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Sample records for acid treated cells

  1. Differential Gene Expression in GPR40-Overexpressing Pancreatic β-cells Treated with Linoleic Acid

    PubMed Central

    Kim, In-Su; Yang, So-Young; Han, Joo-Hui; Jung, Sang-Hyuk; Park, Hyun-Soo

    2015-01-01

    "G protein-coupled receptor 40" (GPR40), a receptor for long-chain fatty acids, mediates the stimulation of glucose-induced insulin secretion. We examined the profiles of differential gene expression in GPR40-activated cells treated with linoleic acid, and finally predicted the integral pathways of the cellular mechanism of GPR40-mediated insulinotropic effects. After constructing a GPR40-overexpressing stable cell line (RIN-40) from the rat pancreatic β-cell line RIN-5f, we determined the gene expression profiles of RIN-5f and RIN-40. In total, 1004 genes, the expression of which was altered at least twofold, were selected in RIN-5f versus RIN-40. Moreover, the differential genetic profiles were investigated in RIN-40 cells treated with 30 µM linoleic acid, which resulted in selection of 93 genes in RIN-40 versus RIN-40 treated with linoleic acid. Based on the Kyoto Encyclopedia of Genes and Genomes Pathway (KEGG, http://www.genome.jp/kegg/), sets of genes induced differentially by treatment with linoleic acid in RIN-40 cells were found to be related to mitogen-activated protein (MAP) kinase- and neuroactive ligand-receptor interaction pathways. A gene ontology (GO) study revealed that more than 30% of the genes were associated with signal transduction and cell proliferation. Thus, this study elucidated a gene expression pattern relevant to the signal pathways that are regulated by GPR40 activation during the acute period. Together, these findings increase our mechanistic understanding of endogenous molecules associated with GPR40 function, and provide information useful for identification of a target for the management of type 2 diabetes mellitus. PMID:25729276

  2. Differential cell fates induced by all-trans retinoic acid-treated HL-60 human leukemia cells.

    PubMed

    Ozeki, Munetaka; Shively, John E

    2008-09-01

    HL-60 human leukemia cells, differentiated into a neutrophil lineage by all-trans retinoic acid (ATRA) treatment, express three members of the carcinoembryonic antigen (CEA) gene family, CEA-related cell adhesion molecule 1 (CEACAM1; CD66a), CEACAM3 (CD66d), and CEACAM6 (CD66c). CD66d is a neutrophil lineage-specific marker, and CD66a and CD66c are found on epithelial and other cells. HL-60 cells continuously treated with ATRA underwent apoptosis, and cells transiently treated for 1 day underwent cell-cycle arrest, entered into senescence, and exhibited reduced apoptosis with CD66-positive cells accounting for the majority of live cells. CD66 antigens were also induced in NB4 leukemic cells upon continuous treatment with ATRA. NB4 cells underwent apoptosis with a higher frequency in transient versus continuous-treated cells (38% vs. 19% at Day 5), in contrast to HL-60 cells that underwent cell-cycle arrest and senescence when transiently treated with ATRA. CD66 antigens were not induced in transient, ATRA-treated NB4 cells compared with HL-60 cells. Cell-cycle arrest in HL-60 cells involved reduction in expression levels of p21, cyclins D and E, while Rb1 exhibited reduction in protein levels without changes in mRNA levels over the time course of ATRA treatment. Analysis of several proapoptotic proteins implicated the activation of calpain and cleavage of Bax in the intrinsic apoptotic pathway, similar to published studies about the apoptosis of neutrophils. CD1d expression was also induced by ATRA in HL-60 cells and ligation with anti-CD1d antibody-induced apoptosis. In contrast, CD1d-positive primary monocytes were protected from spontaneous apoptosis by CD1d ligation. These studies demonstrate distinct cell fates for ATRA-treated HL-60 cells that provide new insights into ATRA-induced cell differentiation.

  3. Carnosic Acid Affords Mitochondrial Protection in Chlorpyrifos-Treated Sh-Sy5y Cells.

    PubMed

    de Oliveira, Marcos Roberto; Peres, Alessandra; Ferreira, Gustavo Costa; Schuck, Patrícia Fernanda; Bosco, Simone Morelo Dal

    2016-10-01

    Carnosic acid (CA; C20H28O4) is a phenolic diterpene found in rosemary (Rosmarinus officinalis L.) and exhibits protective properties, e.g., antioxidant, anti-inflammatory, antitumor, and antimicrobial activities. In this context, CA has been viewed as a neuroprotective agent due to its ability in rescuing neuronal cells from pro-oxidant and pro-apoptotic challenges. In the present work, we found that CA pretreatment at 1 µM for 12 h suppressed the mitochondria-related pro-oxidant and mitochondria-dependent pro-apoptotic effects of chlorpyrifos (CPF) in human neuroblastoma SH-SY5Y cells. CA prevented mitochondrial membrane potential disruption and decreased the levels of oxidative stress markers in mitochondrial membranes obtained from cells exposed to CPF. CA also inhibited cytochrome c release and activation of the caspases-9 and -3, as well as decreased DNA fragmentation, in CPF-treated cells. CA upregulated the content of glutathione (GSH) in mitochondria by a mechanism involving the activation of the phosphoinositide-3-kinase (PI3K)/Akt/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, since inhibition of PI3K/Akt or silencing of Nrf2 using siRNA strategy abolished the protection exerted by CA in SH-SY5Y cells. Therefore, CA protected mitochondria of SH-SY5Y cells through the activation of the PI3K/Akt/Nrf2 axis, causing upregulation of the mitochondrial GSH content and consequent antioxidant and anti-apoptotic effects. PMID:27083155

  4. Increased accumulation of the lipophilic cation tetraphenylphosphonium by cyclopiazonic acid-treated renal epithelial cells

    SciTech Connect

    Riley, R.T.; Norred, W.P.; Dorner, J.W.; Cole, R.J.

    1985-01-01

    Pig kidney renal epithelial cells (LLC-PK1) in culture were used to determine the effects of cyclopiazonic acid (CPA) on the uptake of the transmembrane potential probe, (TH)tetraphenylphosphonium bromide (TPP ). CPA had a significant stimulatory effect on TPP accumulation, which occurred in a dose-related manner. TPP accumulation in the presence of CPA was significantly reduced by high-potassium media (HK) and carbonylcyanide m-chlorophenylhydrazone (CCCP), but neither HK nor the protonophore CCCP, could completely abolish the stimulatory effect of CPA. The apparent transmembrane potential difference, calculated based on the difference in accumulation of TPP in low-potassium and HK media, ranged from -55.9 to -85.7 mV for control cells and -89.4 to -109.0 mV for CPA-treated cells (20 mg CPA/I). The mechanism of CPA stimulation of TPP accumulation was not known. However, it was hypothesized that the effect could be a result of alterations in ion pumps or altered membrane permeability.

  5. Induction of cellular deoxyribonucleic acid synthesis in butyrate-treated cells by simian virus 40 deoxyribonucleic acid

    SciTech Connect

    Kawasaki, S.; Diamond, L.; Baserga, R.

    1981-11-01

    Sodium butyrate (3mM) inhibited the entry into the S phase of quiescent 3T3 cells stimulated by serum, but had no effect on the accumulation of cellular ribonucleic acid. Simian virus 40 infection or manual microinjection of cloned fragments from the simian virus 40 A gene caused quiescent 3T3 cells to enter the S phase even in the presence of butyrate. NGI cells, a line of 3T3 cells transformed by simian virus 40, grew vigorously in 3 mM butyrate. Homokaryons were formed between G/sub 1/ and S-phase 3T3 cells. Butyrate inhibited the induction of deoxyribonucleic acid synthesis that usually occurs in G/sub 1/ nuclei when G/sub 1/ cells are fused with S-phase cells. However, when G/sub 1/ 3T3 cells were fused with exponentially growing NGI cells, the 3T3 nuclei were induced to enter deoxyribonucleic acid synthesis. In tsAF8 cells, a ribonucleic acid polymerase II mutant that stops in the G/sub 1/ phase of the cell cycle, no temporal sequence was demonstrated between the butyrate block and the temperature-sensitive block. These results confirm previous reports that certain virally coded proteins can induce cell deoxyribonucleic acid synthesis in the absence of cellular functions that are required by serum-stimulated cells. The author's interpretation of these data is that butyrate inhibited cell growth by inhibiting the expression of genes required for the G/sub o/ ..-->.. G/sub 1/ ..-->.. S transition and that the product of the simian virus 40 A gene overrode this inhibition by providing all of the necessary functions for the entry into the S phase.

  6. Chaperone-Mediated Autophagy Targets IFNAR1 for Lysosomal Degradation in Free Fatty Acid Treated HCV Cell Culture

    PubMed Central

    Kurt, Ramazan; Chandra, Partha K.; Aboulnasr, Fatma; Panigrahi, Rajesh; Ferraris, Pauline; Aydin, Yucel; Reiss, Krzysztof; Wu, Tong; Balart, Luis A.; Dash, Srikanta

    2015-01-01

    Background Hepatic steatosis is a risk factor for both liver disease progression and an impaired response to interferon alpha (IFN-α)-based combination therapy in chronic hepatitis C virus (HCV) infection. Previously, we reported that free fatty acid (FFA)-treated HCV cell culture induces hepatocellular steatosis and impairs the expression of interferon alpha receptor-1 (IFNAR1), which is why the antiviral activity of IFN-α against HCV is impaired. Aim To investigate the molecular mechanism by which IFNAR1 expression is impaired in HCV cell culture with or without free fatty acid-treatment. Method HCV-infected Huh 7.5 cells were cultured with or without a mixture of saturated (palmitate) and unsaturated (oleate) long-chain free fatty acids (FFA). Intracytoplasmic fat accumulation in HCV-infected culture was visualized by oil red staining. Clearance of HCV in FFA cell culture treated with type I IFN (IFN-α) and Type III IFN (IFN-λ) was determined by Renilla luciferase activity, and the expression of HCV core was determined by immunostaining. Activation of Jak-Stat signaling in the FFA-treated HCV culture by IFN-α alone and IFN-λ alone was examined by Western blot analysis and confocal microscopy. Lysosomal degradation of IFNAR1 by chaperone-mediated autophagy (CMA) in the FFA-treated HCV cell culture model was investigated. Results FFA treatment induced dose-dependent hepatocellular steatosis and lipid droplet accumulation in HCV-infected Huh-7.5 cells. FFA treatment of infected culture increased HCV replication in a concentration-dependent manner. Intracellular lipid accumulation led to reduced Stat phosphorylation and nuclear translocation, causing an impaired IFN-α antiviral response and HCV clearance. Type III IFN (IFN-λ), which binds to a separate receptor, induces Stat phosphorylation, and nuclear translocation as well as antiviral clearance in FFA-treated HCV cell culture. We show here that the HCV-induced autophagy response is increased in FFA-treated

  7. Biostimulatory effects of low-level laser therapy on epithelial cells and gingival fibroblasts treated with zoledronic acid

    NASA Astrophysics Data System (ADS)

    Basso, F. G.; Pansani, T. N.; Turrioni, A. P. S.; Kurachi, C.; Bagnato, V. S.; Hebling, J.; de Souza Costa, C. A.

    2013-05-01

    Low-level laser therapy (LLLT) has been considered as an adjuvant treatment for bisphosphonate-related osteonecrosis, presenting positive clinical outcomes. However, there are no data regarding the effect of LLLT on oral tissue cells exposed to bisphosphonates. This study aimed to evaluate the effects of LLLT on epithelial cells and gingival fibroblasts exposed to a nitrogen-containing bisphosphonate—zoledronic acid (ZA). Cells were seeded in wells of 24-well plates, incubated for 48 h and then exposed to ZA at 5 μM for an additional 48 h. LLLT was performed with a diode laser prototype—LaserTABLE (InGaAsP—780 nm ± 3 nm, 25 mW), at selected energy doses of 0.5, 1.5, 3, 5, and 7 J cm-2 in three irradiation sessions, every 24 h. Cell metabolism, total protein production, gene expression of vascular endothelial growth factor (VEGF) and collagen type I (Col-I), and cell morphology were evaluated 24 h after the last irradiation. Data were statistically analyzed by Kruskal-Wallis and Mann-Whitney tests at 5% significance. Selected LLLT parameters increased the functions of epithelial cells and gingival fibroblasts treated with ZA. Gene expression of VEGF and Col-I was also increased. Specific parameters of LLLT biostimulated fibroblasts and epithelial cells treated with ZA. Analysis of these in vitro data may explain the positive in vivo effects of LLLT applied to osteonecrosis lesions.

  8. Dose-Responsive Gene Expression in Suberoylanilide Hydroxamic Acid (SAHA) Treated Resting CD4+ T Cells

    PubMed Central

    Reardon, Brian; Beliakova-Bethell, Nadejda; Spina, Celsa A.; Singhania, Akul; Margolis, David M.; Richman, Douglas R.; Woelk, Christopher H.

    2015-01-01

    Design Persistent latently infected CD4+ T cells represent a major obstacle to HIV eradication. Histone deacetylase inhibitors (HDACis) are a proposed activation therapy. However, off-target effects on expression in host immune cells are poorly understood. We hypothesized that HDACi-modulated genes would be best identified with dose-response analysis. Methods Resting primary CD4+ T cells were treated with 0.34, 1, 3, or 10 μM of the HDACi, SAHA, for 24 hours and subjected to microarray gene expression analysis. Genes with dose-correlated expression were filtered to identify a subset with consistent up or downregulation at each SAHA dose. Histone modifications were characterized in 6 SAHA dose-responsive genes by chromatin immunoprecipitation (ChIP-RT-qPCR). Results A large number of genes were shown to be up (N=657) or downregulated (N=725) by SAHA in a dose-responsive manner (FDR p-value < 0.05, fold change ≥ |2|). Several genes (CTNNAL1, DPEP2, H1F0, IRGM, PHF15, and SELL) are potential in vivo biomarkers of SAHA activity. SAHA dose-responsive genes included transcription factors, HIV restriction factors, histone methyltransferases, and host proteins that interact with HIV. Pathway analysis suggested net downregulation of T cell activation with increasing SAHA dose. Histone acetylation was not correlated with host gene expression, but plausible alternative mechanisms for SAHA-modulated gene expression were identified. Conclusions Numerous genes in CD4+ T cells are modulated by SAHA in a dose-responsive manner, including genes that may negatively influence HIV activation from latency. Our study suggests that SAHA influences gene expression through a confluence of several mechanisms, including histone modification, and altered expression and activity of transcription factors. PMID:26258524

  9. UPR in palmitate-treated pancreatic beta-cells is not affected by altering oxidation of the fatty acid

    PubMed Central

    2011-01-01

    Background Elevated levels of lipids are detrimental for beta-cell function and mass. One of the mechanisms of how fatty acids induce apoptosis is development of the unfolded protein response (UPR). It is still far from understood how fatty acids activate the UPR, however. Methods We examined how palmitate-induced activation of the UPR was affected by altering the metabolism of the fatty acid in insulin-secreting INS-1E and MIN6 cell lines and intact human islets. To increase oxidation, we used low glucose (5.5 mM) or AICAR; and to reduce oxidation, we used high glucose (25 mM) or etomoxir. UPR was measured after 3, 24 and 48 hours of palmitate treatment. Results Modulation of palmitate oxidation by either glucose or the pharmacological agents did not affect palmitate-induced UPR activation. Conclusion Our finding suggests that other factors than oxidation of palmitate play a role in the activation of UPR in fatty acid-treated beta-cells. PMID:21978671

  10. EPR studies of free radicals in A-2058 human melanoma cells treated by valproic acid and 5,7-dimethoxycoumarin.

    PubMed

    Zdybel, Magdalena; Chodurek, Ewa; Pilawa, Barbara

    2014-01-01

    Free radicals in A-2058 human melanoma cells were studied by the use of electron paramagnetic resonance (EPR) spectroscopy. The aim of this work was to determine the changes in relative free radical concentrations in tumor A-2058 cells after treatment by valproic acid (VPA) and 5,7-dimethoxycoumarin (DMC). The influences of VPA and DMC on free radicals in A-2058 cells were compared with those for human melanoma malignum A-375 and G-361 cells, which were tested by us earlier. Human malignant melanoma A-2058 cells were exposed to interactions with VPA, DMC, and both VPA and DMC. The tumor cells A-2058 were purchased from LGC Standards (Lomianki, Poland), and they were grown in the standard conditions: at 37°C and in an atmosphere containing 95% air and 5% CO2, in the Minimum Essential Medium Eagle (MEM, Sigma-Aldrich). The A-2058 cells were incubated with VPA (1 mM) and DMC (10 μM) for 4 days. The first-derivative EPR spectra of the control A-2058 cells, and the cells treated with VPA, DMC, and both VPA and DMC, were measured by the electron paramagnetic resonance spectrometer of Radiopan (Poznań, Poland) with microwaves from an X-band (9.3 GHz). The parameters of the EPR lines: amplitudes (A), integral intensities (I), line widths (ΔBpp), and g-factors, were analyzed. The changes of amplitudes and line widths with microwave power increasing from 2.2 to 70 mW were drawn evaluated, o-Semiquinone free radicals of melanin biopolymer are mainly responsible for the EPR lines of A-2058 melanoma malignum cells. The amounts of free radicals in A-2058 cells treated with VPA, and both VPA and DMC, were lower than in the untreated control cells. Application of the tested substances (VPA, and both VPA and DMC) as the antitumor compounds was discussed. DMC without VPA did not decrease free radicals concentration in A-2058 cells. The studies con-firmed that EPR spectroscopy may be used to examine interactions of free radicals with antitumor compounds.

