showed that there was no statistically significant difference in the angiogenesis index between the lesions evaluated. The average microvessel density determined for MVC (microvessel count) using CD31 was 60.64 for hemangiomas and 59.64 for pyogenic granulomas, while angiogenic index determined using vWF was 64.24 and 62.20 in these lesions. The results showed that the cells highlighted by staining for vWF were more uniform than in those stained for CD31. There was no statistically significant difference between the lesions for the number of cells highlighted by staining for VEGF-C1. However, the mean number of cells highlighted in pyogenic granuloma specimens was higher (153.23) when compared to oral hemangioma specimens (115.17). The VEGF-positive cells were endothelial cells and fibroblasts in hemangiomas and macrophages and fibroblasts in pyogenic granulomas. These results effort the role of the angiogenic factors in the etiopathogenesis of the hemangiomas and pyogenic granulomas, however, it showed that microvessel quantification is not useful in the differential diagnosis of these lesions.

  16. Researchers Develop Potential Oral Treatment for Hemophilia

    MedlinePlus

    ... and less painful alternative. University of Texas at Austin researchers created an oral treatment for one type ... Journal of Pharmaceutics . SOURCE: University of Texas at Austin, news release HealthDay Copyright (c) 2016 HealthDay . All ...

  17. Chronic oral infection with major periodontal bacteria Tannerella forsythia modulates systemic atherosclerosis risk factors and inflammatory markers.

    PubMed

    Chukkapalli, Sasanka S; Rivera-Kweh, Mercedes F; Velsko, Irina M; Chen, Hao; Zheng, Donghang; Bhattacharyya, Indraneel; Gangula, Pandu R; Lucas, Alexandra R; Kesavalu, Lakshmyya

    2015-04-01

    Tannerella forsythia is a Gram-negative anaerobic organism that inhabits the subgingival cavity and initiates connective tissue destruction and alveolar bone resorption in periodontal disease (PD). PD is a chronic immunoinflammatory disease and has been linked to several systemic diseases including atherosclerosis. This study evaluated the effects of a chronic oral infection with T. forsythia ATCC 43037 on the induction of PD, inflammatory markers and atherosclerosis risk factors in hyperlipidemic ApoE(null) mice. Mice were orally infected for 12 and 24 weeks prior to euthanasia. Bacterial colonization of the oral cavity and bacteremia was confirmed via isolation of genomic DNA from oral plaque and tissues. Oral infection elicited significantly elevated levels of serum IgG and IgM antibodies and alveolar bone resorption compared to control mice. Tannerella forsythia-infected mice had increased serum amyloid A, and significantly reduced serum nitric oxide when compared to controls. Tannerella forsythia chronic infection also significantly increased serum lipoproteins suggesting altered cholesterol metabolism and potential for aortic inflammation. Despite enhanced acute phase reactants and altered lipid profiles, T. forsythia infection was associated with decreased aortic plaque. This study investigates the potential of a known periodontal bacterial pathogen found in atherosclerotic plaque in humans to accelerate atherosclerosis in hyperlipdemic mice.

  18. Prognostic factors, predictive markers and cancer biology: the triad for successful oral cancer chemoprevention.

    PubMed

    Monteiro de Oliveira Novaes, Jose Augusto; William, William N

    2016-10-01

    Oral squamous cell carcinomas represent a significant cancer burden worldwide. Unfortunately, chemoprevention strategies investigated to date have failed to produce an agent considered standard of care to prevent oral cancers. Nonetheless, recent advances in clinical trial design may streamline drug development in this setting. In this manuscript, we review some of these improvements, including risk prediction tools based on molecular markers that help select patients most suitable for chemoprevention. We also discuss the opportunities that novel preclinical models and modern molecular profiling techniques will bring to the prevention field in the near future, and propose a clinical trials framework that incorporates molecular prognostic factors, predictive markers and cancer biology as a roadmap to improve chemoprevention strategies for oral cancers.

  19. Oral strip technology: overview and future potential.

    PubMed

    Dixit, R P; Puthli, S P

    2009-10-15

    Over the recent past, many of the research groups are focusing their research on this technology. Amongst the plethora of avenues explored for rapid drug releasing products, Oral Strip Technology (OST) is gaining much attention. The advantages of OST are the administration to pediatric and geriatric patient population where the difficulty of swallowing larger oral dosage forms is eliminated. This technology has been used for local action, rapid release products and for buccoadhesive systems that are retained for longer period in the oral cavity to release drug in controlled fashion. OST offers an alternate platform for molecules that undergo first pass metabolism and for delivery of peptides. The review article is an overview of OST encompassing materials used in OST, critical manufacturing aspects, applications, commercial technologies and future business prospects of this technology.

  20. Immunological and Biochemical Markers in Oral Carcinogenesis: The Public Health Perspective

    PubMed Central

    Khanna, Sunali

    2008-01-01

    Oral health is an integral component of general health and well being and a basic human right. Dental public health is probably the most challenging specialty of dentistry. Because of the lack of adequate resources among other factors, many people are likely to suffer from dental diseases. Despite great improvements in the oral health status of populations across the world, the burden and impact of dental diseases are still high. This is particularly true among underprivileged groups in both developed and developing communities. Oral diseases and conditions, including oral cancer, oral manifestations of HIV/AIDS, dental trauma, craniofacial anomalies, and noma, all have broad impacts on health and well-being. Oral cancer, the sixth most common cancer worldwide continues to be most prevalent cancer related to the consumption of tobacco, alcohol and other carcinogenic products. Nevertheless, significant reduction in mortality can be achieved by advances in early diagnosis and implementation of multidisciplinary treatment programs leading to improvement of survivorship and better quality of life. The present study was designed to evaluate the immunologic and biochemical markers in oral carcinogenesis using circulating immune complexes (CIC), copper, iron, and selenium concentrations as assessment endpoints. Study results indicated an increase in CIC and copper levels, and a decrease in iron and selenium concentrations in oral cancer patients compared to controls. The implications of these findings for public health are discussed. PMID:19151437

  1. Estimation of Serum Protein in Oral Potentially Malignant Disorders and Oral Malignancy – A Cross-Sectional Study

    PubMed Central

    Shah, Palak H.; Venkatesh, Rashmi

    2017-01-01

    Introduction In carcinogenesis, increased oxidative stress and weakened antioxidant defense produces damage to the macromolecules like proteins. Thus, protein can act as potential biomarker in oral premalignant and malignant lesions. Aim To determine and compare the levels of serum proteins in Oral Submucuous Fibrosis (OSMF), Oral Leukoplakia (OL), Nicotina Stomatitis (NS), Oral Malignancy (OM) and Healthy Controls (HC). Materials and Methods A total of 250 participants, were equally divided in five groups i.e., OSMF, OL, NS, OM and HC. Five ml of blood was collected from antecubital vein from each participant. The serum was analyzed for total protein, albumin and globulin levels using EBRA EM 200 semi-quantitive analyzer with the help of diagnostic kits. Results There were total 193 males and 57 females, who were between 18 to 82 years of age, with a mean of 46.32±13.89 years. The serum protein and globulin levels were significantly decreased in OSMF, OL and NS and increased in OM as compared to HC (p<0.001). No statistically significant difference was found in serum albumin levels between the study groups (p>0.05). Conclusion Serum proteins can be used as diagnostic and prognostic marker for oral premalignant and malignant lesions. PMID:28384973

  2. A potential peptide pathway from viruses to oral lichen planus.

    PubMed

    Lucchese, Alberta

    2015-06-01

    Oral lichen planus is an idiopathic inflammatory disease of oral mucous membranes, characterized by an autoimmune epidermis attack by T cells. It remains unknown, however, how such aggressive T cells are activated in vivo to cause epidermal damage. This study analyzes the relationship at the peptide level between viruses and oral lichen planus disease. Four potentially immunogenic peptides (SSSSSSS, QEQLEKA, LLLLLLA, and MLSGNAG) are found to be shared between HCV, EBV, HHV-7, HSV-1, and CMV and three human proteins (namely pinin, desmoglein-3, and plectin). The described peptide sharing might be of help in deciphering the still unexplained immunopathogenic pathway that leads to oral lichen planus.

  3. GDF 15 as an anti-apoptotic, diagnostic and prognostic marker in oral squamous cell carcinoma.

    PubMed

    Schiegnitz, E; Kämmerer, P W; Koch, F P; Krüger, M; Berres, M; Al-Nawas, B

    2012-07-01

    Growth-differentiation factor 15 (GDF 15) is involved in tumor pathogenesis and its expression is increased in many types of cancers. Functional effects of GDF 15 on oncogenesis of oral squamous cell carcinoma (OSCC) remain unclear. Therefore, the aim of this study was to examine the apoptotic characteristics of GDF 15 in OSCC cell lines in vitro and to analyze serum GDF 15 concentrations as a diagnostic and prognostic tumor marker for OSCC in vivo. Caspase activity was assessed in OSCC cell lines with the Caspase-Glo 3/7 system. Serum GDF 15 concentrations from 64 patients with histopathological proven OSCC and from 30 healthy volunteers were measured using an enzyme-linked immunosorbent assay. In 21 patients, serum GDF 15 was also analyzed postoperatively. In vitro, treatment of OSCC cell lines with GDF 15 reduced Caspase 3/7 activity significantly (p<0.05). In vivo, serum GDF 15 concentrations of the OSCC patients in all stages of OSCC were significantly higher than those of the healthy subjects (p<0.0001). After surgery, GDF 15 concentrations declined significantly from 1545±774pg/ml preoperative to 953±438pg/ml postoperative (p=0.003). The median survival time of OSCC patients with GDF 15 levels below 875pg/ml was significantly higher than of OSCC patients with GDF 15 levels above or equal 875pg/ml (p=0.031). Determination of receiver operating characteristic curves (ROC) showed a respective area under the ROC curve (AUC) of 0.943. The anti-apoptotic effect of GDF 15 in OSCC cell lines was shown in vitro. In vivo, significant elevated serum GDF 15 levels with prognostic value in OSCC-patients were seen for the first time. The results indicate that GDF15 may be used as a potential marker for diagnosis and prognosis of this entity.

  4. Volatile compounds as potential defective coffee beans' markers.

    PubMed

    Toci, Aline T; Farah, Adriana

    2008-06-01

    Although Brazil is the largest raw coffee producer and exporter in the world, a large amount of its Arabica coffee production is considered inappropriate for exportation. This by-product of coffee industry is called PVA due to the presence of black (P), green (V) and sour (A) defective beans, which are known to contribute considerably for cup quality decrease. Data on the volatile composition of Brazilian defective coffee beans are scarce. In this study, we evaluated the volatile composition of defective coffee beans (two lots) compared to good quality beans from the respective lots. Potential defective beans' markers were identified. In the raw samples, 2-methylpyrazine and 2-furylmethanol acetate were identified only in black-immature beans and butyrolactone only in sour beans, while benzaldehyde and 2,3,5,6-tetramethylpyrazine showed to be potential markers of defective beans in general. In the roasted PVA beans, pyrazine, 2,3-butanediol meso, 2-methyl-5-(1-propenyl)pyrazine, hexanoic acid, 4-ethyl-guayacol and isopropyl p-cresol sulfide also showed to be potential defective coffee beans' markers.

  5. Bacteriophage and their potential roles in the human oral cavity

    PubMed Central

    Edlund, Anna; Santiago-Rodriguez, Tasha M.; Boehm, Tobias K.; Pride, David T.

    2015-01-01

    The human oral cavity provides the perfect portal of entry for viruses and bacteria in the environment to access new hosts. Hence, the oral cavity is one of the most densely populated habitats of the human body containing some 6 billion bacteria and potentially 35 times that many viruses. The role of these viral communities remains unclear; however, many are bacteriophage that may have active roles in shaping the ecology of oral bacterial communities. Other implications for the presence of such vast oral phage communities include accelerating the molecular diversity of their bacterial hosts as both host and phage mutate to gain evolutionary advantages. Additional roles include the acquisitions of new gene functions through lysogenic conversions that may provide selective advantages to host bacteria in response to antibiotics or other types of disturbances, and protection of the human host from invading pathogens by binding to and preventing pathogens from crossing oral mucosal barriers. Recent evidence suggests that phage may be more involved in periodontal diseases than were previously thought, as their compositions in the subgingival crevice in moderate to severe periodontitis are known to be significantly altered. However, it is unclear to what extent they contribute to dysbiosis or the transition of the microbial community into a state promoting oral disease. Bacteriophage communities are distinct in saliva compared to sub- and supragingival areas, suggesting that different oral biogeographic niches have unique phage ecology shaping their bacterial biota. In this review, we summarize what is known about phage communities in the oral cavity, the possible contributions of phage in shaping oral bacterial ecology, and the risks to public health oral phage may pose through their potential to spread antibiotic resistance gene functions to close contacts. PMID:25861745

  6. Identification of potential protein markers of noble rot infected grapes.

    PubMed

    Lorenzini, Marilinda; Millioni, Renato; Franchin, Cinzia; Zapparoli, Giacomo; Arrigoni, Giorgio; Simonato, Barbara

    2015-07-15

    The evaluation of Botrytis cinerea as noble rot on withered grapes is of great importance to predict the wine sensory/organoleptic properties and to manage the winemaking process of Amarone, a passito dry red wine. This report describes the first proteomic analysis of grapes infected by noble rot under withering conditions to identify possible markers of fungal infection. 2-D gel electrophoresis revealed that protein profiles of infected and not infected grape samples are significantly different in terms of number of spots and relative abundance. Protein identification by MS analysis allowed to identify only in infected berries proteins of B. cinerea that represent potential markers of the presence of the fungus in the withered grapes.

  7. PDGFRβ Is a Novel Marker of Stromal Activation in Oral Squamous Cell Carcinomas

    PubMed Central

    Han, Rong; Haines, Paul; Gallagher, George; Noonan, Vikki; Kukuruzinska, Maria; Monti, Stefano; Trojanowska, Maria

    2016-01-01

    Carcinoma associated fibroblasts (CAFs) form the main constituents of tumor stroma and play an important role in tumor growth and invasion. The presence of CAFs is a strong predictor of poor prognosis of head and neck squamous cell carcinoma. Despite significant progress in determining the role of CAFs in tumor progression, the mechanisms contributing to their activation remain poorly characterized, in part due to fibroblast heterogeneity and the scarcity of reliable fibroblast surface markers. To search for such markers in oral squamous cell carcinoma (OSCC), we applied a novel approach that uses RNA-sequencing data derived from the cancer genome atlas (TCGA). Specifically, our strategy allowed for an unbiased identification of genes whose expression was closely associated with a set of bona fide stroma-specific transcripts, namely the interstitial collagens COL1A1, COL1A2, and COL3A1. Among the top hits were genes involved in cellular matrix remodeling and tumor invasion and migration, including platelet-derived growth factor receptor beta (PDGFRβ), which was found to be the highest-ranking receptor protein genome-wide. Similar analyses performed on ten additional TCGA cancer datasets revealed that other tumor types shared CAF markers with OSCC, including PDGFRβ, which was found to significantly correlate with the reference collagen expression in ten of the 11 cancer types tested. Subsequent immunostaining of OSCC specimens demonstrated that PDGFRβ was abundantly expressed in stromal fibroblasts of all tested cases (12/12), while it was absent in tumor cells, with greater specificity than other known markers such as alpha smooth muscle actin or podoplanin (3/11). Overall, this study identified PDGFRβ as a novel marker of stromal activation in OSCC, and further characterized a list of promising candidate CAF markers that may be relevant to other carcinomas. Our novel approach provides for a fast and accurate method to identify CAF markers without the need for

  8. Oral potentially malignant disorders: Is malignant transformation predictable and preventable?

    PubMed Central

    van der Waal, Isaäc

    2014-01-01

    Leukoplakia is the most common potentially malignant disorder of the oral mucosa. The prevalence is approximately 1% while the annual malignant transformation ranges from 2% to 3%. At present, there are no reliable clinicopathological or molecular predicting factors of malignant transformation that can be used in an individual patient and such event can not truly be prevented. Furthermore, follow-up programs are of questionable value in this respect. Cessation of smoking habits may result in regression or even disappearance of the leukoplakia and will diminish the risk of cancer development either at the site of the leukoplakia or elsewhere in the mouth or the upper aerodigestive tract. The debate on the allegedly potentially malignant character of oral lichen planus is going on already for several decades. At present, there is a tendency to accept its potentially malignant behaviour, the annual malignant transformation rate amounting less than 0.5%. As in leukoplakia, there are no reliable predicting factors of malignant transformation that can be used in an individual patient and such event can not truly be prevented either. Follow-up visits, e.g twice a year, may be of some value. It is probably beyond the scope of most dentists to manage patients with these lesions in their own office. Timely referral to a specialist seems most appropriate, indeed. Key words:Oral potentially malignant disorders, oral leukoplakia, oral lichen planus. PMID:24905952

  9. Changes in the expression of stem cell markers in oral lichen planus and hyperkeratotic lesions.

    PubMed

    Köse, Osman; Lalli, Anand; Kutulola, Adegun O; Odell, Edward W; Waseem, Ahmad

    2007-06-01

    Despite the pivotal role of stem cells in homeostasis of oral epithelia the location of this cell population within the tissue is uncertain. How disease influences these cells in vivo also remains to be elucidated. In this study we have used six molecular markers to identify stem cells in normal and diseased buccal mucosa. Samples of normal oral mucosa (NOM), hyperkeratosis (OHK) and oral lichen planus (OLP) were immunostained for alpha6 and beta1 integrins, keratin 15 (K15), melanoma-associated chondroitin sulphate proteoglycan (MCSP), NG2 the rat homologue of human MCSP and notch 1. K15, NG2 and beta1 staining was continuous in the basal layer of NOM whilst alpha6 and MCSP were limited to basal cells at the tips of connective tissue papillae. K15 was downregulated in OLP whereas alpha6, beta1 and MCSP were upregulated in both OLP and OHK. NG2 remained unchanged and notch 1 was absent in all samples. Therefore, the stem cell phenotype in OLP and OHK maybe altered in response to pathological signaling. Classification of these changes is essential to understand the role of adult stem cells in the pathogenesis of oral diseases characterised by abnormal keratinocyte proliferation and differentiation.

  10. Oral verrucous hyperplasia versus oral verrucous carcinoma: A clinicopathologic dilemma revisited using p53 as immunohistochemical marker

    PubMed Central

    Sharma, Preeti; Wadhwan, Vijay; Aggarwal, Pooja; Sharma, Anamika

    2016-01-01

    Background: Oral verrucous hyperplasia (OVH) and oral verrucous carcinoma (OVC) are two distinct clinicopathologic verrucous lesions. However, the distinction between the two lesions still remains enigmatic. It is almost impossible to distinguish them clinically. Thus, the final diagnosis rests on the histopathological characteristics of both lesions, being distinguished from each other by an exophytic and endophytic growth pattern, respectively. Methods: This institutional study was planned to review retrospectively two series of patients with histologic diagnoses of VH (n = 27) and VC (n = 27) to investigate their clinicopathological features and to analyze the role of immunohistochemical (IHC) marker p53 protein in distinguishing between the two verrucous lesions. The biopsies of the histopathologically diagnosed cases spanning last 10 years were retrieved from the archives of the Oral Pathology department of the institution. Clinical data were tabulated and analyzed for age, gender, site and tobacco habits. IHC staining was done on all the samples using p53 antibody. Results: Applying Chi-square test, the buccal mucosa was the most common affected site and tobacco chewing was more prevalent habit in both these lesions (P > 0.05). While the elderly males (>60 years) were the most commonly affected group in VC, a relatively younger age group of males (30–39 years) was more commonly affected in VH (P < 0.05). IHC staining with p53 antibody did not show any significant difference between these two verrucous lesions (P > 0.05). Conclusion: VH and VC are closely related lesions distinguished by an adequate biopsy sample. PMID:27721598

  11. Potential usefulness of biological markers in risk assessment

    SciTech Connect

    Perera, F.

    1987-12-01

    Substantial data have been generated during the last 5 years in experimental systems and human populations which shed light on the potential usefulness of biological markers in human cancer risk assessment. Following a brief review of overall progress to date in the biomonitoring of human populations, this paper turns to the growing body of data regarding carcinogen-DNA and protein adducts as illustrative markers of biologically effective dose of carcinogens. The data base illustrates considerable human interindividual variation in binding and the presence of significant background levels of adducts-both of which support the absence of human population thresholds for exposure to carcinogens. The contribution of adduct data to our understanding of the shape of low-dose-response curve and the reliability of interspecies extrapolation, as well as the relevance of adducts to cancer risk, are also discussed. Even though adducts can now be useful in hazard identification or qualitative risk assessment,more research is needed before they can serve as quantitative predictors of human cancer risk.

  12. Labeling and analysis of chicken taste buds using molecular markers in oral epithelial sheets

    PubMed Central

    Rajapaksha, Prasangi; Wang, Zhonghou; Venkatesan, Nandakumar; Tehrani, Kayvan F.; Payne, Jason; Swetenburg, Raymond L.; Kawabata, Fuminori; Tabata, Shoji; Mortensen, Luke J.; Stice, Steven L.; Beckstead, Robert; Liu, Hong-Xiang

    2016-01-01

    In chickens, the sensory organs for taste are the taste buds in the oral cavity, of which there are ~240–360 in total number as estimated by scanning electron microscopy (SEM). There is not an easy way to visualize all taste buds in chickens. Here, we report a highly efficient method for labeling chicken taste buds in oral epithelial sheets using the molecular markers Vimentin and α-Gustducin. Immediate tissue fixation following incubation with sub-epithelially injected proteases enabled us to peel off whole epithelial sheets, leaving the shape and integrity of the tissue intact. In the peeled epithelial sheets, taste buds labeled with antibodies against Vimentin and α-Gustducin were easily identified and counted under a light microscope and many more taste buds, patterned in rosette-like clusters, were found than previously reported with SEM. Broiler-type, female-line males have more taste buds than other groups and continue to increase the number of taste buds over stages after hatch. In addition to ovoid-shaped taste buds, big tube-shaped taste buds were observed in the chicken using 2-photon microscopy. Our protocol for labeling taste buds with molecular markers will factilitate future mechanistic studies on the development of chicken taste buds in association with their feeding behaviors. PMID:27853250

  13. Oral Health Scales: Design of an Oral Health Scale of Infectious Potential

    PubMed Central

    Relvas, Marta; Diz, Pedro; Seoane, Juan

    2013-01-01

    Objectives: In this paper we propose a new Global Oral Health Scale that will allow the infectious potential of the oral cavity, clinically manifest as local and focal infections, to be condensed into a single parameter. Study Design: Based on a number of oral health scales previously designed by our group, we designed a final version that incorporates dental and periodontal variables (some of them evaluated using corroborated objective indices) that reflect the presence of caries and periodontal disease. Results: The application of the proposed oral health scale requires the examination of 6 sites per tooth (mesio-buccal, medio-buccal, disto-buccal, disto-lingual, medio-lingual and mesio-lingual). The following variables are analysed: number of tooth surfaces with supragingival plaque, determined using the O’Leary index; number of teeth with caries and the severity of the caries; number of tooth surfaces with gingival inflammation, determined using the Ainamo and Bay index; and number of tooth surfaces with pockets ?4 mm and severity of the pockets. These variables are then grouped into 2 categories, dental and periodontal. The final grades of dental and periodontal health correspond to the grades assigned to a least 2 of the 3 variables analysed in each of these categories. The category (dental or periodontal) with the highest grade is the one that determines the grade of the Global Oral Health Scale. Conclusion: This scale could be particularly useful for the epidemiological studies comparing different populations and for analysis of the influence of distinct degrees of oral health on the development of certain systemic diseases. Key words:Scale, oral health, infectious potential, systemic disease. PMID:23524418

  14. Potential markers of the nutritional status in an experimental model.

    PubMed

    Feliu, M S; Slobodianik, N H

    2000-01-01

    The activity of adenine deaminase (ADA) and purine nucleoside phosphorylase (PNP) as potential nutritional markers was analyzed in an experimental model. Weanling Wistar rats were fed a protein-free diet ad libitum to obtain a severe degree of wasting. An age-matched control group received a stock diet. At the end of the experiment, body weight (BW) and thymus weight (TW) were determined. Activity of ADA and PNP was determined on thymocytes of protein-deprived and control rats; the results, expressed as micromoles of uric acid x 10(-1)/W (W = TW/BW(0.75)), were 17.0 +/- 2.6 versus 9.1 +/- 3.0 for ADA and 11.5 +/- 4.2 versus 3.9 +/- 1.0 for PNP (P < 0.01). These results suggest that the nutritional stress provoked by the administration of a protein-free diet from weaning onward affects the development of thymocytes. Moreover, the increase in the activity of ADA and PNP would be an alternative mechanism to avoid the accumulation of high levels of deoxynucleotides, which would be toxic for T lymphocytes. However, some investigators have observed an increase of ADA activity in human serum under some adverse conditions; for this reason and taking into account the present findings, it would be interesting to determine the relation between the activity of ADA and PNP in thymocytes and serum in experimental models to analyze and propose these biochemical parameters as potential and useful markers of nutritional status; it also would be interesting to test this relation in human studies.

  15. Hepatitis B serum markers and oral health in a group of Norwegian male prisoners.

    PubMed

    Hurlen, B; Jacobsen, N; Hurlen, P

    1984-02-01

    In 138 male Norwegian prisoners the prevalence of hepatitis B virus (HBV) serum markers was 30.4% and closely related to their drug abuse. The highest frequency of the markers (82.8%) was found in young drug addicts admitting intravenous abuse and the lowest (14.3%) in prisoners denying such abuse. For comparison, the frequency of HBV serum markers in the general male population in Norway is about 4.1%. In young prisoners (less than 30 years), DMF teeth, percentage of gingival bleeding, and percentage of periodontal pockets greater than 4 mm were on an average 18.8, 38.2%, and 7.0%, respectively. These corresponding figures in the older age group (greater than 30 years) were 21.7, 38.5%, and 15.2%. These findings indicate a dental health status somewhere between that of the general population and disadvantaged groups in Norway previously surveyed. Other oral pathological conditions were present in more than one third of the prisoners, but mucosal lesions and disorders of psychosomatic origin did not extend normal ranges. No characteristic lesions attributable to drug abuse were observed. Dental care was given a low priority by the prisoners. Emergency procedures had been the treatment of choice at infrequent, irregular visits to the dentist, leading to enhanced risk of bleeding and of HBV transmission.

  16. Data from human salivary proteome - A resource of potential biomarkers for oral cancer.

    PubMed

    Sivadasan, Priya; Kumar Gupta, Manoj; Sathe, Gajanan J; Balakrishnan, Lavanya; Palit, Priyanka; Gowda, Harsha; Suresh, Amritha; Abraham Kuriakose, Moni; Sirdeshmukh, Ravi

    2015-09-01

    Salivary proteins are an important source for developing marker-based assays for oral cancers. To get an insight into the proteins present in human saliva, we applied multiple strategies involving affinity-based depletion of abundant proteins, fractionation of the resulting proteins or their tryptic peptides followed by LC-MS/MS analysis, using high resolution mass spectrometry. By integrating the protein identifications observed by us with those from similar workflows employed in earlier investigations, we compiled an updated salivary proteome. We have mapped the salivary proteome to the published data on differentially expressed proteins from oral cancer tissues and also for their secretory features using prediction tools, SignalP 4.1, TMHMM 2c and Exocarta. Proteotypic peptides for the subset of proteins implicated in oral cancer and mapped to any two of the prediction tools for secretory potential have been listed. The data here are related to the research article "Human saliva proteome - a resource of potential biomarkers for oral cancer" in the Journal of Proteomics [1].

  17. Data from human salivary proteome – A resource of potential biomarkers for oral cancer

    PubMed Central

    Sivadasan, Priya; Kumar Gupta, Manoj; Sathe, Gajanan J.; Balakrishnan, Lavanya; Palit, Priyanka; Gowda, Harsha; Suresh, Amritha; Abraham Kuriakose, Moni; Sirdeshmukh, Ravi

    2015-01-01

    Salivary proteins are an important source for developing marker-based assays for oral cancers. To get an insight into the proteins present in human saliva, we applied multiple strategies involving affinity-based depletion of abundant proteins, fractionation of the resulting proteins or their tryptic peptides followed by LC–MS/MS analysis, using high resolution mass spectrometry. By integrating the protein identifications observed by us with those from similar workflows employed in earlier investigations, we compiled an updated salivary proteome. We have mapped the salivary proteome to the published data on differentially expressed proteins from oral cancer tissues and also for their secretory features using prediction tools, SignalP 4.1, TMHMM 2c and Exocarta. Proteotypic peptides for the subset of proteins implicated in oral cancer and mapped to any two of the prediction tools for secretory potential have been listed. The data here are related to the research article “Human saliva proteome – a resource of potential biomarkers for oral cancer” in the Journal of Proteomics [1]. PMID:26217819

  18. Expression of matrix metalloproteinase-9 in oral potentially malignant disorders: A systematic review.

    PubMed

    Venugopal, Archana; Uma Maheswari, T N

    2016-01-01

    Matrix metalloproteinase-9 (MMP-9) is an inducible enzyme. Oral potentially malignant disorders (OPMDs) are considered as the early tissue changes that happen due to various habits such as smoking tobacco, chewing tobacco or stress. This alteration in the tissues alters the expression of MMP-9. The rationale of the review is to know the expression of MMP-9 in OPMDs. Hand searching and electronic databases such as PubMed and ScienceDirect were done for mesh terms such as OPMDs and MMP-9. Eight articles were obtained, after applying inclusion and exclusion criteria. These articles were assessed with QUADAS and data were extracted and evaluated. The included eight studies were done in 182 oral squamous cell carcinoma cases, 430 OPMDs (146 oral lichen planus, 264 leukoplakia and 20 oral submucous fibrosis) and 352 healthy controls evaluated for MMP-9. MMP-9 expression was found to be elevated in tissue, serum and saliva samples of OPMDs than in healthy controls. There is only one study in each serum and saliva samples to evaluate MMP-9. Saliva being noninvasive and serum being minimally invasive, more studies need to be done in both serum and saliva to establish MMP-9 as an early diagnostic marker in OPMDs to know its potential in malignant transformation.

  19. Galectin-1 is a useful marker for detecting neoplastic squamous cells in oral cytology smears.

    PubMed

    Noda, Yuri; Kondo, Yuko; Sakai, Manabu; Sato, Sunao; Kishino, Mitsunobu

    2016-06-01

    Cytologic diagnoses in the oral region are very difficult due to the small amount of cells in smears, which are also exposed to many stimulating factors and often show atypical changes. Galectin-1 (Gal1) is a β-galactoside binding protein that modulates tumor progression. Gal1 is very weakly expressed in normal cells, but is often overexpressed in neoplastic lesions. The aim of the present study was to determine whether it is possible to differentiate reactive changes from neoplastic changes in oral cytology smears based on the expression of Gal1. A total of 155 tissue biopsy specimens and 61 liquid-based cytology specimens were immunostained by an anti-Gal1 antibody, and Gal1 expression levels were subsequently evaluated. These samples consisted of oral squamous cell carcinomas, epithelial dysplasia, and oral mucosal diseases. The positive and negative expressions of Gal1 were examined in 37 specimens collected by scalpel and cytobrush biopsy. The sensitivity, specificity, and positive predictive value of Gal1 were also evaluated in smears. In tissue sections, the positive ratio of Gal1 in neoplastic lesions was high (72.3%). In cytology specimens, the positive ratio of Gal1 was higher in neoplastic lesions (79.0%) than in those negative for intraepithelial lesion or malignancy (22.2%). A correlation was found between immunocytochemical Gal1 expression and immunohistochemical Gal1 expression (P < .001). The sensitivity (75.0%), specificity (75.0%), and positive predictive value (91.3%) of Gal1 were also high in smears. In conclusion, Gal1 may be a useful marker for determining whether morphologic changes in cells are reactive or neoplastic.

  20. Network analysis reveals potential markers for pediatric adrenocortical carcinoma

    PubMed Central

    Kulshrestha, Anurag; Suman, Shikha; Ranjan, Rakesh

    2016-01-01

    Pediatric adrenocortical carcinoma (ACC) is a rare malignancy with a poor outcome. Molecular mechanisms of pediatric ACC oncogenesis and advancement are not well understood. Accurate and timely diagnosis of the disease requires identification of new markers for pediatric ACC. Differentially expressed genes (DEGs) were identified from the gene expression profile of pediatric ACC and obtained from Gene Expression Omnibus. Gene Ontology functional and pathway enrichment analysis was implemented to recognize the functions of DEGs. A protein–protein interaction (PPI) and gene–gene functional interaction (GGI) network of DEGs was constructed. Hub gene detection and enrichment analysis of functional modules were performed. Furthermore, a gene regulatory network incorporating DEGs–microRNAs–transcription factors was constructed and analyzed. A total of 431 DEGs including 228 upregulated and 203 downregulated DEGs were screened. These genes were largely involved in cell cycle, steroid biosynthesis, and p53 signaling pathways. Upregulated genes, CDK1, CCNB1, CDC20, and BUB1B, were identified as the common hubs of PPI and GGI networks. All the four common hub genes were also part of modules of the PPI network. Moreover, all the four genes were also present in the largest module of GGI network. A gene regulatory network consisting of 82 microRNAs and 100 transcription factors was also constructed. CDK1, CCNB1, CDC20, and BUB1B may serve as potential biomarker of pediatric ACC and as potential targets for therapeutic approach, although experimental studies are required to authenticate our findings. PMID:27555782

  1. Electrical potentials of restorations in subjects without oral complaints.

    PubMed

    Muller, A W; Van Loon, L A; Davidson, C L

    1990-09-01

    The electrical potentials of 183 amalgam and 11 precious metal restorations, and one set of brackets, were measured. None of the 28 subjects had galvanism, leukoplakia, oral lichen planus, or toxic or allergic reactions to restorations. The potentials of the amalgam restorations increased with age, from about -350 mV NHE at 30 days, to about +100 mV NHE after more than 1000 days. In most subjects potential differences of more than 50 mV were present between restorations; this phenomenon is therefore assumed to be common in healthy populations.

  2. Role of human papillomavirus in oral squamous cell carcinoma and oral potentially malignant disorders: A review of the literature

    PubMed Central

    Gupta, Shikha; Gupta, Sunita

    2015-01-01

    Human papillomaviruses (HPVs) are epitheliotropic viruses with an affinity for keratinocytes and are principally found in the anogenital tract, urethra, skin, larynx, tracheobronchial and oral mucosa. On the basis of high, but variable frequency of HPV in oral squamous cell carcinoma (OSCC), malignant potential of HPV infection has been hypothesized but not definitely confirmed. The aim of this review was to highlight the genomic structure and possible mechanism of infection and carcinogenesis by HPV in the oral mucosa and to review the frequency of HPV prevalence in OSCC and oral potentially malignant disorders. A computer database search was performed through the use of PubMed from 1994 to 2014. Search keywords used were: HPV and oral cancer, HPV and oral leukoplakia, HPV and oral lichen planus, HPV and OSCC, HPV and verrucous carcinoma, HPV and proliferative verrucous leukoplakia, HPV and oral papilloma. PMID:26097339

  3. FAS ligand expression in inflammatory infiltrate lymphoid cells as a prognostic marker in oral squamous cell carcinoma.

    PubMed

    Peterle, G T; Santos, M; Mendes, S O; Carvalho-Neto, P B; Maia, L L; Stur, E; Agostini, L P; Silva, C V M; Trivilin, L O; Nunes, F D; Carvalho, M B; Tajara, E H; Louro, I D; Silva-Conforti, A M A

    2015-09-22

    Currently, the most important prognostic factor in oral squamous cell carcinoma (OSCC) is the presence of regional lymph node metastases, which correlates with a 50% reduction in life expectancy. We have previously observed that expression of hypoxia genes in the tumor inflammatory infiltrate is statistically related to prognosis in OSCC. FAS and FASL expression levels in OSCC have previously been related to patient survival. The present study analyzed the relationship between FASL expression in the inflammatory infiltrate lymphoid cells and clinical variables, tumor histology, and prognosis of OSCC. Strong FASL expression was significantly associated with lymph node metastases (P = 0.035) and disease-specific death (P = 0.014), but multivariate analysis did not confirm FASL expression as an independent death risk factor (OR = 2.78, 95%CI = 0.81-9.55). Disease-free and disease-specific survival were significantly correlated with FASL expression (P = 0.016 and P = 0.005, respectively). Multivariate analysis revealed that strong FASL expression is an independent marker for earlier disease relapse and disease-specific death, with approximately 2.5-fold increased risk compared with weak expression (HR = 2.24, 95%CI = 1.08-4.65 and HR = 2.49, 95%CI = 1.04-5.99, respectively). Our results suggest a potential role for this expression profile as a tumor prognostic marker in OSCC patients.

  4. Molecular markers: a potential resource for ginger genetic diversity studies.

    PubMed

    Ismail, Nor Asiah; Rafii, M Y; Mahmud, T M M; Hanafi, M M; Miah, Gous

    2016-12-01

    Ginger is an economically important and valuable plant around the world. Ginger is used as a food, spice, condiment, medicine and ornament. There is available information on biochemical aspects of ginger, but few studies have been reported on its molecular aspects. The main objective of this review is to accumulate the available molecular marker information and its application in diverse ginger studies. This review article was prepared by combing material from published articles and our own research. Molecular markers allow the identification and characterization of plant genotypes through direct access to hereditary material. In crop species, molecular markers are applied in different aspects and are useful in breeding programs. In ginger, molecular markers are commonly used to identify genetic variation and classify the relatedness among varieties, accessions, and species. Consequently, it provides important input in determining resourceful management strategies for ginger improvement programs. Alternatively, a molecular marker could function as a harmonizing tool for documenting species. This review highlights the application of molecular markers (isozyme, RAPD, AFLP, SSR, ISSR and others such as RFLP, SCAR, NBS and SNP) in genetic diversity studies of ginger species. Some insights on the advantages of the markers are discussed. The detection of genetic variation among promising cultivars of ginger has significance for ginger improvement programs. This update of recent literature will help researchers and students select the appropriate molecular markers for ginger-related research.

  5. Oxidative Stress in COPD: Sources, Markers, and Potential Mechanisms

    PubMed Central

    McGuinness, Adam John Anthony; Sapey, Elizabeth

    2017-01-01

    Markers of oxidative stress are increased in chronic obstructive pulmonary disease (COPD) and reactive oxygen species (ROS) are able to alter biological molecules, signaling pathways and antioxidant molecule function, many of which have been implicated in the pathogenesis of COPD. However, the involvement of ROS in the development and progression of COPD is not proven. Here, we discuss the sources of ROS, and the defences that have evolved to protect against their harmful effects. We address the role that ROS may have in the development and progression of COPD, as well as current therapeutic attempts at limiting the damage they cause. Evidence has indicated that the function of several key cells appears altered in COPD patients, and expression levels of important oxidant and antioxidant molecules may be abnormal. Therapeutic trials attempting to restore equilibrium to these molecules have not impacted upon all facets of disease and whilst the theory behind ROS influence in COPD appears sound, current models testing relevant pathways to tissue damage are limited. The heterogeneity seen in COPD patients presents a challenge to our understanding, and further research is essential to identify potential targets and stratified COPD patient populations where ROS therapies may be maximally efficacious. PMID:28212273

  6. Raman spectroscopy of oral tissues: correlation of spectral and biochemical markers

    NASA Astrophysics Data System (ADS)

    Singh, S. P.; Krishna, C. Murali

    2014-03-01

    Introduction Optical spectroscopic methods are being explored as novel tools for early and non-invasive cancer diagnosis. Both ex vivo and in vivo Raman spectroscopic studies carried out in oral cancer over the past decade have demonstrated that spectra of normal tissues are rich in lipids while tumor spectra show predominance of proteins. An accurate understanding of spectral features with respect to the biochemical composition is a pre-requisite before transferring these technologies for routine clinical usage. Therefore, in the present study, we have carried out Raman and biochemical studies on same tissues to correlate spectral markers and biochemical composition of normal and tumor oral tissues. Materials and Methods Spectra of 20 pairs of normal and tumor oral tissues were acquired using fiber-optic probe coupled HE-785 Raman spectrometer. Intensity associated with lipid (1440 cm-1) and protein (1450 and 1660 cm-1) bands were computed using curve-deconvolution method. Same tissues were then subjected to biochemical estimations of major biomolecules i.e., protein, lipid and phospholipids. Results and Discussion The intensity of the lipid band was found to be higher in normal tissues with respect to tumors, and the protein band was higher in tumors compared to normal tissues. Biochemical estimation yielded similar results i.e. high protein to lipid or phospholipid ratio in tumors with-respect to normal tissues. These differences were found to be statistically significant. Conclusion Findings of curve-deconvolution and biochemical estimation correlate very well and corroborate the spectral profile noted in earlier studies.

  7. Oral bacteria as potential probiotics for the pharyngeal mucosa.

    PubMed

    Guglielmetti, Simone; Taverniti, Valentina; Minuzzo, Mario; Arioli, Stefania; Stuknyte, Milda; Karp, Matti; Mora, Diego

    2010-06-01

    The research described here was aimed at the selection of oral bacteria that displayed properties compatible with their potential use as probiotics for the pharyngeal mucosa. We included in the study 56 bacteria newly isolated from the pharynges of healthy donors, which were identified at the intraspecies level and characterized in vitro for their probiotic potential. The experiments led us to select two potential probiotic bacterial strains (Streptococcus salivarius RS1 and ST3) and to compare them with the prototype oral probiotic S. salivarius strain K12. All three strains efficiently bound to FaDu human epithelial pharyngeal cells and thereby antagonized Streptococcus pyogenes adhesion and growth. All were sensitive to a variety of antibiotics routinely used for the control of upper respiratory tract infections. Immunological in vitro testing on a FaDu layer revealed different responses to RS1, ST3, and K12. RS1 and ST3 modulated NF-kappaB activation and biased proinflammatory cytokines at baseline and after interleukin-1beta (IL-1beta) induction. In conclusion, we suggest that the selected commensal streptococci represent potential pharyngeal probiotic candidates. They could display a good degree of adaptation to the host and possess potential immunomodulatory and anti-inflammatory properties.

  8. Oral Bacteria as Potential Probiotics for the Pharyngeal Mucosa▿

    PubMed Central

    Guglielmetti, Simone; Taverniti, Valentina; Minuzzo, Mario; Arioli, Stefania; Stuknyte, Milda; Karp, Matti; Mora, Diego

    2010-01-01

    The research described here was aimed at the selection of oral bacteria that displayed properties compatible with their potential use as probiotics for the pharyngeal mucosa. We included in the study 56 bacteria newly isolated from the pharynges of healthy donors, which were identified at the intraspecies level and characterized in vitro for their probiotic potential. The experiments led us to select two potential probiotic bacterial strains (Streptococcus salivarius RS1 and ST3) and to compare them with the prototype oral probiotic S. salivarius strain K12. All three strains efficiently bound to FaDu human epithelial pharyngeal cells and thereby antagonized Streptococcus pyogenes adhesion and growth. All were sensitive to a variety of antibiotics routinely used for the control of upper respiratory tract infections. Immunological in vitro testing on a FaDu layer revealed different responses to RS1, ST3, and K12. RS1 and ST3 modulated NF-κB activation and biased proinflammatory cytokines at baseline and after interleukin-1β (IL-1β) induction. In conclusion, we suggest that the selected commensal streptococci represent potential pharyngeal probiotic candidates. They could display a good degree of adaptation to the host and possess potential immunomodulatory and anti-inflammatory properties. PMID:20418429

  9. Oral baclofen in cerebral palsy: possible seizure potentiation?

    PubMed

    Hansel, Donna E; Hansel, Christian R W; Shindle, Michael K; Reinhardt, Elsie M; Madden, LaVerne; Levey, Eric B; Johnston, Michael V; Hoon, Alexander H

    2003-09-01

    Baclofen, a gamma-aminobutyric acid agonist, is widely used to treat spasticity of cerebral and spinal origin. Patients with both acute baclofen overdose and withdrawal have developed seizures. After several reports of new-onset seizures in children treated with oral baclofen at our institution, we reviewed our experience regarding possible effects of baclofen on seizure induction in a childhood movement disorders program over a 2-year period. Of 54 children (ages 1-10) treated with oral baclofen, 19 (35%) had a prior history of seizures. Five children (14%) developed new-onset seizures after starting baclofen. Although epilepsy is very common in children with cerebral palsy, these findings raise the possibility that baclofen may potentiate seizures in certain young children with cerebral palsy. Further study of the effects of baclofen on seizures is warranted.

  10. DNA methylation markers for oral pre-cancer progression: A critical review.

    PubMed

    Shridhar, Krithiga; Walia, Gagandeep Kaur; Aggarwal, Aastha; Gulati, Smriti; Geetha, A V; Prabhakaran, Dorairaj; Dhillon, Preet K; Rajaraman, Preetha

    2016-02-01

    Although oral cancers are generally preceded by a well-established pre-cancerous stage, there is a lack of well-defined clinical and morphological criteria to detect and signal progression from pre-cancer to malignant tumours. We conducted a critical review to summarize the evidence regarding aberrant DNA methylation patterns as a potential diagnostic biomarker predicting progression. We identified all relevant human studies published in English prior to 30th April 2015 that examined DNA methylation (%) in oral pre-cancer by searching PubMed, Web-of-Science and Embase databases using combined key-searches. Twenty-one studies (18-cross-sectional; 3-longitudinal) were eligible for inclusion in the review, with sample sizes ranging from 4 to 156 affected cases. Eligible studies examined promoter region hyper-methylation of tumour suppressor genes in pathways including cell-cycle-control (n=15), DNA-repair (n=7), cell-cycle-signalling (n=4) and apoptosis (n=3). Hyper-methylated loci reported in three or more studies included p16, p14, MGMT and DAPK. Two longitudinal studies reported greater p16 hyper-methylation in pre-cancerous lesions transformed to malignancy compared to lesions that regressed (57-63.6% versus 8-32.1%; p<0.01). The one study that explored epigenome-wide methylation patterns reported three novel hyper-methylated loci (TRHDE; ZNF454; KCNAB3). The majority of reviewed studies were small, cross-sectional studies with poorly defined control groups and lacking validation. Whilst limitations in sample size and study design preclude definitive conclusions, current evidence suggests a potential utility of DNA methylation patterns as a diagnostic biomarker for oral pre-cancer progression. Robust studies such as large epigenome-wide methylation explorations of oral pre-cancer with longitudinal tracking are needed to validate the currently reported signals and identify new risk-loci and the biological pathways of disease progression.

  11. Markers

    ERIC Educational Resources Information Center

    Healthy Schools Network, Inc., 2011

    2011-01-01

    Dry erase whiteboards come with toxic dry erase markers and toxic cleaning products. Dry erase markers labeled "nontoxic" are not free of toxic chemicals and can cause health problems. Children are especially vulnerable to environmental health hazards; moreover, schools commonly have problems with indoor air pollution, as they are more densely…

  12. Evaluating oral noncombustible potential-reduced exposure products for smokers

    PubMed Central

    Eissenberg, Thomas

    2010-01-01

    Introduction: Potential-reduced exposure products (PREPs) are marketed as a way for smokers to continue using tobacco while possibly lessening their tobacco toxicant intake. Some tobacco-based PREPs are combustible and intended to be smoked, while others are noncombustible and intended to be administered orally (e.g., Camel Snus [CS] tobacco sachets and Ariva tobacco tablets). The ability of these noncombustible PREPs to reduce smokers’ exposure to cigarette-delivered toxicants and suppress tobacco abstinence symptoms effectively is unclear. Clinical laboratory methods have been used to measure combustible PREP-associated toxicant exposure and abstinence symptom suppression and could be applied to evaluating the effects of orally administered noncombustible PREPs. Methods: In this study, 21 smokers (6 women) participated in four 5-day conditions that differed by product used: CS, Ariva, own brand cigarettes, or no tobacco. Measures included expired-air carbon monoxide (CO), the urinary metabolite of nicotine (cotinine), the urinary metabolite of the carcinogen NNK (NNAL-T), and subjective effect ratings. Results: Relative to own brand, all other conditions were associated with CO and cotinine levels that were lower and abstinence symptom ratings that were greater. Only no-tobacco use was associated with significantly lower NNAL levels. Acceptability ratings were also lower in all conditions relative to own brand. Discussion: Although these oral products reduce exposure to CO, their ineffective abstinence symptom suppression and low acceptability may limit their viability as PREPs. As with combustible PREPs, clinical laboratory study of orally administered noncombustible PREPs will be a valuable part of any comprehensive PREP evaluation strategy. PMID:20159791

  13. Oral contraceptives moderately effect bone resorption markers and serum-soluble interleukin-6 receptor concentrations.

    PubMed

    Zittermann, A; Rühl, J; Berthold, H K; Sudhop, T; van der Ven, H; Reinsberg, J; Stehle, P

    2002-01-01

    This study investigated the effect of ethinylestradiol(EE2)-containing oral contraceptives on mineral and bone metabolism and on serum soluble-interleukin-6-receptor (sIL-6R) during the menstrual cycle. Twelve women, aged 24.3 +/- 2.9 years, were examined. Blood and 24-hour and fasting urine samples were obtained during one menstrual cycle between cycle day 3-5 (t(1)), cycle day 10-12 (t(2)), cycle day 24-26 (t(3)), and again on day 3-5 of the next cycle (t(4)). EE2 intake was 0 mg at t(1), 30 mg at t(2), 30 mg at t(3) and 0 mg at t(4). Fasting renal phosphorus and calcium excretions were slightly reduced at t(2) and t(3) compared with t(1) and t(4) (P < 0.05-0.001). Moreover, renal excretion of the bone resorption marker C-Teleopeptide was at t(3) reduced by 26% compared with t(1)(P < 0.01) and by 13% compared with t(4)(P > 0.05). Fasting sIL-6R levels were 16.5% lower at t(2) and 12% lower at t(3) than at t(4) (P < 0.01 and P < 0.05). sIL-6R was correlated with total deoxypyridinoline excretion (r = +0.35; P < 0.05) and with fasting renal excretions of calcium (r = +0.36; P < 0.05) and phosphorus (r = +0.29; P < 0.05). In summary, our data suggest that in young women, cyclic monthly oral contraceptive intake is associated with small, but significant variations in bone resorption processes and in serum sIL-6R levels. Results are a further indication that monthly fluctuations of bone resorption in young women are mediated by sex hormones and that osteoclastic activity is stimulated by cytokines in vivo.

  14. Prevalence of salivary epstein-barr virus in potentially malignant oral disorders and oral squamous cell carcinoma

    PubMed Central

    Ocete-Monchon, María-Dolores; Leopoldo-Rodado, Manuel; Murillo-Cortes, Judith; Díaz-Fernández, Jose-M.; Medina-Gonzalez, Rafael; Gimeno-Cardona, Concepción; Bagan, Jose-V.

    2016-01-01

    Background To analyze the presence of salivary Epstein-Barr virus (EBV) DNA in oral squamous cell carcinoma and potentially malignant oral disorders. Material and Methods Three groups were studied: Group 1 (12 oral squamous cell carcinomas (OSCC)), Group 2 (12 potentially malignant oral disorders (PMD)) and Group 3 (47 healthy controls). EBV DNA salivary analysis was performed by PCR. Results The highest percentage of positive salivary EBV DNA corresponded to the OSCC group (58.3%), followed by the PMD group (41.7%) and the controls (40.4%). The differences between groups were not statistically significant, however (p>0.05). Conclusions Salivary EBV DNA was more prevalent in OSCC than in PMD or the controls. Key words:EBV DNA, saliva, oral squamous cell carcinoma, oral leukoplakia. PMID:26827058

  15. EST-SSR markers derived from an elite barley cultivar (Hordeum vulgare L. 'Morex'): polymorphism and genetic marker potential.

    PubMed

    Emebiri, Livinus C

    2009-08-01

    Microsatellites or simple sequence repeats have become the markers of choice for marker-assisted selection because of their low template DNA requirement, high reproducibility, and high level of polymorphism. This study investigated a new set of barley (Hordeum vulgare L.) EST-derived SSR markers designed to target gene sequences expressed during grain development, as they are more likely to be important in determining grain quality. The EST sequences (HVSMEh and HVSMEi) were derived from cDNA libraries of the elite six-rowed cultivar Morex, made from spikes harvested at 5 to 45 days after pollination. Approximately half of the 110 SSR markers derived from the ESTs were polymorphic in a panel of 8 diverse barley genotypes, with PIC values between 0.19 and 0.79. Twenty of the new markers were mapped to chromosomal locations using 2 doubled haploid populations. To demonstrate marker potential, quantitative trait locus (QTL) analyses were carried out with phenotypic data on wort beta-glucan content and beta-glucanase activity, two traits with a long history of genetic studies. Most of the EST-SSR markers mapped to within 10 cM of the cellulose synthase (HvCesA) and cellulose synthase-like (HvCslF) genes, which provides highly informative functional markers for tracking these genes in breeding programs. It was also observed that on any given chromosome, the QTL for beta-glucan content and beta-glucanase activity were rarely coincident but tended to occur in adjacent intervals along chromosomal regions, which agreed with their independent genetic basis; the adjacent localization may be important for coordination of cell wall degradation during germination and malting.

  16. Prognostic potential of AgNORs in oral submucous fibrosis

    PubMed Central

    Murgod, Sanjay; Channabasaviah, Girish Hemadal; Shivamurthy, Dyamenahalli Malleshappa; Ashok, Lingappa; Krishnappa, Savita Jangal

    2016-01-01

    Aim and Objective: The role of prognosis cannot be stressed enough, especially when it comes to potentially malignant lesions. The argyrophilic nucleolar organizer regions (AgNORs), which is simple and cost-effective has been used in diagnostic and prognostic pathologies. This study seeks to identify the nucleolar organizer regions (NORs) in oral submucous fibrosis (OSMF), to correlate the AgNOR count with the histologic grade of OSMF, and to evaluate the prognostic potential of AgNOR. Materials and Methods: The sample size consisted of archival paraffin blocks of 35 cases of varying grades of OSMF and 10 cases of squamous cell carcinoma. Normal mucosa samples served as controls for the study. AgNOR staining in accordance with the method of Smith and Crocker was performed and Student's t-test was used for statistical analysis. Results: The results showed an increase in AgNOR counts with corresponding grades of OSMF, the count being least in normal mucosa and also an increase in AgNOR count with corresponding decrease in differentiation of oral squamous cell carcinoma. Conclusion: AgNOR staining is a rapid and inexpensive procedure representing cellular proliferation that can be used to assess the nature of the lesion and therefore, the prognosis. PMID:27114958

  17. The Late Positive Potential: A Neurophysiological Marker for Emotion Regulation in Children

    ERIC Educational Resources Information Center

    Dennis, Tracy A.; Hajcak, Greg

    2009-01-01

    Background: The ability to modulate emotional responses, or emotion regulation, is a key mechanism in the development of mood disruptions. Detection of a neural marker for emotion regulation thus has the potential to inform early detection and intervention for mood problems. One such neural marker may be the late positive potential (LPP), which is…

  18. Expression of epithelial-mesenchymal transition markers at the invasive front of oral squamous cell carcinoma

    PubMed Central

    COSTA, Liana Cristina Melo Carneiro; LEITE, Camila Ferreira; CARDOSO, Sérgio Vitorino; LOYOLA, Adriano Mota; de FARIA, Paulo Rogério; SOUZA, Paulo Eduardo Alencar; HORTA, Martinho Campolina Rebello

    2015-01-01

    Oral squamous cell carcinoma (OSCC) is one of the most common malignances. In epithelial-mesenchymal transition (EMT), epithelial cells switch to mesenchymal-like cells exhibiting high mobility. This migratory phenotype is significant during tumor invasion and metastasis. Objective : The aim of this study is to evaluate the expression of the EMT markers E-cadherin, N-cadherin and vimentin in OSCC. Material and Methods : Immunohistochemical detection of E-cadherin, N-cadherin and vimentin was performed on 20 OSCC samples. Differences in the expression of each protein at the invasive front (IF) and in the central/superficial areas (CSA) of the tumor were assessed. Differences in the expression of each protein at the IF of both histologically high- and low-invasive OSCCs were evaluated. Associations among expression of proteins at the IF were assessed. Correlations between the expression levels of each protein at the IF and the tumor stage and clinical nodal status were also evaluated. Results : Reduced expression of E-cadherin was detected in 15 samples (75%). E-cadherin expression was reduced at the IF when compared to the CSA and in high-invasive tumors when compared to low-invasive tumors. All samples were negative for N-cadherin, even though one sample showed an inconspicuous expression. Positive expression of vimentin was observed in 6 samples (30%). Nevertheless, there was no difference in vimentin expression between the IF and the CSA regions or between the low- and high-invasive tumors. Furthermore, no association was observed among protein expression levels at the IF. Finally, no correlations were observed between each protein’s expression levels and tumor stage or clinical nodal status. Conclusions : Reduced E-cadherin expression at the IF and its association with histological invasiveness suggest that this protein is a noteworthy EMT marker in OSCC. Although vimentin was also detected as an EMT marker, its expression was neither limited to the IF nor was

  19. Effects of oral D-ribose supplementation on anaerobic capacity and selected metabolic markers in healthy males.

    PubMed

    Kreider, R B; Melton, C; Greenwood, M; Rasmussen, C; Lundberg, J; Earnest, C; Almada, A

    2003-03-01

    Oral D-ribose supplementation has been reported to increase adenine nucleotide synthesis and exercise capacity in certain clinical populations. Theoretically, increasing adenine nucleotide availability may enhance high intensity exercise capacity. This study evaluated the potential ergogenic value of D-ribose supplementation on repetitive high-intensity exercise capacity in 19 trained males. Subjects were familiarized to the testing protocol and performed two practice-testing trials before pre-supplementation testing. Each test involved warming up for 5 min on a cycle ergometer and then performing two 30-s Wingate anaerobic sprint tests on a computerized cycle ergometer separated by 3 min of rest recovery. In the pre- and post-supplementation trials, blood samples were obtained at rest, immediately following the first and second sprints, and following 5 min of recovery from exercise. Subjects were then matched according to body mass and anaerobic capacity and assigned to ingest, in a randomized and double blind manner, capsules containing either 5 g of a dextrose placebo (P) or D-ribose (R) twice daily (10 g/d) for 5 d. Subjects then performed post-supplementation tests on the 6th day. Data were analyzed by ANOVA for repeated measures. Results revealed a significant interaction (p =.04) in total work output. Post hoc analysis revealed that work significantly declined (-18 +/- 51 J) during the second post-supplementation sprint in the P group while being maintained in the R group (-0.0 +/- 31 J). No significant interactions were observed in peak power, average power, torque, fatigue index, lactate, ammonia, glucose, or uric acid. Results indicate that oral ribose supplementation (10 g/d for 5 d) does not affect anaerobic exercise capacity or metabolic markers in trained subjects as evaluated in this study.

  20. Gene expression profiling of craniofacial fibrous dysplasia reveals ADAMTS2 overexpression as a potential marker.

    PubMed

    Zhou, Shang-Hui; Yang, Wen-Jun; Liu, Sheng-Wen; Li, Jiang; Zhang, Chun-Ye; Zhu, Yun; Zhang, Chen-Ping

    2014-01-01

    Fibrous dysplasia (FD) as an abnormal bone growth is one of the common fibro-osseous leasions (FOL) in oral and maxillofacial region, however, its etiology still remains unclear. Here, we performed gene expression profiling of FD using microarray analysis to explore the key molecule events in FD development, and develop potential diagnostic markers or therapeutic targets for FD. We found that 1,881 genes exhibited differential expression with more than two-fold changes in FD compared to normal bone tissues, including 1,200 upregulated genes and 681 downregulated genes. Pathway analysis indicated that obviously activated pathways are Ribosome and ECM-receptor interaction pathways; downregulated pathways are "Hepatitis C" and "cancer" signaling pathways. We further validated the expression of ADAMTS2, one of most differentiated expressed genes, by Immunohistochemistry (IHC) in 40 of FD cases. Results showed that ADAMTS2 was significantly overexpressed in FD tissues, but rarely expressed in normal bone tissues, suggesting that ADAMTS2 could be a potential biomarker for FD. Thus, this study uncovered differentially expressed candidate genes in FD, which provides pilot data for understanding FD pathogenesis, and developing novel biomarkers for diagnosis and targeting of FD.

  1. Effect of low-dose oral contraceptives on androgenic markers and acne.

    PubMed

    Thorneycroft, I H; Stanczyk, F Z; Bradshaw, K D; Ballagh, S A; Nichols, M; Weber, M E

    1999-11-01

    Oral contraceptives (OC) suppress excess androgen production; however, different progestins in combination with low-dose estrogens produce divergent effects on sex hormone-binding globulin (SHBG) and testosterone that may influence clinical outcomes. This multicenter, open-label, randomized study compared biochemical androgen profiles and clinical outcomes associated with two OC containing the same amounts of ethinyl estradiol (EE, 20 micrograms) but different progestins, levonorgestrel (LNG, 100 micrograms), and norethindrone acetate (NETA, 1000 micrograms). Fifty-eight healthy women (18-28 years old) received three cycles of treatment with LNG/EE (n = 30) or NETA/EE (n = 28). The results showed that LNG reduced androgen levels in three compartments--adrenal, ovarian, and peripheral. NETA reduced only adrenal and peripheral androgens. Despite a 2.2-fold greater relative increase in SHBG with NETA than LNG, bioavailable testosterone (T) was reduced by the same amount with LNG and NETA. Both treatments improved acne and were well tolerated. Low-dose OC (EE, 20 micrograms) are effective in reducing circulating androgens and acne lesions without causing weight gain. Although LNG and NETA affected secondary markers differently, both OC formulations produced an equivalent decrease in bioavailable.

  2. Oral glucose tolerance test effects on endothelial inflammation markers in healthy subjects and diabetic patients.

    PubMed

    Derosa, G; D'Angelo, A; Salvadeo, S A T; Ferrari, I; Fogari, E; Gravina, A; Mereu, R; Palumbo, I; Maffioli, P; Randazzo, S; Cicero, A F G

    2010-01-01

    The aim of this study was to evaluate the effect of an oral glucose tolerance test (OGTT) on the level of endothelial dysfunction and vascular inflammation markers in healthy subjects (H) and diabetic overweight patients (D). We enrolled 256 healthy subjects and 274 type 2 diabetic patients. We evaluated blood glucose (BG), soluble intercellular adhesion molecule-1 (sICAM-1), interleukin-6 (IL-6), high-sensitivity C reactive protein (hsCRP), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), and tumor necrosis factor-alpha (TNF-alpha) at baseline and after OGTT. We observed that BG, sICAM-1, IL-6, hs-CRP, sVCAM-1, sE-selectin, and TNF-alpha values were higher in D group than in H group. In a large sample of adult healthy subjects and type 2 diabetics we observed that both answer to an OGTT with a significant increase in biomarkers of systemic low-grade inflammation and endothelial dysfunction such as hsCRP, IL-6, TNF-alpha, sICAM-1, sVCAM-1, and sE-selectin. Type 2 diabetics experienced, however, a more significant increase in TNF-alpha, and sE-selectin.

  3. Oral cancer/endothelial cell fusion experiences nuclear fusion and acquisition of enhanced survival potential

    SciTech Connect

    Song, Kai; Song, Yong; Zhao, Xiao-Ping; Shen, Hui; Wang, Meng; Yan, Ting-lin; Liu, Ke; Shang, Zheng-jun

    2014-10-15

    Most previous studies have linked cancer–macrophage fusion with tumor progression and metastasis. However, the characteristics of hybrid cells derived from oral cancer and endothelial cells and their involvement in cancer remained unknown. Double-immunofluorescent staining and fluorescent in situ hybridization (FISH) were performed to confirm spontaneous cell fusion between eGFP-labeled human umbilical vein endothelial cells (HUVECs) and RFP-labeled SCC9, and to detect the expression of vementin and cytokeratin 18 in the hybrids. The property of chemo-resistance of such hybrids was examined by TUNEL assay. The hybrid cells in xenografted tumor were identified by FISH and GFP/RFP dual-immunofluoresence staining. We showed that SCC9 cells spontaneously fused with cocultured endothelial cells, and the resultant hybrid cells maintained the division and proliferation activity after re-plating and thawing. Such hybrids expressed markers of both parental cells and became more resistant to chemotherapeutic drug cisplatin as compared to the parental SCC9 cells. Our in vivo data indicated that the hybrid cells contributed to tumor composition by using of immunostaining and FISH analysis, even though the hybrid cells and SCC9 cells were mixed with 1:10,000, according to the FACS data. Our study suggested that the fusion events between oral cancer and endothelial cells undergo nuclear fusion and acquire a new property of drug resistance and consequently enhanced survival potential. These experimental findings provide further supportive evidence for the theory that cell fusion is involved in cancer progression. - Highlights: • The fusion events between oral cancer and endothelial cells undergo nuclear fusion. • The resulting hybrid cells acquire a new property of drug resistance. • The resulting hybrid cells express the markers of both parental cells (i.e. vimentin and cytokeratin 18). • The hybrid cells contribute to tumor repopulation in vivo.

  4. Potential immunological markers for diagnosis and therapeutic assessment of toxocariasis.

    PubMed

    Rubinsky-Elefant, Guita; Hoshino-Shimizu, Sumie; Jacob, Cristina Miuki Abe; Sanchez, Maria Carmen Arroyo; Ferreira, Antonio Walter

    2011-01-01

    In human toxocariasis, there are few approaches using immunological markers for diagnosis and therapeutic assessment. An immunoblot (IB) assay using excretory-secretory Toxocara canis antigen was standardized for monitoring IgG, IgE and IgA antibodies in 27 children with toxocariasis (23 visceral, three mixed visceral and ocular, and one ocular form) for 22-116 months after chemotherapy. IB sensitivity was 100% for IgG antibodies to bands of molecular weight 29-38, 48-54, 95-116, 121-162, >205 kDa, 80.8% for IgE to 29-38, 48-54, 95-121, > 205 kDa, and 65.4% for IgA to 29-38, 48-54, 81-93 kDa. Candidates for diagnostic markers should be IgG antibodies to bands of low molecular weight (29-38 and 48-54 kDa). One group of patients presented the same antibody reactivity to all bands throughout the follow-up study; in the other group, antibodies decayed partially or completely to some or all bands, but these changes were not correlated with time after chemotherapy. Candidates for monitoring patients after chemotherapy may be IgG antibodies to > 205 kDa fractions, IgA to 29-38, 48-54, 81-93 kDa and IgE to 95-121 kDa. Further identification of antigen epitopes related to these markers will allow the development of sensitive and specific immunoassays for the diagnosis and therapeutic assessment of toxocariasis.

  5. Improved oral therapeutic potential of nanoencapsulated cryptdin formulation against Salmonella infection.

    PubMed

    Rishi, Praveen; Bhogal, Akanksha; Arora, Sumeha; Pandey, Satish K; Verma, Indu; Kaur, Indu Pal

    2015-05-25

    An encapsulated system for cryptdin-2 (a Paneth cell antimicrobial peptide) was developed, with a view to help it sustain adverse gut conditions and to ensure its bioavailability on oral administration. The formulation was characterized on the basis of particle size, zeta potential and polydispersity index. Cryptdin-2 loaded nanoparticles of size 105±7 nm, formulated by ionotropic gelation method using chitosan: tripolyphosphate (5:2), revealed 60% drug entrapment efficiency with 65% in vitro release in 4.5 h. Developed system was evaluated for its therapeutic application against Salmonella Typhimurium infection in mice, on the basis of survivability of animals, bacterial load in tissues, histo-architecture and oxidative damage markers. Infected mice when treated with the encapsulated peptide showed 83% survivability and approximately 2 log unit reductions in the bacterial load in the tissues versus 100% mortality observed with the free peptide. The encapsulated cryptdin-2 also achieved a decrease in the level of oxidants, particularly nitrite by 3.25 folds and increased the level of antioxidant catalase by 2 folds when compared to the levels exhibited by the free peptide. The bacteriological and biochemical alterations illustrated by encapsulated peptide co-related well with the histo-architectural studies. The study is a first pre-clinical report on the oral effectiveness of cryptdin-2 by its suitable encapsulation and has potential for future clinical applications.

  6. Clinical Utility of Serum Homocysteine and Folate as Tumor Markers in Oral Squamous Cell Carcinoma - A Cross-Sectional Study

    PubMed Central

    Erugula, Sridhar Reddy; Danappanavar, Prasanna M.; Ealla, Kranti Kiran Reddy; Velidandla, Surekha; Manikya, Sangameshwar

    2016-01-01

    Introduction Oral Squamous Cell Carcinoma (OSCC) is a common malignancy involving head and neck. Identifying the markers of molecular levels or biochemical markers involving the various metabolic reactions associated with the initiation and biological behavior of individual tumors are very important in diagnosis and prognosis. Aim To measure and compare the levels of serum Homocysteine (Hcy) and serum folate in OSCC patients, smoking group and healthy subjects and also to assess the clinical utility of serum Hcy as a potential tumor marker in OSCC. Materials and Methods The study group comprised of 60 subjects, of whom 30 were classified as OSCC cases (GROUP I) and 15 were classified as smokers without OSCC (GROUP II). The control group included 15 healthy individuals without smoking habit (Group III). Hcy was measured with High Performance Liquid Chromatography (HPLC). Folate estimation was done by Chemiluminiscence Immuno Assay (CLIA). Comparison of mean Hcy and folate values among the groups was done using ANOVA with Post-Hoc Games Howell test. Gender was compared using Chi-square test. Comparison of mean age was using ANOVA with Post-Hoc Tukey’s test. Results The mean serum folate level in OSCC patients was 5.34ng/mL, 7.68ng/mL in smoking group and 10.99ng/mL in control group. There was a significant difference in the mean serum folate levels among the three study groups (p<0.001). The mean serum Hcy in OSCC patients was 23.58μmol/L, 17.46μmol/L, in smoking group and 10.76μmol/l in controls. There was a significant difference in the mean serum Hcy levels among the three study groups (p<0.001). Conclusion The present study found an interesting association with serum Hcy and folate levels in OSCC which could be useful as a biochemical “Tumor Marker” and thereby providing insights into the onset and progression of the disease. PMID:27891452

  7. Prevalence and Risk Factors for Oral Potentially Malignant Disorders in Indian Population

    PubMed Central

    Kumar, Sandeep; Debnath, Nitai; Ismail, Mohammed B.; Kumar, Arunoday; Kumar, Amit; Badiyani, Bhumika K.; Dubey, Pavan K.; Sukhtankar, Laxmi V.

    2015-01-01

    Objective. To assess the prevalence of oral potentially malignant disorders and to determine the potential risk factors for its development in Indian population. Materials and Methods. This cross-sectional study was carried out on 1241 individuals in Indore, Madhya Pradesh. A questionnaire was designed to record information about sociodemographic characteristics, oral hygiene practices, dietary habits, and risk factors for oral potentially malignant disorders. Oral mucosal lesions were examined by a skilled person. Results. The overall prevalence of oral potentially malignant disorders was found to be 13.7% with oral submucous fibrosis (8.06%) found to be more common and erythroplakia (0.24%) found to be least prevalent. Results of Logistic Regression analysis showed that males (OR = 2.09, P value < 0.0001) who were ever consumers of tobacco (OR = 2.06, P value = 0.030) and areca nut chewing (OR = 2.64, P value = 0.004) were more likely to develop oral potentially malignant disorders compared to never consumers. Diabetic (OR = 2.21, P value = 0.014) and underweight individuals (OR = 2.23, P value = 0.007) were more likely to suffer from oral potentially malignant disorders. Conclusion. The study reinforces the association of tobacco and areca nut consumption with oral potentially malignant disorders. An association of oral potentially malignant disorders with diabetes and BMI was confirmed by this study. PMID:26347822

  8. Advances in Optical Adjunctive Aids for Visualisation and Detection of Oral Malignant and Potentially Malignant Lesions

    PubMed Central

    Bhatia, Nirav; Lalla, Yastira; Vu, An N.; Farah, Camile S.

    2013-01-01

    Traditional methods of screening for oral potentially malignant disorders and oral malignancies involve a conventional oral examination with digital palpation. Evidence indicates that conventional examination is a poor discriminator of oral mucosal lesions. A number of optical aids have been developed to assist the clinician to detect oral mucosal abnormalities and to differentiate benign lesions from sinister pathology. This paper discusses advances in optical technologies designed for the detection of oral mucosal abnormalities. The literature regarding such devices, VELscope and Identafi, is critically analysed, and the novel use of Narrow Band Imaging within the oral cavity is also discussed. Optical aids are effective in assisting with the detection of oral mucosal abnormalities; however, further research is required to evaluate the usefulness of these devices in differentiating benign lesions from potentially malignant and malignant lesions. PMID:24078812

  9. Cortactin is a prognostic marker for oral squamous cell carcinoma and its overexpression is involved in oral carcinogenesis.

    PubMed

    Liu, Yu-Ching; Ho, Heng-Chien; Lee, Miau-Rong; Yeh, Chung-Min; Tseng, Hsien-Chang; Lin, Yung-Chang; Chung, Jing-Gung

    2017-03-01

    EMS1 (chromosome eleven, band q13, mammary tumor and squamous cell carcinoma-associated gene 1) gene amplification and the concomitant cortactin overexpression have been reported to associate with poor prognosis and tumor metastasis. In this study, we examined cortactin expression by immunohistochemistry in human oral tumors and murine tongue tumors which were induced by the carcinogen 4-nitroquinoline 1-oxide (4-NQO). The immunostaining results show over- to moderate expression of cortactin in 85% (104/122) of oral squamous cell carcinoma (OSCC) tissues and in all 15 leukoplakia tissues examined. Further, statistical analysis indicates that cortactin overexpression appears to be a predictor for shorter survival and poorer prognosis in OSCC patients. In an animal model, cortactin is shown to upregulate in infiltrating squamous cell carcinoma, papilloma, and epithelia with squamous hyperplasia, indicating that cortactin induction is an early event during oral carcinogenesis. It is suggested that cortactin expression is mediated in the progression of pre-malignancy to papilloma, based on earlier cortactin induction in pre-malignancy preceding cyclin D1 in papilloma. In conclusion, cortactin overexpression is frequently observed in human OSCC and mouse tongue tumors. Thus, cortactin may have an important role in the development of oral tumors in human and mice. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 799-812, 2017.

  10. The Potential Role of Oral Fluid in Antidoping Testing

    PubMed Central

    Anizan, Sebastien; Huestis, Marilyn A.

    2015-01-01

    BACKGROUND Currently, urine and blood are the only matrices authorized for antidoping testing by the World Anti-Doping Agency (WADA). Although the usefulness of urine and blood is proven, issues remain for monitoring some drug classes and for drugs prohibited only in competition. The alternative matrix oral fluid (OF) may offer solutions to some of these issues. OF collection is easy, noninvasive, and sex neutral and is directly observed, limiting potential adulteration, a major problem for urine testing. OF is used to monitor drug intake in workplace, clinical toxicology, criminal justice, and driving under the influence of drugs programs and potentially could complement urine and blood for antidoping testing in sports. CONTENT This review outlines the present state of knowledge and the advantages and limitations of OF testing for each of the WADA drug classes and the research needed to advance OF testing as a viable alternative for antidoping testing. SUMMARY Doping agents are either prohibited at all times or prohibited in competition only. Few OF data from controlled drug administration studies are available for substances banned at all times, whereas for some agents prohibited only in competition, sufficient data may be available to suggest appropriate analytes and cutoffs (analytical threshold concentrations) to identify recent drug use. Additional research is needed to characterize the disposition of many banned substances into OF; OF collection methods and doping agent stability in OF also require investigation to allow the accurate interpretation of OF tests for antidoping monitoring. PMID:24153253

  11. Analysis of the invasive edge in primary and secondary oral squamous cell carcinoma: An independent prognostic marker: A retrospective study

    PubMed Central

    Nadaf, Afreen; Bavle, Radhika M; Soumya, M; D'mello, Sarah; Kuriakose, Moni Abraham; Govindan, Sindhu

    2016-01-01

    Background and Objectives: Oral squamous cell carcinoma (OSCC) is one of the most common head and neck carcinomas and corresponds to 95% of all oral cancers with an increasing morbidity and mortality. Its prognosis is affected by several clinicopathologic factors, one of which is pattern of invasion (POI). The histological features of OSCC may differ widely, but there is general agreement that the most useful prognostic information can be deduced from the invasive front of the tumor. In this retrospective study, our aim was to compare the POI, the status of connective tissue and the status of inflammation at the tumor–host interface in primary and recurrent (secondary) OSCC and test the validity of POI, to serve as a potential marker to assess the prognosis of the patient. Materials and Methods: Differentiation of tumors, POI, status of connective tissue and inflammation was assessed in 168 cases of primary and recurrent cases of OSCC. Statistical Analysis: Fisher's exact test was used to determine the statistical significance and P < 0.05 was considered to be statistically significant. Results: Our study showed that majority of the primary and secondary tumors were well differentiated, 117 [95.9%] and 34 [73.9%], respectively. Predominant POI in the primary and secondary tumor group was Pattern II and least was Pattern V. Worst pattern in primary tumor and highest distribution was seen for Pattern III (53.3%), and least for Pattern V (0.00%). In secondary tumors, the predominant worst pattern was Pattern IV (50.0%) and least distribution was seen for Pattern I (0.00%). Connective tissue status for both primary and secondary tumors showed the predominance of loose type (85.2% and 79.2%) and least was variable type (0.8% and 0.6%), respectively. Status of inflammation in the primary tumor group showed a predominance of moderate grade of inflammation (50.0%) and very mild grade of inflammation (6.6%) was the least type. In the secondary tumor group, moderate grade

  12. Identification of potential genetic markers for improved growth rate in channel catfish

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Identification of genetic polymorphism associated with muscle growth would improve selection efficiency of channel catfish broodstock. Because faster growth is typically associated with increased food intake, factors involved in food intake regulation may serve as potential gene markers for selecti...

  13. Stock-still behavior: a potential developmental marker.

    PubMed

    Sherkow, Susan P; Weinstein, Lissa; Kamens, Sarah R; Megyes, Matthew; Tishman, Lynn P; Williams, Cheryl

    2008-01-01

    During the course of a pilot study of toddlers' behavior and play, the experimenters observed a previously undocumented behavior. This behavior now labeled "stock-still" behavior, was noted at the age of 17.5 months and consisted of the toddlers' standing motionless at or near the doorway of a nursery when previously they had marched, seemingly intrepid, into the room on their own. A prospective study of eight children was undertaken to test the hypothesis that this behavior reliably occurs at a set time during the child's development. Analysis of videotape footage determined that the behavior did not occur as an isolated event but instead was part of a series of one to six individual events within a window spanning two to eight weeks, during a discrete period of time from ages 15.5 months to 18.5 months. It was hypothesized that this behavior may be a developmental marker of the moment when a toddler cognitively and affectively registers the differences between "inside" and "outside," self and other and inner space and outer space. This developmental step is manifested behaviorally as the child's ability to inhibit her responses to previously compelling external stimuli. This hypothesis, as well as its limitations, is herein discussed, and additional clarifying observations are suggested.

  14. Human salivary proteome--a resource of potential biomarkers for oral cancer.

    PubMed

    Sivadasan, Priya; Gupta, Manoj Kumar; Sathe, Gajanan J; Balakrishnan, Lavanya; Palit, Priyanka; Gowda, Harsha; Suresh, Amritha; Kuriakose, Moni Abraham; Sirdeshmukh, Ravi

    2015-09-08

    Proteins present in human saliva offer an immense potential for clinical applications. However, exploring salivary proteome is technically challenged due to the presence of amylase and albumin in high abundance. In this study, we used four workflows to analyze human saliva from healthy individuals which involved depletion of abundant proteins using affinity-based separation methods followed by protein or peptide fractionation and high resolution mass spectrometry analysis. We identified a total of 1256 human salivary proteins, 292 of them being reported for the first time. All identifications were verified for any shared proteins/peptides from the salivary microbiome that may conflict with the human protein identifications. On integration of our results with the analyses reported earlier, we arrived at an updated human salivary proteome containing 3449 proteins, 808 of them have been reported as differentially expressed proteins in oral cancer tissues. The secretory nature of 598 of the 808 proteins has also been supported on the basis of the presence of signal sequence, transmembrane domain or association with exosomes. From this subset, we provide a priority list of 139 proteins along with their proteotypic peptides, which may serve as a reference for targeted investigations as secretory markers for clinical applications in oral malignancies. This article is part of a Special Issue entitled: Proteomics in India.

  15. Oral cancer/endothelial cell fusion experiences nuclear fusion and acquisition of enhanced survival potential.

    PubMed

    Song, Kai; Song, Yong; Zhao, Xiao-Ping; Shen, Hui; Wang, Meng; Yan, Ting-Lin; Liu, Ke; Shang, Zheng-Jun

    2014-10-15

    Most previous studies have linked cancer-macrophage fusion with tumor progression and metastasis. However, the characteristics of hybrid cells derived from oral cancer and endothelial cells and their involvement in cancer remained unknown. Double-immunofluorescent staining and fluorescent in situ hybridization (FISH) were performed to confirm spontaneous cell fusion between eGFP-labeled human umbilical vein endothelial cells (HUVECs) and RFP-labeled SCC9, and to detect the expression of vementin and cytokeratin 18 in the hybrids. The property of chemo-resistance of such hybrids was examined by TUNEL assay. The hybrid cells in xenografted tumor were identified by FISH and GFP/RFP dual-immunofluoresence staining. We showed that SCC9 cells spontaneously fused with cocultured endothelial cells, and the resultant hybrid cells maintained the division and proliferation activity after re-plating and thawing. Such hybrids expressed markers of both parental cells and became more resistant to chemotherapeutic drug cisplatin as compared to the parental SCC9 cells. Our in vivo data indicated that the hybrid cells contributed to tumor composition by using of immunostaining and FISH analysis, even though the hybrid cells and SCC9 cells were mixed with 1:10,000, according to the FACS data. Our study suggested that the fusion events between oral cancer and endothelial cells undergo nuclear fusion and acquire a new property of drug resistance and consequently enhanced survival potential. These experimental findings provide further supportive evidence for the theory that cell fusion is involved in cancer progression.

  16. Orality, Literacy and Music's Creative Potential: A Comparative Approach.

    ERIC Educational Resources Information Center

    Campbell, Patricia Shehan

    1989-01-01

    Describes the rise of musical notation in the West, showing the relationship between that development and the origin of music literacy in China. Suggests that the balance of oral and literate means of music learning may foster creative expression in performance. Encourages the study and practice of orality in the training of young musicians. (LS)

  17. A comparison of oral and intravenous pimonidazole in canine tumors using intravenous CCI-103F as a control hypoxia marker

    SciTech Connect

    Kleiter, Miriam M.; Thrall, Donald E.; Malarkey, David E.; Ji Xiaoshen; Lee, David Y.W.; Chou, S.-C.; Raleigh, James A. . E-mail: james_raleigh@med.unc.edu

    2006-02-01

    Purpose: Pimonidazole HCl is widely used in immunohistochemical analyses of hypoxia in normal and malignant tissues. The present study investigates oral administration as a means of minimizing invasiveness. Methods and Materials: Twelve dogs with confirmed malignancy received 0.5 g/m{sup 2} of pimonidazole HCl: 6 by mouth and 6 by i.v. infusion. All dogs received i.v. CCI-103F as a control. Plasma levels of pimonidazole, pimonidazole N-oxide, and CCI-103F were measured. Tumor biopsies were formalin fixed, paraffin embedded, sectioned, immunostained, and analyzed for pimonidazole and CCI-103F binding. pH dependence for pimonidazole and CCI-103F binding was studied in vitro. Results: Pimonidazole and CCI-103F binding in carcinomas and sarcomas was strongly correlated for both oral and i.v. pimonidazole HCl (r {sup 2} = 0.97). On average, the extent of pimonidazole binding exceeded that for CCI-103F by a factor of approximately 1.2, with the factor ranging from 1.0 to 1.65. Binding of both markers was pH dependent, but pimonidazole binding was greater at all values of pH. Conclusions: Oral pimonidazole HCl is effective as a hypoxia marker in spontaneously arising canine tumors. Selective cellular uptake and concomitant higher levels of binding in regions of hypoxia at the high end of pH gradients might account for the greater extent of pimonidazole binding.

  18. Microarray analysis of potential genes in the pathogenesis of recurrent oral ulcer.

    PubMed

    Han, Jingying; He, Zhiwei; Li, Kun; Hou, Lu

    2015-01-01

    Recurrent oral ulcer seriously threatens patients' daily life and health. This study investigated potential genes and pathways that participate in the pathogenesis of recurrent oral ulcer by high throughput bioinformatic analysis. RT-PCR and Western blot were applied to further verify screened interleukins effect. Recurrent oral ulcer related genes were collected from websites and papers, and further found out from Human Genome 280 6.0 microarray data. Each pathway of recurrent oral ulcer related genes were got through chip hybridization. RT-PCR was applied to test four recurrent oral ulcer related genes to verify the microarray data. Data transformation, scatter plot, clustering analysis, and expression pattern analysis were used to analyze recurrent oral ulcer related gene expression changes. Recurrent oral ulcer gene microarray was successfully established. Microarray showed that 551 genes involved in recurrent oral ulcer activity and 196 genes were recurrent oral ulcer related genes. Of them, 76 genes up-regulated, 62 genes down-regulated, and 58 genes up-/down-regulated. Total expression level up-regulated 752 times (60%) and down-regulated 485 times (40%). IL-2 plays an important role in the occurrence, development and recurrence of recurrent oral ulcer on the mRNA and protein levels. Gene microarray can be used to analyze potential genes and pathways in recurrent oral ulcer. IL-2 may be involved in the pathogenesis of recurrent oral ulcer.

  19. Oral Potentially Malignant Disorders: An Overview of More than 20 Entities

    PubMed Central

    Mortazavi, Hamed; Baharvand, Maryam; Mehdipour, Masoumeh

    2014-01-01

    Cancer of the oral cavity accounts for approximately 3% of all malignancies diagnosed annually in 270,000 patients world-wide. Oral cancer is the 12th most common cancer in women and the 6th in men. Many oral squamous cell carcinomas develop from potentially malignant disorders (PMDs). Lack of awareness about the signs and symptoms of oralPMDs in the general population and even healthcare providers is believed to be responsible for the diagnostic delay of these entities. The aim of this article is to update and improve the knowledge of healthcare providers about oral PMDs. PMID:25024833

  20. Friend leukaemia insertion (Fli)-1 is a prediction marker candidate for radiotherapy resistant oral squamous cell carcinoma.

    PubMed

    Shintani, S; Hamakawa, H; Nakashiro, K; Shirota, T; Hatori, M; Tanaka, M; Kuroshita, Y; Kurokawa, Y

    2010-11-01

    Radiotherapy is commonly used to treat oral squamous cell carcinoma (OSCC), but its therapeutic effects are unpredictable. To determine which genes correlate with radiation resistance in oral cancer, the authors evaluated radiation sensitivity using a standard colony formation assay with a gene microarray system for seven OSCC cell lines. They found significant associations between dozens of gene-expression levels and radiation resistance of OSCC cell lines. Following analysis of the different radiosensitive cancer cell lines, the friend leukaemia insertion (Fli)-1 gene was selected as a prediction marker gene for OSCC radiotherapy resistance. Fli-1 expression was associated with radiation resistance in OSCC patients. These data help to predict the effects radiation therapy has on OSCC, in turn contributing to the development of alternative radiation therapies.

  1. Plaque autofluorescence as potential diagnostic targets for oral malodor

    NASA Astrophysics Data System (ADS)

    Lee, Eun-Song; Yim, Hyun-Kyung; Lee, Hyung-Suk; Choi, Jong-Hoon; Kwon, Ho-Keun; Kim, Baek-Il

    2016-08-01

    The aim of this study was to determine whether the degree of tongue and interdental plaque can be used to assess oral malodor by quantifying their fluorescence as detected using quantitative light-induced fluorescence (QLF) technology. Ninety-nine subjects who complained of oral malodor were included. The level of oral malodor was quantified using the organoleptic score (OLS) and the concentration of volatile sulfur compounds (VSCs). The fluorescence properties of tongue and interdental plaque were quantified as scores calculated by multiplying the intensity and area of fluorescence in QLF-digital images, and the combined plaque fluorescence (CPF) score was obtained by summing the scores for the two regions. The associations of the scores with malodor levels and the diagnostic accuracy of the CPF score were analyzed. The two plaque fluorescence scores and their combined score differed significantly with the level of oral malodor (p<0.001). The CPF score was moderately correlated with OLS (r=0.64) and VSC levels (r=0.54), and its area under the receiver operating characteristic curve was 0.77 for identifying subjects with definite oral malodor (OLS≥2). In conclusion, plaque fluorescence from tongue and interdental sites as detected using QLF technology can be used to assess the level of oral malodor.

  2. Acne - a potential skin marker of internal disease.

    PubMed

    Pace, Joseph L

    2015-01-01

    Polycystic ovary syndrome (PCOS) is the most prevalent endocrine disorder in adult women. Hyperandrogenism is the crux of the pathogenesis of both acne and hirsutism, the most frequent clinical presentations of the syndrome. The chronic anovulation that may occur, often but not always associated with enlarged cystic ovaries, has long been recognized as an important feature of PCOS. In recent years major changes have occurred with regard to PCOS: Although management of the common cutaneous manifestations, mainly acne, hirsutism, alopecia, and acanthosis nigricans, remains strictly within the realm of daily dermatologic practice, the pendulum is shifting toward greater awareness of the longer-term systemic implications of PCOS, with emphasis on the unique opportunity and privileged position of the dermatologist to diagnose this potentially serious problem at an early stage, when effective long-term treatment can be instituted. Patients need to be advised that PCOS cannot be cured but can be controlled. Management should involve a multidisciplinary team with emphasis on lifestyle change, insulin sensitizing agents, androgen blockers, and attention to specific cutaneous manifestations.

  3. IDENTIFYING POTENTIAL MARKERS OF THE SUN'S GIANT CONVECTIVE SCALE

    SciTech Connect

    McIntosh, Scott W.; Wang, Xin; Leamon, Robert J.; Scherrer, Philip H.

    2014-04-01

    Line-of-sight magnetograms from the Helioseismic and Magnetic Imager (HMI) of the Solar Dynamics Observatory (SDO) are analyzed using a diagnostic known as the magnetic range of influence (MRoI). The MRoI is a measure of the length over which a photospheric magnetogram is balanced and so its application gives the user a sense of the connective length scales in the outer solar atmosphere. The MRoI maps and histograms inferred from the SDO/HMI magnetograms primarily exhibit four scales: a scale of a few megameters that can be associated with granulation, a scale of a few tens of megameters that can be associated with super-granulation, a scale of many hundreds to thousands of megameters that can be associated with coronal holes and active regions, and a hitherto unnoticed scale that ranges from 100 to 250 Mm. We infer that this final scale is an imprint of the (rotationally driven) giant convective scale on photospheric magnetism. This scale appears in MRoI maps as well-defined, spatially distributed concentrations that we have dubbed ''g-nodes''. Furthermore, using coronal observations from the Atmospheric Imaging Assembly on SDO, we see that the vicinity of these g-nodes appears to be a preferred location for the formation of extreme-ultraviolet (and likely X-Ray) brightpoints. These observations and straightforward diagnostics offer the potential of a near real-time mapping of the Sun's largest convective scale, a scale that possibly reaches to the very bottom of the convective zone.

  4. Segmental distribution of some common molecular markers for colorectal cancer (CRC): influencing factors and potential implications.

    PubMed

    Papagiorgis, Petros Christakis

    2016-05-01

    Proximal and distal colorectal cancers (CRCs) are regarded as distinct disease entities, evolving through different genetic pathways and showing multiple clinicopathological and molecular differences. Segmental distribution of some common markers (e.g., KRAS, EGFR, Ki-67, Bcl-2, COX-2) is clinically important, potentially affecting their prognostic or predictive value. However, this distribution is influenced by a variety of factors such as the anatomical overlap of tumorigenic molecular events, associations of some markers with other clinicopathological features (stage and/or grade), and wide methodological variability in markers' assessment. All these factors represent principal influences followed by intratumoral heterogeneity and geographic variation in the frequency of detection of particular markers, whereas the role of other potential influences (e.g., pre-adjuvant treatment, interaction between markers) remains rather unclear. Better understanding and elucidation of the various influences may provide a more accurate picture of the segmental distribution of molecular markers in CRC, potentially allowing the application of a novel patient stratification for treatment, based on particular molecular profiles in combination with tumor location.

  5. Potentially malignant disorders of the oral cavity: a clinical study.

    PubMed

    Shukla, Anirudh

    2014-01-01

    Oral cancers in India, unlike in the West are the most common cancers encountered, be it a primary or a tertiary referral practice. This makes the study and management of these cancers an important issue especially for the otolaryngologist. It is well known that the most common variant of oral cancers is the squamous cell carcinoma. Also the etiology is well established; with tobacco use in both smoking and smokeless forms, alcohol, betel nut and recently the Human Papilloma virus infection being implicated. Certain conditions which definitely increase the probability of getting oral cancers are known and this study aims in revisiting these aspects of pre-malignancy. The progression from a pre-cancerous lesion/condition to frank cancer is well established across many studies and many specialties. Also timely recognizing these pre-cancerous conditions and administration of proper treatment will greatly help in reducing the morbidity and mortality from subsequent much advanced and dangerous oral cancer. Keeping these facts in mind this study was planned to study the established pre-cancerous lesions which are known to progress to oral cancers.

  6. Optical imaging for the diagnosis of oral cancer and oral potentially malignant disorders

    NASA Astrophysics Data System (ADS)

    Yoshida, K.

    2016-03-01

    Optical Imaging is being conducted as a therapeutic non-invasive. Many kinds of the light source are selected for this purpose. Recently the oral cancer screening is conducted by using light-induced tissue autofluorescence examination such as several kinds of handheld devices. However, the mechanism of its action is still not clear. Therefore basic experimental research was conducted. One of auto fluorescence Imaging (AFI) device, VELscopeTM and near-infrared (NIR) fluorescence imaging using ICG-labeled antibody as a probe were compared using oral squamous cell carcinoma (OSCC) mouse models. The experiments revealed that intracutaneous tumor was successfully visualized as low density image by VELscopeTM and high density image by NIR image. In addition, VELscopeTM showed higher sensitivity and lower specificity than that of NIR fluorescence imaging and the sensitivity of identification of carcinoma areas with the VELscopeTM was good results. However, further more studies were needed to enhance the screening and diagnostic uses, sensitivity and specificity for detecting malignant lesions and differentiation from premalignant or benign lesions. Therefore, additional studies were conducted using a new developed near infrared (NIR) fluorescence imaging method targeting podoplanine (PDPN) which consists of indocyanine green (ICG)-labeled anti-human podoplanin antibody as a probe and IVIS imaging system or a handy realtime ICG imaging device that is overexpressed in oral malignant neoplasm to improve imaging for detection of early oral malignant neoplasm. Then evaluated for its sensitivity and specificity for detection of oral malignant neoplasm in xenografted mice model and compared with VELscopeTM. The results revealed that ICG fluorescence imaging method and VELscopeTM had the almost the same sensitivity for detection of oral malignant neoplasm. The current topics of optical imaging about oral malignant neoplasm were reviewed.

  7. An investigation of the potential of DIP-STR markers for DNA mixture analyses.

    PubMed

    Cereda, G; Biedermann, A; Hall, D; Taroni, F

    2014-07-01

    The genetic characterization of unbalanced mixed stains remains an important area where improvement is imperative. In fact, using the standard tools of forensic DNA profiling (i.e., STR markers), the profile of the minor contributor in mixed DNA stains cannot be successfully detected if its quantitative share of DNA is less than 10% of the mixed trace. This is due to the fact that the major contributor's profile "masks" that of the minor contributor. Besides known remedies to this problem, such as Y-STR analysis, a new compound genetic marker that consists of a Deletion/Insertion Polymorphism (DIP) linked to a Short Tandem Repeat (STR) polymorphism, has recently been developed and proposed. These novel markers are called DIP-STR markers. This paper compares, from a statistical and forensic perspective, the potential usefulness of these novel DIP-STR markers (i) with traditional STR markers in cases of moderately unbalanced mixtures, and (ii) with Y-STR markers in cases of female-male mixtures. This is done through a comparison of the distribution of 100,000 likelihood ratio values obtained using each method on simulated mixtures. This procedure is performed assuming, in turn, the prosecution's and the defence's point of view.

  8. Telomeric repeat-binding factor 2: a marker for survival and anti-EGFR efficacy in oral carcinoma

    PubMed Central

    Raybaud, Hélène; Sudaka, Anne; Chamorey, Emmanuel; Brolih, Sanja; Monteverde, Martino; Merlano, Marco; Nigro, Cristiana Lo; Ambrosetti, Damien; Pagès, Gilles

    2016-01-01

    Oral Squamous Cell Carcinoma (OSCC) is the most common oral cancer worldwide. Treatments including surgery, radio- and chemo-therapies mostly result in debilitating side effects. Thus, a more accurate evaluation of patients at risk of recurrence after radio/chemo treatment is important for preserving their quality of life. We assessed whether the Telomeric Repeat-binding Factor 2 (TERF2) influences tumor aggressiveness and treatment response. TERF2 is over-expressed in many cancers but its correlation to patient outcome remains controversial in OSCC. Our retrospective study on sixty-two patients showed that TERF2 overexpression has a negative impact on survival time. TERF2-dependent survival time was independent of tumor size in a multivariate analysis. In vitro, TERF2 knockdown by RNA interference had no effect on cell proliferation, migration, senescence and apoptosis. Instead, TERF2 knockdown increased the expression of cytokines implicated in inflammation and angiogenesis, except for vascular endothelial growth factor. TERF2 knockdown resulted in a decrease vascularization and growth of xenograft tumors. Finally, response to erlotinib/Tarceva and cetuximab/Erbitux treatment was increased in TRF2 knocked-down cells. Hence, TERF2 may represent an independent marker of survival for OSCC and a predictive marker for cetuximab/Erbitux and erlotinib/Tarceva efficacy. PMID:27329590

  9. Potential applications of oral brush cytology with liquid-based technology: results from a cohort of normal oral mucosa.

    PubMed

    Kujan, Omar; Desai, Mina; Sargent, Alexandra; Bailey, Andrew; Turner, Andrew; Sloan, Philip

    2006-09-01

    Fifty healthy volunteers were studied to assess the potential applications of oral brush sampling using liquid-based cytology. Three specimens from the buccal mucosa and lateral border of tongue were collected from each subject by using cervical brushes and brooms. The brush was immersed in a preservative fluid. The sample in the preservative fluid was processed according to the manufacturer's directions (SurePath, UK). Slides were stained by the Papanicolaou method and assessed for squamous cell adequacy by the same criteria used for cervical cytology screening. Immunocytochemical staining for FHIT (Fragile Histidine Triad) was applied in liquid-based preparations following the streptavidin-biotin-peroxidase method. Human papillomavirus (HPV) detection was performed using the Hybrid Capture 2 assay (Digene) and the PCR-based Roche AMPLICOR HPV Test. LBC preparation slides showed good sample preservation, specimen adequacy and visualization of cell morphology. Interestingly, nine cases showed borderline cytological abnormalities from apparently normal oral mucosa. All cases showed good quality positive FHIT immunoreactivity staining. All studied cases were high-risk HPV negative using HC2 assay method. However, the AMPLICOR Roche Test detected four samples with positive results for high-risk HPVs. Liquid-based cytology has potential as a screening tool for oral cancer and precancer. The method may also have applications for research and practice in the field of oral cancer and precancer. However a special custom-designed oral cytobrush is required.

  10. Immunoexpression of tenascin as a predictor of the malignancy potential of oral leukoplakia associated with a tobacco habit.

    PubMed

    Mane, D R; Bhat, K; Kale, A D; Hallikerimath, S

    2015-01-01

    Oral leukoplakia is a morphological alteration of tissue that is an early indicator for malignancy. Tenascin (TN) is a large hexameric extracellular matrix (ECM) protein with anti-adhesive properties that fosters cell migration during development, wound healing and tissue remodeling; it is present in small amounts in adult tissues. Overexpression of TN in a pathological condition may be either a cause or a consequence of the disease. We evaluated the efficacy of TN for early prediction of tobacco-associated oral cancers. We studied retrospectively 95 cases of oral leukoplakia, including mild, moderate and severe cases, using immunohistochemistry for TN. We evaluated the intensity, area and pattern of TN expression. Greater intensity and area of TN expression was observed in mild and severe dysplasia than in moderate dysplasia. Most cases showed a reticular pattern of expression, especially in mild and moderate dysplasia; a fibrillar pattern was more evident in severe dysplasia. We also observed homogeneous expression pattern in some cases. TN is a marker for dysplastic changes in epithelium and its expression may be helpful for predicting the malignancy potential of tobacco-associated oral leukoplakia.

  11. Magnetic marker monitoring: high resolution real-time tracking of oral solid dosage forms in the gastrointestinal tract.

    PubMed

    Weitschies, Werner; Blume, Henning; Mönnikes, Hubert

    2010-01-01

    Knowledge about the performance of dosage forms in the gastrointestinal tract is essential for the development of new oral delivery systems, as well as for the choice of the optimal formulation technology. Magnetic Marker Monitoring (MMM) is an imaging technology for the investigation of the behaviour of solid oral dosage forms within the gastrointestinal tract, which is based on the labelling of solid dosage forms as a magnetic dipole and determination of the location, orientation and strength of the dipole after oral administration using measurement equipment and localization methods that are established in biomagnetism. MMM enables the investigation of the performance of solid dosage forms in the gastrointestinal tract with a temporal resolution in the range of a few milliseconds and a spatial resolution in 3D in the range of some millimetres. Thereby, MMM provides real-time tracking of dosage forms in the gastrointestinal tract. MMM is also suitable for the determination of dosage form disintegration and for quantitative measurement of in vivo drug release in case of appropriate extended release dosage forms like hydrogel-forming matrix tablets. The combination of MMM with pharmacokinetic measurements (pharmacomagnetography) enables the determination of in vitro-in vivo correlations (IVIC) and the delineation of absorption sites in the gastrointestinal tract.

  12. Fenofibrate Suppresses Oral Tumorigenesis via Reprogramming Metabolic Processes: Potential Drug Repurposing for Oral Cancer

    PubMed Central

    Jan, Chia-Ing; Tsai, Ming-Hsui; Chiu, Chang-Fang; Huang, Yi-Ping; Liu, Chia Jen; Chang, Nai Wen

    2016-01-01

    One anticancer strategy suggests targeting mitochondrial metabolism to trigger cell death through slowing down energy production from the Warburg effect. Fenofibrate is a clinical lipid-lowering agent and an effective anticancer drug. In the present study, we demonstrate that fenofibrate provided novel mechanisms for delaying oral tumor development via the reprogramming of metabolic processes. Fenofibrate induced cytotoxicity by decreasing oxygen consumption rate (OCR) that was accompanied with increasing extracellular acidification rate (ECAR) and reducing ATP content. Moreover, fenofibrate caused changes in the protein expressions of hexokinase II (HK II), pyruvate kinase, pyruvate dehydrogenase, and voltage-dependent anion channel (VDAC), which are associated with the Warburg effect. In addition, fenofibrate reprogrammed the metabolic pathway by interrupting the binding of HK II to VDAC. In an oral cancer mouse model, fenofibrate exhibited both preventive and therapeutic efficacy on oral tumorigenesis. Fenofibrate administration suppressed the incidence rate of tongue lesions, reduced the tumor sizes, decreased the tumor multiplicity, and decreased the immunoreactivities of VDAC and mTOR. The molecular mechanisms involved in fenofibrate's ability to delay tumor development included the down-regulation of mTOR activity via TSC1/2-dependent signaling through activation of AMPK and inactivation of Akt, or via a TSC1/2-independent pathway through direct suppression of raptor. Our findings provide a molecular rationale whereby fenofibrate exerts anticancer and additional beneficial effects for the treatment of oral cancer patients. PMID:27313493

  13. Efficacy of light based detection systems for early detection of oral cancer and oral potentially malignant disorders: Systematic review

    PubMed Central

    Reddy-Kantharaj, Yashoda-Bhoomi; Rakesh, Nagaraju; Janardhan-Reddy, Sujatha; Sahu, Shashikant

    2016-01-01

    Background Earlier detection of oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMD) is essential for dental professionals to improve patient survival rates. The aim of this systematic review is to to evaluate the effectiveness of devices that utilise the principles of chemiluminescence and tissue autofluorescence as adjuncts in the detection of OSCC and OPMD. Material and Methods The electronic retrieval systems and databases searched for relevant articles were PubMed [MEDLINE] and Science direct. The search was for limited articles published in English or with an English abstract and articles published during the period from January 2005 to April 2014. Clinical trials utilized ViziLite, Microlux TM/DL and Visual Enhanced Light scope (VELscope) for early detection of OPMD and OSCC. Results Twenty primary studies published satisfied our criteria for selection - 10 utilised chemiluminescence and 10 tissue autofluorescence. Senstivity of Vizilite for detecting OSCC nad OPMD ranged from 77.1 % to 100% and specificity was low that ranged from 0% to 27.8%.Most have shown that chemiluminescence increases the brightness and margins of oral mucosal white lesions and thus assist in identification of mucosal lesions not considered under Conventional visual examination. However, it preferentially detects leukoplakia and may fail to spot red patches. Clinical trials demonstrated that sensitivity of VELscope in detecting malignancy and OPMD ranged from 22 % to 100 % and specificity ranged from 16 % to 100%. Most studies concluded that VELscope can help the experienced clinician to find oral precursor malignant lesions. But it couldnot differentiate between dysplasia and benign inflammatory conditions. Conclusions Both devices are simple, non-invasive test of the oral mucosa but are suited for clinicians with sufficient experience and training. More clinical trials in future should be conducted to establish optical imaging as an efficacious adjunct

  14. Potential Benefits of Oral Cryotherapy for Chemotherapy-Induced Mucositis.

    PubMed

    Wodzinski, Amelia

    2016-10-01

    Mucositis is a common side effect of cancer therapies that causes painful, erythematous lesions to develop in the gastrointestinal tract. These lesions can lead to malnutrition, increased risk for serious infection, prolonged hospital stays, and reduced quality of life. Oral cryotherapy, or the use of ice chips to cool the mucous membranes during bolus chemotherapy infusions (e.g., 5-fluorouracil [Adrucil®] and melphalan [Alkeran®]), is the most readily accessible and cost-effective intervention available. Although many factors may contribute to the development of mucositis during cancer treatment, studies have found a reduction in the incidence and the severity of mucositis with the use of oral cryotherapy.


  15. Role of oral exfoliative cytology in predicting premalignant potential of oral submucous fibrosis: A short study.

    PubMed

    Jaitley, Shweta; Agarwal, Pankaj; Upadhyay, Ramballabh

    2015-01-01

    The present study was undertaken with an aim of determining the cytological features observed in mucosal smears of oral submucous fibrosis (OSF) patients and comparing them with that of features of normal mucosal cells. The observed features were than analyzed for their reliability in detecting malignant changes in this premalignant condition. Objective of the study was to conduct an oral exfoliative cytology (OEC) study on 30 clinically diagnosed cases of OSF and 30 cases of clinically normal mucosa with no other systemic disease. We observed that all the smears from clinically normal buccal mucosa showed Class I cytology. The exfoliated cells were of normal size and shape with normal staining intensity and normal nuclear characteristics. All the 30 cases of our study group showed features suggestive of benign atypical cytological changes (Class II cytology). In the present study, despite the small number of cases, cytological features consistently observed in all the cases, were indicative of a premalignant change and emphasized a regular follow-up of patients. Early detection of a premalignant oral lesion promises to improve the survival rate of patients suffering from these conditions.

  16. Characterization of phenotype markers and neuronotoxic potential of polarised primary microglia in vitro

    PubMed Central

    Chhor, Vibol; Le Charpentier, Tifenn; Lebon, Sophie; Oré, Marie-Virgine; Celador, Idoia Lara; Josserand, Julien; Degos, Vincent; Jacotot, Etienne; Hagberg, Henrik; Sävman, Karin; Mallard, Carina; Gressens, Pierre; Fleiss, Bobbi

    2013-01-01

    Microglia mediate multiple facets of neuroinflammation, including cytotoxicity, repair, regeneration, and immunosuppression due to their ability to acquire diverse activation states, or phenotypes. Modulation of microglial phenotype is an appealing neurotherapeutic strategy but a comprehensive study of classical and more novel microglial phenotypic markers in vitro is lacking. The aim of this study was to outline the temporal expression of a battery of phenotype markers from polarised microglia to generate an in vitro tool for screening the immunomodulatory potential of novel compounds. We characterised expression of thirty-one macrophage/microglial phenotype markers in primary microglia over time (4, 12, 36, and 72 h), using RT-qPCR or multiplex protein assay. Firstly, we selected Interleukin-4 (IL-4) and lipopolysaccharide (LPS) as the strongest M1–M2 polarising stimuli, from six stimuli tested. At each time point, markers useful to identify that microglia were M1 included iNOS, Cox-2 and IL-6 and a loss of M2a markers. Markers useful for quantifying M2b-immunomodulatory microglia included, increased IL-1RA and SOCS3 and for M2a-repair and regeneration, included increased arginase-1, and a loss of the M1 and M2b markers were discriminatory. Additional markers were regulated at fewer time points, but are still likely important to monitor when assessing the immunomodulatory potential of novel therapies. Further, to facilitate identification of how novel immunomodulatory treatments alter the functional affects of microglia, we characterised how the soluble products from polarised microglia affected the type and rate of neuronal death; M1/2b induced increasing and M2a-induced decreasing neuronal loss. We also assessed any effects of prior activation state, to provide a way to identify how a novel compound may alter phenotype depending on the stage of injury/insult progression. We identified generally that a prior M1/2b reduced the ability of microglia to switch to

  17. Molecular trophic markers in marine food webs and their potential use for coral ecology.

    PubMed

    Leal, Miguel Costa; Ferrier-Pagès, Christine

    2016-10-01

    Notable advances in ecological genomics have been driven by high-throughput sequencing technology and taxonomically broad sequence repositories that allow us to accurately assess species interactions with great taxonomic resolution. The use of DNA as a marker for ingested food is particularly relevant to address predator-prey interactions and disentangle complex marine food webs. DNA-based methods benefit from reductionist molecular approaches to address ecosystem scale processes, such as community structure and energy flow across trophic levels, among others. Here we review how molecular trophic markers have been used to better understand trophic interactions in the marine environment and their advantages and limitations. We focus on animal groups where research has been focused, such as marine mammals, seabirds, fishes, pelagic invertebrates and benthic invertebrates, and use case studies to illustrate how DNA-based methods unraveled food-web interactions. The potential of molecular trophic markers for disentangling the complex trophic ecology of corals is also discussed.

  18. Metaproteomics of saliva identifies human protein markers specific for individuals with periodontitis and dental caries compared to orally healthy controls

    PubMed Central

    Damgaard, Christian; Jensen, Lars J.; Holmstrup, Palle

    2016-01-01

    Background The composition of the salivary microbiota has been reported to differentiate between patients with periodontitis, dental caries and orally healthy individuals. To identify characteristics of diseased and healthy saliva we thus wanted to compare saliva metaproteomes from patients with periodontitis and dental caries to healthy individuals. Methods Stimulated saliva samples were collected from 10 patients with periodontitis, 10 patients with dental caries and 10 orally healthy individuals. The proteins in the saliva samples were subjected to denaturing buffer and digested enzymatically with LysC and trypsin. The resulting peptide mixtures were cleaned up by solid-phase extraction and separated online with 2 h gradients by nano-scale C18 reversed-phase chromatography connected to a mass spectrometer through an electrospray source. The eluting peptides were analyzed on a tandem mass spectrometer operated in data-dependent acquisition mode. Results We identified a total of 35,664 unique peptides from 4,161 different proteins, of which 1,946 and 2,090 were of bacterial and human origin, respectively. The human protein profiles displayed significant overexpression of the complement system and inflammatory markers in periodontitis and dental caries compared to healthy controls. Bacterial proteome profiles and functional annotation were very similar in health and disease. Conclusions Overexpression of proteins related to the complement system and inflammation seems to correlate with oral disease status. Similar bacterial proteomes in healthy and diseased individuals suggests that the salivary microbiota predominantly thrives in a planktonic state expressing no disease-associated characteristics of metabolic activity. PMID:27672500

  19. Evaluation of an oral health scale of infectious potential using a telematic survey of visual diagnosis

    PubMed Central

    Relvas, Marta; Limeres, Jacobo; Cabral, Cristina; Velazco, Corsina; Diz, Pedro

    2013-01-01

    Objective: To compare the results of a subjective estimation of oral health through review of a set of intraoral photographs with those of an objective oral health scale of infectious potential. Method: The pool of patients was made up of 100 adults. Using an infectious-potential scale based on dental and periodontal variables, we assigned 1 of the 4 grades of the scale (range, 0 to 3; 0 corresponds to an excellent oral health status and 3 to the poorest oral health status) to each subject. A total of 20 representative subjects were selected from the pool of patients, 5 subjects for each one of the grades of the scale, and a standardized photographic record was made. One thousand dentists practicing in Spain were sent the survey by e-mail and 174 completed forms were received. We then calculated the concordance of the oral health status indicated by the respondents after visualising the photographs on comparison with the results of the oral health scale of infectious potential; concordance was termed correct grade allocation (CGA). Results: The majority of respondents (69.1%) achieved a CGA in 8 to 12 cases and none achieved more than 15 CGAs. The poorest CGA rates were found with grades 1 and 2, with a mean of 1.74 ± 1.09 and 1.87 ± 1.18, respectively, out of a maximum of 5. The concordance in terms of CGA was high for grade 0 (70.5%), very low for grade 1 (10.8%), low for grade 2 (37.3%), and moderate for grade 3 (42.6%). Conclusion: In comparison with visual examination of the oral cavity, the use of objective scale that establishes a reliable diagnosis of oral health in terms of infectious potential was found to be advantageous. Key words:Diagnosis, intraoral photographies, oral health scale, objective estimation, visual examination. PMID:23524432

  20. Antidotes for novel oral anticoagulants: current status and future potential.

    PubMed

    Crowther, Mark; Crowther, Mark A

    2015-08-01

    The direct thrombin inhibitor dabigatran and the anti-Xa agents rivaroxaban, edoxaban, and apixaban are a new generation of oral anticoagulants. Their advantage over the vitamin K antagonists is the lack of the need for monitoring and dose adjustment. Their main disadvantage is currently the absence of a specific reversal agent. Dabigatran's, unlike the anti-Xa agents, absorption can be reduced by activated charcoal if administered shortly after ingestion and it can be removed from the blood with hemodialysis. Prothrombin complex concentrate, activated prothrombin complex concentrate, and recombinant factor VIIa all show some activity in reversing the anticoagulant effect of these drugs but this is based on ex vivo, animal, and volunteer studies. It is unclear, which, if any, of these drugs is the most suitable for emergency reversal. Three novel molecules (idarucizumab, andexanet, and PER977) may provide the most effective and safest way of reversal. These agents are currently in premarketing studies.

  1. Oral health technicians in Brazilian primary health care: potentials and constraints.

    PubMed

    Aguiar, Dulce Maria Lucena de; Tomita, Nilce Emy; Machado, Maria de Fátima Antero Sousa; Martins, Cleide Lavieri; Frazão, Paulo

    2014-07-01

    Different perspectives on the role of mid-level workers in health care might represent a constraint to health policies. This study aimed to investigate how different agents view the participation of oral health technicians in direct activities of oral healthcare with the goal of understanding the related symbolic dispositions. Theoretical assumptions related to inter-professional collaboration and conflicts in the field of healthcare were used for this analysis. A researcher conducted 24 in-depth interviews with general dental practitioners, oral health technicians and local managers. The concepts of Pierre Bourdieu supported the data interpretation. The results indicated inter-professional relations marked by collaboration and conflict that reflect an action space related to different perspectives of primary care delivery. They also unveiled the symbolic devices related to the participation of oral health technicians that represent a constraint to the implementation of oral health policy, thus reducing the potential of primary health care in Brazil.

  2. Cancer stem cell, cytokeratins and epithelial to mesenchymal transition markers expression in oral squamous cell carcinoma derived from ortothopic xenoimplantation of CD44(high) cells.

    PubMed

    de Andrade, Nathália Paiva; Rodrigues, Maria Fernanda Setúbal Destro; Rodini, Camila Oliveira; Nunes, Fabio Daumas

    2017-03-01

    Oral squamous cell carcinoma (OSCC) is the most prevalent neoplasia of oral cavity worldwide and prognosis remains unchanged in decades. Recently, different authors reported that head and neck squamous cell carcinomas have a subpopulation of tumor initiating cells that apparently correspond to cancer stem cells (CSC) and are also responsible for tumor growth and metastasis. The purpose of the present study was to investigate the microscopic and phenotypic characteristics of OSCC tumors induced after orthotopic xenoimplantation of SCC9(WT) cell line and CSC-enriched subpopulation isolated from SCC9 cell line based on high expression of the putative CSC marker CD44. Different numbers of FACS-sorted SCC9 CD44(high) and CD44(low) cells as well as SCC9(WT) (wild type) were transplanted into the tongue of BALB/C nude (NOD/SCID) mice to evaluate their tumorigenic potential. Sixty days post-induction, tumors were morphologically characterized and immunostained for CSC markers (CD44, Nanog and Bmi-1), epithelial-mesenchymal transition (Snail, Slug) and epithelial differentiating cell markers (cytokeratins 4, 13, 15, 17 and 19), as well as E-cadherin and β-catenin. The data presented here shows that SCC9 CD44(high) cells have higher ability to form tumors than SCC9 CD44(low) cells, even when significantly lower numbers of SCC9 CD44(high) cells were transplanted. Immunoassessment of tumors derived from SCC9 CD44(high) cells revealed high expression of cytokeratin CK19, β-catenin, E-cadherin and CD44, and negative or low expression of CK17, CK4, CK15, CK13, Nanog, Bmi-1, Snail and Slug. While tumors derived from SCC9(WT) showed high expression of CK17, CK19, CD44, Nanog, Bmi-1, Snail and Slug, and negative or low expression of CK4, CK15, CK13, β-catenin and E-cadherin. Thus, SCC9 CD44(high) cells were highly tumorigenic, capable of originating heterogeneous tumors and these tumors have a immunohistochemical profile different from those formed by the wild type cell line.

  3. Combination therapy of potential gene to enhance oral cancer therapeutic effect

    NASA Astrophysics Data System (ADS)

    Yeh, Chia-Hsien; Hsu, Yih-Chih

    2015-03-01

    The epidermal growth factor receptor (EGFR) over-regulation related to uncontrolled cell division and promotes progression in tumor. Over-expression of human epidermal growth factor receptor (EGFR) has been detected in oral cancer cells. EGFR-targeting agents are potential therapeutic modalities for treating oral cancer based on our in vitro study. Liposome nanotechnology is used to encapsulate siRNA and were modified with target ligand to receptors on the surface of tumor cells. We used EGFR siRNA to treat oral cancer in vitro.

  4. Plasmodium falciparum kelch 13: a potential molecular marker for tackling artemisinin-resistant malaria parasites.

    PubMed

    Mita, Toshihiro; Tachibana, Shin-Ichiro; Hashimoto, Muneaki; Hirai, Makoto

    2016-01-01

    Although artemisinin combination therapies have been deployed as a first-line treatment for uncomplicated malaria in almost all endemic countries, artemisinin-resistant parasites have emerged and have gradually spread across the Greater Mekong subregions. There is growing concern that the resistant parasites may migrate to or emerge indigenously in sub-Saharan Africa, which might provoke a global increase in malaria-associated morbidity and mortality. Therefore, development of molecular markers that enable identification of artemisinin resistance with high sensitivity is urgently required to combat this issue. In 2014, a potential artemisinin-resistance responsible gene, Plasmodium falciparum kelch13, was discovered. Here, we review the genetic features of P. falciparum kelch13 and discuss its related resistant mechanisms and potential as a molecular marker.

  5. MMP13 is potentially a new tumor marker for breast cancer diagnosis.

    PubMed

    Chang, Hui-Jen; Yang, Ming-Je; Yang, Yu-Hsiang; Hou, Ming-Feng; Hsueh, Er-Jung; Lin, Shiu-Ru

    2009-11-01

    Within the past decade, the incidence of breast cancer in Taiwan has been rising year after year. Breast cancer is the first most prevalent cancer and the fourth leading cause of cancer-related deaths among women in Taiwan. The early stage of breast cancer not only have a wider range of therapeutic options, but also obtain a higher success rate of therapy than those with advanced breast cancer. A test for tumor markers is the most convenient method to screen for breast cancer. However, the tumor markers currently available for breast cancer detection include carcinoembryonic antigen (CEA), carbohydrate antigen 15.3 (CA15.3), and carbohydrate antigen 27.29 (CA27.29) exhibited certain limitations. Poor sensitivity and specificity greatly limits the diagnostic accuracy of these markers. This study aims to identify potential tumor markers for breast cancer. At first, we analyzed genes expression in infiltrating lobular carcinoma, metaplastic carcinoma, and infiltrating ductal carcinoma of paired specimens (tumor and normal tissue) from breast cancer patients using microarray technology. We selected 371 overexpressed genes in all of the three cell type. In advanced breast cancer tissue, we detected four genes MMP13, CAMP, COL10A1 and FLJ25416 from 25 overexpressed genes which encoded secretion protein more specifically for breast cancer than other genes. After validation with 15 pairs of breast cancer tissue and paired to normal adjacent tissues by membrane array and quantitative RT-PCR, we found MMP13 was 100% overexpressed and confirmed to be a secreted protein by Western blot analysis of the cell culture medium. The expression level of MMP13 was also measured by immunohistochemical staining. We suggest that MMP13 is a highly overexpressed secretion protein in breast cancer tissue. It has potential to be a new tumor marker for breast cancer diagnosis.

  6. Sperm midpiece apoptotic markers: impact on fertilizing potential in in vitro fertilization and intracytoplasmic sperm injection.

    PubMed

    Talarczyk-Desole, Joanna; Kotwicka, Małgorzata; Jendraszak, Magdalena; Pawelczyk, Leszek; Murawski, Marek; Jędrzejczak, Piotr

    2016-04-01

    The aim of this study was to investigate the relationship between apoptotic markers present in human spermatozoa, namely phosphatidylserine translocation (PST) from the inner to the outer layer of the cytomembrane and the active form of caspase-3 (c3) versus the fertilizing potential of male gametes in conventional in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) models. A total of 116 male patients treated with their partners for infertility underwent basic semen analysis and an assessment of the presence of PST and the active c3 in sperm using flow cytometry. Forty patients underwent IVF, group A, while 76 patients underwent ICSI, group B. The fertilizing potential of the gametes was measured as the percentage of oocytes with pronuclei present after either procedure. PST and active c3 were identified in vital gametes, mainly in the midpiece area. Concentration, motility, morphology, and viability of spermatozoa strongly negatively correlated with both markers. In group A, a negative correlation between both markers and the success rate of conventional IVF was observed (r = -0.4, p = 0.04 for PST; r = -0.4, p = 0.02 for active c3, respectively). In group B, the success rate of ICSI did not correlate with either marker (r = -0.2, p = 0.85 for PST and r = 0.1, p = 0.51 for active c3). The two apoptotic markers localized in the sperm midpiece area may affect their function not only by decreasing basic andrologic parameters but also by reducing the probability of conception. Therefore, analysis of PST and active c3 in the sperm of patients undergoing infertility treatment should be recommended.

  7. Lipid emulsion administered intravenously or orally attenuates triglyceride accumulation and expression of inflammatory markers in the liver of nonobese mice fed parenteral nutrition formula.

    PubMed

    Ito, Kyoko; Hao, Lei; Wray, Amanda E; Ross, A Catharine

    2013-03-01

    The accumulation of hepatic TG and development of hepatic steatosis (HS) is a serious complication of the use of parenteral nutrition (PN) formulas containing a high percentage of dextrose. But whether fat emulsions or other nutrients can ameliorate the induction of HS by high-carbohydrate diets is still uncertain. We hypothesized that administration of a lipid emulsion (LE; Intralipid) and/or the vitamin A metabolite retinal (RAL) will reduce hepatic TG accumulation and attenuate indicators of inflammation. C57BL/6 male mice were fed PN formula as their only source of hydration and nutrition for 4-5 wk. In Expt. 1, mice were fed PN only or PN plus treatment with RAL (1 μg/g orally), LE (200 μL i.v.), or both LE and RAL. In Expt. 2, LE was orally administered at 4 and 13.5% of energy to PN-fed mice. All PN mice developed HS compared with mice fed normal chow (NC) and HS was reduced by LE. The liver TG mass was lower in the PN+LE and PN+RAL+LE groups compared with the PN and PN+RAL groups (P < 0.01) and in the 4% and 13.5% PN+LE groups compared with PN alone. Hepatic total retinol was higher in the RAL-fed mice (P < 0.0001), but RAL did not alter TG mass. mRNA transcripts for fatty acid synthase (Fasn) and sterol regulatory element-binding protein-1c (Srebpf1) were higher in the PN compared with the NC mice, but FAS protein and Srebpf1 mRNA were lower in the PN+LE groups compared with PN alone. The inflammation marker serum amyloid P component was also reduced. In summary, LE given either i.v. or orally may be sufficient to reduce the steatotic potential of orally fed high-dextrose formulas and may suppress the early development of HS during PN therapy.

  8. Standardized pretreatment inflammatory laboratory markers and calculated ratios in patients with oral squamous cell carcinoma.

    PubMed

    Grimm, Martin; Rieth, Johan; Hoefert, Sebastian; Krimmel, Michael; Rieth, Sven; Teriete, Peter; Kluba, Susanne; Biegner, Thorsten; Munz, Adelheid; Reinert, Siegmar

    2016-10-01

    Analyzing the inflammatory microenvironment has become an important issue in the management of oral squamous cell carcinoma (OSCC). Pretreatment C-reactive protein (CRP) levels, leucocytes, monocytes, lymphocytes, neutrophils, basophils, eosinophils, platelets, neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) derived from the peripheral blood were analyzed. Receiver operating characteristic (ROC) curves determined a cut-off value for each parameter in 146 patients with OSCC compared with 93 controls and the results were associated with clinicopathological characteristics. CRP expression of tumors was measured by immunohistochemistry. ROC analysis determined cut-off values for CRP levels, leucocytes, monocytes, lymphocytes, neutrophils, NLR, dNLR, LMR, PLR and showed significant differences between the OSCC and control group. Compared with single laboratory tests calculated ratios were superior in measuring sensitivity and specificity of OSCC disease. NLR was significant directly associated and correlated with PLR. LMR was significant inversely associated and correlated with NLR and PLR. Immunohistochemical analysis did not show CRP expression of OSCCs. This study highlights the first analysis for cut-off values of pretreatment single laboratory tests and calculated ratios, which are strongly needed for a follow-up of cancer patients. Additionally, the calculated baselines can be used as a goal for successful immunotherapies in the future. The links between NLR, LMR, and PLR might be helpful for the clinical course (monitoring) of cancer patients and have been first described for OSCC in this study. Taken together, analyzing these data provides an additional practical guideline of further postoperative OSCC management.

  9. Molecular Markers of Diabetic Retinopathy: Potential Screening Tool of the Future?

    PubMed Central

    Pusparajah, Priyia; Lee, Learn-Han; Abdul Kadir, Khalid

    2016-01-01

    Diabetic retinopathy (DR) is among the leading causes of new onset blindness in adults. Effective treatment may delay the onset and progression of this disease provided it is diagnosed early. At present retinopathy can only be diagnosed via formal examination of the eye by a trained specialist, which limits the population that can be effectively screened. An easily accessible, reliable screening biomarker of diabetic retinopathy would be of tremendous benefit in detecting the population in need of further assessment and treatment. This review highlights specific biomarkers that show promise as screening markers to detect early diabetic retinopathy or even to detect patients at increased risk of DR at the time of diagnosis of diabetes. The pathobiology of DR is complex and multifactorial giving rise to a wide array of potential biomarkers. This review provides an overview of these pathways and looks at older markers such as advanced glycation end products (AGEs), inflammatory markers, vascular endothelial growth factor (VEGF) as well as other newer proteins with a role in the pathogenesis of DR including neuroprotective factors such as brain derived neurotrophic factor (BDNF) and Pigment Epithelium Derived Factor (PEDF); SA100A12, pentraxin 3, brain natriuretic peptide, apelin 3, and chemerin as well as various metabolites such as lipoprotein A, folate, and homocysteine. We also consider the possible role of proteins identified through proteomics work whose levels are altered in the sera of patients with DR as screening markers though their role in pathophysiology remains to be characterized. The role of microRNA as a promising new screening marker is also discussed. PMID:27313539

  10. Molecular Markers of Diabetic Retinopathy: Potential Screening Tool of the Future?

    PubMed

    Pusparajah, Priyia; Lee, Learn-Han; Abdul Kadir, Khalid

    2016-01-01

    Diabetic retinopathy (DR) is among the leading causes of new onset blindness in adults. Effective treatment may delay the onset and progression of this disease provided it is diagnosed early. At present retinopathy can only be diagnosed via formal examination of the eye by a trained specialist, which limits the population that can be effectively screened. An easily accessible, reliable screening biomarker of diabetic retinopathy would be of tremendous benefit in detecting the population in need of further assessment and treatment. This review highlights specific biomarkers that show promise as screening markers to detect early diabetic retinopathy or even to detect patients at increased risk of DR at the time of diagnosis of diabetes. The pathobiology of DR is complex and multifactorial giving rise to a wide array of potential biomarkers. This review provides an overview of these pathways and looks at older markers such as advanced glycation end products (AGEs), inflammatory markers, vascular endothelial growth factor (VEGF) as well as other newer proteins with a role in the pathogenesis of DR including neuroprotective factors such as brain derived neurotrophic factor (BDNF) and Pigment Epithelium Derived Factor (PEDF); SA100A12, pentraxin 3, brain natriuretic peptide, apelin 3, and chemerin as well as various metabolites such as lipoprotein A, folate, and homocysteine. We also consider the possible role of proteins identified through proteomics work whose levels are altered in the sera of patients with DR as screening markers though their role in pathophysiology remains to be characterized. The role of microRNA as a promising new screening marker is also discussed.

  11. Cell-free methylation markers with diagnostic and prognostic potential in hepatocellular carcinoma

    PubMed Central

    Lu, Chang-Yi; Chen, Shih-Ya; Peng, Hui-Ling; Kan, Pu-Yeh; Chang, Wan-Chi; Yen, Chia-Jui

    2017-01-01

    Hepatocellular carcinoma (HCC) is a highly malignant tumor with poor prognosis and high mortality. There is a dearth of effective early diagnostic tools, so liver resection surgery and liver transplantation are the only effective medical treatments. The most commonly used marker for HCC detection is serum alpha fetoprotein (AFP), which has low sensitivity and specificity. Because aberrant DNA methylation of genes and miRNAs occurs early in most cancers, we explored whether circulating methylation markers could be promising clinical tools for HCC diagnosis. Using a whole-genome approach, we identified many hyper-methylated miRNAs in HCC. Furthermore, three abnormally methylated genes and one miRNA were combined to establish a methylation predictive model and tested for its diagnostic and prognostic potential in HCC. Using plasma samples, the predictive model exhibited high sensitivity and specificity (> 80%) for HBV-related HCC. Most importantly, nearly 75% of patients who could not be diagnosed with AFP at 20 ng/mL were detected by this model. Further, the predictive model exhibited an exceedingly high ability to predict 5-year overall survival in HCC patients. These data demonstrate the high diagnostic and prognostic potential of methylation markers in the plasma of HCC patients. PMID:28031532

  12. Chromogranin A – unspecific neuroendocrine marker. Clinical utility and potential diagnostic pitfalls

    PubMed Central

    Czarnywojtek, Agata; Fischbach, Jakub; Bączyk, Maciej; Ziemnicka, Katarzyna; Wrotkowska, Elżbieta; Gryczyńska, Maria; Ruchała, Marek

    2016-01-01

    Chromogranin A, despite a number of limitations, is still the most valuable marker of neuroendocrine tumors (NETs). Granins belong to the family of acidic proteins that constitute a major component of secretory granules of various endocrine and neuroendocrine cells, which are components of both the classical endocrine glands and the diffuse neuroendocrine system. These cells are a potential source of transformation into neuroendocrine tumors. The awareness of potential causes influencing the false results of its concentrations simplifies diagnosis and treatment. One of the disadvantages of this marker is its non-specificity and the existence of a number of pathological processes leading to an increase in its concentration, which often results in confusion and diagnostic difficulties. The molecular structure is characterized by a number of sites susceptible to the proteolytic activity of enzymes, resulting in the formation of a number of biologically active peptides. Presumably they act as precursors of active proteins. Chromogranin expression correlates with the amount of secretory vesicles in neuroendocrine cells. The peptide chain during biochemical changes becomes a precursor of biologically active proteins with a wide range of activities. There are a number of commercially available kits for the determination of chromogranin A, which differ in methodology. We present the evaluation of chromogranin A as a marker of neuroendocrine tumors in clinical practice and the possible factors that may affect the outcome of its concentration. PMID:26925113

  13. Ability of Dental Students in Spain to Identify Potentially Malignant Disorders and Oral Cancer.

    PubMed

    Cerero-Lapiedra, Rocío; Esparza-Gómez, Germán C; Casado-de la Cruz, Laura; Domínguez-Gordillo, Adelaida A; Corral-Linaza, César; Seoane-Romero, Juan M

    2015-08-01

    The aim of this study was to assess the ability of students at the School of Dentistry, Complutense University of Madrid, Spain, to diagnose oral cancer and other potentially malignant disorders, as well as to compare their ability at different stages of the learning process and evaluate their knowledge retention. Students were surveyed after they had studied oral medicine and oral pathology at two time points: midway through and near the end of their studies. The survey consisted of questions about 40 photographs of benign oral lesions, malignant oral lesions, and potentially malignant disorders. The response rate for all groups was greater than 70%. The results showed that these students' overall success rate in differentiating benign from malignant lesions averaged 73.9%. When the distinction for potentially malignant disorders was included, their average overall success rate decreased to 42.8% (p<0.001). Furthermore, the students' average success rate was at its lowest at the end of the dental program (p<0.001). Results from this study suggest that, given these students' difficulties in identifying potentially malignant disorders, an increased emphasis on cancer education in the dental curriculum may be needed for future practitioners to master this ability.

  14. Novel 2-Aminobenzamides as Potential Orally Active Antithrombotic Agents

    PubMed Central

    2012-01-01

    In an effort to develop potent antithrombotic agents, a series of novel 2-aminobenzamide derivatives were synthesized and screened for their in vivo antithrombotic activity. Among the 23 compounds tested, compound (8g) showed the most promising antithrombotic activity, which was comparable with clinically used aspirin or warfarin, but at variance with these standard drugs, 8g did not exhibit the increased bleeding time, suggesting its potential as a novel antithrombotic agent. PMID:24900559

  15. Analysis of potential markers for detection of submicroscopic lymph node metastases in breast cancer

    PubMed Central

    Merrie, A E H; Yun, K; Gunn, J; Phillips, L V; McCall, J L

    1999-01-01

    We have developed sensitive assays for cytokeratin (K) 8, 16, 19, stromelysin 3 (ST3), MUC1 and maspin mRNAs using reverse transcription polymerase chain reaction (RT-PCR) and used these to assess lymph node status in patients undergoing surgery for breast cancer. In addition the RT-PCR assays were tested against lymph nodes from non-cancer patients to determine their specificity. Despite high sensitivity RT-PCR assays for K8, K16, K19, ST3 and maspin were not found to be useful as markers of submicroscopic disease as transcripts of these genes were detected in the great majority of control lymph nodes tested. Expression of MUC1 was also not found to be useful as it was both insensitive and non-specific. The importance of assessing potential markers against an adequately sized control population is demonstrated, as failure to do so can lead to erroneous conclusions. © 1999 Cancer Research Campaign PMID:10471055

  16. Potential implications of adjuvant endocrine therapy for the oral health of postmenopausal women with breast cancer

    PubMed Central

    Taichman, L. Susan; Havens, Aaron M.

    2012-01-01

    Current adjuvant treatment modalities for breast cancer that express the estrogen receptor or progesterone receptor include adjuvant anti-estrogen therapies, and tamoxifen and aromatase inhibitors. Bone, including the jaw, is an endocrine-sensitive organ, as are other oral structures. This review examines the potential links between adjuvant anti-estrogen treatments in postmenopausal women with hormone receptor positive breast cancer and oral health. A search of PubMed, EMBASE, CENTRAL, and the Web of Knowledge was conducted using combinations of key terms “breast,” “cancer,” “neoplasm,” “Tamoxifen,” “Aromatase Inhibitor,” “chemotherapy,” “hormone therapy,” “alveolar bone loss,” “postmenopausal bone loss,” “estrogen,” “SERM,” “hormone replacement therapy,” and “quality of life.” We selected articles published in peer-reviewed journals in the English. The authors found no studies reporting on periodontal diseases, alveolar bone loss, oral health, or oral health-related quality of life in association with anti-estrogen breast cancer treatments in postmenopausal women. Periodontal diseases, alveolar bone density, tooth loss, and conditions of the soft tissues of the mouth have all been associated with menopausal status supporting the hypothesis that the soft tissues and bone of the oral cavity could be negatively affected by anti-estrogen therapy. As a conclusion, the impact of adjuvant endocrine breast cancer therapy on the oral health of postmenopausal women is undefined. The structures of the oral cavity are influenced by estrogen; therefore, anti-estrogen therapies may carry the risk of oral toxicities. Oral health care for breast cancer patients is an important but understudied aspect of cancer survivorship. PMID:22986813

  17. Cephalothin is not a reliable surrogate marker for oral cephalosporins in susceptibility testing of Enterobacteriaceae causing urinary tract infection.

    PubMed

    López, Itziar Angulo; Montes, Jorge Calvo; Álvarez, Mar Justel; Mazarrasa, Carlos Fernández; Martínez-Martínez, Luis

    2016-12-01

    Vitek® 2 (bioMérieux) is a widely used commercial antimicrobial susceptibility test (AST) system. AST-N244 card includes cephalothin as first-generation cephalosporin. We compared the cephalothin susceptibility results obtained with Vitek® 2 AST-N244 to those obtained by broth microdilution (BMD) and disk diffusion (DD) for 212 urinary Enterobacteriaceae. We also evaluated the differences between cefazolin and cephalothin susceptibility results. The overall performance of Vitek® 2 for cephalothin testing was 74.5% and 76.4% category agreement compared to BMD and DD, respectively; 84.4% essential agreement; very major errors 15.2% and 11.1% compared to BMD and DD; major errors 0% compared to both methods; and minor errors 22.2% and 21.7% compared to BMD and DD. Regarding correlation between cephalothin and cefazolin, the differences observed were statistically significant (P<0.0001) for the 167 Escherichia coli included (39.5% cephalothin susceptible versus 92.2% cefazolin susceptible by BMD; 41.9% cephalothin susceptible versus 93.4% cefazolin susceptible by DD). Vitek® 2 should provide cefazolin instead of cephalothin as a surrogate marker for oral cephalosporins on the urinary AST-244 cards in order to follow the CLSI (2016) recommendations.

  18. Betel Quid and Oral Potentially Malignant Disorders in a Periurban Township in Myanmar

    PubMed Central

    Zaw, Ko-Ko; Ohnmar, Mya; Hlaing, Moh-Moh; Oo, Yin-Thet-Nu; Win, Swe-Swe; Htike, Maung-Maung-Than; Aye, Phyu-Phyu; Shwe, Sein; Htwe, Moe-Thida; Thein, Zaw-Moe

    2016-01-01

    This study aims to describe betel quid chewing practice and compare oral potentially malignant disorders between chewers and non-chewers of betel quid among residents in Dagon Myothit (East) Township, Myanmar. The study used a cross-sectional design conducted with a representative sample of 542 adults aged 18 years and above in the township. The trained interviewers collected data using a pretested structured questionnaire. On-site oral examination was done for suspected oral lesions. The mean age of the respondents was 45 years and 59% were women. Fifty-two percent of the respondents were currently in the habit of chewing betel quids (72% of men and 39% of women). Among 284 current betel quid chewers, 240 (85%) chewed betel quids together with tobacco. Out of 284 current betel quid chewers, 24 (8.5%) were found to have oral potentially malignant disorders; out of 258 betel quid non-chewers, only 1 (0.4%) was found to have oral potentially malignant disorders. This highlights the growing importance of smokeless tobacco use as public health problem. PMID:27611195

  19. MFAP5 and TNNC1: Potential markers for predicting occult cervical lymphatic metastasis and prognosis in early stage tongue cancer.

    PubMed

    Yang, Xi; Wu, Kailiu; Li, Siyi; Hu, Longwei; Han, Jing; Zhu, Dongwang; Tian, Xuerui; Liu, Wei; Tian, Zhen; Zhong, Laiping; Yan, Ming; Zhang, Chenping; Zhang, Zhiyuan

    2017-01-10

    The purpose of this study is to identify candidate genes that could predict prognosis of early-stage tongue squamous cell carcinoma (TSCC) and its occult cervical lymphatic metastasis by large-scale gene expression profiling. Tumor tissue and matched normal mucosa samples were collected from patients with TSCC and analyzed with Affymetrix HTA2.0 high-density oligonucleotide array. Differentially expressed genes in TSCC with cervical lymph node metastasis (CLNM) were further analyzed with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes for their functions and related pathways. A total of 107 differentially expressed genes (p < 0.05) were identified by microarray in TSCC samples with CLNM (n = 6) compared to those without CLNM (n = 6). Genes involved in the cell-matrix adherens junction and migration function including MFAP5, TNNC1, MGP, FBFBP1 and FBXO32 were selected and validated by RT-PCR in TSCC samples (n = 32). Of the five genes, MFAP5 and TNCC1 expressions were further validated by immohistochemistry (n = 61). The significant positive correlation between MFAP5 and TNNC1 expression (p<0.001) was observed. Notably, over-expression of MFAP5 and TNNC1 were correlated with CLNM, metastasis relapse-free survival and overall survival. Our findings indicated that MFAP5 and TNNC1 may be potential markers for predicting occult cervical lymphatic metastasis and prognosis of oral tongue carcinoma.

  20. Effect of Oral Iron on Markers of Oxidative Stress and Antioxidant Status in Children with Iron Deficiency Anaemia

    PubMed Central

    Adnan, Mohammad; Ahmad, Syed Moiz; Islam, Najmul

    2016-01-01

    Introduction Conflicting reports are available on the relationship of Iron Deficiency Anaemia (IDA) and iron therapy with oxidative stress. Aim To study the levels of markers of oxidative stress and anti-oxidant status in children with IDA and to assess the effect of iron therapy on the same. Materials and Methods This prospective, single centre, hospital based study was a sub-study of a randomized controlled trial conducted in the Department of Paediatrics, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh in collaboration with the Department of Biochemistry (of the same institution) between October 2009 to February 2011. The sub-study was conducted in two parts: in the first part, levels of a biomarker of oxidative stress {Malondialdehyde (MDA)} and anti-oxidant enzymes {Superoxide Dismutase (SOD), Catalase (CAT), Glutathione Peroxidase (GPx)} were assessed and compared between 67 children with IDA and 31 non-anaemic controls; in the second part, the effect of oral iron (6mg/kg/day) for eight weeks on these markers was studied in a subset of 35 children with IDA. The Bivariate correlations procedure was used to compute pair wise associations for a set of variables. T-tests (Independent samples t-test/Paired sample t-test) and Non-parametric tests (Mann–Whitney test/Wilcoxon signed-rank test) were applied as applicable for normally and non-normally distributed data, respectively. Results Levels of anti-oxidant enzymes were significantly lower (p<0.001) in children with IDA as compared to controls, viz., SOD {median, 8.63 (IQR, 8.60-8.66) vs. 9.46 (IQR, 9.14-9.62) units/mg protein}, CAT {median, 8.49 (IQR, 8.46-8.50) vs. 9.10 (IQR, 9.04-9.14) μmol H2O2/min/mg protein} and GPx {median, 49.19 (IQR, 48.99-49.60) vs. 56.94(IQR, 56.80-57.14) mol NADPH oxidized /min/ mg protein}. Whereas, levels of MDA were significantly higher (p<0.001) in IDA group {median, 1.50 (IQR, 1.48-1.52) vs. 1.24 (IQR, 1.20-1.27) moles/ml of serum}. Levels

  1. Diagnostic potential in prostate cancer of a panel of urinary molecular tumor markers.

    PubMed

    Talesa, Vincenzo N; Antognelli, Cinzia; Del Buono, Chiara; Stracci, Fabrizio; Serva, Maria R; Cottini, Emanuele; Mearini, Ettore

    2009-01-01

    Prostate cancer (PCa) is a heterogeneous, multifactorial and multifocal disease. Therefore, the search for a combination of assays using a panel of tumor markers is fundamental for a more precise and reliable diagnosis. In the present study we investigated the diagnostic value of five different genes, associated with PCa carcinogenesis, encoding for prostate-specific membrane antigen (PSMA), serine protease Hepsin, PCa antigen 3 (PCA3), UDP-N-acetyl-alpha-D-galatosamine transferase (GalNAC-T3) and prostate-specific antigen (PSA). Forty-four patients, with previously untreated, histologically verified PCa and forty-six patients with benign prostatic hyperplasia (BPH) were enrolled in this study. Absolute concentration of the transcript levels of each gene was calculated by quantitative Real-Time PCR analysis in urine sediments of men suffering from PCa or BPH after prostatic massage. The diagnostic value of a concomitant examination of these markers was evaluated by logistic regression analysis. We demonstrated that the diagnostic potential of the combined urinary PSA and PSMA level was significantly better than that of each singularly considered marker, including total serum PSA, the present gold standard test for PCa diagnosis.

  2. Effect of orally administered L. fermentum NCIMB 5221 on markers of metabolic syndrome: an in vivo analysis using ZDF rats.

    PubMed

    Tomaro-Duchesneau, Catherine; Saha, Shyamali; Malhotra, Meenakshi; Jones, Mitchell L; Labbé, Alain; Rodes, Laetitia; Kahouli, Imen; Prakash, Satya

    2014-01-01

    Metabolic syndrome, encompassing type 2 diabetes mellitus and cardiovascular disease, is a growing health concern of industrialized countries. Ferulic acid (FA) is a phenolic acid found in foods normally consumed by humans that has demonstrated antioxidant activity, cholesterol-lowering capabilities, and anti-tumorigenic properties. Select probiotic bacteria, including Lactobacillus fermentum NCIMB 5221, produce FA due to intrinsic ferulic acid esterase activity. The aim of the present research was to investigate a FA-producing probiotic, L. fermentum NCIMB 5221, as a biotherapeutic for metabolic syndrome. The probiotic formulation was administered daily for 8 weeks to Zucker diabetic fatty (ZDF) rats, a model of hyperlipidemia and hyperglycemia. Results show that the probiotic formulation reduced fasting insulin levels and insulin resistance, significantly reduced serum triglycerides (p = 0.016), lowered serum low-density lipoprotein cholesterol levels (p = 0.008), and significantly reduced the atherogenic (p = 0.016) and atherosclerosis (p = 0.012) index as compared to the control animals. In addition, the probiotic formulation significantly increased high-density lipoprotein cholesterol levels (p = 0.041) as compared to the control animals. This research indicates that administration of the FA-producing L. fermentum NCIMB 5221 has the potential to reduce insulin resistance, hyperinsulinemia, hypercholesterolemia, and other markers involved in the pathogenesis of metabolic syndrome. Further studies are required to investigate the human clinical potential of the probiotic formulation in affecting the markers and pathogenesis of metabolic syndrome.

  3. Use of electrical impedance spectroscopy to detect malignant and potentially malignant oral lesions.

    PubMed

    Murdoch, Craig; Brown, Brian H; Hearnden, Vanessa; Speight, Paul M; D'Apice, Katy; Hegarty, Anne M; Tidy, John A; Healey, T Jamie; Highfield, Peter E; Thornhill, Martin H

    2014-01-01

    The electrical properties of tissues depend on their architecture and cellular composition. We have previously shown that changes in electrical impedance can be used to differentiate between different degrees of cervical dysplasia and cancer of the cervix. In this proof-of-concept study, we aimed to determine whether electrical impedance spectroscopy (EIS) could distinguish between normal oral mucosa; benign, potentially malignant lesions (PML); and oral cancer. EIS data were collected from oral cancer (n=10), PML (n=27), and benign (n=10) lesions. EIS from lesions was compared with the EIS reading from the normal mucosa on the contralateral side of the mouth or with reference spectra from mucosal sites of control subjects (n=51). Healthy controls displayed significant differences in the EIS obtained from different oral sites. In addition, there were significant differences in the EIS of cancer and high-risk PML versus low-risk PML and controls. There was no significant difference between benign lesions and normal controls. Study subjects also deemed the EIS procedure considerably less painful and more convenient than the scalpel biopsy procedure. EIS shows promise at distinguishing among malignant, PML, and normal oral mucosa and has the potential to be developed into a clinical diagnostic tool.

  4. Potential use of oral fluid samples for serological diagnosis of African swine fever.

    PubMed

    Mur, Lina; Gallardo, Carmina; Soler, Alejandro; Zimmermman, Jeffrey; Pelayo, Virginia; Nieto, Raquel; Sánchez-Vizcaíno, José Manuel; Arias, Marisa

    2013-07-26

    African swine fever (ASF) is a complex, highly lethal, notifiable disease of swine. ASF is wide-spread in sub-Saharan Africa and East European countries and there is presently a great risk of spread to neighboring countries. Since there is no vaccine for ASF virus (ASFV), control is based on rapid and early detection of the disease via surveillance. This approach requires collecting blood samples from large number of animals. Laborious and expensive of itself, this process also presents an additional risk because ASFV is present at high concentrations in the blood. The objective of this study was to initiate studies into the potential use of oral fluid as an alternative to serum for ASF diagnosis, for latter studying its possible use in surveillance and control programs. To this end, oral fluid samples collected at different times post infection from eight pigs experimentally inoculated with an attenuated ASFV were assayed using modified protocols of the two validated serological techniques, the enzyme-immune-liked assay (ELISA) and immunoperoxidase technique (IPT). Antibodies against ASFV were detected in oral fluid samples of all animals from early post infection through the end of the experiment by ELISA and IPT. These results confirmed the presence of ASFV antibodies in swine oral fluids samples, the possibility of an oral fluid-based approach in ASF diagnosis and, potentially in ASF surveillance.

  5. It's Story Time!: Exploring the Potential of Multimodality in Oral Storytelling to Support Children's Vocabulary Learning

    ERIC Educational Resources Information Center

    Lwin, Soe Marlar

    2016-01-01

    Although many studies have been done on the benefits of parent/teacher-child interactions during shared storybook reading or read'aloud sessions, very few have examined the potential of professional storytellers' oral discourse to support children's vocabulary learning. In those storytelling sessions conducted by professional storytellers, the…

  6. Chondrogenic potential of subpopulations of cells expressing mesenchymal stem cell markers derived from human synovial membranes.

    PubMed

    Arufe, M C; De la Fuente, A; Fuentes, I; de Toro, F J; Blanco, F J

    2010-11-01

    In this study we analyzed the chondrogenic potential of subpopulations of mesenchymal stem cells (MSCs) derived from human synovial membranes enriched for CD73, CD106, and CD271 markers. Subpopulations of human synovial membrane MSCs enriched for CD73, CD106, and CD271 markers were isolated using a cytometry sorter and characterized by flow cytometry for MSC markers. The expression of Sox9, Nanog, and Runx2 genes by these cells was measured by reverse transcriptase-polymerase chain reaction. The chondrogenesis of each subpopulation was assessed by culturing the cells in a defined medium to produce spontaneous spheroid formation and differentiation towards chondrocyte-like cells. The examination of the spheroids by histological and immunohistochemical analyses for collagen type II (COL2), aggrecan, collagen type I (COL1), metalloprotease 13 (MMP13), and collagen type X (COLX) levels were performed to assess their chondrogenesis capacity. The adipogenesis and osteogenesis potential of each subpopulation was determined using commercial media; the resulting cells were stained with oil red O or red alizarin to test the degree of differentiation. The subpopulations had different profiles of cells positive for the MSC markers CD44, CD69, CD73, CD90, and CD105 and showed different expression levels of the genes Sox9, Nanog, and Runx2 involved in chondrogenesis, undifferentiation, and osteoblastogenesis, respectively. Immunohistochemical analysis demonstrated that COL1, COL2, COLX, MMP13, and aggrecan were expressed in the spheroids as soon as 14 days of culture. The CD271(+) subpopulation expressed the highest levels of COL2 staining compared to the other subpopulations. CD105 and Runx2 were shown by immunohistochemistry and genetic analysis to have significantly higher expression CD271(+) subpopulation than the other subpopulations. Spheroids formed from CD271-enriched and CD73-enriched MSCs from normal human synovial membranes mimic the native cartilage extracellular

  7. MALDI imaging reveals NCOA7 as a potential biomarker in oral squamous cell carcinoma arising from oral submucous fibrosis

    PubMed Central

    Wang, Peiqi; Li, Xinyi; Chen, Fangman; Sun, Chongkui; Zhao, Hang; Zeng, Xin; Jiang, Lu; Zhou, Yu; Dan, Hongxia; Feng, Mingye; Liu, Rui; Chen, Qianming

    2016-01-01

    Oral squamous cell carcinoma (OSCC) ranks among the most common cancer worldwide, and is associated with severe morbidity and high mortality. Oral submucous fibrosis (OSF), characterized by fibrosis of the mucosa of the upper digestive tract, is a pre-malignant lesion, but the molecular mechanisms underlying this malignant transformation remains to be elucidated. In this study, matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS)-based proteomic strategy was employed to profile the differentially expressed peptides/proteins between OSCC tissues and the corresponding adjacent non-cancerous OSF tissues. Sixty-five unique peptide peaks and nine proteins were identified with altered expression levels. Of them, expression of NCOA7 was found to be up-regulated in OSCC tissues by immunohistochemistry staining and western blotting, and correlated with a pan of clinicopathologic parameters, including lesion site, tumor differentiation status and lymph node metastasis. Further, we show that overexpression of NCOA7 promotes OSCC cell proliferation in either in vitro or in vivo models. Mechanistic study demonstrates that NCOA7 induces OSCC cell proliferation probably by activating aryl hydrocarbon receptor (AHR). The present study suggests that NCOA7 is a potential biomarker for early diagnosis of OSF malignant transformation, and leads to a better understanding of the molecular mechanisms responsible for OSCC development. PMID:27509054

  8. Analysis of silver binding nucleolar organizer regions in exfoliative cytology smears of potentially malignant and malignant oral lesions.

    PubMed

    Sowmya, G V; Nahar, P; Astekar, M; Agarwal, H; Singh, M P

    2017-01-01

    Nucleolar organizer regions are nucleolar components that contain proteins that are stained selectively by silver methods; they can be identified as black dots throughout the nucleolus and are known as silver binding nucleolar organizer regions (AgNOR). The number of AgNOR is related to the cell cycle and the proliferative activity of the cells. We investigated AgNOR using exfoliative cytology smears of potentially malignant oral lesions. Eighty individuals were divided into four equal groups: healthy controls, oral leukoplakia, oral submucous fibrosis and oral squamous cell carcinoma. The mean number of AgNOR in each study group gradually increased from control to oral leukoplakia to oral submucous fibrosis to oral squamous cell carcinoma. The proliferative index was increased in the oral premalignant and malignant patients compared to normal subjects. The mean AgNOR size gradually increased from control to oral leukoplakia to oral submucous fibrosis to oral squamous cell carcinoma. Spherical shaped AgNOR were most common in controls, whereas large, clustered and kidney shapes were most common in oral squamous cell carcinoma. Multiparameter analysis of AgNOR in oral exfoliative smears is a simple, sensitive and cost-effective method for differentiating premalignant from malignant lesions and can be used in conjunction with routine cytomorphological evaluation.

  9. Carcinogenesis of the Oral Cavity: Environmental Causes and Potential Prevention by Black Raspberry.

    PubMed

    El-Bayoumy, Karam; Chen, Kun-Ming; Zhang, Shang-Min; Sun, Yuan-Wan; Amin, Shantu; Stoner, Gary; Guttenplan, Joseph B

    2017-01-17

    strain, cellular and molecular targets, and relative carcinogenic potency, our animal model may offer a more realistic platform to study oral carcinogenesis. In this perspective, we also discuss our preclinical studies to demonstrate the potential of black raspberry extracts on the prevention of OSCC. Specifically, we were the first to demonstrate that black raspberry inhibited DB[a,l]P-DNA binding and of particular importance its capacity to enhance the repair of DB[a,l]P-induced bulky lesions in DNA. We believe that the information presented in this perspective will stimulate further research on the impact of environmental carcinogens in the development of oral cancer and may lead to novel strategies toward the control and prevention of this disease.