  11. Treating cutaneous squamous cell carcinoma using 5-aminolevulinic acid polylactic-co-glycolic acid nanoparticle-mediated photodynamic therapy in a mouse model

    PubMed Central

    Wang, Xiaojie; Shi, Lei; Tu, Qingfeng; Wang, Hongwei; Zhang, Haiyan; Wang, Peiru; Zhang, Linglin; Huang, Zheng; Zhao, Feng; Luan, Hansen; Wang, Xiuli

    2015-01-01

    Background Squamous cell carcinoma (SCC) is a common skin cancer, and its treatment is still difficult. The aim of this study was to evaluate the effectiveness of nanoparticle (NP)-assisted 5-aminolevulinic acid (ALA) delivery for topical photodynamic therapy (PDT) of cutaneous SCC. Materials and methods Ultraviolet-induced cutaneous SCCs were established in hairless mice. ALA-loaded polylactic-co-glycolic acid (PLGA) NPs were prepared and characterized. The kinetics of ALA PLGA NP-induced protoporphyrin IX fluorescence in SCCs, therapeutic efficacy of ALA NP-mediated PDT, and immune responses were examined. Results PLGA NPs enhanced protoporphyrin IX production in SCC. ALA PLGA NP-mediated topical PDT was more effective than free ALA of the same concentration in treating cutaneous SCC. Conclusion PLGA NPs provide a promising strategy for delivering ALA in topical PDT of cutaneous SCC. PMID:25609949

  12. Nuclear abnormalities in buccal mucosa cells of patients with type I and II diabetes treated with folic acid.

    PubMed

    Gómez-Meda, B C; Zamora-Perez, A L; Muñoz-Magallanes, T; Sánchez-Parada, M G; García Bañuelos, J J; Guerrero-Velázquez, C; Sánchez-Orozco, L V; Vera-Cruz, J M; Armendáriz-Borunda, J; Zúñiga-González, G M

    2016-02-01

    Diabetes mellitus (DM) is characterized by high blood glucose. Excessive production of free radicals may cause oxidative damage to DNA and other molecules, leading to complications of the disease. It may be possible to delay or reduce such damage by administration of antioxidants such as folic acid (FA). The objective of this study was to determine the effect of FA on nuclear abnormalities (NAs) in the oral mucosa of patients with DM. NAs (micronucleated cells, binucleated cells, pyknotic nuclei, karyorrhexis, karyolysis, abnormally condensed chromatin, and nuclear buds) were analyzed in 2000 cells from 45 healthy individuals (control group) and 55 patients with controlled or uncontrolled type I or II DM; 35 patients in the latter group were treated with FA. Samples were taken from the FA group before and after treatment. An increased rate of NAs was found in patients with DM in comparison with that of the control group (P<0.001). FA supplementation in patients with DM reduced the frequency of NAs (20.4 ± 8.0 before treatment vs. 10.5 ± 5.2 after treatment; P<0.001). The type I and type II DM and controlled and uncontrolled DM subgroups were analyzed in terms of sex, age, and smoking habit. The significantly reduced frequencies of buccal mucosa cells with micronuclei, binucleation, pyknosis, karyorrhexis, karyorrhexis+abnormally condensed chromatin, karyolysis, and nuclear buds produced by FA supplementation in DM patients (P<0.02) are consistent with the idea that free radicals are responsible for the increased frequency of NAs in DM patients.

  13. Nuclear abnormalities in buccal mucosa cells of patients with type I and II diabetes treated with folic acid.

    PubMed

    Gómez-Meda, B C; Zamora-Perez, A L; Muñoz-Magallanes, T; Sánchez-Parada, M G; García Bañuelos, J J; Guerrero-Velázquez, C; Sánchez-Orozco, L V; Vera-Cruz, J M; Armendáriz-Borunda, J; Zúñiga-González, G M

    2016-02-01

    Diabetes mellitus (DM) is characterized by high blood glucose. Excessive production of free radicals may cause oxidative damage to DNA and other molecules, leading to complications of the disease. It may be possible to delay or reduce such damage by administration of antioxidants such as folic acid (FA). The objective of this study was to determine the effect of FA on nuclear abnormalities (NAs) in the oral mucosa of patients with DM. NAs (micronucleated cells, binucleated cells, pyknotic nuclei, karyorrhexis, karyolysis, abnormally condensed chromatin, and nuclear buds) were analyzed in 2000 cells from 45 healthy individuals (control group) and 55 patients with controlled or uncontrolled type I or II DM; 35 patients in the latter group were treated with FA. Samples were taken from the FA group before and after treatment. An increased rate of NAs was found in patients with DM in comparison with that of the control group (P<0.001). FA supplementation in patients with DM reduced the frequency of NAs (20.4 ± 8.0 before treatment vs. 10.5 ± 5.2 after treatment; P<0.001). The type I and type II DM and controlled and uncontrolled DM subgroups were analyzed in terms of sex, age, and smoking habit. The significantly reduced frequencies of buccal mucosa cells with micronuclei, binucleation, pyknosis, karyorrhexis, karyorrhexis+abnormally condensed chromatin, karyolysis, and nuclear buds produced by FA supplementation in DM patients (P<0.02) are consistent with the idea that free radicals are responsible for the increased frequency of NAs in DM patients. PMID:26921015

  14. Comparison of alkaline phosphatase activity of MC3T3-E1 cells cultured on different Ti surfaces: modified sandblasted with large grit and acid-etched (MSLA), laser-treated, and laser and acid-treated Ti surfaces

    PubMed Central

    Li, Lin-Jie; Kim, So-Nam

    2016-01-01

    PURPOSE In this study, the aim of this study was to evaluate the effect of implant surface treatment on cell differentiation of osteoblast cells. For this purpose, three surfaces were compared: (1) a modified SLA (MSLA: sand-blasted with large grit, acid-etched, and immersed in 0.9% NaCl), (2) a laser treatment (LT: laser treatment) titanium surface and (3) a laser and acid-treated (LAT: laser treatment, acid-etched) titanium surface. MATERIALS AND METHODS The MSLA surfaces were considered as the control group, and LT and LAT surfaces as test groups. Alkaline phosphatase expression (ALP) was used to quantify osteoblastic differentiation of MC3T3-E1 cell. Surface roughness was evaluated by a contact profilometer (URFPAK-SV; Mitutoyo, Kawasaki, Japan) and characterized by two parameters: mean roughness (Ra) and maximum peak-to-valley height (Rt). RESULTS Scanning electron microscope revealed that MSLA (control group) surface was not as rough as LT, LAT surface (test groups). Alkaline phosphatase expression, the measure of osteoblastic differentiation, and total ALP expression by surface-adherent cells were found to be highest at 21 days for all three surfaces tested (P<.05). Furthermore, ALP expression levels of MSLA and LAT surfaces were significantly higher than expression levels of LT surface-adherent cells at 7, 14, and 21 days, respectively (P<.05). However, ALP expression levels between MSLA and LAT surface were equal at 7, 14, and 21 days (P>.05). CONCLUSION This study suggested that MSLA and LAT surfaces exhibited more favorable environment for osteoblast differentiation when compared with LT surface, the results that are important for implant surface modification studies. PMID:27350860

  15. Application of acid-treated yeast cell wall (AYC) as a pharmaceutical additive I. AYC as a novel coating material.

    PubMed

    Kasai, T; Eguchi, T; Ishiwaki, N; Kaneshige, J; Ozeki, T; Yuasa, H

    2000-08-25

    Acid-treated yeast cell wall (AYC) was newly prepared by acidifying the cell wall of brewer's yeast and the potential to use AYC as a novel coating material was studied. AYC had an oval shape with the diameter of several microm. The rheogram of AYC aqueous dispersion showed the plastic fluid property that is generally observed in the suspension. Core tablets containing 3% of acetaminophen (AAP) were coated with the AYC aqueous dispersion containing 5% (w/v) of AYC and 0.35% (w/v) of glycerol at various coating percents. The AAP release profile from the AYC-coated tablets was studied by the JP13 paddle method using solutions at various pH. Tensile strength and permeability of oxygen and water vapor of AYC cast film were measured. The AAP release from the AYC-coated tablets showed sigmoidal release profile with an initial lag time and the duration of the lag time depended on the coating percent of AYC. The pH of the dissolution fluid or the storage at room temperature for 120 days had little affect on AAP release from the AYC-coated tablets. These results suggest that it is possible to control the start time of medicine release independent of the pH by coating of AYC, that is the time-controlled release. The AYC cast film showed a large tensile strength and an extremely small oxygen permeability coefficient and a sufficient level of water permeability coefficient in order to protect from moisture. These results present that AYC has the high utility as a novel aqueous coating material for DDS preparations. PMID:11011986

  16. Treating burns caused by hydrofluoric acid.

    PubMed

    Summers, Anthony

    2011-06-01

    Hydrofluoric acid is an ingredient of many common household and industrial solutions. Even seemingly minor burns caused by this acid can have catastrophic effects if they are treated inappropriately or late. This article describes the signs and symptoms, the pathophysiology and the emergency management of hydrofluoric acid burns.

  17. Transcriptome analysis of acetic-acid-treated yeast cells identifies a large set of genes whose overexpression or deletion enhances acetic acid tolerance.

    PubMed

    Lee, Yeji; Nasution, Olviyani; Choi, Eunyong; Choi, In-Geol; Kim, Wankee; Choi, Wonja

    2015-08-01

    Acetic acid inhibits the metabolic activities of Saccharomyces cerevisiae. Therefore, a better understanding of how S. cerevisiae cells acquire the tolerance to acetic acid is of importance to develop robust yeast strains to be used in industry. To do this, we examined the transcriptional changes that occur at 12 h post-exposure to acetic acid, revealing that 56 and 58 genes were upregulated and downregulated, respectively. Functional categorization of them revealed that 22 protein synthesis genes and 14 stress response genes constituted the largest portion of the upregulated and downregulated genes, respectively. To evaluate the association of the regulated genes with acetic acid tolerance, 3 upregulated genes (DBP2, ASC1, and GND1) were selected among 34 non-protein synthesis genes, and 54 viable mutants individually deleted for the downregulated genes were retrieved from the non-essential haploid deletion library. Strains overexpressing ASC1 and GND1 displayed enhanced tolerance to acetic acid, whereas a strain overexpressing DBP2 was sensitive. Fifty of 54 deletion mutants displayed enhanced acetic acid tolerance. Three chosen deletion mutants (hsps82Δ, ato2Δ, and ssa3Δ) were also tolerant to benzoic acid but not propionic and sorbic acids. Moreover, all those five (two overexpressing and three deleted) strains were more efficient in proton efflux and lower in membrane permeability and internal hydrogen peroxide content than controls. Individually or in combination, those physiological changes are likely to contribute at least in part to enhanced acetic acid tolerance. Overall, information of our transcriptional profile was very useful to identify molecular factors associated with acetic acid tolerance.

  18. Distribution of protoporphyrin IX in Bowen's disease and basal cell carcinomas treated with topical 5-aminolaevulinic acid

    NASA Astrophysics Data System (ADS)

    Roberts, David J.; Stables, G. I.; Ash, D. V.; Brown, Stanley B.

    1995-03-01

    We have used ultra-low light level fluorescence microscopy to examine the suggestion that the relatively poor response of human basal cell carcinomas (BCC) to topical 5-aminolaevulinic acid (ALA)-based photodynamic therapy (PDT) arises from limited drug penetration into the lesion. The distribution of ALA-induced protoporphyrin IX (PpIX) in human BCC and Bowen's disease was examined and, in almost all cases, was found to be most intense in those regions of tumor immediately adjacent to the dermis. This distribution was independent of tumor type, and did not appear to be affected by tumor depth in the skin. It is suggested that ALA penetration may not limit the efficacy of ALA-PDT in the treatment of BCC. Failure of superficial ALA-based PDT in basal cell carcinoma may, instead, be related to the histological structure of this type of lesion.

  19. Low-Dose Acetylsalicylic Acid in Treating Patients With Stage I-III Non-Small Cell Lung Cancer

    ClinicalTrials.gov

    2016-06-28

    Adenocarcinoma of the Lung; Recurrent Non-small Cell Lung Cancer; Stage IA Non-small Cell Lung Cancer; Stage IB Non-small Cell Lung Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer

  20. High butyric acid amounts induce oxidative stress, alter calcium homeostasis, and cause neurite retraction in nerve growth factor-treated PC12 cells.

    PubMed

    Cueno, Marni E; Kamio, Noriaki; Seki, Keisuke; Kurita-Ochiai, Tomoko; Ochiai, Kuniyasu

    2015-07-01

    Butyric acid (BA) is a common secondary metabolite by-product produced by oral pathogenic bacteria and is detected in high amounts in the gingival tissue of patients with periodontal disease. Previous works have demonstrated that BA can cause oxidative stress in various cell types; however, this was never explored using neuronal cells. Here, we exposed nerve growth factor (NGF)-treated PC1(2) cells to varying BA concentrations (0.5, 1.0, 5.0 mM). We measured total heme, H(2)O(2), catalase, and calcium levels through biochemical assays and visualized the neurite outgrowth after BA treatment. Similarly, we determined the effects of other common periodontal short-chain fatty acids (SCFAs) on neurite outgrowth for comparison. We found that high (1.0 and 5.0 mM) BA concentrations induced oxidative stress and altered calcium homeostasis, whereas low (0.5 mM) BA concentration had no significant effect. Moreover, compared to other SCFAs, we established that only BA was able to induce neurite retraction.

  1. Preventive effect of geniposide on metabolic disease status in spontaneously obese type 2 diabetic mice and free fatty acid-treated HepG2 cells.

    PubMed

    Kojima, Kazuko; Shimada, Tsutomu; Nagareda, Yasuhiro; Watanabe, Michiru; Ishizaki, Junko; Sai, Yoshimichi; Miyamoto, Ken-ichi; Aburada, Masaki

    2011-01-01

    Accumulation of visceral fat induces various symptoms of metabolic syndrome such as insulin resistance and abnormal glucose/lipid metabolism and eventually leads to the onset of ischemic cerebrovascular diseases. Geniposide, which is iridoid glycoside from the fruit of Gardenia jasminoides ELLIS, is recognized as being useful against hyperlipidemia and fatty liver. In order to clarify the effect of geniposide on metabolic disease-based visceral fat accumulation and the relevant molecular mechanism, experiments were performed in spontaneously obese Type 2 diabetic TSOD mice and the free fatty acid-treated HepG2 cells. In the TSOD mice, geniposide showed suppression of body weight and visceral fat accumulation, alleviation of abnormal lipid metabolism and suppression of intrahepatic lipid accumulation. In addition, geniposide alleviated abnormal glucose tolerance and hyperinsulinemia, suggesting that geniposide has an insulin resistance-alleviating effect. Next, in order to investigate the direct effect of geniposide on the liver, the effect on the free fatty acid-treated HepG2 fatty liver model was investigated using genipin, which is the aglycone portion of geniposide. Genipin suppressed the intracellular lipid accumulation caused by the free fatty acid treatment and also significantly increased the intracellular expression of a fatty acid oxidation-related gene (peroxisomal proliferator-activated receptor: PPARα). From these results, it was confirmed that geniposide has an anti-obesity effect, an insulin resistance-alleviating effect and an abnormal lipid metabolism-alleviating effect, and the metabolite genipin shows a direct effect on the liver, inducing expression of a lipid metabolism-related gene as one of its molecular mechanisms. PMID:21963504

  2. The targeted proteins in tumor cells treated with the α-lactalbumin-oleic acid complex examined by descriptive and quantitative liquid chromatography-tandem mass spectrometry.

    PubMed

    Fang, B; Zhang, M; Fan, X; Ren, F Z

    2016-08-01

    An α-lactalbumin-oleic acid (α-LA-OA) complex has exhibited selective antitumor activity in animal models and clinical trials. Although apoptosis and autophagy are activated and the functions of several organelles are disrupted in response to α-LA-OA, the detailed antitumor mechanism remains unclear. In this study, we used a novel technique, isobaric tags for relative and absolute quantitation, to analyze the proteome of tumor cells treated with α-LA-OA. We identified 112 differentially expressed proteins: 95 were upregulated to satisfy the metabolism of tumor cells; 17 were downregulated and targets of α-LA-OA. According to the differentially expressed proteins, α-LA-OA exerted its antitumor activity by disrupting cytoskeleton stability and cell motility, and by inhibiting DNA, lipid, and ATP synthesis, leading to cellular stress and activation of programmed cell death. This study provides a systematic evaluation of the antitumor activity of α-LA-OA, identifying its interacting targets and establishing the theoretical basis of α-LA-OA for use in cancer therapy. PMID:27236751

  3. [Studies on interaction of acid-treated nanotube titanic acid and amino acids].