  10. Sequence-related amplified polymorphism (SRAP) markers: A potential resource for studies in plant molecular biology1

    PubMed Central

    Robarts, Daniel W. H.; Wolfe, Andrea D.

    2014-01-01

    In the past few decades, many investigations in the field of plant biology have employed selectively neutral, multilocus, dominant markers such as inter-simple sequence repeat (ISSR), random-amplified polymorphic DNA (RAPD), and amplified fragment length polymorphism (AFLP) to address hypotheses at lower taxonomic levels. More recently, sequence-related amplified polymorphism (SRAP) markers have been developed, which are used to amplify coding regions of DNA with primers targeting open reading frames. These markers have proven to be robust and highly variable, on par with AFLP, and are attained through a significantly less technically demanding process. SRAP markers have been used primarily for agronomic and horticultural purposes, developing quantitative trait loci in advanced hybrids and assessing genetic diversity of large germplasm collections. Here, we suggest that SRAP markers should be employed for research addressing hypotheses in plant systematics, biogeography, conservation, ecology, and beyond. We provide an overview of the SRAP literature to date, review descriptive statistics of SRAP markers in a subset of 171 publications, and present relevant case studies to demonstrate the applicability of SRAP markers to the diverse field of plant biology. Results of these selected works indicate that SRAP markers have the potential to enhance the current suite of molecular tools in a diversity of fields by providing an easy-to-use, highly variable marker with inherent biological significance. PMID:25202637

  11. Oral Cell DNA Adducts as Potential Biomarkers for Lung Cancer Susceptibility in Cigarette Smokers.

    PubMed

    Hecht, Stephen S

    2017-01-17

    This perspective considers the use of oral cell DNA adducts, together with exposure and genetic information, to potentially identify those cigarette smokers at highest risk for lung cancer, so that appropriate preventive measures could be initiated at a relatively young age before too much damage has been done. There are now well established and validated analytical methods for the quantitation of urinary and serum metabolites of tobacco smoke toxicants and carcinogens. These metabolites provide a profile of exposure and in some cases lung cancer risk, but they do not yield information on the critical DNA damage parameter that leads to mutations in cancer growth control genes such as KRAS and TP53. Studies demonstrate a correlation between changes in the oral cavity and lung in cigarette smokers, due to the field effect of tobacco smoke. Oral cell DNA is readily obtained in contrast to DNA samples from the lung. Studies in which oral cell DNA and salivary DNA have been analyzed for specific DNA adducts are reviewed; some of the adducts identified have also been previously reported in lung DNA from smokers. The multiple challenges of developing a panel of oral cell DNA adducts that could be routinely quantified by mass spectrometry are discussed.

  12. Evaluating the potential of cubosomal nanoparticles for oral delivery of amphotericin B in treating fungal infection

    PubMed Central

    Yang, Zhiwen; Chen, Meiwan; Yang, Muhua; Chen, Jian; Fang, Weijun; Xu, Ping

    2014-01-01

    The oral administration of amphotericin B (AmB) has a major drawback of poor bioavailability. The aim of this study was to investigate the potential of glyceryl monoolein (GMO) cubosomes as lipid nanocarriers to improve the oral efficacy of AmB. Antifungal efficacy was determined in vivo in rats after oral administration, to investigate its therapeutic use. The human colon adenocarcinoma cell line (Caco-2) was used in vitro to evaluate transport across a model of the intestinal barrier. In vivo antifungal results showed that AmB, loaded in GMO cubosomes, could significantly enhance oral efficacy, compared against Fungizone®, and that during a 2 day course of dosage 10 mg/kg the drug reached effective therapeutic concentrations in renal tissue for treating fungal infections. In the Caco-2 transport studies, GMO cubosomes resulted in a significantly larger amount of AmB being transported into Caco-2 cells, via both clathrin- and caveolae-mediated endocytosis, but not macropinocytosis. These results suggest that GMO cubosomes, as lipid nanovectors, could facilitate the oral delivery of AmB. PMID:24421641

  13. Programmable Bio-Nano-Chip based Cytologic Testing of Oral Potentially Malignant Disorders in Fanconi Anemia

    PubMed Central

    Floriano, Pierre; Abram, Tim; Taylor, Leander; Le, Cathy; Talavera, Humberto; Nguyen, Michael; Raja, Rameez; Gillenwater, Ann; McDevitt, John; Vigneswaran, Nadarajah

    2015-01-01

    Fanconi anemia (FA) is caused by mutations of DNA repair genes. The risk of oral squamous cell carcinoma (OSCC) among FA patients is 800-folds higher than in the general population. Early detection of OSCC, preferably at it precursor stage is critical in FA patients to improve their survival. In an ongoing clinical trial, we are evaluating the effectiveness of the programmable bio-nano-chip (p-BNC)-based oral cytology test in diagnosing oral potentially malignant disorders (OPMD) in non-FA patients. We used this test to compare the cytomorphometric and molecular biomarkers in OSCC cell lines derived from FA patients and non-FA patients and brush biopsy samples of a FA patient’s OPMD and normal mucosa of healthy volunteers. Our data showed that expression patterns of molecular biomarkers were not notably different between sporadic and FA OSCC cell lines. The p-BNC assay revealed significant differences in cytometric parameters and biomarker MCM2 expression between cytobrush samples of the FA patient and cytobrush samples of normal oral mucosa obtained from healthy volunteers. Microscopic examination of the FA patient’s OPMD confirmed the presence of dysplasia. Our pilot data suggests that p-BNC brush biopsy test recognizes dysplastic oral epithelial cells in a brush biopsy sample of a FA patient. PMID:25662766

  14. Evaluating the potential of cubosomal nanoparticles for oral delivery of amphotericin B in treating fungal infection.

    PubMed

    Yang, Zhiwen; Chen, Meiwan; Yang, Muhua; Chen, Jian; Fang, Weijun; Xu, Ping

    2014-01-01

    The oral administration of amphotericin B (AmB) has a major drawback of poor bioavailability. The aim of this study was to investigate the potential of glyceryl monoolein (GMO) cubosomes as lipid nanocarriers to improve the oral efficacy of AmB. Antifungal efficacy was determined in vivo in rats after oral administration, to investigate its therapeutic use. The human colon adenocarcinoma cell line (Caco-2) was used in vitro to evaluate transport across a model of the intestinal barrier. In vivo antifungal results showed that AmB, loaded in GMO cubosomes, could significantly enhance oral efficacy, compared against Fungizone, and that during a 2 day course of dosage 10 mg/kg the drug reached effective therapeutic concentrations in renal tissue for treating fungal infections. In the Caco-2 transport studies, GMO cubosomes resulted in a significantly larger amount of AmB being transported into Caco-2 cells, via both clathrin- and caveolae-mediated endocytosis, but not macropinocytosis. These results suggest that GMO cubosomes, as lipid nanovectors, could facilitate the oral delivery of AmB.

  15. Oral Cell DNA Adducts as Potential Biomarkers for Lung Cancer Susceptibility in Cigarette Smokers

    PubMed Central

    Hecht, Stephen S.

    2017-01-01

    This perspective considers the use of oral cell DNA adducts, together with exposure and genetic information, to potentially identify those cigarette smokers at highest risk for lung cancer, so that appropriate preventive measures could be initiated at a relatively young age before too much damage has been done. There are now well established and validated analytical methods for the quantitation of urinary and serum metabolites of tobacco smoke toxicants and carcinogens. These metabolites provide a profile of exposure and in some cases lung cancer risk. But they do not yield information on the critical DNA damage parameter that leads to mutations in cancer growth control genes such as KRAS and TP53. Studies demonstrate a correlation between changes in the oral cavity and lung in cigarette smokers, due to the field effect of tobacco smoke. Oral cell DNA is readily obtained in contrast to DNA samples from the lung. Studies in which oral cell DNA and salivary DNA have been analyzed for specific DNA adducts are reviewed; some of the adducts identified have also been previously reported in lung DNA from smokers. The multiple challenges of developing a panel of oral cell DNA adducts that could be routinely quantified by mass spectrometry are discussed. PMID:28092948

  16. Trehalose as an indicator of desiccation stress in Drosophila melanogaster larvae: A potential marker of anhydrobiosis

    SciTech Connect

    Thorat, Leena J.; Gaikwad, Sushama M.; Nath, Bimalendu B.

    2012-03-23

    Highlights: Black-Right-Pointing-Pointer First report confirming anhydrobiosis in Drosophila melanogaster larvae. Black-Right-Pointing-Pointer Trehalose synthesis and accumulation in larvae that hydrolyzed on rehydration. Black-Right-Pointing-Pointer Trehalose synthesis in concert with the enzymes involved in trehalose metabolism. Black-Right-Pointing-Pointer Inhibition of trehalose hydrolysis in presence of a specific trehalase inhibitor. Black-Right-Pointing-Pointer Trehalose proposed as a reliable marker for biomonitoring of climate change studies. -- Abstract: In the current scenario of global climate change, desiccation is considered as one of the major environmental stressors for the biota exposed to altered levels of ambient temperature and humidity. Drosophila melanogaster, a cosmopolitan terrestrial insect has been chosen as a humidity-sensitive bioindicator model for the present study since its habitat undergoes frequent stochastic and/or seasonally aggravated dehydration regimes. We report here for the first time the occurrence of anhydrobiosis in D. melanogaster larvae by subjecting them to desiccation stress under laboratory conditions. Larvae desiccated for ten hours at <5% relative humidity could enter anhydrobiosis and could revive upon rehydration followed by resumption of active metabolism. As revealed by FTIR and HPLC analyzes, our findings strongly indicated the synthesis and accumulation of trehalose in the desiccating larvae. Biochemical measurements pointed out the desiccation-responsive trehalose metabolic pathway that was found to be coordinated in concert with the enzymes trehalose 6-phosphate synthase and trehalase. Further, an inhibitor-based experimental approach using deoxynojirimycin, a specific trehalase inhibitor, demonstrated the pivotal role of trehalose in larval anhydrobiosis of D. melanogaster. We therefore propose trehalose as a potential marker for the assessment of anhydrobiosis in Drosophila. The present findings thus add

  17. Senescence marker protein 30 (SMP30) serves as a potential prognostic indicator in hepatocellular carcinoma

    PubMed Central

    Mo, Zhijing; Zheng, Shunxin; Lv, Zhilue; Zhuang, Yuan; Lan, Xiuwan; Wang, Feng; Lu, Xiaoling; Zhao, Yongxiang; Zhou, Sufang

    2016-01-01

    Senescence marker protein 30 (SMP30) has been identified as a tumor-related molecule of hepatocellular carcinoma (HCC). Its clinical significance and underlying mechanisms in HCC tissues, however, remain largely unexplored. We have demonstrated a preferentially expressed SMP30 in normal liver using a tissue microarray. By employing real-time quantitative PCR, two tissue microarrays and Oncomine database analysis, we have also shown that the SMP30 in HCC tissues has significantly reduced when compared with that in paired adjacent non-tumor tissues (P = 0.0037). The reduced expression of SMP30 is very noticeably related to larger tumor size (P = 0.012), enhanced TNM (P = 0.009) and worse survival (P < 0.0001) in HCC patients. The analyses using Cox regression have indicated that the decreased SMP30 expression is an independent risk to the reduced overall survival rate of HCC patients (P = 0.001), and the down-regulation of SMP30 in HCC might be mediated by DNA methylation. Moreover, genes co-expressed with SMP30 may affect the prognosis through apoptotic process, biological adhesion and blood coagulation by PANTHER analyses. Our studies have indicated that the SMP30 may serve as a candidate of HCC clinical prognostic marker and a potential therapeutic target. PMID:27991558

  18. Quantification of plasma exosome is a potential prognostic marker for esophageal squamous cell carcinoma.

    PubMed

    Matsumoto, Yasunori; Kano, Masayuki; Akutsu, Yasunori; Hanari, Naoyuki; Hoshino, Isamu; Murakami, Kentaro; Usui, Akihiro; Suito, Hiroshi; Takahashi, Masahiko; Otsuka, Ryota; Xin, Hu; Komatsu, Aki; Iida, Keiko; Matsubara, Hisahiro

    2016-11-01

    Exosomes play important roles in cancer progression. Although its contents (e.g., proteins and microRNAs) have been focused on in cancer research, particularly as potential diagnostic markers, the exosome behavior and methods for exosome quantification remain unclear. In the present study, we analyzed the tumor-derived exosome behavior and assessed the quantification of exosomes in patient plasma as a biomarker for esophageal squamous cell carcinoma (ESCC). A CD63-GFP expressing human ESCC cell line (TE2-CD63-GFP) was made by transfection, and mouse subcutaneous tumor models were established. Fluorescence imaging was performed on tumors and plasma exosomes harvested from mice. GFP-positive small vesicles were confirmed in the plasma obtained from TE2-CD63-GFP tumor-bearing mice. Patient plasma was collected in Chiba University Hospital (n=86). Exosomes were extracted from 100 µl of the plasma and quantified by acetylcholinesterase (AChE) activity. The relationship between exosome quantification and the patient clinical characteristics was assessed. The quantification of exosomes isolated from the patient plasma revealed that esophageal cancer patients (n=66) expressed higher exosome levels than non-malignant patients (n=20) (P=0.0002). Although there was no correlation between the tumor progression and the exosome levels, exosome number was the independent prognostic marker and low levels of exosome predicted a poor prognosis (P=0.03). In conclusion, exosome levels may be useful as an independent prognostic factor for ESCC patients.

  19. Marine-continental tephra correlations (Pantelleria, Italy, and Ionian Basin): the potential for Mediterranean marker horizons

    NASA Astrophysics Data System (ADS)

    Jordan, Nina

    2016-04-01

    Palaeo-environmental records from marine and terrestrial archives in the Mediterranean show broad-scale and millennial-scale climatic changes. Synchronising these records requires robust chronological control which may be achieved using isochronous tephra marker horizons. These need to be widespread and sufficiently unique in chemistry to be distinguished from each other. Pantelleria volcano, Italy, satisfies these criteria, with eruptions blanketing the Mediterranean Sea and being distinct from every other volcano in the region. This peralkaline volcano is already well-known for its 46 ka marker horizon (Y-6) but there is potential for extending correlations further back in time. Until recently, correlations were limited by scarce onshore glass data and few sediment cores covering sufficiently long time periods to compare with Pantelleria's >200 ka explosive volcanic history. Building on recent work that has established a detailed onshore stratigraphy, glass data are presented from Pantelleria and site 964 of ODP leg 160 which is situated ~400 km downwind from the volcano. New correlations can be established and previous suggestions are discussed in the light of this new data, representing a significant step forward in confident marine-continental tephra correlations.

  20. Assessment of eccentric exercise-induced oxidative stress using oxidation-reduction potential markers.

    PubMed

    Stagos, Dimitrios; Goutzourelas, Nikolaos; Ntontou, Amalia-Maria; Kafantaris, Ioannis; Deli, Chariklia K; Poulios, Athanasios; Jamurtas, Athanasios Z; Bar-Or, David; Kouretas, Dimitrios

    2015-01-01

    The aim of the present study was to investigate the use of static (sORP) and capacity ORP (cORP) oxidation-reduction potential markers as measured by the RedoxSYS Diagnostic System in plasma, for assessing eccentric exercise-induced oxidative stress. Nineteen volunteers performed eccentric exercise with the knee extensors. Blood was collected before, immediately after exercise, and 24, 48, and 72 h after exercise. Moreover, common redox biomarkers were measured, which were protein carbonyls, thiobarbituric acid-reactive substances, total antioxidant capacity in plasma, and catalase activity and glutathione levels in erythrocytes. When the participants were examined as one group, there were not significant differences in any marker after exercise. However, in 11 participants there was a high increase in cORP after exercise, while in 8 participants there was a high decrease. Thus, the participants were divided in low cORP group exhibiting significant decrease in cORP after exercise and in high cORP group exhibiting significant increase. Moreover, only in the low cORP group there was a significant increase in lipid peroxidation after exercise suggesting induction of oxidative stress. The results suggested that high decreases in cORP values after exercise may indicate induction of oxidative stress by eccentric exercise, while high increases in cORP values after exercise may indicate no existence of oxidative stress.

  1. Identification of Meflin as a Potential Marker for Mesenchymal Stromal Cells

    PubMed Central

    Maeda, Keiko; Enomoto, Atsushi; Hara, Akitoshi; Asai, Naoya; Kobayashi, Takeshi; Horinouchi, Asuka; Maruyama, Shoichi; Ishikawa, Yuichi; Nishiyama, Takahiro; Kiyoi, Hitoshi; Kato, Takuya; Ando, Kenju; Weng, Liang; Mii, Shinji; Asai, Masato; Mizutani, Yasuyuki; Watanabe, Osamu; Hirooka, Yoshiki; Goto, Hidemi; Takahashi, Masahide

    2016-01-01

    Bone marrow-derived mesenchymal stromal cells (BM-MSCs) in culture are derived from BM stromal cells or skeletal stem cells. Whereas MSCs have been exploited in clinical medicine, the identification of MSC-specific markers has been limited. Here, we report that a cell surface and secreted protein, Meflin, is expressed in cultured MSCs, fibroblasts and pericytes, but not other types of cells including epithelial, endothelial and smooth muscle cells. In vivo, Meflin is expressed by immature osteoblasts and chondroblasts. In addition, Meflin is found on stromal cells distributed throughout the BM, and on pericytes and perivascular cells in multiple organs. Meflin maintains the undifferentiated state of cultured MSCs and is downregulated upon their differentiation, consistent with the observation that Meflin-deficient mice exhibit increased number of osteoblasts and accelerated bone development. In the bone and BM, Meflin is more highly expressed in primitive stromal cells that express platelet-derived growth factor receptor α and Sca-1 than the Sca-1-negative adipo-osteogenic progenitors, which create a niche for hematopoiesis. Those results are consistent with a decrease in the number of clonogenic colony-forming unit-fibroblasts within the BM of Meflin-deficient mice. These preliminary data suggest that Meflin is a potential marker for cultured MSCs and their source cells in vivo. PMID:26924503

  2. Evaluation of DNA methylation markers and their potential to predict human aging.

    PubMed

    Soares Bispo Santos Silva, Deborah; Antunes, Joana; Balamurugan, Kuppareddi; Duncan, George; Sampaio Alho, Clarice; McCord, Bruce

    2015-08-01

    We present epigenetic methylation data for two genetic loci, GRIA2, and NPTX2, which were tested for prediction of age from different donors of biofluids. We analyzed 44 saliva samples and 23 blood samples from volunteers with ages ranging from 5 to 72 years. DNA was extracted and bisulfite modified using commercial kits. Specific primers were used for amplification and methylation profiles were determined by pyrosequencing. Methylation data from both markers and their relationship with age were determined using linear regression analysis, which indicates a positive correlation between methylation and age. Older individuals tend to have increased methylation in both markers compared to younger individuals and this trend was more pronounced in the GRIA2 locus when compared to NPTX2. The epigenetic predicted age, calculated using a GRIA2 regression analysis model, was strongly correlated to chronological age (R(2) = 0.801), with an average difference of 6.9 years between estimated and observed ages. When using a NPTX2 regression model, we observed a lower correlation between predicted and chronological age (R(2) = 0.654), with an average difference of 9.2 years. These data indicate these loci can be used as a novel tool for age prediction with potential applications in many areas, including clinical and forensic investigations.

  3. Mucosal-Associated Invariant T Cell Is a Potential Marker to Distinguish Fibromyalgia Syndrome from Arthritis

    PubMed Central

    Konno, Takahiko; Wakao, Rika; Fujita, Hiroko; Fujita, Hiroyoshi

    2015-01-01

    Background Fibromyalgia (FM) is defined as a widely distributed pain. While many rheumatologists and pain physicians have considered it to be a pain disorder, psychiatry, psychology, and general medicine have deemed it to be a syndrome (FMS) or psychosomatic disorder. The lack of concrete structural and/or pathological evidence has made patients suffer prejudice that FMS is a medically unexplained symptom, implying inauthenticity. Furthermore, FMS often exhibits comorbidity with rheumatoid arthritis (RA) or spondyloarthritis (SpA), both of which show similar indications. In this study, disease specific biomarkers were sought in blood samples from patients to facilitate objective diagnoses of FMS, and distinguish it from RA and SpA. Methods Peripheral blood mononuclear cells (PBMCs) from patients and healthy donors (HD) were subjected to multicolor flow cytometric analysis. The percentage of mucosal-associated invariant T (MAIT) cells in PBMCs and the mean fluorescent intensity (MFI) of cell surface antigen expression in MAIT cells were analyzed. Results There was a decrease in the MAIT cell population in FMS, RA, and SpA compared with HD. Among the cell surface antigens in MAIT cells, three chemokine receptors, CCR4, CCR7, and CXCR1, a natural killer (NK) receptor, NKp80, a signaling lymphocyte associated molecule (SLAM) family, CD150, a degrunulation marker, CD107a, and a coreceptor, CD8β emerged as potential biomarkers for FMS to distinguish from HD. Additionally, a memory marker, CD44 and an inflammatory chemokine receptor, CXCR1 appeared possible markers for RA, while a homeostatic chemokine receptor, CXCR4 deserved for SpA to differentiate from FMS. Furthermore, the drug treatment interruption resulted in alternation of the expression of CCR4, CCR5, CXCR4, CD27, CD28, inducible costimulatory molecule (ICOS), CD127 (IL-7 receptor α), CD94, NKp80, an activation marker, CD69, an integrin family member, CD49d, and a dipeptidase, CD26, in FMS. Conclusions

  4. Neck circumference as a potential marker of metabolic syndrome among college students1

    PubMed Central

    Pereira, Dayse Christina Rodrigues; de Araújo, Márcio Flávio Moura; de Freitas, Roberto Wagner Júnior Freire; Teixeira, Carla Regina de Souza; Zanetti, Maria Lúcia; Damasceno, Marta Maria Coelho

    2014-01-01

    OBJECTIVE: to relate neck circumference with metabolic syndrome and its criteria among college students. METHOD: cross-sectional study conducted with 702 college students in Fortaleza, CE, Brazil from September 2010 to June 2011. Socio-demographic data, waist circumference and neck circumference were collected together with blood pressure, fasting blood sugar, triglyceride levels, and HDL-C. RESULTS: 1.7% of the studied sample presented metabolic syndrome. Of these, 58.3% presented altered neck circumference (p<0.006). As neck circumference decreases, pressure levels improve (p<0.001). Additionally, college students with high fasting blood sugar (p=0.003) and high triglyceride levels (p<0.001) presented higher values of neck circumference. CONCLUSION: neck circumference is a potential predictive marker in the detection of metabolic syndrome and its components among college students. PMID:25591092

  5. Adenosine deaminase complexing protein (ADCP): a transformation sensitive protein with potentials of a cancer marker.

    PubMed

    Herbschleb-Voogt, E; Ten Kate, J; Meera Khan, P

    1983-01-01

    Several observations by independent investigators in the past have indicated that adenosine deaminase complexing protein (ADCP), present in considerable quantities in certain human tissues, was absent or decreased in the cancers originated from them. During the present study, electrophoretic analysis of adenosine deaminase (ADA) isozymes and radioimmunoassay for ADCP in the primary fibroblasts and the transformed as well as certain tumor derived cell lines have demonstrated that ADCP present in large quantities in the primary cells was absent or nearly absent in the transformed or tumor-derived cell lines. Though the mechanisms involved are not yet clear, the above observations indicate that ADCP has the potentials of a useful marker in the studies on transformed cells and cancer tissues.

  6. From regenerative dentistry to regenerative medicine: progress, challenges, and potential applications of oral stem cells.

    PubMed

    Xiao, Li; Nasu, Masanori

    2014-01-01

    Adult mesenchymal stem cells (MSCs) and epithelial stem cells play essential roles in tissue repair and self-healing. Oral MSCs and epithelial stem cells can be isolated from adult human oral tissues, for example, teeth, periodontal ligament, and gingiva. Cocultivated adult oral epithelial stem cells and MSCs could represent some developmental events, such as epithelial invagination and tubular structure formation, signifying their potentials for tissue regeneration. Oral epithelial stem cells have been used in regenerative medicine over 1 decade. They are able to form a stratified cell sheet under three-dimensional culture conditions. Both experimental and clinical data indicate that the cell sheets can not only safely and effectively reconstruct the damaged cornea in humans, but also repair esophageal ulcer in animal models. Oral MSCs include dental pulp stem cells (DPSCs), stem cells from exfoliated deciduous teeth (SHED), stem cells from apical papilla (SCAP), periodontal ligament stem cells (PDLSCs), and mesenchymal stem cells from gingiva (GMSCs). They are widely applied in both regenerative dentistry and medicine. DPSCs, SHED, and SCAP are able to form dentin-pulp complex when being transplanted into immunodeficient animals. They have been experimentally used for the regeneration of dental pulp, neuron, bone muscle and blood vessels in animal models and have shown promising results. PDLSCs and GMSCs are demonstrated to be ideal cell sources for repairing the damaged tissues of periodontal, muscle, and tendon. Despite the abovementioned applications of oral stem cells, only a few human clinical trials are now underway to use them for the treatment of certain diseases. Since clinical use is the end goal, their true regenerative power and safety need to be further examined.

  7. Intracellular TCR-signaling pathway: novel markers for lymphoma diagnosis and potential therapeutic targets.

    PubMed

    Agostinelli, Claudio; Rizvi, Hasan; Paterson, Jennifer; Shende, Vishvesh; Akarca, Ayse U; Agostini, Elena; Fuligni, Fabio; Righi, Simona; Spagnolo, Sebastiano; Piccaluga, Pier Paolo; Clark, Edward A; Pileri, Stefano A; Marafioti, Teresa

    2014-10-01

    Despite the immunologic functions of T-cell receptor signaling molecules being extensively investigated, their potential as immunohistochemical markers has been poorly explored. With this background, we evaluated the expression of 5 intracellular proteins-GADS, DOK2, SKAP55, ITK, and PKCα-involved in T-cell receptor signaling in normal and neoplastic hematologic tissue samples, using antibodies raised against fixation-resistant epitopes of the 5 molecules. All 5 antibodies were associated with normal T-cell differentiation. GADS, DOK2, SKAP55, and ITK turned out to be T-cell lineage-specific markers in the setting of lymphoid and myeloid precursor neoplasms but showed differential expression in peripheral T-cell lymphoma (PTCL) subtypes, being detected in PTCL/not otherwise specified (NOS) and angioimmunoblastic T-cell lymphoma but negative in anaplastic large cell lymphoma (ALCL). Peripheral B-cell lymphomas were consistently negative for ITK, with occasional cases showing expression of DOK2 and SKAP55, and a proportion (47%) of hairy cell leukemias were GADS. Notably, PKCα highlighted a defective antigen in both PTCL/NOS (6%) and angioimmunoblastic T-cell lymphoma (10%), mostly negative in ALCL, and was aberrantly expressed in classical Hodgkin lymphoma (65%), Burkitt lymphoma (48%), and plasma cell myeloma (48%). In conclusion, all five molecules evaluated play a role in T-cell differentiation in normal and neoplastic tissues. They can be applied confidently to routine sections contributing primarily to assignment of T-lineage differentiation in the setting of hematopoietic precursor neoplasms (GADS/DOK2/SKAP55/ITK) and for the differential diagnosis between ALCL and PTCL/NOS (GADS/DOK2/SKAP55/ITK) or classical Hodgkin lymphoma (PKCα). Finally, association with specific tumor subtypes may have therapeutic potential.

  8. Therapeutic Potential of Natural Product-Based Oral Nanomedicines for Stroke Prevention.

    PubMed

    Mutoh, Tatsushi; Mutoh, Tomoko; Taki, Yasuyuki; Ishikawa, Tatsuya

    2016-06-01

    Cerebral stroke is the leading cause of death and permanent disability in elderly persons. The impaired glucose and oxygen transport to the brain during ischemia causes bioenergetic failure, leading to oxidative stress, inflammation, blood-brain barrier dysfunction, and eventually cell death. However, the development of effective therapies against stroke has been hampered by insufficient oral absorption of pharmaceuticals and subsequent delivery to the brain. Nanotechnology has emerged as a new method of treating cerebral diseases, with the potential to fundamentally change currently available therapeutic approaches using compounds with low bioavailability. This perspective review provides an overview of the therapeutic potential of oral nanomedicines for stroke, focusing on novel natural product-loaded delivery system with potent antioxidant and anti-inflammatory effects.

  9. Effect of glucose ingestion in plasma markers of inflammation and oxidative stress: analysis of 16 plasma markers from oral glucose tolerance test samples of normal and diabetic patients.

    PubMed

    Choi, Hyung Jin; Jeon, Soon Young; Hong, Won Kyung; Jung, Seung Eun; Kang, Hyun Ju; Kim, Jun-Woo; Jeon, Jae-Pil; Han, Bok-Ghee

    2013-02-01

    Sixteen plasma markers of inflammation and oxidative stress were measured during OGTT in 54 subjects. Leptin, RBP4, CRP, OPN, ANG, MDC, and MCSF concentrations significantly decreased during OGTT (P<0.05). IL6, IL8, and MCP3 concentrations significantly increased during OGTT (P<0.05). These results provide evidence that glucose ingestion affects systemic inflammation and oxidative stress.

  10. Parental potentiation of vocalization as a marker for filial bonds in infant animals.

    PubMed

    Shair, Harry N

    2014-12-01

    Maternal and paternal potentiation of vocalization are two parts of a promising model of early life social bonds that has been and can be a useful tool in research. Most mammalian infants vocalize when isolated. Interactions with adult females just before isolation have been found to increase vocalizations in several species. Interactions with littermates and other social stimuli do not. In guinea pigs and pigs, the response is specific to the dam. In rats and octagon degus, an unrelated adult female from the colony is sufficient. The presence of an intact adult male in the test chamber with dam-reared pups evokes behavioral inhibition, a fear response. Previous exposure to the male in the home cage, biparental rearing, dramatically transforms the response of the pup. The pup treats the adult male as it does its dam, including potentiation of vocalization during a subsequent isolation. This article outlines the methods, advantages, and disadvantages of parental potentiation as a research tool, as well as a brief review of the evidence supporting its use as a marker for filial attachment. Future research directions are outlined.

  11. Realizing the Translational Potential of Telomere Length Variation as a Tissue-Based Prognostic Marker for Prostate Cancer

    DTIC Science & Technology

    2014-10-01

    Telomere Length Variation as a Tissue- Based Prognostic Marker for Prostate Cancer PRINCIPAL INVESTIGATOR: Elizabeth A. Platz CONTRACTING...Translational Potential of Telomere Length Variation as a Tissue- Based Prognostic Marker for Prostate Cancer 5b. GRANT NUMBER W81XWH-12-1-0545 5c...combination of telomere length variability in prostate cancer cells and short telomere length in cancer -associated stromal cells is an independent

  12. Effects of N-acetylcysteine, oral glutathione (GSH) and a novel sublingual form of GSH on oxidative stress markers: A comparative crossover study.

    PubMed

    Schmitt, Bernard; Vicenzi, Morgane; Garrel, Catherine; Denis, Frédéric M

    2015-12-01

    Glutathione (GSH) is critical to fight against oxidative stress. Its very low bioavailability limits the interest of a supplementation. The purpose of this study was to compare the bioavailability, the effect on oxidative stress markers and the safety of a new sublingual form of GSH with two commonly used dietary supplements, N-acetylcysteine (NAC) and oral GSH. The study was a three-week randomized crossover trial. 20 Volunteers with metabolic syndrome were enrolled. GSH levels and several oxidative stress markers were determined at different times during each 21-days period. Compared to oral GSH group, an increase of total and reduced GSH levels in plasma and a higher GSH/GSSG ratio (p=0.003) was observed in sublingual GSH group. After 3 weeks of administration, there was a significant increase of vitamin E level in plasma only in sublingual GSH group (0.83 µmol/g; p=0.04). Our results demonstrate the superiority of a new sublingual form of GSH over the oral GSH form and NAC in terms of GSH supplementation.

  13. Oral andro-related prohormone supplementation: do the potential risks outweigh the benefits?

    PubMed

    Broeder, Craig E

    2003-02-01

    Androstenedione, 4-androstenediol, 5-androstenediol, 19-norandrostenediol and 19-norandrostenedione are commonly referred to as "Andro" prohormones. Over the last few years, supplementation using these prohormones has been aggressively marketed to the general public. Supplement manufacturers often claim that Andro use improves serum testosterone concentrations, increases muscular strength and muscle mass, helps to reduce body fatness, enhances mood, and improves sexual performance. However, to date, most studies contradict these claims. In contrast, several studies using oral Andro related prohormones show that Andro use can abnormally elevate estrogen related hormones as well as alterations in hormonal markers (i.e., abnormal elevations in serum estrogen) thought to increase a person's risk for developing prostate or pancreatic cancers. In addition, most studies also indicate that significant declines in high-density lipoproteins occur leading to an increased cardiovascular disease risk. Thus, to date, the current research base suggests that Andro prohormone use does not support manufacturer claims. But it does suggest there should be strong concerns regarding long-term oral Andro prohormone use, especially regarding its effects on blood lipids and estrogen hormone profiles.

  14. Telangiectases in Scleroderma: A Potential Clinical Marker of Pulmonary Arterial Hypertension

    PubMed Central

    Shah, Ami A.; Wigley, Fredrick M.; Hummers, Laura K.

    2012-01-01

    Objective Clinical markers are needed to identify scleroderma patients at risk for pulmonary arterial hypertension (PAH) since early therapy may improve survival. We investigated whether increased numbers of telangiectases in scleroderma associate with measures of pulmonary vascular disease. Methods One hundred forty-seven consecutive adult patients with scleroderma were enrolled in this cross-sectional study and scored for the presence of matted telangiectases on 11 body areas. Per body area, telangiectases were scored as 0 if none were present, 1 if there were fewer than 10 telangiectases, and 2 if 10 or more telangiectases were counted. Linear regression analysis was performed to assess the association between right ventricular systolic pressure (RVSP) and telangiectasia score, adjusted for age, race, smoking status, scleroderma subtype, disease duration, and autoantibody status. Logistic regression analysis was performed with PAH by right-heart catheterization (RHC) as the dependent variable. Results The mean telangiectasia score was 6.0 (SD 4.5, range 0–20). RVSP and telangiectasia score were positively correlated (r = 0.271, p = 0.001). The mean RVSP increased by 10.9 mm Hg for every 10-point increase in telangiectasia score (95% CI 3.6–18.3 mm Hg, p = 0.004), adjusted for potential confounders. The adjusted relative odds of PAH by RHC were 12.4 for patients with a 10-point increase in telangiectasia score (95% CI 1.78–85.9, p = 0.01). Conclusion Increased numbers of telangiectases strongly associate with the presence of pulmonary vascular disease. Telangiectases may be a clinical marker of more widespread aberrant microvascular disease in scleroderma. PMID:19955048

  15. Molecular markers and imaging tools to identify malignant potential in Barrett's esophagus

    PubMed Central

    Bennett, Michael; Mashimo, Hiroshi

    2014-01-01

    Due to its rapidly rising incidence and high mortality, esophageal adenocarcinoma is a major public health concern, particularly in Western countries. The steps involved in the progression from its predisposing condition, gastroesophageal reflux disease, to its premalignant disorder, Barrett’s esophagus, and to cancer, are incompletely understood. Current screening and surveillance methods are limited by the lack of population-wide utility, incomplete sampling of standard biopsies, and subjectivity of evaluation. Advances in endoscopic ablation have raised the hope of effective therapy for eradication of high-risk Barrett’s lesions, but improvements are needed in determining when to apply this treatment and how to follow patients clinically. Researchers have evaluated numerous potential molecular biomarkers with the goal of detecting dysplasia, with varying degrees of success. The combination of biomarker panels with epidemiologic risk factors to yield clinical risk scoring systems is promising. New approaches to sample tissue may also be combined with these biomarkers for less invasive screening and surveillance. The development of novel endoscopic imaging tools in recent years has the potential to markedly improve detection of small foci of dysplasia in vivo. Current and future efforts will aim to determine the combination of markers and imaging modalities that will most effectively improve the rate of early detection of high-risk lesions in Barrett’s esophagus. PMID:25400987

  16. S100B is a potential disease activity marker in non-segmental vitiligo.

    PubMed

    Speeckaert, Reinhart; Voet, Sofie; Hoste, Esther; van Geel, Nanja

    2017-02-14

    Vitiligo is a chronic skin condition characterized by progressive depigmentation of the skin. S100B is a damage-associated molecular pattern (DAMP) protein expressed in melanocytes, which has been proposed as a marker of melanocyte cytotoxicity. While the use of S100B as a biomarker in melanoma is well established, its association with vitiligo activity has not yet been investigated. Here, we show that S100B serum levels were significantly increased in patients with active non-segmental vitiligo and strongly correlated with the affected body surface area. Prospective follow-up showed a predictive value of serum S100B levels on disease progression. In vitro experiments using repeated freeze-thaw procedures demonstrated an intracellular upregulation of S100B in normal and vitiligo melanocytes prior to an extensive release in the environment. This phenomenon may explain the increased S100B serum values in the active phase of vitiligo. In a monobenzone-induced vitiligo mouse model we could show the potential of S100B inhibition as a therapeutic strategy in vitiligo. In conclusion, this report demonstrates the possible use of S100B as a biomarker for disease activity in vitiligo. Our data suggest that this DAMP protein could play a substantial role in the pathogenesis of vitiligo and may be a potential new target for treatment.

  17. Preparation and investigation of Ulex europaeus agglutinin I-conjugated liposomes as potential oral vaccine carriers.

    PubMed

    Li, KeXin; Chen, DaWei; Zhao, XiuLi; Hu, HaiYang; Yang, ChunRong; Pang, DaHai

    2011-11-01

    We prepared and optimized Ulex europaeus agglutinin I (UEAI)-modified Bovine serum albumin (BSA)-encapsulating liposomes (UEAI-LIP) as oral vaccine carriers and examined the feasibility of inducing systemic and mucosal immune responses by oral administration of UEAILIP. The prepared systems were characterized in vitro for their average size, zeta potential, encapsulation efficiency (EE%) and conjugation efficiency (CE%). In vitro release studies indicated that the presence of UEAI around the optimized liposomes was able to prevent a burst release of loaded BSA and provide sustained release of the encapsulated protein. In vivo immune-stimulating results in KM mice showed that BSA given intramuscularly generated systemic response only but both systemic and mucosal immune responses could be induced simultaneously in the groups in which BSA-loaded liposomes (LIP) and UEAI-LIP were administered intragastrically. Furthermore, the modification of UEAI on the surface of liposomes could further enhance the IgA and IgG levels obviously. In conclusion, this study demonstrated the high potential of lectin-modified liposomes containing the antigen as carriers for oral vaccine.

  18. Complete Genome Sequence of Lactobacillus oris J-1, a Potential Probiotic Isolated from the Human Oral Microbiome

    PubMed Central

    2016-01-01

    Lactobacilli can exert health-promoting effects in the human oral microbiome through many mechanisms, including pathogen inhibition, maintenance of microbial balance, immunomodulation, and enhancement of the epithelial barrier function. Here, we present the complete genome sequence of a potential probiotic, Lactobacillus oris J-1, that was isolated from the oral cavity of a health child. PMID:27634996

  19. First assessment of classical swine fever marker vaccine candidate CP7_E2alf for oral immunization of wild boar under field conditions.

    PubMed

    Feliziani, Francesco; Blome, Sandra; Petrini, Stefano; Giammarioli, Monica; Iscaro, Carmen; Severi, Giulio; Convito, Luca; Pietschmann, Jana; Beer, Martin; De Mia, Gian Mario

    2014-04-11

    Oral vaccination against classical swine fever (CSF) is a potent tool to control disease outbreaks in wild boar. So far, vaccination campaigns have been carried out using live attenuated vaccines that do not allow serological differentiation of infected from vaccinated animals (DIVA). Although this drawback is acceptable for wild boar, the use of marker vaccines would facilitate studies on disease and vaccination dynamics. Recently, the CSF marker vaccine candidate CP7_E2alf was assessed for oral immunization under laboratory conditions. Promising results prompted efforts to study the vaccine candidate under field conditions and in bait formulation. In this context, two oral vaccination campaigns were carried out with CP7_E2alf bait vaccines in two areas called 'faunistic-hunting farms' in the region of Umbria, Italy. One campaign was conducted using single vaccination, the second with the routinely employed double vaccination strategy. Both campaigns were carried out before concerted hunting actions were performed. Bait uptake, vaccine virus detection and antibody responses were assessed along with inspections upon gutting. As a comparator, seven wild boar were hand-fed with baits under laboratory conditions. In the field, bait uptake ranged from 63.7% to 98.7%, whereas antibody prevalence reached only 33.3-35.1%. The marker serology showed a strong influence of sample quality on the test outcome with a total of 85% of samples being classified correctly. Vaccine virus was not detectable. Under hand feeding conditions, six out of seven wild boar took up at least one bait, and five of them showed detectable antibody levels seven weeks after vaccination. These results were supplemented by stability tests. Appropriate stability of vaccine virus was shown both under field and laboratory conditions. In total, most results were in line with our expectations. However, optimization of the DIVA assay has to be attempted in the future.

  20. A Case-Control Study of Oral Epithelial Proliferative Markers among Sudanese Toombak Dippers Using Micronuclei Assay, Argyrophilic Nucleolar Organizer Region, Papanicolaou and Crystal Violet Methods

    PubMed Central

    Anass, M. Abbas; G. Ahmed, Hussain

    2013-01-01

    The use of Toombak has been reported to play a major role in the etiology of oral cancer in Sudan. The cellular proliferative activity on the oral epithelium of 210 Toombak dippers was assessed by applying the micronuclei frequency, mean argyrophilic nucleolar organizer region (AgNOR) counts, Papanicolaou method, and 1% crystal violet stain. Participants were divided into 3 groups: 200 were apparently healthy individuals, 100 were Toombak users (cases), 100 were non-tobacco users (control) and 10 were patients with oral squamous cell carcinomas. Cytological atypia was identified among 4 (4%). Toombak users and was not found among the control group (P<0.04). The micronuclei frequencies were higher in Toombak users (1.026) than in the control group (0.356) (P<0.0001). The mean AgNOR counts in Toombak users (2.423) were higher than control group (1.303) (P<0.0001). Neither Toombak users nor control group showed mitotic figures in 1% crystal violet method. The results of this research showed that Toombak dipping is a high risk factor for increase in the cellular proliferation in the oral mucosa. The cytological proliferative marker methods used are useful for screening Toombak users. PMID:24179643

  1. Circulating Immune Complexes and trace elements (Copper, Iron and Selenium) as markers in oral precancer and cancer : a randomised, controlled clinical trial

    PubMed Central

    Khanna, Sunali S; Karjodkar, Freny R

    2006-01-01

    Aim To evaluate the levels of circulating immune complexes, trace elements (copper, iron and selenium) in serum of patients with oral submucous fibrosis (OSMF), oral leukoplakia (L), and oral squamous cell carcinoma (SCC), analyze the alteration and identify the best predictors amongst these parameters for disease occurrence and progression. Methods Circulating immune complexes (CIC) were estimated using 37.5% Polyethylene Glycol 6000(PEG) serum precipitation. Serum estimation of copper (Cu), Iron (Fe) and selenium (Se) was done using the Oxalyl Dihydrazide method, Colorimetric Dipyridyl method and the Differential Pulse Cathodic Stripping Voltametry respectively. Results The data analysis revealed increased circulating immune complex levels in the precancer and cancer patients. Serum copper levels showed gradual increase from precancer to cancer patients. However, serum iron levels were decreased significantly in the cancer group. Selenium levels showed marked decrease in the cancer group. Among CIC, serum, copper, iron and selenium the best predictors for the occurrence of lesions were age, serum iron, CIC, serum selenium in the decreasing order. Conclusion The present study shows that these immunological and biological markers may be associated with the pathogenesis of oral premalignant and malignant lesions and their progressions. Concerted efforts would, therefore, help in early detection, management, and monitoring the efficacy of treatment. PMID:17040577

  2. Tumor-targeting bacterial therapy: A potential treatment for oral cancer (Review)

    PubMed Central

    LIU, SAI; XU, XIAOPING; ZENG, XIN; LI, LONGJIANG; CHEN, QIANMING; LI, JING

    2014-01-01

    Certain obligate or facultative anaerobic bacteria, which exhibit an inherent ability to colonize solid tumors in vivo, may be used in tumor targeting. As genetically manipulated bacteria may actively and specifically penetrate into the tumor tissue, bacterial therapy is becoming a promising approach in the treatment of tumors. However, to the best of our knowledge, no reports have been published thus far regarding the bacterial treatment of oral cancer, one of the most common types of cancer worldwide. In this review, the progress in the understanding of bacterial strategies used in tumor-targeted therapy is discussed and particular bacterial strains that may have great therapeutic potential in oral squamous cell carcinoma (OSCC) tumor-targeted therapy are predicted as determined by previous studies. PMID:25364397

  3. The Effects of Long-Term Oral Benfotiamine Supplementation on Peripheral Nerve Function and Inflammatory Markers in Patients With Type 1 Diabetes

    PubMed Central

    Fraser, David A.; Diep, Lien M.; Hovden, Inger Anette; Nilsen, Kristian B.; Sveen, Kari Anne; Seljeflot, Ingebjørg; Hanssen, Kristian F.

    2012-01-01

    OBJECTIVE To study the effects of long-term oral benfotiamine supplementation on peripheral nerve function and soluble inflammatory markers in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS The study randomly assigned 67 patients with type 1 diabetes to receive 24-month benfotiamine (300 mg/day) or placebo supplementation. Peripheral nerve function and levels of soluble inflammatory variables were assessed at baseline and at 24 months. RESULTS Fifty-nine patients completed the study. Marked increases in whole-blood concentrations of thiamine and thiamine diphosphate were found in the benfotiamine group (both P < 0.001 vs. placebo). However, no significant differences in changes in peripheral nerve function or soluble inflammatory biomarkers were observed between the groups. CONCLUSIONS Our findings suggest that high-dose benfotiamine (300 mg/day) supplementation over 24 months has no significant effects upon peripheral nerve function or soluble markers of inflammation in patients with type 1 diabetes. PMID:22446172

  4. Prevalence of potentially malignant oral mucosal lesions among tobacco users in Jeddah, Saudi Arabia.

    PubMed

    Al-Attas, Safia Ali; Ibrahim, Suzan Seif; Amer, Hala Abbas; Darwish, Zeinab El-Said; Hassan, Mona Hassan

    2014-01-01

    Smoking is recognized as a health problem worldwide and there is an established tobacco epidemic in Saudi Arabia as in many other countries, with tobacco users at increased risk of developing many diseases. This cross sectional study was conducted to assess the prevalence of oral mucosal, potentially malignant or malignant, lesions associated with tobacco use among a stratified cluster sample of adults in Jeddah, Saudi Arabia. A sample size of 599 was collected and each participant underwent clinical conventional oral examination and filled a questionnaire providing information on demographics, tobacco use and other relevant habits. The most common form of tobacco used was cigarette smoking (65.6 %) followed by Shisha or Moasel (38.1%), while chewing tobacco, betel nuts and gat accounted for 21-2%, 7.7%, and 5% respectively. A high prevalence (88.8%) of soft tissue lesions was found among the tobacco users examined, and a wide range of lesions were detected, about 50% having hairy tongue, 36% smoker's melanosis, 28.9% stomatitis nicotina, 27% frictional keratosis, 26.7% fissured tongue, 26% gingival or periodontal inflammation and finally 20% leukodema. Suspicious potentially malignant lesions affected 10.5% of the subjects, most prevalent being keratosis (6.3%), leukoplakia (2.3%), erythroplakia (0.7%), oral submucous fibrosis (0.5%) and lichenoid lesions (0.4%), these being associated with male gender, lower level of education, presence of diabetes and a chewing tobacco habit. It is concluded that smoking was associated with a wide range of oral mucosal lesions , those suspicious for malignancy being linked with chewable forms, indicating serious effects.

  5. Anabolic potential of bone mineral in human periosteal fibroblasts using steroid markers of healing.

    PubMed

    Suchak, A; Soory, M

    2013-05-01

    A deproteinized natural cancellous bone mineral (B) was studied in a cell culture model for its anabolic potential using two radiolabelled steroid substrates, 14C-testosterone (14C-T) and 14C-4-androstenedione (14C-4-A) independently; in the presence or absence of the anti-androgen finasteride (F) and minocycline (M). Culture medium was assayed for the biologically active metabolite 5 alpha-dihydrotestosterone (DHT) a marker of regenerative potential and wound healing. Confluent monolayer cultures of human periosteal fibroblasts were incubated in Eagle's minimum essential medium with each of the substrates 14C-T and 14C-4-A. Incubations were performed with previously established optimal concentrations of B5 (milligrams/ml), M25 (μg/ml) and F5 (μg/ml) alone and in combination (n=6) for 24h. The eluent was solvent extracted with ethyl acetate (2 ml x 2) and subjected to TLC in a benzene/acetone solvent system (4:1 v/v) for separation of metabolites; they were quantified using a radioisotope scanner. The yield of DHT was increased over controls in response to B and M with both substrates 14C-T and 14C-4-A by 1.7, 1.8-fold and 1.7, 1.6-fold respectively (n=6; p<0.001; one way ANOVA). Combined incubations of B and M resulted in similar yields. F inhibited DHT yields with both radiolabelled substrates by 2-3-fold (n=6; p<0.001) which was overcome by a combined incubation of F+B to values similar to those of controls (p<0.01). Documented pro-anabolic effects of minocycline were applicable as a standard for confirmation of responses to B. Significant increases in yields of DHT in response to B and M with both substrates indicate their anabolic potential in periosteal fibroblasts with implications for wound healing.

  6. Identification and evaluation of potential forensic marker proteins in vaginal fluid by liquid chromatography/mass spectrometry.

    PubMed

    Igoh, Akihisa; Doi, Yusuke; Sakurada, Koichi

    2015-09-01

    Vaginal fluid is one of the most common body fluids found at crime scenes. Discriminating vaginal fluid from other body fluids is important in forensic science; however, few potential protein markers have been reported to date. Proteomic methods for identifying protein markers have gained attention, although few reports have applied this technology to forensic protein markers. Therefore, to identify characteristic vaginal proteins, we examined various body fluids (nasal secretions, saliva, urine, semen, vaginal fluids, and sweat) using liquid chromatography/electrospray ionization time-of-flight mass spectrometry and peptide mass fingerprinting. We identified three components (average molecular mass values 17,237 ± 2, 18,063 ± 2, and 15,075 ± 1) detectable only in vaginal samples: two human small proline-rich protein 3 (SPRR3) isoforms and a human fatty acid-binding protein 5 (FABP5) with an acetylated (+42) N-terminal region lacking the initiator methionine residue (-131). Using ELISA, these yielded markedly high average values in vaginal fluids. The mass spectra of these proteins were not detected in infant saliva but were detected in the vaginal fluid throughout the menstrual cycle. The results of forensic analysis (detection limit, mixed body fluid samples, casework samples, and blind samples) suggest that these proteins are potential forensic markers. In conclusion, high SPRR3 and FABP5 expression levels, which may be used as potential markers for vaginal fluid identification in forensic science, were detected in vaginal fluids from healthy adults.

  7. Fluorescence spectroscopy for the detection of potentially malignant disorders and squamous cell carcinoma of the oral cavity.

    PubMed

    Francisco, Ana Lucia Noronha; Correr, Wagner Rafael; Azevedo, Luciane Hiramatsu; Kern, Vivian Galletta; Pinto, Clóvis Antônio Lopes; Kowalski, Luiz Paulo; Kurachi, Cristina

    2014-06-01

    Oral cancer is a public health problem with relevant incidence in the world population. The affected patient usually presents advanced stage disease and the consequence of this delay is a reduction in survival rates. Given this, it is essential to detect oral cancer at early stages. Fluorescence spectroscopy is a non-invasive diagnostic tool that can improve cancer detection in real time. It is a fast and accurate technique, relatively simple, which evaluates the biochemical composition and structure using the tissue fluorescence spectrum as interrogation data. Several studies have positive data regarding the tools for differentiating between normal mucosa and cancer, but the difference between cancer and potentially malignant disorders is not clear. The aim of this study was to evaluate the efficacy of fluorescence spectroscopy in the discrimination of normal oral mucosa, oral cancer, and potentially malignant disorders. The fluorescence spectroscopy was evaluated in 115 individuals, of whom 55 patients presented oral squamous cell carcinoma, 30 volunteers showing normal oral mucosa, and 30 patients having potentially malignant disorders. The spectra were classified and compared to histopathology to evaluate the efficiency in diagnostic discrimination employing fluorescence. In order to classify the spectra, a decision tree algorithm (C4.5) was applied. Despite of the high variance observed in spectral data, the specificity and sensitivity obtained were 93.8% and 88.5%, respectively at 406 nm excitation. These results point to the potential use of fluorescence spectroscopy as an important tool for oral cancer diagnosis and potentially malignant disorders.

  8. Pairwise diversity and tMRCA as potential markers for HIV infection recency

    PubMed Central

    Moyo, Sikhulile; Wilkinson, Eduan; Vandormael, Alain; Wang, Rui; Weng, Jia; Kotokwe, Kenanao P.; Gaseitsiwe, Simani; Musonda, Rosemary; Makhema, Joseph; Essex, Max; Engelbrecht, Susan; de Oliveira, Tulio; Novitsky, Vladimir

    2017-01-01

    Abstract Intrahost human immunodeficiency virus (HIV)-1 diversity increases linearly over time. We assessed the extent to which mean pairwise distances and the time to the most recent common ancestor (tMRCA) inferred from intrahost HIV-1C env sequences were associated with the estimated time of HIV infection. Data from a primary HIV-1C infection study in Botswana were used for this analysis (N = 42). A total of 2540 HIV-1C env gp120 variable loop region 1 to conserved region 5 (V1C5) of the HIV-1 envelope gp120 viral sequences were generated by single genome amplification and sequencing, with an average of 61 viral sequences per participant and 11 sequences per time point per participant. Raw pairwise distances were calculated for each time point and participant using the ape package in R software. The tMRCA was estimated using phylogenetic inference implemented in Bayesian Evolutionary Analysis by Sampling Trees v1.8.2. Pairwise distances and tMRCA were significantly associated with the estimated time since HIV infection (both P < 0.001). Taking into account multiplicity of HIV infection strengthened these associations. HIV-1C env-based pairwise distances and tMRCA can be used as potential markers for HIV recency. However, the tMRCA estimates demonstrated no advantage over the pairwise distances estimates. PMID:28178146

  9. Assessment of volatile profile as potential marker of chilling injury of basil leaves during postharvest storage.

    PubMed

    Cozzolino, Rosaria; Pace, Bernardo; Cefola, Maria; Martignetti, Antonella; Stocchero, Matteo; Fratianni, Florinda; Nazzaro, Filomena; De Giulio, Beatrice

    2016-12-15

    The volatile profile of three sweet basil cultivars, "Italico a foglia larga", "Cammeo" and "Italiano classico", packaged in air at 4 or 12°C until 9days, was monitored by solid phase microextraction with GC-MS. Chilling injury (CI) score and electrolyte leakage were also assessed. In total, 71 volatile organic compounds (VOCs) were identified in the headspace of basil samples. A preliminary principal component analysis highlighted the dominant effect of the cultivar on VOCs profiles. Data analysis by post-transformation of projection to latent structures regression (ptPLS2) clarified the role played by time and temperature of storage. Temperature influenced the emission of volatiles during storage, with much lower total volatile emissions at 4°C compared to 12°C. Finally, a ptPLS2 regression model performed on VOCs and the two CI parameters allowed selection of 10 metabolites inversely correlated to both CI parameters, which can be considered potential markers of CI in basil leaves.

  10. Oxidized macrophage migration inhibitory factor is a potential new tissue marker and drug target in cancer

    PubMed Central

    Schinagl, Alexander; Thiele, Michael; Douillard, Patrice; Völkel, Dirk; Kenner, Lukas; Kazemi, Zahra; Freissmuth, Michael; Scheiflinger, Friedrich; Kerschbaumer, Randolf J.

    2016-01-01

    Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine, which was shown to be upregulated in cancers and to exhibit tumor promoting properties. Unlike other cytokines, MIF is ubiquitously present in the circulation and tissue of healthy subjects. We recently described a previously unrecognized, disease-related isoform of MIF, designated oxMIF, which is present in the circulation of patients with different inflammatory diseases. In this article, we report that oxMIF is also linked to different solid tumors as it is specifically expressed in tumor tissue from patients with colorectal, pancreatic, ovarian and lung cancer. Furthermore, oxMIF can be specifically targeted by a subset of phage display-derived fully human, monoclonal anti-MIF antibodies (mAbs) that were shown to neutralize pro-tumorigenic activities of MIF in vivo. We further demonstrate that anti-oxMIF mAbs sensitize human cancer cell lines (LNCaP, PC3, A2780 and A2780ADR) to the action of cytotoxic drugs (mitoxantrone, cisplatin and doxorubicin) in vitro and in an A2780 xenograft mouse model of ovarian cancer. We conclude that oxMIF is the disease related isoform of MIF in solid tumors and a potential new diagnostic marker and drug target in cancer. PMID:27636991

  11. Cytoglobin: a potential marker for adipogenic differentiation in preadipocytes in vitro.

    PubMed

    Doğan, Ayşegül; Demirci, Selami; Kıratlı, Binnur; Şahin, Fikrettin

    2017-02-01

    Obesity, mainly characterized by the excess fat storage, is a global health problem resulting in serious morbidity and mortality. Identification of molecular mechanisms in adipogenic differentiation pathway might lead to development of new strategies for diagnosis, prevention and therapy of obesity and associated diseases. Discovery of new genes and proteins in the differentiation pathway could help to understand the key specific regulators of the adipogenesis. Cytoglobin (Cygb), identified as a new globin family member protein, is expressed in various tissues. Although its interaction with oxygen and nitric oxide indicates the potential role in antioxidant pathways, the exact role remains unclear. In the current study, expression level of Cygb was determined in proliferating and differentiating 3T3-F442A cells by gene expression and protein expression analysis. Results revealed that Cygb expression up-regulated in differentiated cells in parallel with adipogenic differentiation markers; PPARγ, CEBPα and FABP4 expressions. Besides, Cygb overexpression in preadipocytes contributed to the adipogenic differentiation as verified by detection of higher lipid droplets and increased PPARγ, CEBPα and FABP4 expressions with respect to control cells. These findings will shed light on the unknown roles of Cygb in adipogenesis and obesity.

  12. Plasma DNA integrity index as a potential molecular diagnostic marker for breast cancer.

    PubMed

    Kamel, Azza M; Teama, Salwa; Fawzy, Amal; El Deftar, Mervat

    2016-06-01

    Plasma DNA integrity index is increased in various malignancies including breast cancer, the most common cancer in women worldwide; early detection is crucial for successful treatment. Current screening methods fail to detect many cases of breast cancer at an early stage. In this study, we evaluated the level of plasma DNA integrity index in 260 females (95 with breast cancer, 95 with benign breast lesions, and 70 healthy controls) to verify its potential value in discriminating malignant from benign breast lesions. The criteria of the American Joint Committee on Cancer were used for staging of breast cancer patients. DNA integrity index was measured by real-time PCR. DNA integrity index was significantly higher in breast cancer than in benign breast patients and healthy subjects (P = <0.001). DNA integrity index is correlated with TNM stage. Given 100 % specificity, the highest sensitivity achieved in detecting cancer group was 85.3 % at 0.55 DNA integrity index cutoff. In conclusion, the plasma DNA integrity index may be a promising molecular diagnostic marker of malignancy in breast lesions.

  13. Calponin-h2: a potential serum marker for the early detection of human breast cancer?

    PubMed

    Debald, Manuel; Jin, Jian-Ping; Linke, Andrea; Walgenbach, Klaus-Jürgen; Rauch, Peter; Zellmer, Angela; Fimmers, Rolf; Kuhn, Walther; Hartmann, Gunther; Walgenbach-Brünagel, Gisela

    2014-11-01

    Early diagnosis is the key for the successful treatment of breast cancer. A serum marker for the early detection of breast cancer could significantly reduce breast cancer morbidity and mortality by bringing the time of diagnosis at an earlier and therefore still curable stage. So far, no biomarker for the early detection is available for the clinical routine. The aim of the present study was to evaluate the use of calponin-h2 as a blood-based biomarker for the early diagnosis of this disease. Using two monoclonal antibodies against calponin-h2, we developed a sandwich ELISA to analyze the serum levels of calponin-h2. In order to evaluate the diagnostic potential of this biomarker, patients with breast cancer (n = 76), benign diseases of the breast (n = 51) and healthy females (n = 24) were analyzed. Serum levels above 10 ng/ml were only observed in patients with breast cancer (n = 8; 10.5%). Further large-scale studies and preanalytic evaluations are necessary to clarify the definite role of calponin-h2 as a biomarker in breast cancer management.

  14. The Impact of AD Drug Treatments on Event-Related Potentials as Markers of Disease Conversion

    PubMed Central

    Chapman, Robert M.; Porsteinsson, Anton P.; Gardner, Margaret N.; Mapstone, Mark; McCrary, John W.; Sandoval, Tiffany C.; Guillily, Maria D.; Reilly, Lindsey A.; DeGrush, Elizabeth

    2013-01-01

    This paper investigates how commonly prescribed pharmacologic treatments for Alzheimer’s disease (AD) affect Event-Related Potential (ERP) biomarkers as tools for predicting AD conversion in individuals with Mild Cognitive Impairment (MCI). We gathered baseline ERP data from two MCI groups (those taking AD medications and those not) and later determined which subjects developed AD (Convert->AD) and which subjects remained cognitively stable (Stable). We utilized a previously developed and validated multivariate system of ERP components to measure medication effects among these four subgroups. Discriminant analysis produced classification scores for each individual as a measure of similarity to each clinical group (Convert->AD, Stable), and we found a large significant main Group effect but no main AD Medications effect and no Group by Medications interaction. This suggested AD medications have negligible influence on this set of ERP components as weighted markers of disease progression. These results provide practical information to those using ERP measures as a biomarker to identify and track AD in individuals in a clinical or research setting. PMID:23905997

  15. Platelet–lymphocyte ratios: a potential marker for pulmonary tuberculosis diagnosis in COPD patients

    PubMed Central

    Chen, Guozhong; Wu, Chunling; Luo, Zhiying; Teng, Yiming; Mao, Suping

    2016-01-01

    Background In recent decades, morbidity and mortality have been found to be significantly increased in patients with chronic obstructive pulmonary disease (COPD) complicated with pulmonary tuberculosis (PTB). Platelet–lymphocyte ratio (PLR) is an indicator for inflammatory diseases. This study aims to investigate whether PLR could act as a potential marker for patients with COPD complicated with PTB. Methods In this retrospective study, laboratory characteristics of 87 COPD patients complicated with PTB (determined by Mycobacterium tuberculosis positive culture from sputum or bronchial lavage fluid) and 83 COPD patients (as the control group, determined by M. tuberculosis culture negativity from sputum or bronchial lavage fluid) were investigated. Data obtained on the day of admission were analyzed. Results PLR >216.82 was identified as the optimal cutoff value for discriminating COPD patients with PTB (sensitivity 92.4%, specificity 84.5%, positive-predictive value 91.6%, negative-predictive value 86.2%, and area under the curve [AUC] was 0.87) from patients with COPD alone. The AUC of PLR was significantly greater than that of neutrophil–lymphocyte count ratio (AUC, 0.74; 95% confidence interval, 0.67–0.81; P<0.01). Conclusion PLR could be developed as a valuable maker for identifying tuberculosis infection in COPD patients. PMID:27843310

  16. FXYD5 is a Marker for Poor Prognosis and a Potential Driver for Metastasis in Ovarian Carcinomas

    PubMed Central

    Raman, Pichai; Purwin, Timothy; Pestell, Richard; Tozeren, Aydin

    2015-01-01

    Ovarian cancer (OC) is a leading cause of cancer mortality, but aside from a few well-studied mutations, very little is known about its underlying causes. As such, we performed survival analysis on ovarian copy number amplifications and gene expression datasets presented by The Cancer Genome Atlas in order to identify potential drivers and markers of aggressive OC. Additionally, two independent datasets from the Gene Expression Omnibus web platform were used to validate the identified markers. Based on our analysis, we identified FXYD5, a glycoprotein known to reduce cell adhesion, as a potential driver of metastasis and a significant predictor of mortality in OC. As a marker of poor outcome, the protein has effective antibodies against it for use in tissue arrays. FXYD5 bridges together a wide variety of cancers, including ovarian, breast cancer stage II, thyroid, colorectal, pancreatic, and head and neck cancers for metastasis studies. PMID:26494976

  17. The anti-tubercular drug delamanid as a potential oral treatment for visceral leishmaniasis

    PubMed Central

    Patterson, Stephen; Wyllie, Susan; Norval, Suzanne; Stojanovski, Laste; Simeons, Frederick RC; Auer, Jennifer L; Osuna-Cabello, Maria; Read, Kevin D; Fairlamb, Alan H

    2016-01-01

    There is an urgent requirement for safe, oral and cost-effective drugs for the treatment of visceral leishmaniasis (VL). We report that delamanid (OPC-67683), an approved drug for multi-drug resistant tuberculosis, is a potent inhibitor of Leishmania donovani both in vitro and in vivo. Twice-daily oral dosing of delamanid at 30 mg kg-1 for 5 days resulted in sterile cures in a mouse model of VL. Treatment with lower doses revealed a U-shaped (hormetic) dose-response curve with greater parasite suppression at 1 mg kg-1 than at 3 mg kg-1 (5 or 10 day dosing). Dosing delamanid for 10 days confirmed the hormetic dose-response and improved the efficacy at all doses investigated. Mechanistic studies reveal that delamanid is rapidly metabolised by parasites via an enzyme, distinct from the nitroreductase that activates fexinidazole. Delamanid has the potential to be repurposed as a much-needed oral therapy for VL. DOI: http://dx.doi.org/10.7554/eLife.09744.001 PMID:27215734

  18. Clinical applications of palifermin: amelioration of oral mucositis and other potential indications

    PubMed Central

    Vadhan-Raj, Saroj; Goldberg, Jenna D; Perales, Miguel-Angel; Berger, Dietmar P; Brink, Marcel RM

    2013-01-01

    Mucositis is one of the most significant toxicities in cancer patients undergoing cytotoxic treatment. It can have a negative impact on both quality of life and health economics. Severe oral mucositis can contribute to hospitalization, need for narcotic analgesics, total parentral nutrition, suboptimal delivery of anti-neoplastic treatment, and morbidity and mortality. Palifermin, a recombinant derivative of human keratinocyte growth factor, is the first active agent approved by the FDA for the prevention of severe oral mucositis in patients undergoing haematopoietic stem cell transplantation (HSCT). Several studies have also shown significant reduction in the incidence, severity and/or duration of oral mucositis in other high-risk settings such as concurrent chemoradiotherapy (CT/RT) for patients with head and neck cancer, and use of mucotoxic chemotherapeutic agents such as doxorubicin in sarcoma and fluorouracil for the treatment of colorectal cancer. The reduction in mucositis has translated into amelioration of symptoms and improvement in daily functioning as measured by patient-reported outcome in multiple studies. The clinical response to palifermin appears to be related in part to epithelial proliferation and mucosal thickening. Palifermin also has other potential clinical applications including the acceleration of immune reconstitution and inhibition of graft-versus-host disease in patients undergoing HSCT, and mitigation of dysphagia in lung cancer patients treated with concurrent CT/RT. Palifermin is generally well tolerated with mild-to-moderate skin and oral adverse events. Future studies may expand the use of palifermin into other areas that would benefit from its cytoprotective and regenerative effects. PMID:24251854

  19. Long-term stability, biocompatibility and oral delivery potential of risperidone-loaded solid lipid nanoparticles.

    PubMed

    Silva, A C; Kumar, A; Wild, W; Ferreira, D; Santos, D; Forbes, B

    2012-10-15

    A solid lipid nanoparticles (SLN) formulation to improve the oral delivery of risperidone (RISP), a poorly water-soluble drug, was designed and tested. Initially, lipid-RISP solubility was screened to select the best lipid for SLN preparation. Compritol(®)-based formulations were chosen and their long-term stability was assessed over two years of storage (at 25 °C and 4 °C) by means of particle size, polydispersity index (PI), zeta potential (ZP) and encapsulation efficiency (EE) measurements. SLN shape was observed by transmission electron microscopy (TEM) at the beginning and end of the study. The oxidative potential (OP) of the SLN was measured and their biocompatibility with Caco-2 cells was evaluated using the (4,5-dimethylthiazol-2-yl)2,5-dyphenyl-tetrazolium bromide (MTT) assay. In vitro drug release and transport studies were performed to predict the in vivo release profile and to evaluate the drug delivery potential of the SLN formulations, respectively. The RISP-loaded SLN systems were stable and had high EE and similar shape to the placebo formulations before and after storage. Classical Fickian diffusion was identified as the release mechanism for RISP from the SLN formulation. Biocompatibility and dose-dependent RISP transport across Caco-2 cells were observed for the prepared SLN formulations. The viability of SLN as formulations for oral delivery of poorly water-soluble drugs such as RISP was illustrated.

  20. Clinical Evaluation of Specific Oral Manifestations in Pediatric Patients with Ascertained versus Potential Coeliac Disease: A Cross-Sectional Study

    PubMed Central

    Matacena, Giada; Costa, Stefano; Magazzù, Giuseppe

    2014-01-01

    Patients involved on coeliac disease (CD) have atypical symptoms and often remain undiagnosed. Specific oral manifestations are effective risk indicators of CD and for this reason an early diagnosis with a consequent better prognosis can be performed by the dentist. There are not researches analysing the frequency of these oral manifestations in potential coeliac patients. The aim of this study is to investigate the oral hard and soft tissue lesions in potential and ascertained coeliac children in comparison with healthy controls. 50 ascertained children, 21 potential coeliac patients, and 54 controls were recruited and the oral examination was performed. The overall oral lesions were more frequently present in CD patients than in controls. The prevalence of oral soft tissue lesions was 62% in ascertained coeliac, 76.2% in potential coeliac patients, and 12.96% in controls (P < 0.05). Clinical dental delayed eruption was observed in 38% of the ascertained coeliac and 42.5% of the potential coeliac versus 11.11% of the controls (P < 0.05). The prevalence of specific enamel defects (SED) was 48% in ascertained coeliac and 19% in potential coeliac versus 0% in controls (P < 0.05; OR = 3.923). The SED seem to be genetically related to the histological damage and villous atrophy. PMID:25197270

  1. Osteogenic Potential of Human Oral-Periosteal Cells (PCs) Isolated From Different Oral Origin: An In Vitro Study.

    PubMed

    Ceccarelli, Gabriele; Graziano, Antonio; Benedetti, Laura; Imbriani, Marcello; Romano, Federica; Ferrarotti, Francesco; Aimetti, Mario; Cusella de Angelis, Gabriella M

    2016-03-01

    The periosteum is a specialized connective tissue containing multipotent stem cells capable of bone formation. In this study, we aimed at demonstrating that human oral periosteal cells derived from three different oral sites (upper vestibule, lower vestibule, and hard palate) represent an innovative cell source for maxillo-facial tissue engineering applications in terms of accessibility and self-commitment towards osteogenic lineage. Periosteal cells (PCs) were isolated from patients with different ages (20-30 yy, 40-50 yy, 50-60 yy); we then analyzed the in vitro proliferation capacity and the bone self-commitment of cell clones culturing them without any osteogenic supplement to support their differentiation. We found that oral PCs, independently of their origin and age of patients, are mesenchymal stem cells with stem cell characteristics (clonogenical and proliferative activity) and that, even in absence of any osteogenic induction, they undertake the osteoblast lineage after 45 days of culture. These results suggest that oral periosteal cells could replace mesenchymal cells from bone marrow in oral tissue-engineering applications.

  2. Metabolomic profiling reveals potential markers and bioprocesses altered in bladder cancer progression.

    PubMed

    Putluri, Nagireddy; Shojaie, Ali; Vasu, Vihas T; Vareed, Shaiju K; Nalluri, Srilatha; Putluri, Vasanta; Thangjam, Gagan Singh; Panzitt, Katrin; Tallman, Christopher T; Butler, Charles; Sana, Theodore R; Fischer, Steven M; Sica, Gabriel; Brat, Daniel J; Shi, Huidong; Palapattu, Ganesh S; Lotan, Yair; Weizer, Alon Z; Terris, Martha K; Shariat, Shahrokh F; Michailidis, George; Sreekumar, Arun

    2011-12-15

    Although alterations in xenobiotic metabolism are considered causal in the development of bladder cancer, the precise mechanisms involved are poorly understood. In this study, we used high-throughput mass spectrometry to measure over 2,000 compounds in 58 clinical specimens, identifying 35 metabolites which exhibited significant changes in bladder cancer. This metabolic signature distinguished both normal and benign bladder from bladder cancer. Exploratory analyses of this metabolomic signature in urine showed promise in distinguishing bladder cancer from controls and also nonmuscle from muscle-invasive bladder cancer. Subsequent enrichment-based bioprocess mapping revealed alterations in phase I/II metabolism and suggested a possible role for DNA methylation in perturbing xenobiotic metabolism in bladder cancer. In particular, we validated tumor-associated hypermethylation in the cytochrome P450 1A1 (CYP1A1) and cytochrome P450 1B1 (CYP1B1) promoters of bladder cancer tissues by bisulfite sequence analysis and methylation-specific PCR and also by in vitro treatment of T-24 bladder cancer cell line with the DNA demethylating agent 5-aza-2'-deoxycytidine. Furthermore, we showed that expression of CYP1A1 and CYP1B1 was reduced significantly in an independent cohort of bladder cancer specimens compared with matched benign adjacent tissues. In summary, our findings identified candidate diagnostic and prognostic markers and highlighted mechanisms associated with the silencing of xenobiotic metabolism. The metabolomic signature we describe offers potential as a urinary biomarker for early detection and staging of bladder cancer, highlighting the utility of evaluating metabolomic profiles of cancer to gain insights into bioprocesses perturbed during tumor development and progression.

  3. Saliva proteome profiling reveals potential salivary biomarkers for detection of oral cavity squamous cell carcinoma.

    PubMed

    Wu, Chih-Ching; Chu, Hao-Wei; Hsu, Chia-Wei; Chang, Kai-Ping; Liu, Hao-Ping

    2015-10-01

    Oral cavity squamous cell carcinoma (OSCC), which is frequently associated with poor prognosis and mortality, is a leading cause of cancer-related death worldwide. Discovery of body fluid accessible biomarkers is needed to improve OSCC screening. To this end, we profiled proteomes of saliva from the healthy volunteers, the individuals with oral potentially malignant disorders (OPMD), and the OSCC patients by means of SDS-PAGE coupled with LC-MS/MS. In the control, the OPMD, and the OSCC groups, 958, 845, and 1030 salivary proteins were detected, respectively. With spectral counting-based label-free quantification, 22 overexpressed salivary proteins were identified in the OSCC group compared with the healthy controls and the OPMD individuals. Among them, resistin (RETN) was subjected to further validation with an independent cohort using ELISA. The data confirmed that the salivary RETN levels in the OSCC patients were significantly higher than that in the healthy or in the OPMD group. Moreover, the elevated levels of salivary RETN were highly correlated with late-stage primary tumors, advanced overall stage, and lymph-node metastasis. Our results not only reveal that profiling of saliva proteome is feasible for discovery of OSCC biomarkers, but also identify RETN as a potential salivary biomarker for OSCC detection.

  4. Evaluation of oral bioavailability and anticancer potential of raloxifene solid lipid nanoparticles.

    PubMed

    Battani, Somashekhar; Pawar, Harish; Suresh, Sarasija

    2014-08-01

    The objective of the present investigation was formulation of raloxifene loaded solid lipid nanoparticles (R-SLN) for oral administration and evaluation of its anticancer potential in 7,12- dimethylbenzanthracene (DMBA)-induced breast cancer in Sprague-Dawley rats. Optimized R-SLN formulation prepared by modified micro-emulsion method resulted in R-SLN of 288.0±28.5 nm size and 95.56% entrapment efficiency. R-SLN exhibited in vitro prolonged release of raloxifene for 72 h in phosphate buffered saline. R-SLN was stable in simulated gastro-intestinal (GIT) fluids consisting of pH 1.2, pH 7.4, simulated gastric fluid and simulated intestinal fluid. A two-fold increase was observed in raloxifene oral bioavailability from R-SLN. R-SLN exhibited enhanced efficacy and chemopreventive activity over pure raloxifene as indicated by evaluation of tumor burden (P < 0.001) and tumor incidence (P < 0.001). The results indicate the potential of raloxifene solid lipid nanoparticles in optimizing chemoprevention of breast cancer by R-SLN.

  5. Analysis of potential oral cleft risk factors in the Kosovo population.

    PubMed

    Salihu, Sami; Krasniqi, Blerim; Sejfija, Osman; Heta, Nijazi; Salihaj, Nderim; Geci, Agreta; Sejdini, Milaim; Arifi, Hysni; Isufi, Ramazan; Ueeck, Brett A

    2014-01-01

    The aim of this study was to analyze the association of potential risk factors such as positive family cleft history, smoking, use of drugs during pregnancy, and parental age with oral clefts in offspring within the Kosovo population. We conducted a population-based case-control study of live births in Kosovo from 1996 to 2005. Using a logistic regression model, 244 oral cleft cases were compared with 488 controls. We have excluded all syndromic clefts. Heredity increases the risk of clefts in newborns [odds ratio (OR) = 8.25, 95% confidence interval (CI) 3.12-23.52]. Clefts were also associated with smoking (OR = 1.87, 95% CI 0.75-4.08), use of drugs during pregnancy (OR = 2.25, 95% CI 0.82-5.12), increasing maternal age (OR = 1.83, 95% CI 1.42-2.49), and increasing paternal age (OR = 1.3, 95% CI 1.2- 1.4). We found heredity to be the most important factor for cleft occurrence in Kosovar newborns. Another significant potential risk factor for occurrence of clefts is the parental age. We found the use of drugs and smoking during pregnancy to be less significant.

  6. Quality of life in patients with oral potentially malignant disorders: a systematic review.

    PubMed

    Tadakamadla, Jyothi; Kumar, Santhosh; Johnson, Newell W

    2015-06-01

    There is a paucity of literature on quality of life (QoL) in patients with oral potentially malignant disorders (OPMDs) despite these conditions being relatively common, chronic, and potentially debilitating. The aim of this paper is to systematically review the literature on QoL in patients with OPMDs. A search from electronic databases PUBMED, MEDLINE, and CINAHL Plus retrieved 180 titles after removing duplicates, and a further 4 papers were identified by hand searching. Study of the abstracts identified 25 truly relevant articles, which were studied in full. Of these, 14 met our strict inclusion criteria. Most studies were cross-sectional; most were from Europe and have evaluated QoL in patients with oral lichen planus (OLP). The findings differ but, overall, do not provide evidence that patients with OPMDs have a poorer QoL compared with healthy patients. Several things may explain this apparently surprising conclusion. First, the quality of most articles was moderate or weak; second, most studies assessed QoL only in patients with OLP and cannot be generalized to all patients with OPMDs; last, direct comparisons between patients with OPMD and healthy controls were rarely included. The validity of the QoL instrument used for patients with OLP was frequently inadequate.

  7. Characterization of the osteogenic potential of mesenchymal stem cells from human periodontal ligament based on cell surface markers.

    PubMed

    Alvarez, Ruth; Lee, Hye-Lim; Wang, Cun-Yu; Hong, Christine

    2015-12-18

    Mesenchymal stem cell (MSC)-mediated therapy has been shown to be clinically effective in regenerating tissue defects. For improved regenerative therapy, it is critical to isolate homogenous populations of MSCs with high capacity to differentiate into appropriate tissues. The utilization of stem cell surface antigens provides a means to identify MSCs from various tissues. However, few surface markers that consistently isolate highly regenerative MSCs have been validated, making it challenging for routine clinical applications and making it all the more imperative to identify reliable surface markers. In this study, we used three surface marker combinations: CD51/CD140α, CD271, and STRO-1/CD146 for the isolation of homogenous populations of dental mesenchymal stem cells (DMSCs) from heterogeneous periodontal ligament cells (PDLCs). Fluorescence-activated cell sorting analysis revealed that 24% of PDLCs were CD51(+)/CD140α(+), 0.8% were CD271(+), and 2.4% were STRO-1(+)/CD146(+). Sorted cell populations were further assessed for their multipotent properties by inducing osteogenic and chondrogenic differentiation. All three subsets of isolated DMSCs exhibited differentiation capacity into osteogenic and chondrogenic lineages but with varying degrees. CD271(+) DMSCs demonstrated the greatest osteogenic potential with strong induction of osteogenic markers such as DLX5, RUNX2, and BGLAP. Our study provides evidence that surface marker combinations used in this study are sufficient markers for the isolation of DMSCs from PDLCs. These results provide important insight into using specific surface markers for identifying homogenous populations of DMSCs for their improved utilization in regenerative medicine.

  8. Markers of erectile dysfunction

    PubMed Central

    Davies, Kelvin P.; Melman, Arnold

    2008-01-01

    With the development and marketing of oral pharmacotherapy that is both noninvasive and successful in treating erectile dysfunction (ED), the quest to identify markers of organic ED lost ground. Indeed, the multi-factorial nature of ED may have led many researchers to conclude that searching for a universal marker of ED was futile. However, the realization that ED is strongly correlated with the overall health of men, and may act as a predictor for the development of cardiovascular disease (CVD) and diabetes, has stimulated interest in identifying genes that can distinguish organic ED. In addition, the potential ability to suggest to the patient that ED is reversible (i.e., psychogenic) with a simple test would be of significance to both the physician and patient, as well as for reimbursement issues for therapy by insurance companies. Such a marker may also act as a non-subjective measure of the degree of ED and the efficacy of treatment. This review discusses the importance of identifying such markers and recent work identifying potential markers in human patients. PMID:19468461

  9. Potential Compounds for Oral Cancer Treatment: Resveratrol, Nimbolide, Lovastatin, Bortezomib, Vorinostat, Berberine, Pterostilbene, Deguelin, Andrographolide, and Colchicine

    PubMed Central

    Bundela, Saurabh; Sharma, Anjana; Bisen, Prakash S.

    2015-01-01

    Oral cancer is one of the main causes of cancer-related deaths in South-Asian countries. There are very limited treatment options available for oral cancer. Research endeavors focused on discovery and development of novel therapies for oral cancer, is necessary to control the ever rising oral cancer related mortalities. We mined the large pool of compounds from the publicly available compound databases, to identify potential therapeutic compounds for oral cancer. Over 84 million compounds were screened for the possible anti-cancer activity by custom build SVM classifier. The molecular targets of the predicted anti-cancer compounds were mined from reliable sources like experimental bioassays studies associated with the compound, and from protein-compound interaction databases. Therapeutic compounds from DrugBank, and a list of natural anti-cancer compounds derived from literature mining of published studies, were used for building partial least squares regression model. The regression model thus built, was used for the estimation of oral cancer specific weights based on the molecular targets. These weights were used to compute scores for screening the predicted anti-cancer compounds for their potential to treat oral cancer. The list of potential compounds was annotated with corresponding physicochemical properties, cancer specific bioactivity evidences, and literature evidences. In all, 288 compounds with the potential to treat oral cancer were identified in the current study. The majority of the compounds in this list are natural products, which are well-tolerated and have minimal side-effects compared to the synthetic counterparts. Some of the potential therapeutic compounds identified in the current study are resveratrol, nimbolide, lovastatin, bortezomib, vorinostat, berberine, pterostilbene, deguelin, andrographolide, and colchicine. PMID:26536350

  10. Testing the potential of a ribosomal 16S marker for DNA metabarcoding of insects

    PubMed Central

    Elbrecht, Vasco; Taberlet, Pierre; Dejean, Tony; Valentini, Alice; Usseglio-Polatera, Philippe; Beisel, Jean-Nicolas; Coissac, Eric; Boyer, Frederic

    2016-01-01

    Cytochrome c oxidase I (COI) is a powerful marker for DNA barcoding of animals, with good taxonomic resolution and a large reference database. However, when used for DNA metabarcoding, estimation of taxa abundances and species detection are limited due to primer bias caused by highly variable primer binding sites across the COI gene. Therefore, we explored the ability of the 16S ribosomal DNA gene as an alternative metabarcoding marker for species level assessments. Ten bulk samples, each containing equal amounts of tissue from 52 freshwater invertebrate taxa, were sequenced with the Illumina NextSeq 500 system. The 16S primers amplified three more insect species than the Folmer COI primers and amplified more equally, probably due to decreased primer bias. Estimation of biomass might be less biased with 16S than with COI, although variation in read abundances of two orders of magnitudes is still observed. According to these results, the marker choice depends on the scientific question. If the goal is to obtain a taxonomic identification at the species level, then COI is more appropriate due to established reference databases and known taxonomic resolution of this marker, knowing that a greater proportion of insects will be missed using COI Folmer primers. If the goal is to obtain a more comprehensive survey the 16S marker, which requires building a local reference database, or optimised degenerated COI primers could be more appropriate. PMID:27114891

  11. HuR knockdown changes the oncogenic potential of oral cancer cells.

    PubMed

    Kakuguchi, Wataru; Kitamura, Tetsuya; Kuroshima, Takeshi; Ishikawa, Makoto; Kitagawa, Yoshimasa; Totsuka, Yasunori; Shindoh, Masanobu; Higashino, Fumihiro

    2010-04-01

    HuR binds to AU-rich element-containing mRNA to protect them from rapid degradation. Here, we show that knockdown of HuR changes the oncogenic properties of oral cancer cells. Oral squamous cell carcinoma cell lines, HSC-3 and Ca9.22, which express HuR protein and cytoplasmic AU-rich element mRNA more abundantly than normal cells, were subjected to HuR knockdown. In the HuR-knockdown cancer cells, the cytoplasmic expression of c-fos, c-myc, and COX-2 mRNAs was inhibited compared with those in cells that had been transfected with a control small interfering RNA, and the half-lives of these mRNAs were shorter than those of their counterparts in the control cells. HuR-knockdown cells failed to make colonies in soft agar, suggesting that the cells had lost their ability for anchorage-independent cell growth. Additionally, the motile and invasive activities of the cells decreased remarkably by HuR knockdown. Furthermore, the expression of cell cycle-related proteins, such as cyclin A, cyclin B1, cyclin D1, and cyclin-dependent kinase 1, was reduced in HuR-knockdown cancer cells, and HuR bound to cdk1 mRNA to stabilize it. These findings suggest that HuR knockdown changes the features of oral cancer cells, at least in part, by affecting their cell cycle and shows potential as an effective therapeutic approach.

  12. Potential of Start Codon Targeted (SCoT) markers for DNA fingerprinting of newly synthesized tritordeums and their respective parents.

    PubMed

    Cabo, Sandra; Ferreira, Luciana; Carvalho, Ana; Martins-Lopes, Paula; Martín, António; Lima-Brito, José Eduardo

    2014-08-01

    Hexaploid tritordeum (H(ch)H(ch)AABB; 2n = 42) results from the cross between Hordeum chilense (H(ch)H(ch); 2n = 14) and cultivated durum wheat (Triticum turgidum ssp. durum (AABB; 2n = 28). Morphologically, tritordeum resembles the wheat parent, showing promise for agriculture and wheat breeding. Start Codon Targeted (SCoT) polymorphism is a recently developed technique that generates gene-targeted markers. Thus, we considered it interesting to evaluate its potential for the DNA fingerprinting of newly synthesized hexaploid tritordeums and their respective parents. In this study, 60 SCoT primers were tested, and 18 and 19 of them revealed SCoT polymorphisms in the newly synthesized tritordeum lines HT27 and HT22, respectively, and their parents. An analysis of the presence/absence of bands among tritordeums and their parents revealed three types of polymorphic markers: (i) shared by tritordeums and one of their parents, (ii) exclusively amplified in tritordeums, and (iii) exclusively amplified in the parents. No polymorphism was detected among individuals of each parental species. Three SCoT markers were exclusively amplified in tritordeums of lines HT22 and HT27, being considered as polyploidization-induced rearrangements. About 70% of the SCoT markers of H. chilense origin were not transmitted to the allopolyploids of both lines, and most of the SCoTs scored in the newly synthesized allopolyploids originated from wheat, reinforcing the potential use of tritordeum as an alternative crop.

  13. Congruence and indifference between two molecular markers for understanding oral evolution in the Marynidae sensu lato (Ciliophora, Colpodea)

    PubMed Central

    Dunthorn, Micah; Katz, Laura A.; Stoeck, Thorsten; Foissner, Wilhelm

    2012-01-01

    Our understanding of the evolution of oral structures within the Colpodida is confounded by the low number of morphological characters that can be used in constructing hypotheses, and by the low taxon and character sampling in molecular phylogenetic analyses designed to assess these hypotheses. Here we increase character sampling by sequencing the mitochondrial SSU-rDNA locus for three isolates of the Marynidae sensu lato. We show that the inferred mitochondrial and nuclear SSU-rDNA trees, as well as concatenated and constrained analyses, are congruent in not recovering a monophyletic Marynidae. However, due to low node support, the trees are indifferent to whether the morphological characters used to unite the Marynidae are the result of retention of ancestral states or convergence. In light of this indifference and an increased amount of nuclear and mitochondrial SSU-rDNA data, alternative hypotheses of oral evolution in the Colpodida are presented. PMID:22356924

  14. Oral Human Abuse Potential of Oxycodone DETERx® (Xtampza® ER)

    PubMed Central

    Kopecky, Ernest A.; Levy‐Cooperman, Naama; O'Connor, Melinda; M. Sellers, Edward

    2016-01-01

    Abstract Oxycodone DETERx® (Collegium Pharmaceutical Inc, Canton, Massachusetts) is an extended‐release, microsphere‐in‐capsule, abuse‐deterrent formulation designed to retain its extended‐release properties after tampering (eg, chewing/crushing). This randomized, double‐blind, placebo‐controlled, triple‐dummy study evaluated the oral abuse potential of intact and chewed oxycodone DETERx capsules compared with crushed immediate‐release oxycodone. Subjects with a history of recreational opioid use who were nondependent/nontolerant to opioids were enrolled. Treatments included intact oxycodone DETERx (high‐fat, high‐calorie meal and fasted), chewed oxycodone DETERx (high‐fat, high‐calorie meal and fasted), crushed immediate‐release oxycodone (fasted), and placebo (high‐fat, high‐calorie meal). Plasma samples were collected to determine pharmacokinetic parameters. The primary endpoint was drug liking at the moment; other endpoints included drug effects questionnaire scores, Addiction Research Center Inventory/Morphine Benzedrine Group score, pupillometry measurements, and safety. Thirty‐eight subjects completed the study. Chewed and intact oxycodone DETERx were bioequivalent, unlike crushed immediate‐release oxycodone, which yielded higher peak oxycodone plasma concentrations compared with all methods of oxycodone DETERx administration. The mean maximum (peak) effect (Emax) for drug liking was significantly lower for chewed and intact oxycodone DETERx than for crushed immediate‐release oxycodone (P < .01). The time to Emax was significantly longer for chewed and intact oxycodone DETERx than for crushed immediate‐release oxycodone (P < .0001). Scores for feeling high and Addiction Research Center Inventory/Morphine Benzedrine Group scores demonstrated lower abuse potential for chewed and intact oxycodone DETERx compared with crushed immediate‐release oxycodone. Study treatments were well tolerated; no subjects experienced

  15. Copeptin - A potential endocrine surrogate marker of CCK-4-induced panic symptoms?

    PubMed

    Demiralay, Cüneyt; Agorastos, Agorastos; Yassouridis, Alexander; Jahn, Holger; Wiedemann, Klaus; Kellner, Michael

    2017-02-01

    Intravenous cholecystokinin-tetrapeptide (CCK-4) administration reliably and dose-dependently provokes panic anxiety in man, accompanied by adrenocorticotropic hormone (ACTH) and cortisol release. Preclinical findings suggest that behavioral and endocrine effects of CCK-4 are mediated via corticotropin-releasing hormone (CRH) release. Anxiogenic stimulation of the central CCK-receptors in man was shown to increase as well vasopressin (AVP), which acts synergistically with CRH as pituitary-adrenocortical axis stimulator during stress. Copeptin (CoP), the C-terminal part of pre-pro-AVP, is released in an equimolar ratio to AVP. It is more stable in the circulation and easier to determine than AVP and it was found to closely mirror the production of AVP. So far, CoP secretion has not been characterized during panic provocation. In 30 healthy male human subjects, we repeatedly measured CoP in plasma during a panic challenge and studied its correlation to Acute Panic Inventory (API) ratings and plasma ACTH and cortisol. CoP levels correlated positively with the increase in API ratings (r=0.41, p=0.03), while ACTH or cortisol did not (r=0.08, p=0.68 and r=0.12, p=0.53, respectively). CoP levels correlated also positively with ACTH (r=0.48, p=0.009) and cortisol (r=0.48, p=0.01) concentrations throughout the CCK-4 challenge. As expected, we found a positive correlation between plasma ACTH and cortisol levels (r=0.57, p=0.001). A vasopressinergic activation during CCK-4 induced panic was demonstrated, which was correlated positively to panic symptoms and pituitary-adrenocortical release. Our findings suggest a role of CoP as a potential surrogate marker of CCK-4 panic symptoms. Further studies are needed to replicate our results and to further clarify the role of CoP as a stress-sensitive hormone in different panic paradigms as well as in panic patients.

  16. In vivo confocal microscopy for the oral cavity: Current state of the field and future potential.

    PubMed

    Maher, N G; Collgros, H; Uribe, P; Ch'ng, S; Rajadhyaksha, M; Guitera, P

    2016-03-01

    Confocal microscopy (CM) has been shown to correlate with oral mucosal histopathology in vivo. The purposes of this review are to summarize what we know so far about in vivo CM applications for oral mucosal pathologies, to highlight some current developments with CM devices relevant for oral applications, and to formulate where in vivo CM could hold further application for oral mucosal diagnosis and management. Ovid Medline® and/or Google® searches were performed using the terms 'microscopy, confocal', 'mouth neoplasms', 'mouth mucosa', 'leukoplakia, oral', 'oral lichen planus', 'gingiva', 'cheilitis', 'taste', 'inflammatory oral confocal', 'mucosal confocal' and 'confocal squamous cell oral'. In summary, inclusion criteria were in vivo use of any type of CM for the human oral mucosa and studies on normal or pathological oral mucosa. Experimental studies attempting to identify proteins of interest and microorganisms were excluded. In total 25 relevant articles were found, covering 8 main topics, including normal oral mucosal features (n=15), oral dysplasia or neoplasia (n=7), inflamed oral mucosa (n=3), taste impairment (n=3), oral autoimmune conditions (n=2), pigmented oral pathology/melanoma (n=1), delayed type hypersensitivity (n=1), and cheilitis glandularis (n=1). The evidence for using in vivo CM in these conditions is poor, as it is limited to mainly small descriptive studies. Current device developments for oral CM include improved probe design. The authors propose that future applications for in vivo oral CM may include burning mouth syndrome, intra-operative mapping for cancer surgery, and monitoring and targeted biopsies within field cancerization.

  17. Proteomic identification of cyclophilin A as a potential biomarker and therapeutic target in oral submucous fibrosis

    PubMed Central

    Xu, Hao; Gong, Wang; Deng, Jing; Sun, Chongkui; Gao, Yijun; Peng, Jieying; Wu, Yingfang; Li, Jiang; Fang, Changyun; Chen, Qianming

    2016-01-01

    Oral submucous fibrosis (OSF) is a pre-cancerous lesion, which is characterized by fibrosis of the oral submucosa. Despite large body of studies focusing on this disease, the molecular mechanisms underlying the progression of OSF remained unclear. In this study, 2-DE-based proteomic approaches were employed to identify the differently expressed proteins between OSF and normal tissues. In total, 88 proteins were identified with altered expression levels, including CypA. Upregulation of CypA was further validated through immunohistochemistry staining combined with Q-PCR and western blot by using clinical samples. Statistical analyses reveal that CypA expression level is correlated to the progression of OSF. Finally, functional study reveals a pro-proliferative property of CypA in fibroblast cells by using multiple in vitro models. The present data suggest that CypA might be a potential biomarker and therapeutic target for OSF, and will lead to a better understanding of OSF pathogenesis. PMID:27533088

  18. Acute oral toxicity and bacterial translocation studies on potentially probiotic strains of lactic acid bacteria.

    PubMed

    Zhou, J S; Shu, Q; Rutherfurd, K J; Prasad, J; Gopal, P K; Gill, H S

    2000-01-01

    Three potentially probiotic lactic acid bacteria (LAB) strains, Lactobacillus rhamnosus HN001 (DR20(TM)), Lb. acidophilus HN017 and Bifidobacterium lactis HN019 (DR10()), have recently been identified and characterized. The present study was designed to evaluate the acute oral toxicity of these strains to mice, and also to investigate bacterial translocation and gut mucosal pathology in BALB/c mice fed HN019, HN001 or HN017 for 8 consecutive days at a high dose of 10(11)cfu/mouse/day. Results showed that these probiotic strains had no adverse effect on general health status, feed intake, body weight gain and intestinal mucosal morphology (villus height, crypt depth, epithelial cell height and mucosal thickness). No viable bacteria were recovered from blood and tissue samples (mesenteric lymph nodes, liver and spleen) of mice, and no treatment-associated illness or death was observed. According to these results, the oral LD(50) of HN019, HN001 and HN017 is more than 50g/kg/day for mice, and their acceptable daily intake (ADI) value is 35g dry bacteria per day for a 70-kg person. This suggests that the probiotic strains HN019, HN001 and HN017 are non-pathogenic and likely to be safe for human consumption.

  19. Investigation of the Enteric Pathogenic Potential of Oral Campylobacter concisus Strains Isolated from Patients with Inflammatory Bowel Disease

    PubMed Central

    Octavia, Sophie; Day, Andrew S.; Riordan, Stephen M.; Grimm, Michael C.; Lan, Ruiting; Lemberg, Daniel; Tran, Thi Anh Tuyet; Zhang, Li

    2012-01-01

    Background Campylobacter concisus, a bacterium colonizing the human oral cavity, has been shown to be associated with inflammatory bowel disease (IBD). This study investigated if patients with IBD are colonized with specific oral C. concisus strains that have potential to cause enteric diseases. Methodology Seventy oral and enteric C. concisus isolates obtained from eight patients with IBD and six controls were examined for housekeeping genes by multilocus sequence typing (MLST), Caco2 cell invasion by gentamicin-protection-assay, protein analysis by mass spectrometry and SDS-PAGE, and morphology by scanning electron microscopy. The whole genome sequenced C. concisus strain 13826 which was isolated from an individual with bloody diarrhea was included in MLST analysis. Principal Findings MLST analysis showed that 87.5% of individuals whose C. concisus belonged to Cluster I had inflammatory enteric diseases (six IBD and one with bloody diarrhea), which was significantly higher than that in the remaining individuals (28.6%) (P<0.05). Enteric invasive C. concisus (EICC) oral strain was detected in 50% of patients with IBD and none of the controls. All EICC strains were in Cluster 1. The C. concisus strain colonizing intestinal tissues of patient No. 1 was closely related to the oral C. concisus strain from patient No. 6 and had gene recombination with the patient’s own oral C. concisus. The oral and intestinal C. concisus strains of patient No. 3 were the same strain. Some individuals were colonized with multiple oral C. concisus strains that have undergone natural recombination. Conclusions This study provides the first evidence that patients with IBD are colonized with specific oral C. concisus strains, with some being EICC strains. C. concisus colonizing intestinal tissues of patients with IBD at least in some instances results from an endogenous colonization of the patient’s oral C. concisus and that C. concisus strains undergo natural recombination. PMID

  20. Absence of the Epithelial Glycocalyx As Potential Tumor Marker for the Early Detection of Colorectal Cancer

    PubMed Central

    Ramaker, Katrin; Bade, Steffen; Röckendorf, Niels; Meckelein, Barbara; Vollmer, Ekkehard; Schultz, Holger; Fröschle, Günter-Willi; Frey, Andreas

    2016-01-01

    Detection of cancer at an early stage is pivotal for successful treatment and long term survival, yet early diagnosis requires sensitive and specific markers that can be easily detected by screening procedures. Differences in the surface structure of tumor and healthy cells, if sufficiently pronounced and discernible, may serve that purpose. We analyzed the luminal surface of healthy and neoplastic human colorectal tissues for the presence and architecture of the glycocalyx—a dense network of highly glycosylated proteins—using transmission electron microscopy. The ultrastructural analyses showed that 93% of healthy mucosae were covered by an intact glycocalyx. Contrarily, on over 90% of the surface of neoplastic cells the glycocalyx was absent. The sensitivity and specificity of our marker “absence of a glycocalyx” are excellent, being 91% (83–96%) and 96% (89–99%) for adenocarcinomas and 94% (73–100%) and 92% (85–97%) for precancerous polyps (means and 95% confidence intervals). Using a cell culture model we could demonstrate that a particulate probe targeting a cell surface receptor usually concealed beneath the glycocalyx can bind selectively to glycocalyx-free areas of a tumor cell layer. We propose that the absence of a glycocalyx may serve as novel type of tumor marker. If the absence of the glycocalyx can be detected e.g. via binding of imaging probes to non-shielded surface receptors of anomalously differentiated cells, this tumor marker could be used to enable early diagnosis of colorectal cancer. PMID:28033349

  1. Resistance to tetracycline and β-lactams and distribution of resistance markers in enteric microorganisms and pseudomonads isolated from the oral cavity.

    PubMed

    Ramos, Marcelle Marie Buso; Gaetti-Jardim, Ellen Cristina; Gaetti-Jardim Junior, Elerson

    2009-01-01

    This study evaluated the occurrence of enteric bacteria and pseudomonads resistant to tetracycline and β-lactams in the oral cavity of patients exhibiting gingivitis (n=89), periodontitis (n=79), periodontally healthy (n=50) and wearing complete dentures (n=41). Microbial identification and presence of resistance markers associated with the production of β-lactamases and tetracycline resistance were performed by using biochemical tests and PCR. Susceptibility tests were carried out in 201 isolates of enteric cocci and rods. Resistance to ampicillin, amoxicillin/clavulanic acid, imipenem, meropenem and tetracycline was detected in 57.4%, 34.6%, 2.4%, 1.9% and 36.5% of the isolates, respectively. β-lactamase production was observed in 41.2% of tested microorganisms, while the most commonly found β-lactamase genetic determinant was gene blaTEM. Tetracycline resistance was disseminated and a wide scope of tet genes were detected in all studied microbial genus.

  2. The potential role of microbes in oncogenesis with particular emphasis on oral cancer

    PubMed Central

    Faden, Asmaa A.

    2016-01-01

    For over a century, non-virus microorganisms, notably bacteria have been implicated as causal agents of cancers, a relatively small number of researchers have provided evidence to support the so-called “cancer germ” hypothesis. With the exception of the link between Helicobacter pylori and stomach cancer, other supposed links have been ignored. A wide range of bacteria and other non-virus microbes, including fungi, have been implicated over the years in oncogenesis, as well as the ability to induce inflammation, which may cause cancer. It seems that there is no single “cancer germ,” as most bacteria can apparently induce cancer. Here, the role of bacteria and other non-virus microorganisms and oral cancers will be discussed. By ignoring bacteria as a causal agent of cancer, we set back our understanding of this crucially important disease and, as a result, have hindered the development of potential cures. PMID:27279505

  3. Geriatric forensics - Part 2 “Prevalence of elder abuse and their potential forensic markers among medical and dental patients”

    PubMed Central

    Mattoo, Khurshid A.; Garg, Rishabh; Kumar, Shalabh

    2015-01-01

    Context: This study is a continuation of the earlier studies and has been extended to investigate the potential forensic markers of elder abuse. Aims: To determine the prevalence of elder abuse in various outpatient departments (OPDs). To study the associated parameters related to the abuser and the abused. To determine the existence of potential forensic markers of elder abuse. Settings and Design: The subjects were randomly selected from the medical and the dental OPDs of the university. Materials and Methods: Eight hundred and thirty two elderly subjects in the age range 40-60 years were interviewed using a questionnaire to determine the existence of elder abuse. The subjects were investigated and examined for weight, nutrition and hydration, vital signs, habits, existing visual and auditory capabilities, medications, disclosure of wills/deeds, signs of depression, and documented cleanliness. The mini-mental state examination, the Geriatric Depression Scale, the Clock drawing test, and the Brief Psychiatric Rating Scale were used to determine the potential forensic markers. Statistical Analysis Used: Mean values in percentage were determined by dividing the number of determined subjects by the total number of subjects for that parameter. Results: About 37% in medical and 41% in dental OPDs were found to have suffered from abuse, mostly in the age group 60-70 years. Females received more abuse and a combination of son and daughter-in-law constituted most abusers. Various potential markers of elder abuse and neglect investigated among the elder abuse victims included depression (89%), signs of improper feeding (83%), changes in personal hygiene (69%), need for medical/dental treatment (78%), medication misuse (67%), changes in wills/deeds (26%), decubiti (10%), bruises (17%), skin tears (27%), and confusion (23%). Conclusions: Elder abuse exists in one or more forms in both medical and dental OPDs among both males and females in all age groups. PMID:26816460

  4. Comparison of breast cancer to healthy control tissue discovers novel markers with potential for prognosis and early detection.

    PubMed

    Schummer, Michèl; Green, Ann; Beatty, J David; Karlan, Beth Y; Karlan, Scott; Gross, Jenny; Thornton, Sean; McIntosh, Martin; Urban, Nicole

    2010-02-09

    This study was initiated to identify biomarkers with potential value for the early detection of poor-outcome breast cancer. Two sets of well-characterized tissues were utilized: one from breast cancer patients with favorable vs. poor outcome and the other from healthy women undergoing reduction mammaplasty. Over 46 differentially expressed genes were identified from a large list of potential targets by a) mining publicly available expression data (identifying 134 genes for quantitative PCR) and b) utilizing a commercial PCR array. Three genes show elevated expression in cancers with poor outcome and low expression in all other tissues, warranting further investigation as potential blood markers for early detection of cancers with poor outcome. Twelve genes showed lower expression in cancers with poor outcome than in cancers with favorable outcome but no differential expression between aggressive cancers and most healthy controls. These genes are more likely to be useful as prognostic tissue markers than as serum markers for early detection of aggressive disease. As a secondary finding was that, when histologically normal breast tissue was removed from a distant site in a breast with cancer, 7 of 38 specimens displayed a cancer-like expression profile, while the remaining 31 were genetically similar to the reduction mammaplasty control group. This finding suggests that some regions of ipsilateral histologically 'normal' breast tissue are predisposed to becoming malignant and that normal-appearing tissue with malignant signature might warrant treatment to prevent new primary tumors.

  5. DNA methylome profiling of maternal peripheral blood and placentas reveal potential fetal DNA markers for non-invasive prenatal testing.

    PubMed

    Xiang, Yuqian; Zhang, Junyu; Li, Qiaoli; Zhou, Xinyao; Wang, Teng; Xu, Mingqing; Xia, Shihui; Xing, Qinghe; Wang, Lei; He, Lin; Zhao, Xinzhi

    2014-09-01

    Utilizing epigenetic (DNA methylation) differences to differentiate between maternal peripheral blood (PBL) and fetal (placental) DNA has been a promising strategy for non-invasive prenatal testing (NIPT). However, the differentially methylated regions (DMRs) have yet to be fully ascertained. In the present study, we performed genome-wide comparative methylome analysis between maternal PBL and placental DNA from pregnancies of first trimester by methylated DNA immunoprecipitation-sequencing (MeDIP-Seq) and Infinium HumanMethylation450 BeadChip assays. A total of 36 931 DMRs and 45 804 differentially methylated sites (DMSs) covering the whole genome, exclusive of the Y chromosome, were identified via MeDIP-Seq and Infinium 450k array, respectively, of which 3759 sites in 2188 regions were confirmed by both methods. Not only did we find the previously reported potential fetal DNA markers in our identified DMRs/DMSs but also we verified fully the identified DMRs/DMSs in the validation round by MassARRAY EpiTYPER. The screened potential fetal DNA markers may be used for NIPT on aneuploidies and other chromosomal diseases, such as cri du chat syndrome and velo-cardio-facial syndrome. In addition, these potential markers may have application in the early diagnosis of placental dysfunction, such as pre-eclampsia.

  6. Therapeutic effects of cinnamaldehyde and potentiation of its efficacy in combination with methylcellulose on murine oral candidiasis.

    PubMed

    Taguchi, Yuuki; Hayama, Kazumi; Okada, Masashi; Sagawa, Takehito; Arai, Ryo; Abe, Shigeru

    2011-01-01

    We examined the therapeutic effects of cinnamaldehyde and the potentiation of those effects with cassia and cinnamaldehyde when combined with the food additive methylcellulose against murine oral candidiasis. When 19.5mg/ml of cinnamaldehyde was administered in the oral cavity of Candida infected mice, the oral symptoms were improved. Furthermore, when either a cassia or a cinnamaldehyde preparation in combination with methylcellulose was administered to oral candidiasis-inflicted mice, the therapeutic effects of cassia or cinnamaldehyde potentiated. Methylcellulose itself did not affect the oral symptoms or the viable number of C. albicans cells. GC/MS analysis showed that the dose of cinnamaldehyde remaining in the tongue tissue of mice treated with the cinnamaldehyde-methylcellulose mixture was higher than that in mice administered cinnamaldehyde alone, and also showed that cinnamaldehyde was not detected in the blood of any of the tested mice. These findings suggested that the combination of cassia or cinnamaldehyde and methylcellulose may be a useful prophylactic or therapeutic tool against oral candidiasis.

  7. Hypoxia in human colorectal adenocarcinoma: Comparison between extrinsic and potential intrinsic hypoxia markers

    SciTech Connect

    Goethals, Laurence; Debucquoy, Annelies; Perneel, Christiaan; Geboes, Karel; Ectors, Nadine; De Schutter, Harlinde; Penninckx, Freddy; McBride, William H.; Begg, Adrian C.; Haustermans, Karin M. . E-mail: karin.haustermans@uzleuven.be

    2006-05-01

    Purpose: To detect and quantify hypoxia in colorectal adenocarcinomas by use of pimonidazole and iododeoxyuridine (IdUrd) as extrinsic markers and carbonic anhydrase IX (CA IX), microvessel density (MVD), epidermal growth-factor receptor (EGFR), and vascular endothelial growth factor (VEGF) as intrinsic markers of hypoxia. Methods and Material: Twenty patients with an adenocarcinoma of the left colon and rectum treated by primary surgery were injected with pimonidazole and IdUrd. Serial sections of tumor biopsies were single stained for VEGF, EGFR, Ki67, and double stained for blood vessels in combination with either pimonidazole, IdUrd, or CA IX. Percentage of expression was scored as well as colocalization of pimonidazole with CA IX. Results: The median percentage of hypoxia, as judged by pimonidazole staining, was 16.7% (range, 0-52.4%). The expression of pimonidazole correlated inversely with the total MVD and endothelial cord MVD (R = -0.55, p = 0.01; R = -0.47, p = 0.04). Good colocalization was found between pimonidazole and CA IX in only 30% of tumors, with no correlation overall between pimonidazole and CA IX, VEGF, or EGFR or between the different intrinsic markers. Cells around some vessels (0.08-11%) were negative for IdUrd but positive for Ki 67, which indicated their lack of perfusion at the time of injection. Conclusion: Chronic and acute hypoxic regions are present in colorectal tumors, as shown by pimonidazole and IdUrd staining. Only in a minority of tumors did an association exist between the areas stained by pimonidazole and those positive for CA IX. Pimonidazole also did not correlate with expression of other putative intrinsic hypoxia markers (VEGF, EGFR)

  8. Mirror-like slip surfaces in dolostone: natural and experimental constraints on a potential seismic marker

    NASA Astrophysics Data System (ADS)

    Fondriest, M.; Smith, S. A.; Di Toro, G.; Nielsen, S. B.

    2012-12-01

    The lack of clear geological markers of seismic faulting represents a major limitation in our current comprehension of earthquake physics. At present pseudotachylytes (i.e. friction-induced melts) are the only unambiguously identified indicator of ancient seismicity in exhumed fault zones, but pseudotachylytes are not found in many rock types, including carbonates. We report the occurrence of small-displacement, mirror-like slip surfaces from a fault zone cutting dolostones. A combination of field observations and rotary shear friction experiments suggests that such slip surfaces: 1) are formed only at seismic slip rates, and 2) could potentially be used to estimate power dissipation during individual slip events. The Foiana Line (FL) is a major NNE-SSW-trending sinistral transpressive fault in the Italian Southern Alps. The outcropping fault zone consists of a <300 m wide zone of heavily fractured ("pulverized") dolostones cut by a network of mirror-like slip surfaces. The slip surfaces have displacements ranging between 0.04 m and 0.5 m and their mirror-like appearance indicates that the wavelength of surface roughness is <1 μm. The slip surfaces have mainly dip-slip reverse kinematics and were exhumed from ~2 km depth. Resolved normal stress on the slip surfaces is estimated in the range 30-50 MPa. To understand how the mirror-like slip surfaces may have developed, slow- to high-velocity rotary-shear experiments using SHIVA (INGV, Rome) were performed on 3 mm thick layers of dolomite gouge (grain size <250 μm) collected from the FL. Tests were conducted using a purpose-built gouge sample holder at slip rates of 0.0001-1.13 m/s, normal stresses up to 26 MPa and displacements in the range 0.02-3.5 m. At seismic slip rates of 1.13 m/s the dolomite gouge shows a dramatic reduction of the friction coefficient (μ) from a peak value of ~0.7 to a steady-state value of ~0.25. The gouge starts to weaken above a threshold velocity in the range 0.19-0.49 m/s following a

  9. Enteral resuscitation of burn shock using World Health Organization oral rehydration solution: a potential solution for mass casualty care.

    PubMed

    Michell, Michael W; Oliveira, Hermes M; Kinsky, Michael P; Vaid, Sumreen U; Herndon, David N; Kramer, George C

    2006-01-01

    Enteral resuscitation could provide a means to resuscitate burn shock when intravenous (IV) therapy is unavailable, such as in mass disasters. We evaluated the extent of intestinal absorption and resuscitative effects of World Health Organization Oral Rehydration Solution after a 40% TBSA burn in anesthetized swine compared with the IV infusion of lactated Ringer's infused by Parkland formula. Plasma volume (PV) was measured using indocyanine green dye dilution. Intestinal absorption was assessed using phenol red as a nonabsorbable marker. Changes in hematocrit, hemodynamics, and measured PV showed equivalent resuscitative effects of enteral and IV resuscitation. The duodenal fluid absorption rate started at 77 +/- 32 ml/hr per meter of intestine during the first hour and increased to 296 +/- 40 ml/hr during the fourth hour of resuscitation, with a total of 93 +/- 2% of World Health Organization Oral Rehydration Solution infused into the intestine being absorbed. Intestinal absorption rates after burn injury are sufficient to resuscitate a 40% TBSA burn.

  10. Identification of innovative potential quality markers in rocket and melon fresh-cut produce.

    PubMed

    Cavaiuolo, Marina; Cocetta, Giacomo; Bulgari, Roberta; Spinardi, Anna; Ferrante, Antonio

    2015-12-01

    Ready-to-eat fresh cut produce are exposed to pre- and postharvest abiotic stresses during the production chain. Our work aimed to identify stress responsive genes as new molecular markers of quality that can be widely applied to leaves and fruits and easily determined at any stage of the production chain. Stress responsive genes associated with quality losses were isolated in rocket and melon fresh-cut produce and their expression levels analyzed by quantitative real time PCR (qRT-PCR) at different time points after harvest at 20 °C and 4 °C. qRT-PCR results were supported by correlation analysis with physiological and biochemical determinations evaluated at the same conditions such as chlorophyll a fluorescence indices, total, reducing sugars, sucrose, ethylene, ascorbic acid, lipid peroxidation and reactive oxygen species. In both species the putative molecular markers increased their expression soon after harvest suggesting a possible use as novel and objective quality markers of fresh-cut produces.

  11. Antibacterial potential of Manuka honey against three oral bacteria in vitro.

    PubMed

    Schmidlin, PatrickSchmidlin R; English, Helen; Duncan, Warwick; Belibasakis, Georgios N; Thurnheer, Thomas

    2014-01-01

    Honey is an ancient natural remedy for the treatment of infected wounds. It has regained attention in the medical profession, as it has recently been reported to have a broad-spectrum inhibitory effect against bacteria. Data concerning Manuka honey of New Zealand origin, which is claimed to provide additional non-peroxide antimicrobial activity (so-called standard NPA) against oral pathogens, is still scarce. Therefore, this study aimed to screen for the antibacterial efficacy of different Manuka honey products against S. mutans (OMZ 918), P. gingivalis (OMZ 925) and A. actinomycetemcomitans (OMZ 299). Chlorhexidine and saline served as positive and negative controls, respectively, whereas a Swiss multifloral honey served as control honey without intrinsic non-peroxide activity. Chlorhexidine showed the highest inhibiting potential against all specimens tested. Manuka honey below an NPA value of 15 showed the least bacterial growth-inhibiting potential, even less – although not significantly so – than multifloral Swiss honey. Manuka honey above an NPA value of 15 showed a significantly higher antibacterial effect compared to the other honeys tested. All Manuka honey preparations were more effective in inhibiting the growth of P. gingivalis and A. actinomycetemcomitans, rather than S. mutans. In conclusion, the study showed an NPA dose-dependent antibacterial efficacy of Manuka honey. Further investigations of this natural product are now open for scrutiny.

  12. Benefit cost scenarios of potential oral rabies vaccination for skunks in California.

    PubMed

    Shwiff, Stephanie A; Sterner, Ray T; Hale, Robert; Jay, Michele T; Sun, Ben; Slate, Dennis

    2009-01-01

    Scenario-based analyses were computed for benefits and costs linked with hypothetical oral rabies vaccination (ORV) campaigns to contain or eliminate skunk-variant rabies in skunks (Mephitis mephitis) in California, USA. Scenario 1 assumed baiting eight zones (43,388 km(2) total) that comprised 73% of known skunk rabies locations in the state. Scenario 2 also assumed baiting these eight zones, but further assumed that added benefits would result from preventing the spread of skunk-variant rabies into Los Angeles County, USA. Scenarios assumed a fixed bait cost ($1.24 each) but varied campaigns (one, two and three annual ORV applications), densities of baits (37.5/km(2), 75/km(2) and 150/km(2)), levels of prevention (50%, 75%, and 100%), and contingency expenditures if rabies recurred (20%, 40%, and 60% of campaign costs). Prorating potential annual benefits during a 12-yr time horizon yielded benefit-cost ratios (BCRs) between 0.16 and 2.91 and between 0.34 and 6.35 for Scenarios 1 and 2, respectively. Economic issues relevant to potentially managing skunk-variant rabies with ORV are discussed.

  13. Antibacterial peptide nisin: a potential role in the inhibition of oral pathogenic bacteria.

    PubMed

    Tong, Zhongchun; Ni, Longxing; Ling, Junqi

    2014-10-01

    Although the antimicrobial peptide nisin has been extensively studied in the food industry for decades, its application in the oral cavity remains to develop and evaluate its feasibility in treating oral common diseases. Nisin is an odorless, colorless, tasteless substance with low toxicity and with antibacterial activities against Gram-positive bacteria. These biologic properties may establish its use in promising products for oral diseases. This article summarizes the antibacterial efficiency of nisin against pathogenic bacteria related to dental caries and root canal infection and discusses the combination of nisin and common oral drugs.

  14. Caffeic Acid Phenethyl Ester Is a Potential Therapeutic Agent for Oral Cancer

    PubMed Central

    Kuo, Ying-Yu; Jim, Wai-Tim; Su, Liang-Cheng; Chung, Chi-Jung; Lin, Ching-Yu; Huo, Chieh; Tseng, Jen-Chih; Huang, Shih-Han; Lai, Chih-Jen; Chen, Bo-Chih; Wang, Bi-Juan; Chan, Tzu-Min; Lin, Hui-Ping; Chang, Wun-Shaing Wayne; Chang, Chuang-Rung; Chuu, Chih-Pin

    2015-01-01

    Head and neck cancers, which affect 650,000 people and cause 350,000 deaths per year, is the sixth leading cancer by cancer incidence and eighth by cancer-related death worldwide. Oral cancer is the most common type of head and neck cancer. More than 90% of oral cancers are oral and oropharyngeal squamous cell carcinoma (OSCC). The overall five-year survival rate of OSCC patients is approximately 63%, which is due to the low response rate to current therapeutic drugs. In this review we discuss the possibility of using caffeic acid phenethyl ester (CAPE) as an alternative treatment for oral cancer. CAPE is a strong antioxidant extracted from honeybee hive propolis. Recent studies indicate that CAPE treatment can effectively suppress the proliferation, survival, and metastasis of oral cancer cells. CAPE treatment inhibits Akt signaling, cell cycle regulatory proteins, NF-κB function, as well as activity of matrix metalloproteinase (MMPs), epidermal growth factor receptor (EGFR), and Cyclooxygenase-2 (COX-2). Therefore, CAPE treatment induces cell cycle arrest and apoptosis in oral cancer cells. According to the evidence that aberrations in the EGFR/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling, NF-κB function, COX-2 activity, and MMPs activity are frequently found in oral cancers, and that the phosphorylation of Akt, EGFR, and COX-2 correlates to oral cancer patient survival and clinical progression, we believe that CAPE treatment will be useful for treatment of advanced oral cancer patients. PMID:25984601

  15. Statistical strategies to reveal potential vibrational markers for in vivo analysis by confocal Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Oliveira Mendes, Thiago de; Pinto, Liliane Pereira; Santos, Laurita dos; Tippavajhala, Vamshi Krishna; Téllez Soto, Claudio Alberto; Martin, Airton Abrahão

    2016-07-01

    The analysis of biological systems by spectroscopic techniques involves the evaluation of hundreds to thousands of variables. Hence, different statistical approaches are used to elucidate regions that discriminate classes of samples and to propose new vibrational markers for explaining various phenomena like disease monitoring, mechanisms of action of drugs, food, and so on. However, the technical statistics are not always widely discussed in applied sciences. In this context, this work presents a detailed discussion including the various steps necessary for proper statistical analysis. It includes univariate parametric and nonparametric tests, as well as multivariate unsupervised and supervised approaches. The main objective of this study is to promote proper understanding of the application of various statistical tools in these spectroscopic methods used for the analysis of biological samples. The discussion of these methods is performed on a set of in vivo confocal Raman spectra of human skin analysis that aims to identify skin aging markers. In the Appendix, a complete routine of data analysis is executed in a free software that can be used by the scientific community involved in these studies.

  16. Potential Therapeutic Targets for Oral Cancer: ADM, TP53, EGFR, LYN, CTLA4, SKIL, CTGF, CD70

    PubMed Central

    Bundela, Saurabh; Sharma, Anjana; Bisen, Prakash S.

    2014-01-01

    In India, oral cancer has consistently ranked among top three causes of cancer-related deaths, and it has emerged as a top cause for the cancer-related deaths among men. Lack of effective therapeutic options is one of the main challenges in clinical management of oral cancer patients. We interrogated large pool of samples from oral cancer gene expression studies to identify potential therapeutic targets that are involved in multiple cancer hallmark events. Therapeutic strategies directed towards such targets can be expected to effectively control cancer cells. Datasets from different gene expression studies were integrated by removing batch-effects and was used for downstream analyses, including differential expression analysis. Dependency network analysis was done to identify genes that undergo marked topological changes in oral cancer samples when compared with control samples. Causal reasoning analysis was carried out to identify significant hypotheses, which can explain gene expression profiles observed in oral cancer samples. Text-mining based approach was used to detect cancer hallmarks associated with genes significantly expressed in oral cancer. In all, 2365 genes were detected to be differentially expressed genes, which includes some of the highly differentially expressed genes like matrix metalloproteinases (MMP-1/3/10/13), chemokine (C-X-C motif) ligands (IL8, CXCL-10/-11), PTHLH, SERPINE1, NELL2, S100A7A, MAL, CRNN, TGM3, CLCA4, keratins (KRT-3/4/13/76/78), SERPINB11 and serine peptidase inhibitors (SPINK-5/7). XIST, TCEAL2, NRAS and FGFR2 are some of the important genes detected by dependency and causal network analysis. Literature mining analysis annotated 1014 genes, out of which 841 genes were statistically significantly annotated. The integration of output of various analyses, resulted in the list of potential therapeutic targets for oral cancer, which included targets such as ADM, TP53, EGFR, LYN, CTLA4, SKIL, CTGF and CD70. PMID:25029526

  17. Pharmacodynamic effects of oral contraceptive steroids on biochemical markers for arterial thrombosis. Studies in non-diabetic women and in women with insulin-dependent diabetes mellitus.

    PubMed

    Petersen, Kresten Rubeck

    2002-02-01

    Even small increases in the frequency of thrombotic disease in users of OCs have general health impact because of their widespread use, which is currently expanding to potential risk groups. The present investigations were launched to study the effects of OCs containing 20-40 micrograms of EE combined with the latest developed gonane progestogens on biochemical risk markers within metabolic systems involved in the development of arterial thrombotic disease. The studies included evaluation of carbohydrate and lipid metabolism as well as the haemostatic system and were performed in non-diabetic women and in women with IDDM, who are prone to the development of arterial thrombosis. In the evaluation of the carbohydrate metabolism in non-diabetic women, we found no effect on fasting glucose or insulin and no effect on the insulin response to oral glucose in women using monophasic OCs containing EE combined with DSG or GST. This contrasts the evaluation of triphasic OCs containing EE combined with GST or NGT, which increased fasting insulin and reduced insulin sensitivity without affecting the glucose-effectiveness or the beta-cell function. Impaired glucose tolerance developed in 10% of the women after 6 months. These finding suggest that OCs are able to induce a state of insulin resistance, which should be considered in the prescription for women with potential disturbed insulin sensitivity or reduced beta-cell secretory capacity e.g. women with ovarian hyperandrogenism, obesity, previous GDM or perimenopausal women. We found no change in glycaemic control in 22 women with well-regulated IDDM treated with a monophasic combination of EE and GST for one year and none of the women developed microalbuminuria during treatment. In the women with diabetes we observed an increase in fasting levels of triglycerides, a decrease in LDL-cholesterol, and unchanged concentrations of total cholesterol and HDL-cholesterol during treatment. In non-diabetic women treated with the same

  18. Detection of urinary markers for thiazide diuretics after oral administration of hydrochlorothiazide and altizide-relevance to doping control analysis.

    PubMed

    Deventer, K; Pozo, O J; Van Eenoo, P; Delbeke, F T

    2009-03-20

    In sports, thiazide diuretics are used to flush out previously taken prohibited substances with forced diuresis and in sports where weight classes are involved to achieve acute weight loss. Thiazide diuretics include compounds which are very unstable and hydrolyse in aqueous media. Because information regarding the urinary detection of the hydrolysis products is limited, urinary excretion profiles for the hydrolysis product 4-amino-6-chloro-1,3-benzenedisulphonamide were established in 6 healthy volunteers after oral administration of altizide (15 mg per tablet) and hydrochlorothiazide (25mg per tablet). Additionally, the excretion profile of chlorothiazide, a metabolite of altizide and hydrochlorothiazide, was also determined. A quantitative liquid-chromatographic tandem mass spectrometric method to detect the 4 substances was developed and validated. The result of this work shows that altizide is eliminated within 48 h in urine whereas hydrochlorothiazide was detectable after 120 h. Chlorothiazide was determined to be a minor metabolite of altizide and hydrochlorothiazide and could be detected up to 120 h. The hydrolysis product, 4-amino-6-chloro-1,3-benzenedisulphonamide, was detectable 120 h after administration, with concentrations at least 10 times higher than the parent drug. Concentrations ranged between 41-239 and 60-287 ng/mL after altizide and hydrochlorothiazide administration, respectively. The study shows that 4-amino-6-chloro-1,3-benzenedisulphonamide is an important target compound for the long time detection of thiazide diuretics in urine.

  19. Fluorescence spectroscopy for the detection of potentially malignant disorders of the oral cavity: analysis of 30 cases

    NASA Astrophysics Data System (ADS)

    Francisco, A. L. N.; Correr, W. R.; Azevedo, L. H.; Galletta, V. K.; Pinto, C. A. L.; Kowalski, L. P.; Kurachi, C.

    2014-01-01

    Oral cancer is a major health problem worldwide and although early diagnosis of potentially malignant and malignant diseases is associated with better treatment results, a large number of cancers are initially misdiagnosed, with unfortunate consequences for long-term survival. Fluorescence spectroscopy is a noninvasive modality of diagnostic approach using induced fluorescence emission in tumors that can improve diagnostic accuracy. The objective of this study was to determine the ability to discriminate between normal oral mucosa and potentially malignant disorders by fluorescence spectroscopy. Fluorescence investigation under 408 and 532 nm excitation wavelengths was performed on 60 subjects, 30 with potentially malignant disorders and 30 volunteers with normal mucosa. Data was analyzed to correlate fluorescence patterns with clinical and histopathological diagnostics. Fluorescence spectroscopy used as a point measurement technique resulted in a great variety of spectral information. In a qualitative analysis of the fluorescence spectral characteristics of each type of injury evaluated, it was possible to discriminate between normal and abnormal oral mucosa. The results show the potential use of fluorescence spectroscopy for an improved discrimination of oral disorders.

  20. Genome-wide association analysis of bacterial cold water disease resistance in rainbow trout reveals the potential of a hybrid approach between genomic selection and marker assisted selection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genomic selection (GS) simultaneously incorporates dense SNP marker genotypes with phenotypic data from related animals to predict animal-specific genomic breeding value (GEBV), which circumvents the need to measure the disease phenotype in potential breeders. Marker assisted selection (MAS) involv...

  1. Expression Profiling of Ribosome Biogenesis Factors Reveals Nucleolin as a Novel Potential Marker to Predict Outcome in AML Patients.

    PubMed

    Marcel, Virginie; Catez, Frédéric; Berger, Caroline M; Perrial, Emeline; Plesa, Adriana; Thomas, Xavier; Mattei, Eve; Hayette, Sandrine; Saintigny, Pierre; Bouvet, Philippe; Diaz, Jean-Jacques; Dumontet, Charles

    2017-01-01

    Acute myeloid leukemia (AML) is a heterogeneous disease. Prognosis is mainly influenced by patient age at diagnosis and cytogenetic alterations, two of the main factors currently used in AML patient risk stratification. However, additional criteria are required to improve the current risk classification and better adapt patient care. In neoplastic cells, ribosome biogenesis is increased to sustain the high proliferation rate and ribosome composition is altered to modulate specific gene expression driving tumorigenesis. Here, we investigated the usage of ribosome biogenesis factors as clinical markers in adult patients with AML. We showed that nucleoli, the nucleus compartments where ribosome production takes place, are modified in AML by analyzing a panel of AML and healthy donor cells using immunofluorescence staining. Using four AML series, including the TCGA dataset, altogether representing a total of about 270 samples, we showed that not all factors involved in ribosome biogenesis have clinical values although ribosome biogenesis is increased in AML. Interestingly, we identified the regulator of ribosome production nucleolin (NCL) as over-expressed in AML blasts. Moreover, we found in two series that high NCL mRNA expression level was associated with a poor overall survival, particular in elderly patients. Multivariate analyses taking into account age and cytogenetic risk indicated that NCL expression in blast cells is an independent marker of reduced survival. Our study identifies NCL as a potential novel prognostic factor in AML. Altogether, our results suggest that the ribosome biogenesis pathway may be of interest as clinical markers in AML.

  2. [Polymorphism of DNA nucleotide sequence as a source of enhancement of the discrimination potential of the STR-markers].

    PubMed

    Zemskova, E Yu; Timoshenko, T V; Leonov, S N; Ivanov, P L

    2016-01-01

    The objective of the present pilot investigation was to reveal and to study polymorphism of nucleotide sequence in the alleles of STR loci of human autosomal DNA with special reference to the role of this phenomenon as a source of the differences between homonymous allelic variants. The secondary objection was to evaluate the possibility of using the data thus obtained for the enhancement of the informative value of the forensic medical genotyping of STR loci by means of identification of single nucleotide polymorphisms (SNP) for the purpose of extending their allelic spectrum. The methodological basis of the study was constituted by the comprehensive amplified fragment length polymorphism (AFLP) analysis and amplified fragment sequence polymorphisms (AFSP) analysis of DNA with the use of the PLEX-ID^TM analytical mass-spectrometry platform (Abbot Molecular, USA). The study has demonstrated that polymorphism of DNA nucleotide sequence can be regarded as the possible source of enhancement of the discriminating potential of STR markers. It means that the analysis of polymorphism of DNA nucleotide sequence for genotyping AFLP-type markers of chromosomal DNA can considerably increase the effectiveness of their application as individualizing markers for the purpose of molecular genetic expertises.

  3. Expression Profiling of Ribosome Biogenesis Factors Reveals Nucleolin as a Novel Potential Marker to Predict Outcome in AML Patients

    PubMed Central

    Berger, Caroline M.; Perrial, Emeline; Plesa, Adriana; Thomas, Xavier; Mattei, Eve; Hayette, Sandrine; Saintigny, Pierre; Bouvet, Philippe; Diaz, Jean-Jacques; Dumontet, Charles

    2017-01-01

    Acute myeloid leukemia (AML) is a heterogeneous disease. Prognosis is mainly influenced by patient age at diagnosis and cytogenetic alterations, two of the main factors currently used in AML patient risk stratification. However, additional criteria are required to improve the current risk classification and better adapt patient care. In neoplastic cells, ribosome biogenesis is increased to sustain the high proliferation rate and ribosome composition is altered to modulate specific gene expression driving tumorigenesis. Here, we investigated the usage of ribosome biogenesis factors as clinical markers in adult patients with AML. We showed that nucleoli, the nucleus compartments where ribosome production takes place, are modified in AML by analyzing a panel of AML and healthy donor cells using immunofluorescence staining. Using four AML series, including the TCGA dataset, altogether representing a total of about 270 samples, we showed that not all factors involved in ribosome biogenesis have clinical values although ribosome biogenesis is increased in AML. Interestingly, we identified the regulator of ribosome production nucleolin (NCL) as over-expressed in AML blasts. Moreover, we found in two series that high NCL mRNA expression level was associated with a poor overall survival, particular in elderly patients. Multivariate analyses taking into account age and cytogenetic risk indicated that NCL expression in blast cells is an independent marker of reduced survival. Our study identifies NCL as a potential novel prognostic factor in AML. Altogether, our results suggest that the ribosome biogenesis pathway may be of interest as clinical markers in AML. PMID:28103300

  4. Potential of Text-Based Internet Chats for Improving Oral Fluency in a Second Language

    ERIC Educational Resources Information Center

    Blake, Christopher

    2009-01-01

    Although a number of studies have reported on the positive effects of Internet chats in the second language classroom, to the best of my knowledge no studies to date have examined the effect of text-based chats on oral fluency development. This exploratory study addressed the above question by examining the oral fluency development of 34 English…

  5. VDAC3 As a Potential Marker of Mitochondrial Status Is Involved in Cancer and Pathology

    PubMed Central

    Reina, Simona; Guarino, Francesca; Magrì, Andrea; De Pinto, Vito

    2016-01-01

    VDAC3 is the least known isoform of the mammalian voltage-dependent anion selective channels of the outer mitochondrial membrane. It has been recently shown that cysteine residues of VDAC3 are found over-oxidized. The VDAC3 cysteine over-oxidation was associated with the oxidizing environment and the abundance of reactive oxygen species (ROS) in the intermembrane space. In this work, we have examined the role of VDAC3 in general pathogenic mechanisms at the basis of mitochondrial dysfunction and involving the mitochondrial quality control. Many of the diseases reported here, including cancer and viral infections, are often associated with significant changes in the intracellular redox state. In this sense, VDAC3 bearing oxidative modifications could become marker of the oxidative load in the mitochondria and part of the ROS signaling pathway. PMID:28066720

  6. MTHFR Gene Mutations: A Potential Marker of Late-Onset Alzheimer's Disease?

    PubMed

    Román, Gustavo C

    2015-01-01

    Recent epigenome-wide association studies have confirmed the importance of epigenetic effects mediated by DNA methylation in late-onset Alzheimer's disease (LOAD). Metabolic folate pathways and methyl donor reactions facilitated by B-group vitamins may be critical in the pathogenesis of LOAD. Methylenetetrahydrofolate reductase (MTHFR) gene mutations were studied in consecutive Alzheimer's Disease & Memory Clinic patients up to December 2014. DNA analyses of MTHFR-C667T and - A1298C homozygous and heterozygous polymorphisms in 93 consecutive elderly patients revealed high prevalence of MTHFR mutations (92.5%). Findings require confirmation in a larger series, but MTHFR mutations may become a LOAD marker, opening novel possibilities for prevention and treatment.

  7. Smoking-related DNA adducts as potential diagnostic markers of lung cancer: new perspectives.

    PubMed

    Grigoryeva, E S; Kokova, D A; Gratchev, A N; Cherdyntsev, E S; Buldakov, M A; Kzhyshkowska, J G; Cherdyntseva, N V

    2015-03-01

    In recent years, the new direction such as identification of informative circulating markers reflecting molecular genetic changes in the DNA of tumor cells was actively developed. Smoking-related DNA adducts are very promising research area, since they indicate high pathogenetic importance in the lung carcinogenesis and can be identified in biological samples with high accuracy and reliability using highly sensitive mass spectrometry methods (TOF/TOF, TOF/MS, MS/MS). The appearance of DNA adducts in blood or tissues is the result of the interaction of carcinogenic factors, such as tobacco constituents, and the body reaction which is determined by individual characteristics of metabolic and repair systems. So, DNA adducts may be considered as a cumulative mirror of heterogeneous response of different individuals to smoking carcinogens, which finally could determine the risk for lung cancer. This review is devoted to analysis of the role of DNA adducts in lung carcinogenesis in order to demonstrate their usefulness as cancer associated markers. Currently, there are some serious limitations impeding the widespread use of DNA adducts as cancer biomarkers, due to failure of standardization of mass spectrometry analysis in order to correctly measure the adduct level in each individual. However, it is known that all DNA adducts are immunogenic, their accumulation over some threshold concentration leads to the appearance of long-living autoantibodies. Thus, detection of an informative pattern of autoantibodies against DNA adducts using innovative multiplex ELISA immunoassay may be a promising approach to find lung cancer at an early stage in high-risk groups (smokers, manufacturing workers, urban dwellers).

  8. Assessment of four molecular markers as potential DNA barcodes for red algae Kappaphycus Doty and Eucheuma J. Agardh (Solieriaceae, Rhodophyta).

    PubMed

    Tan, Ji; Lim, Phaik-Eem; Phang, Siew-Moi; Hong, Dang Diem; Sunarpi, H; Hurtado, Anicia Q

    2012-01-01

    DNA barcoding has been a major advancement in the field of taxonomy, seeing much effort put into the barcoding of wide taxa of organisms, macro and microalgae included. The mitochondrial-encoded cox1 and plastid-encoded rbcL has been proposed as potential DNA barcodes for rhodophytes, but are yet to be tested on the commercially important carrageenophytes Kappaphycus and Eucheuma. This study gauges the effectiveness of four markers, namely the mitochondrial cox1, cox2, cox2-3 spacer and the plastid rbcL in DNA barcoding on selected Kappaphycus and Eucheuma from Southeast Asia. Marker assessments were performed using established distance and tree-based identification criteria from earlier studies. Barcoding patterns on a larger scale were simulated by empirically testing on the commonly used cox2-3 spacer. The phylogeny of these rhodophytes was also briefly described. In this study, the cox2 marker which satisfies the prerequisites of DNA barcodes was found to exhibit moderately high interspecific divergences with no intraspecific variations, thus a promising marker for the DNA barcoding of Kappaphycus and Eucheuma. However, the already extensively used cox2-3 spacer was deemed to be in overall more appropriate as a DNA barcode for these two genera. On a wider scale, cox1 and rbcL were still better DNA barcodes across the rhodophyte taxa when practicality and cost-efficiency were taken into account. The phylogeny of Kappaphycus and Eucheuma were generally similar to those earlier reported. Still, the application of DNA barcoding has demonstrated our relatively poor taxonomic comprehension of these seaweeds, thus suggesting more in-depth efforts in taxonomic restructuring as well as establishment.

  9. Assessment of Four Molecular Markers as Potential DNA Barcodes for Red Algae Kappaphycus Doty and Eucheuma J. Agardh (Solieriaceae, Rhodophyta)

    PubMed Central

    Tan, Ji; Lim, Phaik-Eem; Phang, Siew-Moi; Hong, Dang Diem; Sunarpi, H.; Hurtado, Anicia Q.

    2012-01-01

    DNA barcoding has been a major advancement in the field of taxonomy, seeing much effort put into the barcoding of wide taxa of organisms, macro and microalgae included. The mitochondrial-encoded cox1 and plastid-encoded rbcL has been proposed as potential DNA barcodes for rhodophytes, but are yet to be tested on the commercially important carrageenophytes Kappaphycus and Eucheuma. This study gauges the effectiveness of four markers, namely the mitochondrial cox1, cox2, cox2-3 spacer and the plastid rbcL in DNA barcoding on selected Kappaphycus and Eucheuma from Southeast Asia. Marker assessments were performed using established distance and tree-based identification criteria from earlier studies. Barcoding patterns on a larger scale were simulated by empirically testing on the commonly used cox2-3 spacer. The phylogeny of these rhodophytes was also briefly described. In this study, the cox2 marker which satisfies the prerequisites of DNA barcodes was found to exhibit moderately high interspecific divergences with no intraspecific variations, thus a promising marker for the DNA barcoding of Kappaphycus and Eucheuma. However, the already extensively used cox2-3 spacer was deemed to be in overall more appropriate as a DNA barcode for these two genera. On a wider scale, cox1 and rbcL were still better DNA barcodes across the rhodophyte taxa when practicality and cost-efficiency were taken into account. The phylogeny of Kappaphycus and Eucheuma were generally similar to those earlier reported. Still, the application of DNA barcoding has demonstrated our relatively poor taxonomic comprehension of these seaweeds, thus suggesting more in-depth efforts in taxonomic restructuring as well as establishment. PMID:23285223

  10. Label-free visualization of collagen in submucosa as a potential diagnostic marker for early detection of colorectal cancer

    NASA Astrophysics Data System (ADS)

    Qiu, Jingting; Yang, Yinghong; Jiang, Weizhong; Feng, Changyin; Chen, Zhifen; Guan, Guoxian; Zhu, Xiaoqin; Zhuo, Shuangmu; Chen, Jianxin

    2014-09-01

    The collagen signature in colorectal submucosa is changed due to remodeling of the extracellular matrix during the malignant process and plays an important role in noninvasive early detection of human colorectal cancer. In this work, multiphoton microscopy (MPM) was used to monitor the changes of collagen in normal colorectal submucosa (NCS) and cancerous colorectal submucosa (CCS). What's more, the collagen content was quantitatively measured. It was found that in CCS the morphology of collagen becomes much looser and the collagen content is significantly reduced compared to NCS. These results suggest that MPM has the ability to provide collagen signature as a potential diagnostic marker for early detection of colorectal cancer.

  11. KAI-1 and p53 expression in oral squamous cell carcinomas: Markers of significance in future diagnostics and possibly therapeutics

    PubMed Central

    Patil, Namrata N; Wadhwan, Vijay; Chaudhary, Minal; Nayyar, Abhishek Singh

    2016-01-01

    Context: KAI-1/CD82 is a tumor suppressor gene with decreased gene expression being associated with increased invasive ability of oral squamous cell carcinomas (OSCCs). p53 protein functions in the G1-S phase of the cell cycle to allow repair of damaged DNA. In the present study, p53 and KAI-1 expression was investigated using monoclonal antibodies in OSCC. Aims: The aim of this study was to detect KAI-1 and p53 expression in OSCCs and to assess the relation between both in OSCCs. Materials and Methods: The present study included histopathologically diagnosed thirty cases of well- and moderately differentiated OSCCs to study the expression of KAI-1 and p53 antibodies. Statistical Analysis: The results obtained were tabulated and statistically analyzed using descriptive statistical analysis; one-way ANOVA; least square difference method and independent t-test. Results: OSCCs exhibited 41.62% positivity for KAI-1 while p53 positive cells were recorded to an extent of 60.82%. A significant positive correlation was observed between KAI-1 and p53 expression in OSCCs. Conclusions: Although a significant amount of work is still required to uncover the mechanisms of action and regulation of KAI-1 and p53 expression, control of the complex metastatic processes would be of interest in controlling the tumor biology in OSCCs as well as other types of malignancies to enhance prognosis in the affected patients and to help protect against future metastasis in the going to be treated and treated patients. PMID:27721601

  12. Early loss of mitochondrial inner transmembrane potential in khat-induced cell death of primary normal human oral cells.

    PubMed

    Lukandu, Ochiba M; Bredholt, Therese; Neppelberg, Evelyn; Gjertsen, Bjørn T; Johannessen, Anne C; Vintermyr, Olav K; Costea, Daniela Elena

    2009-09-19

    Previous studies suggest the use of khat, a psychostimulant plant used by millions of people in Middle East and Africa, as risk factor for oral cancer. We previously reported that khat is able to induce adverse affects, as cell cycle arrest and apoptosis, in normal human oral cells cultured in vitro. This study further investigates the more specific role played by mitochondria in khat-induced cell death and the kinetics of the events involved in this process. Exposure of primary normal human oral keratinocytes and fibroblasts to khat extract resulted in a swift and sustained decrease of the mitochondrial inner transmembrane potential occurring within 0.5-1h. Loss of mitochondrial membrane potential preceded all other biochemical and morphologic changes, and was associated with a significant decrease in cell survival. Subsequently, apoptosis-inducing factor was released from mitochondria into cytosol and relocated to nucleus. Cyclosporine A and bongkrekic acid delayed both the loss of mitochondrial inner transmembrane potential and the onset of cell death. This study describes a novel mechanism of khat-induced cell death in primary normal oral keratinocytes and fibroblasts involving an early pivotal effect on mitochondrial function and integrity.

  13. 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

  14. Solid lipid nanoparticles (SLN)--based hydrogels as potential carriers for oral transmucosal delivery of risperidone: preparation and characterization studies.

    PubMed

    Silva, A C; Amaral, M H; González-Mira, E; Santos, D; Ferreira, D

    2012-05-01

    Two different solid lipid nanoparticles (SLN)-based hydrogels (HGs) formulations were developed as potential mucoadhesive systems for risperidone (RISP) oral transmucosal delivery. The suitability of the prepared semi-solid formulations for application on oral mucosa was assessed by means of rheological and textural analysis, during 30 days. Plastic flows with thixotropy and high adhesiveness were obtained for all the tested systems, which predict their success for the oral transmucosal application proposed. The SLN remained within the colloidal range after HGs preparation. However, after 30 days of storage, a particle size increase was detected in one type of the HGs formulations. In vitro drug release studies revealed a more pronounced RISP release after SLN hydrogel entrapment, when compared to the dispersions alone. In addition, a pH-dependent release was observed as well. The predicted in vivo RISP release mechanism was Fickian diffusion alone or combined with erosion.

  15. The chloroplast DNA locus psbZ-trnfM as a potential barcode marker in Phoenix L. (Arecaceae).

    PubMed

    Ballardini, Marco; Mercuri, Antonio; Littardi, Claudio; Abbas, Summar; Couderc, Marie; Ludeña, Bertha; Pintaud, Jean-Christophe

    2013-12-30

    The genus Phoenix (Arecaceae) comprises 14 species distributed from Cape Verde Islands to SE Asia. It includes the economically important species Phoenix dactylifera. The paucity of differential morphological and anatomical useful characters, and interspecific hybridization, make identification of Phoenix species difficult. In this context, the development of reliable DNA markers for species and hybrid identification would be of great utility. Previous studies identified a 12 bp polymorphic chloroplast minisatellite in the trnG (GCC)-trnfM (CAU) spacer, and showed its potential for species identification in Phoenix. In this work, in order to develop an efficient DNA barcode marker for Phoenix, a longer cpDNA region (700 bp) comprising the mentioned minisatellite, and located between the psbZ and trnfM (CAU) genes, was sequenced. One hundred and thirty-six individuals, representing all Phoenix species except P. andamanensis,were analysed. The minisatellite showed 2-7 repetitions of the 12 bp motif, with 1-3 out of seven haplotypes per species. Phoenix reclinata and P. canariensis had species-specific haplotypes. Additional polymorphisms were found in the flanking regions of the minisatellite, including substitutions, indels and homopolymers. All this information allowed us to identify unambiguously eight out of the 13 species, and overall 80% of the individuals sampled. Phoenix rupicola and P. theophrasti had the same haplotype, and so had P. atlantica, P. dactylifera, and P. sylvestris (the "date palm complex" sensu Pintaud et al. 2013). For these species, additional molecular markers will be required for their unambiguous identification. The psbZ-trnfM (CAU) region therefore could be considered as a good basis for the establishment of a DNA barcoding system in Phoenix, and is potentially useful for the identification of the female parent in Phoenix hybrids.

  16. Potential of optical coherence tomography for early diagnosis of oral malignancies

    PubMed Central

    DeCoro, Michael; Wilder-Smith, Petra

    2014-01-01

    With nearly 1,500,000 new patients diagnosed every year in the USA, cancer poses a considerable challenge to healthcare today. Oral cancer is responsible for a sizeable portion of deaths due to cancer, primarily because it is diagnosed at a late stage when the prognosis is poor. Current methods for diagnosing oral cancer need to be augmented by better early detection, monitoring and screening modalities. A new approach is needed that provides real-time, accurate, noninvasive diagnosis. The results of early clinical trials using in vivo optical coherence tomography for the diagnosis of oral dysplasia and malignancy are encouraging. PMID:20214513

  17. Personality traits as potential susceptibility markers: differential susceptibility to support among parents.

    PubMed

    Slagt, Meike; Dubas, Judith Semon; Denissen, Jaap J A; Deković, Maja; van Aken, Marcel A G

    2015-04-01

    In this study, we examined whether parents are differentially susceptible to support from their spouse and adolescent child depending on their personality traits, and whether differences in susceptibility to support among parents, in turn, are linked to the quality of support parents give to their children. Participants in this three-wave longitudinal study were 288 two-parent Dutch families with an adolescent child. Fathers were on average 43.9 years old (SD = 3.7 years), mothers were 41.7 years old (SD = 3.3 years), and adolescents (50% girls) were 14.5 years old (SD = 0.8 years). We found that the association between support from children toward their parents and subsequent support from parents toward their children was more pronounced for parents high on Openness, for better and for worse. Extraversion, Agreeableness, Conscientiousness, and Emotional Stability did not emerge as markers of differences in susceptibility. Also, parents did not differ in their susceptibility to support from their spouse, nor were differences in susceptibility found a year later when using data from a third wave. We found very modest support for differential susceptibility, only for Openness, and depending on the source of perceived support and on the timing of measurement.

  18. Mutations in p53 as potential molecular markers for human breast cancer

    SciTech Connect

    Runnebaum, I.B.; Nagarajan, M.; Bowman, M.; Soto, D.; Sukumar, S. )

    1991-12-01

    Based on the high incidence of loss of heterozygosity for loci on chromosome 17p in the vicinity of the p53 locus in human breast tumors. The authors investigated the frequency and effects of mutations in the p53 tumor suppressor gene in mammary neoplasia. They examined the p53 gene in 20 breast cancer cell lines and 59 primary breast tumors. Northern blot analysis, immunoprecipitation, and nucleotide sequencing analysis revealed aberrant mRNA expression, over-expression of protein, and point mutations in the p53 gene in 50% of the cell line tested. A multiplex PCR assay was developed to search for deletions in the p53 genomic locus. Multiplex PCR of genomic DNA showed that up to 36% of primary tumors contained aberrations in the p53 locus. Mutations in exons 5-9 of the p53 gene were found in 10 out of 59 (17%) of the primary tumors studied by single-stranded conformation polymorphism analysis. They conclude that, compared to amplification of HER2/NEU, MYC, or INT2 oncogene loci, p53 gene mutations and deletions are the most frequently observed genetic change in breast cancer related to a single gene. Correlated to disease status, p53 gene mutations could prove to be a valuable marker for diagnosis and/or prognosis of breast neoplasia.

  19. MicroRNA-155 is a potential molecular marker of natural killer/T-cell lymphoma

    PubMed Central

    Huang, Ruixia; Li, Lifeng; Wang, Xinhua; Li, Ling; Fu, Xiaorui; Sun, Zhenchang; Li, Zhaoming; Chen, Qingjiang; Zhang, Mingzhi

    2016-01-01

    Natural killer/T-cell lymphoma (NKTCL) is characterized by its highly aggressive nature and rapid progression. MicroRNAs (miRNAs) play key roles in the development of NKTCL. We utilized next-generation Solexa high-throughput sequencing to compare miRNA expression in the SNK-6 and YTS NKTCL cell lines with expression in normal NK cells. We found that 195 miRNAs were upregulated in the SNK-6 cells and 286 miRNAs were upregulated in the YTS cells. Based on those results, we selected six miRNAs, including miRNA-155, and confirmed their expression using real-time polymerase chain reaction. Expression of miRNA-155 was higher in SNK-6 and YKS cells than in normal NK cells. We next determined the levels of miRNA-155 in the serum of healthy individuals and NKTCL patients, and correlated its expression with clinical parameters and inflammatory factors detected using enzyme-linked immunoabsorbent assays. Levels of miRNA-155 were higher in NKTCL patients’ serum than in serum from healthy individuals. miRNA-155 expression was higher in patients with stable or progressive disease (SD+PD) than in those with partial or complete remission (PR+CR). While further studies are needed to clarify the underlying molecular mechanisms, it appears miRNA-155 may be a molecular marker of NKTCL. PMID:27462776

  20. Basal cytokeratin as a potential marker of low risk of invasion in ductal carcinoma in situ

    PubMed Central

    Aguiar, Fernando N.; Mendes, Henrique N.; Cirqueira, Cinthya S.; Bacchi, Carlos E.; Carvalho, Filomena M.

    2013-01-01

    OBJECTIVES: Biological markers that predict the development of invasive breast cancer are needed to improve personalized therapy for patients diagnosed with ductal carcinoma in situ. We investigated the role of basal cytokeratin 5/6 in the risk of invasion in breast ductal carcinoma in situ. METHODS: We constructed tissue microarrays using 236 ductal carcinoma in situ samples: 90 pure samples (group 1) and 146 samples associated with invasive carcinoma (group 2). Both groups had similar nuclear grades and were obtained from patients of similar ages. The groups were compared in terms of estrogen (ER) and progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER2) expression, cytokeratin 5/6 immunostaining, human epidermal growth factor receptor 1 (EGFR) membrane staining and molecular subtype, as indicated by their immunohistochemistry profiles. RESULTS: ER/PR-negative status was predictive of invasion, whereas HER2 superexpression and cytokeratin 5/6-positive status were negatively associated with invasion. Among the high-grade ductal carcinoma in situ cases, a triple-positive profile (positive for estrogen receptor, progesterone receptor, and HER2) and cytokeratin 5/6 expression by neoplastic cells were negatively associated with invasion. In the low-grade ductal carcinoma in situ subgroup, only cytokeratin 5/6 expression exhibited a negative association with the probability of invasion. CONCLUSION: The immunohistochemical expression of cytokeratin 5/6 by ductal carcinoma in situ epithelial cells may provide clinically useful information regarding the risk of progression to invasive disease. PMID:23778411

  1. Investigating the potential of fluorescent fingerprint powders as a marker for blow fly larvae (Diptera: calliphoridae).

    PubMed

    Rosati, Jennifer Y; Robinson, Scott D; Devine, Richard

    2015-05-01

    Four fluorescent fingerprint powders (RedWop(™) , GreenWop(™) , Basic Yellow(™) , and Yellow Powder(™) ) were evaluated as a marker for blow fly larvae. Administration methods included ingestion (high vs. low concentration) or topical. Ingestion of high concentrations of Basic Yellow(™) and RedWop(™) caused higher larval mortality. Basic Yellow(™) delayed development and adult emergence while RedWop(™) and Yellow Powder(™) had a significant effect on particular stages of development, however, emergence time was not altered. Optimal administration is through ingestion at low concentration levels (<10%) or topically, with GreenWop(™) demonstrating minimal adverse effects. Optimum wavelength for discrimination between powders was 450 nm. This research can aid in investigative training to increase visibility of larval and pupal blow flies. It can also be used in entomological studies to differentiate between larval blow flies (or other dipteran) species or individuals to further understand complex interactions and behavior during larval development.