    PubMed

    Zhang, Huqin; Chen, Xuemei; Jin, Zhensheng; Liao, Guangxi; Wu, Xiaoming; Du, Jianqiang; Cao, Xiang

    2010-06-01

    Nanotube titanic acid (NTA) has distinct optical and electrical character, and has photocatalysis character. In accordance with these qualities, NTA was treated with acid so as to enhance its surface activity. Surface structures and surface groups of acid-treated NTA were characterized and analyzed by Transmission Electron Microscope (TEM) and Fourier Transform Infrared Spectrometry (FT-IR). The interaction between acid-treated NTA and amino acids was investigated. Analysis results showed that the lengths of acid-treated NTA became obviously shorter. The diameters of nanotube bundles did not change obviously with acid-treating. Meanwhile, the surface of acid-treated NTA was cross-linked with carboxyl or esterfunction. In addition, acid-treated NTA can catch amino acid residues easily, and then form close combination.

  4. In vitro cultivation of canine multipotent mesenchymal stromal cells on collagen membranes treated with hyaluronic acid for cell therapy and tissue regeneration

    PubMed Central

    Wodewotzky, T.I.; Lima-Neto, J.F.; Pereira-Júnior, O.C.M.; Sudano, M.J.; Lima, S.A.F.; Bersano, P.R.O.; Yoshioka, S.A.; Landim-Alvarenga, F.C.

    2012-01-01

    Support structures for dermal regeneration are composed of biodegradable and bioresorbable polymers, animal skin or tendons, or are bacteria products. The use of such materials is controversial due to their low efficiency. An important area within tissue engineering is the application of multipotent mesenchymal stromal cells (MSCs) to reparative surgery. The combined use of biodegradable membranes with stem cell therapy may lead to promising results for patients undergoing unsuccessful conventional treatments. Thus, the aim of this study was to test the efficacy of using membranes composed of anionic collagen with or without the addition of hyaluronic acid (HA) as a substrate for adhesion and in vitro differentiation of bone marrow-derived canine MSCs. The benefit of basic fibroblast growth factor (bFGF) on the differentiation of cells in culture was also tested. MSCs were collected from dog bone marrow, isolated and grown on collagen scaffolds with or without HA. Cell viability, proliferation rate, and cellular toxicity were analyzed after 7 days. The cultured cells showed uniform growth and morphological characteristics of undifferentiated MSCs, which demonstrated that MSCs successfully adapted to the culture conditions established by collagen scaffolds with or without HA. This demonstrates that such scaffolds are promising for applications to tissue regeneration. bFGF significantly increased the proliferative rate of MSCs by 63% when compared to groups without the addition of the growth factor. However, the addition of bFGF becomes limiting, since it has an inhibitory effect at high concentrations in culture medium. PMID:22983182

  5. Nitric acid requirement for treating sludge

    SciTech Connect

    Hsu, C.W.

    1992-09-04

    The hydroxylamine nitrate (HAN) precipitate hydrolysis process produces sufficient oxidant (nitrate) such that the resulting blend of formic acid treated sludge and the aqueous product from hydrolysis (PHA) produces a melter feed of acceptable redox (i.e. Fe+2/Total Fe <0.33). With implementation of Late Washing (to reduce the nitrite content of the tetraphenyborate slurry produced during In-Tank Precipitation to 0.01M or less), HAN is no longer required during hydrolysis. As a result, the nitrate content of the melter feed will be reduced greater than an order-of-magnitude and the resulting melter feed produced will be too reducing. If formic acid treatment of the sludge is retained, it will be necessary to trim the melter feed with an oxidant to attain a proper redox. Rather than trimming the melter feed with an oxidant subsequent to the SRAT cycle in which formic acid is used to acidify the sludge, the Savannah River Technology Center (SRTC) has recommended this be accomplished by conversion to nitric acid addition to the Sludge Receipt and Adjustment Tank (SRAT) in place of formic acid (1). This memorandum specifies the stoichiometric bases for determining the nitric acid requirement for the SRAT.

  6. Application of acid-treated yeast cell wall (AYC) as a pharmaceutical additive. III. AYC aqueous coating onto granules and film formation mechanism of AYC.

    PubMed

    Yuasa, Hiroshi; Kaneshige, Junichi; Ozeki, Tetsuya; Kasai, Takahide; Eguchi, Takahiro; Ishiwaki, Naomu

    2002-04-26

    From the viewpoint of effective utilization of natural resources and development of new pharmaceutical materials, acid-treated yeast cell wall (AYC) was prepared via a novel approach involving acidification of brewers' yeast cell wall. AYC aqueous dispersion containing 5% (w/v) AYC and 0.5% (w/v) glycerol was prepared. Subsequently, AYC was coated onto core granules containing acetaminophen (AAP). Spray mist size under various spray conditions and viscosity of the AYC aqueous dispersion at various AYC concentrations were measured. AYC spray mists were optically observed. The surface of AYC cast film and AYC-coated granules were observed with a confocal scanning laser microscope. We attempted to show the utility of AYC as a novel material for granule coating, following the tablet coating in our previous report. In addition, the film formation mechanism of AYC was investigated. A smooth surface of the AYC-coated granules was obtained at a coating ratio of only 5%, which generally requires approximately 15-30% coating against the core granule weight, with no aggregation. These results are attributable to the fact that the granules were coated with a large number of small mists of AYC and the coating progressed efficiently, and the thin film layer of AYC was formed on the granules by mutual tangling of the hydrogel layers of AYC polysaccharides. AAP release from AYC-coated granules was obviously rapid, suggesting the high utility of AYC as a coating material for the rapidly releasing granules.

  7. Retinoic acid treated human dendritic cells induce T regulatory cells via the expression of CD141 and GARP which is impaired with age.

    PubMed

    Agrawal, Sudhanshu; Ganguly, Sreerupa; Tran, Alexander; Sundaram, Padmaja; Agrawal, Anshu

    2016-06-01

    Aged subjects display increased susceptibility to mucosal diseases. Retinoic Acid (RA) plays a major role in inducing tolerance in the mucosa. RA acts on Dendritic cells (DCs) to induce mucosal tolerance. Here we compared the response of DCs from aged and young individuals to RA with a view to understand the role of DCs in age-associated increased susceptibility to mucosal diseases. Our investigations revealed that compared to young DCs, RA stimulated DCs from aged subjects are defective in inducing IL-10 and T regulatory cells. Examinations of the underlying mechanisms indicated that RA exposure led to the upregulation of CD141 and GARP on DCs which rendered the DCs tolerogenic. CD141(hi), GARP(+) DCs displayed enhanced capacity to induce T regulatory cells compared to CD141(lo) and GARP(-) DCs. Unlike RA stimulated DCs from young, DCs from aged subjects exhibited diminished upregulation of both CD141 and GARP. The percentage of DCs expressing CD141 and GARP on RA treatment was significantly reduced in DCs from aged individuals. Furthermore, the remaining CD141(hi), GARP(+) DCs from aged individuals were also deficient in inducing T regs. In summary, reduced response of aged DCs to RA enhances mucosal inflammation in the elderly, increasing their susceptibility to mucosal diseases. PMID:27244900

  8. Retinoic acid treated human dendritic cells induce T regulatory cells via the expression of CD141 and GARP which is impaired with age

    PubMed Central

    Agrawal, Sudhanshu; Ganguly, Sreerupa; Tran, Alexander; Sundaram, Padmaja; Agrawal, Anshu

    2016-01-01

    Aged subjects display increased susceptibility to mucosal diseases. Retinoic Acid (RA) plays a major role in inducing tolerance in the mucosa. RA acts on Dendritic cells (DCs) to induce mucosal tolerance. Here we compared the response of DCs from aged and young individuals to RA with a view to understand the role of DCs in age-associated increased susceptibility to mucosal diseases. Our investigations revealed that compared to young DCs, RA stimulated DCs from aged subjects are defective in inducing IL-10 and T regulatory cells. Examinations of the underlying mechanisms indicated that RA exposure led to the upregulation of CD141 and GARP on DCs which rendered the DCs tolerogenic. CD141hi, GARP+ DCs displayed enhanced capacity to induce T regulatory cells compared to CD141lo and GARP− DCs. Unlike RA stimulated DCs from young, DCs from aged subjects exhibited diminished upregulation of both CD141 and GARP. The percentage of DCs expressing CD141 and GARP on RA treatment was significantly reduced in DCs from aged individuals. Furthermore, the remaining CD141hi, GARP+ DCs from aged individuals were also deficient in inducing T regs. In summary, reduced response of aged DCs to RA enhances mucosal inflammation in the elderly, increasing their susceptibility to mucosal diseases. PMID:27244900

  9. Retinoic acid treated human dendritic cells induce T regulatory cells via the expression of CD141 and GARP which is impaired with age.

    PubMed

    Agrawal, Sudhanshu; Ganguly, Sreerupa; Tran, Alexander; Sundaram, Padmaja; Agrawal, Anshu

    2016-06-01

    Aged subjects display increased susceptibility to mucosal diseases. Retinoic Acid (RA) plays a major role in inducing tolerance in the mucosa. RA acts on Dendritic cells (DCs) to induce mucosal tolerance. Here we compared the response of DCs from aged and young individuals to RA with a view to understand the role of DCs in age-associated increased susceptibility to mucosal diseases. Our investigations revealed that compared to young DCs, RA stimulated DCs from aged subjects are defective in inducing IL-10 and T regulatory cells. Examinations of the underlying mechanisms indicated that RA exposure led to the upregulation of CD141 and GARP on DCs which rendered the DCs tolerogenic. CD141(hi), GARP(+) DCs displayed enhanced capacity to induce T regulatory cells compared to CD141(lo) and GARP(-) DCs. Unlike RA stimulated DCs from young, DCs from aged subjects exhibited diminished upregulation of both CD141 and GARP. The percentage of DCs expressing CD141 and GARP on RA treatment was significantly reduced in DCs from aged individuals. Furthermore, the remaining CD141(hi), GARP(+) DCs from aged individuals were also deficient in inducing T regs. In summary, reduced response of aged DCs to RA enhances mucosal inflammation in the elderly, increasing their susceptibility to mucosal diseases.

  10. Activation of Inactive Nitrogenase by Acid-Treated Component I

    PubMed Central

    Nagatani, H. H.; Shah, Vinod K.; Brill, Winston J.

    1974-01-01

    When Azotobacter vinelandii was derepressed for nitrogenase synthesis in a N-free medium containing tungstate instead of molybdate, an inactive component I was synthesized. Although this inactive component I could be activated in vivo upon addition of molybdate to the medium, it could not be activated in vitro when molybdate was added to the extracts. Activation occurred, however, when an acid-treated component I was added to extracts of cells derepressed in medium containing tungstate. Acid treatment completely abolished component I activity. Mutant strains UW45 and UW10 were unable to fix N2. Both strains synthesized normal levels of component II but produced inactive component I. Acid-treated component I activated inactive component I in extracts of mutant strain UW45 but not mutant strain UW10. This activating factor could be obtained from N2-fixing Klebsiella pneumoniae, Clostridium pasteurianum, and Rhodospirillum rubrum. PMID:4218230

  11. Application of acid-treated yeast cell wall (AYC) as a pharmaceutical additive. II: effects of curing on the medicine release from AYC-coated tablets.

    PubMed

    Yuasa, H; Kaneshige, J; Ozeki, T; Kasai, T; Eguchi, T; Ishiwaki, N

    2000-11-19

    Acid-treated yeast cell wall (AYC) was newly prepared by acidifying brewers' yeast cell wall. Core tablets containing 3% of acetaminophen (AAP) were coated with the AYC aqueous dispersion containing 5% (w/v) of AYC and 0.35% (w/v) of glycerol. The curing of AYC-coated tablets was performed at various curing periods of time and temperatures. The effects of curing on AAP release from AYC-coated tablets, the weight and thickness of the coated layer of AYC and the water sorption into the AYC-coated tablets were studied. The tensile strength and pore size distribution of the AYC cast film were measured. In the case of 60, 80, or 100 degrees C curing, AAP release from AYC-coated tablets showed a sigmoidal release profile with an initial lag time. The duration of the lag time increased with the increasing curing time and temperature, though the release rate after the lag time hardly changed. At 120 degrees C curing, the release rate after the lag time decreased with the increasing curing time and a sustained release was observed. The weight and thickness of the AYC-coated layer and the water sorption rate into AYC-coated tablets decreased with the increasing curing time and temperature. The tensile strength of the AYC cast film increased with increasing the curing temperature, particularly at 120 degrees C curing. It is considered that the water was evaporated from the AYC-coated layer and the adhesion force between AYC particles increased during curing, making the structure of the AYC-coated layer densely firm. The changes in the duration of lag time and the release rate may be due to changes in the structure of the AYC-coated layer caused by curing. These results show that it is feasible to control the lag time and the release rate of AAP from AYC-coated tablets by varying the curing time and temperature.

  12. T-box binding protein type two (TBX2) is an immediate early gene target in retinoic-acid-treated B16 murine melanoma cells.

    PubMed

    Boskovic, Goran; Niles, Richard M

    2004-05-01

    Retinoic acid induces growth arrest and differentiation in B16 mouse melanoma cells. Using gene arrays, we identified several early response genes whose expression is altered by retinoic acid. One of the genes, tbx2, is a member of T-box nuclear binding proteins that are important morphogens in developing embryos. Increased TBX2 mRNA is seen within 2 h after addition of retinoic acid to B16 cells. The effect of retinoic acid on gene expression is direct since it does not require any new protein synthesis. We identified a degenerate retinoic acid response element (RARE) between -186 and -163 in the promoter region of the tbx2 gene. A synthetic oligonucleotide spanning this region was able to drive increased expression of a luciferase reporter gene in response to retinoic acid; however, this induction was lost when a point mutation was introduced into the RARE. This oligonucleotide also specifically bound RAR in nuclear extracts from B16 cells. TBX2 expression and its induction by retinoic acid was also observed in normal human and nonmalignant mouse melanocytes. PMID:15093729

  13. AMPKα, C/EBPβ, CPT1β, GPR43, PPARγ, and SCD Gene Expression in Single- and Co-cultured Bovine Satellite Cells and Intramuscular Preadipocytes Treated with Palmitic, Stearic, Oleic, and Linoleic Acid.

    PubMed

    Choi, S H; Park, S K; Johnson, B J; Chung, K Y; Choi, C W; Kim, K H; Kim, W Y; Smith, B

    2015-03-01

    We previously demonstrated that bovine subcutaneous preadipocytes promote adipogenic gene expression in muscle satellite cells in a co-culture system. Herein we hypothesize that saturated fatty acids would promote adipogenic/lipogenic gene expression, whereas mono- and polyunsaturated fatty acids would have the opposite effect. Bovine semimembranosus satellite cells (BSC) and intramuscular preadipocytes (IPA) were isolated from crossbred steers and cultured with 10% fetal bovine serum (FBS)/Dulbecco's Modified Eagle Medium (DMEM) and 1% antibiotics during the 3-d proliferation period. After proliferation, cells were treated for 3 d with 3% horse serum/DMEM (BSC) or 5% FBS/DMEM (IPA) with antibiotics. Media also contained 10 μg/mL insulin and 10 μg/mL pioglitazone. Subsequently, differentiating BSC and IPA were cultured in their respective media with 40 μM palmitic, stearic, oleic, or linoleic acid for 4 d. Finally, BSC and IPA were single- or co-cultured for an additional 2 h. All fatty acid treatments increased (p = 0.001) carnitine palmitoyltransferase-1 beta (CPT1β) gene expression, but the increase in CPT1β gene expression was especially pronounced in IPA incubated with palmitic and stearic acid (6- to 17- fold increases). Oleic and linoleic acid decreased (p = 0.001) stearoyl-CoA desaturase (SCD) gene expression over 80% in both BSC and IPA. Conversely, palmitic and stearic acid increased SCD gene expression three fold in co-cultured in IPA, and stearic acid increased AMPKα gene expression in single- and co-cultured BSC and IPA. Consistent with our hypothesis, saturated fatty acids, especially stearic acid, promoted adipogenic and lipogenic gene expression, whereas unsaturated fatty acids decreased expression of those genes associated with fatty acid metabolism.

  14. AMPKα, C/EBPβ, CPT1β, GPR43, PPARγ, and SCD Gene Expression in Single- and Co-cultured Bovine Satellite Cells and Intramuscular Preadipocytes Treated with Palmitic, Stearic, Oleic, and Linoleic Acid

    PubMed Central

    Choi, S. H.; Park, S. K.; Johnson, B. J.; Chung, K. Y.; Choi, C. W.; Kim, K. H.; Kim, W. Y.; Smith, B.