  2. Antibodies to endothelial cells in systemic lupus erythematosus: a potential marker for nephritis and vasculitis.

    PubMed

    D'Cruz, D P; Houssiau, F A; Ramirez, G; Baguley, E; McCutcheon, J; Vianna, J; Haga, H J; Swana, G T; Khamashta, M A; Taylor, J C

    1991-08-01

    Using an ELISA, anti-endothelial cell antibodies (AECA) have been found in sera obtained at the time of renal biopsy in 46 out of 57 patients (81%) with systemic lupus erythematosus (SLE) and nephritis (mean binding index (BI) = 84% +/- 52.8) compared with 22 out of 50 SLE patients (44%) without nephritis (mean BI = 45% +/- 35.9). Seventy normal human sera had a mean BI of 10% +/- 9.8. The highest levels were seen in patients with diffuse proliferative glomerulonephritis (WHO grade IV) and in patients with proteinuria and nephrotic syndrome. When the biopsies were assessed for activity and chronicity scores, AECA were associated with active renal lesions (P less than 0.001). AECA levels correlated with low complement levels but not with anti-DNA antibodies to extractable nuclear antigens (ENA), anti-cardiolipin or anti-neutrophil cytoplasmic antibodies. The presence of AECA conferred a positive predictive value of 0.68 for the presence of nephritis. Twenty-five patients had active vasculitis at the time of assay and the highest AECA values were seen in patients with both nephritis and vasculitis. No correlation was seen with serum immunoglobulin levels and immune complexes did not bind significantly to the endothelial surface. The possible role of these antibodies as a marker in lupus nephritis is discussed.

  3. Gene Expression Changes in Developing Zebrafish as Potential Markers for Rapid Developmental Neurotoxicity Screening

    EPA Science Inventory

    Sparse information exists on many chemicals to guide developmental neurotoxicity (DNT) risk assessments. As DNT testing using rodents is laborious and expensive, alternative species such as zebrafish are being adapted for toxicity screening. Assessing the DNT potential of chem...

  4. Volatile fingerprint of Brazilian defective coffee seeds: corroboration of potential marker compounds and identification of new low quality indicators.

    PubMed

    Toci, Aline T; Farah, Adriana

    2014-06-15

    In the present work, the volatile profiles of green and roasted Brazilian defective coffee seeds and their controls were characterised, totalling 159 compounds. Overall, defective seeds showed higher number and concentration of volatile compounds compared to those of control seeds, especially pyrazines, pyrroles and phenols. Corroborating our previous results, butyrolactone and hexanoic acid, previously considered as potential defective seeds' markers, were observed only in raw and roasted defective seeds, respectively, and not in control seeds. New compounds were suggested as potential defective seeds' markers: hexanoic acid (for raw and roasted defective seeds in general), butyrolactone (for raw defective seeds in general), and 3-ethyl-2-methyl-1,3-hexadiene (for raw black seeds); β-linalool and 2-butyl-3,5-dimethylpyrazine (for roasted defective seeds in general), and 2-pentylfuran (for roasted black seeds). Additional compounds suggested as low quality indicators were 2,3,5,6-tetramethylpyrazine,2,3-butanediol and 4-ethylguaiacol, β-linalool, 2-,3-dimethylbutyl butanoate, 2-phenylethyl acetate, 2,3-butanedione, hexanedioic acid, guaiacol, 2,3-dihydro-2-methyl-1H-benzopyrrol, 3-methylpiperidine, 2-pentylpiperidine, 3-octen-2-one, 2-octenal, 2-pentylfuran and 2-butyl-3-methylpyrazine.

  5. Hypoxia-Related Marker GLUT-1, CAIX, Proliferative Index and Microvessel Density in Canine Oral Malignant Neoplasia

    PubMed Central

    Meier, Valeria; Guscetti, Franco; Roos, Malgorzata; Ohlerth, Stefanie; Pruschy, Martin; Rohrer Bley, Carla

    2016-01-01

    For various types of tumor therapy, it is suggested that co-targeting of tumor microenvironment, mainly tumor vasculature, mediates tumor response mechanisms. Immunohistochemistry for glucose transporter-1 (GLUT-1), carbonic anhydrase-IX (CAIX), Ki-67, and von Willebrand factor VIII for microvessel density (MVD) were performed on formalin-fixed paraffin-embedded samples of canine oral malignant neoplasms. Polarographic oxygen measurements (median pO2) and perfusion data via contrast-enhanced power Doppler ultrasound (median vascularity, median blood volume) provided additional information. Ninety-two samples were analyzed: sarcomas (n = 32), carcinomas (n = 30), and malignant melanomas (n = 30). Polarographic oxygen and perfusion data was available in 22.8% (sarcomas n = 9, carcinomas n = 7, melanomas n = 5), and 27.1% (sarcomas n = 10, carcinomas n = 8, melanomas n = 7) of cases, respectively. GLUT-1 expression was detected in 46.7% of all samples, and was generally weak. CAIX expression was found in 34.8% of all samples. Median Ki-67 score and MVD count was 19% and 17, respectively. The evaluation of the GLUT-1 score and continuous data showed significantly lower GLUT-1 levels in sarcomas (mean 5.1%, SD 6.2) versus carcinomas and melanomas (mean 16.5%/ 19.0%, SD 17.3/ 20.9, p = 0.001). The expression of CAIX correlated mildly positively with GLUT-1 (p = 0.018, rho = 0.250) as well as with Ki-67 (p = 0.014, rho = 0.295). MVD showed a significantly lower level in melanomas (mean 12.6, SD 7.7) versus sarcomas and carcinomas (mean 21.8/ 26.9, SD 13.0/20.4, p = 0.001). Median vascularity and blood volume were significantly lower in sarcomas (mean 10.4%, SD 11.0, and mean 6.3%, SD 6.5, respectively) versus carcinomas (mean 39.2%, SD 16.4 and mean 33.0%, SD 25.6, respectively) and melanomas (mean 36.0%, SD 18.3, and 31.5%, SD 24.5). Between the 3 histological groups, there was neither a significant difference in the GLUT-1 and CAIX score and continuous data, nor the Ki

  6. Hypoxia-Related Marker GLUT-1, CAIX, Proliferative Index and Microvessel Density in Canine Oral Malignant Neoplasia.

    PubMed

    Meier, Valeria; Guscetti, Franco; Roos, Malgorzata; Ohlerth, Stefanie; Pruschy, Martin; Rohrer Bley, Carla

    2016-01-01

    For various types of tumor therapy, it is suggested that co-targeting of tumor microenvironment, mainly tumor vasculature, mediates tumor response mechanisms. Immunohistochemistry for glucose transporter-1 (GLUT-1), carbonic anhydrase-IX (CAIX), Ki-67, and von Willebrand factor VIII for microvessel density (MVD) were performed on formalin-fixed paraffin-embedded samples of canine oral malignant neoplasms. Polarographic oxygen measurements (median pO2) and perfusion data via contrast-enhanced power Doppler ultrasound (median vascularity, median blood volume) provided additional information. Ninety-two samples were analyzed: sarcomas (n = 32), carcinomas (n = 30), and malignant melanomas (n = 30). Polarographic oxygen and perfusion data was available in 22.8% (sarcomas n = 9, carcinomas n = 7, melanomas n = 5), and 27.1% (sarcomas n = 10, carcinomas n = 8, melanomas n = 7) of cases, respectively. GLUT-1 expression was detected in 46.7% of all samples, and was generally weak. CAIX expression was found in 34.8% of all samples. Median Ki-67 score and MVD count was 19% and 17, respectively. The evaluation of the GLUT-1 score and continuous data showed significantly lower GLUT-1 levels in sarcomas (mean 5.1%, SD 6.2) versus carcinomas and melanomas (mean 16.5%/ 19.0%, SD 17.3/ 20.9, p = 0.001). The expression of CAIX correlated mildly positively with GLUT-1 (p = 0.018, rho = 0.250) as well as with Ki-67 (p = 0.014, rho = 0.295). MVD showed a significantly lower level in melanomas (mean 12.6, SD 7.7) versus sarcomas and carcinomas (mean 21.8/ 26.9, SD 13.0/20.4, p = 0.001). Median vascularity and blood volume were significantly lower in sarcomas (mean 10.4%, SD 11.0, and mean 6.3%, SD 6.5, respectively) versus carcinomas (mean 39.2%, SD 16.4 and mean 33.0%, SD 25.6, respectively) and melanomas (mean 36.0%, SD 18.3, and 31.5%, SD 24.5). Between the 3 histological groups, there was neither a significant difference in the GLUT-1 and CAIX score and continuous data, nor the Ki

  7. Corrosion in the oral cavity--potential local and systemic effects.

    PubMed

    Bergman, M

    1986-03-01

    The main current-generating corrosion cells in the oral cavity are the bimetallic cell and the concentration cell, the latter mainly occurring due to differences in access to oxygen in the various parts of the metallic material. Corrosion resistance is not an intrinsic property of a metal or an alloy for it depends on an interaction with the environment. Thus, the contents of the oral cavity, have a decisive influence. This implies that corrosion tests in vitro are of limited value in predicting the clinical corrosion behaviour of a metallic material. Results from a series of clinical studies concerning a possible relationship between galvanic currents and certain oral and other symptoms in a group of patients who had been referred to the Faculty of Odontology, University of Umeå, are briefly presented. The possibility of local and systemic effects of intra-oral galvanic cells is discussed.

  8. Leukocytosis after routine cranial surgery: A potential marker for brain damage in intracranial surgery

    PubMed Central

    Agrawal, Deepak; Kurwale, Nilesh; Sharma, Bhawani Shankar

    2016-01-01

    Aims and Objectives: Leukocytosis after intracranial surgery may create concern about possible infection, especially when associated with fever. Knowledge of the expected degree of leukocytosis after surgery would assist in the interpretation of leukocytosis. It was hypothesized that the degree of leukocytosis after intracranial surgery correlated with the extent of brain damage inflicted during the surgery. Materials and Methods: In this prospective study conducted over 6 months, consecutive patients undergoing either elective resections of brain tumors (having significant collateral brain damage) or aneurysm clipping (with minimal collateral brain damage) were studied. Total blood leukocyte count was checked daily in the morning for the first five postoperative days in both the groups. The mean of the leukocyte count ratio (postoperative leukocyte count/preoperative leukocyte count) on each day was calculated for each group. Results: There were 76 patients, 46 in the test group and 30 controls. Both groups were well matched in age, sex, duration of surgery, and intraoperative fluid balance. The mean leukocyte count ratio on POD1 in the tumor group was significantly higher (1.87) as compared to 1.1 in the aneurysm group (P = 0.001). This difference in the leukocyte count ratio between the groups was maintained on the second and third postoperative days, with decreasing level of significance after the third day. Conclusions: This study shows that intraoperative brain injury is associated with leukocytosis in the immediate postoperative period. This can assist in the interpretation of leukocytosis after intracranial surgeries and could be a quantitative marker for brain injury in patients undergoing intracranial surgery. PMID:27057215

  9. Autoantibodies to Ca2+ binding protein Calnuc is a potential marker in colon cancer detection.

    PubMed

    Chen, Yao; Lin, Ping; Qiu, Suimin; Peng, Xuan-Xian; Looi, Koksun; Farquhar, Marilyn Gist; Zhang, Jian-Ying

    2007-05-01

    Calnuc is a calcium (Ca2+) binding protein found in both Golgi and cytoplasm, and it may play a role in G protein- and Ca2+-regulated signal transduction events. This study was designed to investigate the possibility of whether Calnuc protein might be a tumor-associated antigen (TAA) that induces autoantibody response in human cancers, and to evaluate the feasibility of the Calnuc antigen-antibody system as a marker in cancer detection. Purified full-length recombinant Calnuc protein was used as an antigen in enzyme-linked immunoassay and Western blotting for the detection of autoantibodies in cancers. Sera from 447 patients with 9 different types of cancer were analyzed. Although the frequency of autoantibody to Calnuc was found to be 4.7% in total groups of cancer, it was not significantly different to that of normal individuals (1.2%). However, the frequency of autoantibody to Calnuc in colon cancer (11.5%) was significantly higher than that in normal individuals (1.2%). The expression analysis of Calnuc in multiple colon cancer tissues by immunohistochemistry on tissue array further confirmed the high specificity of Calnuc in colon cancer. Of 69 colon cancer tissue specimens examined, 41 tissues (59.4%) overexpressed Calnuc, while normal colon tissues did not show any expression of Calnuc. The subcellular distribution analysis of Calnuc examined by subcellular fractionation and immunofluorescence indicates that Calnuc is a membrane associated protein and mostly distributed in Golgi, which is consistent with previous reports. With adding Calnuc into a TAA array (including p53, c-myc, cyclin B1, cyclin D1), the cumulative frequency of antibody to multiple TAAs in colon cancer was raised to 65.4% which is significantly higher than the cumulative frequency in normal individuals (6.1%). This indicates that a mini-array of multiple TAAs which includes Calnuc might provide a novel non-invasive approach to enhance antibody detection for colon cancer diagnosis.

  10. Microglial CD206 Gene Has Potential as a State Marker of Bipolar Disorder

    PubMed Central

    Ohgidani, Masahiro; Kato, Takahiro A.; Haraguchi, Yoshinori; Matsushima, Toshio; Mizoguchi, Yoshito; Murakawa-Hirachi, Toru; Sagata, Noriaki; Monji, Akira; Kanba, Shigenobu

    2017-01-01

    The pathophysiology of bipolar disorder, especially the underlying mechanisms of the bipolarity between manic and depressive states, has yet to be clarified. Microglia, immune cells in the brain, play important roles in the process of brain inflammation, and recent positron emission tomography studies have indicated microglial overactivation in the brain of patients with bipolar disorder. We have recently developed a technique to induced microglia-like (iMG) cells from peripheral blood (monocytes). We introduce a novel translational approach focusing on bipolar disorder using this iMG technique. We hypothesize that immunological conditional changes in microglia may contribute to the shift between manic and depressive states, and thus we herein analyzed gene profiling patterns of iMG cells from three patients with rapid cycling bipolar disorder during both manic and depressive states, respectively. We revealed that the gene profiling patterns are different between manic and depressive states. The profiling pattern of case 1 showed that M1 microglia is dominant in the manic state compared to the depressive state. However, the patterns of cases 2 and 3 were not consistent with the pattern of case 1. CD206, a mannose receptor known as a typical M2 marker, was significantly downregulated in the manic state among all three patients. This is the first report to indicate the importance of shifting microglial M1/M2 characteristics, especially the CD206 gene expression pattern between depressive and manic states. Further translational studies are needed to dig up the microglial roles in the underlying biological mechanisms of bipolar disorder. PMID:28119691

  11. Marker-Trait Association for Biomass Yield of Potential Bio-fuel Feedstock Miscanthus sinensis from Southwest China

    PubMed Central

    Nie, Gang; Huang, Linkai; Zhang, Xinquan; Taylor, Megan; Jiang, Yiwei; Yu, Xiaoqing; Liu, Xinchun; Wang, Xinyu; Zhang, Yajie

    2016-01-01

    As a great potential bio-fuel feedstock, the genus Miscanthus has been widely studied around the world, especially Miscanthus × giganteus owing to its high biomass yield in Europe and North America. However, the narrow genetic basis and sterile characteristics of M. × giganteus have become a limitation for utilization and adaptation to extreme climate conditions. In this study, we focused on one of the progenitors of M. × giganteus, Miscanthus sinensis, which was originally distributed in East Asia with abundant genetic resources and comparable biomass yield potential to M. × giganteus in some areas. A collection of 138 individuals was selected for conducting a 3-year trial of biomass production and analyzed by using 104 pairs of SRAP, ISAP, and SSR primers for genetic diversity as well as marker-trait association. Significant differences in biomass yield and related traits were observed among individuals. Tiller number, fresh biomass yield per plant and dry biomass yield per plant had a high level of phenotypic variation among individuals and the coefficient of variation were all above 40% in 2011, 2012, and 2013. The majority of the traits had a significant correlation with the biomass yield except for the length and width of flag leaves. Plant height was a highly stable trait correlated with biomass yield. A total of 1059 discernible loci were detected by markers across individuals. The population structure (Q) and cluster analyses identified three subpopulations in the collection and family relative kinship (K) represented high gene flow among M. sinensis populations from Southwest China. Model testing identified that Q+K was the best model for describing the associations between the markers and traits, compared to the simple linear, Q or K model. Using the Q+K model, 12 significant associations (P < 0.001) were identified including four markers with plant height and one with biomass yield. Such associations would serve an efficient tool for an early

  12. Marker-Trait Association for Biomass Yield of Potential Bio-fuel Feedstock Miscanthus sinensis from Southwest China.

    PubMed

    Nie, Gang; Huang, Linkai; Zhang, Xinquan; Taylor, Megan; Jiang, Yiwei; Yu, Xiaoqing; Liu, Xinchun; Wang, Xinyu; Zhang, Yajie

    2016-01-01

    As a great potential bio-fuel feedstock, the genus Miscanthus has been widely studied around the world, especially Miscanthus × giganteus owing to its high biomass yield in Europe and North America. However, the narrow genetic basis and sterile characteristics of M. × giganteus have become a limitation for utilization and adaptation to extreme climate conditions. In this study, we focused on one of the progenitors of M. × giganteus, Miscanthus sinensis, which was originally distributed in East Asia with abundant genetic resources and comparable biomass yield potential to M. × giganteus in some areas. A collection of 138 individuals was selected for conducting a 3-year trial of biomass production and analyzed by using 104 pairs of SRAP, ISAP, and SSR primers for genetic diversity as well as marker-trait association. Significant differences in biomass yield and related traits were observed among individuals. Tiller number, fresh biomass yield per plant and dry biomass yield per plant had a high level of phenotypic variation among individuals and the coefficient of variation were all above 40% in 2011, 2012, and 2013. The majority of the traits had a significant correlation with the biomass yield except for the length and width of flag leaves. Plant height was a highly stable trait correlated with biomass yield. A total of 1059 discernible loci were detected by markers across individuals. The population structure (Q) and cluster analyses identified three subpopulations in the collection and family relative kinship (K) represented high gene flow among M. sinensis populations from Southwest China. Model testing identified that Q+K was the best model for describing the associations between the markers and traits, compared to the simple linear, Q or K model. Using the Q+K model, 12 significant associations (P < 0.001) were identified including four markers with plant height and one with biomass yield. Such associations would serve an efficient tool for an early

  13. Investigation of the potential of Raman spectroscopy for oral cancer detection in surgical margins.

    PubMed

    Cals, Froukje L J; Bakker Schut, Tom C; Hardillo, José A; Baatenburg de Jong, Robert J; Koljenović, Senada; Puppels, Gerwin J

    2015-10-01

    The poor prognosis of oral cavity squamous cell carcinoma (OCSCC) patients is associated with residual tumor after surgery. Raman spectroscopy has the potential to provide an objective intra-operative evaluation of the surgical margins. Our aim was to understand the discriminatory basis of Raman spectroscopy at a histological level. In total, 127 pseudo-color Raman images were generated from unstained thin tissue sections of 25 samples (11 OCSCC and 14 healthy) of 10 patients. These images were clearly linked to the histopathological evaluation of the same sections after hematoxylin and eosin-staining. In this way, Raman spectra were annotated as OCSCC or as a surrounding healthy tissue structure (i.e., squamous epithelium, connective tissue (CT), adipose tissue, muscle, gland, or nerve). These annotated spectra were used as input for linear discriminant analysis (LDA) models to discriminate between OCSCC spectra and healthy tissue spectra. A database was acquired with 88 spectra of OCSCC and 632 spectra of healthy tissue. The LDA models could distinguish OCSCC spectra from the spectra of adipose tissue, nerve, muscle, gland, CT, and squamous epithelium in 100%, 100%, 97%, 94%, 93%, and 75% of the cases, respectively. More specifically, the structures that were most often confused with OCSCC were dysplastic epithelium, basal layers of epithelium, inflammation- and capillary-rich CT, and connective and glandular tissue close to OCSCC. Our study shows how well Raman spectroscopy enables discrimination between OCSCC and surrounding healthy tissue structures. This knowledge supports the development of robust and reliable classification algorithms for future implementation of Raman spectroscopy in clinical practice.

  14. The potential of immobilized artificial membrane chromatography to predict human oral absorption.

    PubMed

    Tsopelas, Fotios; Vallianatou, Theodosia; Tsantili-Kakoulidou, Anna

    2016-01-01

    The potential of immobilized artificial membrane (IAM) chromatography to estimate human oral absorption (%HOA) was investigated. For this purpose, retention indices on IAM stationary phases reported previously by our group or measured by other authors under similar conditions were used to model %HOA data, compiled from literature sources. Considering the pH gradient in gastrointestinal tract, the highest logkw(IAM) values were considered, obtained either at pH7.4 or 5.5, defined as logkw(IAM)(best). Non linear models were established upon introduction of additional parameters and after exclusion of drugs which are substrates either to efflux or uptake transporters. The best model included Abraham's hydrogen-bond acidity parameter, molecular weight as well as the positively and negatively charged molecular fractions. For reasons of comparison between IAM chromatography and traditional lipophilicity, corresponding models were derived by replacing IAM retention factors with octanol-water distribution coefficients (logD). An overexpression of electrostatic interactions with phosphate anions was observed in the case of IAM retention as expressed by the negative contribution of the positively charged fraction F(+). The same parameter is statistically significant also in the logD model, but with a positive sign, indicating the attraction of basic drugs in the negatively charged inner membrane. To validate the obtained models a blind test set of 22 structurally diverse drugs was used, whose logkw(IAM)(best) values were determined and analyzed in the present study under similar conditions. IAM retention factors were further compared with MDCK cell lines permeability data taken from literature for a set of validation drugs. The overexpression of electrostatic interactions with phosphate anions on IAM surface was also evident in respect to MDCK permeability. In contrast to the clear classification between drugs with high and poor (or intermediate) absorption provided by MDCK

  15. Mesenchymal stem cells from the oral cavity and their potential value in tissue engineering.

    PubMed

    Sanz, Antonio R; Carrión, Flavio S; Chaparro, Alejandra P

    2015-02-01

    Periodontal disease is one of the most common conditions affecting humans, and current treatment strategies, which focus on the removal and long-term control of dental plaque, are generally successful in eliminating active disease and promoting tissue repair. However, regeneration of the supporting structures of the tooth remains an elusive goal and a challenge. The formation of new bone and cementum with supportive periodontal ligament is the ultimate objective, but current regeneration therapies are incapable of achieving this in a predictable way. The regeneration of periodontal tissue requires a combination of fundamental events, such as appropriate level and sequencing of regulatory signals, the presence of progenitor cells, an extracellular matrix or carrier and an adequate blood supply. Based on tissue-engineering concepts, the regeneration process may be modulated by manipulating the signaling pathways of regulatory molecules, the extracellular matrix or scaffold, or the cellular components. The identification of mesenchymal stem cells from bone marrow started a new era in regenerative medicine. Tissue engineering using mesenchymal stem cells became a therapeutic option with several advantages, including high-quality regeneration of damaged tissues without the formation of fibrous tissue, minimal donor-site morbidity compared with autografts and a low risk of autoimmune rejection and disease transmission. The aim of this review was to describe the main sources of mesenchymal stem cells from tissues in the oral cavity and the potential of these cells in regenerative therapy. Special attention is paid to gingival tissue-derived mesenchymal stem cells because they represent the most accessible source of stem cells in the human mouth.

  16. Potential for Metabolomics-Based Markers of Exposure:Encouraging Evidence from Studies using Model Organisms

    EPA Science Inventory

    Genomic techniques (transcriptomics, proteomics, and metabolomics) have the potential to significantly improve the way chemical risk is managed in the 21st century. Indeed, a significant amount of research has been devoted to the use of these techniques to screen chemicals for h...

  17. Is poor oral health a risk marker for incident cardiovascular disease hospitalisation and all-cause mortality? Findings from 172 630 participants from the prospective 45 and Up Study

    PubMed Central

    Joshy, Grace; Arora, Manish; Korda, Rosemary J; Chalmers, John; Banks, Emily

    2016-01-01

    Objective To investigate the relationship between oral health and incident hospitalisation for ischaemic heart disease (IHD), heart failure (HF), ischaemic stroke and peripheral vascular disease (PVD) and all-cause mortality. Design Prospective population-based study of Australian men and women aged 45 years or older, who were recruited to the 45 and Up Study between January 2006 and April 2009; baseline questionnaire data were linked to hospitalisations and deaths up to December 2011. Study exposures include tooth loss and self-rated health of teeth and gums at baseline. Setting New South Wales, Australia. Participants Individuals aged 45–75 years, excluding those with a history of cancer/cardiovascular disease (CVD) at baseline; n=172 630. Primary outcomes Incident hospitalisation for IHD, HF, ischaemic stroke and PVD and all-cause mortality. Results During a median follow-up of 3.9 years, 3239 incident hospitalisations for IHD, 212 for HF, 283 for ischaemic stroke and 359 for PVD, and 1908 deaths, were observed. Cox proportional hazards models examined the relationship between oral health indicators and incident hospitalisation for CVD and all-cause mortality, adjusting for potential confounding factors. All-cause mortality and incident CVD hospitalisation risk increased significantly with increasing tooth loss for all outcomes except ischaemic stroke (ptrend<0.05). In those reporting no teeth versus ≥20 teeth left, risks were increased for HF (HR, 95% CI 1.97, 1.27 to 3.07), PVD (2.53, 1.81 to 3.52) and all-cause mortality (1.60, 1.37 to 1.87). The risk of IHD, PVD and all-cause mortality (but not HF or ischaemic stroke) increased significantly with worsening self-rated health of teeth and gums (ptrend<0.05). In those reporting poor versus very good health of teeth and gums, risks were increased for IHD (1.19, 1.03 to 1.38), PVD (1.66, 1.13 to 2.43) and all-cause mortality (1.76, 1.50 to 2.08). Conclusions Tooth loss and, to a lesser extent, self

  18. The proepicardium keeps a potential for glomerular marker expression which supports its evolutionary origin from the pronephros.

    PubMed

    Cano, Elena; Carmona, Rita; Velecela, Víctor; Martínez-Estrada, Ofelia; Muñoz-Chápuli, Ramón

    2015-01-01

    The proepicardium is the embryonic primordium of the epicardium. This transient structure is essential for cardiac development giving rise to the epicardium and supplying the heart with vascular and cardiac connective tissue progenitors. However, their nature and evolutionary origin are poorly-known. We have suggested elsewhere (Pombal et al. Evol. Dev. 10: 210-216, 2008; Cano et al., J. Dev. Biol. 1: 3-19, 2013) that the proepicardium is an evolutionary derivative of the primordium of an ancient external pronephric glomerulus, devoid of its original excretory function. In this study, we describe for the first time expression of two podocyte markers in the chick proepicardium (glepp1 and synaptopodin) and we have shown how these podocyte markers as well as the intermediate mesoderm marker Pax2 are strongly upregulated when the proepicardium is cultured with nephrogenic inducers. Retinoic acid treatment also induced in the proepicardium expression of Hoxb4, a gene which confers to intermediate mesoderm competence to respond to nephrogenic signals. Thus, a latent nephrogenic potential persists in the proepicardium and also that its original glomerular fate can be partially rescued. The transcription factor Wt1, essential for kidney and epicardial development, plays opposite roles in both tissues, inducing epithelial-mesenchymal transition in the proepicardium and promoting epithelialization in the kidneys (Essafi et al., Dev. Cell 21: 559-574, 2011). Consistently with this antithetical function of Wt1, we have observed an upregulation of podocalyxin in the epicardium of mouse embryos with conditional deletion of the Wt1 gene, while this protein is transcriptionally activated by Wt1 in podocytes.

  19. Biochemical markers and somatosensory evoked potentials in patients after cardiac arrest: the role of neurological outcome scores.

    PubMed

    Rana, Obaida R; Saygili, Erol; Schiefer, Johannes; Marx, Nikolaus; Schauerte, Patrick

    2011-06-15

    Biochemical markers, e.g. NSE or S100B, and somatosensory evoked potentials (SSEP) are considered promising candidates for neurological prognostic predictors in patients after cardiac arrest (CA). The Utstein Templates recommend the use of the Glasgow-Pittsburgh Cerebral Performance Categories (GP-CPC) to divide patients according to their neurological outcome. However, several studies investigating biochemical markers and SSEP are based on the Glasgow Outcome Score (GOS). We noticed that many studies failed to exclude patients who died without certified brain damage from patients classified as poor outcome, instead including all patients who died into this category. Therefore, we summarized the published NSE cut-off values and the derived sensitivity and specificity to predict poor outcome of those studies which only included patients with certified brain death in GOS-1 or GP-CPC-5 (group A) vs. those studies which did not differentiate between death from any cause or death due to primary brain damage (group B). On average, mean NSE cut-off values and sensitivity were higher (56 ± 35 ng/ml, 56 ± 18%) in group A than in group B (41 ± 17 ng/ml, 44 ± 25%), respectively. The specificity remained equally high in both groups. In analogy, the average sensitivity of SSEP to predict poor outcome was higher in group A (76 ± 11%) than in group B (50 ± 15%), while the specificity was similar in both groups. Conclusively, inclusion of deaths without certified brain damage after CA in neurological outcome studies will lead to underestimation of the prognostic power of biochemical or electrophysiological markers for brain damage. A modified GOS and GP-CPC score might help to avoid this bias.

  20. Assessment of Environmental and Hereditary Influence on Development of Pituitary Tumors Using Dermatoglyphic Traits and Their Potential as Screening Markers.

    PubMed

    Gradiser, Marina; Matovinovic Osvatic, Martina; Dilber, Dario; Bilic-Curcic, Ines

    2016-03-17

    The aim of this study was to assess environmental and hereditary influence on development of pituitary tumors using dermatoglyphic traits. The study was performed on 126 patients of both genders with pituitary tumors (60 non-functional and 66 functional pituitary tumor patients) in comparison to the control group of 400 phenotypically healthy individuals. Statistical analysis of quantitative and qualitative traits of digito-palmar dermatoglyphics was performed, and hormonal status was determined according to the standard protocols. Although we did not find markers that could specifically distinguish functional from non-functional tumors, we have found markers predisposing to the development of tumors in general (a small number of ridges between triradius of both hands, a smaller number of ridges between the triradius of c-d rc R), those for endocrine dysfunction (increased number of arches and reduced number of whorls, difference of pattern distribution in the I3 and I4 interdigital space), and some that could potentially be attributed to patients suffering from pituitary tumors (small number of ridges for variables FRR 5, smaller number of ridges in the FRL 4 of both hands and difference of pattern distribution at thenar of I1 and I2 interdigital space). The usage of dermatoglyphic traits as markers of predisposition of pituitary tumor development could facilitate the earlier detection of patients in addition to standard methods, and possibly earlier treatment and higher survival rate. Finally, our results are consistent with the hypothesis about multifactorial nature of pituitary tumor etiology comprised of both gene instability and environmental factors.

  1. Assessment of Environmental and Hereditary Influence on Development of Pituitary Tumors Using Dermatoglyphic Traits and Their Potential as Screening Markers

    PubMed Central

    Gradiser, Marina; Matovinovic Osvatic, Martina; Dilber, Dario; Bilic-Curcic, Ines

    2016-01-01

    The aim of this study was to assess environmental and hereditary influence on development of pituitary tumors using dermatoglyphic traits. The study was performed on 126 patients of both genders with pituitary tumors (60 non-functional and 66 functional pituitary tumor patients) in comparison to the control group of 400 phenotypically healthy individuals. Statistical analysis of quantitative and qualitative traits of digito-palmar dermatoglyphics was performed, and hormonal status was determined according to the standard protocols. Although we did not find markers that could specifically distinguish functional from non-functional tumors, we have found markers predisposing to the development of tumors in general (a small number of ridges between triradius of both hands, a smaller number of ridges between the triradius of c–d rc R), those for endocrine dysfunction (increased number of arches and reduced number of whorls, difference of pattern distribution in the I3 and I4 interdigital space), and some that could potentially be attributed to patients suffering from pituitary tumors (small number of ridges for variables FRR 5, smaller number of ridges in the FRL 4 of both hands and difference of pattern distribution at thenar of I1 and I2 interdigital space). The usage of dermatoglyphic traits as markers of predisposition of pituitary tumor development could facilitate the earlier detection of patients in addition to standard methods, and possibly earlier treatment and higher survival rate. Finally, our results are consistent with the hypothesis about multifactorial nature of pituitary tumor etiology comprised of both gene instability and environmental factors. PMID:26999178

  2. Genome-wide survey and analysis of microsatellites in the Pacific oyster genome: abundance, distribution, and potential for marker development

    NASA Astrophysics Data System (ADS)

    Wang, Jiafeng; Qi, Haigang; Li, Li; Zhang, Guofan

    2014-01-01

    Microsatellites are a ubiquitous component of the eukaryote genome and constitute one of the most popular sources of molecular markers for genetic studies. However, no data are currently available regarding microsatellites across the entire genome in oysters, despite their importance to the aquaculture industry. We present the first genome-wide investigation of microsatellites in the Pacific oyster Crassostrea gigas by analysis of the complete genome, resequencing, and expression data. The Pacific oyster genome is rich in microsatellites. A total of 604 653 repeats were identified, in average of one locus per 815 base pairs (bp). A total of 12 836 genes had coding repeats, and 7 332 were expressed normally, including genes with a wide range of molecular functions. Compared with 20 different species of animals, microsatellites in the oyster genome typically exhibited 1) an intermediate overall frequency; 2) relatively uniform contents of (A)n and (C)n repeats and abundant long (C)n repeats (≥24 bp); 3) large average length of (AG)n repeats; and 4) scarcity of trinucleotide repeats. The microsatellite-flanking regions exhibited a high degree of polymorphism with a heterozygosity rate of around 2.0%, but there was no correlation between heterozygosity and microsatellite abundance. A total of 19 462 polymorphic microsatellites were discovered, and dinucleotide repeats were the most active, with over 26% of loci found to harbor allelic variations. In all, 7 451 loci with high potential for marker development were identified. Better knowledge of the microsatellites in the oyster genome will provide information for the future design of a wide range of molecular markers and contribute to further advancements in the field of oyster genetics, particularly for molecular-based selection and breeding.

  3. Pharmacokinetics of orally administered terbinafine in African penguins (Spheniscus demersus) for potential treatment of aspergillosis.

    PubMed

    Bechert, Ursula; Christensen, J Mark; Poppenga, Robert; Le, Hang; Wyatt, Jeff; Schmitt, Todd

    2010-06-01

    The objective of this study was to determine the pharmacokinetic parameters of orally administered terbinafine hydrochloride based on 3, 7, and 15 mg/kg single- as well as multiple-dosage trials in order to calculate dosing requirements for potential treatment of aspergillosis in African penguins (Spheniscus demersus). Ten adult African penguins were used in each of these trials, with a 2-wk washout period between trials. Mean plasma concentrations of terbinafine peaked in approximately 4 hrs at 0.11 +/- 0.017 microg/ml (mean +/- SD) following administration of 3 mg/kg terbinafine, while 7 mg/kg and 15 mg/kg dosages resulted in peak plasma concentrations of 0.37 +/- 0.105 and 0.33 +/- 0.054 microg/ml, respectively. The volume of distribution increased with increasing dosages, being 37 +/- 28.5, 40 +/- 28.1, and 52 +/- 18.6 mg/L for 3, 7, and 15 mg/kg doses, respectively. The mean half-life was biphasic with initial terminal half-life (t(1/2)) values of 9.9 +/- 4.5, 17.2 +/- 4.9 and 16.9 +/- 5.4 hrs, for 3, 7, and 15 mg/kg doses, respectively. A rapid first elimination phase was followed by a slower second phase, and final elimination was estimated to be 136 +/- 9.7 and 131 +/- 9.9 hrs, for 7 and 15 mg/kg doses, respectively. Linearity was demonstrated for area under the curve but not for peak plasma concentrations for the three dosages used. Calculations based on pharmacokinetic parameter values indicate that a 15 mg/kg terbinafine q24h dosage regimen would result in steady-state trough plasma concentrations above the minimum inhibitory concentration (0.8-1.6 microg/ ml), and this dosage is recommended as a potential treatment option for aspergillosis in penguins. However, additional research is required to determine both treatment efficacy and safety.

  4. How biomarkers will change psychiatry. Part II: Biomarker selection and potential inflammatory markers of depression.

    PubMed

    Macaluso, Matthew; Drevets, Wayne C; Preskorn, Sheldon H

    2012-07-01

    Part I of this series defined biomarkers and discussed their current use in general medicine and their potential research and clinical utility in psychiatry. In this second column in the series, the authors first discuss the rationale for selecting a biomarker. The second half of the column discusses the potential use of inflammatory biomarkers in depression, with a specific focus on derivatives of the inflammatory biomarker, thromboxane, to illustrate how biomarkers can be developed for use in clinical practice. In the future, biomarkers are likely to become an integral component of psychiatric treatment, providing information about a patient's odds of developing an illness, the severity of illness, and level of response to therapeutic interventions.

  5. The metabolic impact of methamphetamine on the systemic metabolism of rats and potential markers of methamphetamine abuse.

    PubMed

    Zheng, Tian; Liu, Linsheng; Shi, Jian; Yu, Xiaoyi; Xiao, Wenjing; Sun, Runbing; Zhou, Yahong; Aa, Jiye; Wang, Guangji

    2014-07-01

    Although the stimulating and psychotropic effects of methamphetamine (METH) on the nervous system are well documented, the impact of METH abuse on biological metabolism and the turnover of peripheral transmitters are poorly understood. Metabolomics has the potential to reveal the effect of METH abuse on systemic metabolism and potential markers suggesting the underlying mechanism of toxicity. In this study, male Sprague Dawley rats were intraperitoneally injected with METH at escalating doses of mg kg(-1) for 5 consecutive days and then were withdrawn for 2 days. The metabolites in the serum and urine were profiled and the systemic effects of METH on metabolic pathways were evaluated. Multivariate statistical analysis showed that METH caused distinct deviations, whereas the withdrawal of METH restored the metabolic patterns towards baseline. METH administration elevated energy metabolism, which was manifested by the distinct depletion of branched-chain amino acids, accelerated tricarboxylic-acid cycle and lipid metabolism, reduced serum glycerol-3-phosphate, and elevated serum and urinary 3-hydroxybutyrate and urinary glycerol. In addition to the increased serum levels of the excitatory amino acids glutamate and aspartate (the inhibitory neurotransmitters in the brain), a marked decline in serum alanine and glycine after METH treatment suggested the activation and decreased inhibition of the nervous system and hence elevated nervous activity. Withdrawal of METH for 2 days efficiently restored all but a few metabolites to baseline, including serum creatinine, citrate, 2-ketoglutarate, and urinary lactate. Therefore, these metabolites are potential markers of METH use, and they may be used to facilitate the diagnosis of METH abuse.

  6. Potential Use of Salivary Markers for Longitudinal Monitoring of Inflammatory Immune Responses to Vaccination

    PubMed Central

    Garssen, Johan; Sandalova, Elena

    2016-01-01

    Vaccination, designed to trigger a protective immune response against infection, is a trigger for mild inflammatory responses. Vaccination studies can address the question of inflammation initiation, levels, and resolution as well as its regulation for respective studied pathogens. Such studies largely based on analyzing the blood components including specific antibodies and cytokines were usually constrained by number of participants and volume of collected blood sample. Hence, blood-based studies may not be able to cover the full dynamic range of inflammation responses induced by vaccination. In this review, the potential of using saliva in addition to blood for studying the kinetics of inflammatory response studies was assessed. Saliva sampling is noninvasive and has a great potential to be used for studies aimed at analysing the magnitude, time course, and variance in immune responses, including inflammation after vaccination. Based on a literature survey of inflammatory biomarkers that can be determined in saliva and an analysis of how these biomarkers could help to understand the mechanisms and dynamics of immune reactivity and inflammation, we propose that the saliva-based approach might have potential to add substantial value to clinical studies, particularly in vulnerable populations such as infants, toddlers, and ill individuals. PMID:27022211

  7. Identification of species-specific nuclear insertions of mitochondrial DNA (numts) in gorillas and their potential as population genetic markers.

    PubMed

    Soto-Calderón, Iván Darío; Clark, Nicholas Jonathan; Wildschutte, Julia Vera Halo; DiMattio, Kelly; Jensen-Seaman, Michael Ignatius; Anthony, Nicola Mary

    2014-12-01

    The first hyper-variable region (HV1) of the mitochondrial control region (MCR) has been widely used as a molecular tool in population genetics, but inadvertent amplification of nuclear translocated copies of mitochondrial DNA (numts) in gorillas has compromised the use of mitochondrial DNA in population genetic studies. At least three putative classes (I, II, III) of gorilla-specific HV1 MCR numts have been uncovered over the past decade. However, the number, size and location of numt loci in gorillas and other apes are completely unknown. Furthermore, little work to date has assessed the utility of numts as candidate population genetic markers. In the present study, we screened Bacterial Artificial Chromosome (BAC) genomic libraries in the chimpanzee and gorilla to compare patterns of mitochondrial-wide insertion in both taxa. We conducted an intensive BLAST search for numts in the gorilla genome and compared the prevalence of numt loci originating from the MCR with other great ape taxa. Additional gorilla-specific MCR numts were retrieved either through BAC library screens or using an anchored-PCR (A-PCR) amplification using genomic DNA from five unrelated gorillas. Locus-specific primers were designed to identify numt insertional polymorphisms and evaluate their potential as population genetic markers. Mitochondrial-wide surveys of chimpanzee and gorilla BACs showed that the number of numts does not differ between these two taxa. However, MCR numts are more abundant in chimpanzees than in other great apes. We identified and mapped 67 putative gorilla-specific numts, including two that contain the entire HV1 domain, cluster with sequences from two numt classes (I, IIb) and will likely co-amplify with mitochondrial sequences using most published HV1 primers. However, phylogenetic analysis coupled with post-hoc analysis of mitochondrial variation can successfully differentiate nuclear sequences. Insertional polymorphisms were evident in three out of five numts

  8. Mitosis Is a Source of Potential Markers for Screening and Survival and Therapeutic Targets in Cervical Cancer

    PubMed Central

    Espinosa, Ana María; Alfaro, Ana; Roman-Basaure, Edgar; Guardado-Estrada, Mariano; Palma, Ícela; Serralde, Cyntia; Medina, Ingrid; Juárez, Eligia; Bermúdez, Miriam; Márquez, Edna; Borges-Ibáñez, Manuel; Muñoz-Cortez, Sergio; Alcántara-Vázquez, Avissai; Alonso, Patricia; Curiel-Valdez, José; Kofman, Susana; Villegas, Nicolas; Berumen, Jaime

    2013-01-01

    The effect of preventive human papillomavirus (HPV) vaccination on the reduction of the cervical cancer (CC) burden will not be known for 30 years. Therefore, it’s still necessary to improve the procedures for CC screening and treatment. The objective of this study was to identify and characterize cellular targets that could be considered potential markers for screening or therapeutic targets. A pyramidal strategy was used. Initially the expression of 8,638 genes was compared between 43 HPV16-positive CCs and 12 healthy cervical epitheliums using microarrays. A total of 997 genes were deregulated, and 21 genes that showed the greatest deregulation were validated using qRT-PCR. The 6 most upregulated genes (CCNB2, CDC20, PRC1, SYCP2, NUSAP1, CDKN3) belong to the mitosis pathway. They were further explored in 29 low-grade cervical intraepithelial neoplasias (CIN1) and 21 high-grade CIN (CIN2/3) to investigate whether they could differentiate CC and CIN2/3 (CIN2+) from CIN1 and controls. CCNB2, PRC1, and SYCP2 were mostly associated with CC and CDC20, NUSAP1, and CDKN3 were also associated with CIN2/3. The sensitivity and specificity of CDKN3 and NUSAP1 to detect CIN2+ was approximately 90%. The proteins encoded by all 6 genes were shown upregulated in CC by immunohistochemistry. The association of these markers with survival was investigated in 42 CC patients followed up for at least 42 months. Only CDKN3 was associated with poor survival and it was independent from clinical stage (HR = 5.9, 95%CI = 1.4–23.8, p = 0.01). CDKN3 and NUSAP1 may be potential targets for the development of screening methods. Nevertheless, further studies with larger samples are needed to define the optimal sensitivity and specificity. Inhibition of mitosis is a well-known strategy to combat cancers. Therefore, CDKN3 may be not only a screening and survival marker but a potential therapeutic target in CC. However, whether it’s indispensable for tumor growth remains to be

  9. Chimeric foot-and-mouth disease viruses: evaluation of their efficacy as potential marker vaccines in cattle.

    PubMed

    Fowler, V L; Paton, D J; Rieder, E; Barnett, P V

    2008-04-07

    Previous work in pigs, has demonstrated that full protection against foot-and-mouth disease (FMD) can be achieved following vaccination with chimeric foot-and-mouth disease virus (FMDV) vaccines, in which the VP1 G-H loop had been substituted with that from another serotype. If proven to be effective in other economically important species such as cattle, such vaccine constructs could be trialed as potential marker vaccines. Here, we determine if G-H loop chimera FMDV vaccines can: (i) protect cattle from virus challenge and (ii) induce an antibody response that would enable the identification of infection, regardless of vaccination status. Inactivated, oil adjuvanated, chimeric vaccine constructs, based on the backbone sequence of the A(12)119 serotype virus, fully protected cattle from challenge 21 days post-vaccination. Differentiation assays developed for use in this study were able to identify sub-clinical infection, which in one vaccinated animal, persisted beyond day 32 post-challenge. This paper emphasises the importance of epitopes outside of the VP1 G-H loop for protective immunity in cattle, and demonstrates that chimeric FMDV vaccines could prove to be useful marker vaccines for the future.

  10. Unique cyanide adduct in human serum albumin: potential as a surrogate exposure marker.

    PubMed

    Fasco, Michael J; Stack, Robert F; Lu, Shijun; Hauer, Charles R; Schneider, Erasmus; Dailey, Michael; Aldous, Kenneth M

    2011-04-18

    Cyanide (CN = HCN + CN(-)) is a renowned poison and neurotoxicant that is prevalent throughout the environment. Despite a plethora of studies conducted over the last half century, relatively little is known of its potential to cause adverse health outcomes at sublethal exposures. CN exposure is normally determined from blood, but because CN is rapidly metabolized and cleared from this compartment (t(1/2) < 1 h), it is common for several half-lives to have passed before blood samples are drawn for analysis. This variable, coupled with a very narrow toxic index and metabolic diversity within the human population, has rendered accurate assessment of CN exposure, and consequently any predictions of possible adverse health outcomes, highly problematic. Prior studies by us showed the potential of Cys-SCN adducts within human serum albumin (HSA) to act as retrospective surrogates of CN exposure. Here, we report the discovery of a stable, SCN adduct at Cys(567) formed by the reaction of CN with the C-terminal Cys(558)Cys(567) disulfide bond of HSA. Treatment of HSA purified from human serum with base in guanidine hydrochloride releases a readily detectable, uniquely modified, C-terminal-19-mer peptide from Cys(567)-SCN moieties in all the samples examined thus far. Inclusion of a HSA-Cys(567)-S(13)C(15)N labeled internal standard permits quantitation of the Cys(567)-SCN adduct by LC-MS/MS in selective reaction monitoring (SRM) of the surrogate peptide with high sensitivity and good precision. Reaction of CN in vitro with the Cys(558)Cys(567) disulfide bond in HSA is specific, rapid, and concentration dependent within a putative, physiologically relevant range. Data from various human sera demonstrate the potential usefulness of this adduct as a biomarker of CN exposure.

  11. Potential risk of salivary-mediated viral hepatitis type B transmission from oral exposure to fomites.

    PubMed

    Osterholm, M T; Max, B J; Hanson, M; Polesky, H F

    1979-12-01

    Twelve grade school and junior high school students had oral exposures to hepatitis B surface antigen (HBsAg) positive saliva via contact with contaminated musical instruments. The 12 exposed students and 18 students who served as age and sex matched controls were tested for the presence of HBsAg and antibody to the hepatitis surface antigen (anti-HBs) at 2 weeks, 8 weeks and 6 months after exposure. All students were negative for HBsAg and anti-HBs on all dates tested and reported no illness during that time suggestive of viral hepatitis. There was no evidence of viral hepatitis, type B transmission from the exposure. The students probably experienced the maximum possible oral exposure from direct or fomites contact, since there was no cleaning of the musical instruments between use by the students and teacher. Based on these results, the risk of transmission of viral hepatitis, type B from oral contact with fomites is unlikely.

  12. Potential novel markers to discriminate between active and latent tuberculosis infection in Chinese individuals.

    PubMed

    Bai, Xue-juan; Liang, Yan; Yang, You-rong; Feng, Jin-dong; Luo, Zhan-peng; Zhang, Jun-Xian; Wu, Xue-qiong

    2016-02-01

    Latent tuberculosis infection (LTBI) constitutes the main reservoir for reactivation tuberculosis. The finding of potential biomarkers for differentiating between TB and LTBI is very necessary. In this study, the immunological characteristics and potential diagnostic utility of Rv2029c, Rv2628 and Rv1813c proteins were assessed. These three proteins stimulated PBMCs from ELISPOT-positive LTBI subjects produced higher levels of IFN-γ in comparison with TB patients and ELISPOT-negative healthy subjects (p<0.05). BCG vaccination and non-TB respiratory disease had little influence on the immunological responses of Rv2029c and Rv2628 proteins (p>0.05). The LTBI diagnostic performance of Rv2029c was higher than Rv2628 and Rv1813c by ROC evaluation. But Rv2628 had much higher specificity than Rv2029c in active TB patients and uninfected healthy subjects. The IgG level against Rv1813c was higher in the TB group than in LTBI and uninfected healthy subjects (p<0.05). These results suggest that T cell response to Rv2628 and antibody against Rv1813c might be applicable as biomarkers to distinguish TB from LTBI and uninfected individuals.

  13. ADHD and schizophrenia phenomenology: visual scanpaths to emotional faces as a potential psychophysiological marker?

    PubMed

    Marsh, Pamela J; Williams, Leanne M

    2006-01-01

    Commonalities in the clinical phenomenology and psychopharmacology of ADHD and schizophrenia are reviewed. The potential of psychostimulants to produce psychotic symptoms emphasizes the need for objective psychophysiological distinctions between these disorders. Impaired emotion perception in both disorders is discussed. It is proposed that visual scanpaths to facial expressions of emotion might prove a potentially useful psychophysiological distinction between ADHD and schizophrenia. There is consistent evidence that both facial affect recognition and scanpaths to facial expressions are impaired in schizophrenia, with emerging empirical evidence showing that facial affect recognition is impaired in ADHD also. Brain imaging studies show reduced activity in the medial prefrontal and limbic (amygdala) brain regions required to process emotional faces in schizophrenia, but suggest more localized loss of activity in these regions in ADHD. As amygdala activity in particular has been linked to effective visual scanning of face stimuli, it is postulated that condition-specific breakdowns in these brain regions that subserve emotional behavior might manifest as distinct scanpath aberrations to facial expressions of emotion in schizophrenia and ADHD.

  14. The potential of oral vaccines for disease control in wildlife species.

    PubMed

    Cross, M L; Buddle, B M; Aldwell, F E

    2007-11-01

    Numerous infectious diseases caused by bacteria or viruses persist in developed and developing countries due to ongoing transmission among wildlife reservoir species. Such diseases become the target of control and management programmes in cases where they represent a threat to public health (for example rabies, sylvatic plague, Lyme disease), or livestock production (for example bovine tuberculosis, brucellosis, pseudorabies), or where they threaten the survival of endangered animal populations. In the majority of cases, lethal control operations are neither economically feasible nor publicly supported as a practical means for disease management. Prophylactic vaccination has emerged over the last 15 years as an alternative control strategy for wildlife diseases, mainly driven by the success of widescale oral rabies vaccination programmes for meso-carnivores in North America and Northern Europe. Different methods have been trialled for the effective delivery of wildlife vaccines in the field, however oral vaccination remains the most widely used approach. Successful implementation of an oral wildlife vaccine is dependent on a combination of three components: an efficacious immunogen, a suitable delivery vehicle, and a species-specific bait. This review outlines the major wildlife disease problems for which oral vaccination is currently under consideration as a disease management tool, and also focuses on the technological challenges that face wildlife vaccine development. The major conclusion is that attenuated or recombinant live microbes represent the most widely-used vaccines that can be delivered by the oral route; this in turn places major emphasis on effective delivery systems (to maintain vaccine viability), and on selective baiting systems, as the keys to wildlife vaccine success. Oral vaccination is a valuable adjunct or alternative strategy to culling for the control of diseases which persist in wildlife reservoirs.

  15. SOCS3 tyrosine phosphorylation as a potential bio-marker for myeloproliferative neoplasms associated with mutant JAK2 kinases

    PubMed Central

    Elliott, Joanne; Suessmuth, Yvonne; Scott, Linda M.; Nahlik, Krystyna; McMullin, Mary Frances; Constantinescu, Stefan N.; Green, Anthony R.; Johnston, James A.

    2009-01-01

    JAK2 V617F, identified in the majority of patients with myeloproliferative neoplasms, tyrosine phosphorylates SOCS3 and escapes its inhibition. Here, we demonstrate that the JAK2 exon 12 mutants described in a subset of V617F-negative MPN cases, also stabilize tyrosine phosphorylated SOCS3. SOCS3 tyrosine phosphorylation was also observed in peripheral blood mononuclear cells and granulocytes isolated from patients with JAK2 H538QK539L or JAK2 F537-K539delinsL mutations. JAK kinase inhibitors, which effectively inhibited the proliferation of cells expressing V617F or K539L, also caused a dose-dependent reduction in both mutant JAK2 and SOCS3 tyrosine phosphorylation. We propose, therefore, that SOCS3 tyrosine phosphorylation may be a novel bio-marker of myeloproliferative neoplasms resulting from a JAK2 mutation and a potential reporter of effective JAK2 inhibitor therapy currently in clinical development. PMID:19229050

  16. Assessing cardiovascular risk in children with chronic kidney disease. B-type natriuretic peptide: a potential new marker.

    PubMed

    Ariceta, Gema; Brooks, Ellen R; Langman, Craig B

    2005-12-01

    Elevated plasma B-type natriuretic peptide (BNP) level is a hallmark of altered left ventricular (LV) structure and function. Measurement of circulating BNP has proved to be a sensitive and specific diagnostic test for congestive heart failure (CHF) and coronary syndrome in adults. Further, BNP levels constitute a strong predictive marker for future cardiovascular (CV) events. In high CV risk populations, such as adults with hypertension or chronic kidney disease (CKD), increased BNP predicts CV morbidity and mortality in symptomatic or asymptomatic patients. However, caution is needed in interpreting plasma BNP levels, as they increase with both age and decreased renal function. Despite increasing evidence of the value of BNP in the medical literature in adults, data in children are limited to those with congenital heart disease. It is appropriate to analyze the potential application of this tool in children with CKD, a well-known factor for CV disease.

  17. Differential proteomics of human seminal plasma: A potential target for searching male infertility marker proteins.

    PubMed

    Tomar, Anil Kumar; Sooch, Balwinder Singh; Singh, Sarman; Yadav, Savita

    2012-04-01

    The clinical fertility tests, available in the market, fail to define the exact cause of male infertility in almost half of the cases and point toward a crucial need of developing better ways of infertility investigations. The protein biomarkers may help us toward better understanding of unknown cases of male infertility that, in turn, can guide us to find better therapeutic solutions. Many clinical attempts have been made to identify biomarkers of male infertility in sperm proteome but only few studies have targeted seminal plasma. Human seminal plasma is a rich source of proteins that are essentially required for development of sperm and successful fertilization. This viewpoint article highlights the importance of human seminal plasma proteome in reproductive physiology and suggests that differential proteomics integrated with functional analysis may help us in searching potential biomarkers of male infertility.

  18. Microbial inhibition of oral epithelial wound recovery: potential role for quorum sensing molecules?

    PubMed

    De Ryck, Tine; Vanlancker, Eline; Grootaert, Charlotte; Roman, Bart I; De Coen, Laurens M; Vandenberghe, Isabel; Stevens, Christian V; Bracke, Marc; Van de Wiele, Tom; Vanhoecke, Barbara

    2015-01-01

    Awareness of the impact of microbiota in both health and disease is growing. Using a new in vitro oral mucosa co-culture model, we recently showed a clear inhibition of epithelial wound healing in the presence of an oral microbial community. In this paper, we have used the same model in combination with specific oral microbial species to obtain a better insight into the role of the oral microbiota in wound healing. Monocultures of Klebsiella oxytoca and Lactobacillus salivarius significantly inhibited wound healing with ~20%, whereas Streptococcus mitis and S. oralis enhanced the healing process with ~15% in 24 h. Yet, neither S. oralis or S. mitis were able to counteract the inhibitory effects from K. oxytoca on wound healing. Other tested microbial species had no effect on wound healing. Apart from this species-dependency, the inhibitory effect on wound healing depended on a microbial threshold concentration. Further mechanistic experiments with K. oxytoca excluded different microbial factors and hypothesized that quorum sensing molecules might play a role in the inter-kingdom signalling during wound healing. These results are important for the development of new strategies for the management of (infected) wounds and ulcerations.

  19. CO2 lasers in the management of potentially malignant and malignant oral disorders.

    PubMed

    Jerjes, Waseem; Hamdoon, Zaid; Hopper, Colin

    2012-04-30

    The CO2 laser was invented in 1963 by Kumar Patel. Since the early 1970s, CO2 laser has proved to be an effective method of treatment for patients with several types of oral lesions, including early squamous cell carcinoma.Laser surgery of oral premalignant disorders is an effective tool in a complete management strategy which includes careful clinical follow-up, patient education to eliminate risk factors, reporting and biopsying of suspicious lesions and any other significant lesions. However, in a number of patients, recurrence and progression to malignancy remains a risk. CO2 laser resection has become the preferred treatment for small oral and oropharyngeal carcinomas. Laser resection does not require reconstructive surgery. There is minimal scarring and thus, optimum functional results can be expected.New and improved applications of laser surgery in the treatment of oral and maxillofacial/head and neck disorders are being explored. As more surgeons become experienced in the use of lasers and as our knowledge of the capabilities and advantages of this tool expands, lasers may play a significant role in the management of different pathologies.

  20. Low-dose oral contraceptives: progestin potency, androgenicity, and atherogenic potential.

    PubMed

    Ellis, J

    1986-01-01

    The effects of oral contraceptives and estrogen replacement drugs on blood lipids that affect cardiovascular disease (atherogenic effects) are reviewed by comparing their androgenicity and progestin potency. Although early oral contraceptives with high doses of estrogen were indicted for increasing risk of thromboembolic disorders and heart attacks, today's pills low in estrogen still bear the same risk for cardiovascular events. A brief explanation of the lipoproteins is presented, emphasizing the importance of High Density Lipoprotein (HDL) in protecting against heart disease and stroke. Menstruating women have naturally high HDL. The estrogen in oral contraceptives and postmenopausal estrogen replacements increases HDL as much as 30%, while decreasing LDL, the component carrying most of the cholesterol. It seems that the progestin in oral contraceptives will lower HDL, and studies show that this action is related to androgenicity and dose of the progestin. Progestins such as levonorgestrel and norgestrel are more androgenic, while norethynodrel, ethynodiol diacetate and norethindrone are less so. When used in combination with estrogens, progestins are less androgenic, but when used alone, the androgenic and atherogenic effects dominate. The lower the estrogen dose in the combination, say around 20-35 mcg ethinyl estradiol, the more atherogenic the progestin. These actions are confirmed theoretically by measurements of sex hormone binding globulin, a blood protein that reflects estrogen activity, as well as by epidemiologic studies in Sweden and Great Britain, where rates of heart attack and stroke in pill users remain as high as they were when pills contained high doses of estrogen.

  1. [The potential financial impact of oral health problems in the families of preschool children].

    PubMed

    Ribeiro, Gustavo Leite; Gomes, Monalisa Cesarino; de Lima, Kenio Costa; Martins, Carolina Castro; Paiva, Saul Martins; Granville-Garcia, Ana Flávia

    2016-04-01

    The aim of the study was to evaluate the perception of parents/caregivers regarding the financial impact of oral health problems on the families of preschool children. A preschool-based, cross-sectional study was conducted with 834 preschool children in Campina Grande, Brazil. Parents/caregivers answered the Early Childhood Oral Health Impact Scale. "Financial impact" was the dependent variable. Questionnaires addressing socio-demographic variables, history of toothache and health perceptions were administered. Clinical exams were performed by three dentists previously calibrated (Kappa: 0.85-0.90). Descriptive statistics were performed, followed by logistic regression for complex samples (α = 5%). The frequency of financial impact due to oral health problems in preschool children was 7.7%. The following variables were significantly associated with financial impact: parental perception of child's oral health as poor, the interaction between history of toothache and absence of dental caries and the interaction between history of toothache and presence of dental caries. It is concluded that often parents/caregivers reported experiencing a financial impact due to seeking treatment late, mainly by the presence of toothache and complications of the clinical condition.

  2. Salivary Acetylcholinesterase Activity Is Increased in Parkinson's Disease: A Potential Marker of Parasympathetic Dysfunction

    PubMed Central

    Fedorova, Tatyana; Knudsen, Cindy Soendersoe; Mouridsen, Kim; Nexo, Ebba; Borghammer, Per

    2015-01-01

    Introduction. Decreased salivary flow and xerostomia are frequent findings in Parkinson's disease (PD), possibly caused by alterations in the parasympathetic tonus. Here we explore salivary acetylcholinesterase (AChE) activity as a potential biomarker in PD. Methods. We measured salivary flow, AChE activity, and total protein concentration in 30 PD patients and 49 healthy controls. We also performed exploratory correlation analyses with disease duration, motor symptom severity, autonomic complaints, and other nonmotor symptoms. Results. PD patients displayed significantly decreased salivary flow rate, significantly increased salivary AChE activity, and total protein concentration. Importantly, the AChE activity/total protein ratio was significantly increased in PD patients, suggesting that increased AChE activity cannot be explained solely by upconcentration of saliva. The Unified PD Rating Scale (UPDRS) score displayed significant correlation with total salivary protein (P = 0.002) and near-significant correlation with salivary flow (P = 0.07). Color vision test scores were also significantly correlated with AChE activity (P = 0.04) and total protein levels (P = 0.002). Conclusion. Salivary AChE activity is increased in PD patients compared to healthy controls. Future studies are needed to elucidate whether this parameter reflects the extent of neuronal damage and parasympathetic denervation in the salivary glands of PD patients. PMID:25767737

  3. MSRV pol sequence copy number as a potential marker of multiple sclerosis.

    PubMed

    Zawada, Mariola; Liwień, Izabela; Pernak, Monika; Januszkiewicz-Lewandowska, Danuta; Nowicka-Kujawska, Karina; Rembowska, Jolanta; Lewandowski, Krzysztof; Hertmanowska, Hanna; Wender, Mieczysław; Nowak, Jerzy

    2003-01-01

    Multiple sclerosis (MS) is a neurological disease in which demyelination in the brain and spinal cord is observed. The causal influence of bacterial/viral infections and genetic/immune factors in the etiology of multiple sclerosis is suggested. Multiple sclerosis-related retrovirus (MSRV) is one of the potential agents, which can lead to development of the disease. The aim of cytogenetic studies was assessment of MSRV pol sequence copy number in patients with MS compared to normal individuals. Cytogenetic slides with interphase nuclei and extended chromatin fibers were prepared from peripheral blood of 16 patients with MS and 10 healthy individuals. Fluorescence in situ hybridization (FISH) with biotinylated product of polymerase chain reaction was used in order to analyze MSRV pol sequence copy number in the examined material. Detection of MSRV pol probe was carried out by immunological reaction with avidin-fluorescein and biotinylated anti-avidin. MSRV pol sequence copy number was significantly greater in MS patients than in normal individuals. Using FISH technique to extended chromatin fibers, it was observed that MSRV pol exists as tandem repeats on various chromosomes. The increased number of MSRV pol sequence has been found on chromatin fibers of MS patients as compared to healthy controls.

  4. MicroRNAs in plasma and cerebrospinal fluid as potential markers for Alzheimer's disease.

    PubMed

    Kiko, Takehiro; Nakagawa, Kiyotaka; Tsuduki, Tsuyoshi; Furukawa, Katsutoshi; Arai, Hiroyuki; Miyazawa, Teruo

    2014-01-01

    The development of Alzheimer's disease (AD) biomarkers remains an unmet challenge, and new approaches that can improve current AD biomarker strategies are needed. Recent reports suggested that microRNA (miRNA) profiling of biological fluids has emerged as a diagnostic tool for several pathologic conditions. In this study, we measured six candidate miRNAs (miR-9, miR-29a, miR-29b, miR-34a, miR-125b, and miR-146a) in plasma and cerebrospinal fluid (CSF) of AD and normal subjects by using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) to evaluate their potential usability as AD biomarkers. The qRT-PCR results showed that plasma miR-34a and miR-146a levels, and CSF miR-34a, miR-125b, and miR-146a levels in AD patients were significantly lower than in control subjects. On the other hand, CSF miR-29a and miR-29b levels were significantly higher than in control subjects. Our results provide a possibility that miRNAs detected in plasma and CSF can serve as biomarkers for AD.

  5. CFTR is a potential marker for nasopharyngeal carcinoma prognosis and metastasis

    PubMed Central

    Tu, Ziwei; Chen, Qu; Zhang, Jie Ting; Jiang, Xiaohua; Xia, Yunfei; Chan, Hsiao Chang

    2016-01-01

    While there is an increasing interest in the correlation of cystic fibrosis transmembrane conductance regulator (CFTR) and cancer incidence, the role of CFTR in nasopharyngeal carcinoma (NPC) development remains unknown. In this study, we aimed to explore the prognostic value of CFTR in NPC patients. The expression of CFTR was determined in NPC cell lines and tissues. Statistical analysis was utilized to evaluate the correlation between CFTR expression levels and clinicopathological characteristics and prognosis in 225 cases of NPC patients. The results showed that CFTR was down-regulated in NPC tissues and cell lines. Low expression of CFTR was correlated with advanced stage (p = 0.026), distant metastasis (p < 0.001) and poor prognosis (p < 0.01). Multivariate analysis identified CFTR as an independent prognostic factor (p = 0.003). Additionally, wound healing and transwell assays revealed that overexpression of CFTR inhibited NPC cell migration and invasion, whereas knockdown of CFTR promoted cell migration and invasion. Thus, the current study indicates that CFTR, as demonstrated to play an important role in tumor migration and invasion, may be used as a potential prognostic indicator in NPC. PMID:27769067

  6. Serum serotonin as unexpected potential marker for staging of experimental hepatocellular carcinoma.

    PubMed

    Abdel-Hamid, N M; Shehata, Dalia E; Abdel-Ghany, Ahmed A; Ragaa, Ahmed; Wahid, Ahmed

    2016-10-01

    Hepatocellular carcinoma (HCC) is the primary cancer of the liver. The present study aimed to assess the potential role of the endogenous regulators of angiogenesis like neurotransmitters, as possible HCC biomarkers. Five groups of rats were used in this study (8 rats per each): control healthy group (I), four intoxicated groups (II, III, IV, and V) used for induction of HCC with a single IP dose of diethylnitrosamine (DENA), 200mg/kg. Groups II, III, IV, and V were sacrificed after 8, 16, 24, and 32 weeks of DENA injection respectively. Serum levels of epinephrine, nor-epinephrine, serotonin, and dopamine of all animals were estimated using high performance liquid chromatography technique coupled with fluorescence detector (HPLC-FLD). Development of HCC was confirmed histopathologically. Our results showed a significant increase in 3 neurotransmitters (epinephrine, nor-epinephrine, and serotonin) in DENA intoxicated HCC rat model. Only serotonin exhibited a significant increase in early histological stage HCC development (16 weeks post DENA injection) in comparison to alpha-fetoprotein (AFP), (24 weeks post DENA injection). These results suggest that neurotransmitters (Epinephrine and Norepinephrine) may have a role as a biomarker for late histological stage HCC. Like AFP, while serotonin may be used for early stage HCC.

  7. Potential of carotenoids in aquatic yeasts as a phylogenetically reliable marker and natural colorant for aquaculture.

    PubMed

    Ueno, Ryohei; Hamada-Sato, Naoko; Ishida, Masami; Urano, Naoto

    2011-01-01

    Apart from Xanthophyllomyces dendrorhous, pink colony-forming yeasts have not been examined as a pigmentation source in captive animals. In this study, aquatic yeasts were screened with a view to abundances of carotenoids. Phylogenetic analyses of these caroetnoid-rich yeasts based on large subunit ribosomal RNA gene (LSU rDNA) partial sequences showed that all belonged to the order Sporidiobolales. Both the qualitative and the quantitative differences in carotenoids between the yeasts appeared to be consistent with their phylogenetic affiliations. This information might be useful in the selection of pigment-rich yeasts containing specific carotenoids from a large number of strains. We also found, for the first time, the potential of a pigment-rich Rhodotorula strain as a colorant for aquaculture. The integuments of tilapia and carp fed the alkali-treated cells of strain Rhodotorula dairenensis Sag 17 were pigmented after 3 months of cultivation. The fish integuments retained the yeast carotenes shortly after the start of feeding, and were converted to the fish-specific xanthophylls in vivo.

  8. APRIL, a proliferation-inducing ligand, as a potential marker of lupus nephritis

    PubMed Central

    2012-01-01

    Introduction BLyS and APRIL are cytokines from the tumor necrosis factor family which play an important role in systemic lupus erythematosus (SLE). Previous works suggested an association between both molecules and SLE disease activity although their correlation with lupus nephritis is not known. We therefore assessed serum BLyS and APRIL in active lupus nephritis patients. Methods Serum samples from active lupus nephritis and at 6 months post-treatment were obtained. Serum levels of BLyS and APRIL (n = 47) as well as renal mRNA expression were measured. Serum levels of both molecules and clinical data (n = 27) were available at 6 months follow-up. All biopsy-proven lupus nephritis patients were treated with similar immunosuppressive drugs. Results Serum levels of APRIL were associated with proteinuria (Rs = 0.44, P value < 0.01) and degree of histological activity (Rs = 0.34; P value < 0.05) whereas BLyS levels were associated with complement levels (Rs = 0.46; P value < 0.01) and dosage of immunosuppressant. Interestingly, serum APRIL as well as its intrarenal mRNA levels were associated with resistance to treatment. From the receiver operating characteristic (ROC) analysis, high levels (> 4 ng/mL) of serum APRIL predicted treatment failure with a positive predictive value of 93 percent. Conclusion APRIL could be a potential biomarker for predicting difficult-to-treat cases of lupus nephritis. PMID:23171638

  9. Transcriptome sequencing of HER2-positive breast cancer stem cells identifies potential prognostic marker.

    PubMed

    Lei, Bo; Zhang, Xian-Yu; Zhou, Jia-Peng; Mu, Guan-Nan; Li, Yi-Wen; Zhang, You-Xue; Pang, Da

    2016-11-01

    In cancer stem cell theory, breast cancer stem cells (BCSCs) are postulated to be the root cause of recurrence and metastasis in breast cancer. Discovery of new biomarkers and development of BCSC-targeted therapy are practical issues that urgently need to be addressed in the clinic. However, few breast cancer stem cell targets are known. Given that there are few BCSCs, performing transcriptome sequencing on them thus far has not been possible. With the emergence of single-cell sequencing technology, we have now undertaken such a study. We prepared single-cell suspensions, which were sorted using flow cytometry from breast tumor tissue and adjacent normal breast tissue from two HER2-positive patients. We obtained BCSCs, breast cancer cells, mammary cells, and CD44(+) mammary cells. Transcriptome sequencing was then performed on these four cell types. Using bioinformatics, we identified 404 differentially expressed BCSC genes from the HER2-positive tumors and preliminary explored transcriptome characteristics of BCSCs. Finally, by querying a public database, we found that CA12 was a novel prognostic biomarker in HER2-positive breast cancer, which also had prognostic value in all breast cancer types. In conclusion, our results suggest that CA12 may be associated with BCSCs, especially HER2-positive BCSCs, and is a potential novel therapeutic target and biomarker.

  10. CFTR is a potential marker for nasopharyngeal carcinoma prognosis and metastasis.

    PubMed

    Tu, Ziwei; Chen, Qu; Zhang, Jie Ting; Jiang, Xiaohua; Xia, Yunfei; Chan, Hsiao Chang

    2016-11-22

    While there is an increasing interest in the correlation of cystic fibrosis transmembrane conductance regulator (CFTR) and cancer incidence, the role of CFTR in nasopharyngeal carcinoma (NPC) development remains unknown. In this study, we aimed to explore the prognostic value of CFTR in NPC patients. The expression of CFTR was determined in NPC cell lines and tissues. Statistical analysis was utilized to evaluate the correlation between CFTR expression levels and clinicopathological characteristics and prognosis in 225 cases of NPC patients. The results showed that CFTR was down-regulated in NPC tissues and cell lines. Low expression of CFTR was correlated with advanced stage (p = 0.026), distant metastasis (p < 0.001) and poor prognosis (p < 0.01). Multivariate analysis identified CFTR as an independent prognostic factor (p = 0.003). Additionally, wound healing and transwell assays revealed that overexpression of CFTR inhibited NPC cell migration and invasion, whereas knockdown of CFTR promoted cell migration and invasion. Thus, the current study indicates that CFTR, as demonstrated to play an important role in tumor migration and invasion, may be used as a potential prognostic indicator in NPC.

  11. Expression of Potential Cancer Stem Cell Marker ABCG2 is Associated with Malignant Behaviors of Hepatocellular Carcinoma

    PubMed Central

    Luo, Weihuan; Jiao, Hongbo; Jiang, Chunping

    2013-01-01

    Background. Despite improvement in treatment, the prognosis of hepatocellular carcinoma (HCC) remains disastrous. Cancer stem cells (CSCs) may be responsible for cancer malignant behaviors. ATP-binding cassette, subfamily G, member 2 (ABCG2) is widely expressed in both normal and cancer stem cells and may play an important role in cancer malignant behaviors. Methods. The expression of ABCG2 in HCC tissues and SMMC-7721 cells was examined, and the relevance of ABCG2 expression with clinical characteristics was analyzed. ABCG2+ and ABCG2− cells were sorted, and the potential of tumorigenicity was determined. Expression level of ABCG2 was manipulated by RNA interference and overexpression. Malignant behaviors including proliferation, drug resistance, migration, and invasion were studied in vitro. Results. Expression of ABCG2 was found in a minor group of cells in HCC tissues and cell lines. ABCG2 expression showed tendencies of association with unfavorable prognosis factors. ABCG2 positive cells showed a superior tumorigenicity. Upregulation of ABCG2 enhanced the capacity of proliferation, doxorubicin resistance, migration, and invasion potential, while downregulation of ABCG2 significantly decreased these malignant behaviors. Conclusion. Our results indicate that ABCG2 is a potential CSC marker for HCC. Its expression level has a close relationship with tumorigenicity, proliferation, drug resistance, and metastasis ability. PMID:24194752

  12. Theta Burst Stimulation of the Cerebellum Modifies the TMS-Evoked N100 Potential, a Marker of GABA Inhibition

    PubMed Central

    2015-01-01

    Theta burst stimulation (TBS) of the cerebellum, a potential therapy for neurological disease, can modulate corticospinal excitability via the dentato-thalamo-cortical pathway, but it is uncertain whether its effects are mediated via inhibitory or facilitatory networks. The aim of this study was to investigate the effects of 30Hz cerebellar TBS on the N100 waveform of the TMS-evoked potential (TEP), a marker of intracortical GABAB-mediated inhibition. 16 healthy participants (aged 18–30 years; 13 right handed and 3 left handed) received 30Hz intermittent TBS (iTBS), continuous TBS (cTBS) or sham stimulation over the right cerebellum, in three separate sessions. The first 8 participants received TBS at a stimulus intensity of 80% of active motor threshold (AMT), while the remainder received 90% of AMT. Motor evoked potentials (MEP) and TEP were recorded before and after each treatment, by stimulating the first dorsal interosseus area of the left motor cortex. Analysis of the 13 right handed participants showed that iTBS at 90% of AMT increased the N100 amplitude compared to sham and cTBS, without significantly altering MEP amplitude. cTBS at 80% of active motor threshold decreased the N100 amplitude and cTBS overall reduced resting MEP amplitude. The study demonstrates effects of 30Hz cerebellar TBS on inhibitory cortical networks that may be useful for treatment of neurological conditions associated with dysfunctional intracortical inhibition. PMID:26529225

  13. Mathematically combined half-cell reduction potentials of low-molecular-weight thiols as markers of seed ageing.

    PubMed

    Birtić, Simona; Colville, Louise; Pritchard, Hugh W; Pearce, Stephen R; Kranner, Ilse

    2011-09-01

    The half-cell reduction potential of the glutathione disulphide (GSSG)/glutathione (GSH) redox couple appears to correlate with cell viability and has been proposed to be a marker of seed viability and ageing. This study investigated the relationship between seed viability and the individual half-cell reduction potentials (E(i)s) of four low-molecular-weight (LMW) thiols in Lathyrus pratensis seeds subjected to artificial ageing: GSH, cysteine (Cys), cysteinyl-glycine (Cys-Gly) and γ-glutamyl-cysteine (γ-Glu-Cys). The standard redox potential of γ-Glu-Cys was previously unknown and was experimentally determined. The E(i)s were mathematically combined to define a LMW thiol-disulphide based redox environment (E(thiol-disulphide)). Loss of seed viability correlated with a shift in E(thiol-disulphide) towards more positive values, with a LD(50) value of -0.90 ± 0.093 mV M (mean ± SD). The mathematical definition of E(thiol-disulphide) is envisaged as a step towards the definition of the overall cellular redox environment, which will need to include all known redox-couples.

  14. Hydrogen emission in meteors as a potential marker for the exogenous delivery of organics and water

    NASA Technical Reports Server (NTRS)

    Jenniskens, Peter; Mandell, Avram M.

    2004-01-01

    We detected hydrogen Balmer-alpha (H(alpha)) emission in the spectra of bright meteors and investigated its potential use as a tracer for exogenous delivery of organic matter. We found that it is critical to observe the meteors with high enough spatial resolution to distinguish the 656.46 nm H(alpha) emission from the 657.46 nm intercombination line of neutral calcium, which was bright in the meteor afterglow. The H(alpha) line peak stayed in constant ratio to the atmospheric emissions of nitrogen during descent of the meteoroid. If all of the hydrogen originates in the Earth's atmosphere, the hydrogen atoms are expected to have been excited at T = 4400 K. In that case, we measured an H(2)O abundance in excess of 150 +/- 20 ppm at 80-90 km altitude (assuming local thermodynamic equilibrium in the air plasma). This compares with an expected <20 ppm from H(2)O in the gas phase. Alternatively, meteoric refractory organic matter (and water bound in meteoroid minerals) could have caused the observed H(alpha) emission, but only if the line is excited in a hot T approximately 10000 K plasma component that is unique to meteoric ablation vapor emissions such as Si(+). Assuming that the Si(+) lines of the Leonid spectrum would need the same hot excitation conditions, and a typical [H]/[C] = 1 in cometary refractory organics, we calculated an abundance ratio [C]/[Si] = 3.9 +/- 1.4 for the dust of comet 55P/Tempel-Tuttle. This range agreed with the value of [C]/[Si] = 4.4 measured for comet 1P/Halley dust. Unless there is 10 times more water vapor in the upper atmosphere than expected, we conclude that a significant fraction of the hydrogen atoms in the observed meteor plasma originated in the meteoroid.

  15. Cholinergic muscarinic M4 receptor gene polymorphisms: a potential risk factor and pharmacogenomic marker for schizophrenia.

    PubMed

    Scarr, Elizabeth; Um, Jung Yoon; Cowie, Tiffany Frances; Dean, Brian

    2013-05-01

    Although schizophrenia is a widespread disorder of unknown aetiology, we have previously shown that muscarinic M4 receptor (CHRM4) expression is decreased in the hippocampus and caudate-putamen from subjects with the disorder, implicating the receptor in its pathophysiology. These findings led us to determine whether variation in the CHRM4 gene sequence was associated with an altered risk of schizophrenia by sequencing the CHRM4 gene from the brains of 76 people with the disorder and 74 people with no history of psychiatric disorders. In addition, because the CHRM4 is a potential target for antipsychotic drug development, we investigated whether variations in CHRM4 sequence were associated with final recorded doses of, and life-time exposure to, antipsychotic drugs. Gene sequencing identified two single nucleotide polymorphisms (SNPs; rs2067482 and rs72910092) in the CHRM4 gene. For rs2067482, our data suggested that both genotype (1341C/C; p = 0.05) and allele (C; p = 0.03) were associated with an increased risk of schizophrenia. In addition, there was a strong trend (p = 0.08) towards an association between CHRM4 sequence and increased lifetime exposure to antipsychotic drugs. Furthermore, there was a trend for people with the C allele to be prescribed benzodiazepines more frequently (p = 0.06) than those with the T allele. These data, albeit on small cohorts, are consistent with genetic variance at rs2067482 contributing to an altered risk of developing schizophrenia which requires more forceful pharmacotherapy to achieve a clinical response.

  16. A Preclinical Study of Laryngeal Motor-Evoked Potentials as a Marker Vagus Nerve Activation.

    PubMed

    Grimonprez, Annelies; Raedt, Robrecht; De Taeye, Leen; Larsen, Lars Emil; Delbeke, Jean; Boon, Paul; Vonck, Kristl

    2015-12-01

    Vagus nerve stimulation (VNS) is a treatment for refractory epilepsy and depression. Previous studies using invasive recording electrodes showed that VNS induces laryngeal motor-evoked potentials (LMEPs) through the co-activation of the recurrent laryngeal nerve and subsequent contractions of the laryngeal muscles. The present study investigates the feasibility of recording LMEPs in chronically VNS-implanted rats, using a minimally-invasive technique, to assess effective current delivery to the nerve and to determine optimal VNS output currents for vagal fiber activation. Three weeks after VNS electrode implantation, signals were recorded using an electromyography (EMG) electrode in the proximity of the laryngeal muscles and a reference electrode on the skull. The VNS output current was gradually ramped up from 0.1 to 1.0 mA in 0.1 mA steps. In 13/27 rats, typical LMEPs were recorded at low VNS output currents (median 0.3 mA, IQR 0.2-0.3 mA). In 11/27 rats, significantly higher output currents were required to evoke electrophysiological responses (median 0.7 mA, IQR 0.5-0.7 mA, p < 0.001). The latencies of these responses deviated significantly from LMEPs (p < 0.05). In 3/27 rats, no electrophysiological responses to simulation were recorded. Minimally invasive LMEP recordings are feasible to assess effective current delivery to the vagus nerve. Furthermore, our results suggest that low output currents are sufficient to activate vagal fibers.

  17. Molecular signature of salivary gland tumors: potential use as diagnostic and prognostic marker.

    PubMed

    Fonseca, Felipe Paiva; Sena Filho, Marcondes; Altemani, Albina; Speight, Paul M; Vargas, Pablo Agustin

    2016-02-01

    Salivary gland tumors are a highly heterogeneous group of lesions with diverse microscopic appearances and variable clinical behavior. The use of clinical and histological parameters to predict patient prognosis and survival rates has been of limited utility, and the search for new biomarkers that could not only aid in a better understanding of their pathogenesis but also be reliable auxiliaries for prognostic determination and useful diagnostic tools has been performed in the last decades with very exciting results. Hence, gene rearrangements such as CRTC1-MAML2 in mucoepidermoid carcinomas have shown excellent specificity, and more than that, it has been strongly correlated with low-grade tumors and consequently with an increased survival rate and better prognosis of patients affected by neoplasms carrying this translocation. Moreover, MYB-NFIB and EWSR1-ATF1 gene fusions were shown to be specifically found in cases of adenoid cystic carcinomas and hyalinizing clear cell carcinomas, respectively, in the context of salivary gland tumors, becoming reliable diagnostic tools for these entities and potential therapeutic targets for future therapeutic protocols. Finally, the identification of ETV6-NTRK3 in cases previously diagnosed as uncommon acinic cell carcinomas, cystadenocarcinomas, and adenocarcinomas not otherwise specified led to the characterization of a completely new and now widely accepted entity, including, therefore, mammary analogue secretory carcinoma in the list of well-recognized salivary gland carcinomas. Thus, further molecular investigations of salivary gland tumors are warranted, and the recognition of other genetic abnormalities can lead to the acknowledgment of new entities and the acquirement of reliable biomarkers.

  18. Predictive value of bovine follicular components as markers of oocyte developmental potential.

    PubMed

    Matoba, Satoko; Bender, Katrin; Fahey, Alan G; Mamo, Solomon; Brennan, Lorraine; Lonergan, Patrick; Fair, Trudee

    2014-01-01

    The follicle is a unique micro-environment within which the oocyte can develop and mature to a fertilisable gamete. The aim of this study was to investigate the ability of a panel of follicular parameters, including intrafollicular steroid and metabolomic profiles and theca, granulosa and cumulus cell candidate gene mRNA abundance, to predict the potential of bovine oocytes to develop to the blastocyst stage in vitro. Individual follicles were dissected from abattoir ovaries, carefully ruptured under a stereomicroscope and the oocyte was recovered and individually processed through in vitro maturation, fertilisation and culture. The mean (±s.e.m.) follicular concentrations of testosterone (62.8±4.8 ngmL(-1)), progesterone (616.8±31.9 ngmL(-1)) and oestradiol (14.4±2.4 ngmL(-1)) were not different (P>0.05) between oocytes that formed (competent) or failed to form (incompetent) blastocysts. Principal-component analysis of the quantified aqueous metabolites in follicular fluid showed differences between oocytes that formed blastocysts and oocytes that degenerated; l-alanine, glycine and l-glutamate were positively correlated and urea was negatively correlated with blastocyst formation. Follicular fluid associated with competent oocytes was significantly lower in palmitic acid (P=0.023) and total fatty acids (P=0.031) and significantly higher in linolenic acid (P=0.036) than follicular fluid from incompetent oocytes. Significantly higher (P<0.05) transcript abundance of LHCGR in granulosa cells, ESR1 and VCAN in thecal cells and TNFAIP6 in cumulus cells was associated with competent compared with incompetent oocytes.

  19. Hydrogen emission in meteors as a potential marker for the exogenous delivery of organics and water.

    PubMed

    Jenniskens, Peter; Mandell, Avram M

    2004-01-01

    We detected hydrogen Balmer-alpha (H(alpha)) emission in the spectra of bright meteors and investigated its potential use as a tracer for exogenous delivery of organic matter. We found that it is critical to observe the meteors with high enough spatial resolution to distinguish the 656.46 nm H(alpha) emission from the 657.46 nm intercombination line of neutral calcium, which was bright in the meteor afterglow. The H(alpha) line peak stayed in constant ratio to the atmospheric emissions of nitrogen during descent of the meteoroid. If all of the hydrogen originates in the Earth's atmosphere, the hydrogen atoms are expected to have been excited at T = 4400 K. In that case, we measured an H(2)O abundance in excess of 150 +/- 20 ppm at 80-90 km altitude (assuming local thermodynamic equilibrium in the air plasma). This compares with an expected <20 ppm from H(2)O in the gas phase. Alternatively, meteoric refractory organic matter (and water bound in meteoroid minerals) could have caused the observed H(alpha) emission, but only if the line is excited in a hot T approximately 10000 K plasma component that is unique to meteoric ablation vapor emissions such as Si(+). Assuming that the Si(+) lines of the Leonid spectrum would need the same hot excitation conditions, and a typical [H]/[C] = 1 in cometary refractory organics, we calculated an abundance ratio [C]/[Si] = 3.9 +/- 1.4 for the dust of comet 55P/Tempel-Tuttle. This range agreed with the value of [C]/[Si] = 4.4 measured for comet 1P/Halley dust. Unless there is 10 times more water vapor in the upper atmosphere than expected, we conclude that a significant fraction of the hydrogen atoms in the observed meteor plasma originated in the meteoroid.

  20. Modulation of growth and angiogenic potential of oral squamous carcinoma cells in vitro using salvianolic acid B

    PubMed Central

    2011-01-01

    Background Our previous studies showed that Salvianolic acid B (Sal B) inhibited 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamsters and such anti-cancer effects might be related to the inhibition of angiogenesis. This study was aimed to further investigate the anti-proliferative effect of Sal B on the most common type of oral cancer, oral squamous cell carcinoma (OSCC) and the possible mechanisms of action with respect to angiogenesis inhibition. Methods Two well-characterized oral squamous cell carcinoma cell lines, CAL27 and SCC4, and premalignant leukoplakia cells were treated with different concentrations of Sal B. Cytotoxicity was assessed by MTT assay. cDNA microarray was utilized to evaluate the expression of 96 genes known to be involved in modulating the biological processes of angiogenesis. Real-time reverse transcription-polymerase chain reaction analysis was conducted to confirm the cDNA microarray data. Results Sal B induced growth inhibition in OSCC cell lines but had limited effects on premalignant cells. A total of 17 genes showed a greater than 3-fold change when comparing Sal B treated OSCC cells to the control. Among these genes, HIF-1α, TNFα and MMP9 are specifically inhibited, expression of THBS2 was up-regulated. Conclusions Sal B has inhibitory effect on OSCC cell growth. The antitumor effect can be attributed to anti-angiogenic potential induced by a decreased expression of some key regulator genes of angiogenesis. Sal B may be a promising modality for treating oral squamous cell carcinoma. PMID:21726465

  1. Growth Differentiation Factor-15 (GDF-15) is a potential marker of radiation response and radiation sensitivity.

    PubMed

    Sándor, Nikolett; Schilling-Tóth, Boglárka; Kis, Enikő; Benedek, Anett; Lumniczky, Katalin; Sáfrány, Géza; Hegyesi, Hargita

    2015-11-01

    We have investigated the importance of GDF-15 (secreted cytokine belonging to the TGF-β superfamily) in low and high dose radiation-induced cellular responses. A telomerase immortalized human fibroblast cell line (F11hT) was used in the experiments. A lentiviral system encoding small hairpin RNAs (shRNA) was used to establish GDF-15 silenced cells. Secreted GDF-15 levels were measured in culture medium by ELISA. Cell cycle analysis was performed by flow cytometry. The experiments demonstrated that in irradiated human fibroblasts GDF-15 expression increased with dose starting from 100mGy. Elevated GDF-15 expression was not detected in bystander cells. The potential role of GDF-15 in radiation response was investigated by silencing GDF-15 in immortalized human fibroblasts with five different shRNA encoded in lentiviral vectors. Cell lines with considerably reduced GDF-15 levels presented increased radiation sensitivity, while a cell line with elevated GDF-15 was more radiation resistant than wild type cells. We have investigated how the reduced GDF-15 levels alter the response of several known radiation inducible genes. In F11hT-shGDF-15 cells the basal expression level of CDKN1A was unaltered relative to F11hT cells, while GADD45A and TGF-β1 mRNA levels were slightly higher, and TP53INP1 was considerably reduced. The radiation-induced expression of TP53INP1 was lower in the silenced than in wild type fibroblast cells. Cell cycle analysis indicated that radiation-induced early G2/M arrest was abrogated in GDF-15 silenced cells. Moreover, radiation-induced bystander effect was less pronounced in GDF-15 silenced fibroblasts. In conclusion, the results suggest that GDF-15 works as a radiation inducible radiation resistance increasing factor in normal human fibroblast cells, acts by regulating the radiation-induced transcription of several genes and might serve as a radiation-induced early biomarker in exposed cells.

  2. Potential use of iodine-123 metaiodobenzylguanidine radioaerosol as a marker of pulmonary neuroadrenergic function.

    PubMed

    Giordano, A; Calcagni, M L; Rossi, B; Fuso, L; Accardo, D; Valente, S; Pistelli, R; Franceschini, R; Troncone, L

    1997-01-01

    Iodine-123 metaiodobenzylguanidine (123I-MIBG) radioaerosol is of potential use in the investigation of the neuroadrenergic function of the lungs; however, before the method can be successfully employed the following issues need to be clarified: (1) Does the nebulization affect the radiochemical purity of 123I-MIBG? (2) Is the pulmonary distribution of inhaled 123I-MIBG homogeneous in normal subjects? (3) Does the pulmonary clearance of inhaled 123I-MIBG reflect the functional status of the neuroadrenergic system of the lungs? In this study we performed: (1) a chromatographic study of nebulized 123I-MIBG; (2) a quantitative evaluation of the lung distribution of 123I-MIBG radioaerosol in normal subjects as compared with that of technetium-99m diethylene triamine penta-acetic acid (99mTc-DTPA) and (3) an assessment of 123I-MIBG lung clearance both under control conditions and after pharmacologically induced beta-blockade, again compared with 99mTc-DTPA. For these purposes, eight normal subjects were divided randomly into an "MIBG group" and a "DTPA group" (four subjects each) and submitted to three scintigraphic studies each: a baseline study, and studies after the administration of a low (80 mg) and a high (160 mg) dose of propranolol. Radiochemical purity of nebulized 123I-MIBG ranged between 97.18% and 98.70%. The lung distribution of 123I-MIBG, as judged by the aerosol penetration index, was identical to that of 99mTc-DTPA under all study conditions. The 123I-MIBG clearance rate was slower than that of 99mTc-DTPA under baseline conditions (135+/-32 min vs 69+/-27 min, P<0.01) and increased significantly after propranolol administrations, while the 99mTc-DTPA clearance did not change. The following conclusions were drawn: (1) the nebulization does not affect the radiochemical purity of 123I-MIBG; (2) the lung distribution of 123I-MIBG is homogeneous in normal subjects; (3) the pulmonary clearance of 123I-MIBG reflects the functional status of the neuroadrenergic

  3. Diffusion imaging changes in grey matter in Alzheimer's disease: a potential marker of early neurodegeneration.

    PubMed

    Weston, Philip S J; Simpson, Ivor J A; Ryan, Natalie S; Ourselin, Sebastien; Fox, Nick C

    2015-01-01

    Alzheimer's disease (AD) is recognized to have a long presymptomatic period, during which there is progressive accumulation of molecular pathology, followed by inexorable neuronal damage. The ability to identify presymptomatic individuals with evidence of neurodegenerative change, to stage their disease, and to track progressive changes will be important for early diagnosis and for prevention trials. Despite recent advances, particularly in magnetic resonance imaging, our ability to identify early neurodegenerative changes reliably is limited. The development of diffusion-weighted magnetic resonance imaging, which is sensitive to microstructural changes not visible with conventional volumetric techniques, has led to a number of diffusion imaging studies in AD; these have largely focused on white matter changes. However, in AD cerebral grey matter is affected very early, with pathological studies suggesting that grey matter changes predate those in white matter. In this article we review the growing number of studies that assess grey matter diffusivity changes in AD. Although use of the technique is still at a relatively early stage, results so far have been promising. Initial studies identified changes in diffusion measures in the hippocampi of patients with mild cognitive impairment, which predated macroscopic volume loss, with positive predictive value for progression to AD dementia. More recent studies have identified abnormalities in multiple neocortical areas (particularly the posterior cingulate) at various stages of disease progression. Studies of patients who carry genetic mutations predisposing to autosomal dominant familial AD have shown cortical and subcortical grey matter diffusivity changes several years before the expected onset of the first clinical symptoms. The technique is not without potential methodological difficulties, especially relating to partial volume effects, although recent advances appear to be reducing such issues. Going forward

  4. Genome-Wide Gene Expression Profile Analyses Identify CTTN as a Potential Prognostic Marker in Esophageal Cancer

    PubMed Central

    He, Wei; Wang, Jin; Jia, Yongxu; Sun, Yan; Tang, Senwei; Fu, Li; Qin, Yanru

    2014-01-01

    Aim Esophageal squamous cell carcinoma (ESCC) is one of the most common fatal malignances of the digestive tract. Its prognosis is poor mainly due to the lack of reliable markers for early detection and prognostic prediction. Here we aim to identify the molecules involved in ESCC carcinogenesis and those as potential markers for prognosis and as new molecular therapeutic targets. Methods We performed genome-wide gene expression profile analyses of 10 primary ESCCs and their adjacent normal tissues by cDNA microarrays representing 47,000 transcripts and variants. Candidate genes were then validated by semi quantitative reverse transcription-PCR (RT-PCR), tissue microarrays (TMAs) and immunohistochemistry (IHC) staining. Results Using an arbitrary cutoff line of signal log ratio of ≥1.5 or ≤−1.5, we observed 549 up-regulated genes and 766 down-regulated genes in ESCCs compared with normal esophageal tissues. The functions of 302 differentially expressed genes were associated with cell metabolism, cell adhesion and immune response. Several candidate deregulated genes including four overexpressed (CTTN, DMRT2, MCM10 and SCYA26) and two underexpressed (HMGCS2 and SORBS2) were subsequently verified, which can be served as biomarkers for ESCC. Moreover, overexpression of cortactin (CTTN) was observed in 126/198 (63.6%) of ESCC cases and was significantly associated with lymph node metastasis (P = 0.000), pathologic stage (P = 0.000) and poor survival (P<0.001) of ESCC patients. Furthermore, a significant correlation between CTTN overexpression and shorter disease-specific survival rate was found in different subgroups of ESCC patient stratified by the pathologic stage (P<0.05). Conclusion Our data provide valuable information for establishing molecules as candidates for prognostic and/or as therapeutic targets. PMID:24551190

  5. Pulmonary neuroendocrine cells and neuroepithelial bodies in sudden infant death syndrome: potential markers of airway chemoreceptor dysfunction.

    PubMed

    Cutz, Ernest; Perrin, Donald G; Pan, Jie; Haas, Elisabeth A; Krous, Henry F

    2007-01-01

    Pulmonary neuroendocrine cells (PNEC), including neuroepithelial bodies (NEB), are amine- and peptide (for example, bombesin)-producing cells that function as hypoxia/hypercapnia-sensitive chemoreceptors that could be involved in the pathophysiology of sudden infant death syndrome (SIDS). We assessed morphometrically the frequency and size of PNEC/NEB in lungs of infants who died of SIDS (n = 21) and compared them to an equal number PNEC/NEB in lungs of age-matched control infants who died of accidental death or homicide, with all cases obtained from the San Diego SIDS/SUDC Research Project database. As a marker for PNEC/NEB we used an antibody against chromogranin A (CGA), and computer-assisted morphometric analysis was employed to determine the relative frequency of PNEC per airway epithelial area (% immunostained area, %IMS), the size of NEB, the number of nuclei/NEB, and the size of the NEB cells. The lungs of SIDS infants showed significantly greater %IMS of airway epithelium (2.72 +/- 0.28 [standard error of the mean, SEM] versus 1.88 +/- 0.24; P < 0.05) and larger NEB (1557 +/- 153 microm(2) versus 1151 +/- 106 microm(2); P < 0.05) compared to control infants. The size of NEB cells was also significantly increased in SIDS cases compared to the controls (180 +/- 6.39 microm(2) versus 157 +/- 8.0 microm(2); P < 0.05), indicating the presence of hypertrophy in addition to hyperplasia. Our findings support previous studies demonstrating hyperplasia of PNEC/NEB in lungs of infants who died of SIDS. These changes could be secondary to chronic hypoxia and/or could be attributable to maturational delay. Morphometric assessment and/or measurement of the secretory products of these cells (for example, CGA, bombesin) could provide a potential biological marker for SIDS.

  6. Association between Mutation and Expression of TP53 as a Potential Prognostic Marker of Triple-Negative Breast Cancer

    PubMed Central

    Kim, Ji-Yeon; Park, Kyunghee; Jung, Hae Hyun; Lee, Eunjin; Cho, Eun Yoon; Lee, Kwang Hee; Bae, Soo Youn; Lee, Se Kyung; Kim, Seok Won; Lee, Jeong Eon; Nam, Seok Jin; Ahn, Jin Seok; Im, Young-Hyuck; Park, Yeon Hee

    2016-01-01

    Purpose TP53, the most frequently mutated gene in breast cancer, is more frequently altered in HER2-enriched and basal-like breast cancer. However, no studies have clarified the role of TP53 status as a prognostic and predictive marker of triple-negative breast cancer (TNBC). Materials and Methods We performed p53 immunohistochemistry (IHC), nCounter mRNA expression assay, and DNA sequencing to determine the relationship between TP53 alteration and clinical outcomes of TNBC patients. Results Seventy-seven of 174 TNBC patients were found to harbor a TP53 mutation. Patients with missense mutations showed high protein expression in contrast to patients with deletion mutations (positivity of IHC: wild type vs. missense vs. deletion mutation, 53.6% vs. 89.8% vs. 25.0%, respectively; p < 0.001). TP53 mRNA expression was influenced by mutation status (mRNA expression [median]: wild type vs. missense vs. deletion mutation, 207.36± 132.73 vs. 339.61±143.21 vs. 99.53±99.57, respectively; p < 0.001). According to survival analysis, neither class of mutation nor protein or mRNA expression status had any impact on patient prognosis. In subgroup analysis, low mRNA expression was associated with poor prognosis in patients with a TP53 missense mutation (5-year distant recurrence-free survival [5Y DRFS]: low vs. high, 50.0% vs. 87.8%; p=0.009), while high mRNA expression with a TP53 deletion mutation indicated poor prognosis (5Y DRFS: low vs. high, 91.7% vs. 75.0%; p=0.316). Conclusion Association between TP53 mutation and expression indicates a potential prognostic marker of TNBC; hence both DNA sequencing and mRNA expression analysis may be required to predict the prognosis of TNBC patients. PMID:26910472

  7. Genetic Structure and Inferences on Potential Source Areas for Bactrocera dorsalis (Hendel) Based on Mitochondrial and Microsatellite Markers

    PubMed Central

    Shi, Wei; Kerdelhué, Carole; Ye, Hui

    2012-01-01

    Bactrocera dorsalis (Diptera: Tephritidae) is mainly distributed in tropical and subtropical Asia and in the Pacific region. Despite its economic importance, very few studies have addressed the question of the wide genetic structure and potential source area of this species. This pilot study attempts to infer the native region of this pest and its colonization pathways in Asia. Combining mitochondrial and microsatellite markers, we evaluated the level of genetic diversity, genetic structure, and the gene flow among fly populations collected across Southeast Asia and China. A complex and significant genetic structure corresponding to the geographic pattern was found with both types of molecular markers. However, the genetic structure found was rather weak in both cases, and no pattern of isolation by distance was identified. Multiple long-distance dispersal events and miscellaneous host selection by this species may explain the results. These complex patterns may have been influenced by human-mediated transportation of the pest from one area to another and the complex topography of the study region. For both mitochondrial and microsatellite data, no signs of bottleneck or founder events could be identified. Nonetheless, maximal genetic diversity was observed in Myanmar, Vietnam and Guangdong (China) and asymmetric migration patterns were found. These results provide indirect evidence that the tropical regions of Southeast Asia and southern coast of China may be considered as the native range of the species and the population expansion is northward. Yunnan (China) is a contact zone that has been colonized from different sources. Regions along the southern coast of Vietnam and China probably served to colonize mainly the southern region of China. Southern coastal regions of China may also have colonized central parts of China and of central Yunnan. PMID:22615898

  8. Smokeless Tobacco and Oral Potentially Malignant Disorders in South Asia: A Systematic Review and Meta-analysis.

    PubMed

    Khan, Zohaib; Khan, Sheraz; Christianson, Lara; Rehman, Sara; Ekwunife, Obinna; Samkange-Zeeb, Florence

    2016-12-07

    Oral Potentially Malignant Disorders (OPMDs) are chronic lesions or conditions characterized by a potential for malignant transformation. While recent meta-analyses show that smokeless tobacco (SLT) use is a risk factor for oral cancer in South Asia, there is a lack of pooled evidence regarding SLT use and the development of OPMDs. We searched Medline via PubMed, the Science Citation Index (SCI) via Web of Science, Scopus, CINAHL, Global Index Medicus and Google Scholar databases for relevant literature using a combination of keywords and MeSH terms. Eighteen case-control studies were included in the review, all of which reported significantly elevated risk estimates for OPMDs associated with SLT use. Overall and subgroup, Meta Odds Ratios (mOR) were calculated through a random effects analysis using "generic inverse variance" method in Rev Man 5.3. Heterogeneity was quantified by calculating the I (2) statistic. The mOR for any OPMD with the use of any SLT product was 15.5 [95% Confidence Interval (CI), 9.9-24.2]. Women had a higher risk, mOR = 22.2 (95% CI, 9.1-54.1) compared to men, mOR = 8.7 (95% CI, 2.1-34.8). Betel quid with tobacco carried the highest risk for OPMD, mOR = 16.1 (95% CI, 7.8-33.5). Although the cumulative evidence is informed by case-control studies only, the magnitude of the pooled estimates and the presence of exposure-response indicate a very strong association between OPMDs and SLT use. In addition to tobacco control, results of this review may help in informing oral cancer control policies in South Asia, since OPMDs lie on the causal pathway for oral cancer.

  9. Potent and Orally Bioavailable Antiplatelet Agent, PLD-301, with the Potential of Overcoming Clopidogrel Resistance

    PubMed Central

    Chen, Jingyu; Wang, Michael Zhiyan

    2016-01-01

    PLD-301, a phosphate prodrug of clopidogrel thiolactone discovered by Prelude Pharmaceuticals with the aim to overcome clopidogrel resistance, was evaluated for its in vivo inhibitory effect on ADP-induced platelet aggregation in rats. The potency of PLD-301 was similar to that of prasugrel, but much higher than that of clopidogrel. The results of pharmacokinetic analysis showed that the oral bioavailability of clopidogrel thiolactone converted from PLD-301 was 4- to 5-fold higher than that of the one converted from clopidogrel, suggesting that in comparison with clopidogrel, lower doses of PLD-301 could be used clinically. In summary, PLD-301 presents a potent and orally bioavailable antiplatelet agent that might have some advantages over clopidogrel, such as overcoming clopidogrel resistance for CYP2C19-allele loss-of-function carriers, and lowering dose-related toxicity due to a much lower effective dose. PMID:27594816

  10. Aerobic bacterial oral flora of garter snakes: development of normal flora and pathogenic potential for snakes and humans.

    PubMed

    Goldstein, E J; Agyare, E O; Vagvolgyi, A E; Halpern, M

    1981-05-01

    Garter snakes that are used for scientific laboratory studies or kept as exotic pets often become ill and die early in captivity. They may also act as reservoirs of potential human pathogens or transmit infection to man. A total of 126 strains of aerobic and facultative bacteria, most potential human and snake pathogens, were isolated from 82 garter snake oropharyngeal cultures. Coagulase-negative Staphylococcus species were the most common species isolated. Acinetobacter calcoaceticus var. anitratus, Hafnia alvei, Arizona hinshawii, Salmonella species, Shigella species, Klebsiella oxytoca, and Pseudomonas aeruginosa were among the potential pathogens isolated. The spectrum of bacteria with potential for causing oral and pulmonary infections in garter snakes is greater than has been previously appreciated. Garter snakes should also be considered reservoirs of human pathogens, and appropriate precautions should be taken by laboratory personnel and pet owners.

  11. Moisture sorption as a potential condition marker for historic silks: noninvasive determination by near-infrared spectroscopy.

    PubMed

    Zhang, Xiaomei; Wyeth, Paul

    2007-02-01

    Given their ephemeral nature, the preservation of historic silks can be problematic. Rapid, on-site condition monitoring would offer significant benefits to conservators and museum curators concerned with continued access to collections. In this paper, near-infrared spectroscopy (NIR) is investigated as a noninvasive approach to the characterization of silk fabrics and particularly for determining the moisture content of silks as a potential age-related marker. Bands within the NIR spectrum of silk are assigned to contributions from water and the silk fibroin polymer. The water bands may be deconvolved to show separate contributions from bound and structural water. When silk is exposed to deuterium oxide, the water OH NIR bands are rapidly lost. The accompanying changes in the amide-related NIR absorptions reflect differential accessibility of regions within the semi-crystalline fibroin aggregate. NIR spectra were recorded while silk was maintained at a range of relative humidity; complementary gravimetry provided absolute reference data for moisture sorption. A single spectral parameter, the intensity of the water combination band, is sufficient to indicate the relative moisture content of silk and allows distinction of unaged and heat, light, and humidity aged silks. The results confirm that NIR has significant potential for on-site studies at collections in support of the preservation and access of our silk heritage.

  12. Stroma derived COL6A3 is a potential prognosis marker of colorectal carcinoma revealed by quantitative proteomics

    PubMed Central

    Chen, Sun-Xia; Wang, Xiao-Qing; Cui, Shu-Jian; Liu, Xiao-Hui; Jiang, Ying-Hua; Wang, Jie; Zhang, Yang; Yang, Peng-Yuan; Liu, Feng

    2015-01-01

    Colorectal cancer (CRC) represents the third most common cancer in males and second in females worldwide. Here, we performed a quantitative 8-plex iTRAQ proteomics analysis of the secreted proteins from five colonic fibroblast cultures and three colon cancer epithelial cell lines. We identified 1114 proteins at 0% FDR, including 587 potential secreted proteins. We further recognized 116 fibroblast-enriched proteins which were significantly associated with cell movement, angiogenesis, proliferation and wound healing, and 44 epithelial cell-enriched proteins. By interrogation of Oncomine database, we found that 20 and 8 fibroblast-enriched proteins were up- and downregulated in CRC, respectively. Western blots confirmed the fibroblast-specific secretion of filamin C, COL6A3, COL4A1 and spondin-2. Upregulated mRNA and stroma expression of COL6A3 in CRC, which were revealed by Oncomine analyses and tissue-microarray-immunohistochemistry, indicated poor prognosis. COL6A3 expression was significantly associated with Dukes stage, T stage, stage, recurrence and smoking status. Circulating plasma COL6A3 in CRC patients was upregulated significantly comparing with healthy peoples. Receiver operating characteristic curve analysis revealed that COL6A3 has better predictive performance for CRC with an area under the curve of 0.885 and the best sensitivity/specificity of 92.9%/81.3%. Thus we demonstrated that COL6A3 was a potential diagnosis and prognosis marker of CRC. PMID:26338966

  13. Hypoxia inducible factor: a potential prognostic biomarker in oral squamous cell carcinoma.

    PubMed

    Qian, Jiang; Wenguang, Xu; Zhiyong, Wang; Yuntao, Zou; Wei, Han

    2016-08-01

    Oral squamous cell carcinoma (OSCC) is the most common oral cancer. Hypoxia inducible factor (HIF) is involved in many malignant tumors' growth and metastasis and upregulated by hypoxia, including oral cancer. Many studies have studied about the prognostic value of HIF expression in OSCC; however, they do not get the consistent results. Therefore, this study explored the correlation between the HIF expression and the prognosis of OSCC. It conducted a meta-analysis of relevant publications searched in the Web of Science, PubMed, and ISI Web of Knowledge databases. Totally, this study identified 12 relevant articles reporting a total of 1112 patients. This analysis revealed a significant association between increased risk of mortality (RR = 1.20; 95 % CI 0.74-1.95; I (2) 85.4 %) and overexpression of HIFs. Furthermore, different HIF isoforms were associated with overall survival [HIF-1α (RR = 1.18; 95 % CI 0.66-2.11; I (2) 87.2 %) and HIF-2α (RR = 1.40; 95 % CI 0.93-2.09; I(2) 0.0 %)]. These results show that overexpression of HIFs, regardless of whether the HIF-1α or HIF-2α isoforms are overexpressed is significantly associated with increased risk of mortality in OSCC patients. In this study, the funnel is symmetric, suggesting existed no publication bias.

  14. Significantly different proliferative potential of oral mucosal epithelial cells between six animal species.

    PubMed

    Kondo, Makoto; Yamato, Masayuki; Takagi, Ryo; Murakami, Daisuke; Namiki, Hideo; Okano, Teruo

    2014-06-01

    There has been an upsurge in regenerative medicine in recent years. In particular, because oral mucosal epithelial cells can be obtained noninvasively, cultured epithelial cell sheets have been used in a number of ectopic transplantations. Additionally, the verification of the properties of experimental animals' cultured cells has accelerated the application of regenerative medicine. In the present study, the properties of oral mucosal epithelial cells were compared between six animal species. The human and pig epithelia were relatively thicker than the epithelia of the other species. The colony-forming efficiency of the rat was the highest, followed by those of the dog, human, rabbit, and pig, whereas the colonies of the mouse cells were all paraclone and uncountable in the colony-forming assay. We also found that the rabbit and pig cells proliferated poorly and were unable to form cell sheets without feeder layers. In contrast, even in the absence of feeder layers and cholera toxin, cultured dog and mouse cells formed contiguous sheets, when the cell seeding density was high. These results indicate that interspecies variation is considerable in oral mucosal epithelial cells and that specific experimental animal or human cells must be chosen according to the intended use.

  15. Potential for use of retinoic acid as an oral vaccine adjuvant

    PubMed Central

    Mwanza-Lisulo, Mpala; Kelly, Paul

    2015-01-01

    Despite the heavy burden of diarrhoeal disease across much of the tropical world, only two diarrhoea-causing pathogens, cholera and rotavirus, are the target of commercially available vaccines. Oral vaccines are generally less immunogenic than the best parenteral vaccines, but the reasons for this are still debated. Over the past decade, several lines of evidence from work in experimental animals have suggested that all-trans retinoic acid (ATRA), a form of vitamin A which is highly transcriptionally active, can alter the homing receptor expression of T lymphocytes. Increased expression of α4β7 integrin and the chemokine receptor CCR9 following exposure to ATRA can be used to redirect T cells to the gut. Early work in human volunteers suggests that oral ATRA administration 1 h prior to dosing with oral typhoid vaccine can augment secretion of specific IgA against vaccine-derived lipopolysaccharide into gut secretions. In this review, we set out the rationale for using ATRA in this way and assess its likely applicability to vaccination programmes for protection of children in low-income countries from the considerable mortality caused by diarrhoeal disease. Comparison of recent work in experimental animals, non-human primates and men suggests that a more detailed understanding of ATRA dosage and kinetics will be important to taking forward translational work into human vaccinology. PMID:25964457

  16. Evaluation of a 3A-truncated foot-and-mouth disease virus in pigs for its potential as a marker vaccine.

    PubMed

    Li, Pinghua; Lu, Zengjun; Bai, Xingwen; Li, Dong; Sun, Pu; Bao, Huifang; Fu, Yuanfang; Cao, Yimei; Chen, Yingli; Xie, Baoxia; Yin, Hong; Liu, Zaixin

    2014-05-01

    Foot-and-mouth disease (FMD) is a highly contagious and economically devastating disease of cloven-hoofed animals in the world. The disease can be effectively controlled by vaccination of susceptible animals with the conventional inactivated vaccine. However, one major concern of the inactivated FMD virus (FMDV) vaccine is that it does not allow serological discrimination between infected and vaccinated animals, and therefore interferes with serologic surveillance and the epidemiology of disease. A marker vaccine has proven to be of great value in disease eradication and control programs. In this study, we constructed a marker FMDV containing a deletion of residues 93 to 143 in the nonstructural protein 3A using a recently developed FMDV infectious cDNA clone. The marker virus, r-HN/3A93-143, had similar growth kinetics as the wild type virus in culture cell and caused a symptomatic infection in pigs. Pigs immunized with chemically inactivated marker vaccine were fully protected from the wild type virus challenge, and the potency of this marker vaccine was 10 PD50 (50% pig protective dose) per dose, indicating it could be an efficacious vaccine against FMDV. In addition, we developed a blocking ELISA targeted to the deleted epitope that could clearly differentiate animals infected with the marker virus from those infected with the wild type virus. These results indicate that a marker FMDV vaccine can be potentially developed by deleting an immunodominant epitope in NSP 3A.

  17. Prevalence and potential influencing factors of non-nutritive oral behaviors of veal calves on commercial farms.

    PubMed

    Leruste, H; Brscic, M; Cozzi, G; Kemp, B; Wolthuis-Fillerup, M; Lensink, B J; Bokkers, E A M; van Reenen, C G

    2014-11-01

    Veal calves raised under intensive conditions may express non-nutritive oral behaviors. When expressed in an abnormal way, these behaviors can be a sign of mental suffering and reduced welfare due to a mismatch between environmental or management features and the animal's needs. The aims of this study were to estimate the prevalence of non-nutritive oral behaviors in a large sample of veal farms in Europe and to determine the potential influencing factors present at farm level. Data were collected on 157 commercial veal farms in the 3 main veal-producing countries in Europe (the Netherlands, France, and Italy). Observations of 3 non-nutritive oral behaviors (manipulating substrates, tongue rolling, and manipulating a penmate) were performed when calves were aged 14 wk, and the prevalence of these behaviors was calculated. Information on management practices and characteristics of the building and equipment were collected on all farms to assess potential influencing factors for each of the 3 behaviors. Odds ratios and 95% confidence intervals were calculated to evaluate the effect of each individual factor within a generalized linear model. The mean percentage of calves per farm performing manipulating substrates was 11.0 ± 0.46%, performing tongue rolling 2.8 ± 0 .18%, and manipulating a penmate 2.7 ± 0.09%, with a high range between farms. Allowing more space for calves than the legal minimum requirement of 1.8 m(2)/ calf and housing them in groups of >10 calves/pen reduced the incidences of manipulating substrates and tongue rolling. Incidence of manipulating substrates was lower for calves fed maize silage compared with calves fed cereal grain, pellets, or muesli. A higher risk of tongue rolling was found when baby-boxes (i.e., single housing during the first 5 to 8 wk) were not used. Risk of calves manipulating a penmate was higher for calves of milk- or meat-type breeds compared with dual-purpose breeds and for calves fed with 280 to 380 kg compared with

  18. Microsatellite markers for the endangered Roanoke logperch, Percina rex (Percidae) and their potential utility for other darter species

    USGS Publications Warehouse

    Dutton, D.J.; Roberts, J.H.; Angermeier, P.L.; Hallerman, E.M.

    2008-01-01

    The Roanoke logperch (Percina rex Jordan and Evermann), an endangered fish, occurs in only six watersheds in the Roanoke and Chowan river drainages of Virginia, USA. The species' population genetic structure is poorly known. We developed 16 microsatellite markers that were reliably scorable and polymorphic P. rex. Markers were also screened in seven other darter species of the genus Percina. Most markers exhibited successful amplification and polymorphism in several species. These markers may therefore prove useful for population genetic studies in other darters, a diverse but highly imperiled group. ?? 2008 The Authors.

  19. Transcription Profiling Reveals Potential Mechanisms of Dysbiosis in the Oral Microbiome of Rhesus Macaques with Chronic Untreated SIV Infection

    PubMed Central

    Ocon, Susan; Murphy, Christina; Dang, Angeline T.; Sankaran-Walters, Sumathi; Li, Chin-Shang; Tarara, Ross; Borujerdpur, Niku; Dandekar, Satya; Paster, Bruce J.; George, Michael D.

    2013-01-01

    A majority of individuals infected with human immunodeficiency virus (HIV) have inadequate access to antiretroviral therapy and ultimately develop debilitating oral infections that often correlate with disease progression. Due to the impracticalities of conducting host-microbe systems-based studies in HIV infected patients, we have evaluated the potential of simian immunodeficiency virus (SIV) infected rhesus macaques to serve as a non-human primate model for oral manifestations of HIV disease. We present the first description of the rhesus macaque oral microbiota and show that a mixture of human commensal bacteria and “macaque versions” of human commensals colonize the tongue dorsum and dental plaque. Our findings indicate that SIV infection results in chronic activation of antiviral and inflammatory responses in the tongue mucosa that may collectively lead to repression of epithelial development and impact the microbiome. In addition, we show that dysbiosis of the lingual microbiome in SIV infection is characterized by outgrowth of Gemella morbillorum that may result from impaired macrophage function. Finally, we provide evidence that the increased capacity of opportunistic pathogens (e.g. E. coli) to colonize the microbiome is associated with reduced production of antimicrobial peptides. PMID:24312248

  20. Investigations on the potential of a low power diode pumped Er:YAG laser system for oral surgery

    NASA Astrophysics Data System (ADS)

    Stock, Karl; Wurm, Holger; Hausladen, Florian; Wagner, Sophia; Hibst, Raimund

    2015-02-01

    Flash lamp pumped Er:YAG-lasers are used in clinical practice for dental applications successfully. As an alternative, several diode pumped Er:YAG laser systems (Pantec Engineering AG) become available, with mean laser power of 2W, 15W, and 30W. The aim of the presented study is to investigate the potential of the 2W Er:YAG laser system for oral surgery. At first an appropriate experimental set-up was realized with a beam delivery and both, a focusing unit for non-contact tissue cutting and a fiber tip for tissue cutting in contact mode. In order to produce reproducible cuts, the samples (porcine gingiva) were moved by a computer controlled translation stage. On the fresh samples cutting depth and quality were determined by light microscopy. Afterwards histological sections were prepared and microscopically analyzed regarding cutting depth and thermal damage zone. The experiments show that low laser power ≤ 2W is sufficient to perform efficient oral soft tissue cutting with cut depth up to 2mm (sample movement 2mm/s). The width of the thermal damage zone can be controlled by the irradiation parameters within a range of about 50μm to 110μm. In general, thermal injury is more pronounced using fiber tips in contact mode compared to the focused laser beam. In conclusion the results reveal that even the low power diode pumped Er:YAG laser is an appropriate tool for oral surgery.

  1. Readily restoring freeze-dried probilosomes as potential nanocarriers for enhancing oral delivery of cyclosporine A.

    PubMed

    Guan, Peipei; Lu, Yi; Qi, Jianping; Wu, Wei

    2016-08-01

    Formulating vesicular nanocarriers into dried precursors so as to overcome the drawbacks associated with liquid formulations is challengeable due to low efficiency of restoration. In this study, bilosomes interiorly thickened with gelatin (G-BLs) was evaluated for the ability to withstand freeze-drying stress and enhanced oral bioavailability of a model drug, cyclosporine A (CyA). The restoration efficiency of freeze-dried pro-G-BLs is investigated by comparing the particle size distribution, entrapment efficiency and morphology of the bilosomes before and after freeze-drying. Particle size and polydispersity index (PI) of pro-G-BLs after restoration was similar to that before freeze-drying, whereas freeze-dried bilosomes without gelatin thickening (pro-BLs) show irreversible damage and aggregation along with significantly increased particle size and PI after restoration. Entrapment efficiency of pro-G-BLs remains as high as 83.7%, in sharp contrast with 66.7% for pro-BLs. Pharmacokinetics in beagle dogs show improved absorption of CyA in pro-G-BLs as compared to pro-BLs, G-BLs and microemulsion-based Sandimmun Neoral(®). The relative oral bioavailability of CyA-loaded pro-G-BLs, pro-BLs and G-BLs was 165.2%, 123.5% and 130.1%, respectively, with Neoral(®) as the reference. It is concluded that interior thickening with gelatin significantly enhanced the stability against freeze-drying stress, which as a result improves the restoring efficiency and oral bioavailability.

  2. Microsatellite Markers of Willow Species and Characterization of 11 Polymorphic Microsatellites for Salix eriocephala (Salicaceae), a Potential Native Species for Biomass Production in Canada.

    PubMed

    Lauron-Moreau, Aurélien; Pitre, Frédéric E; Brouillet, Luc; Labrecque, Michel

    2013-03-27

    Biomass produced from dedicated plantations constitutes a source of renewable energy and is expected to play an important role in several countries in the coming decades. The cultivation of woody crops such as willows therefore raises several environmental issues. In North America, several native willows are potentially interesting for biomass producers. Willow trees are diverse but few species used for environmental applications have been the object of molecular genetic studies. Based on the sequenced poplar genome, 24 microsatellite markers were assayed on five native North American willow species: Salix amygdaloides, S. discolor, S. eriocephala, S. interior and S. nigra. Polymorphic microsatellite markers were used to characterize the allele data on the shrub Salix eriocephala, a North American species with economic potential. Eleven markers amplified and confirmed the potential of this species. Analysis of samples from six populations in eastern Canada showed that all markers were variable as well as polymorphic in at least one population. The number of alleles per locus ranged from 1 to 9 (mean 2.95) and showed that these microsatellite markers can be used to assess genetic diversity of North American willow species.

  3. The chloroplast psbK-psbI intergenic region, a potential genetic marker for broad sectional relationships in Anthurium

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nuclear and chloroplast genetic markers have been extensively used for plant identification and molecular taxonomy studies. The efficacy of genetic markers to be used as DNA barcodes is under constant evaluation and improvement, with identification of new barcodes that provide greater resolution an...

  4. Traditional Medicinal Plant Extracts and Natural Products with Activity against Oral Bacteria: Potential Application in the Prevention and Treatment of Oral Diseases

    PubMed Central

    Palombo, Enzo A.

    2011-01-01

    Oral diseases are major health problems with dental caries and periodontal diseases among the most important preventable global infectious diseases. Oral health influences the general quality of life and poor oral health is linked to chronic conditions and systemic diseases. The association between oral diseases and the oral microbiota is well established. Of the more than 750 species of bacteria that inhabit the oral cavity, a number are implicated in oral diseases. The development of dental caries involves acidogenic and aciduric Gram-positive bacteria (mutans streptococci, lactobacilli and actinomycetes). Periodontal diseases have been linked to anaerobic Gram-negative bacteria (Porphyromonas gingivalis, Actinobacillus, Prevotella and Fusobacterium). Given the incidence of oral disease, increased resistance by bacteria to antibiotics, adverse affects of some antibacterial agents currently used in dentistry and financial considerations in developing countries, there is a need for alternative prevention and treatment options that are safe, effective and economical. While several agents are commercially available, these chemicals can alter oral microbiota and have undesirable side-effects such as vomiting, diarrhea and tooth staining. Hence, the search for alternative products continues and natural phytochemicals isolated from plants used as traditional medicines are considered as good alternatives. In this review, plant extracts or phytochemicals that inhibit the growth of oral pathogens, reduce the development of biofilms and dental plaque, influence the adhesion of bacteria to surfaces and reduce the symptoms of oral diseases will be discussed further. Clinical studies that have investigated the safety and efficacy of such plant-derived medicines will also be described. PMID:19596745

  5. Induction of hairy roots and characterization of peroxidase expression as a potential root growth marker in sesame.

    PubMed

    Chun, J-A; Lee, J-W; Yi, Y-B; Park, G-Y; Chung, C-H

    2009-01-01

    Using hypocotyl and cotyledon of sesame seedlings, hairy root cultures were established and cDNA coding for a peroxidase was cloned from the roots. The frequency of sesame hairy root formation was higher in hypocotyl (33.4%) than cotyledon (9.3%). Applicable levels of kanamycin and hygromycin as a selectable marker were 100 microg/mL and 30 microg/mL, respectively. The peroxidase cDNA showed relatively high sequence identity with and similarity to plant class III peroxidase family. The cDNA encoded polypeptide was identified with the presence of three sequence features: 1) the putative 4 disulfide bridges, 2) an ER-targeted signal sequence in the N-terminus, and 3) two triplets, NXS for glycosylation. A real-time RT-PCR exhibited an abrupt increase in the peroxidase transcription activity after 4-week cultures of the sesame hairy roots and its highest level in 6-week cultured hairy roots. In contrast, the growth pattern of sesame hairy roots showed a typical sigmoidal curve. The active hairy root growth began after 2-week culture and their stationary growth phase occurred after 5-week culture. These results suggested that the peroxidase expression patterns at its transcription level could be used a potential indicator signaling a message that there will be no longer active growth in hairy root cultures. The sesame peroxidase gene was differentially expressed in different tissues.

  6. Androgen receptor is a potential novel prognostic marker and oncogenic target in osteosarcoma with dependence on CDK11

    PubMed Central

    Liao, Yunfei; Sassi, Slim; Halvorsen, Stefan; Feng, Yong; Shen, Jacson; Gao, Yan; Cote, Gregory; Choy, Edwin; Harmon, David; Mankin, Henry; Hornicek, Francis; Duan, Zhenfeng

    2017-01-01

    Osteosarcoma is the most common bone cancer in children and adolescents. Previously, we have found that cyclin-dependent kinase 11 (CDK11) signaling was essential for osteosarcoma cell growth and survival. Subsequently, CDK11 siRNA gene targeting, expression profiling, and network reconstruction of differentially expressed genes were performed between CDK11 knock down and wild type osteosarcoma cells. Reconstructed network of the differentially expressed genes pointed to the AR as key to CDK11 signaling in osteosarcoma. CDK11 increased transcriptional activation of AR gene in osteosarcoma cell lines. AR protein was highly expressed in various osteosarcoma cell lines and patient tumor tissues. Tissue microarray analysis showed that the disease-free survival rate for patients with high-expression of AR was significantly shorter than for patients with low-expression of AR. In addition, AR gene expression knockdown via siRNA greatly inhibited cell growth and viability. Similar results were found in osteosarcoma cells treated with AR inhibitor. These findings suggest that CDK11 is involved in the regulation of AR pathway and AR can be a potential novel prognostic marker and therapeutic target for osteosarcoma treatment. PMID:28262798

  7. Investigation and Sensory Characterization of 1,4-Cineole: A Potential Aromatic Marker of Australian Cabernet Sauvignon Wine.

    PubMed

    Antalick, Guillaume; Tempère, Sophie; Šuklje, Katja; Blackman, John W; Deloire, Alain; de Revel, Gilles; Schmidtke, Leigh M

    2015-10-21

    This work reports the quantitation and sensory characterization of 1,4-cineole in red wine for the first time. A headspace-solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) method was developed to quantitate 1,4-cineole and 1,8-cineole in 104 commercial Australian red wines. 1,4-Cineole was detected in all of the wines analyzed, with concentrations ranging from 0.023 to 1.6 μg/L. An important varietal effect was observed, with concentrations of 1,4-cineole in Cabernet Sauvignon wines (mean of 0.6 ± 0.3 μg/L) significantly higher than in Shiraz (0.07 ± 0.04 μg/L) and Pinot Noir (0.2 ± 0.2 μg/L) wines. Regional variations of both cineole isomer concentrations have been measured between wines originating from different Australian regions. Sensory studies demonstrated that the addition of 0.54 μg/L 1,4-cineole in a Cabernet Sauvignon wine, to produce a final concentration of 0.63 μg/L, was perceived significantly by a sensory panel (p < 0.05). Descriptive analyses revealed that 1,4-cineole and 1,8-cineole may contribute to the hay, dried herbs, and blackcurrant aromas reported in Australian Cabernet Sauvignon wines and may be potential markers of regional typicality of these wines.

  8. Do oral bacteria alter the regenerative potential of stem cells? A concise review

    PubMed Central

    Chatzivasileiou, Kyriaki; Kriebel, Katja; Steinhoff, Gustav; Kreikemeyer, Bernd; Lang, Hermann

    2015-01-01

    Mesenchymal stem cells (MSCs) are widely recognized as critical players in tissue regeneration. New insights into stem cell biology provide evidence that MSCs may also contribute to host defence and inflammation. In case of tissue injury or inflammatory diseases, e.g. periodontitis, stem cells are mobilized towards the site of damage, thus coming in close proximity to bacteria and bacterial components. Specifically, in the oral cavity, complex ecosystems of commensal bacteria live in a mutually beneficial state with the host. However, the formation of polymicrobial biofilm communities with pathogenic properties may trigger an inadequate host inflammatory-immune response, leading to the disruption of tissue homoeostasis and development of disease. Because of their unique characteristics, MSCs are suggested as crucial regulators of tissue regeneration even under such harsh environmental conditions. The heterogeneous effects of bacteria on MSCs across studies imply the complexity underlying the interactions between stem cells and bacteria. Hence, a better understanding of stem cell behaviour at sites of inflammation appears to be a key strategy in developing new approaches for in situ tissue regeneration. Here, we review the literature on the effects of oral bacteria on cell proliferation, differentiation capacity and immunomodulation of dental-derived MSCs. PMID:26058313

  9. Investigation of in vivo potential of scorpion venom against skin tumorigenesis in mice via targeting markers associated with cancer development

    PubMed Central

    Al Asmari, Abdulrahman K; Khan, Abdul Quaiyoom

    2016-01-01

    Cancer is the leading cause of morbidity and mortality all over the world in spite of the advances made in its management. In this study, we investigated the in vivo anti-tumorigenic potential of the venom obtained from a medically important scorpion species Leiurus quinquestriatus on chemically induced skin cancer in mice. Animals were divided into five groups, with 13 animals in each group. All the treatments were given topically on the shaved dorsal surface of the skin. Animals in Group 1 received vehicle only (0.2 mL acetone). Moreover, 7,12-dimethylbenz[a]anthracene (DMBA, 400 nmol per mouse) was applied to all the animals in the remaining four groups. After 1 week, different concentrations of venom (17.5 μg, 35 μg, and 52.5 μg per animal) were applied to each animal in the Groups III–V. Thirty minutes after the application of venom, croton oil was applied on the same position where venom was administered to the animals of Groups III–V. Animals in Group II were treated as the positive control (without venom) and received croton oil as in Groups III–V. The findings of this study revealed that venom extract of L. quinquestriatus inhibits DMBA + croton oil-induced mouse skin tumor incidence and tumor multiplicity. Venom treatment also decreased the expression of proinflammatory cytokines. Immunohistochemistry results showed a downregulation of the expression of molecular markers such as Ki-67, nuclear factor kappa-B, cyclooxygenase-2, B-cell lymphoma-2, and vascular endothelial growth factor, in venom-treated animals. Our findings suggest that the venom of L. quinquestriatus possesses in vivo anticancer potential and may be used in the development of anticancer molecules. PMID:27799739

  10. Oral biomarkers in exercise-induced neuroplasticity in Parkinson's disease.

    PubMed

    Mougeot, J-Lc; Hirsch, M A; Stevens, C B; Mougeot, Fkb

    2016-11-01

    In this article, we review candidate biomarkers for Parkinson's disease (PD) in oral cavity, potential of oral biomarkers as markers of neuroplasticity, and literature on the effects of exercise on oral cavity biomarkers in PD. We first describe how pathophysiological pathways of PD may be transduced from brain stem and ganglia to oral cavity through the autonomic nervous system or transduced by a reverse path. Next we describe the effects of exercise in PD and potential impact on oral cavity. We propose that biomarkers in oral cavity may be useful targets for describing exercise-induced brain neuroplasticity in PD. Nevertheless, much research remains to be carried out before applying these biomarkers for the determination of disease state and therapeutic response to develop strategies to mitigate motor or non-motor symptoms in PD.

  11. Arginine metabolism in the salivary glands of protein-deficient rats and its potential association with the oral microflora.

    PubMed

    Enwonwu, C O; Ilupeju, F; Warren, R C

    1994-01-01

    Salivary glands and their secretions play key roles in the prevention of dental diseases. The antibacterial and physicochemical properties of saliva are compromised in chronic malnutrition. The present study has examined the possibility that some malnutrition-induced changes in salivary gland function are potentially capable of promoting growth and metabolic activities of pathogenic oral microorganisms. Compared to well-fed controls, rats fed a 3% protein diet for 18 days showed a significant reduction (p < 0.001) in the submandibular gland arginase (L-arginine amidinohydrolase, EC 3.5.3.1) activity. Associated with the latter finding was a marked increase (+85%) in the glandular level of free arginine, this basic amino acid accounting for 12.2% of the total essential amino acids as compared with a figure of only 4.6% for the controls. The total free amino acid pool in whole saliva was relatively unaffected by malnutrition, but the levels of the basic amino acids arginine and histidine were marginally increased. Many oral bacterial species, some of which are dominant plaque microorganisms, utilize the arginine deiminase (EC 3.5.3.6) pathway. Thus, increased availability of free arginine from salivary glands offers a plausible explanation for the frequently reported observation of differential overgrowth of several potentially pathogenic microorganisms including some mutants streptococci in protein-deficient laboratory animals and may well apply to similar findings in malnourished populations in Third World countries.

  12. Synthesis and characterization of low surface energy fluoropolymers as potential barrier coatings in oral care.

    PubMed

    Churchley, David P; Barbu, Eugen; Ewen, Richard J; Shen, Zhihao; Kim, Yongchul; McHugh, Mark A; Zhang, Zhong Yi; Nevell, Thomas G; Rees, Gareth D; Tsibouklis, John

    2008-03-15

    A series of low surface energy fluorinated homopolymers and copolymers has been synthesized and characterized using thermal, optical, spectroscopic, and chromatographic techniques. Their utility as barrier technologies in oral care has been considered, and aqueous nanosuspensions of the materials have been deposited as films on model dental hard surfaces in the presence and absence of a salivary pellicle. Calcium hydroxyapatite has been used as a model for enamel, as has PMMA due to its widespread use in denture fabrication. Surface energy determinations, combined with XPS studies, have provided insights into the molecular-level organization at the surface of the film structures. Studies of solubility in supercritical carbon dioxide have identified the polymers that are suitable for processing in this medium.

  13. Impairment of mesenchymal stem cells derived from oral leukoplakia.

    PubMed

    Zhang, Zhihui; Song, Jiangyuan; Han, Ying; Mu, Dongdong; Su, Sha; Ji, Xiaoli; Liu, Hongwei

    2015-01-01

    Oral leukoplakia is one of the common precancerous lesions in oral mucosa. To compare the biological characteristics and regenerative capacities of mesenchymal stem cells (MSCs) from oral leukoplakia (epithelial hyperplasia and dysplasia) and normal oral mucosa, MSCs were isolated by enzyme digestion. Then these cells were identified by the expression of MSC related markers, STRO-1, CD105 and CD90, with the absent for the hematopoietic stem cell marker CD34 by flow cytometric detection. The self-renewal ability of MSCs from oral leukoplakia was enhanced, while the multipotent differentiation was descended, compared with MSCs from normal oral mucosa. Fibrin gel was used as a carrier for MSCs transplanted into immunocompromised mice to detect their regenerative capacity. The regenerative capacities of MSCs from oral leukoplakia became impaired partly. Collagen IV (Col IV) and matrix metalloproteinases-9 (MMP-9) were selected to analyze the potential mechanism for the functional changes of MSCs from oral leukoplakia by immunochemical and western blot analysis. The expression of Col IV was decreased and that of MMP-9 was increased by MSCs with the progression of oral leukoplakia, especially in MSCs from epithelial dysplasia. The imbalance between regenerative and metabolic self-regulatory functions of MSCs from oral leukoplakia may be related to the progression of this premalignant disorder.

  14. Quantum dots based potential-resolution dual-targets electrochemiluminescent immunosensor for subtype of tumor marker and its serological evaluation.

    PubMed

    Liu, Xuan; Jiang, Hui; Fang, Yuan; Zhao, Wei; Wang, Nianyue; Zang, Guizhen

    2015-09-15

    The identification of subtypes of known tumor markers is of great importance for clinical diagnosis but still a great challenge in novel detection methodologies with simple operation and acceptable sensitivity. This work for the first time reported a quantum dots (QDs) based potential-resolved electrochemiluminescent (ECL) immunosensor to realize simultaneous detection of dual targets. Because of different surface microstructures, dimercaptosuccinic acid stabilized CdTe (DMSA-CdTe) QDs and TiO2 nanoparticles-glutathione stabilized CdTe (TiO2-GSH-CdTe) QDs composites showed a large difference of ECL peak potential (∼360 mV), which provided an access for potential-resolution detection. The ECL emission on indium tin oxide electrodes showed consistent strength during the cyclic scan, and intensity data were collected at -0.89 V and -1.25 V (vs Ag/AgCl) for DMSA-CdTe QDs and TiO2-GSH-CdTe QDs composites, respectively. The interface modification procedures of immunosensor construction were characterized by atomic force microscopy. The portion of Lens culinaris lectin affiliated isoform of alpha fetoprotein (AFP), AFP-L3%, in total AFP, is recently a novel criteria showing even higher sensitivity and specificity than AFP at the early stage of cancer. Combined with the enzyme cyclic amplification strategy, linear ranges for AFP-L3 and AFP dual-targets detection were 3.24 pg mL(-1)-32.4 ng mL(-1) and 1.0 pg mL(-1)-20 ng mL(-1), with limits of detection of 3.24 pg mL(-1) and 1.0 pg mL(-1), respectively. Compared with clinical detection data, the calculated portion of AFP-L3% by as-prepared immunosensor showed acceptable accuracy. These results open a new avenue for facile and rapid multiple-components detection based on the nano-ECL technique and provide a new clinical diagnosis platform for HCC.

  15. Mutagenesis and carcinogenesis induced by dibenzo[a,l]pyrene in the mouse oral cavity: a potential new model for oral cancer.

    PubMed

    Guttenplan, Joseph B; Kosinska, Wieslawa; Zhao, Zhong-Lin; Chen, Kun-Ming; Aliaga, Cesar; DelTondo, Joseph; Cooper, Timothy; Sun, Yuan-Wan; Zhang, Shang-Min; Jiang, Kun; Bruggeman, Richard; Sharma, Arun K; Amin, Shantu; Ahn, Kwangmi; El-Bayoumy, Karam

    2012-06-15

    Cancer of the oral cavity is a serious disease, affecting about 30,000 individuals in US annually. There are several animal models of oral cancer, but each has certain disadvantages. As a new model, we investigated whether topical application of the tobacco smoke carcinogen, dibenzo[a,l]pyrene (DB[a,l]P) is mutagenic and carcinogenic in the oral cavity of the B6C3F1 lacI and B6C3F1 mouse, respectively. B6C3F1 lacI mice received DB[a,l]P (0, 3, 6, 12 nmol) 3× per week. B6C3F1 mice received the same doses and also 24 nmol. At 38 weeks mutagenesis was measured in oral tissues in lacI mice. For the high dose group, the mutant fraction (MF) in upper mucosa and tongue increased about twofold relative to that in vehicle-alone. The increases were statistically significant. The mutational profile in the DB[a,l]P-induced mutants was compared with that induced by benzo[a]pyrene (BaP) in oral tissue. BaP is mutagenic in many tissues when administered by gavage. The mutational profile for DB[a,l]P was more similar to that reported for p53 mutations in head and neck cancers than was that of BaP. At 47 weeks, oral squamous cell carcinomas (OSCC) were found in 31% of the high-dose B6C3F1 group. Elevations of p53 and COX-2 protein were observed in tumor and dysplastic tissue. As DB[a,l]P induces mutations and tumors in the oral cavity, and has a mutational profile in oral tissue similar to that found in p53 in human OSCC, the treatment protocol described here may represent a new and relevant model for cancer of the oral cavity.

  16. Gross cystic disease fluid protein 15 in stratum corneum is a potential marker of decreased eccrine sweating for atopic dermatitis.

    PubMed

    Kamiya, Koji; Sakabe, Jun-Ichi; Yamaguchi, Hayato; Suzuki, Takahiro; Yatagai, Tsuyoshi; Aoshima, Masahiro; Ito, Taisuke; Tokura, Yoshiki

    2015-01-01

    It is well known that eccrine sweating is attenuated in patients with atopic dermatitis (AD). We have reported by using proteome analysis that gross cystic disease fluid protein 15 (GCDFP15), a substance secreted from eccrine sweat glands, is decreased in tape-stripped stratum corneum (SC) samples from AD patients. The aim of this study was to evaluate GCDFP15 production by eccrine glands with SC samples and to assess sweating in AD. SC samples were obtained from 51 healthy control (HC) and 51 AD individuals. Sweat samples were from 18 HC and 12 AD subjects. GCDFP15 was quantified by ELISA. By immunohistochemistry, the expression of GCDFP15 in eccrine glands was examined in normal and AD skin specimens. To identify GCDFP15-producing cells, double immunofluorescence staining for GCDFP15 and S100 protein was performed in frozen sections. To address the mechanism underlying the decreased eccrine sweating in AD patients, we examined the expression of cholinergic receptor M3 (CHRM3), a receptor for acetylcholine-induced sweating, in eccrine sweat glands. The amounts of GCDFP15 in the SC extracts were significantly lower in AD than HC (P < 0.0001). The sweat samples from AD patients also had lower levels of GCDFP15 concentration (P < 0.05). Immunohistochemistry showed positive GCDFP15 staining in the eccrine gland secretory cells and the ductal and acrosyringial lumen in normal skin, but AD lacked clear staining. Immunofluorescence staining revealed that GCDFP15 was co-expressed with S100 protein, suggesting that the clear cell of eccrine glands produces GCDFP15. Finally, we found that the expression of CHRM3 was depressed in AD, suggesting contribution to the low sweating. The SC of AD patients contains a low amount of GCDFP15 due to both low sweating and low GCDFP15 concentration in the sweat. GCDFP15 in SC is a potential marker for dysregulated sweating in AD.

  17. Modeling of the total antioxidant capacity of rooibos (Aspalathus linearis) tea infusions from chromatographic fingerprints and identification of potential antioxidant markers.

    PubMed

    Orzel, Joanna; Daszykowski, Michal; Kazura, Malgorzata; de Beer, Dalene; Joubert, Elizabeth; Schulze, Alexandra E; Beelders, Theresa; de Villiers, André; Malherbe, Christiaan J; Walczak, Beata

    2014-10-31

    Models to predict the total antioxidant capacity (TAC) of rooibos tea infusions from their chromatographic fingerprints and peak table data (content of individual phenolic compounds), obtained using HPLC with diode array detection, were developed in order to identify potential antioxidant markers. Peak table data included the content of 12 compounds, namely phenylpyruvic acid-2-O-glucoside, aspalathin, nothofagin, isoorientin, orientin, ferulic acid, quercetin-3-O-robinobioside, vitexin, hyperoside, rutin, isovitexin and isoquercitrin. The TAC values, measured using the oxygen radical absorbance capacity (ORAC) and DPPH radical scavenging assays, could be predicted from the peak table data or the chromatographic fingerprints (prediction errors 9-12%) using partial least squares (PLS) regression. Prediction models created from samples of only two production years could additionally be used to predict the TAC of samples from another production year (prediction errors<13%) indicating the robustness of the models in a quality control environment. Furthermore, the uninformative variable elimination (UVE)-PLS method was used to identify potential antioxidant markers for rooibos infusions. All individual phenolic compounds that were quantified were selected as informative variables, except vitexin, while UVE-PLS models developed from chromatographic fingerprints indicated additional antioxidant markers, namely (S)-eriodictyol-6-C-glucoside, (R)-eriodictyol-6-C-glucoside, aspalalinin and two unidentified compounds. The potential antioxidant markers should be validated prior to use in quality control of rooibos tea.

  18. Computer vision approach to morphometric feature analysis of basal cell nuclei for evaluating malignant potentiality of oral submucous fibrosis.

    PubMed

    Muthu Rama Krishnan, M; Pal, Mousumi; Paul, Ranjan Rashmi; Chakraborty, Chandan; Chatterjee, Jyotirmoy; Ray, Ajoy K

    2012-06-01

    This research work presents a quantitative approach for analysis of histomorphometric features of the basal cell nuclei in respect to their size, shape and intensity of staining, from surface epithelium of Oral Submucous Fibrosis showing dysplasia (OSFD) to that of the Normal Oral Mucosa (NOM). For all biological activity, the basal cells of the surface epithelium form the proliferative compartment and therefore their morphometric changes will spell the intricate biological behavior pertaining to normal cellular functions as well as in premalignant and malignant status. In view of this, the changes in shape, size and intensity of staining of the nuclei in the basal cell layer of the NOM and OSFD have been studied. Geometric, Zernike moments and Fourier descriptor (FD) based as well as intensity based features are extracted for histomorphometric pattern analysis of the nuclei. All these features are statistically analyzed along with 3D visualization in order to discriminate the groups. Results showed increase in the dimensions (area and perimeter), shape parameters and decreasing mean nuclei intensity of the nuclei in OSFD in respect to NOM. Further, the selected features are fed to the Bayesian classifier to discriminate normal and OSFD. The morphometric and intensity features provide a good sensitivity of 100%, specificity of 98.53% and positive predicative accuracy of 97.35%. This comparative quantitative characterization of basal cell nuclei will be of immense help for oral onco-pathologists, researchers and clinicians to assess the biological behavior of OSFD, specially relating to their premalignant and malignant potentiality. As a future direction more extensive study involving more number of disease subjects is observed.

  19. Evaluation of the Antibacterial Potential of Liquid and Vapor Phase Phenolic Essential Oil Compounds against Oral Microorganisms.

    PubMed

    Wang, Tong-Hong; Hsia, Shih-Min; Wu, Chi-Hao; Ko, Shun-Yao; Chen, Michael Yuanchien; Shih, Yin-Hua; Shieh, Tzong-Ming; Chuang, Li-Chuan; Wu, Ching-Yi

    The aim of the present study was to determine the antibacterial activities of the phenolic essential oil (EO) compounds hinokitiol, carvacrol, thymol, and menthol against oral pathogens. Aggregatibacter actinomycetemcomitans, Streptococcus mutans, Methicillin-resistant Staphylococcus aureus (MRSA), and Escherichia. coli were used in this study. The minimum inhibitory concentrations (MICs), minimum bactericidal concentrations (MBCs), bacterial growth curves, temperature and pH stabilities, and synergistic effects of the liquid and vapor EO compounds were tested. The MIC/MBC of the EO compounds, ranging from the strongest to weakest, were hinokitiol (40-60 μg/mL/40-100 μg/mL), thymol (100-200 μg/mL/200-400 μg/mL), carvacrol (200-400 μg/mL/200-600 μg/mL), and menthol (500-more than 2500 μg/mL/1000-more than 2500 μg/mL). The antibacterial activities of the four EO phenolic compound based on the agar diffusion test and bacterial growth curves showed that the four EO phenolic compounds were stable under different temperatures for 24 h, but the thymol activity decreased when the temperature was higher than 80°C. The combination of liquid carvacrol with thymol did not show any synergistic effects. The activities of the vaporous carvacrol and thymol were inhibited by the presence of water. Continual violent shaking during culture enhanced the activity of menthol. Both liquid and vaporous hinokitiol were stable at different temperatures and pH conditions. The combination of vaporous hinokitiol with zinc oxide did not show synergistic effects. These results showed that the liquid and vapor phases of hinokitiol have strong anti-oral bacteria abilities. Hinokitiol has the potential to be applied in oral health care products, dental materials, and infection controls to exert antimicrobial activity.

  20. Evaluation of the Antibacterial Potential of Liquid and Vapor Phase Phenolic Essential Oil Compounds against Oral Microorganisms

    PubMed Central

    Wu, Chi-Hao; Ko, Shun-Yao; Chen, Michael Yuanchien; Shih, Yin-Hua; Shieh, Tzong-Ming; Chuang, Li-Chuan; Wu, Ching-Yi

    2016-01-01

    The aim of the present study was to determine the antibacterial activities of the phenolic essential oil (EO) compounds hinokitiol, carvacrol, thymol, and menthol against oral pathogens. Aggregatibacter actinomycetemcomitans, Streptococcus mutans, Methicillin-resistant Staphylococcus aureus (MRSA), and Escherichia. coli were used in this study. The minimum inhibitory concentrations (MICs), minimum bactericidal concentrations (MBCs), bacterial growth curves, temperature and pH stabilities, and synergistic effects of the liquid and vapor EO compounds were tested. The MIC/MBC of the EO compounds, ranging from the strongest to weakest, were hinokitiol (40–60 μg/mL/40-100 μg/mL), thymol (100–200 μg/mL/200-400 μg/mL), carvacrol (200–400 μg/mL/200-600 μg/mL), and menthol (500-more than 2500 μg/mL/1000-more than 2500 μg/mL). The antibacterial activities of the four EO phenolic compound based on the agar diffusion test and bacterial growth curves showed that the four EO phenolic compounds were stable under different temperatures for 24 h, but the thymol activity decreased when the temperature was higher than 80°C. The combination of liquid carvacrol with thymol did not show any synergistic effects. The activities of the vaporous carvacrol and thymol were inhibited by the presence of water. Continual violent shaking during culture enhanced the activity of menthol. Both liquid and vaporous hinokitiol were stable at different temperatures and pH conditions. The combination of vaporous hinokitiol with zinc oxide did not show synergistic effects. These results showed that the liquid and vapor phases of hinokitiol have strong anti-oral bacteria abilities. Hinokitiol has the potential to be applied in oral health care products, dental materials, and infection controls to exert antimicrobial activity. PMID:27681039

  1. The MiiA motif is a common marker present in polytopic surface proteins of oral and urinary tract invasive bacteria.

    PubMed

    Martín-Galiano, Antonio J

    2017-04-01

    Many surface virulence factors of bacterial pathogens show mosaicism and confounding phylogenetic origin. The Streptococcus gordonii platelet-binding GspB protein, the Streptococcus sanguinis SrpA adhesin and the Streptococcus pneumoniae DiiA protein, share an imperfect 27-residue motif. Given the disparate domain architectures of these proteins and its association to invasive disease, this motif was named MiiA from Multiarchitecture invasion-involved motif A. MiiA is predicted to adopt a beta-sheet folding, probably related to the Ig-like fold, with a symmetrical positioning of two conserved aspartic residues. A specific hidden Markov model profiling MiiA was built, which specifically detected the motif in proteins from 58 species, mainly in cell-wall proteins from Gram-positive bacteria. These proteins contained one to ten MiiA motifs, which were embedded within larger repeat units of 70-82 residues. MiiA motifs combined to other domains and elements such as coiled-coils and low-complexity regions. The species carrying MiiA-proteins included commensals from the urogenital tract and the oral cavity, which can cause opportunistic endocarditis and sepsis. Intra-protein MiiA repeats showed a complex mixture of orthologal, paralogal and inter-species relationships, suggestive of a multistep origin. Presence of these repeats in proteins involved in oligosaccharide recognition and lifestyle of species suggest a putative function for MiiA repeats in sugars binding, probably those present in receptors of epithelial and blood cells. MiiA modules appear to have been transferred horizontally between species co-habiting in the same niche to create their own MiiA-containing determinants. The present work provides a global study and a catalog of potential MiiA virulence factors that should be analyzed experimentally.

  2. Tropomyosin-1 acts as a potential tumor suppressor in human oral squamous cell carcinoma

    PubMed Central

    Pan, Hao; Gu, Liqun; Liu, Binjie; Li, Yiping; Wang, Yuehong; Bai, Xinna; Li, Long; Wang, Baisheng; Peng, Qian; Yao, Zhigang; Tang, Zhangui

    2017-01-01

    It is widely accepted that oral squamous cell carcinoma (OSCC) is a major contributor to the incidence and mortality of neck and head cancer. Tropomyosin-1 (TPM1), which is expressed at a low level, has been considered a prominent tumor-suppressing gene in a variety of solid tumors, although the precise mechanism of the TPM1 gene in OSCC progression remains unknown. We found that TPM1 expression levels decreased in OSCC patients and OSCC cell lines. The overall and cancer-specific survival of patients who exhibited low TPM1 levels were inferior to those of patients who had high TPM1 levels. It was also found that OSCC patients who suffered from disease stageⅠ-Ⅱ were more likely to have an up-regulated TPM1 expression level, and OSCC patients with lymph node metastasis had a higher probability of exhibiting reduced TPM1 expression. We show that overexpression of TPM1 can promote cell apoptosis and inhibit migration. Our results suggest that TPM1 can suppress tumors in OSCC, and the TPM1 expression level is related to OSCC patient prognosis. PMID:28182650

  3. Tropomyosin-1 acts as a potential tumor suppressor in human oral squamous cell carcinoma.

    PubMed

    Pan, Hao; Gu, Liqun; Liu, Binjie; Li, Yiping; Wang, Yuehong; Bai, Xinna; Li, Long; Wang, Baisheng; Peng, Qian; Yao, Zhigang; Tang, Zhangui

    2017-01-01

    It is widely accepted that oral squamous cell carcinoma (OSCC) is a major contributor to the incidence and mortality of neck and head cancer. Tropomyosin-1 (TPM1), which is expressed at a low level, has been considered a prominent tumor-suppressing gene in a variety of solid tumors, although the precise mechanism of the TPM1 gene in OSCC progression remains unknown. We found that TPM1 expression levels decreased in OSCC patients and OSCC cell lines. The overall and cancer-specific survival of patients who exhibited low TPM1 levels were inferior to those of patients who had high TPM1 levels. It was also found that OSCC patients who suffered from disease stageⅠ-Ⅱ were more likely to have an up-regulated TPM1 expression level, and OSCC patients with lymph node metastasis had a higher probability of exhibiting reduced TPM1 expression. We show that overexpression of TPM1 can promote cell apoptosis and inhibit migration. Our results suggest that TPM1 can suppress tumors in OSCC, and the TPM1 expression level is related to OSCC patient prognosis.