    2015-01-01

    We previously demonstrated that bovine subcutaneous preadipocytes promote adipogenic gene expression in muscle satellite cells in a co-culture system. Herein we hypothesize that saturated fatty acids would promote adipogenic/lipogenic gene expression, whereas mono- and polyunsaturated fatty acids would have the opposite effect. Bovine semimembranosus satellite cells (BSC) and intramuscular preadipocytes (IPA) were isolated from crossbred steers and cultured with 10% fetal bovine serum (FBS)/Dulbecco’s Modified Eagle Medium (DMEM) and 1% antibiotics during the 3-d proliferation period. After proliferation, cells were treated for 3 d with 3% horse serum/DMEM (BSC) or 5% FBS/DMEM (IPA) with antibiotics. Media also contained 10 μg/mL insulin and 10 μg/mL pioglitazone. Subsequently, differentiating BSC and IPA were cultured in their respective media with 40 μM palmitic, stearic, oleic, or linoleic acid for 4 d. Finally, BSC and IPA were single- or co-cultured for an additional 2 h. All fatty acid treatments increased (p = 0.001) carnitine palmitoyltransferase-1 beta (CPT1β) gene expression, but the increase in CPT1β gene expression was especially pronounced in IPA incubated with palmitic and stearic acid (6- to 17- fold increases). Oleic and linoleic acid decreased (p = 0.001) stearoyl-CoA desaturase (SCD) gene expression over 80% in both BSC and IPA. Conversely, palmitic and stearic acid increased SCD gene expression three fold in co-cultured in IPA, and stearic acid increased AMPKα gene expression in single- and co-cultured BSC and IPA. Consistent with our hypothesis, saturated fatty acids, especially stearic acid, promoted adipogenic and lipogenic gene expression, whereas unsaturated fatty acids decreased expression of those genes associated with fatty acid metabolism. PMID:25656188

  15. Varying butyric acid amounts induce different stress- and cell death-related signals in nerve growth factor-treated PC12 cells: implications in neuropathic pain absence during periodontal disease progression.

    PubMed

    Seki, Keisuke; Cueno, Marni E; Kamio, Noriaki; Saito, Yuko; Kamimoto, Atsushi; Kurita-Ochiai, Tomoko; Ochiai, Kuniyasu

    2016-06-01

    Neuropathic pain is absent from the early stages of periodontal disease possibly due to neurite retraction. Butyric acid (BA) is a periodontopathic metabolite that activates several stress-related signals and, likewise, induce neurite retraction. Neuronal cell death is associated to neurite retraction which would suggest that BA-induced neurite retraction is ascribable to neuronal cell death. However, the underlying mechanism of BA-related cell death signaling remains unknown. In this study, we exposed NGF-treated PC12 cells to varying BA concentrations [0 (control), 0.5, 1.0, 5.0 mM] and determined selected stress-related (H2O2, glutathione reductase, calcium (Ca(2+)), plasma membrane Ca(2+) ATPase (PMCA), and GADD153/CHOPS) and cell death-associated (extrinsic: FasL, TNF-α, TWEAK, and TRAIL; intrinsic: cytochrome C (CytC), NF-kB, CASP8, CASP9, CASP10, and CASP3) signals. Similarly, we confirmed cell death execution by chromatin condensation. Our results showed that low (0.5 mM) and high (1.0 and 5.0 mM) BA levels differ in stress and cell death signaling. Moreover, at periodontal disease-level BA concentration (5 mM), we observed that only FasL amounts were affected and occurred concurrently with chromatin condensation insinuating that cells have fully committed to neurodegeneration. Thus, we believe that both stress and cell death signaling in NGF-treated PC12 cells are affected differently depending on BA concentration. In a periodontal disease scenario, we hypothesize that during the early stages, low BA amounts accumulate resulting to both stress- and cell death-related signals that favor neurite non-proliferation, whereas, during the later stages, high BA amounts accumulate resulting to both stress- and cell death-related signals that favor neurodegeneration. More importantly, we propose that neuropathic pain absence at any stage of periodontal disease progression is ascribable to BA accumulation regardless of amount. PMID:26994613

  16. Gelled acidic well treating composition and process

    SciTech Connect

    Swanson, B.L.

    1981-01-13

    Gelled acidic compositions suitable for either matrix-acidizing or fracture-acidizing of subterranean formations comprising water , a water-dispersible polymer selected from cellulose ethers and polymers of acrylamides, an acid, an aldehyde, and a phenolic compound capable of causing gelation of an aqueous dispersion of the polymer, acid, aldehyde, and phenolic compound are provided. In another embodiment, guar gum, polyvinylpyrrolidone and biopolysaccharides can also be used as the polymeric component in said compositions.

  17. Monitoring of very long-chain fatty acids levels in X-linked adrenoleukodystrophy, treated with haematopoietic stem cell transplantation and Lorenzo's Oil.

    PubMed

    Stradomska, Teresa J; Drabko, Katarzyna; Moszczyńska, Elżbieta; Tylki-Szymańska, Anna

    2014-01-01

    X-linked adrenoleukodystrophy is a rare, neurodegenerative peroxisomal disorder connected with mutation in the ABCD1 gene, causing impairment of the peroxisomal β-oxidation process and in consequence, accumulation of very long-chain fatty acids (VLCFA) in blood and tissues. In this study we present serum very long-chain fatty acids levels during clinical course in an X-linked adrenoleukodystrophy patient after haematopoietic stem cell transplantation (HSCT) and on Lorenzo's Oil in a 11 years' period. The patient was diagnosed at the age of 8 months by family screening. The administration of LO was started at 2 years of age. HSCT from a family donor was performed twice. VLCFA serum levels were detected by the GC method. Chimaerism subsequent to HSCT was also analyzed. Increasing very long-chain fatty acids levels correlate with a decreasing chimaerism level after haematopoietic stem cell transplantation. The sequential monitoring of very long-chain fatty acids serum levels is important and useful for assessment of engraftment, graft failure or rejection.

  18. Acid distribution in phosphoric acid fuel cells

    SciTech Connect

    Okae, I.; Seya, A.; Umemoto, M.

    1996-12-31

    Electrolyte acid distribution among each component of a cell is determined by capillary force when the cell is not in operation, but the distribution under the current load conditions had not been clear so far. Since the loss of electrolyte acid during operation is inevitable, it is necessary to store enough amount of acid in every cell. But it must be under the level of which the acid disturbs the diffusion of reactive gases. Accordingly to know the actual acid distribution during operation in a cell is very important. In this report, we carried out experiments to clarify the distribution using small single cells.

  19. Biotransformation of cinnamic acid, p-coumaric acid, caffeic acid, and ferulic acid by plant cell cultures of Eucalyptus perriniana.

    PubMed

    Katsuragi, Hisashi; Shimoda, Kei; Kubota, Naoji; Nakajima, Nobuyoshi; Hamada, Hatsuyuki; Hamada, Hiroki

    2010-01-01

    Biotransformations of phenylpropanoids such as cinnamic acid, p-coumaric acid, caffeic acid, and ferulic acid were investigated with plant-cultured cells of Eucalyptus perriniana. The plant-cultured cells of E. perriniana converted cinnamic acid into cinnamic acid β-D-glucopyranosyl ester, p-coumaric acid, and 4-O-β-D-glucopyranosylcoumaric acid. p-Coumaric acid was converted into 4-O-β-D-glucopyranosylcoumaric acid, p-coumaric acid β-D-glucopyranosyl ester, 4-O-β-D-glucopyranosylcoumaric acid β-D-glucopyranosyl ester, a new compound, caffeic acid, and 3-O-β-D-glucopyranosylcaffeic acid. On the other hand, incubation of caffeic acid with cultured E. perriniana cells gave 3-O-β-D-glucopyranosylcaffeic acid, 3-O-(6-O-β-D-glucopyranosyl)-β-D-glucopyranosylcaffeic acid, a new compound, 3-O-β-D-glucopyranosylcaffeic acid β-D-glucopyranosyl ester, 4-O-β-D-glucopyranosylcaffeic acid, 4-O-β-D-glucopyranosylcaffeic acid β-D-glucopyranosyl ester, ferulic acid, and 4-O-β-D-glucopyranosylferulic acid. 4-O-β-D-Glucopyranosylferulic acid, ferulic acid β-D-glucopyranosyl ester, and 4-O-β-D-glucopyranosylferulic acid β-D-glucopyranosyl ester were isolated from E. perriniana cells treated with ferulic acid.

  20. Tracking and treating activated T cells

    PubMed Central

    Kim, N.H.; Nadithe, V.; Elsayed, M.; Merkel, O.M.

    2014-01-01

    Upon activation, T cells of various subsets are the most important mediators in cell-mediated immune responses. Activated T cells play an important role in immune system related diseases such as chronic inflammatory diseases, viral infections, autoimmune disease, transplant rejection, Crohn disease, diabetes, and many more. Therefore, efforts have been made to both visualize and treat activated T cells specifically. This review summarizes imaging approaches and selective therapeutics for activated T cells and gives an outlook on how tracking and treating can be combined into theragnositc agents for activated T cells. PMID:24660025

  1. ROS-Mediated Autophagy Induced by Dysregulation of Lipid Metabolism Plays a Protective Role in Colorectal Cancer Cells Treated with Gambogic Acid

    PubMed Central

    Zhang, Haiyuan; Lei, Yunlong; Yuan, Ping; Li, Lingjun; Luo, Chao; Gao, Rui; Tian, Jun; Feng, Zuohua; Nice, Edouard C.; Sun, Jun

    2014-01-01

    Gambogic acid (GA), the main active component of gamboge resin, has potent antitumor activity both in vivo and in vitro. However, the underlying molecular mechanisms remain unclear. In this study, we found that GA could initiate autophagy in colorectal cancer cells, and inhibition of the autophagy process accelerated the effect of proliferative inhibition and apoptotic cell death induced by GA, implying a protective role of autophagy. Two-dimensional electrophoresis-based proteomics showed that GA treatment altered the expression of multiple proteins involved in redox signaling and lipid metabolism. Functional studies revealed that GA-induced dysregulation of lipid metabolism could activate 5-lipoxygenase (5-LOX), resulting in intracellular ROS accumulation, followed by inhibition of Akt-mTOR signaling and autophagy initiation. Finally, results using a xenograft model suggested ROS-induced autophagy protect against the antitumor effect of GA. Taken together, these data showed new biological activities of GA against colorectal cancer underlying the protective role of ROS-induced autophagy. This study will provide valuable insights for future studies regarding the anticancer mechanisms of GA. PMID:24810758

  2. Induction of Mitochondrial Changes Associated with Oxidative Stress on Very Long Chain Fatty Acids (C22:0, C24:0, or C26:0)-Treated Human Neuronal Cells (SK-NB-E)

    PubMed Central

    Zarrouk, Amira; Vejux, Anne; Nury, Thomas; El Hajj, Hammam I.; Haddad, Madouda; Cherkaoui-Malki, Mustapha; Riedinger, Jean-Marc; Hammami, Mohamed; Lizard, Gérard

    2012-01-01

    In Alzheimer's disease, lipid alterations point towards peroxisomal dysfunctions. Indeed, a cortical accumulation of saturated very long chain fatty acids (VLCFAs: C22:0, C24:0, C26:0), substrates for peroxisomal β-oxidation, has been found in Alzheimer patients. This study was realized to investigate the effects of VLCFAs at the mitochondrial level since mitochondrial dysfunctions play crucial roles in neurodegeneration. On human neuronal SK-NB-E cells treated with C22:0, C24:0, or C26:0 (0.1–20 μM; 48 h), an inhibition of cell growth and mitochondrial dysfunctions were observed by cell counting with trypan blue, MTT assay, and measurement of mitochondrial transmembrane potential (Δψm) with DiOC6(3). A stimulation of oxidative stress was observed with DHE and MitoSOX used to quantify superoxide anion production on whole cells and at the mitochondrial level, respectively. With C24:0 and C26:0, by Western blotting, lower levels of mitochondrial complexes III and IV were detected. After staining with MitoTracker and by transmission electron microscopy used to study mitochondrial topography, mass and morphology, major changes were detected in VLCFAs treated-cells: modification of the cytoplasmic distribution of mitochondria, presence of large mitochondria, enhancement of the mitochondrial mass. Thus, VLCFAs can be potential risk factors contributing to neurodegeneration by inducing neuronal damages via mitochondrial dysfunctions. PMID:22919440

  3. Ultrastructural changes in the ovary cells of engorged Rhipicephalus sanguineus female ticks treated with esters of ricinoleic acid from castor oil (Ricinus communis).

    PubMed

    Sampieri, Bruno Rodrigues; Arnosti, André; Nunes, Pablo Henrique; Furquim, Karim Christina Scopinho; Chierice, Gilberto Orivaldo; Mathias, Maria Izabel Camargo

    2012-05-01

    Rhipicephalus sanguineus is a widely distributed tick species that has adapted to the urban environment, and the dog is its main host. This species is also known as a vector and reservoir of diseases caused by bacteria, protozoa, and viruses. Currently, acaricides of synthetic chemical origin have been widely and indiscriminately used, leading to the development of resistance to these products by ticks and causing damage to the environment. Thus, these issues have made it necessary to seek other forms of controlling these ectoparasites. R. sanguineus was artificially infested in host New Zealand White rabbits, which were divided into four treatment groups: control (CG1 and CG2) and treatment (TG1 and TG2) groups. TG1 and TG2 hosts were provided with feed supplemented with esters of ricinoleic acid from castor oil at a concentration of 5 g/kg of feed for 7 and 15 days. Afterward, the ovaries of the female ticks were removed for analysis by transmission electron microscopy. The results showed ultrastructural changes in the somatic and germ cells of ovaries from TG1 and TG2 females, particularly with respect to chorion deposition, a protective membrane of the oocyte, as well as in the transport process of vitellogenic materials via the hemolymph and pedicel cells. Moreover, the mitochondria were less electron-dense and had cristae that were more disorganized than the mitochondria from CG1 and CG2 individuals. Thus, this study demonstrated the action of esters on the ovaries of R. sanguineus, signaling the prospect of a way to control this ectoparasite without affecting nontarget organisms or the environment.

  4. Regulated expression of the MRP8 and MRP14 genes in human promyelocytic leukemic HL-60 cell treated with the differentiation-inducing agents mycophenolic acid and 1{alpha},25-Dihydroxyvitamin D{sub 3}

    SciTech Connect

    Warner-Bartnicki, A.L.; Murao, S.; Collart, F.R.; Huberman, E.

    1992-12-31

    The calcium-binding proteins MRP8 and MEP14 are present in mature monomyelocytic cells and are induced during differentiation. Previous studies have demonstrated that the proteins may mediate the growth arrest in differentiating HL-60 cells. We determined the levels of a protein complex (PC) containing MRP8 and MRP14 and investigated the mechanism by which the genes encoding these proteins are regulated in HL-60 cells treated with the differentiation-inducing agent mycophenorc acid (MPA)While the PC was barely detectable in untreated cells, MPA treatment resulted in elevated levels of the PC which were maximal at 3-4 d, and were found to directly parallel gains in the steady-state levels of MRP8 and MRP14 MRNA. Transcription studies with the use of nuclear run-on experiments revealed increased transcription initiation at the MRP8 and MRP14 promoters after MPA treatment. 1{alpha},25-Dihydroxyvitamin D{sub 3}, which induces HL-60 cell differentiation by another mechanism, was also found to increase transcription initiation at the MRP8 and MRP14 promoters. Our results suggest that this initiation is the major control of maturation agent-mediated increases in MRP8 and MRPl4 gene expression, and support a role for the PC in terminal differentiation of human monomyelocytic cells.

  5. PHENOTYPE AND POLARIZATION OF AUTOLOGOUS T CELLS BY BIOMATERIAL-TREATED DENDRITIC CELLS

    PubMed Central

    Park, Jaehyung; Gerber, Michael H.; Babensee, Julia E.

    2014-01-01

    Given the central role of dendritic cells (DCs) in directing T cell phenotypes, the ability of biomaterial-treated DCs to dictate autologous T cell phenotype was investigated. Here, we demonstrate that differentially biomaterial-treated DCs differentially directed autologous T cell phenotype and polarization, depending on the biomaterial used to pre-treat the DCs. Immature DCs (iDCs) were derived from human peripheral blood monocytes, and treated with biomaterial films of alginate, agarose, chitosan, hyaluronic acid, or 75:25 poly(lactic-co-glycolic acid) (PLGA), followed by co-culture of these biomaterial-treated DCs and autologous T cells. When autologous T cells were co-cultured with DCs treated with biomaterial film/antigen (ovalbumin, OVA) combinations, different biomaterial films induced differential levels of T cell marker (CD4, CD8, CD25, CD69) expression, as well as differential cytokine profiles [interferon (IFN)-γ, interleukin (IL)-12p70, IL-10, IL-4] in the polarization of T helper types. Dendritic cells treated with agarose films/OVA induced CD4+CD25+FoxP3+ (T regulatory cells) expression, comparable to untreated iDCs, on autologous T cells in the DC-T co-culture system. Furthermore, in this co-culture, agarose treatment induced release of IL-12p70 and IL-10 at higher levels, as compared to DC treatment with other biomaterial films/OVA, suggesting Th1 and Th2 polarization, respectively. Dendritic cells treated with PLGA film/OVA treatment induced release of IFN-γ at higher levels compared to that observed for co-cultures with iDCs or DCs treated with all other biomaterial films. These results indicate that DC treatment with different biomaterial films has potential as a tool for immunomodulation by directing autologous T cell responses. PMID:24616366

  6. Data on (+)-usnic acid: A new application to treat toxoplasmosis.

    PubMed

    Si, Kaiwei; Wei, Linlin; Yu, Xiaozhuo; Wu, Feng; Li, Xiaoqi; Li, Chen; Cheng, Yanbin

    2016-09-01

    Toxoplasma gondii pathogen is a threat to human health that results in economic burden. Unfortunately, there are very few high-efficiency and low-toxicity drugs for toxoplasmosis in the clinic. (+)-Usnic acid derived from lichen species has been reported to have anti-inflammatory, antibacterial, anti-parasitology, and even anti-cancer activities. In associated with the published article "Effects of (+)-Usnic Acid and (+)-Usnic Acid-Liposome on Toxoplasma gondii" [1], this dataset article provided the detailed information of experimental designing, methods, features as well as the raw data of (+)-usnic acid and (+)-usnic acid-liposome on toxoplasma in vivo and vitro. (+)-Usnic acid may be a potential agent for treating toxoplasmosis. PMID:27437438

  7. Live imaging of transforming growth factor-β activated kinase 1 activation in Lewis lung carcinoma 3LL cells implanted into syngeneic mice and treated with polyinosinic:polycytidylic acid.

    PubMed

    Takaoka, Saori; Kamioka, Yuji; Takakura, Kanako; Baba, Ai; Shime, Hiroaki; Seya, Tsukasa; Matsuda, Michiyuki

    2016-05-01

    Transforming growth factor-β activated kinase 1 (TAK1) has been shown to play a crucial role in cell death, differentiation, and inflammation. Here, we live-imaged robust TAK1 activation in Lewis lung carcinoma 3LL cells implanted into the s.c. tissue of syngeneic C57BL/6 mice and treated with polyinosinic:polycytidylic acid (PolyI:C). First, we developed and characterized a Förster resonance energy transfer-based biosensor for TAK1 activity. The TAK1 biosensor, named Eevee-TAK1, responded to stress-inducing reagents such as anisomycin, tumor necrosis factor-α, and interleukin1-β. The anisomycin-induced increase in Förster resonance energy transfer was abolished by the TAK1 inhibitor (5z)-7-oxozeaenol. Activity of TAK1 in 3LL cells was markedly increased by PolyI:C in the presence of macrophages. 3LL cells expressing Eevee-TAK1 were implanted into mice and observed through imaging window by two-photon excitation microscopy. During the growth of tumor, the 3LL cells at the periphery of the tumor showed higher TAK1 activity than the 3LL cells located at the center of the tumor, suggesting that cells at the periphery of the tumor mass were under stronger stress. Injection of PolyI:C, which is known to induce regression of the implanted tumors, induced marked and homogenous TAK1 activation within the tumor tissues. The effect of PolyI:C faded within 4 days. These observations suggest that Eevee-TAK1 is a versatile tool to monitor cellular stress in cancer tissues. PMID:26931406

  8. ELEMENTAL MERCURY ADSORPTION BY ACTIVATED CARBON TREATED WITH SULFURIC ACID

    EPA Science Inventory

    The paper gives results of a study of the adsorption of elemental mercury at 125 C by a sulfuric-acid (H2S04, 50% w/w/ solution)-treated carbon for the removal of mercury from flue gas. The pore structure of the sample was characterized by nitrogen (N2) at -196 C and the t-plot m...

  9. Indeterminate cell histiocytosis successfully treated with phototherapy

    PubMed Central

    Sotto, Mirian Nacagami; de Campos, Fernando Peixoto Ferraz; Abdo, Andre Neder Ramires; Pereira, Juliana; Sanches, José Antônio; Martins, Jade Cury

    2016-01-01

    First described in 1985, intermediate cell histiocytosis is a rare disorder of the cutaneous dendritic cell group with a varied clinical presentation and evolution. The pathologic substrate is constituted by the proliferation of indeterminate cells (ICs) that are immunophenotypically characterized by the positivity of CD1a, CD68, and faint/focal S100, plus the negativity for CD207 (langerin). The authors present the case of a healthy elderly woman who presented generalized dome-shaped reddish cutaneous nodules over her trunk, neck, face, and extremities over a period of 18 months. A laboratory and imaging work-up ruled out internal involvement. The skin biopsy was consistent with IC histiocytosis. The patient was treated with narrowband ultraviolet B phototherapy, which resulted in an excellent short-term outcome. PMID:27547741

  10. Suitability of bronopol preservative treated milk for fatty acid determination.

    PubMed

    Butler, Gillian; Stergiadis, Sokratis

    2011-05-01

    This work aimed to test if milk preserved with bronopol can be reliably used for fatty acid determination. Dairy production and milk quality are often monitored regularly to assess performance and contribute to selection indices. With evidence that fat composition can be influenced by selective breeding, there might be an interest in using samples collected in routine testing to evaluate individual cow fatty acid profiles, contributing to breeding indices. However, most recording services use a preservative such as bronopol and there is no published record if this influences subsequent fatty acid analysis. This study used milk from an oil seed supplementation trial, generating a wide range of milk fatty acid profiles, to test if the concentration of 31 individual fatty acids determined by GC were influenced by bronopol. Provided preserved samples are subsequently frozen, milk treated with bronopol can reliably be used to evaluate fatty acid composition in most cases; however bronopol might influence a few long-chain fatty acids present in relatively low concentrations. This is one small step towards simplifying milk compositional analysis but it could ultimately streamline the inclusion of milk fat quality into breeding indices, either with a view to 'healthier' milk or potentially reducing methane output and the environmental impact of dairy production.

  11. Fluoroalkyl chloroformates in treating amino acids for gas chromatographic analysis.

    PubMed

    Husek, Petr; Simek, Petr; Hartvich, Petr; Zahradnícková, Helena

    2008-04-01

    Novel fluoroalkyl chloroformates with three and four carbon atoms were investigated for the immediate conversion of amino acids into hydrophobic derivatives in water-containing media. Derivatization conditions were extensively studied and optimized sample preparation protocols elaborated. More than 30 amino acids were treated with the particular reagent in isooctane by simply vortexing the reactive organic phase with a slightly basified aqueous medium containing pyridine or 3-picoline as a catalyst. Outstanding separation of nearly all components on 5% phenylmethylsilicone phase in gas chromatographic (GC) analysis with mass spectrometric (MS) or flame ionization detection (FID) required <10 min. Quantitation characteristics involving linearity in the range of 0.1-100 nmol, regression coefficients of 0.999-0.953 (histidine), MS limit of detection (LOD) reaching 0.03 pmol at proline to nearly 20 pmol at glutamic acid, plus electron impact (EI) spectra and diagnostic SIM fragment ions of the derivatives are reported. The novel method is simple, robust and rapid, enabling to treat amino acids in aqueous environment and to analyze them in <15 min. PMID:18242622

  12. Acid Black 48 dye biosorption using Saccharomyces cerevisiae immobilized with treated sugarcane bagasse.

    PubMed

    Mitter, E K; Corso, C R

    2012-01-01

    The textile industry consumes large quantities of water and chemicals, especially in dyeing and finishing processes. Textile dye adsorption can be accomplished with natural or synthetic compounds. Cell immobilization using biomaterials allows the reduction of toxicity and mechanical resistance and opens spaces within the matrix for cell growth. The use of natural materials, such as sugarcane bagasse, is promising due to the low costs involved. The aim of the present study was to evaluate the use of sugarcane bagasse treated with either polyethyleneimine (PEI), NaOH or distilled water in the cell immobilization of Saccharomyces cerevisiae for textile dye removal. Three different adsorption tests were conducted: treated sugarcane bagasse alone, free yeast cells and bagasse-immobilized yeast cells. Yeast immobilization was 31.34% with PEI-treated bagasse, 8.56% with distilled water and 22.54% with NaOH. PEI-treated bagasse exhibited the best removal rates of the dye at all pH values studied (2.50, 4.50 and 6.50). The best Acid Black 48 adsorption rates were obtained with use of free yeast cells. At pH 2.50, 1 mg of free yeast cells was able to remove 5488.49 g of the dye. The lowest adsorption capacity rates were obtained using treated bagasse alone. However, the use of bagasse-immobilized cells increased adsorption efficiency from 20 to 40%. The use of immobilized cells in textile dye removal is very attractive due to adsorbed dye precipitation, which eliminates the industrial need for centrifugation processes. Dye adsorption using only yeast cells or sugarcane bagasse requires separation methods.

  13. Electrical Properties of Heat-Treated Poly-Lactic Acid

    NASA Astrophysics Data System (ADS)

    Oi, Toru; Shinyama, Katsuyoshi; Fujita, Shigetaka

    Poly-lactic acid (PLA), a biodegradable plastic, has excellent electrical insulation properties at temperatures ranging from room temperature to around 70°C. At temperatures higher than 70°C, however, the insulation performance of PLA deteriorates due to its poor heat resistance. In this study, PLA was heat-treated at 100°C to endow it with greater heat resistance, and the effects that this heat treatment had on the electrical properties of PLA were investigated. Before being subjected to heat treatment, crystallinity (xc) of PLA was about 6%. After the heat treatment was begun, xc increased in proportion to the heat treatment time, such that measurements revealed that xc had increased to about 42% by the time 15 minutes had passed since the start of the heat treatment. The temperature dependence of the insulation breakdown strength (EB) of heat-treated PLA was investigated, and it was found that EB of heat-treated PLA (PLA-A) decreases at a more moderate rate at temperatures higher than 60°C.

  14. Diffuse alveolar hemorrhage: retrospective review of clinical outcome in allogeneic transplant recipients treated with aminocaproic acid.

    PubMed

    Wanko, Sam O; Broadwater, Gloria; Folz, Rodney J; Chao, Nelson J

    2006-09-01

    Diffuse alveolar hemorrhage (DAH) after allogeneic hematopoietic stem cell transplantation (HSCT) is often fatal. Standard therapy with high-dose corticosteroid is not always effective. There is paucity of data in the literature about other potentially useful agents, such as aminocaproic acid (Amicar) in the post-transplantation setting. We retrospectively reviewed our data on 115 consecutive patients who underwent HSCT and had pulmonary complications, with the aim of determining the overall clinical outcome in recipients of allogeneic transplants and in the subgroup of these patients who were treated with concomitant Solu-Medrol and aminocaproic acid. Aminocaproic acid was added at the discretion of the attending physician. We identified 14 allogeneic transplant recipients (median age, 41 years) with 15 episodes of DAH who were treated with Solu-Medrol (250 mg to 1 g intravenously per day). Of these, 8 patients also received concomitant aminocaproic acid at 1000 mg intravenously every 6 hours. Failure to improve was the most common reason for adding aminocaproic acid. The incidence of DAH was 12.2% (10.3% in myeloablative versus 1.9% in nonmyeloablative recipients). The overall 100-day DAH mortality and median transplantation survival were 60% and 99 days, respectively. Among the subset of patients treated with the combination of Solu-Medrol and aminocaproic acid, we observed a 100-day DAH mortality and median transplantation survival of 44% and 167 days, respectively, compared with 83% and 96.5 days in those treated with Solu-Medrol alone. The median time to DAH was 40.5 days, and the median time to death was 53 days in the combined treatment group compared with 29.5 days in those treated with steroid alone. There were no significant differences in coagulation parameters between subsets. Infections (yeast, respiratory syncytial virus, herpes simplex virus, and parainfluenza) were isolated and treated from 6 diagnostic bronchial alveolar lavage samples and were

  15. Molecular spectroscopic study of acid treated fenugreek seeds

    NASA Astrophysics Data System (ADS)

    Ibrahim, Medhat

    2010-12-01

    Fenugreek seeds were subjected to acid treatment in order to activate its surface. XRF indicated that there was no change in the level of metals and metal oxides as a result of the treatment. FTIR of the treated fenugreek showed no change in the characteristic bands and/or structure of the fenugreek. A shift in both OH and metal oxide bands suggest a role for metal, hydrated metal and metal oxide in fenugreek seed. Molecular modeling suggests that metal oxides such as Al 16O 24 offer its surface for the adsorption of gases. The interaction of gases with metal oxide is depending on the type of gas rather than the type of coordination. Finally results indicate that fenugreek could be used safely to control the level of gases in stomach.

  16. Metabolomics Analysis and Biosynthesis of Rosmarinic Acid in Agastache rugosa Kuntze Treated with Methyl Jasmonate

    PubMed Central

    Uddin, Md. Romij; Xu, Hui; Park, Woo Tae; Tuan, Pham Anh; Li, Xiaohua; Chung, Eunsook; Lee, Jai-Heon; Park, Sang Un

    2013-01-01

    This study investigated the effect of methyl jasmonate (MeJA) on metabolic profiles and rosmarinic acid (RA) biosynthesis in cell cultures of Agastache rugosa Kuntze. Transcript levels of phenylpropanoid biosynthetic genes, i.e., ArPAL, Ar4CL, and ArC4H, maximally increased 4.5-fold, 3.4-fold, and 3.5-fold, respectively, compared with the untreated controls, and the culture contained relatively high amounts of RA after exposure of cells to 50 µM MeJA. RA levels were 2.1-, 4.7-, and 3.9-fold higher after exposure to 10, 50, and 100 µM MeJA, respectively, than those in untreated controls. In addition, the transcript levels of genes attained maximum levels at different time points after the initial exposure. The transcript levels of ArC4H and Ar4CL were transiently induced by MeJA, and reached a maximum of up to 8-fold at 3 hr and 6 hr, respectively. The relationships between primary metabolites and phenolic acids in cell cultures of A. rugosa treated with MeJA were analyzed by gas chromatography coupled with time-of-flight mass spectrometry. In total, 45 metabolites, including 41 primary metabolites and 4 phenolic acids, were identified from A. rugosa. Metabolite profiles were subjected to partial least square-discriminate analysis to evaluate the effects of MeJA. The results indicate that both phenolic acids and precursors for the phenylpropanoid biosynthetic pathway, such as aromatic amino acids and shikimate, were induced as a response to MeJA treatment. Therefore, MeJA appears to have an important impact on RA accumulation, and the increased RA accumulation in the treated cells might be due to activation of the phenylpropanoid genes ArPAL, ArC4H, and Ar4CL. PMID:23724034

  17. Retinoic acid stimulate differentiation of hippocampal stem cells into opsin expressing cells in vitro.

    PubMed

    Safari, M; Nobakht, M; Roshandel, N Rahbar; Ghazi, F; Joghataee, M T

    2009-09-01

    The results of several studies have demonstrated that cell differentiation influenced by derivatives of retinoic acid. To determine whether retinoic acid mediate the differentiation of neural stem cells we treated dissociated hippocampal stem cells with different concentrations of all trans or 9-cis retinoic acid and analyzed the effects on cell fate by specific monoclonal antibody for photoreceptors. Addition of exogenous retinoic acid caused a dose dependent specific in the elevation of the cell number that developed as photoreceptors in culture. Also results ofimmunohistochemical studies using monoclonal antibody demonstrated that the primary effect ofretinoic acid was to influence progenitor cells the developed as mature and immature photoreceptors. These results suggest that retinoic acid may play an important effect in the normal development of photoreceptor cells in vitro.

  18. Effects of chrysotile and acid-treated chrysotile on macrophage cultures

    PubMed Central

    Beck, E. G.; Holt, P. F.; Nasrallah, E. T.

    1971-01-01

    Beck, E. G., Holt, P. F., and Nasrallah, E. T. (1971).Brit. J. industr. Med.,28, 179-185. Effects of chrysotile and acid-treated chrysotile on macrophage cultures. The addition of chrysotile asbestos to monolayer cultures of peritoneal and alveolar macrophages produces an increase in membrane permeability, as measured by eosin uptake and lactic dehydrogenase activity of the supernatant fluid. The lactate synthesis is increased, however. It is suggested that the permeability of the cell membrane is increased while dust particles are being phagocytosed, which may take several hours when the particles are fibrous, but that this does not imply cell damage. Treatment of chrysotile with acid, which leaves a silica surface, results in a product that reduces lactate synthesis, implying cytotoxicity. This change is counteracted by poly(2-vinyl-pyridine 1-oxide). The polymer does not affect the properties of the native chrysotile. PMID:5572686

  19. Chlorogenic Acids Biosynthesis in Centella asiatica Cells Is not Stimulated by Salicylic Acid Manipulation.

    PubMed

    Ncube, E N; Steenkamp, P A; Madala, N E; Dubery, I A

    2016-07-01

    Exogenous application of synthetic and natural elicitors of plant defence has been shown to result in mass production of secondary metabolites with nutraceuticals properties in cultured cells. In particular, salicylic acid (SA) treatment has been reported to induce the production of phenylpropanoids, including cinnamic acid derivatives bound to quinic acid (chlorogenic acids). Centella asiatica is an important medicinal plant with several therapeutic properties owing to its wide spectrum of secondary metabolites. We investigated the effect of SA on C. asiatica cells by monitoring perturbation of chlorogenic acids in particular. Different concentrations of SA were used to treat C. asiatica cells, and extracts from both treated and untreated cells were analysed using an optimised UHPLC-QTOF-MS/MS method. Semi-targeted multivariate data analyses with the aid of principal component analysis (PCA) and orthogonal projection to latent structures-discriminant analysis (OPLS-DA) revealed a concentration-dependent metabolic response. Surprisingly, a range of chlorogenic acid derivatives were found to be downregulated as a consequence of SA treatment. Moreover, irbic acid (3,5-O-dicaffeoyl-4-O-malonilquinic acid) was found to be a dominant CGA in C. asiatica cells, although the SA treatment also had a negative effect on its concentration. Overall SA treatment was found to be an ineffective elicitor of CGA production in cultured C. asiatica cells.