  4. Expression of VP1 protein in the milk of transgenic mice: a potential oral vaccine protects against enterovirus 71 infection.

    PubMed

    Chen, Hsiao-Ling; Huang, Jiun-Yan; Chu, Te-Wei; Tsai, Tung-Chou; Hung, Che-Ming; Lin, Chih-Cheng; Liu, Fang-Chueh; Wang, Li-Chung; Chen, Yi-Ju; Lin, Ming-Fong; Chen, Chuan-Mu

    2008-06-02

    Enterovirus 71 (EV71) is the most common etiological agent detected in cases of hand-foot-and-mouth disease (HFMD) resulting in incidences of neurological complications and fatality in recent years. The clinical data have already shown the significant increase in recent EV71 epidemic activity throughout the Asia-Pacific region. Due to the lack of an effective antiviral agent, primary prevention of the disease, including the development of an effective vaccine, has been the top priority in terms of control strategies. In this study, we first generated a transgenic animal system to produce the EV71 VP1 capsid protein under the control of alpha-lactalbumin promoter and alpha-casein leader sequences. A high level of recombinant VP1 protein (2.51 mg/ml) was expressed and secreted into the milk of transgenic mice. Mouse pups that received VP1-transgenic milk orally demonstrated relatively better health conditions after challenge with the respective virus as compared with the non-transgenic milk fed group; moreover, the mice fed with the VP1-milk had body weights similar to those of the PBS placebo control groups. According to the serum-neutralization assay and serum antibody detection, the littermates suckling VP1-milk generated antibodies specific to EV71. Our data suggest that EV71 VP1-containing milk is suitable for development as a potential oral vaccine.

  5. Plasma levels of the tissue inhibitor matrix metalloproteinase-3 as a potential biomarker in oral cancer progression

    PubMed Central

    Su, Chun-Wen; Su, Bo-Feng; Chiang, Whei-Ling; Yang, Shun-Fa; Chen, Mu-Kuan; Lin, Chiao-Wen

    2017-01-01

    Oral cancer is the most common malignancy with poor prognosis and is the fourth most common cancer in men in Taiwan. The tissue inhibitor of metalloproteinase-3 (TIMP3) acts as a tumor suppressor gene by inhibiting the growth, angiogenesis, migration, and invasion of cancer cells. However, few studies have examined the association of plasma TIMP3 levels with oral squamous cell carcinoma (OSCC), and the role of plasma TIMP3 levels in OSCC progression is still unclear. We measured the plasma TIMP3 levels of 450 OSCC patients and 64 healthy controls by using a commercial enzyme-linked immunosorbent assay. We also analyzed TIMP3 mRNA levels of 328 OSCC patients and 32 normal tissues from The Cancer Genome Atlas (TCGA) dataset. Our results revealed that plasma TIMP3 levels were significantly lower in patients with OSCC than in healthy controls (p < 0.001). Moreover, plasma TIMP3 levels in patients with OSCC were significantly associated with the tumor stage and tumor status but not with the lymph node status, metastasis, and cell differentiation. To verify our findings, we also examined TCGA bioinformatics database and discovered similar results for the association with the pathological stage of OSCC. In conclusion, our results suggest that plasma TIMP3 is a potential biomarker for predicting the tumor stage and T status in patients with OSCC. PMID:28138307

  6. Mathematical Models to Explore Potential Effects of Supersaturation and Precipitation on Oral Bioavailability of Poorly Soluble Drugs.

    PubMed

    Kleppe, Mary S; Forney-Stevens, Kelly M; Haskell, Roy J; Bogner, Robin H

    2015-07-01

    Poorly soluble drugs are increasingly formulated into supersaturating drug delivery systems which may precipitate during oral delivery. The link between in vitro drug concentration profiles and oral bioavailability is under intense investigation. The objective of the present work was to develop closed-form analytical solutions that relate in vitro concentration profiles to the amount of drug absorbed using several alternate assumptions and only six parameters. Three parameters define the key features of the in vitro drug concentration-time profile. An additional three parameters focus on physiological parameters. Absorption models were developed based on alternate assumptions; the drug concentration in the intestinal fluid: (1) peaks at the same time and concentration as in vitro, (2) peaks at the same time as in vitro, or (3) reaches the same peak concentration as in vitro. The three assumptions provide very different calculated values of bioavailability. Using Case 2 assumptions, bioavailability enhancement was found to be less than proportional to in silico examples of dissolution enhancement. Case 3 assumptions lead to bioavailability enhancements that are more than proportional to dissolution enhancements. Using Case 1 predicts drug absorption amounts that fall in between Case 2 and 3. The equations developed based on the alternate assumptions can be used to quickly evaluate the potential improvement in bioavailability due to intentional alteration of the in vitro drug concentration vs. time curve by reformulation. These equations may be useful in making decisions as to whether reformulation is expected to provide sufficient bioavailability enhancement to justify the effort.

  7. A potential oral anticancer drug candidate, Moringa oleifera leaf extract, induces the apoptosis of human hepatocellular carcinoma cells

    PubMed Central

    JUNG, IL LAE; LEE, JU HYE; KANG, SE CHAN

    2015-01-01

    It has previously been reported that cold water-extracts of Moringa oleifera leaf have anticancer activity against various human cancer cell lines, including non-small cell lung cancer. In the present study, the anticancer activity of M. oleifera leaf extracts was investigated in human hepatocellular carcinoma HepG2 cells. By the analysis of apoptotic signals, including the induction of caspase or poly(ADP-ribose) polymerase cleavage, and the Annexin V and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assays, it was demonstrated that M. oleifera leaf extracts induce the apoptosis of HepG2 cells. In the hollow fiber assay, oral administration of the leaf extracts significantly reduced (44–52%) the proliferation of the HepG2 cells and A549 non-small cell lung cancer cells. These results support the potential of soluble extracts of M. oleifera leaf as orally administered therapeutics for the treatment of human liver and lung cancers. PMID:26622717

  8. A potential oral anticancer drug candidate, Moringa oleifera leaf extract, induces the apoptosis of human hepatocellular carcinoma cells.

    PubMed

    Jung, Il Lae; Lee, Ju Hye; Kang, Se Chan

    2015-09-01

    It has previously been reported that cold water-extracts of Moringa oleifera leaf have anticancer activity against various human cancer cell lines, including non-small cell lung cancer. In the present study, the anticancer activity of M. oleifera leaf extracts was investigated in human hepatocellular carcinoma HepG2 cells. By the analysis of apoptotic signals, including the induction of caspase or poly(ADP-ribose) polymerase cleavage, and the Annexin V and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assays, it was demonstrated that M. oleifera leaf extracts induce the apoptosis of HepG2 cells. In the hollow fiber assay, oral administration of the leaf extracts significantly reduced (44-52%) the proliferation of the HepG2 cells and A549 non-small cell lung cancer cells. These results support the potential of soluble extracts of M. oleifera leaf as orally administered therapeutics for the treatment of human liver and lung cancers.

  9. Lipocalin 2 (LCN2) is a promising target for cholangiocarcinoma treatment and bile LCN2 level is a potential cholangiocarcinoma diagnostic marker

    PubMed Central

    Chiang, Kun-Chun; Yeh, Ta-Sen; Wu, Ren-Chin; Pang, Jong-Hwei S.; Cheng, Chi-Tung; Wang, Shang-Yu; Juang, Horng-Heng; Yeh, Chun-Nan

    2016-01-01

    Cholangiocarcinoma (CCA) is a devastating disease due to resistance to traditional chemotherapies and radiotherapies. New therapeutic strategies against CCA are urgently needed. This study investigated the role of lipocalin-2 (LCN2) in human cholangiocarcinoma as a potential therapeutic target and diagnostic marker. So far, the role of LCN2 in cancer is still controversial and studies regarding the role of LCN2 in CCA are limited. LCN2 knockdown inhibited CCA cell growth in vitro and in vivo through induction of cell cycle arrest at G0/G1 phases and decreased metastatic potential due to repression of epithelial-mesenchymal transition (EMT). Overexpression of LCN2 in CCA cells increased cell metastatic potential. We showed for the first time that the N-myc downstream regulated gene 1 (NDRG1) and NDRG2, known as tumor suppressor genes, are negatively regulated by LCN2 in CCA cells. LCN2 concentration in bile was higher in patients with CCA than that in patients with gallstones, with a cutoff value of 20.08 ng/ml making this a potential diagnostic marker. Higher LCN2 expression was associated with worse survival in patients with CCA. LCN2 is a promising target for CCA treatment and bile LCN2 level is a potential diagnostic marker for CCA. PMID:27782193

  10. Development of simple sequence repeat markers in persimmon (Diospyros L.) and their potential use in related species.

    PubMed

    Yang, Y; Jing, Z B; Ruan, X F; Cheng, J M

    2015-01-30

    Persimmon (Diospyros L.) is an economically important fruit in the world, and it has been recognized as a healthy nutrient supply for human consumption. In this study, 14 microsatellite markers were developed from an AG/TC and AC/TG-enriched genomic library of Chinese persimmon Mopanshi. Twelve polymorphic markers were selected in 4 related species; these markers showed transferability to the 4 related persimmon species. In addition, 10 simple sequence repeat (SSR) markers were used to detect the genetic diversity among 51 persimmon accessions from China, Japan, and Korea. A total of 57 polymorphic bands with an average of 5.7 bands per primer pair were observed. According to cluster analysis and principal coordinate analysis, all persimmon accessions could be divided into 4 groups. A close relationship existed between D. kaki and D. oleifera, and D. glaucifolia and D. lotus. Jinzaoshi could be considered a separate species of persimmon. These new SSR markers provide tools for evaluating genetic relatedness among different persimmon species.

  11. Summary of impact markers and potential impact mechanisms for the YDB impact event at 12.9 ka

    NASA Astrophysics Data System (ADS)

    Bunch, T. E.; Schultz, P. H.; Wittke, J. H.; West, A.; Kennett, J.; Kennett, D. J.

    2009-12-01

    Until the announcements of a possible impact event (Firestone et al. 2007; Kennett et al., 2009a; 2009b) at the beginning of the Younger Dryas (YD) around 12.9 ka, the KT impact layer (KTB) that resulted from the Chicxulub impact at 65 mya was the only geological boundary layer known to contain coeval peaks in various impact markers, including diamonds. Here, we compare impact markers from the KTB, YD boundary layer (YDB), and the 1908 Tunguska airburst layer (TAL). First order markers, related to impact and biomass burning, include: magnetic spherules, carbon spherules, nanodiamonds (cubic and lonsdaleite), iridium anomalies, charcoal, fullerenes (with high 3He to 4He ratio), grape-like soot, and widespread extinctions. Observations and analytical data for the YDB are consistent with all of the KTB markers, while the last three markers are unknown or inconclusive for the Tunguska layer. Selected markers for cratering events, e.g, Chicxulub, are: a visible crater, shocked minerals, impact breccia, and microtektites. None of these are known for the YD event or Tunguska. The discussion here is limited to possible origins of the impact markers and not with impact consequences (climate change, extinctions, etc.). Several origins may account for impact materials in the YDB: (1) An extraordinary accretion of micrometeorites (Pinter and Ishman, 2008). However, this is inconsistent with YDB carbon spherule compositions, including the large concentrations of nanodiamonds found embedded in those carbon spherules. (2) Oblique impact(s) into the Laurentide Ice Sheet. This model is consistent with the lack of a visible crater and apparent lack of cratering markers (above), and yet also provides for shock production of the many cubic nanodiamonds and lonsdaleite found in the YDB. (3) Impact-induced aerial burst. e.g, Boslough and Crawford (2007); Shuvalov (2008). The lack of high shock pressures in an aerial detonation does not necessarily preclude the formation of cubic and

  12. Proteomic analysis allows for early detection of potential markers of metabolic impairment in very young obese children

    PubMed Central

    2014-01-01

    Apo A1 (IR vs. non-IR). Assays routinely used in the clinical setting (ELISA/kinetic nephelometry), only partially confirmed the changes observed by proteomic analysis (ApoA1 and haptoglobin). Conclusion Proteomic analysis can allow for the identification of potential new candidate biomarkers as a complement to routinely used assays to detect initial changes in serum markers of inflammation and lipid metabolism impairment in young obese children. PMID:24949022

  13. Short-term Effects of Air Temperature on Blood Markers of Coagulation and Inflammation in Potentially Susceptible Individuals

    EPA Science Inventory

    Objectives: Changes in air temperature are associated with an increase in cardiovascular events, but the role of pro-coagulant and pro-inflammatory blood markers is still poorly understood. We investigated the association between air temperature and fibrinogen, plasminogen act...

  14. Acylcarnitines as markers of exercise-associated fuel partitioning, xenometabolism, and potential signals to muscle afferent neurons

    Technology Transfer Automated Retrieval System (TEKTRAN)

    With insulin-resistance or type 2 diabetes mellitus, mismatches between mitochondrial fatty acid fuel delivery and oxidative phosphorylation/tricarboxylic acid cycle activity may contribute to inordinate accumulation of short- or medium-chain acylcarnitine fatty acid derivatives (markers of incomple...

  15. ANO1 as a marker of oral squamous cell carcinoma and silencing ANO1 suppresses migration of human scc-25 cells

    PubMed Central

    Li, Yadong; Zhang, Jinsong

    2014-01-01

    Objectives: The purpose of this study is to confirm that ANO1 correlates with occurrence and metastasis of OSCC. Study Design: Immunohistochemistry was used to detect the expression of ANO1 in 160 specimens of OSCC and normal tissues. Lentiviral silencing ANO1 was used in scc-25 cell line to study the cell migration and cell detachment. Results: Immunohistochemical staining revealed that ANO1 was expressed in a large majority (132 out of 160, 82.5%) of OSCC specimens and that the rate of ANO1 expression in OSCC was significantly higher than that of normal tissue (P<0.05); The rate of ANO1 expression was higher in metastatic tumors than in non-metastatic tumors, and the difference was significant (P<0.05). The results of cell migration assay showed that the percentage of cells through the membrane was 26.61 ±0.81 in assay group, and 54.26 ±3.74 in control group, respectively (t=-16.22,P<0.0001). The results of cell detachment assay showed that the percentage of cells detachment was 37.42 ±0.90 in assay group, and 87.38 ±1.59 in control group, respectively (t=-62.34, P<0.0001). The results of wound healing assay showed the assay group had a reduced migration rate compared with the control group in 32 h (F=1038.78, P<0.0001). Wound closure was no significantly different between the assay and control cells when DIDS was used in wound healing assay (F=4.61,P>0.05). Conclusions: Our study shows that abnormal expression of ANO1 correlated with the occurrence and metastasis of OSCC in clinical specimens and that silencing ANO1 greatly reduced migration ability of scc-25 cells. Calcium activated chloride channel activity of ANO1 promoted the cell migration. Thus, ANO1 could represent a new diagnostic biomarker and a potentially important therapeutic target of OSCC. Key words:Oral squamous cell carcinoma, chloride channel, metastasis. PMID:24316695

  16. Dental pulp stem cells express tendon markers under mechanical loading and are a potential cell source for tissue engineering of tendon-like tissue.

    PubMed

    Chen, Yu-Ying; He, Sheng-Teng; Yan, Fu-Hua; Zhou, Peng-Fei; Luo, Kai; Zhang, Yan-Ding; Xiao, Yin; Lin, Min-Kui

    2016-12-16

    Postnatal mesenchymal stem cells have the capacity to differentiate into multiple cell lineages. This study explored the possibility of dental pulp stem cells (DPSCs) for potential application in tendon tissue engineering. The expression of tendon-related markers such as scleraxis, tenascin-C, tenomodulin, eye absent homologue 2, collagens I and VI was detected in dental pulp tissue. Interestingly, under mechanical stimulation, these tendon-related markers were significantly enhanced when DPSCs were seeded in aligned polyglycolic acid (PGA) fibre scaffolds. Furthermore, mature tendon-like tissue was formed after transplantation of DPSC-PGA constructs under mechanical loading conditions in a mouse model. This study demonstrates that DPSCs could be a potential stem cell source for tissue engineering of tendon-like tissue.

  17. Dental pulp stem cells express tendon markers under mechanical loading and are a potential cell source for tissue engineering of tendon-like tissue

    PubMed Central

    Chen, Yu-Ying; He, Sheng-Teng; Yan, Fu-Hua; Zhou, Peng-Fei; Luo, Kai; Zhang, Yan-Ding; Xiao, Yin; Lin, Min-Kui

    2016-01-01

    Postnatal mesenchymal stem cells have the capacity to differentiate into multiple cell lineages. This study explored the possibility of dental pulp stem cells (DPSCs) for potential application in tendon tissue engineering. The expression of tendon-related markers such as scleraxis, tenascin-C, tenomodulin, eye absent homologue 2, collagens I and VI was detected in dental pulp tissue. Interestingly, under mechanical stimulation, these tendon-related markers were significantly enhanced when DPSCs were seeded in aligned polyglycolic acid (PGA) fibre scaffolds. Furthermore, mature tendon-like tissue was formed after transplantation of DPSC-PGA constructs under mechanical loading conditions in a mouse model. This study demonstrates that DPSCs could be a potential stem cell source for tissue engineering of tendon-like tissue. PMID:27811845

  18. Evaluating the acute effects of oral, non-combustible potential reduced exposure products marketed to smokers

    PubMed Central

    Cobb, CO; Weaver, MF; Eissenberg, T

    2011-01-01

    Background Non-combustible potential reduced exposure products (PREPs; eg, Star Scientific’s Ariva; a variety of other smokeless tobacco products) are marketed to reduce the harm associated with smoking. This marketing occurs despite an absence of objective data concerning the toxicant exposure and effects of these PREPs. Methods used to examine combustible PREPs were adapted to assess the acute effects of non-combustible PREPs for smokers. Methods 28 overnight abstinent cigarette smokers (17 men, 14 non-white) each completed seven, Latin-squared ordered, approximately 2.5 h laboratory sessions that differed by product administered: Ariva, Marlboro Snus (Philip Morris, USA), Camel Snus (RJ Reynolds, Winston-Salem, North Carolina, USA), Commit nicotine lozenge (GlaxoSmithKline; 2 mg), own brand cigarettes, Quest cigarettes (Vector Tobacco; delivers very low levels of nicotine) and sham smoking (ie, puffing on an unlit cigarette). In each session, the product was administered twice (separated by 60 min), and plasma nicotine levels, expired air CO and subjective effects were assessed regularly. Results Non-combustible products delivered less nicotine than own brand cigarettes, did not expose smokers to CO and failed to suppress tobacco abstinence symptoms as effectively as combustible products. Conclusions While decreased toxicant exposure is a potential indicator of harm reduction potential, a failure to suppress abstinence symptoms suggests that currently marketed non-combustible PREPs may not be a viable harm reduction strategy for US smokers. This study demonstrates how clinical laboratory methods can be used to evaluate the short-term effects of non-combustible PREPs for smokers. PMID:19346218

  19. Marker vaccine potential of a foot-and-mouth disease virus with a partial VP1 G-H loop deletion.

    PubMed

    Fowler, V L; Knowles, N J; Paton, D J; Barnett, P V

    2010-04-26

    Previous work in cattle and pigs demonstrated that protection against foot-and-mouth disease (FMD) could be achieved following vaccination with chimeric foot-and-mouth disease virus (FMDV) vaccines, in which the VP1 G-H loop had been substituted with that from another serotype. This indicated that the VP1 G-H loop may not be essential for the protection of natural hosts against FMDV. If this could be substantiated there would be potential to develop FMD marker vaccines, characterised by the absence of this region. Here, we investigate the serological responses to vaccination with a virus with a partial VP1 G-H loop deletion in order to determine the likelihood of achieving protection and the potential of this virus as a marker vaccine. Inactivated, oil adjuvanted, vaccines, consisting of chemically inactivated virus with or without a partially deleted VP1 G-H loop, were used to immunise cattle. Serum was collected on days 0, 7, 14 and 21 and antibody titres calculated using the virus neutralisation test (VNT) to estimate the likelihood of protection. We predict a good likelihood that cattle vaccinated with a vaccine characterised by a partial VP1 G-H loop would be protected against challenge with the same virus containing the VP1 G-H loop. We also present evidence on the potential of such a construct to act as a marker vaccine, when used in conjunction with a novel serological test.

  20. The overexpressed functional transient receptor potential channel TRPM2 in oral squamous cell carcinoma

    PubMed Central

    Zhao, Ling-Yan; Xu, Wan-Lin; Xu, Zeng-Qi; Qi, Cui; Li, Yang; Cheng, Jie; Liu, Lai-Kui; Wu, Yu-Nong; Gao, Jun; Ye, Jin-Hai

    2016-01-01

    TRPM2, one member of the transient receptor potential (TRP) protein super-family, is a Ca2+-permeable channel that is activated by oxidative stress and confers susceptibility to cell death. In the human tongue specimens of carcinoma and the tongue carcinoma SCC cell lines, we observed the enhanced expression of TRPM2. By means of the whole-cell electrophysiological recording, the ADPR-induced currents mediated by TRPM2 were recorded in cultured SCC9 cells. Moreover, after H2O2 treatment for 24 hours, the apoptotic number of SCC9 cells was significantly increased. However, the selectively knocked-down TRPM2 with the small interfering RNA technique inhibited the survival and migration of the SCC9 cancer cells, which was independent of the p53-p21 pathway, since the expression of p21 was enhanced after TRPM2 knockdown. Furthermore, the sub-cellular localization of TRPM2 was remarkably different between cancerous and non-cancerous cells. A significant amount of the TRPM2 proteins were located in the nuclei in cancer cells. All these data suggest that TRPM2 is essential for the survival and migration of SCC cancer cells and may be a potential target for the selective treatment of tongue cancer. PMID:28008929

  1. Reducing the Risk of Xerostomia and Mandibular Osteoradionecrosis: The Potential Benefits of Intensity Modulated Radiotherapy in Advanced Oral Cavity Carcinoma

    SciTech Connect

    Ahmed, Merina; Hansen, Vibeke N.; Harrington, Kevin J.; Nutting, Christopher M.

    2009-10-01

    Radiation therapy for squamous cell carcinoma of the oral cavity may be curative, but carries a risk of permanent damage to bone, salivary glands, and other soft tissues. We studied the potential of intensity modulated radiotherapy (IMRT) to improve target volume coverage, and normal tissue sparing for advanced oral cavity carcinoma (OCC). Six patients with advanced OCC requiring bilateral irradiation to the oral cavity and neck were studied. Standard 3D conformal radiotherapy (3DCRT) and inverse-planned IMRT dose distributions were compared by using dose-volume histograms. Doses to organs at risk, including spinal cord, parotid glands, and mandible, were assessed as surrogates of radiation toxicity. PTV1 mean dose was 60.8 {+-} 0.8 Gy for 3DCRT and 59.8 {+-} 0.1 Gy for IMRT (p = 0.04). PTV1 dose range was 24.7 {+-} 6 Gy for 3DCRT and 15.3 {+-} 4 Gy for IMRT (p = 0.001). PTV2 mean dose was 54.5 {+-} 0.8 Gy for 3DCRT and for IMRT was 54.2 {+-} 0.2 Gy (p = 0.34). PTV2 dose range was improved by IMRT (7.8 {+-} 3.2 Gy vs. 30.7 {+-} 12.8 Gy, p = 0.006). Homogeneity index (HI) values for PTV2 were closer to unity using IMRT (p = 0.0003). Mean parotid doses were 25.6 {+-} 2.7 Gy for IMRT and 42.0 {+-} 8.8 Gy with 3DCRT (p = 0.002). The parotid V30 in all IMRT plans was <45%. The mandible V50, V55, and V60 were significantly lower for the IMRT plans. Maximum spinal cord and brain stem doses were similar for the 2 techniques. IMRT provided superior target volume dose homogeneity and sparing of organs at risk. The magnitude of reductions in dose to the salivary glands and mandible are likely to translate into reduced incidence of xerostomia and osteoradionecrosis for patients with OCC.

  2. Reducing the risk of xerostomia and mandibular osteoradionecrosis: the potential benefits of intensity modulated radiotherapy in advanced oral cavity carcinoma.

    PubMed

    Ahmed, Merina; Hansen, Vibeke N; Harrington, Kevin J; Nutting, Christopher M

    2009-01-01

    Radiation therapy for squamous cell carcinoma of the oral cavity may be curative, but carries a risk of permanent damage to bone, salivary glands, and other soft tissues. We studied the potential of intensity modulated radiotherapy (IMRT) to improve target volume coverage, and normal tissue sparing for advanced oral cavity carcinoma (OCC). Six patients with advanced OCC requiring bilateral irradiation to the oral cavity and neck were studied. Standard 3D conformal radiotherapy (3DCRT) and inverse-planned IMRT dose distributions were compared by using dose-volume histograms. Doses to organs at risk, including spinal cord, parotid glands, and mandible, were assessed as surrogates of radiation toxicity. PTV1 mean dose was 60.8 +/- 0.8 Gy for 3DCRT and 59.8 +/- 0.1 Gy for IMRT (p = 0.04). PTV1 dose range was 24.7 +/- 6 Gy for 3DCRT and 15.3 +/- 4 Gy for IMRT (p = 0.001). PTV2 mean dose was 54.5 +/- 0.8 Gy for 3DCRT and for IMRT was 54.2 +/- 0.2 Gy (p = 0.34). PTV2 dose range was improved by IMRT (7.8 +/- 3.2 Gy vs. 30.7 +/- 12.8 Gy, p = 0.006). Homogeneity index (HI) values for PTV2 were closer to unity using IMRT (p = 0.0003). Mean parotid doses were 25.6 +/- 2.7 Gy for IMRT and 42.0 +/- 8.8 Gy with 3DCRT (p = 0.002). The parotid V30 in all IMRT plans was <45%. The mandible V50, V55, and V60 were significantly lower for the IMRT plans. Maximum spinal cord and brain stem doses were similar for the 2 techniques. IMRT provided superior target volume dose homogeneity and sparing of organs at risk. The magnitude of reductions in dose to the salivary glands and mandible are likely to translate into reduced incidence of xerostomia and osteoradionecrosis for patients with OCC.

  3. Thiolated polycarbophil/glutathione: defining its potential as a permeation enhancer for oral drug administration in comparison to sodium caprate.

    PubMed

    Perera, Glen; Barthelmes, Jan; Vetter, Anja; Krieg, Christof; Uhlschmied, Cindy; Bonn, Günther K; Bernkop-Schnürch, Andreas

    2011-08-01

    Thiolated polyacrylates were shown to be permeation enhancers with notable potential. The aim of this study was to evaluate the permeation enhancing properties of a thiolated polycarbophil/glutathione (PCP-Cys/GSH) system for oral drug application in comparison to a well-established permeation enhancer, namely sodium caprate. In vitro permeation studies were conducted in Ussing-type chambers with sodium fluoresceine (NaFlu) and fluoresceine isothiocyanate labeled dextran (molecular mass 4 kDa; FD4) as model compounds. Bioavailability studies were carried out in Sprague Dawley rats with various formulations. Moreover, cytotoxic effects of both permeation enhancers were compared. Permeation enhancement ratios of 1% sodium caprate were found to be 3.0 (FD4) and 2.3 (NaFlu), whereas 1% PCP-Cys/0.5% GSH displayed enhancement ratios of 2.4 and 2.2. Both excipients performed at a similar level in vivo. Sodium caprate solutions increased oral bioavailability 2.2-fold (FD4) and 2.3-fold (NaFlu), while PCP-Cys hydrogels led to a 3.2-fold and 2.2-fold enhancement. Cell viability experiments revealed a significantly higher tolerance of Caco-2 cells towards 0.5% PCP-Cys (81% survival) compared to 0.5% sodium caprate (5%). As PCP-Cys is not absorbed from mucosal membranes due to its comparatively high molecular mass, systemic side-effects can be excluded. In conclusion, both systems displayed a similar potency for permeation enhancement of hydrophilic compounds. However, PCP-Cys seems to be less harmful to cultured cells.

  4. Number of STR repeats as a potential new quantitative genetic marker for complex diseases, illustrated by schizophrenia.

    PubMed

    Liu, Hui; Yu, Weijian; Wang, Xuebin; Fang, Fang; Yang, Guang; Zhou, Jie; Liang, Xiaohua; An, Wanxin

    2007-10-01

    It has proved difficult to find strong and replicable genetic linkages for complex diseases, since each susceptibility gene makes only a modest contribution to onset. This is partly because high-efficacy genetic markers are not usually available. The aim of this article is to explore the possibility that the total number of tandem repeats in one STR locus, rather than the frequencies of different alleles, is a higher efficacy quantitative genetic marker. DNA samples were collected from schizophrenic patients and from a control population. Alleles of the short tandem repeats (STR) loci D3S1358, vWA, and FGA were determined using the STR Profiler Plus PCR amplification kit. The two groups did not differ statistically in the frequencies of alleles at the D3S1358, vWA, or FGA loci. However, a significant difference was obtained in the vWA locus when the total number of core unit repeats was compared between the schizophrenia and control groups (33.28+/-2.61 vs. 32.35+/-2.58, P<0.05). It seems that the number of STR repeats may be a new, quantitative, and higher efficacy genetic marker for directly indicating genetic predisposition to complex hereditary diseases such as schizophrenia.

  5. Evaluation of amitrole (aminotriazole) for potential carcinogenicity in orally dosed rats, mice, and golden hamsters

    SciTech Connect

    Steinhoff, D.; Weber, H.; Mohr, U.; Boehme, K.

    1983-06-30

    Amitrole was evaluated for carcinogenic potential in lifespan studies on Wistar rats, NMRI mice, and golden hamsters. At the start of the studies the animals were 6 weeks old. Amitrole was administered, mixed with pulverized chow, at dietary concentrations of 0, 1, 10, and 100 micrograms/g (ppm). Each treated group and control group consisted of 75 male and 75 female rats and mice and of 76 male and 76 female golden hamsters. Additional animals were used to evaluate the functional state of the thyroid. Somewhat lower body weights, slightly reduced survival times, and transient effects on thyroid function were observed in golden hamsters at 100 ppm. In mice, a slight increase in pituitary gland hyperemias was seen at 100 ppm; also an effect on thyroid function usually occurred at the same concentration. In rats, a very large number of cystic dilatations of follicles in the thyroid at 100 ppm and a dose-unrelated increase in hemorrhages and hyperemias in the pituitary gland were indicative of an effect of amitrole on these organs. The strongest effect of amitrole on thyroid function, as compared to golden hamsters and mice, was seen in rats at 100 ppm. At this concentration a highly increased number of thyroid and pituitary gland tumors was observed in rats. In golden hamsters and mice, no tumor induction was seen.

  6. The Potential for Glycemic Control Monitoring and Screening for Diabetes at Dental Visits Using Oral Blood

    PubMed Central

    Rosedale, Mary T.; Pesce, Michael A.; Rindskopf, David M.; Kaur, Navjot; Juterbock, Caroline M.; Wolff, Mark S.; Malaspina, Dolores; Danoff, Ann

    2015-01-01

    Objectives. We examined the potential for glycemic control monitoring and screening for diabetes in a dental setting among adults (n = 408) with or at risk for diabetes. Methods. In 2013 and 2014, we performed hemoglobin A1c (HbA1c) tests on dried blood samples of gingival crevicular blood and compared these with paired “gold-standard” HbA1c tests with dried finger-stick blood samples in New York City dental clinic patients. We examined differences in sociodemographics and diabetes-related risk and health care characteristics for 3 groups of at-risk patients. Results. About half of the study sample had elevated HbA1c values in the combined prediabetes and diabetes ranges, with approximately one fourth of those in the diabetes range. With a correlation of 0.991 between gingival crevicular and finger-stick blood HbA1c, measures of concurrence between the tests were extremely high for both elevated HbA1c and diabetes-range HbA1c levels. Persons already diagnosed with diabetes and undiagnosed persons aged 45 years or older could especially benefit from HbA1c testing at dental visits. Conclusions. Gingival crevicular blood collected at the dental visit can be used to screen for diabetes and monitor glycemic control for many at-risk patients. PMID:25713975

  7. Has oral fluid the potential to replace serum for the evaluation of population immunity levels? A study of measles, rubella and hepatitis B in rural Ethiopia.

    PubMed Central

    Nokes, D. J.; Enquselassie, F.; Nigatu, W.; Vyse, A. J.; Cohen, B. J.; Brown, D. W.; Cutts, F. T.

    2001-01-01

    OBJECTIVE: To assess the suitability of using oral-fluid samples for determining the prevalence of immunity to vaccine-preventable infections. METHODS: Paired blood and oral-fluid samples were obtained from 853 individuals of all ages from a rural Ethiopian community. Oral fluid around the gums was screened for measles- and rubella-specific antibodies using enhanced IgG antibody capture (GAC) enzyme-linked immunosorbent assays (ELISAs), and for anti-HBc antibodies using a prototype GACELISA. IgG antibodies in serum to measles, rubella and HBc were determined using commercial ELISAs. FINDINGS: Relative to serum, oral fluid assay sensitivity and specificity were as follows: 98% and 87% for measles, 79% and 90% for rubella, and 43% and 87% for anti-HBc. These assay characteristics yielded population prevalence estimates from oral fluid with a precision equal to that of serum for measles (all ages) and rubella (ages < 20 years). CONCLUSION: Our results suggest that oral fluid could have the potential to replace serum in IgG antibody prevalence surveys. Further progress requires assessment of variation in assay performance between populations as well as the availability of standardized, easy to use assays. PMID:11477961

  8. Developmental toxic potential of di-n-propyl phthalate administered orally to rats.

    PubMed

    Saillenfait, Anne-Marie; Roudot, Alain-Claude; Gallissot, Frédéric; Sabaté, Jean-Philippe; Chagnon, Marie-Christine

    2011-01-01

    The objective of this study was to evaluate the developmental toxic potential of di-n-propyl phthalate (DnPP) in rats. Pregnant Sprague-Dawley rats were given DnPP at doses of 0 (olive oil), 0.5, 1 and 1.5 g kg⁻¹ per day, by gavage, on gestation days 6-20. Benchmark doses were calculated for the effects of DnPP on fetal weight and anogenital distance of the male fetuses. Maternal body weight gain was significantly reduced at 1.5 g kg⁻¹ per day, over gestation days 6-9. DnPP-treated dams also showed a statistically significant increase in liver weight and a mild but statistically significant peroxisomal enzyme induction at 1 or 1.5 g kg⁻¹ per day. Male and female fetal body weights were significantly reduced at 1.5 g kg⁻¹ per day. There was a statistically significant decrease in the anogenital distance of the male fetuses at 1 and 1.5 g kg⁻¹ per day, and three males (of 75) showed malpositioned testis at the high dose. The mean percentage of fetuses per litter with cervical and thoracic rudimentary ribs was significantly increased at 1 and 1.5 g kg⁻¹ per day. Delayed ossification was seen at 1 g kg⁻¹ per day (phalanges) and 1.5 g kg⁻¹ per day (hyoid, sternebrae, and phalanges). No treatment-related effects on prenatal viability or on fetal external or visceral malformations or variations were observed at any dose. Thus, there was no evidence of teratogenicity up to the high dose of 1.5 g kg⁻¹ per day. The no-observed-adverse-effect level (NOAEL) for developmental toxicity was 0.5 g kg⁻¹ per day.

  9. Subthalamic and Cortical Local Field Potentials Associated with Pilocarpine-Induced Oral Tremor in the Rat

    PubMed Central

    Long, Lauren L.; Podurgiel, Samantha J.; Haque, Aileen F.; Errante, Emily L.; Chrobak, James J.; Salamone, John D.

    2016-01-01

    Tremulous jaw movements (TJMs) are rapid vertical deflections of the lower jaw that resemble chewing but are not directed at any particular stimulus. In rodents, TJMs are induced by neurochemical conditions that parallel those seen in human Parkinsonism, including neurotoxic or pharmacological depletion of striatal dopamine (DA), DA antagonism, and cholinomimetic administration. Moreover, TJMs in rodents can be attenuated by antiparkinsonian agents, including levodopa (L-DOPA), DA agonists, muscarinic antagonists, and adenosine A2A antagonists. In human Parkinsonian patients, exaggerated physiological synchrony is seen in the beta frequency band in various parts of the cortical/basal ganglia/thalamic circuitry, and activity in the tremor frequency range (3–7 Hz) also has been recorded. The present studies were undertaken to determine if tremor-related local field potential (LFP) activity could be recorded from motor cortex (M1) or subthalamic nucleus (STN) during the TJMs induced by the muscarinic agonist pilocarpine, which is a well-known tremorogenic agent. Pilocarpine induced a robust TJM response that was marked by rhythmic electromyographic (EMG) activity in the temporalis muscle. Compared to periods with no tremor activity, TJM epochs were characterized by increased LFP activity in the tremor frequency range in both neocortex and STN. Tremor activity was not associated with increased synchrony in the beta frequency band. These studies identified tremor-related LFP activity in parts of the cortical/basal ganglia circuitry that are involved in the pathophysiology of Parkinsonism. This research may ultimately lead to identification of the oscillatory neural mechanisms involved in the generation of tremulous activity, and promote development of novel treatments for tremor disorders. PMID:27378874

  10. Comparative Correlation Structure of Colon Cancer Locus Specific Methylation: Characterisation of Patient Profiles and Potential Markers across 3 Array-Based Datasets

    PubMed Central

    Barat, Ana; Ruskin, Heather J.

    2015-01-01

    Abnormal DNA-methylation is well known to play an important role in cancer onset and development, and colon cancer is no exception to this rule. Recent years have seen the increased use of large-scale technologies, (such as methylation microarray assays or specific sequencing of methylated DNA), to determine whole genome profiles of CpG island methylation in tissue samples. Comprehensive study of methylation array data from transcriptome high-throughput platforms permits determination of gene methylation markers, important for cancer profiling. Here, three large-scale methylation datasets for colon cancer have been compared to determine locus-specific methylation agreement. These data are from the GEO database, where colon cancer and apparently healthy adjacent tissues are represented by sample sizes 125 and 29 respectively in the first dataset, 24 of each in the second and 118 of each in the third. Several data analysis techniques have been employed, including Clustering, Discriminant Principal Component Analysis, Discriminant Analysis and ROC curves, in order (i) to obtain a better insight on the locus-specific concomitant methylation structures for these diverse data and (ii) to determine a robust potential marker set for indicative screening, drawn from all data taken together. The extent of the agreement between the analysed datasets is reported. Further, potential screening methylation markers, for which methylation profiles are consistent across tissue samples and several datasets, are highlighted and discussed. PMID:26185542

  11. VEGF-A immunohistochemical and mRNA expression in tissues and its serum levels in potentially malignant oral lesions and oral squamous cell carcinomas.

    PubMed

    Nayak, Seema; Goel, Madhu Mati; Chandra, Saumya; Bhatia, Vikram; Mehrotra, Divya; Kumar, Sandeep; Makker, Annu; Rath, S K; Agarwal, S P

    2012-03-01

    The aim of the study was to investigate whether the estimation of circulating Vascular endothelial growth factor-A (VEGF-A) levels by ELISA could be used as surrogate of VEGF-A expression in tissues of pre-malignant oral lesions (PMOLs) and oral squamous cell carcinoma (OSCC) as compared to that in healthy controls. The study samples comprised of tissue and blood samples from 60 PMOLs, 60 OSCC, and 20 healthy controls. Serum VEGF-A levels were determined by an ELISA based assay (Quantikine human VEGF; R & D System, Minneapolis USA). Tissue VEGF-A expression and microvessel density (MVD) were assessed by immunohistochemistry (IHC) using antibodies against VEGF-A and CD-34 on formalin fixed paraffin embedded (FFPE) tissue sections. VEGF-A mRNA expression was analyzed by real-time PCR in snap frozen tissues. Serum VEGF-A levels and immunohistochemical VEGF-A expression were significantly high in PMOLs and OSCC in comparison with controls. VEGF mRNA gene expression showed more than 50-fold increase in PMOLs and OSCC. VEGF-A levels in serum correlated in a linear fashion with the tissue expression in oral pre-malignant and malignant lesions, suggesting that the serum levels may serve as surrogate material for tissue expression of VEGF-A.

  12. Abuse Potential and Pharmacodynamic Characteristics of Oral and Intranasal Eluxadoline, a Mixed μ- and κ-Opioid Receptor Agonist and δ-Opioid Receptor Antagonist

    PubMed Central

    McIntyre, G.; Bonifacio, L.; McDonnell, M.; Davenport, J. M.; Covington, P. S.; Dove, L. S.; Sellers, E. M.

    2016-01-01

    Drugs with μ-opioid receptor (OR) activity can be associated with abuse and misuse. The peripherally acting mixed μ-OR and κ-OR agonist and δ-OR antagonist eluxadoline is approved in the United States for the treatment of irritable bowel syndrome with diarrhea. In two separate crossover studies, we evaluated the oral and intranasal abuse potential of eluxadoline versus placebo and the active control oxycodone. Healthy recreational opioid users received eluxadoline 100, 300, and 1000 mg, oxycodone 30 and 60 mg, and placebo (oral study), or eluxadoline 100 and 200 mg, oxycodone 15 and 30 mg, and placebos matched to eluxadoline and oxycodone (intranasal study). In the oral study, Drug Liking Visual Analog Scale (VAS) peak (maximum) effect (Emax) score (primary endpoint) was significantly greater with eluxadoline 300 and 1000 mg versus placebo, but scores were significantly lower versus oxycodone. Following intranasal insufflation of eluxadoline, Drug Liking VAS Emax scores were not statistically different versus placebo, and were significantly lower versus oxycodone. Across other subjective measures, eluxadoline was generally similar to or disliked versus placebo. Pupillometry indicated no or minimal central effects with oral and intranasal eluxadoline, respectively. Adverse events of euphoric mood were reported with oral and intranasal eluxadoline but at a far lower frequency versus oxycodone. These data demonstrate that eluxadoline has less abuse potential than oxycodone in recreational opioid users. PMID:27647873

  13. Brain natriuretic peptide as a potential novel marker of salt-sensitivity in chronic kidney disease patients without cardiac dysfunction.

    PubMed

    Hayashi, Mutsuharu; Yasuda, Yoshinari; Suzuki, Susumu; Tagaya, Manaka; Ito, Takehiro; Kamada, Tomohito; Yoshinaga, Masataka; Sugishita, Yoshinori; Fujiwara, Wakaya; Yokoi, Hiroatsu; Ozaki, Yukio; Izawa, Hideo

    2017-03-01

    Although the renin-angiotensin system (RAS) is counter-balanced by a salt-sensitive mechanism in the hypertensive state, both are reported to be up-regulated in chronic kidney disease (CKD) patients. We conducted this study to evaluate the associations among the RAS, renal function, hypertension, and atherosclerosis, as well as to identify markers for salt-sensitivity. A total of 213 pre-dialysis CKD patients with preserved cardiac function (EF >50 %) were enrolled. Their renal and cardiac biochemical markers and plasma renin activity (PRA) were measured, and echocardiography and carotid artery ultrasound were performed. Their salt intake was estimated by the NaCl excretion from a 24-h collected urine sample. The PRA was higher in patients with hypertension (p = 0.018), and had a significant negative correlation with the eGFR (r = -0.23, p = 0.0067). Importantly, the PRA had a strong negative correlation with the brain natriuretic peptide (BNP) level (r = -0.28, p = 0.017) regardless of whether the patients were being treated with RAS inhibitors. The BNP level was related to the renal functions (eGFR: p = 0.001, ACR: p = 0.009). There was a significant positive correlation between the BNP level and carotid intima-media thickness (p < 0.001). A multivariate analysis revealed that older age and an excess of NaCl excretion were independent predictors of BNP elevation (p = 0.02 and 0.003, respectively). Our analysis revealed details of the counterbalance between BNP and PRA, as well as identifying that excess salt intake is a predictor of BNP elevation. These results indicate that the BNP could be a possible valuable marker for salt sensitivity, and that high salt sensitivity could facilitate atherosclerosis in CKD patients.

  14. Marker development

    SciTech Connect

    Adams, M.R.

    1987-05-01

    This report is to discuss the marker development for radioactive waste disposal sites. The markers must be designed to last 10,000 years, and place no undue burdens on the future generations. Barriers cannot be constructed that preclude human intrusion. Design specifications for surface markers will be discussed, also marker pictograms will also be covered.

  15. Claudin-3 expression in radiation-exposed rat models: A potential marker for radiation-induced intestinal barrier failure

    SciTech Connect

    Shim, Sehwan; Lee, Jong-geol; Bae, Chang-hwan; Lee, Seung Bum; Jang, Won-Suk; Lee, Sun-Joo; Lee, Seung-Sook; Park, Sunhoo

    2015-01-02

    Highlights: • Irradiation increased intestinal bacterial translocation, accompanied by claudin protein expression in rats. • Neurotensin decreased the bacterial translocation and restored claudin-3 expression. • Claudin-3 can be used as a marker in evaluating radiation induced intestinal injury. - Abstract: The molecular events leading to radiation-induced intestinal barrier failure are not well known. The influence of the expression of claudin proteins in the presence and absence of neurotensin was investigated in radiation-exposed rat intestinal epithelium. Wistar rats were randomly divided into control, irradiation, and irradiation + neurotensin groups, and bacterial translocation to the mesenteric lymph node and expression of claudins were determined. Irradiation led to intestinal barrier failure as demonstrated by significant bacterial translocation. In irradiated terminal ilea, expression of claudin-3 and claudin-4 was significantly decreased, and claudin-2 expression was increased. Administration of neurotensin significantly reduced bacterial translocation and restored the structure of the villi as seen by histologic examination. Among the three subtype of claudins, only claudin-3 expression was restored. These results suggest that the therapeutic effect of neurotensin on the disruption of the intestinal barrier is associated with claudin-3 alteration and that claudin-3 could be used as a marker in evaluating radiation-induced intestinal injury.

  16. Positive/negative surface charge of chitosan based nanogels and its potential influence on oral insulin delivery.

    PubMed

    Wang, Juan; Xu, Mengxue; Cheng, Xiaojie; Kong, Ming; Liu, Ya; Feng, Chao; Chen, Xiguang

    2016-01-20

    To develop insulin delivery system for the treatment of diabetes, two insulin-loaded nanogels with opposite zeta potential (-15.94 ± 0.449 mV for insulin:CMCS/CS-NGs(-) and +17.15 ± 0.492 mV for insulin:CMCS/CS-NGs(+)) were obtained. Ex vivo results showed that the nanogels with opposite surface charge exhibited different adhesion and permeation in specific intestinal segments. There was no significant differences in adhesion and permeation in rat duodenum, but in rat jejunum, insulin:CMCS/CS-NGs(-) exhibited enhanced adhesion and permeation, which were about 3 folds (adhesion) and 1.7 folds (permeation) higher than insulin:CMCS/CS-NGs(+). These results demonstrated that the surface charge property of nanogels determined the absorption sites of CMCS/CS-NGs in small intestine. In vivo study, the blood glucose level in insulin:CMCS/CS-NGs(-) group had 3 mmol/L lower than insulin:CMCS/CS-NGs(+) group during 1h to 11h after the oral administration, which demonstrated that negative insulin:CMCS/CS-NGs had a better management of blood glucose than positive ones.

  17. Comparison of the single dose pharmacokinetics, pharmacodynamics, and safety of two novel oral formulations of dimethandrolone undecanoate (DMAU): a potential oral, male contraceptive.

    PubMed

    Ayoub, R; Page, S T; Swerdloff, R S; Liu, P Y; Amory, J K; Leung, A; Hull, L; Blithe, D; Christy, A; Chao, J H; Bremner, W J; Wang, C

    2017-03-01

    Dimethandrolone (DMA, 7α,11β-dimethyl-19-nortestosterone) has both androgenic and progestational activities, ideal properties for a male hormonal contraceptive. In vivo, dimethandrolone undecanoate (DMAU) is hydrolyzed to DMA. We showed previously that single oral doses of DMAU powder in capsule taken with food are well tolerated and effective at suppressing both LH and testosterone (T), but absorption was low. We compared the pharmacokinetics and pharmacodynamics of two new formulations of DMAU, in castor oil and in self-emulsifying drug delivery systems (SEDDS), with the previously tested powder formulation. DMAU was dosed orally in healthy adult male volunteers at two academic medical centers. For each formulation tested in this double-blind, placebo-controlled study, 10 men received single, escalating, oral doses of DMAU (100, 200, and 400 mg) and two subjects received placebo. All doses were evaluated for both fasting and with a high fat meal. All three formulations were well tolerated without clinically significant changes in vital signs, blood counts, or serum chemistries. For all formulations, DMA and DMAU showed higher maximum (p < 0.007) and average concentrations (p < 0.002) at the 400 mg dose, compared with the 200 mg dose. The powder formulation resulted in a lower conversion of DMAU to DMA (p = 0.027) compared with both castor oil and SEDDS formulations. DMAU in SEDDS given fasting resulted in higher serum DMA and DMAU concentrations compared to the other two formulations. Serum LH and sex hormone concentrations were suppressed by all formulations of 200 and 400 mg DMAU when administered with food, but only the SEDDS formulation was effectively suppressed serum T when given fasting. We conclude that while all three formulations of oral DMAU are effective and well tolerated when administered with food, DMAU in oil and SEDDS increased conversion to DMA, and SEDDS may have some effectiveness when given fasting. These properties might be

  18. C-deletion in exon 4 codon 63 of p53 gene as a molecular marker for oral squamous cell carcinoma: A preliminary study

    PubMed Central

    Sukhija, Hemani; Krishnan, Rajkumar; Balachander, N.; Raghavendhar, Karthik; Ramadoss, Ramya; Sen, Sukanta

    2015-01-01

    Background: Exfoliated oral cancer cells in saliva samples from patients with oral squamous cell carcinoma (OSCC) can be used to determine the incidence and type of mutations of the p53 tumor suppressor gene. The purpose of this study was to identify C-deletion mutation in exon 4 codon 63 of p53 gene in the saliva of OSCC patients by polymerase chain reaction (PCR). Materials and Methods: Saliva samples of 20 newly histopathologically diagnosed OSCC patients and 5 healthy volunteers were subjected to isolation of the total genomic DNA and PCR amplification for C-deletion on exon 4 of p53 gene. The resulting products were resolved by agarose gel electrophoresis, viewed and photographed on ultraviolet-transilluminator. Results: The relationship between the frequencies of genetic alterations was assessed by Chi-square test. Differences with values of P < 0.05 were statistically significant. Conclusion: The study concluded a 100% presence of C-deletion mutation in exon 4 codon 63 of p53 in the saliva of OSCC patients. This study suggests that detection of mutation in exon 4 codon 63 of p53 by PCR is a fast, reliable, accurate, and sensitive molecular method for OSCC diagnosis. PMID:26604578

  19. Evaluating the potential impact of a mobile telemedicine system on coordination of specialty care for patients with complicated oral lesions in Botswana.

    PubMed

    Tesfalul, Martha; Littman-Quinn, Ryan; Antwi, Cynthia; Ndlovu, Siphiwo; Motsepe, Didintle; Phuthego, Motsholathebe; Tau, Boitumelo; Mohutsiwa-Dibe, Neo; Kovarik, Carrie

    2016-04-01

    Mobile telemedicine involves the use of mobile device (e.g., cell phones, tablets) technology to exchange information to assist in the provision of patient care. Throughout the world, mobile telemedicine initiatives are increasing in number and in scale, but literature on their impact on patient outcomes in low-resource areas is limited. This study explores the potential impact of a mobile oral telemedicine system on the oral health specialty referral system in Botswana. Analysis of 26 eligible cases from June 2012 to July 2013 reveals high diagnosis concordance between dental officers and oral health specialists at 91.3% (21/23) but significant management plan discordance at 64.0% (16/25), over two-thirds of which involved the specialists disagreeing with the referring clinicians about the need for a visit to a specialist. These findings suggest mobile telemedicine can optimize the use of insights and skills of specialists remotely in regions where they are scarce.

  20. Strong Relationship between Oral Dose and Tenofovir Hair Levels in a Randomized Trial: Hair as a Potential Adherence Measure for Pre-Exposure Prophylaxis (PrEP)

    PubMed Central

    Liu, Albert Y.; Yang, Qiyun; Huang, Yong; Bacchetti, Peter; Anderson, Peter L.; Jin, Chengshi; Goggin, Kathy; Stojanovski, Kristefer; Grant, Robert; Buchbinder, Susan P.; Greenblatt, Ruth M.; Gandhi, Monica

    2014-01-01

    Background Pre-exposure prophylaxis (PrEP) trials using tenofovir-based regimens have demonstrated that high levels of adherence are required to evaluate efficacy; the incorporation of objective biomarkers of adherence in trial design has been essential to interpretation, given the inaccuracy of self-report. Antiretroviral measurements in scalp hair have been useful as a marker of long-term exposure in the HIV treatment setting, and hair samples are relatively easy and inexpensive to collect, transport, and store for analysis. To evaluate the relationship between dose and tenofovir concentrations in hair, we examined the dose proportionality of tenofovir in hair in healthy, HIV-uninfected adults. Methods A phase I, crossover pharmacokinetic study was performed in 24 HIV-negative adults receiving directly-observed oral tenofovir tablets administered 2, 4, and 7 doses/week for 6 weeks, with a ≥3-week break between periods. Small samples of hair were collected after each six-week period and analyzed for tenofovir concentrations. Geometric-mean-ratios compared levels between each pair of dosing conditions. Intensive plasma pharmacokinetic studies were performed during the daily-dosing period to calculate areas-under-the-time-concentration curves (AUCs). Results Over 90% of doses were observed per protocol. Median tenofovir concentrations in hair increased monotonically with dose. A log-linear relationship was seen between dose and hair levels, with an estimated 76% (95% CI 60–93%) increase in hair level per 2-fold dose increase. Tenofovir plasma AUCs modestly predicted drug concentrations in hair. Conclusions This study found a strong linear relationship between frequency of dosing and tenofovir levels in scalp hair. The analysis of quantitative drug levels in hair has the potential to improve adherence measurement in the PrEP field and may be helpful in determining exposure thresholds for protection and explaining failures in PrEP trials. Hair measures for

  1. Evaluation and Elucidation Studies of Natural Aglycones for Anticancer Potential using Apoptosis-Related Markers: An In silico Study.

    PubMed

    Akhtar, Salman; Khan, M Kalim A; Arif, Jamal M

    2016-10-05

    Exposure to exogenous and endogenous chemicals and subsequent cellular and molecular changes has been linked to enhanced cell proliferation and restricted apoptosis phenomenon. Though in the past decades numerous anticancer drugs inducing programmed cell death in cancer cells by targeting specific apoptotic markers have reached the market, they have been allied with unwanted side effects, ranging from mild to severe toxicity. With further understanding on the functional mechanism of p53 and MDM2 in apoptosis and in our continuous search for new and potent multi-target anticancer lead compounds, we have carried out molecular docking and inhibition studies of the selected aglycones along with selected anticancer leads, against the specific apoptotic and cell cycle markers using AutoDock Tools 4.0 and other computational softwares. The docking results have been analyzed in terms of binding energies (kcal/mol) and inhibition constant (µM). The study clearly proposes our aglycones [solanidine (Solanid-5-en-3β-ol), solasodine (Solasod-5-en-3β-ol), and tomatidine (5α-Tomatidan-3β-ol)] induce apoptosis by inhibiting the p53-MDM2 complex, p21(Waf1/Cip1), and Bcl-2 proteins, which were even found comparable with the anticancer drugs nutlin and/or halofuginone. The work further emphasizes that the individual molecular targets such as BAX and Bcl-2 may result in misleading data at any level; however, ratio of responses to BAX and Bcl-2 shall be considered for better clue about a compound to be pro- or anti-apoptotic.

  2. DNA barcoding in the cycadales: testing the potential of proposed barcoding markers for species identification of cycads.

    PubMed

    Sass, Chodon; Little, Damon P; Stevenson, Dennis Wm; Specht, Chelsea D

    2007-11-07

    Barcodes are short segments of DNA that can be used to uniquely identify an unknown specimen to species, particularly when diagnostic morphological features are absent. These sequences could offer a new forensic tool in plant and animal conservation-especially for endangered species such as members of the Cycadales. Ideally, barcodes could be used to positively identify illegally obtained material even in cases where diagnostic features have been purposefully removed or to release confiscated organisms into the proper breeding population. In order to be useful, a DNA barcode sequence must not only easily PCR amplify with universal or near-universal reaction conditions and primers, but also contain enough variation to generate unique identifiers at either the species or population levels. Chloroplast regions suggested by the Plant Working Group of the Consortium for the Barcode of Life (CBoL), and two alternatives, the chloroplast psbA-trnH intergenic spacer and the nuclear ribosomal internal transcribed spacer (nrITS), were tested for their utility in generating unique identifiers for members of the Cycadales. Ease of amplification and sequence generation with universal primers and reaction conditions was determined for each of the seven proposed markers. While none of the proposed markers provided unique identifiers for all species tested, nrITS showed the most promise in terms of variability, although sequencing difficulties remain a drawback. We suggest a workflow for DNA barcoding, including database generation and management, which will ultimately be necessary if we are to succeed in establishing a universal DNA barcode for plants.

  3. Gastric Proteins MUC5AC and TFF1 as Potential Diagnostic Markers of Colonic Sessile Serrated Adenomas/Polyps

    PubMed Central

    Khaidakov, Magomed; Lai, Keith K.; Roudachevski, D.; Sargsyan, Julietta; Goyne, Hannah E.; Pai, Rish K.; Lamps, Laura W.

    2016-01-01

    Objectives: A subset of colon cancers originates from sessile serrated adenomas/polyps (SSA/Ps). Our goal was to identify markers for SSA/Ps that could aid in distinguishing them from hyperplastic polyps (HPs). Methods: We performed immunostaining for gastric proteins MUC5AC and TFF1 in formalin-fixed, paraffin-embedded (FFPE) samples of HPs (n = 47), SSA/Ps (n = 37), and normal colon (n = 30). Results: Control mucosa expressed only trace amounts of MUC5AC and TFF1. HPs exhibited an 11.3- and 11.4-fold increase in MUC5AC and TFF1 expression confined to the upper segments of the crypts near the luminal surface of the polyps. SSA/Ps displayed on average 1.6-fold (MUC5AC, P < .008) and 1.4-fold (TFF1, P < .03) higher signal intensity for these markers than HPs, with a dramatic coexpression of MUC5AC and TFF1 typically occupying the entire length of the crypt. Immunoperoxidase results were similar to immunofluorescence staining for both MUC5AC and TFF1. Conclusions: Our results suggest that the analysis of expression of MUC5AC and TFF1 may be useful for differentiating SSA/Ps from HPs. We also suggest the possibility that crypt morphology may be at least partly due to overproduction of highly viscous gastric mucins and that these proteins may play a role in the serrated pathway to colon carcinogenesis.

  4. Genetic expression of adipose derived stem cell and smooth muscle cell markers to monitor differentiation potential following low intensity laser irradiation

    NASA Astrophysics Data System (ADS)

    Abrahamse, Heidi

    2014-02-01

    Mesenchymal stem cells (MSCs) have the capacity to differentiate into a variety of cell types that could potentially be used in tissue engineering and regenerative medicine. Low intensity laser irradiation (LILI) has been shown to induce a significant increase in cell viability and proliferation. Growth factors such as retinoic acid (RA) and transforming growth factor β1 (TGF-β1) play important roles in the differentiation of cells. The aim of this study was to investigate whether LILI in combination with growth factors could induce the differentiation of adipose derived stem cells (ADSCs) cocultured with smooth muscle cells (SMCs). The study used primary and continuous ADSC cell lines and a SMC line (SKUT-1) as control. Cells were co-cultured directly at a ratio of 1:1 using established methods, with and without growth factors and then exposed to LILI at 5 J/cm2 using a 636 nm diode laser. The cellular morphology, viability and proliferation of the co-cultures were assessed over a period of one week. The study also monitored the expression of cell specific markers over the same period of time. Genetic expression of the markers for both adipose derived stem cells (β1 Integrin and Thymidine 1) and smooth muscle cells (Heavy Myosin Chain) was monitored using flow cytometry. Cell viability and proliferation increased significantly in the co-cultured groups that were exposed to laser alone, as well as in combination with growth factors. Furthermore, there was a significant decrease in the expression of stem cell markers in the ADSCs over time. The results indicate that LILI in combination with growth factors not only increases the viability and proliferation of co-cultured cells but also decreases the expression of ADSC stem cell markers. This could indicate the possible differentiation of ADSCs into SMCs.

  5. Prolactin-induced protein as a potential therapy response marker of adjuvant chemotherapy in breast cancer patients

    PubMed Central

    Jablonska, Karolina; Grzegrzolka, Jedrzej; Podhorska-Okolow, Marzenna; Stasiolek, Mariusz; Pula, Bartosz; Olbromski, Mateusz; Gomulkiewicz, Agnieszka; Piotrowska, Aleksandra; Rys, Janusz; Ambicka, Aleksandra; Ong, Siew Hwa; Zabel, Maciej; Dziegiel, Piotr

    2016-01-01

    Many studies are dedicated to exploring the molecular mechanisms of chemotherapy-resistance in breast cancer (BC). Some of them are focused on searching for candidate genes responsible for this process. The aim of this study was typing the candidate genes associated with the response to standard chemotherapy in the case of invasive ductal carcinoma. Frozen material from 28 biopsies obtained from IDC patients with different responses to chemotherapy were examined using gene expression microarray, Real-Time PCR (RT-PCR) and Western blot (WB). Based on the microarray results, further analysis of candidate gene expression was evaluated in 120 IDC cases by RT-PCR and in 224 IDC cases by immunohistochemistry (IHC). The results were correlated with clinical outcome and molecular subtype of the BC. Gene expression microarray revealed Prolactin-Induced Peptide (PIP) as a single gene differentially expressed in BC therapy responder or non-responder patients (p <0.05). The level of PIP expression was significantly higher in the BC therapy responder group than in the non-responder group at mRNA (p=0.0092) and protein level (p=0.0256). Expression of PIP mRNA was the highest in estrogen receptor positive (ER+) BC cases (p=0.0254) and it was the lowest in triple negative breast cancer (TNBC) (p=0.0336). Higher PIP mRNA expression was characterized by significantly longer disease free survival (DFS, p=0.0093), as well as metastasis free survival (MFS, p=0.0144). Additionally, PIP mRNA and PIP protein expression levels were significantly higher in luminal A than in other molecular subtypes and TNBC. Moreover significantly higher PIP expression was observed in G1, G2 vs. G3 cases (p=0.0027 and p=0.0013, respectively). Microarray analysis characterized PIP gene as a candidate for BC standard chemotherapy response marker. Analysis of clinical data suggests that PIP may be a good prognostic and predictive marker in IDC patients. Higher levels of PIP were related to longer DFS and MFS

  6. In Vivo Curative and Protective Potential of Orally Administered 5-Aminolevulinic Acid plus Ferrous Ion against Malaria

    PubMed Central

    Suzuki, Shigeo; Hikosaka, Kenji; Balogun, Emmanuel O.; Komatsuya, Keisuke; Niikura, Mamoru; Kobayashi, Fumie; Takahashi, Kiwamu; Tanaka, Tohru; Nakajima, Motowo

    2015-01-01

    5-Aminolevulinic acid (ALA) is a naturally occurring amino acid present in diverse organisms and a precursor of heme biosynthesis. ALA is commercially available as a component of cosmetics, dietary supplements, and pharmaceuticals for cancer diagnosis and therapy. Recent reports demonstrated that the combination of ALA and ferrous ion (Fe2+) inhibits the in vitro growth of the human malaria parasite Plasmodium falciparum. To further explore the potential application of ALA and ferrous ion as a combined antimalarial drug for treatment of human malaria, we conducted an in vivo efficacy evaluation. Female C57BL/6J mice were infected with the lethal strain of rodent malaria parasite Plasmodium yoelii 17XL and orally administered ALA plus sodium ferrous citrate (ALA/SFC) as a once-daily treatment. Parasitemia was monitored in the infected mice, and elimination of the parasites was confirmed using diagnostic PCR. Treatment of P. yoelii 17XL-infected mice with ALA/SFC provided curative efficacy in 60% of the mice treated with ALA/SFC at 600/300 mg/kg of body weight; no mice survived when treated with vehicle alone. Interestingly, the cured mice were protected from homologous rechallenge, even when reinfection was attempted more than 230 days after the initial recovery, indicating long-lasting resistance to reinfection with the same parasite. Moreover, parasite-specific antibodies against reported vaccine candidate antigens were found and persisted in the sera of the cured mice. These findings provide clear evidence that ALA/SFC is effective in an experimental animal model of malaria and may facilitate the development of a new class of antimalarial drug. PMID:26324278

  7. Preservation of high phenylalanine ammonia lyase activities in roots of Japanese Striped corn: a potential oral therapeutic to treat phenylketonuria.

    PubMed

    López-Villalobos, Arturo; Lücker, Joost; López-Quiróz, Ana Angela; Yeung, Edward C; Palma, Kristoffer; Kermode, Allison R

    2014-06-01

    Phenylketonuria (PKU) is an inherited metabolic disorder caused by deficient phenylalanine hydroxylase (PAH) activity, the enzyme responsible for the disposal of excess amounts of the essential amino acid phenylalanine (Phe). Phenylalanine ammonia-lyase (PAL, EC 4.3.1.5) has potential to serve as an enzyme substitution therapy for this human genetic disease. Using 7-day-old Japanese Striped corn seedlings (Japonica Striped maize, Zea mays L. cv. japonica) that contain high activities of PAL, we investigated a number of methods to preserve the roots as an intact food and for long-term storage. The cryoprotectant effects of maple syrup and other edible sugars (mono- and oligosaccharides) were evaluated. Following thawing, the preserved roots were then examined to determine whether the rigid plant cell walls could protect the PAL enzyme from proteolysis during simulated (in vitro) digestion comprised of gastric and intestinal phases. While several treatments led to retention of PAL activity during freezing, upon thawing and in vitro digestion, root tissues that had been previously frozen in the presence of maple syrup exhibited the highest residual PAL activities (∼50% of the initial enzyme activity), in marked contrast to all of the treatments using other edible sugars. The structural integrity of the root cells, and the stability of the functional PAL tetramer were also preserved with the maple syrup protocol. These results have significance for the formulation of oral enzyme/protein therapeutics. When plant tissues are adequately preserved, the rigid cell walls constitute a protective barrier even under harsh (e.g. gastrointestinal-like) conditions.

  8. Construction of chimeric bovine viral diarrhea viruses containing glycoprotein E rns of heterologous pestiviruses and evaluation of the chimeras as potential marker vaccines against BVDV.

    PubMed

    Luo, Yugang; Yuan, Ying; Ankenbauer, Robert G; Nelson, Lynn D; Witte, Steven B; Jackson, James A; Welch, Siao-Kun W

    2012-06-06

    Bovine viral diarrhea virus (BVDV) infections are enzootic in the cattle population and continue to cause significant economic losses to the beef and dairy industries worldwide. Extent of the damages has stimulated increasing interest in control programs directed at eradicating BVDV infections. Use of a BVDV marker vaccine would facilitate eradication efforts as a negatively marked vaccine would enable differentiation of infected from vaccinated animals (DIVA). We describe here the construction of three chimeric BVDVs containing glycoprotein E(rns) of heterologous pestiviruses and the evaluation of the chimera viruses as potential marker vaccines against BVDV infections. Chimeric NADL/G-E(rns), NADL/R-E(rns), and NADL/P-E(rns) were constructed by replacing the E(rns) gene of the full-length BVDV (NADL strain) genome with the E(rns) genes of giraffe (G-E(rns)), reindeer (R-E(rns)), or pronghorn antelope (P-E(rns)) pestiviruses, respectively. Each chimeric NADL virus was viable and infectious in RD 420 (bovine testicular) and BK-6 (bovine kidney) cells. By immunohistochemistry assays, NADL/G-E(rns) and NADL/R-E(rns) chimeric viruses reacted to BVDV E(rns) specific monoclonal antibody (mAb) 15C5, whereas the NADL/P-E(rns) chimeric virus did not. In an animal vaccination study, inactivated vaccines made from two chimeric viruses and the wild type NADL BVDV induced similar neutralizing antibody responses. NADL/P-E(rns)-vaccinated animals were distinguished from animals vaccinated with the wild type virus by means of a companion serological DIVA assay. These results show that chimeric NADL/P-E(rns) virus containing the E(rns) gene of pronghorn antelope pestivirus could be a potential marker vaccine candidate for use in a BVDV control and eradication program.

  9. Mutation at embB Codon 306, a Potential Marker for the Identification of Multidrug Resistance Associated with Ethambutol in Mycobacterium tuberculosis

    PubMed Central

    Cuevas-Córdoba, Betzaida; Juárez-Eusebio, Dulce María; Almaraz-Velasco, Raquel; Muñiz-Salazar, Raquel; Laniado-Laborin, Rafael

    2015-01-01

    Ethambutol inhibits arabinogalactan and lipoarabinomannan biosynthesis in mycobacteria. The occurrence of mutations in embB codon 306 in ethambutol-susceptible isolates and their absence in resistant isolates has raised questions regarding the utility of this codon as a potential marker for resistance against ethambutol. The characterization of mutations on embB 306 will contribute to a better understanding of the mechanisms of resistance to this drug; therefore, the purpose of this study was to investigate the association between embB 306 mutations and first-line drug resistance profiles in tuberculosis isolates. We sequenced the region surrounding the embB 306 codon in 175 tuberculosis clinical isolates, divided according to drug sensitivity, in three groups: 110 were resistant to at least one first-line drug, of which 61 were resistant to ethambutol (EMBr), 49 were sensitive to ethambutol (EMBs) but were resistant to another drug, and 65 were pansensitive isolates (Ps). The associations between embB 306 mutations and phenotypic resistance to all first-line drugs were determined, and their validity and safety as a diagnostic marker were assessed. One of the Ps isolates (1/65), one of the EMBs isolates (1/49), and 20 of the EMBr isolates (20/61) presented with an embB 306 mutation. Four different single-nucleotide polymorphisms (SNPs) at embB 306 were associated with simultaneous resistance to ethambutol, isoniazid, and rifampin (odds ratio [OR], 17.7; confidence interval [CI], 5.6 to 56.1) and showed a positive predictive value of 82%, with a specificity of 97% for diagnosing multidrug resistance associated with ethambutol, indicating its potential as a molecular marker for several drugs. PMID:26124153

  10. Mutation at embB codon 306, a potential marker for the identification of multidrug resistance associated with ethambutol in Mycobacterium tuberculosis.

    PubMed

    Cuevas-Córdoba, Betzaida; Juárez-Eusebio, Dulce María; Almaraz-Velasco, Raquel; Muñiz-Salazar, Raquel; Laniado-Laborin, Rafael; Zenteno-Cuevas, Roberto

    2015-09-01

    Ethambutol inhibits arabinogalactan and lipoarabinomannan biosynthesis in mycobacteria. The occurrence of mutations in embB codon 306 in ethambutol-susceptible isolates and their absence in resistant isolates has raised questions regarding the utility of this codon as a potential marker for resistance against ethambutol. The characterization of mutations on embB 306 will contribute to a better understanding of the mechanisms of resistance to this drug; therefore, the purpose of this study was to investigate the association between embB 306 mutations and first-line drug resistance profiles in tuberculosis isolates. We sequenced the region surrounding the embB 306 codon in 175 tuberculosis clinical isolates, divided according to drug sensitivity, in three groups: 110 were resistant to at least one first-line drug, of which 61 were resistant to ethambutol (EMB(r)), 49 were sensitive to ethambutol (EMB(s)) but were resistant to another drug, and 65 were pansensitive isolates (P(s)). The associations between embB 306 mutations and phenotypic resistance to all first-line drugs were determined, and their validity and safety as a diagnostic marker were assessed. One of the P(s) isolates (1/65), one of the EMB(s) isolates (1/49), and 20 of the EMB(r) isolates (20/61) presented with an embB 306 mutation. Four different single-nucleotide polymorphisms (SNPs) at embB 306 were associated with simultaneous resistance to ethambutol, isoniazid, and rifampin (odds ratio [OR], 17.7; confidence interval [CI], 5.6 to 56.1) and showed a positive predictive value of 82%, with a specificity of 97% for diagnosing multidrug resistance associated with ethambutol, indicating its potential as a molecular marker for several drugs.

  11. Microsatellite DNA markers: evaluating their potential for estimating the proportion of hatchery-reared offspring in a stock enhancement programme.

    PubMed

    Bravington, M V; Ward, R D

    2004-05-01

    We describe a statistical method for estimating the effectiveness of a stock enhancement programme using nuclear DNA loci. It is based on knowing the population allele frequencies and the genotypes of the hatchery parents (mother only, or mother and father), and on determining the probability that a wild-born animal will by chance have a genotype consistent with hatchery origin. We show how to estimate the proportion of released animals in the wild population, and its standard error. The method is applied to a data set of eight microsatellite loci in brown tiger prawns (Penaeus esculentus), prior to the start of a possible enhancement programme. We conclude that, for this particular data set, the effectiveness of such an enhancement programme could be quantified accurately if both maternal and paternal genotypes are known, but not if maternal genotypes only are known. Full paternal genotyping would require offspring genotyping and thus would be expensive, but a partly typed paternal genotype from a mass homogenate of offspring would be almost as effective and much cheaper. The experiment would become feasible based on maternal genotypes alone, if a further three typical microsatellite loci could be found to add to the existing panel of eight. The methods detailed should be of interest to any enhancement project that relies on nuclear DNA markers to provide tags.

  12. A panel of ancestry informative markers to estimate and correct potential effects of population stratification in Han Chinese.

    PubMed

    Qin, Pengfei; Li, Zhiqiang; Jin, Wenfei; Lu, Dongsheng; Lou, Haiyi; Shen, Jiawei; Jin, Li; Shi, Yongyong; Xu, Shuhua

    2014-02-01

    Population stratification acts as a confounding factor in genetic association studies and may lead to false-positive or false-negative results. Previous studies have analyzed the genetic substructures in Han Chinese population, the largest ethnic group in the world comprising ∼20% of the global human population. In this study, we examined 5540 Han Chinese individuals with about 1 million single-nucleotide polymorphisms (SNPs) and screened a panel of ancestry informative markers (AIMs) to facilitate the discerning and controlling of population structure in future association studies on Han Chinese. Based on genome-wide data, we first confirmed our previous observation of the north-south differentiation in Han Chinese population. Second, we developed a panel of 150 validated SNP AIMs to determine the northern or southern origin of each Han Chinese individual. We further evaluated the performance of our AIMs panel in association studies in simulation analysis. Our results showed that this AIMs panel had sufficient power to discern and control population stratification in Han Chinese, which could significantly reduce false-positive rates in both genome-wide association studies (GWAS) and candidate gene association studies (CGAS). We suggest this AIMs panel be genotyped and used to control and correct population stratification in the study design or data analysis of future association studies, especially in CGAS which is the most popular approach to validate previous reports on genetic associations of diseases in post-GWAS era.

  13. Orphan nuclear receptor Nurr1 as a potential novel marker for progression in human pancreatic ductal adenocarcinoma

    PubMed Central

    Ji, Li; Gong, Chen; Ge, Liangyu; Song, Linping; Chen, Fenfen; Jin, Chunjing; Zhu, Hongyan; Zhou, Guoxiong

    2017-01-01

    Nuclear receptor related-1 protein (Nurr1) is a novel orphan member of the nuclear receptor superfamily (the NR4A family) involved in tumorigenesis. The aim of the present study was to investigate the expression and possible function of Nurr1 in pancreatic ductal adenocarcinoma (PDAC). The expression pattern of Nurr1 protein was determined using immunohistochemical staining in 138 patients with PDAC. Elevated Nurr1 expression was more commonly observed in PDAC tissues and cell lines compared with healthy controls. Elevated expression was significantly associated with histological differentiation (P=0.041), lymph node metastasis (P=0.021), TNM classification of malignant tumors stage (P=0.031) and poor survival (P=0.001). Further experiments demonstrated that suppression of endogenous Nurr1 expression attenuated cell proliferation, migration and invasion, and induced apoptosis of PDAC cells. In conclusion, these results suggest that Nurr1 has an important role in the progression of PDAC and may be used as a novel marker for therapeutic targets. PMID:28352330

  14. Increased sialylation of oligosaccharides on IgG paraproteins--a potential new tumour marker in multiple myeloma.

    PubMed Central

    Fleming, S C; Smith, S; Knowles, D; Skillen, A; Self, C H

    1998-01-01

    AIMS: To investigate whether changes in carbohydrate structure of IgG are related to malignancy and stage of disease in myeloma and monoclonal gammopathy of uncertain significance (MGUS). METHODS: 61 patients were studied at diagnosis: 14 with MGUS, nine with stage I multiple myeloma, 11 with stage II, 21 with stage III, and five with solitary plasmacytoma. IgG was extracted from serum by protein G affinity chromatography. Oligosaccharides were cleaved from the protein backbone enzymatically by N-glycosidase F. Oligosaccharide analysis was performed by high pressure anion exchange chromatography with pulsed electrochemical detection (HPAE-PED). RESULTS: Up to 15 oligosaccharide peaks were identified in three major fractions: neutral, monosialylated, and disialylated. Patients with myeloma showed an increase in the proportion of sialylated oligosaccharides in comparison with patients with MGUS. The ratio of neutral to sialylated oligosaccharides (N:S) was reduced at all stages of myeloma compared with MGUS: MGUS, 11.35; myeloma stage I, 7.6 (p = 0.047); stage II, 5.20 (p = 0.035); stage III, 3.60 (p = 0.0002); plasmacytoma, 7.5 (p = 0.046). The N:S ratio was independent of paraprotein concentration (r = 0.05). CONCLUSIONS: The ratio of neutral to sialylated oligosaccharides may act as a new marker of malignancy in IgG paraproteinaemia and warrants further investigation. Images PMID:10193323

  15. Demonstration of Purkinje potential during idiopathic left ventricular tachycardia: a marker for ablation site by transient entrainment.