  20. Water, treated as the continuous liquid in and around cells.

    PubMed

    Van Oss, C J; Giese, R F; Docoslis, A

    2001-07-01

    In the quantitative treatment of non-covalent inter- and intra-cellular interactions taking place in water, in vitro as well as in vivo, it is essential to treat the surrounding and pervading liquid medium as the continuous medium. In the close vicinity of inter- and intra-cellular surfaces and of biopolymers the various different non-covalent forces may locally alter the structure of water in a number of ways, but these local structural changes can be quantitatively taken into account. The operative forces are: Lifshitz-van der Waals (LW) forces. Lewis acid-base (AB) forces and electrostatic (EL) forces. Of these, the AB forces are generally the preponderant ones, in aqueous media. This is due, inter alia, to the strong cohesive and adhesive hydrogen-bonding interactions typically occurring in and by water. Among the strong AB interactions occurring in water are hydrophobic attraction (the hydrophobic effect) and hydrophilic repulsion (hydration pressure). Also treated is the function of LW, AB and EL forces in: hydration; in the stability of particle and cell suspensions, the solubility of biopolymers, small organic solutes, and electrolytes; and in specific ligand-receptor (such as antigen-antibody) interactions.

  1. 'Particle genetics': treating every cell as unique.

    PubMed

    Yvert, Gaël

    2014-02-01

    Genotype-phenotype relations are usually inferred from a deterministic point of view. For example, quantitative trait loci (QTL), which describe regions of the genome associated with a particular phenotype, are based on a mean trait difference between genotype categories. However, living systems comprise huge numbers of cells (the 'particles' of biology). Each cell can exhibit substantial phenotypic individuality, which can have dramatic consequences at the organismal level. Now, with technology capable of interrogating individual cells, it is time to consider how genotypes shape the probability laws of single cell traits. The possibility of mapping single cell probabilistic trait loci (PTL), which link genomic regions to probabilities of cellular traits, is a promising step in this direction. This approach requires thinking about phenotypes in probabilistic terms, a concept that statistical physicists have been applying to particles for a century. Here, I describe PTL and discuss their potential to enlarge our understanding of genotype-phenotype relations. PMID:24315431

  2. Characterization of intracellular viral RNA in interferon-treated cells chronically infected with murine leukemia virus.

    PubMed Central

    Salzberg, S; Bakhanashvili, M; Bari, S; Berman, I; Aboud, M

    1980-01-01

    We have recently found that Moloney murine leukemia virus assembles within cytoplasmic vacuoles of chronically infected NIH/3T3 cells rather than at their surface (submitted for publication). In the present study we found that if these cells were treated with interferon (IF) for 24 to 48 h the intracellular virus particles accumulated at a two- to threefold-higher level than that observed in untreated cells. Nevertheless, despite this accumulation, no difference between IF-treated and untreated cells was observed in the amount of the total cytoplasmic viral RNA or in its 35S or 21S species. When cellular virions were sedimented from the cytoplasmic fraction, a markedly higher amount of viral RNA was detected in the viral pellet of IF-treated cells than was detected in untreated cells, whereas the amount of viral RNA left in the virus-free cytoplasm of IF-treated cells was much lower than that in the untreated cells. Furthermore, the amount of the cytoplasmic polyriboadenylic acid-containing viral RNA was also remarkably higher in the IF-treated cells. Viral polyribosomes appeared to be fully functional in IF-treated cells, since no effect of IF on viral protein synthesis could be detected. Analysis of the nuclear viral RNA showed no difference between IF-treated and untreated cells after 24 h of IF treatment. Both contained a comparable amount of 35S viral RNA. However, at 48 h a significant accumulation of viral RNA was observed in the nucleus of the IF-treated cells as compared with the untreated cells, although in both cases only 35S species were evident. This accumulation appeared to activate a degradation process which destroyed nuclear viral RNA, since a dramatic shift toward smaller-sized molecules of viral RNA and a remarkable reduction in its amount were observed after 72 h of IF treatment. PMID:6158581

  3. Ultrastructural evidence for differentiation in a human glioblastoma cell line treated with inhibitors of eicosanoid metabolism

    SciTech Connect

    Wilson, D.E.; Anderson, K.M. ); Seed, T.M. )

    1990-01-01

    Human glioblastoma cells incubated in the presence of inhibitors of eicosanoid biosynthesis show decreased cellular proliferation without cytotoxicity. The authors studied the ultrastructural morphology of a human glioblastoma cell line cultured with nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor, or 5,8,11,14-eicosatetraynoic acid, a cyclooxygenase and lipoxygenase inhibitor. When glioblastoma cells were treated for 3 days with antiproliferative concentrations of either agent, they shared many morphological characteristics, including evidence for increased astrocytic differentiation with only limited signs of toxicity. The inhibited glioma cells demonstrated an increase in the number and length of astrocytic processes containing greater numbers of glial filaments, and the NDGA-treated cells also demonstrated extensive lateral pseudopod formation along the processes. The glioblastoma cell shape also become more elongated, losing the usual nuclear lobularity and nuclear inclusions, especially in NDGA-treated cells. Many cytoplasmic organelles packed the cytosol of the inhibited glioma cells, including prominent Golgi apparatus, dilated smooth endoplasmic reticulum evolving into dilated vesicles, cytoplasmic vacuoles, and numerous concentric laminations. There was limited evidence for toxicity, however, as the mitochondria were more pleomorphic with some mitochondrial distension and disruption of the cristae along with an increase in cytoplasmic vacuolization. The authors conclude that the inhibitors of eicosanoid biosynthesis. NDGA and 5,8,11,14-eicosatetraynoic acid, not only suppress glioblastoma cell proliferation, but also include increased astrocytic differentiation.

  4. Protein Analysis of Sapienic Acid-Treated Porphyromonas gingivalis Suggests Differential Regulation of Multiple Metabolic Pathways

    PubMed Central

    Dawson, Deborah V.; Blanchette, Derek R.; Drake, David R.; Wertz, Philip W.; Brogden, Kim A.

    2015-01-01

    ABSTRACT Lipids endogenous to skin and mucosal surfaces exhibit potent antimicrobial activity against Porphyromonas gingivalis, an important colonizer of the oral cavity implicated in periodontitis. Our previous work demonstrated the antimicrobial activity of the fatty acid sapienic acid (C16:1Δ6) against P. gingivalis and found that sapienic acid treatment alters both protein and lipid composition from those in controls. In this study, we further examined whole-cell protein differences between sapienic acid-treated bacteria and untreated controls, and we utilized open-source functional association and annotation programs to explore potential mechanisms for the antimicrobial activity of sapienic acid. Our analyses indicated that sapienic acid treatment induces a unique stress response in P. gingivalis resulting in differential expression of proteins involved in a variety of metabolic pathways. This network of differentially regulated proteins was enriched in protein-protein interactions (P = 2.98 × 10−8), including six KEGG pathways (P value ranges, 2.30 × 10−5 to 0.05) and four Gene Ontology (GO) molecular functions (P value ranges, 0.02 to 0.04), with multiple suggestive enriched relationships in KEGG pathways and GO molecular functions. Upregulated metabolic pathways suggest increases in energy production, lipid metabolism, iron acquisition and processing, and respiration. Combined with a suggested preferential metabolism of serine, which is necessary for fatty acid biosynthesis, these data support our previous findings that the site of sapienic acid antimicrobial activity is likely at the bacterial membrane. IMPORTANCE P. gingivalis is an important opportunistic pathogen implicated in periodontitis. Affecting nearly 50% of the population, periodontitis is treatable, but the resulting damage is irreversible and eventually progresses to tooth loss. There is a great need for natural products that can be used to treat and/or prevent the overgrowth of

  5. Steroidogenesis in amlodipine treated purified Leydig cells

    SciTech Connect

    Latif, Rabia; Lodhi, Ghulam Mustafa; Hameed, Waqas; Aslam, Muhammad

    2012-01-01

    Drugs have been shown to adversely affect male fertility and recently anti-hypertensive drugs were added to the list. The anti-fertility effects of amlodipine, a calcium channel blocker, are well-illustrated in in vivo experiments but lack an in vitro proof. The present study was designed to experimentally elucidate the effects of amlodipine on Leydig cell steroidogenesis and intracellular calcium in vitro. Leydig cells of Sprague–Dawley rats were isolated and purified by Percoll. Cells were incubated for 3 h with/without amlodipine in the presence/absence of LH, dbcAMP, Pregnenolone and 25-Hydroxycholesterol. Cytosolic calcium was measured in purified Leydig cells by fluorometric technique. The results showed significantly reduced (P < 0.05) steroidogenesis and intracellular calcium in amlodipine exposed rats. The site of amlodipine induced steroidogenic inhibition seems to be prior to the formation of Pregnenolone at the level of StAR protein. -- Highlights: ► Inhibition of steroidogenesis in isolated and purified Leydig cells by amlodipine. ► Site of inhibition was before Pregnenolone formation, at the level of StAR protein. ► Inhibition of LH stimulated rise in cytosolic calcium by amlodipine.

  6. Epidermodysplasia verruciformis treated using topical 5-aminolaevulinic acid photodynamic therapy.

    PubMed

    Karrer, S; Szeimies, R M; Abels, C; Wlotzke, U; Stolz, W; Landthaler, M

    1999-05-01

    We describe a 65-year-old woman who had had wart-like lesions on the hands, lower arms and forehead for about 45 years. She had already had several basal cell carcinomas excised. Histological study, electron microscopy and in situ hybridization [human papilloma virus (HPV)-types 5/8/12/14/19-23/25/36] of skin biopsies confirmed a diagnosis of epidermodysplasia verruciformis (EV). Photodynamic therapy (PDT) was performed using a 20% 5-aminolaevulinic acid ointment applied for 6 h to the lesions and irradiating using an incoherent light source (lambda = 580-740 nm, 160 mW/cm2, 160 J/cm2). Following PDT, blistering and crusting of the lesions occurred, but these healed completely within 2-3 weeks without scarring, and the cosmetic result was excellent. Six months after PDT a skin biopsy was taken. In situ hybridization was positive for HPV type 8 in skin which was clinically and histologically normal. Twelve months after PDT a few lesions had recurred on the hands. Although permanent cure of EV cannot be achieved by any therapy at present and single lesions continue to appear in this patient, topical PDT might result in better control of HPV-induced lesions.

  7. Epidermodysplasia verruciformis treated using topical 5-aminolaevulinic acid photodynamic therapy.

    PubMed

    Karrer, S; Szeimies, R M; Abels, C; Wlotzke, U; Stolz, W; Landthaler, M

    1999-05-01

    We describe a 65-year-old woman who had had wart-like lesions on the hands, lower arms and forehead for about 45 years. She had already had several basal cell carcinomas excised. Histological study, electron microscopy and in situ hybridization [human papilloma virus (HPV)-types 5/8/12/14/19-23/25/36] of skin biopsies confirmed a diagnosis of epidermodysplasia verruciformis (EV). Photodynamic therapy (PDT) was performed using a 20% 5-aminolaevulinic acid ointment applied for 6 h to the lesions and irradiating using an incoherent light source (lambda = 580-740 nm, 160 mW/cm2, 160 J/cm2). Following PDT, blistering and crusting of the lesions occurred, but these healed completely within 2-3 weeks without scarring, and the cosmetic result was excellent. Six months after PDT a skin biopsy was taken. In situ hybridization was positive for HPV type 8 in skin which was clinically and histologically normal. Twelve months after PDT a few lesions had recurred on the hands. Although permanent cure of EV cannot be achieved by any therapy at present and single lesions continue to appear in this patient, topical PDT might result in better control of HPV-induced lesions. PMID:10354037

  8. Enhanced lymphocyte proliferation in patients with adrenoleukodystrophy treated with erucic acid (22:1)-rich triglycerides.

    PubMed

    Pour, R B; Stöckler-Ipsiroglu, S; Hunneman, D H; Gahr, M; Korenke, G C; Pabst, W; Hanefeld, F; Peters, A

    2000-03-01

    Lymphocytopenia and depression of natural killer cells have been observed in patients with adrenoleukodystrophy (ALD) treated with glycerol trioleate and glycerol trierucate ('Lorenzo's oil'). To investigate possible alterations of cellular immunoreactivity, we measured lymphocyte proliferation in response to mitogens (PHA, Con A, PWM, OKT3) in 27 patients on treatment and in 14 patients without treatment. In patients on treatment, lymphocyte proliferation in response to the mitogens PHA and Con A was significantly higher than in patients without treatment. Lymphocyte proliferation in patients without treatment was comparable to that of normal control lymphocytes. Additionally, we found increased concentrations of erucic acid, C22:1, in lymphocytes from patients with treatment. The enhanced proliferation of lymphocytes in response to mitogens is an indication of increased reactivity of cellular immunity to unspecific immunological stimuli. Long-term side-effects on cellular immunoreactivity have to be considered in ALD patients treated with Lorenzo's oil.

  9. Osteoclasts but not osteoblasts are affected by a calcified surface treated with zoledronic acid in vitro

    SciTech Connect

    Schindeler, Aaron . E-mail: AaronS@chw.edu.au; Little, David G.

    2005-12-16

    Bisphosphonates are potent inhibitors of osteoclast-mediated bone resorption. Recent interest has centered on the effects of bisphosphonates on osteoblasts. Chronic dosing of osteoblasts with solubilized bisphosphonates has been reported to enhance osteogenesis and mineralization in vitro. However, this methodology poorly reflects the in vivo situation, where free bisphosphonate becomes rapidly bound to mineralized bone surfaces. To establish a more clinically relevant cell culture model, we cultured bone cells on calcium phosphate coated quartz discs pre-treated with the potent nitrogen-containing bisphosphonate, zoledronic acid (ZA). Binding studies utilizing [{sup 14}C]-labeled ZA confirmed that the bisphosphonate bound in a concentration-dependent manner over the 1-50 {mu}M dose range. When grown on ZA-treated discs, the viability of bone-marrow derived osteoclasts was greatly reduced, while the viability and mineralization of the osteoblastic MC3T3-E1 cell line were largely unaffected. This suggests that only bone resorbing cells are affected by bound bisphosphonate. However, this system does not account for transient exposure to unbound bisphosphonate in the hours following a clinical dosing. To model this event, we transiently treated osteoblasts with ZA in the absence of a calcified surface. Osteoblasts proved highly resistant to all transitory treatment regimes, even when utilizing ZA concentrations that prevented mineralization and/or induced cell death when dosed chronically. This study represents a pharmacologically more relevant approach to modeling bisphosphonate treatment on cultured bone cells and implies that bisphosphonate therapies may not directly affect osteoblasts at bone surfaces.

  10. How I treat Langerhans cell histiocytosis

    PubMed Central

    Allen, Carl E.; Ladisch, Stephan

    2015-01-01

    “Langerhans cell histiocytosis” (LCH) describes a spectrum of clinical presentations ranging from a single bone lesion or trivial skin rash to an explosive disseminated disease. Regardless of clinical severity, LCH lesions share the common histology of CD1a+/CD207+ dendritic cells with characteristic morphology among an inflammatory infiltrate. Despite historical uncertainty defining LCH as inflammatory vs neoplastic and incomplete understanding of mechanisms of pathogenesis, clinical outcomes have improved markedly over the past decades through cooperative randomized clinical trials based on empiric therapeutic strategies. Significant advances include recognition of high- and low-risk clinical groups defined by hematopoietic and/or hepatic involvement, and of the importance of optimal intensity and of duration of chemotherapy. Nevertheless, mortality of high-risk patients, disease recurrence, lack of robustly tested salvage strategies, and significant disease morbidity of both high- and low-risk patients remain challenges. Recent discovery of recurrent somatic mutations in mitogen-activated protein kinase pathway genes at critical stages of myeloid hematopoietic differentiation in LCH patients supports redefinition of the disease as a myeloproliferative disorder and provides opportunities to develop novel approaches to diagnosis and therapy. PMID:25827831

  11. The importance of 1,2-dithiolane structure in α-lipoic acid for the downregulation of cell surface β1-integrin expression of human bladder cancer cells.

    PubMed

    Yamasaki, Masao; Soda, Shozen; Sakakibara, Yoichi; Suiko, Masahito; Nishiyama, Kazuo

    2014-01-01

    Here, we show that cell surface β1-integrin expression, cell adhesion to fibronectin, migration, and invasion were all significantly inhibited by α-lipoic acid. These effects were not observed when cells were treated with dihydrolipoic acid or caprylic acid. These data reveal that the 1,2-dithiolane structure plays an important role in the action of α-lipoic acid.

  12. Immunological considerations for treating globoid cell leukodystrophy.

    PubMed

    Karumuthil-Melethil, Subha; Gray, Steven J

    2016-11-01

    Globoid cell leukodystrophy (GLD, or Krabbe's disease) is a severe inherited neurodegenerative disease caused by the lack of a lysosomal enzyme, GALC. The disease has been characterized in humans as well as three naturally occurring animal models, murine, canine, and nonhuman primate. Multiple treatment strategies have been explored for GLD, including enzyme replacement therapy, small-molecule pharmacological approaches, gene therapy, and bone marrow transplant. No single therapeutic approach has proved to be entirely effective, and the reason for this is not well understood. It is unclear whether initiation of a neuroinflammatory cascade in GLD precedes demyelination, a hallmark of the disease, but it does precede overt symptoms. This Review explores what is known about the role of inflammation and the immune response in the progression of GLD as well as how various treatment strategies might interplay with innate and adaptive immune responses involved in GLD. The focus of this Review is on GLD, but these concepts may have relevance for other, related diseases. © 2016 Wiley Periodicals, Inc. PMID:27638617

  13. Valproic Acid Induced Hyperammonemia in a Long Time Treated Patient

    PubMed Central

    Seide, Margaret; Stern, Robert G.

    2016-01-01

    We report a case of a patient who had been on long time valproic acid for treatment of bipolar affective disorder. While being an inpatient, serology ammonia level testing revealed a very high ammonia level despite being asymptomatic. Dual therapy of carnitine and lactulose was provided to the patient for treatment of the hyperammonemia. It should also be noted that, during this treatment, valproic acid was not stopped. Consequently, this case illustrates that patients can present asymptomatically despite very high ammonia levels and hyperammonemia can occur in chronic valproic acid despite not increasing the dose of the medication and psychiatrists do not need to discontinue valproic acid in the presence of elevated levels of ammonia if the patient shows no signs of encephalopathy or delirium. PMID:27516916

  14. Valproic Acid Induced Hyperammonemia in a Long Time Treated Patient.

    PubMed

    Aiyer, Rohit; Seide, Margaret; Stern, Robert G

    2016-01-01

    We report a case of a patient who had been on long time valproic acid for treatment of bipolar affective disorder. While being an inpatient, serology ammonia level testing revealed a very high ammonia level despite being asymptomatic. Dual therapy of carnitine and lactulose was provided to the patient for treatment of the hyperammonemia. It should also be noted that, during this treatment, valproic acid was not stopped. Consequently, this case illustrates that patients can present asymptomatically despite very high ammonia levels and hyperammonemia can occur in chronic valproic acid despite not increasing the dose of the medication and psychiatrists do not need to discontinue valproic acid in the presence of elevated levels of ammonia if the patient shows no signs of encephalopathy or delirium. PMID:27516916

  15. [Studies on transdermal delivery of ferulic acid through rat skin treated by microneedle arrays].

    PubMed

    Yang, Bing; Du, Shou-ying; Bai, Jie; Shang, Ke-xin; Lu, Yang; Li, Peng-yue

    2014-12-01

    In order to investigate the characteristics of transdermal delivery of ferulic acid under the treated of microneedle arrays and the influence on permeability of rat skin capillaries, improved Franz-cells were used in the transdermal delivery experiment with the rat skin of abdominal wall and the length of microneedle arrays, different insertion forces, retention time were studied in the influence of characteristics of transdermal delivery of FA. The amount of FA was determined by HPLC system. Intravenous injection Evans blue and FA was added after microneedle arrays treated. Established inflammation model was built by daubing dimethylbenzene. The amount of Evans blue in the rat skin was read at 590 nm wavelength with a Multiskan Go microplate reader. Compared with passive diffusion group the skin pretreated with microneedle arrays had a remarkable enhancement of FA transport (P <0.01). The accumulation of FA increased with the enhancement of insertion force as to as the increase of retention time. Microneedle arrays with different length had a remarkable enhancement of FA transport, but was not related to the increase of the length. The research of FA on the reduce of permeability of rat skin capillaries indicated that the skin pretreated with microneedle arrays could reduce the content of Evans blue in the skins of rat significantly compared with the untreated group. The permeation rate of ferulic acid transdermal delivery had remarkable increase under the treated of microneedle arrays and the length of microneedle arrays ,the retention time so as to the insertion force were important to the transdermal delivery of ferulic acid. PMID:25898576

  16. ER-Dependent Ca++-mediated Cytosolic ROS as an Effector for Induction of Mitochondrial Apoptotic and ATM-JNK Signal Pathways in Gallic Acid-treated Human Oral Cancer Cells.

    PubMed

    Lu, Yao-Cheng; Lin, Meng-Liang; Su, Hong-Lin; Chen, Shih-Shun

    2016-02-01

    Release of calcium (Ca(++)) from the endoplasmic reticulum (ER) has been proposed to be involved in induction of apoptosis by oxidative stress. Using inhibitor of ER Ca(++) release dantrolene and inhibitor of mitochondrial Ca(++) uptake Ru-360, we demonstrated that Ca(++) release from the ER was associated with generation of reactive oxygen species (ROS), loss of mitochondrial membrane potential, and apoptosis of human oral cancer (OC) cells induced by gallic acid (GA). Small interfering RNA-mediated suppression of protein kinase RNA-like endoplasmic reticulum kinase inhibited tunicamycin-induced induction of 78 kDa glucose-regulated protein, C/EBP homologous protein, pro-caspase-12 cleavage, cytosolic Ca(++) increase and apoptosis, but did not attenuate the increase in cytosolic Ca(++) level and apoptosis induced by GA. Ataxia telangiectasia mutated (ATM)-mediated c-Jun N-terminal kinase (JNK) phosphorylation and apoptosis by GA was blocked by dantrolene. The specificity of ROS-mediated ATM-JNK activation was confirmed by treatment with N-acetylcysteine, a ROS scavenger. Blockade of ATM activation by specific inhibitor KU55933, short hairpin RNA, or kinase-dead ATM overexpression suppressed JNK phosphorylation but did not completely inhibit cytosolic ROS production, mitochondrial cytochrome c release, pro-caspase-3 cleavage, and apoptosis induced by GA. Taken together, these results indicate that GA induces OC cell apoptosis by inducing the activation of mitochondrial apoptotic and ATM-JNK signal pathways, likely through ER Ca(++)-mediated ROS production. PMID:26851027

  17. ER-Dependent Ca++-mediated Cytosolic ROS as an Effector for Induction of Mitochondrial Apoptotic and ATM-JNK Signal Pathways in Gallic Acid-treated Human Oral Cancer Cells.

    PubMed

    Lu, Yao-Cheng; Lin, Meng-Liang; Su, Hong-Lin; Chen, Shih-Shun

    2016-02-01

    Release of calcium (Ca(++)) from the endoplasmic reticulum (ER) has been proposed to be involved in induction of apoptosis by oxidative stress. Using inhibitor of ER Ca(++) release dantrolene and inhibitor of mitochondrial Ca(++) uptake Ru-360, we demonstrated that Ca(++) release from the ER was associated with generation of reactive oxygen species (ROS), loss of mitochondrial membrane potential, and apoptosis of human oral cancer (OC) cells induced by gallic acid (GA). Small interfering RNA-mediated suppression of protein kinase RNA-like endoplasmic reticulum kinase inhibited tunicamycin-induced induction of 78 kDa glucose-regulated protein, C/EBP homologous protein, pro-caspase-12 cleavage, cytosolic Ca(++) increase and apoptosis, but did not attenuate the increase in cytosolic Ca(++) level and apoptosis induced by GA. Ataxia telangiectasia mutated (ATM)-mediated c-Jun N-terminal kinase (JNK) phosphorylation and apoptosis by GA was blocked by dantrolene. The specificity of ROS-mediated ATM-JNK activation was confirmed by treatment with N-acetylcysteine, a ROS scavenger. Blockade of ATM activation by specific inhibitor KU55933, short hairpin RNA, or kinase-dead ATM overexpression suppressed JNK phosphorylation but did not completely inhibit cytosolic ROS production, mitochondrial cytochrome c release, pro-caspase-3 cleavage, and apoptosis induced by GA. Taken together, these results indicate that GA induces OC cell apoptosis by inducing the activation of mitochondrial apoptotic and ATM-JNK signal pathways, likely through ER Ca(++)-mediated ROS production.

  18. Ascorbic acid transport into cultured pituitary cells

    SciTech Connect

    Cullen, E.I.; May, V.; Eipper, R.A.

    1986-05-01

    An amidating enzyme designated peptidyl-glycine ..cap alpha..-amidating monooxygenase (PAM) has been studied in a variety of tissues and is dependent on molecular oxygen and stimulated by copper and ascorbic acid. To continue investigating the relationship among cellular ascorbic acid concentrations, amidating ability, and PAM activity, the authors studied ascorbic acid transport in three cell preparations that contain PAM and produce amidated peptides: primary cultures of rat anterior and intermediate pituitary and mouse AtT-20 tumor cells. When incubated in 50 ..mu..M (/sup 14/C)ascorbic acid all three cell preparations concentrated ascorbic acid 20- to 40-fold, producing intracellular ascorbate concentrations of 1 to 2 mM, based on experimentally determined cell volumes. All three cell preparations displayed saturable ascorbic acid uptake with half-maximal initial rates occurring between 9 and 18 ..mu..M ascorbate. Replacing NaCl in the uptake buffer with choline chloride significantly diminished ascorbate uptake in all three preparations. Ascorbic acid efflux from these cells was slow, displaying half-lives of 7 hours. Unlike systems that transport dehydroascorbic acid, the transport system for ascorbic acid in these cells was not inhibited by glucose. Thus, ascorbate is transported into pituitary cells by a sodium-dependent, active transport system.

  19. Electrochemical activity of iron in acid treated bentonite and influence of added nickel

    NASA Astrophysics Data System (ADS)

    Mudrinić, T.; Mojović, Z.; Milutinović-Nikolić, A.; Mojović, M.; Žunić, M.; Vukelić, N.; Jovanović, D.

    2015-10-01

    Bentonite originated from Mečji Do, Serbia, was submitted to acid treatment at 70 °C for 30 min, while only the concentration of applied HCl varied. The obtained acid treated samples were used to modify glassy carbon (GC) electrode. The effect of applied acid treatment on the electrochemical behavior of GC electrodes modified with these materials was investigated. Furthermore, the effect of the introduction of nickel into acid treated samples was studied. The incorporation of nickel into acid treated bentonite was achieved by either ion exchange or impregnation/decomposition method. The obtained samples were characterized using the following methods: inductively coupled plasma (ICP), X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy and electron spin resonance (ESR) spectroscopy. The electrochemical behavior of these samples was tested by cyclic voltammetry in 0.1 mol dm-3 H2SO4 solution. The ICP, FTIR and ESR results exhibited a slight decrease of iron content in the acid treated samples. XRD and FTIR results confirmed that the conditions applied for the acid treatment were mild enough for the smectite structure to be preserved. The electrocatalytic test showed that the current response of Fe2+/Fe3+ oxidation/reduction process increased on the GC electrodes separately modified with each of the acid treated samples in comparison with current obtained on the GC electrode modified with untreated sample. These results indicated that applied acid treatment probably increased the accessibility of the electroactive iron within smectite. Cyclic voltammograms obtained for the GC electrodes modified with acid treated bentonite materials showed greater anodic charge (qa) than cathodic charge (qc). This difference might be due to iron detachment from smectite structure during the oxidation process. Further modification of the selected acid treated sample with nickel species resulted in decreased current response of the Fe2+/Fe3+ oxidation

  20. Aminomethylphosphonic acid accumulation in plant species treated with glyphosate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aminomethylphosphonic acid (AMPA) is the most frequently detected metabolite of glyphosate in plants. Greenhouse studies were conducted to determine the glyphosate I50 values (rate required to cause a 50% reduction in plant growth) and to quantify AMPA and shikimate concentrations in selected legum...

  1. Decreased stability of DNA in cells treated with alkylating agents

    SciTech Connect

    Frankfurt, O.S. )

    1990-12-01

    A modified highly sensitive procedure for the evaluation of DNA damage in individual cells treated with alkylating agents is reported. The new methodology is based on the amplification of single-strandedness in alkylated DNA by heating in the presence of Mg{sup 2+}. Human ovarian carcinoma cells A2780 were treated with nitrogen mustard (HN2), fixed in methanol, and stained with monoclonal antibody (MOAB) F7-26 generated against HN2-treated DNA. Binding of MOAB was measured by flow cytometry with indirect immunofluorescence. Intensive binding of MOAB to control and drug-treated cells was observed after heating in Tris buffer supplemented with MgCl{sub 2}. Thus, the presence of phosphates and MgCl{sub 2} during heating was necessary for the detection of HN2-induced changes in DNA stability. Fluorescence of HN2-treated cells decreased to background levels after treatment with single-strand-specific S{sub 1} nuclease. MOAB F7-26 interacted with single-stranded regions in DNA and did not bind to dsDNA or other cellular antigens. It is suggested that alkylation of guanines decreased the stability of the DNA molecule and increased the access of MOAB F7-26 to deoxycytidines on the opposite DNA strand.

  2. Stabilizing platinum in phosphoric acid fuel cells

    NASA Technical Reports Server (NTRS)

    Remick, R. J.

    1982-01-01

    Platinum sintering on phosphoric acid fuel cell cathodes is discussed. The cathode of the phosphoric acid fuel cell uses a high surface area platinum catalyst dispersed on a conductive carbon support to minimize both cathode polarization and fabrication costs. During operation, however, the active surface area of these electrodes decreases, which in turn leads to decreased cell performance. This loss of active surface area is a major factor in the degradation of fuel cell performance over time.

  3. Raman spectroscopic analysis of cytotoxic effect of cisplatin-treated leukemic cells

    NASA Astrophysics Data System (ADS)

    Lin, Juqiang; Li, Yongzeng; Feng, Shangyuan; Chen, Rong; Chen, Guannan; Chen, Qisong; Pan, Jianji; Lin, Shaojun; Yu, Yun

    2009-08-01

    An antitumor drug cisplatin was employed to treat the leukemic cells and induce apoptosis of the cancer cells. Confocal Raman micro-spectroscopy has been applied to investigate the effectiveness of the treatment using near-infrared laser (785nm) excitation, scanning range from 500 to 2000 cm-1. The Raman spectra of leukemic cell treated with cisplatin for 4, 6, 8, 12 and 14 h were measured separately. The major difference of the apoptotic cells from the cancer cells are the reduction in intensities of vibration bands generated by cellular lipids, proteins and nucleic acids. In particular, large intensity reduction in nucleic vibrations at 782, 1092, 1320, 1340, and 1578 cm-1 was observed upon apoptosis of the leukemic cells. Up to 45% reduction in the magnitude of the 782 cm-1 peak in Raman spectra of the apoptotic cells was observed, which suggests the breakdown of phosphodiester bonds and DNA bases. We showed that the principal components analysis (PCA), a multivariate statistical tool, can be used to distinguish single apoptotic cells and leukemic cells based on their Raman spectra. Our results indicate that the Raman spectroscopy with PCA is a novel, nondestructive mean for studying the cisplatin -treated leukemic cells, which could also provide useful data for clinical dosage optimization for cisplatin.

  4. Heterologous mesenchymal stem cells successfully treat femoral pseudarthrosis in rats

    PubMed Central

    2012-01-01

    Background This study evaluated the effectiveness of treating pseudarthrosis in rats by using bone marrow cell suspensions or cultures of bone marrow mesenchymal stromal cells Methods Thirty-eight specific pathogen-free (SPF) animals were randomly assigned to four groups: Group 1, Control, without surgical intervention; Group 2 (Placebo), experimental model of femoral pseudarthrosis treated only with saline solution; Group 3, experimental model of femoral pseudarthrosis treated with heterologous bone marrow cells suspension; Group 4, experimental model of femoral pseudarthrosis treated with cultures of heterologous mesenchymal stromal cells from bone marrow. When pseudarthrosis was confirmed by simple radiological studies, digital radiography and histopathology after a 120-day postoperative period, Groups 2, 3 and 4 were treated as above. At 30, 60 and 90 days after the treatment, all animals were evaluated by simple radiological studies, and at the end of the experiment, the animals were assessed by computed axial tomography and anatomopathological and histomorphometric examinations. Results Injected cells were detected in the areas affected by pseudarthrosis using scintigraphy within the first 24 hours after their administration. After 60 days, the animals of Group 3 showed callus formation while the animals of Group 4 presented periosteal reaction and had some consolidated areas. In contrast, Group 2 showed a predominance of fibro-osteoid tissue. After 90 days, bone consolidation and remodeling was observed in all animals from Group 3 whereas animals from Group 4 exhibited partial consolidation and those ones from Group 2 persisted with pseudarthrosis. Conclusion The treatment with heterologous bone marrow cells suspension proved to be effective in the treatment of pseudarthrosis whereas cultures of heterologous bone marrow mesenchymal stromal cells did not show the same potential to aid bone healing. PMID:22429995

  5. Alpha-amino acid behaves differently from beta- or gamma-amino acids as treated by trimetaphosphate.

    PubMed

    Gao, X; Liu, Y; Xu, P X; Cai, Y M; Zhao, Y F

    2008-01-01

    The condensation reactions of sodium trimetaphosphate with single amino acids, namely glycine, L-alanine, beta-alanine and gamma-aminobutyric acid or pairs of these amino acids were reinvestigated by electrospray ion-trap mass spectrometry and high performance liquid chromatography. It was found when mixtures were treated by sodium trimetaphosphate only in the presence of alpha-amino acid dipeptides were formed. Without addition of alpha-amino acids, the beta-amino acid or gamma-aminobutyric acid could not form peptide either by themselves or with their mixtures under the same conditions. From the data it is concluded that phosphate might select alpha-amino acids to produce the peptides being important precursors for the origin of life. PMID:17973074

  6. Quantitative Proteomics Reveals the Flooding-Tolerance Mechanism in Mutant and Abscisic Acid-Treated Soybean.

    PubMed

    Yin, Xiaojian; Nishimura, Minoru; Hajika, Makita; Komatsu, Setsuko

    2016-06-01

    Flooding negatively affects the growth of soybean, and several flooding-specific stress responses have been identified; however, the mechanisms underlying flooding tolerance in soybean remain unclear. To explore the initial flooding tolerance mechanisms in soybean, flooding-tolerant mutant and abscisic acid (ABA)-treated plants were analyzed. In the mutant and ABA-treated soybeans, 146 proteins were commonly changed at the initial flooding stress. Among the identified proteins, protein synthesis-related proteins, including nascent polypeptide-associated complex and chaperonin 20, and RNA regulation-related proteins were increased in abundance both at protein and mRNA expression. However, these proteins identified at the initial flooding stress were not significantly changed during survival stages under continuous flooding. Cluster analysis indicated that glycolysis- and cell wall-related proteins, such as enolase and polygalacturonase inhibiting protein, were increased in abundance during survival stages. Furthermore, lignification of root tissue was improved even under flooding stress. Taken together, these results suggest that protein synthesis- and RNA regulation-related proteins play a key role in triggering tolerance to the initial flooding stress in soybean. Furthermore, the integrity of cell wall and balance of glycolysis might be important factors for promoting tolerance of soybean root to flooding stress during survival stages.