    PubMed

    Nishizaki, M; Arita, M; Sakurada, H; Ashikaga, T; Yamawake, N; Numano, F; Hiraoka, M

    1997-12-01

    During VT of QRS morphology with right bundle branch block and left axis deviation in a patient without obvious structural heart disease, entrainment by pacing from the right ventricular outflow tract and high right atrium was demonstrated. During entrainment of VT, a Purkinje potential preceding the QRS and recorded at the left ventricular mid-septum was activated by orthodromic impulses in the reentry circuit. The interval between the Purkinje potential and the earliest left ventricular activation was decrementally prolonged with shortening of pacing cycle length. Radiofrequency energy was applied to this site, resulting in successful elimination of VT. Therefore, the Purkinje potential represented activation by an orthodromic wavefront in the reentry circuit, while the orthodromically distal site to this potential showed an area of slow conduction with decremental property.

  16. Marker chromosomes.

    PubMed

    Rao, Kiran Prabhaker; Belogolovkin, Victoria

    2013-04-01

    Marker chromosomes are a morphologically heterogeneous group of structurally abnormal chromosomes that pose a significant challenge in prenatal diagnosis. Phenotypes associated with marker chromosomes are highly variable and range from normal to severely abnormal. Clinical outcomes are very difficult to predict when marker chromosomes are detected prenatally. In this review, we outline the classification, etiology, cytogenetic characterization, and clinical consequences of marker chromosomes, as well as practical approaches to prenatal diagnosis and genetic counseling.

  17. Iophenoxic acid derivatives as markers of oral baits to wildlife. New tools for their detection in tissues of a game species and safety considerations for human exposure.

    PubMed

    Sage, Mickael; Fourel, Isabelle; Lahoreau, Jennifer; Siat, Vivien; Berny, Philippe; Rossi, Sophie

    2013-05-01

    The bait-marker iophenoxic acid (IPA) and its derivatives are increasingly used for evaluating and optimizing the cost-effectiveness of baiting campaigns on wildlife, particularly on game species such as the wild boar. We aimed to determine whether concentrations of the three main IPA derivatives ethyl, methyl and propyl-IPA measured on thoracic liquid extracts (TLE) of hunted wild boars may be representative of two exposure doses, 40 and 200 mg, from 20 to 217 days after ingestion. Then we developed a method of detection of the three IPA derivatives by LC/ESI-MS-MS in muscle and liver to evaluate the suitability of these two other tissues for monitoring the marked bait consumption and for measuring available residues in the meat of marked animals. Three semi-captive wild boars received 40 mg of each IPA derivative, three received 200 mg, and three, as controls, did not receive IPA. Blood serum was sampled 20, 197 or 217 days after IPA exposure according to animals and to the derivative. Wild boars were shot by gun after the different times of serum sampling times, and TLE, muscle and liver were sampled. Our results suggest that TLE is not a relevant tissue for quantitatively expressing IPA exposure. Due to interference, no analytical method was validated on TLE containing digestive material. On the other hand, quantifications in the muscle and particularly in the liver could discriminate wild boars that had ingested the two IPA doses from 20 days until 7 months after exposure, especially for the two long term markers ethyl and propyl-IPA. So IPA quantifications in the liver sampled on hunted animals appear to be a reliable tool for monitoring bait consumption in the field at a large scale. Nevertheless, whatever the ingested dose, ethyl- and propyl-IPA concentrations measured in the muscle and the liver of tested animals until 217 days after exposure, remained higher than 0.01 mg/kg, the Maximal Residue Limit (MRL) is recommended for molecules for which no

  18. Survey and analysis of microsatellites from transcript sequences in Phytophthora species: frequency, distribution, and potential as markers for the genus

    PubMed Central

    Garnica, Diana P; Pinzón, Andrés M; Quesada-Ocampo, Lina M; Bernal, Adriana J; Barreto, Emiliano; Grünwald, Niklaus J; Restrepo, Silvia

    2006-01-01

    Background Members of the genus Phytophthora are notorious pathogens with world-wide distribution. The most devastating species include P. infestans, P. ramorum and P. sojae. In order to develop molecular methods for routinely characterizing their populations and to gain a better insight into the organization and evolution of their genomes, we used an in silico approach to survey and compare simple sequence repeats (SSRs) in transcript sequences from these three species. We compared the occurrence, relative abundance, relative density and cross-species transferability of the SSRs in these oomycetes. Results The number of SSRs in oomycetes transcribed sequences is low and long SSRs are rare. The in silico transferability of SSRs among the Phytophthora species was analyzed for all sets generated, and primers were selected on the basis of similarity as possible candidates for transferability to other Phytophthora species. Sequences encoding putative pathogenicity factors from all three Phytophthora species were also surveyed for presence of SSRs. However, no correlation between gene function and SSR abundance was observed. The SSR survey results, and the primer pairs designed for all SSRs from the three species, were deposited in a public database. Conclusion In all cases the most common SSRs were trinucleotide repeat units with low repeat numbers. A proportion (7.5%) of primers could be transferred with 90% similarity between at least two species of Phytophthora. This information represents a valuable source of molecular markers for use in population genetics, genetic mapping and strain fingerprinting studies of oomycetes, and illustrates how genomic databases can be exploited to generate data-mining filters for SSRs before experimental validation. PMID:17007642

  19. High expression of stathmin 1 is a strong prognostic marker in oral squamous cell carcinoma patients treated by docetaxel-containing regimens.

    PubMed

    Harada, Koji; Ferdous, Tarannum; Harada, Toyoko; Ueyama, Yoshiya

    2017-02-01

    Stathmin 1 is an oncoprotein that regulates cell cycle by modulating microtubule dynamics and can cause uncontrolled cell proliferation in mutated state. The present study examined stathmin 1 expression in 49 patients with oral squamous cell carcinoma (OSCC) treated with docetaxel (Doc)-containing regimens by immunohistochemical staining. Moreover, we investigated the relationship between stathmin 1 expression and clinicopathological features, as well as the prognosis of above patients. Stathmin 1 could be detected in the cytoplasm of tumor cells in OSCC tissues though its expression level was variable. There was no correlation between stathmin 1 expression and patient gender, or age in OSCC. However, stathmin 1 expression of tumor cell was significantly correlated with T classification (P = 0.0017), N classification (P = 0.0171), stage (P < 0.0001), therapeutic efficacy (P < 0.0001), and patient outcome (P = 0.0387). In addition, high expression of stathmin 1 in tumor cells was associated with shorter overall survival (OS, P = 0.0017). Multivariate analysis also revealed that high expression of stathmin 1 was a predictor of reduced survival (P = 0.0241). These findings suggest that patients with OSCC tumors showing high expression of stathmin 1 might have poor therapeutic effects and worse clinical outcomes in OSCC treated with Doc-containing regimen.

  20. Another promising treatment option for neuroblastoma-associated opsoclonus-myoclonus syndrome by oral high-dose dexamethasone pulse: lymphocyte markers as disease activity.

    PubMed

    Oguma, Makiko; Morimoto, Akira; Takada, Akiko; Kashii, Yoshifumi; Fukuda, Tokiko; Mori, Masato; Yamagata, Takanori; Sugie, Hideo; Momoi, Mariko Y

    2012-03-01

    A one-year-old boy with neuroblastoma (NBoma)-associated opsoclonus-myoclonus syndrome (OMS) was treated by oral high-dose dexamethasone (DEX) pulses (20 mg/m(2)/day of DEX for three consecutive days) every 28 days for 6 months after resection of the tumor. All OMS symptoms improved after the first course of DEX pulse therapy and disappeared after the last course. No adverse effects were observed. Minor deterioration of his developmental quotient was noted 33 months after the onset of the disease. NBoma remission has been maintained since treatment. Before DEX pulse therapy, frequency of T lymphocyte, in particular CD4-positive cell decreased markedly resulted in low CD4/8 ratio in the peripheral blood (PB). The frequency of B lymphocyte increased, especially in cerebrospinal fluid. These aberrant values in PB were reversed by DEX pulse therapy and correlated well with the neurological symptoms. A prospective study that assesses the efficacy of this promising and inexpensive treatment for OMS is warranted.

  1. Physical Fitness Measures as Potential Markers of Low Cognitive Function in Japanese Community-Dwelling Older Adults without Apparent Cognitive Problems.

    PubMed

    Narazaki, Kenji; Matsuo, Eri; Honda, Takanori; Nofuji, Yu; Yonemoto, Koji; Kumagai, Shuzo

    2014-09-01

    Detecting signs of cognitive impairment as early as possible is one of the most urgent challenges in preventive care of dementia. It has still been unclear whether physical fitness measures can serve as markers of low cognitive function, a sign of cognitive impairment, in older people free from dementia. The aim of the present study was to examine an association between each of five physical fitness measures and global cognition in Japanese community-dwelling older adults without apparent cognitive problems. The baseline research of the Sasaguri Genkimon Study was conducted from May to August 2011 in Sasaguri town, Fukuoka, Japan. Of the 2,629 baseline subjects who were aged 65 years or older and not certified as individuals requiring nursing care by the town, 1,552 participants without apparent cognitive problems (Mini-Mental State Examination score ≥24) were involved in the present study (59.0% of the baseline subjects, median age: 72 years, men: 40.1%). Global cognitive function was measured by the Japanese version of the Montreal Cognitive Assessment. Handgrip strength, leg strength, sit-to-stand rate, gait speed, and one-leg stand time were examined as physical fitness measures. In multiple linear regression analyses, each of the five physical fitness measures was positively associated with the Montreal Cognitive Assessment score after adjusting for age and sex (p < 0.001). These associations were preserved after additional adjustment for years of formal education, body mass index, and other confounding factors (p < 0.001). The present study first demonstrated the associations between multiple aspects of physical fitness and global cognitive function in Japanese community-dwelling older people without apparent cognitive problems. These results suggest that each of the physical fitness measures has a potential as a single marker of low cognitive function in older populations free from dementia and thereby can be useful in community-based preventive care of

  2. Glucose tolerance factor extracted from yeast: oral insulin-mimetic and insulin-potentiating agent: in vivo and in vitro studies.

    PubMed

    Weksler-Zangen, Sarah; Mizrahi, Tal; Raz, Itamar; Mirsky, Nitsa

    2012-09-01

    In search for an effective oral treatment for diabetes, we examined the capacity of glucose tolerance factor (GTF) extracted from yeast and administered orally to reduce hyperglycaemia in rat models exhibiting insulin deficiency. The cellular effect of GTF on the insulin signalling pathway was investigated in vitro. GTF (oral bolus), insulin (intraperitoneal) or their combination was administered to streptozotocin-diabetic (STZ) or hyperglycaemic Cohen diabetic-sensitive (hyp-CDs) rats. Blood glucose (BG) and insulin levels were measured in the postprandial (PP) state and during an oral glucose tolerance test. Deoxy-glucose transport and insulin signal transduction were assessed in 3T3-L1 adipocytes and myoblasts incubated with the GTF. Low dose of insulin produced a 34 and 12·5 % reduction in the PP-BG levels of hyp-CDs and STZ rats, respectively. GTF induced a 33 and 17 % reduction in the PP-BG levels of hyp-CDs and STZ rats, respectively. When combined with insulin, a respective decrease (58 and 42 %) in BG levels was observed, suggesting a partially additive (hyp-CDs) or synergistic (STZ rats) effect of the GTF and insulin. GTF did not induce insulin secretion in hyp-CDs rats, yet it lowered their BG levels, proposing an effect on glucose clearance by peripheral tissues. GTF induced a dose-dependent increase in deoxy-glucose transport into myoblasts and fat cells similar to insulin, while the combined treatment resulted in augmented transport rate. GTF induced a dose- and time-dependent phosphorylation of insulin receptor substrate 1, Akt and mitogen-activated protein kinase independent of insulin receptor phosphorylation. GTF exerts remarkable insulin-mimetic and insulin-potentiating effects, both in vivo and in vitro. It produces an insulin-like effect by acting on cellular signals downstream of the insulin receptor. These results demonstrate a potential source for a novel oral medication for diabetes.

  3. Assessment in Higher Education: The Potential for a Community of Practice to Improve Inter-Marker Reliability

    ERIC Educational Resources Information Center

    Herbert, Ian P.; Joyce, John; Hassall, Trevor

    2014-01-01

    The design, delivery and assessment of a complete educational scheme, such as a degree programme or a professional qualification course, is a complex matter. Maintaining alignment between the stated aims of the curriculum and the scoring of student achievement is an overarching concern. The potential for drift across individual aspects of an…

  4. The potential role of oral pH in the persistence of Trichomonas gallinae in Cooper's Hawks (Accipiter cooperii).

    PubMed

    Urban, Elizabeth H; Mannan, R William

    2014-01-01

    Trichomoniasis, caused by the protozoan Trichomonas gallinae, affects a variety of species worldwide including avivorious raptors. Existing information suggests that the disease is most prevalent in young birds, and differential susceptibility to trichomoniasis among individuals in different age groups was documented in Cooper's Hawks (Accipiter cooperii) nesting in Tucson, Arizona. In that population, 85% of nestling Cooper's Hawks had T. gallinae in their oral cavity, compared to only 1% of breeding-age hawks. Trichomonads generally are sensitive to environmental pH and we explored the possibility that differences in oral pH may contribute to the differential prevalence of infection between age groups. We measured the pH of the fluid in the oral cavity in 375 Cooper's Hawks from three age groups (nestlings, fledglings, and breeding age) in Tucson, Arizona, in 2010 and 2011 and clinically tested for T. gallinae in a subsample of hawks. Oral pH of nestlings (∼ 6.8) was 7.3 times less acidic than in fledgling or breeding Cooper's Hawks (∼ 6.1). The incidence of T. gallinae was higher in nestlings (16%) than in either fledglings or breeding hawks (0%). Our findings indicate that oral pH becomes more acidic in Cooper's Hawks soon after they leave the nest. Trichomonas gallinae thrives when pH is between 6.5 and 7.5 (optimum 7.2), but is less viable in more acidic conditions. Higher levels of acidity in the oral cavity of fledglings and breeding Cooper's Hawks may reduce their susceptibility to trichomoniasis, and play a role in the differential prevalence of infection among age groups.

  5. Essential and Toxic Metals in Oral Fluid-a Potential Role in the Diagnosis of Periodontal Diseases.

    PubMed

    Herman, Malgorzata; Golasik, Magdalena; Piekoszewski, Wojciech; Walas, Stanislaw; Napierala, Marta; Wyganowska-Swiatkowska, Marzena; Kurhanska-Flisykowska, Anna; Wozniak, Anna; Florek, Ewa

    2016-10-01

    Recently, many studies have investigated the relationship between the level of metals in the body and various diseases. The objective of this study was to examine any possible influence of periodontal disease upon the concentration of metals in oral fluid and blood and to explore the usability of applying cluster analysis coupled with the analysis of selected elements in oral fluid, calcium (Ca), copper (Cu), iron (Fe), magnesium (Mg), manganese (Mn), zinc (Zn), cadmium (Cd) and lead (Pb), for effectively distinguishing people affected by periodontitis from healthy individuals. The quantification of eight metals in oral fluid and blood samples was performed by two inductively coupled plasma techniques-inductively coupled plasma mass spectrometry (ICP-MS) and inductively coupled plasma optical emission spectrometry (ICP-OES). Most of the examined elements were detected at elevated concentration in the oral fluid of periodontal patients. However, the differences were statistically significant in the case of three metals: Cu, Mg and Mn (p < 0.05). Approximately, fivefold increase in the concentration of Cu, threefold-elevated levels of Mn and a twofold increase in the concentration of Mg were found in the oral fluid of the periodontal patients compared to the controls. Cluster analysis confirmed the statistical significance of the differences in the level of metals in the oral fluid between the two groups in most cases, plus enabled the correct classification of the subjects into patients and controls. The relationship between concentrations of metals and periodontal disease may in the future serve to prevent the development of such disease.

  6. Spatial variation in fatty acid trophic markers in albacore tuna from the southwestern Pacific Ocean-A potential 'tropicalization' signal

    NASA Astrophysics Data System (ADS)

    Parrish, Christopher C.; Pethybridge, Heidi; Young, Jock W.; Nichols, Peter D.

    2015-03-01

    Signature fatty acids were used to explore trophic variations in albacore and skipjack tuna sampled from the southwestern Pacific Ocean. There were clear spatial differences in fatty acid profiles between albacore sampled in the Coral (tropical zone centered at ~20°S) and Tasman (temperate zone centered at ~42°S) Seas; however, few differences were observed in fatty acid profiles of albacore sampled off Tasmania and New Zealand. Fatty acid signatures of the Tasman Sea samples reflected a food web based more on diatoms and included: 20:5ω3 (EPA), 18:1ω7, 22:1ω11, 18:2ω6, 18:4ω3, 18:3ω3, and 20:4ω3. In contrast, albacore from the Coral Sea had a distinct fatty acid signature which included 20:4ω6, 22:5ω6, 17:0, 22:4ω6, 24:0, and 17:1. Multivariate analyses revealed the importance of 22:6ω3 (DHA) in Coral Sea-caught albacore which also had a DHA/EPA ratio more than twice that in all other groups suggesting a greater dinoflagellate contribution and/or a higher trophic position. Fatty acid markers indicative of krill consumption were significantly higher in temperate-caught albacore although skipjack were closest in fatty acid composition to krill. These results were likely due to differences at the base of the food web in these two seas suggesting that signature fatty acids can be used as indicators of ecosystem change: in this case the gradual 'tropicalization' of the eastern seaboard of Australia through the southward extension of the East Australian Current. Our findings also indicate comparatively lower concentrations of healthful ω3 long-chain polyunsaturated fatty acids, in particular the content of DHA and EPA, in the tropical samples. This suggests that tropicalization could adversely affect the dietary intake of albacore and other marine predators in the region. Such changes are readily detectable by fatty acid analysis.

  7. A tetrameric peptide derived from bovine lactoferricin as a potential therapeutic tool for oral squamous cell carcinoma: A preclinical model

    PubMed Central

    Solarte, Víctor Alfonso; Conget, Paulette; Vernot, Jean-Paul; Rosas, Jaiver Eduardo; Rivera, Zuly Jenny; García, Javier Eduardo; Arango-Rodríguez, Martha Ligia

    2017-01-01

    Oral squamous cell carcinoma is the fifth most common epithelial cancer in the world, and its current clinical treatment has both low efficiency and poor selectivity. Cationic amphipathic peptides have been proposed as new drugs for the treatment of different types of cancer. The main goal of the present work was to determine the potential of LfcinB(20–25)4, a tetrameric peptide based on the core sequence RRWQWR of bovine lactoferricin LfcinB(20–25), for the treatment of OSCC. In brief, OSCC was induced in the buccal pouch of hamsters by applying 7,12-Dimethylbenz(a)anthracene, and tumors were treated with one of the following peptides: LfcinB(20–25)4, LfcinB(20–25), or vehicle (control). Lesions were macroscopically evaluated every two days and both histological and serum IgG assessments were conducted after 5 weeks. The size of the tumors treated with LfcinB(20–25)4 and LfcinB(20–25) was smaller than that of the control group (46.16±4.41 and 33.92±2.74 mm3 versus 88.77±10.61 mm3, respectively). Also, LfcinB(20–25)4 caused acellularity in the parenchymal tumor compared with LfcinB(20–25) and vehicle treatments. Furthermore, our results demonstrated that both LfcinB(20–25)4 and LfcinB(20–25) induced higher degree of apoptosis relative to the untreated tumors (75–86% vs 8%, respectively). Moreover, although the lowest inflammatory response was achieved when LfcinB(20–25)4 was used, this peptide appeared to induce higher levels of IgG antibodies relative to the vehicle and LfcinB(20–25). In addition the cellular damage and selectivity of the LfcinB(20–25)4 peptide was evaluated in vitro. These assays showed that LfcinB(20–25)4 triggers a selective necrotic effect in the carcinoma cell line. Cumulatively, these data indicate that LfcinB(20–25)4 could be considered as a new therapeutic agent for the treatment of OSCC. PMID:28358840

  8. Enhanced oral bioavailability of a sterol-loaded microemulsion formulation of Flammulina velutipes, a potential antitumor drug

    PubMed Central

    Yi, Chengxue; Zhong, Hui; Tong, Shanshan; Cao, Xia; Firempong, Caleb K; Liu, Hongfei; Fu, Min; Yang, Yan; Feng, Yingshu; Zhang, Huiyun; Xu, Ximing; Yu, Jiangnan

    2012-01-01

    Purpose To investigate the growth inhibition activity of Flammulina velutipes sterol (FVS) against certain human cancer cell lines (gastric SGC and colon LoVo) and to evaluate the optimum microemulsion prescription, as well as the pharmacokinetics of encapsulated FVS. Methods Molecules present in the FVS isolate were identified by gas chromatography/mass spectrometry analysis. The cell viability of FVS was assessed with methyl thiazolyl tetrazolium (MTT) bioassay. Based on the solubility study, phase diagram and stability tests, the optimum prescription of F. velutipes sterol microemulsions (FVSMs) were determined, followed by FVSMs characterization, and its in vivo pharmacokinetic study in rats. Results The chemical composition of FVS was mainly ergosterol (54.8%) and 22,23-dihydroergosterol (27.9%). After 72 hours of treatment, both the FVS (half-maximal inhibitory concentration [IC50] = 11.99 μg · mL−1) and the standard anticancer drug, 5-fluorouracil (IC50 = 0.88 μg · mL−1) exhibited strong in vitro antiproliferative activity against SGC cells, with IC50 > 30.0 μg · mL−1; but the FVS performed poorly against LoVo cells (IC50 > 40.0 μg · mL−1). The optimal FVSMs prescription consisted of 3.0% medium chain triglycerides, 5.0% ethanol, 21.0% Cremophor EL and 71.0% water (w/w) with associated solubility of FVS being 0.680 mg · mL−1 as compared to free FVS (0.67 μg · mL−1). The relative oral bioavailability (area-under-the-curve values of ergosterol and 22,23-dihydroergosterol showed a 2.56-fold and 4.50-fold increase, respectively) of FVSMs (mean diameter ~ 22.9 nm) as against free FVS were greatly enhanced. Conclusion These results indicate that the FVS could be a potential candidate for the development of an anticancer drug and it is readily bioavailable via microemulsion formulations. PMID:23049254

  9. A tetrameric peptide derived from bovine lactoferricin as a potential therapeutic tool for oral squamous cell carcinoma: A preclinical model.

    PubMed

    Solarte, Víctor Alfonso; Conget, Paulette; Vernot, Jean-Paul; Rosas, Jaiver Eduardo; Rivera, Zuly Jenny; García, Javier Eduardo; Arango-Rodríguez, Martha Ligia

    2017-01-01

    Oral squamous cell carcinoma is the fifth most common epithelial cancer in the world, and its current clinical treatment has both low efficiency and poor selectivity. Cationic amphipathic peptides have been proposed as new drugs for the treatment of different types of cancer. The main goal of the present work was to determine the potential of LfcinB(20-25)4, a tetrameric peptide based on the core sequence RRWQWR of bovine lactoferricin LfcinB(20-25), for the treatment of OSCC. In brief, OSCC was induced in the buccal pouch of hamsters by applying 7,12-Dimethylbenz(a)anthracene, and tumors were treated with one of the following peptides: LfcinB(20-25)4, LfcinB(20-25), or vehicle (control). Lesions were macroscopically evaluated every two days and both histological and serum IgG assessments were conducted after 5 weeks. The size of the tumors treated with LfcinB(20-25)4 and LfcinB(20-25) was smaller than that of the control group (46.16±4.41 and 33.92±2.74 mm3 versus 88.77±10.61 mm3, respectively). Also, LfcinB(20-25)4 caused acellularity in the parenchymal tumor compared with LfcinB(20-25) and vehicle treatments. Furthermore, our results demonstrated that both LfcinB(20-25)4 and LfcinB(20-25) induced higher degree of apoptosis relative to the untreated tumors (75-86% vs 8%, respectively). Moreover, although the lowest inflammatory response was achieved when LfcinB(20-25)4 was used, this peptide appeared to induce higher levels of IgG antibodies relative to the vehicle and LfcinB(20-25). In addition the cellular damage and selectivity of the LfcinB(20-25)4 peptide was evaluated in vitro. These assays showed that LfcinB(20-25)4 triggers a selective necrotic effect in the carcinoma cell line. Cumulatively, these data indicate that LfcinB(20-25)4 could be considered as a new therapeutic agent for the treatment of OSCC.

  10. Urinary excretion study following consumption of various poppy seed products and investigation of the new potential street heroin marker ATM4G.

    PubMed

    Maas, Alexandra; Krämer, Michael; Sydow, Konrad; Chen, Pai-Shan; Dame, Torsten; Musshoff, Frank; Diehl, Bernd W K; Madea, Burkhard; Hess, Cornelius

    2017-03-01

    Discrimination between street heroin consumption and poppy seed ingestion represents a major toxicological challenge in daily routine work. Several difficulties associated with conventional street heroin markers originate from their versatile occurrence in various poppy seed products and medications, respectively, as well as to small windows of detection. A novel opportunity to overcome these hindrances is represented by the new potential street heroin marker acetylated-thebaine-4-metabolite glucuronide (ATM4G), originating from thebaine during street heroin synthesis followed by metabolic reactions after administration. In this study, urine samples after consumption of different German poppy seed products and urine samples from subjects with suspicion of preceding heroin consumption were tested for ATM4G, 6-AC (6-acetylcodeine), papaverine, noscapine, 6-MAM (6-monoacetylmorphine), morphine, and codeine. Neither 6-AC and 6-MAM nor ATM4G but morphine and codeine could be detected in urine samples following poppy seed ingestion. As well, neither papaverine nor noscapine could be observed even after consumption of poppy seeds containing up to 37 µg noscapine and up to 9.8 µg papaverine, respectively. Concerning the urine samples with suspicion of preceding heroin consumption, ATM4G could be detected in 9 of 43 cases. By contrast, evidence of 6-AC and 6-MAM, respectively, could only be seen in 7 urine samples. In conclusion, ATM4G should be measured additionally in cases requiring discrimination of street heroin consumption from poppy seed intake. Copyright © 2016 John Wiley & Sons, Ltd.

  11. Strategies of targeting oral drug delivery systems to the colon and their potential use for the treatment of colorectal cancer.

    PubMed

    Krishnaiah, Yellela S R; Khan, Mansoor A

    2012-01-01

    Colorectal cancer (CRC) is the third most common cause of cancer-related death in both men and women. Often, surgical intervention remains the choice in treating CRC. Traditional dosage forms used for treating CRC deliver drug to wanted as well as unwanted sites of drug action resulting in several adverse side effects. Targeted oral drug delivery systems are being investigated to target and deliver chemotherapeutic and chemopreventive agents directly to colon and rectum. Site-specific delivery of a drug to colon increases its concentration at the target site, and thus requires a lower dose with reduced incidence of side effects. The major obstacle to be overcome for successful targeting of drug to colon through oral route is that drug absorption/degradation must be avoided in stomach and small intestine before the dosage form reaches colon. The review includes discussion of physiological factors that must be considered when targeting drugs directly to colorectal region, an outline on drugs used for treatment and prevention of CRC, and a brief description of various types of colon-targeted oral drug delivery systems. The focus is on the assessment of various formulation approaches being investigated for oral colon-specific delivery of drugs used in the treatment and prevention of CRC.

  12. Mechanisms of the harmful effects of bacterial semen infection on ejaculated human spermatozoa: potential inflammatory markers in semen.

    PubMed

    Fraczek, Monika; Kurpisz, Maciej

    2015-01-01

    The invasion of the male reproductive tract by microorganisms, and its subsequent consequences for sperm fertilizing potential, has been intensely discussed. The role of the bacteria that are responsible for the colonization and contamination of the male urogenital tract, rather than its infection, in diminished sperm parameters raises the most controversy. There are numerous premises suggesting that bacterial semen infection is associated with male infertility. However, the molecular mechanism by which the fertility is affected is complex and multifactorial, and still presents a puzzle. Some authors have suggested that direct interactions between bacteria and human spermatozoa facilitate sperm immobilization, affect sperm morphology, and thus weaken the ability of sperm to fertilize. On the other hand, the massive infiltration of activated leukocytes into the inflammatory site may be associated with impairment of sperm fertilizing potential, due to oxidative, apoptotic, and immune processes. This review presents current research trends and aims to summarize the present knowledge of semen inflammation and causative bacterial agents in the male urogenital tract, with its consequence on seminological parameters, and male fertility status.

  13. Measurement of peroxiredoxin-4 serum levels in rat tissue and its use as a potential marker for hepatic disease.

    PubMed

    Ito, Ritsu; Takahashi, Motoko; Ihara, Hideyuki; Tsukamoto, Hiroki; Fujii, Junichi; Ikeda, Yoshitaka

    2012-08-01

    Peroxiredoxin (Prx)-4, a secretable endoplasmic reticulum (ER)-resident isoform of the mammalian Prx family, functions as a thioredoxin-dependent peroxidase. It is acknowledged that Prx-4 plays a role in the detoxification of hydrogen peroxide, and potentially other peroxides, which may be generated during the oxidative folding of proteins and oxidative stress in the ER. The present study was undertaken in order to specifically quantify the tissue levels of Prx-4. To accomplish this, an enzyme-linked immunosorbent assay was developed using a specific polyclonal antibody produced by immunizing a rabbit with native recombinant rat Prx-4 protein. The assay was used to detect Prx-4 in the range of 0.1 and 10 ng/ml, and to investigate tissue distribution in rats. Using this immunoassay, we found that the serum levels of Prx-4 were substantially lower in asymptomatic Long-Evans Cinnamon rats, a rat model of Wilson's disease, compared to normal rats. In addition, the treatment of rat hepatoma cells with N-acetylcysteine led to a significant increase in the release of Prx-4 protein into the medium; thus, it appears likely that the secretion of Prx-4 is associated with the redox state within cells. These results suggest that serum Prx-4 has potential for use as a biomarker for hepatic oxidative stress.

  14. Non-small cell lung cancer: quantitative phenotypic analysis of CT images as a potential marker of prognosis

    PubMed Central

    Song, Jiangdian; Liu, Zaiyi; Zhong, Wenzhao; Huang, Yanqi; Ma, Zelan; Dong, Di; Liang, Changhong; Tian, Jie

    2016-01-01

    This was a retrospective study to investigate the predictive and prognostic ability of quantitative computed tomography phenotypic features in patients with non-small cell lung cancer (NSCLC). 661 patients with pathological confirmed as NSCLC were enrolled between 2007 and 2014. 592 phenotypic descriptors was automatically extracted on the pre-therapy CT images. Firstly, support vector machine (SVM) was used to evaluate the predictive value of each feature for pathology and TNM clinical stage. Secondly, Cox proportional hazards model was used to evaluate the prognostic value of these imaging signatures selected by SVM which subjected to a primary cohort of 138 patients, and an external independent validation of 61 patients. The results indicated that predictive accuracy for histopathology, N staging, and overall clinical stage was 75.16%, 79.40% and 80.33%, respectively. Besides, Cox models indicated the signatures selected by SVM: “correlation of co-occurrence after wavelet transform” was significantly associated with overall survival in the two datasets (hazard ratio [HR]: 1.65, 95% confidence interval [CI]: 1.41–2.75, p = 0.010; and HR: 2.74, 95%CI: 1.10–6.85, p = 0.027, respectively). Our study indicates that the phenotypic features might provide some insight in metastatic potential or aggressiveness for NSCLC, which potentially offer clinical value in directing personalized therapeutic regimen selection for NSCLC. PMID:27922113

  15. Oral Cancer

    MedlinePlus

    Oral Cancer Basic description Cancer can affect any part of the oral cavity, including the lips, tongue, mouth, and throat. There are 2 kinds of oral cancer: oral cavity cancer and oropharyngeal cancer. The most ...

  16. RAPD and SCAR markers as potential tools for detection of milk origin in dairy products: Adulterant sheep breeds in Serra da Estrela cheese production.

    PubMed

    Cunha, Joana T; Ribeiro, Tânia I B; Rocha, João B; Nunes, João; Teixeira, José A; Domingues, Lucília

    2016-11-15

    Serra da Estrela Protected Designation of Origin (PDO) cheese is the most famous Portuguese cheese and has a high commercial value. However, the adulteration of production with cheaper/lower-quality milks from non-autochthones ovine breeds compromises the quality of the final product and undervalues the original PDO cheese. A Randomly Amplified Polymorphic DNA (RAPD) method was developed for efficient detection of adulterant breeds in milk mixtures used for fraudulent production of this cheese. Furthermore, Sequence Characterized Amplified Region (SCAR) markers were designed envisioning the detection of milk adulteration in processed dairy foods. The RAPD-SCAR technique is here described, for the first time, to be potentially useful for detection of milk origin in dairy products. In this sense, our findings will play an important role on the valorization of Serra da Estrela cheese, as well as on other high-quality dairy products prone to adulteration, contributing to the further development of the dairy industry.

  17. Peptides in oral diseases.

    PubMed

    Lucchese, Alberta; Guida, Agostino; Petruzzi, Massimo; Capone, Giovanni; Laino, Luigi; Serpico, Rosario

    2012-01-01

    The oral cavity is home to numerous viruses and micro-organisms recognized as having a role in various oral diseases as well as in infections in other parts of the body. Indeed, in general a microbial infection underlies or is believed to underlie the ample spectrum of oral diseases, from tooth enamel decay to periodontal lesions, from candidiasis to virus-induced oral squamous cell carcinomas, and bullous autoimmune oral disorders. This clinico-pathological context stresses the need of targeted therapies to specifically kill infectious agents in a complex environment such as the oral cavity, and explains the current interest in exploring peptide-based therapeutic approaches in oral and dental research. Here, we review the therapeutic potential of antimicrobial peptides such as LL-37, beta defensins, adrenomedullin, histatins, and of various peptides modulating gene expression and immuno-biological interaction(s) in oral diseases.

  18. Metabolic profiling reveals potential metabolic markers associated with Hypoxia Inducible Factor-mediated signalling in hypoxic cancer cells

    PubMed Central

    Armitage, Emily G.; Kotze, Helen L.; Allwood, J. William; Dunn, Warwick B.; Goodacre, Royston; Williams, Kaye J.

    2015-01-01

    Hypoxia inducible factors (HIFs) plays an important role in oxygen compromised environments and therefore in tumour survival. In this research, metabolomics has been applied to study HIFs metabolic function in two cell models: mouse hepatocellular carcinoma and human colon carcinoma, whereby the metabolism has been profiled for a range of oxygen potentials. Wild type cells have been compared to cells deficient in HIF signalling to reveal its effect on cellular metabolism under normal oxygen conditions as well as low oxygen, hypoxic and anoxic environments. Characteristic responses to hypoxia that were conserved across both cell models involved the anti-correlation between 2-hydroxyglutarate, 2-oxoglutarate, fructose, hexadecanoic acid, hypotaurine, pyruvate and octadecenoic acid with 4-hydroxyproline, aspartate, cysteine, glutamine, lysine, malate and pyroglutamate. Further to this, network-based correlation analysis revealed HIF specific pathway responses to each oxygen condition that were also conserved between cell models. From this, 4-hydroxyproline was revealed as a regulating hub in low oxygen survival of WT cells while fructose appeared to be in HIF deficient cells. Pathways surrounding these hubs were built from the direct connections of correlated metabolites that look beyond traditional pathways in order to understand the mechanism of HIF response to low oxygen environments. PMID:26508589

  19. Comparative study of Saccharomyces cerevisiae wine strains to identify potential marker genes correlated to desiccation stress tolerance.

    PubMed

    Capece, Angela; Votta, Sonia; Guaragnella, Nicoletta; Zambuto, Marianna; Romaniello, Rossana; Romano, Patrizia

    2016-05-01

    The most diffused formulation of starter for winemaking is active dry yeast (ADY). ADYs production process is essentially characterized by air-drying stress, a combination of several stresses, including thermal, hyperosmotic and oxidative and cell capacity to counteract such multiple stresses will determine its survival. The molecular mechanisms underlying cell stress response to desiccation have been mostly studied in laboratory and commercial yeast strains, but a growing interest is currently developing for indigenous yeast strains which represent a valuable and alternative source of genetic and molecular biodiversity to be exploited. In this work, a comparative study of different Saccharomyces cerevisiae indigenous wine strains, previously selected for their technological traits, has been carried out to identify potentially relevant genes involved in desiccation stress tolerance. Cell viability was evaluated along desiccation treatment and gene expression was analyzed by real-time PCR before and during the stress. Our data show that the observed differences in individual strain sensitivity to desiccation stress could be associated to specific gene expression over time. In particular, either the basal or the stress-induced mRNA levels of certain genes, such as HSP12, SSA3, TPS1, TPS2, CTT1 and SOD1, result tightly correlated to the strain survival advantage. This study provides a reliable and sensitive method to predict desiccation stress tolerance of indigenous wine yeast strains which could be preliminary to biotechnological applications.

  20. Comparative genotyping of Clostridium thermocellum strains isolated from biogas plants: genetic markers and characterization of cellulolytic potential.

    PubMed

    Koeck, Daniela E; Zverlov, Vladimir V; Liebl, Wolfgang; Schwarz, Wolfgang H

    2014-07-01

    Clostridium thermocellum is among the most prevalent of known anaerobic cellulolytic bacteria. In this study, genetic and phenotypic variations among C. thermocellum strains isolated from different biogas plants were determined and different genotyping methods were evaluated on these isolates. At least two C. thermocellum strains were isolated independently from each of nine different biogas plants via enrichment on cellulose. Various DNA-based genotyping methods such as ribotyping, RAPD (Random Amplified Polymorphic DNA) and VNTR (Variable Number of Tandem Repeats) were applied to these isolates. One novel approach - the amplification of unknown target sequences between copies of a previously discovered Random Inserted Mobile Element (RIME) - was also tested. The genotyping method with the highest discriminatory power was found to be the amplification of the sequences between the insertion elements, where isolates from each biogas plant yielded a different band pattern. Cellulolytic potentials, optimal growth conditions and substrate spectra of all isolates were characterized to help identify phenotypic variations. Irrespective of the genotyping method used, the isolates from each individual biogas plant always exhibited identical patterns. This is suggestive of a single C. thermocellum strain exhibiting dominance in each biogas plant. The genotypic groups reflect the results of the physiological characterization of the isolates like substrate diversity and cellulase activity. Conversely, strains isolated across a range of biogas plants differed in their genotyping results and physiological properties. Both strains isolated from one biogas plant had the best specific cellulose-degrading properties and might therefore achieve superior substrate utilization yields in biogas fermenters.

  1. Metabolic profiling reveals potential metabolic markers associated with Hypoxia Inducible Factor-mediated signalling in hypoxic cancer cells.

    PubMed

    Armitage, Emily G; Kotze, Helen L; Allwood, J William; Dunn, Warwick B; Goodacre, Royston; Williams, Kaye J

    2015-10-28

    Hypoxia inducible factors (HIFs) plays an important role in oxygen compromised environments and therefore in tumour survival. In this research, metabolomics has been applied to study HIFs metabolic function in two cell models: mouse hepatocellular carcinoma and human colon carcinoma, whereby the metabolism has been profiled for a range of oxygen potentials. Wild type cells have been compared to cells deficient in HIF signalling to reveal its effect on cellular metabolism under normal oxygen conditions as well as low oxygen, hypoxic and anoxic environments. Characteristic responses to hypoxia that were conserved across both cell models involved the anti-correlation between 2-hydroxyglutarate, 2-oxoglutarate, fructose, hexadecanoic acid, hypotaurine, pyruvate and octadecenoic acid with 4-hydroxyproline, aspartate, cysteine, glutamine, lysine, malate and pyroglutamate. Further to this, network-based correlation analysis revealed HIF specific pathway responses to each oxygen condition that were also conserved between cell models. From this, 4-hydroxyproline was revealed as a regulating hub in low oxygen survival of WT cells while fructose appeared to be in HIF deficient cells. Pathways surrounding these hubs were built from the direct connections of correlated metabolites that look beyond traditional pathways in order to understand the mechanism of HIF response to low oxygen environments.

  2. Assessment of eosinophil peroxidase as a potential diagnostic and prognostic marker in dogs with inflammatory bowel disease.

    PubMed

    Bastan, Idil; Robinson, Nicholas A; Ge, Xiao Na; Rendahl, Aaron K; Rao, Savita P; Washabau, Robert J; Sriramarao, P

    2017-01-01

    OBJECTIVE To evaluate a method for identifying intact and degranulated eosinophils in the small intestine of dogs with inflammatory bowel disease (IBD) by use of a monoclonal antibody (mAb) against eosinophil peroxidase (EPX). ANIMALS 11 untreated dogs with IBD, 5 dogs with IBD treated with prednisolone, and 8 control dogs with no clinical evidence of gastrointestinal tract disease and no immunosuppressive treatment. PROCEDURES 4-μm-thick sections of paraffin-embedded tissues from necropsy specimens were immunostained with EPX mAb. Stained intact and degranulated eosinophils in consecutive microscopic fields (400X magnification) of the upper (villus tips) and lower (between the muscularis mucosae and crypts) regions of the lamina propria of the jejunum were manually counted. RESULTS Compared with control and treated IBD dogs, untreated IBD dogs had a significantly higher number of degranulated eosinophils in the lower region of the lamina propria. However, no significant differences were detected in the number of intact eosinophils in this region among groups. In the upper region of the lamina propria, untreated IBD dogs had a significantly higher number of degranulated and intact eosinophils, compared with control and treated IBD dogs. Number of degranulated and intact eosinophils did not differ significantly between control and treated IBD dogs. CONCLUSIONS AND CLINICAL RELEVANCE Immunohistologic analysis with EPX mAb yielded prominent granule staining that allowed reliable morphological identification of degranulated and intact eosinophils, which may provide a strategy for quantitative and selective evaluation of eosinophils in gastrointestinal biopsy specimens and a potential method to diagnose IBD and evaluate treatment outcome.

  3. Implication of the intestinal microbiome as a potential surrogate marker of immune responsiveness to experimental therapies in autoimmune diabetes

    PubMed Central

    Needell, James C.; Dinarello, Charles A.; Ir, Diana; Robertson, Charles E.; Ryan, Sarah M.; Kroehl, Miranda E.; Frank, Daniel N.; Zipris, Danny

    2017-01-01

    Type 1 diabetes (T1D) is an autoimmune proinflammatory disease with no effective intervention. A major obstacle in developing new immunotherapies for T1D is the lack of means for monitoring immune responsiveness to experimental therapies. The LEW1.WR1 rat develops autoimmunity following infection with the parvovirus Kilham rat virus (KRV) via mechanisms linked with activation of proinflammatory pathways and alterations in the gut bacterial composition. We used this animal to test the hypothesis that intervention with agents that block innate immunity and diabetes is associated with a shift in the gut microbiota. We observed that infection with KRV results in the induction of proinflammatory gene activation in both the spleen and pancreatic lymph nodes. Furthermore, administering animals the histone deacetylase inhibitor ITF-2357 and IL-1 receptor antagonist (Anakinra) induced differential STAT-1 and the p40 unit of IL-12/IL-23 gene expression. Sequencing of bacterial 16S rRNA genes demonstrated that both ITF-2357 and Anakinra alter microbial diversity. ITF-2357 and Anakinra modulated the abundance of 23 and 8 bacterial taxa in KRV-infected animals, respectively, of which 5 overlapped between the two agents. Lastly, principal component analysis implied that ITF-2357 and Anakinra induce distinct gut microbiomes compared with those from untreated animals or rats provided KRV only. Together, the data suggest that ITF-2357 and Anakinra differentially influence the innate immune system and the intestinal microbiota and highlight the potential use of the gut microbiome as a surrogate means of assessing anti-inflammatory immune effects in type 1 diabetes. PMID:28301545

  4. Implication of the intestinal microbiome as a potential surrogate marker of immune responsiveness to experimental therapies in autoimmune diabetes.

    PubMed

    Needell, James C; Dinarello, Charles A; Ir, Diana; Robertson, Charles E; Ryan, Sarah M; Kroehl, Miranda E; Frank, Daniel N; Zipris, Danny

    2017-01-01

    Type 1 diabetes (T1D) is an autoimmune proinflammatory disease with no effective intervention. A major obstacle in developing new immunotherapies for T1D is the lack of means for monitoring immune responsiveness to experimental therapies. The LEW1.WR1 rat develops autoimmunity following infection with the parvovirus Kilham rat virus (KRV) via mechanisms linked with activation of proinflammatory pathways and alterations in the gut bacterial composition. We used this animal to test the hypothesis that intervention with agents that block innate immunity and diabetes is associated with a shift in the gut microbiota. We observed that infection with KRV results in the induction of proinflammatory gene activation in both the spleen and pancreatic lymph nodes. Furthermore, administering animals the histone deacetylase inhibitor ITF-2357 and IL-1 receptor antagonist (Anakinra) induced differential STAT-1 and the p40 unit of IL-12/IL-23 gene expression. Sequencing of bacterial 16S rRNA genes demonstrated that both ITF-2357 and Anakinra alter microbial diversity. ITF-2357 and Anakinra modulated the abundance of 23 and 8 bacterial taxa in KRV-infected animals, respectively, of which 5 overlapped between the two agents. Lastly, principal component analysis implied that ITF-2357 and Anakinra induce distinct gut microbiomes compared with those from untreated animals or rats provided KRV only. Together, the data suggest that ITF-2357 and Anakinra differentially influence the innate immune system and the intestinal microbiota and highlight the potential use of the gut microbiome as a surrogate means of assessing anti-inflammatory immune effects in type 1 diabetes.

  5. limited potentiation of blood pressure in response to oral tyramine by the anti-Parkinson brain selective multifunctional monoamine oxidase-AB inhibitor, M30.

    PubMed

    Gal, Shunit; Abassi, Zaid A; Youdim, Moussa B H

    2010-08-01

    One of the limitations of non-selective monoamine oxidase (MAO) inhibitors as anti-depressant or anti-Parkinson drugs is their ability to potentiate the cardiovascular effect of oral tyramine, resulting from inhibition of systemic MAO-A and release of noradrenaline. We have investigated the cardiovascular effect of oral tyramine in response to the novel multifunctional, brain selective MAO-AB inhibitor, M30 [5-(N-methyl-N-propargylaminomethyl)-8-hydroxyquinoline], and compared it to the classical non-selective inhibitor tranylcypromine (TCP) in rats. We also measured MAO-A and B in the striatum, hippocampus, liver, and small intestine and determined brain levels of dopamine, noradrenaline, and serotonin. At the doses employed, intraperitoneal (i.p.) M30 (5 and 10 mg/kg) selectively inhibited brain MAO-A and B by more than 85%, with little inhibition of liver and small intestine enzymes while raising striatal levels of dopamine, noradrenaline, and serotonin. In contrast to TCP (10 mg/kg, i.p.), which fully inhibits both enzymes in the brain and systemic organs and significantly potentiates the tyramine pressor effect, M30 had a limited pressor effect as compared to it and controls. The limited potentiation of tyramine pressor effect by M30, its ability to raise brain levels of aminergic neurotransmitters together with its neuroprotective and neurorestorative activities make this drug potentially important as an anti-depressant and anti-Parkinsonian agent, for which it is being developed.

  6. Gene expression profiles of progressive pancreatic endocrine tumours and their liver metastases reveal potential novel markers and therapeutic targets.

    PubMed

    Capurso, G; Lattimore, S; Crnogorac-Jurcevic, T; Panzuto, F; Milione, M; Bhakta, V; Campanini, N; Swift, S M; Bordi, C; Delle Fave, G; Lemoine, N R

    2006-06-01

    The intrinsic nature of tumour behaviour (stable vs progressive) and the presence of liver metastases are key factors in determining the outcome of patients with a pancreatic endocrine tumour (PET). Previous expression profile analyses of PETs were limited to non-homogeneous groups or to primary lesions only. The aim of this study was to investigate the gene expression profiles of a more uniform series of sporadic, non-functioning (NF) PETs with progressive disease and, for the first time, their liver metastases, on the Affymetrix human genome U133A and B GeneChip set. Thirteen NF PET samples (eight primaries and five liver metastases) from ten patients with progressive, metastatic disease, three cell lines (BON, QGP and CM) and four purified islet samples were analysed. The same samples were employed for confirmation of candidate gene expression by means of quantitative RT-PCR, while a further 37 PET and 15 carcinoid samples were analysed by immunohistochemistry. Analysis of genes differentially expressed between islets and primaries and metastases revealed 667 up- and 223 down-regulated genes, most of which have not previously been observed in PETs, and whose gene ontology molecular function has been detailed. Overexpression of bridging integrator 1 (BIN1) and protein Z dependent protease inhibitor (SERPINA10) which may represent useful biomarkers, and of lymphocyte specific protein tyrosine kinase (LCK) and bone marrow stromal cell antigen (BST2) which could be used as therapeutic targets, has been validated. When primary tumours were compared with metastatic lesions, no significantly differentially expressed genes were found, in accord with cluster analysis which revealed a striking similarity between primary and metastatic lesions, with the cell lines clustering separately. We have provided a comprehensive list of differentially expressed genes in a uniform set of aggressive NF PETs. A number of dysregulated genes deserve further in-depth study as potentially

  7. Essentials of oral cancer.

    PubMed

    Rivera, César

    2015-01-01

    Oral cancer is one of the 10 most common cancers in the world, with a delayed clinical detection, poor prognosis, without specific biomarkers for the disease and expensive therapeutic alternatives. This review aims to present the fundamental aspects of this cancer, focused on squamous cell carcinoma of the oral cavity (OSCC), moving from its definition and epidemiological aspects, addressing the oral carcinogenesis, oral potentially malignant disorders, epithelial precursor lesions and experimental methods for its study, therapies and future challenges. Oral cancer is a preventable disease, risk factors and natural history is already being known, where biomedical sciences and dentistry in particular are likely to improve their poor clinical indicators.

  8. Essentials of oral cancer

    PubMed Central

    Rivera, César

    2015-01-01

    Oral cancer is one of the 10 most common cancers in the world, with a delayed clinical detection, poor prognosis, without specific biomarkers for the disease and expensive therapeutic alternatives. This review aims to present the fundamental aspects of this cancer, focused on squamous cell carcinoma of the oral cavity (OSCC), moving from its definition and epidemiological aspects, addressing the oral carcinogenesis, oral potentially malignant disorders, epithelial precursor lesions and experimental methods for its study, therapies and future challenges. Oral cancer is a preventable disease, risk factors and natural history is already being known, where biomedical sciences and dentistry in particular are likely to improve their poor clinical indicators. PMID:26617944

  9. Association of p62/SQSTM1 Excess and Oral Carcinogenesis

    PubMed Central

    Inui, Takuma; Chano, Tokuhiro; Takikita-Suzuki, Mikiko; Nishikawa, Masanori; Yamamoto, Gaku; Okabe, Hidetoshi

    2013-01-01

    p62/SQSTM1 (sequestosome1) has never been evaluated in oral epithelium. In order to clarify the role of p62/SQSTM1 in carcinogenesis in oral epithelium, both p62/SQSTM1 and Nrf2 were immunohistochemically evaluated in 54 carcinomas and 14 low grade dysplasias. p62/SQSTM1 knockdowns were also designed in oral cancer cells, and we analyzed the Nrf2 pathway, GSH contents and ROS accumulation. The association between p62/SQSTM1 excess and prognosis was addressed in a clinical cohort of oral carcinoma cases. p62/SQSTM1 excess was more obvious in carcinomas, but Nrf2 was abundant in almost all samples of the oral epithelium. In oral carcinoma cells, p62/SQSTM1 knockdown did not affect the Nrf2-Keap1 pathway but did significantly reduce GSH content with subsequent ROS accumulation, and caused cell growth inhibition in the irradiated condition. Finally, p62/SQSTM1 excess was associated with poor prognosis in a clinical cohort. In oral epithelial carcinogenesis, p62/SQSTM1 excess played a role in GSH induction rather than Nrf2 accumulation, and may cause resistance to cytotoxic stresses such as radiation or chemotherapy. Immunohistochemical evaluation of p62/SQSTM1 may be a potential significant marker to identify early carcinogenesis, chemo-radiotherapeutic resistance or poor prognosis of oral squamous cell carcinomas. PMID:24086340

  10. Fibroblast Growth Factor (FGF-2) and Its Receptors FGFR-2 and FGFR-3 May Be Putative Biomarkers of Malignant Transformation of Potentially Malignant Oral Lesions into Oral Squamous Cell Carcinoma

    PubMed Central

    Nayak, Seema; Goel, Madhu Mati; Makker, Annu; Bhatia, Vikram; Chandra, Saumya; Kumar, Sandeep; Agarwal, S. P.

    2015-01-01

    There are several factors like angiogenesis, lymphangiogenesis, genetic alterations, mutational factors that are involved in malignant transformation of potentially malignant oral lesions (PMOLs) to oral squamous cell carcinoma (OSCC). Fibroblast growth factor-2 (FGF-2) is one of the prototypes of the large family of growth factors that bind heparin. FGF-2 induces angiogenesis and its receptors may play a role in synthesis of collagen. FGFs are involved in transmission of signals between the epithelium and connective tissue, and influence growth and differentiation of a wide variety of tissue including epithelia. The present study was undertaken to analyze expression of FGF-2 and its receptors FGFR-2 and FGFR-3 in 72 PMOLs, 108 OSCC and 52 healthy controls, and their role in risk assessment for malignant transformation of Leukoplakia (LKP) and Oral submucous fibrosis (OSMF) to OSCC. Immunohistochemistry was performed using antibodies against FGF-2, FGFR-2 and FGFR-3. IHC results were validated by Real Time PCR. Expression of FGF-2, FGFR-2 and FGFR-3 was upregulated from PMOLs to OSCC. While 90% (9/10) of PMOLs which showed malignant transformation (transformed) expressed FGF-2, only 24.19% cases (15/62) of PMOLs which were not transformed (untransformed) to OSCC expressed FGF-2. Similarly, FGFR-2 expression was seen in 16/62 (25.81%) of untransformed PMOLs and 8/10 (80%) cases of transformed PMOLs. FGFR-3 expression was observed in 23/62 (37.10%) cases of untransformed PMOLs and 6/10 (60%) cases of transformed PMOLs. A significant association of FGF-2 and FGFR-2 expression with malignant transformation from PMOLs to OSCC was observed both at phenotypic and molecular level. The results suggest that FGF-2 and FGFR-2 may be useful as biomarkers of malignant transformation in patients with OSMF and LKP. PMID:26465941

  11. Fibroblast Growth Factor (FGF-2) and Its Receptors FGFR-2 and FGFR-3 May Be Putative Biomarkers of Malignant Transformation of Potentially Malignant Oral Lesions into Oral Squamous Cell Carcinoma.

    PubMed

    Nayak, Seema; Goel, Madhu Mati; Makker, Annu; Bhatia, Vikram; Chandra, Saumya; Kumar, Sandeep; Agarwal, S P

    2015-01-01

    There are several factors like angiogenesis, lymphangiogenesis, genetic alterations, mutational factors that are involved in malignant transformation of potentially malignant oral lesions (PMOLs) to oral squamous cell carcinoma (OSCC). Fibroblast growth factor-2 (FGF-2) is one of the prototypes of the large family of growth factors that bind heparin. FGF-2 induces angiogenesis and its receptors may play a role in synthesis of collagen. FGFs are involved in transmission of signals between the epithelium and connective tissue, and influence growth and differentiation of a wide variety of tissue including epithelia. The present study was undertaken to analyze expression of FGF-2 and its receptors FGFR-2 and FGFR-3 in 72 PMOLs, 108 OSCC and 52 healthy controls, and their role in risk assessment for malignant transformation of Leukoplakia (LKP) and Oral submucous fibrosis (OSMF) to OSCC. Immunohistochemistry was performed using antibodies against FGF-2, FGFR-2 and FGFR-3. IHC results were validated by Real Time PCR. Expression of FGF-2, FGFR-2 and FGFR-3 was upregulated from PMOLs to OSCC. While 90% (9/10) of PMOLs which showed malignant transformation (transformed) expressed FGF-2, only 24.19% cases (15/62) of PMOLs which were not transformed (untransformed) to OSCC expressed FGF-2. Similarly, FGFR-2 expression was seen in 16/62 (25.81%) of untransformed PMOLs and 8/10 (80%) cases of transformed PMOLs. FGFR-3 expression was observed in 23/62 (37.10%) cases of untransformed PMOLs and 6/10 (60%) cases of transformed PMOLs. A significant association of FGF-2 and FGFR-2 expression with malignant transformation from PMOLs to OSCC was observed both at phenotypic and molecular level. The results suggest that FGF-2 and FGFR-2 may be useful as biomarkers of malignant transformation in patients with OSMF and LKP.

  12. Down-regulation of microRNA-181b is a potential prognostic marker of non-small cell lung cancer.

    PubMed

    Yang, Junquan; Liu, Hongxia; Wang, Hongbin; Sun, Yuman

    2013-08-01

    The aim of this study was to investigate the clinical significance of microRNA-181b (miR-181b) expression in non-small cell lung cancer (NSCLC). MiR-181b expression in 126 pairs of surgically removed NSCLC tissues and their corresponding normal lung tissues was measured by real-time quantitative RT-PCR assay. Additionally, the correlation of miR-181b expression with clinicopathological factors or prognosis of patients was analyzed. At first, miR-181b expression was significantly down-regulated in NSCLC tissues as compared with their normal counterparts (P<0.001). Then, the low miR-181b expression was found to be closely correlated with larger tumor size (P=0.02), higher p-TNM stage (P=0.008) and positive lymph node metastasis (P=0.03) of NSCLC patients. After that, survival analysis found that the overall survival (P=0.001) and disease-free survival (P=0.008) of NSCLC patients with low miR-181b expression were both significantly poorer compared to those patients with high miR-181b expression. Finally, both univariate and multivariate analyses demonstrated that low miR-181b expression may be a poor prognostic marker of NSCLC patients. This is the first study to indicate that down-regulation of miR-181b may be correlated with aggressive disease progression and poor prognosis of NSCLC patients, suggesting that miR-181b might be involved in lung carcinogenesis and become a potential prognostic marker for NSCLC.

  13. MicroRNA-196a Is a Potential Marker of Progression during Barrett’s Metaplasia-Dysplasia-Invasive Adenocarcinoma Sequence in Esophagus

    PubMed Central

    Maru, Dipen M.; Singh, Rajesh R.; Hannah, Christina; Albarracin, Constance T.; Li, Yong X.; Abraham, Ronald; Romans, Angela M.; Yao, Hui; Luthra, Madan G.; Anandasabapathy, Sharmila; Swisher, Stephen G.; Hofstetter, Wayne L.; Rashid, Asif; Luthra, Rajyalakshmi

    2009-01-01

    Barrett’s esophagus (BE)/Barrett’s metaplasia (BM) is a recognized precursor of esophageal adenocarcinoma (EA) with an intermediary stage of dysplasia. The low yield and high cost of endoscopic screening of patients with BE underscores the need for novel biomarkers, such as microRNA (miRNA), which have emerged as important players in neoplastic progression for risk assessment of developing dysplasia/adenocarcinoma. Recently, we reported highly elevated levels of miRNA-196a (miR-196a) in EA and demonstrated its growth-promoting and anti-apoptotic functions. Here, we evaluated miR-196a as a marker of BE progression to low-grade dysplasia, high-grade dysplasia, and EA using microdissected paraffin-embedded tissues from 11 patients. Higher levels of miR-196a were observed in EA, BE, and dysplastic lesions compared with normal squamous mucosa, and in high-grade dysplasia compared with BE and low-grade dysplasia. Using frozen tumor tissues from 10 additional patients who had advanced EA, we evaluated the correlation of miR-196a with its in silico-predicted targets, keratin 5 (KRT5), small proline-rich protein 2C (SPRR2C), and S100 calcium-binding protein A9 (S100A9), which are down-regulated during BE progression. MiR-196a levels inversely correlated with the predicted target mRNA levels in EA. We confirmed that miR-196a specifically targets KRT5, SPRR2C, and S100A9 3′ UTRs using miR-196a-mimic and luciferase reporter-based assays. In conclusion, this study identified miR-196a as a potential marker of progression of BE and KRT5, SPRR2C, and S100A9 as its targets. PMID:19342367

  14. Effects of amitriptyline and intra-oral device appliance on clinical and laser-evoked potentials features in chronic tension-type headache.

    PubMed

    de Tommaso, M; Shevel, E; Libro, G; Guido, M; Di Venere, D; Genco, S; Monetti, C; Serpino, C; Barile, G; Lamberti, P; Livrea, P

    2005-05-01

    In the present study, we examined clinical and laser-evoked potentials (LEP) features in two groups of chronic tension-type headache (CTTH) patients treated with two different approaches: intra-oral appliance of prosthesis, aiming to reduce muscular tenderness, and 10 mg daily amitriptyline. Eighteen patients suffering from CTTH (IHS, 2004) participated in the study. We performed a basal evaluation of clinical features and LEPs in all patients (T0) vs. 12 age- and sex-matched controls; successively, patients were randomly assigned to a two-month treatment by amitriptyline or intra-oral device appliance. The later LEPs, especially the P2 component, were significantly increased in amplitude in the CTTH group. Both the intra-oral prosthesis and amitriptyline significantly reduced headache frequency. Total Tenderness Score was significantly reduced in the group treated by the prosthesis. The amplitude of P2 response elicited by stimulation of pericranial zones showed a reduction after amitriptyline treatment. The results of this study may confirm that pericranial tenderness is primarily a phenomenon initiating a self-perpetuating circuit, favoured by central sensitisation at the level of the cortical nociceptive areas devoted to the attentive and emotive compounds of pain. Both the interventions at the peripheral and central levels may interrupt this reverberating circuit, improving the outcome of headache.

  15. Potential involvement of miR-375 in the premalignant progression of oral squamous cell carcinoma mediated via transcription factor KLF5.

    PubMed

    Shi, Wen; Yang, Jing; Li, Siyuan; Shan, Xiaofeng; Liu, Xiaosong; Hua, Hong; Zhao, Chuanke; Feng, Zhendong; Cai, Zhigang; Zhang, Lihe; Zhou, Demin

    2015-11-24

    To elucidate the genetic effect involved in the premalignant progression of chronic inflammation to cancer, we performed microRNA and mRNA profiling in oral lichen planus (OLP), oral squamous cell carcinoma (OSCC), and normal tissue from the same patients. We demonstrate the involvement of a suppressive microRNA, miR-375, in the regulation of this premalignant progression via KLF5, a transcription factor that modulates the expression of genes contributing to proliferation and apoptosis. We found that miR-375 abundance decreased in tissues with progression from the normal state to OLP and subsequently to OSCC. Restoration of miR-375 by transduction of a synthetic mimic into OSCC cells repressed cellular proliferation and promoted apoptosis, with concomitant down-regulation of KLF5, and vice versa. The direct binding of miR-375 to the 3'-untranslated region of KLF5 was further confirmed. Additionally, Survivin (BIRC5), a target of KLF5, was also regulated by miR-375, explaining the susceptibility of miR-375-mimic transfected cells to apoptosis. Further analysis of clinical specimens suggested that expression of KLF5 and BIRC5 is up-regulated during the progression from inflammation to cancer. Our findings provide novel insights into the involvement of microRNAs in progression of inflammation to carcinoma and suggest a potential early-stage biomarker or therapy target for oral carcinoma.

  16. Protection against cognitive deficits and markers of neurodegeneration by long-term oral administration of melatonin in a transgenic model of Alzheimer disease.

    PubMed

    Olcese, James M; Cao, Chuanhai; Mori, Takashi; Mamcarz, Malgorzata B; Maxwell, Anne; Runfeldt, Melissa J; Wang, Li; Zhang, Chi; Lin, Xiaoyang; Zhang, Guixin; Arendash, Gary W

    2009-08-01

    The neurohormone melatonin has been reported to exert anti-beta-amyloid aggregation, antioxidant, and anti-inflammatory actions in various in vitro and animal models. To comprehensively determine the potential for long-term melatonin treatment to protect Alzheimer's transgenic mice against cognitive impairment and development of beta-amyloid (Abeta) neuropathology, we administered melatonin (100 mg/L drinking water) to APP + PS1 double transgenic (Tg) mice from 2-2.5 months of age to their killing at age 7.5 months. A comprehensive behavioral battery administered during the final 6 weeks of treatment revealed that Tg mice given melatonin were protected from cognitive impairment in a variety of tasks of working memory, spatial reference learning/memory, and basic mnemonic function; Tg control mice remained impaired in all of these cognitive tasks/domains. Immunoreactive Abeta deposition was significantly reduced in hippocampus (43%) and entorhinal cortex (37%) of melatonin-treated Tg mice. Although soluble and oligomeric forms of Abeta1-40 and 1-42 were unchanged in the hippocampus and cortex of the same melatonin-treated Tg mice, their plasma Abeta levels were elevated. These Abeta results, together with our concurrent demonstration that melatonin suppresses Abeta aggregation in brain homogenates, are consistent with a melatonin-facilitated removal of Abeta from the brain. Inflammatory cytokines such as tumor necrosis factor (TNF)-alpha were decreased in hippocampus (but not plasma) of Tg+ melatonin mice. Finally, the cortical mRNA expression of three antioxidant enzymes (SOD-1, glutathione peroxidase, and catalase) was significantly reduced to non-Tg levels by long-term melatonin treatment in Tg mice. Thus, melatonin's cognitive benefits could involve its anti-Abeta aggregation, anti-inflammatory, and/or antioxidant properties. Our findings provide support for long-term melatonin therapy as a primary or complementary strategy for abating the progression of

  17. CPM Is a Useful Cell Surface Marker to Isolate Expandable Bi-Potential Liver Progenitor Cells Derived from Human iPS Cells

    PubMed Central

    Kido, Taketomo; Koui, Yuta; Suzuki, Kaori; Kobayashi, Ayaka; Miura, Yasushi; Chern, Edward Y.; Tanaka, Minoru; Miyajima, Atsushi

    2015-01-01

    Summary To develop a culture system for large-scale production of mature hepatocytes, liver progenitor cells (LPCs) with a high proliferation potential would be advantageous. We have found that carboxypeptidase M (CPM) is highly expressed in embryonic LPCs, hepatoblasts, while its expression is decreased along with hepatic maturation. Consistently, CPM expression was transiently induced during hepatic specification from human-induced pluripotent stem cells (hiPSCs). CPM+ cells isolated from differentiated hiPSCs at the immature hepatocyte stage proliferated extensively in vitro and expressed a set of genes that were typical of hepatoblasts. Moreover, the CPM+ cells exhibited a mature hepatocyte phenotype after induction of hepatic maturation and also underwent cholangiocytic differentiation in a three-dimensional culture system. These results indicated that hiPSC-derived CPM+ cells share the characteristics of LPCs, with the potential to proliferate and differentiate bi-directionally. Thus, CPM is a useful marker for isolating hiPSC-derived LPCs, which allows development of a large-scale culture system for producing hepatocytes and cholangiocytes. PMID:26365514

  18. Collagen-graft mixed cellulose esters membrane maintains undifferentiated morphology and markers of potential pluripotency in feeder-free culture of induced pluripotent stem cells.

    PubMed

    Lotfalah Moradi, Sadegh; Hajishafieeha, Zahra; Nojedehi, Shahrzad; Dinarvand, Vida; Hesami Tackallou, Saeed; Roy, Ram V; Ardeshirylajimi, Abdolreza; Soleimani, Masoud

    2016-09-01

    Induced pluripotent stem cells (iPSCs) are unique and unlimited clinical sources of stem cell therapy for the regenerative medicine. Feeder layer preparation is an important step for iPSCs production, which is expensive, time-consuming and requires conversance. In the present study, we investigated the maintenance of pluripotency, and stemness of the iPSCs through feeder-free culture on a collagen-grafted Mixed Cellulose Esters membrane (MCE-COL) after three passages during twelve days. Results have demonstrated that the iPSCs cultured on MCE-COL membrane had a fine, typical undifferentiated morphology, increased proliferation rate and significant multi-lineage differentiation potential. Alkaline phosphatase (ALP) staining and pluripotency associated gene markers expression further confirmed that iPSCs cultured on the surface of MCE-COL had more ALP positive colonies and enhanced expression of Oct-4, Nanog, Sox-2 and ALP in comparison with MCE and control groups. Since MCE-COL membrane has three dimensional structure and bioactivity, it has the potential for usage in the feeder-free culture of iPSCs, and could be a suitable candidate to use as a feeder layer in stem cells preparation.

  19. CPM Is a Useful Cell Surface Marker to Isolate Expandable Bi-Potential Liver Progenitor Cells Derived from Human iPS Cells.

    PubMed

    Kido, Taketomo; Koui, Yuta; Suzuki, Kaori; Kobayashi, Ayaka; Miura, Yasushi; Chern, Edward Y; Tanaka, Minoru; Miyajima, Atsushi

    2015-10-13

    To develop a culture system for large-scale production of mature hepatocytes, liver progenitor cells (LPCs) with a high proliferation potential would be advantageous. We have found that carboxypeptidase M (CPM) is highly expressed in embryonic LPCs, hepatoblasts, while its expression is decreased along with hepatic maturation. Consistently, CPM expression was transiently induced during hepatic specification from human-induced pluripotent stem cells (hiPSCs). CPM(+) cells isolated from differentiated hiPSCs at the immature hepatocyte stage proliferated extensively in vitro and expressed a set of genes that were typical of hepatoblasts. Moreover, the CPM(+) cells exhibited a mature hepatocyte phenotype after induction of hepatic maturation and also underwent cholangiocytic differentiation in a three-dimensional culture system. These results indicated that hiPSC-derived CPM(+) cells share the characteristics of LPCs, with the potential to proliferate and differentiate bi-directionally. Thus, CPM is a useful marker for isolating hiPSC-derived LPCs, which allows development of a large-scale culture system for producing hepatocytes and cholangiocytes.

  20. Cytoplasmic expression of HuR may be a valuable diagnostic tool for determining the potential for malignant transformation of oral verrucous borderline lesions

    PubMed Central

    HABIBA, UMMA; KITAMURA, TETSUYA; YANAGAWA-MATSUDA, AYA; HIDA, KYOKO; HIGASHINO, FUMIHIRO; OHIRO, YOICHI; TOTSUKA, YASUNORI; SHINDOH, MASANOBU

    2014-01-01

    Oral verrucous carcinoma (OVC) is a low grade variant of oral squamous cell carcinoma, and oral verrucous hyperplasia (OVH) is a benign lesion without malignant features. However, pathologists are sometimes presented with borderline lesions and are indecisive as to diagnose them as benign or malignant. Thus, these lesions are tentatively termed oral verrucous lesions (OVLs). HuR is an ARE mRNA-binding protein, normally localized in the nucleus but cytoplasmic exportation is frequently observed in cancer cells. The present study aimed to elucidate whether expression of the HuR protein facilitates the diagnosis of true malignant lesions. Clinicopathological features were evaluated, and immunohistochemical analysis for p53, Ki67 and HuR proteins was performed in 48 cases of OVH, OVC and OVL, and the outcomes were correlated using appropriate statistical analysis. The association of these three proteins in relation to malignant transformation was analyzed after a 3-year follow-up of 25 OVL cases. The basal characteristics (age, gender and location) of all cases had no significant association with the types of lesions. Gingiva (39.4%) was the common site for all lesions. Distribution of the examined proteins had a significant association with the lesions. As compared with the OVLs, the number of immunostained-positive cells was significantly higher in the OVCs and lower in the OVH cases. During follow-up, 24% of the OVLs underwent malignant transformation for which high HuR expression and a diffuse staining pattern in the epithelium were observed. Taken together, the high degree of HuR expression with diffuse staining pattern in the epithelium may be an effective diagnostic tool that determines the potential of OVLs for malignant transformation. PMID:24534848

  1. The cultivable human oral gluten-degrading microbiome and its potential implications in coeliac disease and gluten sensitivity.

    PubMed

    Fernandez-Feo, M; Wei, G; Blumenkranz, G; Dewhirst, F E; Schuppan, D; Oppenheim, F G; Helmerhorst, E J

    2013-09-01

    Coeliac disease is characterized by intestinal inflammation caused by gluten, proteins which are widely contained in the Western diet. Mammalian digestive enzymes are only partly capable of cleaving gluten, and fragments remain that induce toxic responses in patients with coeliac disease. We found that the oral microbiome is a novel and rich source of gluten-degrading organisms. Here we report on the isolation and characterization of the cultivable resident oral microbes that are capable of cleaving gluten, with special emphasis on the immunogenic domains. Bacteria were obtained by a selective culturing approach and enzyme activities were characterized by: (i) hydrolysis of paranitroanilide-derivatized gliadin-derived tripeptide substrates; (ii) gliadin degradation in-gel (gliadin zymography); (iii) gliadin degradation in solution; (iv) proteolysis of the highly immunogenic α-gliadin-derived 33-mer peptide. For selected strains pH activity profiles were determined. The culturing strategy yielded 87 aerobic and 63 anaerobic strains. Species with activity in at least two of the four assays were typed as: Rothia mucilaginosa HOT-681, Rothia aeria HOT-188, Actinomyces odontolyticus HOT-701, Streptococcus mitis HOT-677, Streptococcus sp. HOT-071, Neisseria mucosa HOT-682 and Capnocytophaga sputigena HOT-775, with Rothia species being active in all four assays. Cleavage specificities and substrate preferences differed among the strains identified. The approximate molecular weights of the enzymes were ~75 kD (Rothia spp.), ~60 kD (A. odontolyticus) and ~150 kD (Streptococcus spp.). In conclusion, this study identified new gluten-degrading microorganisms in the upper gastrointestinal tract. A cocktail of the most active oral bacteria, or their isolated enzymes, may offer promising new treatment modalities for coeliac disease.

  2. A fusion protein derived from plants holds promising potential as a new oral therapy for type 2 diabetes.

    PubMed

    Choi, Jeehye; Diao, Hong; Feng, Zhi-Chao; Lau, Arthur; Wang, Rennian; Jevnikar, Anthony M; Ma, Shengwu

    2014-05-01

    The incretin hormone glucagon-like peptide-1 (GLP-1) is recognized as a promising candidate for the treatment of type 2 diabetes (T2D), with one of its mimetics, exenatide (synthetic exendin-4) having already been licensed for clinical use. We seek to further improve the therapeutic efficacy of exendin-4 (Ex-4) using innovative fusion protein technology. Here, we report the production in plants a fusion protein containing Ex-4 coupled with human transferrin (Ex-4-Tf) and its characterization. We demonstrated that plant-made Ex-4-Tf retained the activity of both proteins. In particular, the fusion protein stimulated insulin release from pancreatic β-cells, promoted β-cell proliferation, stimulated differentiation of pancreatic precursor cells into insulin-producing cells, retained the ability to internalize into human intestinal cells and resisted stomach acid and proteolytic enzymes. Importantly, oral administration of partially purified Ex-4-Tf significantly improved glucose tolerance, whereas commercial Ex-4 administered by the same oral route failed to show any significant improvement in glucose tolerance in mice. Furthermore, intraperitoneal (IP) injection of Ex-4-Tf showed a beneficial effect in mice similar to IP-injected Ex-4. We also showed that plants provide a robust system for the expression of Ex-4-Tf, producing up to 37 μg prEx-4-Tf/g fresh leaf weight in transgenic tobacco and 137 μg prEx-4-Tf/g freshweight in transiently transformed leaves of N. benthamiana. These results indicate that Ex-4-Tf holds substantial promise as a new oral therapy for type 2 diabetes. The production of prEx-4-Tf in plants may offer a convenient and cost-effective method to deliver the antidiabetic medicine in partially processed plant food products.

  3. Brain-Penetrant, Orally Bioavailable Microtubule-Stabilizing Small Molecules Are Potential Candidate Therapeutics for Alzheimer’s Disease and Related Tauopathies

    PubMed Central

    2015-01-01

    Microtubule (MT) stabilizing drugs hold promise as potential treatments for Alzheimer’s disease (AD) and related tauopathies. However, thus far epothilone D has been the only brain-penetrant MT-stabilizer to be evaluated in tau transgenic mice and in AD patients. Furthermore, this natural product exhibits potential deficiencies as a drug candidate, including an intravenous route of administration and the inhibition of the P-glycoprotein (Pgp) transporter. Thus, the identification of alternative CNS-active MT-stabilizing agents that lack these potential limitations is of interest. Toward this objective, we have evaluated representative compounds from known classes of non-naturally occurring MT-stabilizing small molecules. This led to the identification of selected triazolopyrimidines and phenylpyrimidines that are orally bioavailable and brain-penetrant without disruption of Pgp function. Pharmacodynamic studies confirmed that representative compounds from these series enhance MT-stabilization in the brains of wild-type mice. Thus, these classes of MT-stabilizers hold promise for the development of orally active, CNS-directed MT-stabilizing therapies. PMID:24992153

  4. A family of LRR sequences in the vicinity of the Co-2 locus for anthracnose resistance in Phaseolus vulgaris and its potential use in marker-assisted selection.

    PubMed

    Geffroy, V; Creusot, F; Falquet, J; Sévignac, M; Adam-Blondon, A F; Bannerot, H; Gepts, P; Dron, M

    1998-03-01

    Molecular markers offer new opportunities for breeding for disease resistance. Resistance gene pyramiding in a single cultivar, as a strategy for durable resistance, can be facilitated by marker-assisted selection (MAS). A RAPD marker, ROH20(450), linked to the Mesoamerican Co-2 anthracnose resistance gene, was previously transformed into a SCAR marker, SCH20. In the present paper we have further characterized the relevance of the SCH20 SCAR marker in different genetic backgrounds. Since this SCAR marker was found to be useful mainly in the Andean gene pool, we identified a new PCR-based marker (SCAreoli) for indirect scoring of the presence of the Co-2 gene. The SCAreoli SCAR marker is polymorphic in the Mesoamerican as well as in the Andean gene pool and should be useful in MAS. We also report that PvH20, the cloned sequence corresponding to the 450-bp RAPD marker ROH20(450), contains six imperfect leucine-rich repeats, and reveals a family of related sequences in the vicinity of the Co-2 locus. These results are discussed in the context of the recent cloning of some plant resistance genes.

  5. In vitro Evaluation of Copaifera oblongifolia Oleoresin Against Bacteria Causing Oral Infections and Assessment of Its Cytotoxic Potential.

    PubMed

    da S Moraes, Thaís; Leandro, Luis F; de O Silva, Larissa; Santiago, Mariana B; Souza, Ariana B; Furtado, Ricardo A; Tavares, Denise C; Veneziani, Rodrigo C S; Ambrósio, Sérgio R; Bastos, Jairo K; Martins, Carlos H G

    The oral cavity, which harbors more than 750 bacterial species, is one of the most diverse sites of the human body. Some of these bacteria have been associated with