  7. Constructed wetlands for treating acid drainage at TVA Facilities: Progress report

    SciTech Connect

    Tomljanovich, D.A.; Brodie, G.A.; Hammer, D.A.

    1988-03-01

    A comprehensive overview is presented of TVA's use of constructed wetlands to naturally treat water quality problems associated with acid drainage at its fossil plants and the inactive Fabius Coal Mine and Preparation Plant in Jackson County, Alabama. TVA constructed its first wetland in May 1985. As of December 1987, a total of eight constructed wetlands, one enhanced natural wetland receiving acid drainage, and one former chemical treatment pond were being monitored as treatment wetlands. Some measure of success is being achieved at all the wetland systems. However, to achieve compliance quality effluent (total Fe <3.0 mg/L, total Mn <2.0 mg/L, pH 6.0--9.0 s.u., and total suspended solids <32.0 mg/L) interim chemical treatment is being used at COF to treat manganese, and at WCF to treat low pH. At KIF, water is being pumped from the final cell of the wetland to the active ashpond as an interim measure until it is shown to consistently yield compliance quality effluent. Chemical treatment is also being used to augment wetlands treatment at the Fabius Impoundment 2 and Impoundment 4 wetlands. Where chemical treatment is required, reduced chemical costs result from some level of wetlands treatment. Successful wetlands treatment has been demonstrated at three sites, where no chemical treatment is required. In the remaining two newly constructed wetlands, insufficient data exist to assess their treatment capability. Overall average construction cost based on nine wetlands was $1.13/ft/sup 2/ ($49,223/ac). Before converting one chemical treatment pond (Fabius Impoundment 3) to a wetland, TVA was annually spending $12,000 to $15,000 for chemicals and $10,000 for pond maintenance that failed to maintain complying discharges. Complying discharges and an annual wetland maintenance cost of about $1000 make the wetland an attractive and cost-beneficial treatment method. 2 refs., 15 figs., 10 tabs.

  8. An analysis of the effectiveness of a constructed wetland treating acid mine drainage

    SciTech Connect

    Huddleston, G.M. III; Grant, A.J.; Ramey, B.A.

    1994-12-31

    Acid mine drainage (AMD) from an abandoned coal mine in southcentral Kentucky had pH levels as low as 2.3 and iron concentrations as high as 641 mg/L. In the summer of 1992, the US Soil Conservation Service constructed a wetland system to treat the AMD that incorporated both physical and biological treatments. The AMD was initially fed into three anoxic limestone beds followed by an aeration pond and four cattail cells. A polishing pond served as the final stage of treatment. Flow of AMD was initiated in the fall of 1992, and treatment effectiveness was monitored for the next year. Chemical analysis and the cladoceran (Ceriodaphnia dubia) survival and reproduction test were performed on water samples collected along the flow path. Water chemistry analysis and determination of toxic levels indicated a substantial increase in pH and removal of metals prior to entering the cattail cells. Water quality in the cattail cells and polishing pond varied throughout the seasons, but had improved substantially by the end of the one-year monitoring period. The use of the wetland system by macroinvertebrates also was evaluated. Results indicated that a limited number of species were found in the cattail cells, while larger numbers were recovered from the polishing pond.

  9. The phosphorylation status and cytoskeletal remodeling of striatal astrocytes treated with quinolinic acid

    SciTech Connect

    Pierozan, Paula; Ferreira, Fernanda; Ortiz de Lima, Bárbara; Gonçalves Fernandes, Carolina; Totarelli Monteforte, Priscila; Castro Medaglia, Natalia de; Bincoletto, Claudia; Soubhi Smaili, Soraya; Pessoa-Pureur, Regina

    2014-04-01

    Quinolinic acid (QUIN) is a glutamate agonist which markedly enhances the vulnerability of neural cells to excitotoxicity. QUIN is produced from the amino acid tryptophan through the kynurenine pathway (KP). Dysregulation of this pathway is associated with neurodegenerative conditions. In this study we treated striatal astrocytes in culture with QUIN and assayed the endogenous phosphorylating system associated with glial fibrillary acidic protein (GFAP) and vimentin as well as cytoskeletal remodeling. After 24 h incubation with 100 µM QUIN, cells were exposed to {sup 32}P-orthophosphate and/or protein kinase A (PKA), protein kinase dependent of Ca{sup 2+}/calmodulin II (PKCaMII) or protein kinase C (PKC) inhibitors, H89 (20 μM), KN93 (10 μM) and staurosporin (10 nM), respectively. Results showed that hyperphosphorylation was abrogated by PKA and PKC inhibitors but not by the PKCaMII inhibitor. The specific antagonists to ionotropic NMDA and non-NMDA (50 µM DL-AP5 and CNQX, respectively) glutamate receptors as well as to metabotropic glutamate receptor (mGLUR; 50 µM MCPG), mGLUR1 (100 µM MPEP) and mGLUR5 (10 µM 4C3HPG) prevented the hyperphosphorylation provoked by QUIN. Also, intra and extracellular Ca{sup 2+} quelators (1 mM EGTA; 10 µM BAPTA-AM, respectively) prevented QUIN-mediated effect, while Ca{sup 2+} influx through voltage-dependent Ca{sup 2+} channel type L (L-VDCC) (blocker: 10 µM verapamil) is not implicated in this effect. Morphological analysis showed dramatically altered actin cytoskeleton with concomitant change of morphology to fusiform and/or flattened cells with retracted cytoplasm and disruption of the GFAP meshwork, supporting misregulation of actin cytoskeleton. Both hyperphosphorylation and cytoskeletal remodeling were reversed 24 h after QUIN removal. Astrocytes are highly plastic cells and the vulnerability of astrocyte cytoskeleton may have important implications for understanding the neurotoxicity of QUIN in neurodegenerative

  10. Effects of citric acid on cultured human osteoblastic cells.

    PubMed

    Guimarães, Lizandra Ferrari; Fidalgo, Tatiana Kelly da Silva; Menezes, Gustavo Conde; Primo, Laura Guimarães; Costa e Silva-Filho, Fernando

    2010-11-01

    We investigated the effects of citric acid (CA) on cultured human osteoblastic (HOB) cells by evaluating cell adhesion, proliferation, and cytotoxicity. (3)H-Thymidine-labeled HOB cells were incubated in culture medium supplemented or not with 4%, 6%, 8%, or 10% CA for 1 minute. After incubation, cell morphology was evaluated by Nomarski interferential light microscopy, cell proliferation was accessed by measurements of (3)H-thymidine associated to the cells, and cell lysis was monitored by measuring the amount of (3)H-thymidine released by cells. We observed that most of the CA-treated cells presented numerous atypical vacuoles, and such cells were also highly polymorphic, exhibiting round-shaped cells. Nonetheless, CA at all concentrations assayed did not yield cytotoxicity as measured by (3)H-containing DNA release, although significant decrease in cell proliferation was observed (P > .05). Furthermore, cells which were treated with CA at the lowest concentration assayed (4%) restored normal proliferation rates 3 days after treatment.

  11. T cells cooperate with palmitic acid in induction of beta cell apoptosis

    PubMed Central

    Cvjetićanin, Tamara; Stojanović, Ivana; Timotijević, Gordana; Stošić-Grujičić, Stanislava; Miljković, Djordje

    2009-01-01

    Background Diabetes is characterized by progressive failure of insulin producing beta cells. It is well known that both saturated fatty acids and various products of immune cells can contribute to the reduction of beta cell viability and functionality during diabetes pathogenesis. However, their joint action on beta cells has not been investigated, so far. Therefore, we explored the possibility that leukocytes and saturated fatty acids cooperate in beta cell destruction. Results Rat pancreatic islets or insulinoma cells (RIN) were co-cultivated with concanavalin A (ConA)-stimulated rat lymph node cells (LNC), or they were treated with cell-free supernatants (Sn) obtained from ConA-stimulated spleen cells or from activated CD3+ cells, in the absence or presence of palmitic acid (PA). ConA-stimulated LNC or Sn and PA cooperated in inducing caspase-3-dependent RIN cell apoptosis. The observed effect of PA and Sn on RIN cell viability was mediated by p38 mitogen-activated protein kinase (MAPK)-signaling and was achieved through auto-destructive nitric oxide (NO) production. The cooperative effect of Sn was mimicked with the combination of interleukin-1β, interleukin-2, interleukin-6, interleukin-17, interferon-γ and tumor necrosis factor-α. Conclusion These results imply that stimulated T cells produce cytokines that cooperate with saturated free fatty acids in beta cell destruction during diabetes pathogenesis. PMID:19463182

  12. Brain Pathology in Adult Rats Treated With Domoic Acid.

    PubMed

    Vieira, A C; Alemañ, N; Cifuentes, J M; Bermúdez, R; Peña, M López; Botana, L M

    2015-11-01

    Domoic acid (DA) is a neurotoxin reported to produce damage to the hippocampus, which plays an important role in memory. The authors inoculated rats intraperitoneally with an effective toxic dose of DA to study the distribution of the toxin in major internal organs by using immunohistochemistry, as well as to evaluate the induced pathology by means of histopathologic and immunohistochemical methods at different time points after toxin administration (6, 10, and 24 hours; 5 and 54 days). DA was detected by immunohistochemistry exclusively in pyramidal neurons of the hippocampus at 6 and 10 hours after dosing. Lesions induced by DA were prominent at 5 days following treatment in selected regions of the brain: hippocampus, amygdala, piriform and perirhinal cortices, olfactory tubercle, septal nuclei, and thalamus. The authors found 2 types of lesions: delayed death of selective neurons and large areas of necrosis, both accompanied by astrocytosis and microgliosis. At 54 days after DA exposure, the pathology was characterized by still-distinguishable dying neurons, calcified lesions in the thalamus, persistent astrocytosis, and pronounced microgliosis. The expression of nitric oxide synthases suggests a role for nitric oxide in the pathogenesis of neuronal degeneration and chronic inflammation induced by DA in the brain.

  13. Inhibitory Activity of (+)-Usnic Acid against Non-Small Cell Lung Cancer Cell Motility

    PubMed Central

    Yang, Yi; Nguyen, Thanh Thi; Jeong, Min-Hye; Crişan, Florin; Yu, Young Hyun; Ha, Hyung-Ho; Choi, Kyung Hee; Jeong, Hye Gwang; Jeong, Tae Cheon; Lee, Kwang Youl; Kim, Kyung Keun; Hur, Jae-Seoun; Kim, Hangun

    2016-01-01

    Lichens are symbiotic organisms that produce various unique chemicals that can be used for pharmaceutical purposes. With the aim of screening new anti-cancer agents that inhibit cancer cell motility, we tested the inhibitory activity of seven lichen species collected from the Romanian Carpathian Mountains against migration and invasion of human lung cancer cells and further investigated the molecular mechanisms underlying their anti-metastatic activity. Among them, Alectoria samentosa, Flavocetraria nivalis, Alectoria ochroleuca, and Usnea florida showed significant inhibitory activity against motility of human lung cancer cells. HPLC results showed that usnic acid is the main compound in these lichens, and (+)-usnic acid showed similar inhibitory activity that crude extract have. Mechanistically, β-catenin-mediated TOPFLASH activity and KITENIN-mediated AP-1 activity were decreased by (+)-usnic acid treatment in a dose-dependent manner. The quantitative real-time PCR data showed that (+)-usnic acid decreased the mRNA level of CD44, Cyclin D1 and c-myc, which are the downstream target genes of both β-catenin/LEF and c-jun/AP-1. Also, Rac1 and RhoA activities were decreased by treatment with (+)-usnic acid. Interestingly, higher inhibitory activity for cell invasion was observed when cells were treated with (+)-usnic acid and cetuximab. These results implied that (+)-usnic acid might have potential activity in inhibition of cancer cell metastasis, and (+)-usnic acid could be used for anti-cancer therapy with a distinct mechanisms of action. PMID:26751081

  14. Spectra investigation on surface characteristics of graphene oxide nanosheets treated with tartaric, malic and oxalic acids.

    PubMed

    Teng, Xiyao; Yan, Manqing; Bi, Hong

    2014-01-24

    The surface characteristics of graphene oxide nanosheets (GO) treated respectively with tartaric acid, malic acid and oxalic acid, have been investigated by mainly using optical spectroscopic methods including Fourier transform infrared spectroscopy (FT-IR), Ultraviolet-visible (UV-Vis) absorption and Raman spectroscopy. Additionally, the electrochemical property of the products has also been studied. The data revealed that oxygen-containing groups such as OH, COOH and CO on the GO surface have been almost removed and thus reduced graphene oxide nanosheets (RGN) were obtained. Interestingly, the number of sp(2) domains of RGN increases as treated by tartaric acidacidacid whereas the steric hindrance (SH) decreases and the ionization constant (IC) differs among these three acids. Furthermore, the specific capacitances (Cs) of GO have been greatly promoted from 2.4 F g(-1) to 100.8, 112.4, and 147 F g(-1) after treated with tartaric, malic and oxalic acids, respectively. This finding agrees well with the spectra result of the tendency of surface conjugated degree alteration. We claim that the difference in both SH and IC among these acids is the main reason for the diverse surface characteristics as well as the improved Cs of the RGN.

  15. Stem cell transplantation and mesenchymal cells to treat autoimmune diseases.

    PubMed

    Tyndall, Alan; van Laar, Jacob M

    2016-06-01

    Since the start of the international stem cell transplantation project in 1997, over 2000 patients have received a haematopoietic stem cell transplant (HSCT), mostly autologous, as treatment for a severe autoimmune disease, the majority being multiple sclerosis (MS), systemic sclerosis (SSc) and Crohn's disease. There was an overall 85% 5-year survival and 43% progression-free survival. Around 30% of patients in all disease subgroups had a complete response, often durable despite full immune reconstitution. In many cases, e.g. systemic sclerosis, morphological improvement such as reduction of skin collagen and normalization of microvasculature was documented, beyond any predicted known effects of intense immunosuppression alone. It is hoped that the results of the three running large prospective randomized controlled trials will allow modification of the protocols to reduce the high transplant-related mortality which relates to regimen intensity, age of patient, and comorbidity. Mesenchymal stromal cells (MSC), often incorrectly called stem cells, have been the intense focus of in vitro studies and animal models of rheumatic and other diseases over more than a decade. Despite multiple plausible mechanisms of action and a plethora of positive in vivo animal studies, few randomised controlled clinical trials have demonstrated meaningful clinical benefit in any condition so far. This could be due to confusion in cell product terminology, complexity of clinical study design and execution or agreement on meaningful outcome measures. Within the rheumatic diseases, SLE and rheumatoid arthritis (RA) have received most attention. Uncontrolled multiple trial data from over 300 SLE patients have been published from one centre suggesting a positive outcome; one single centre comparative study in 172 RA was positive. In addition, small numbers of patients with Crohn's disease, multiple sclerosis, primary Sjögren's disease, polymyositis/dermatomyositis and type II diabetes

  16. Acid-induced secretory cell metaplasia in hamster bronchi

    SciTech Connect

    Christensen, T.G.; Lucey, E.C.; Breuer, R.; Snider, G.L.

    1988-02-01

    Hamsters were exposed to an intratracheal instillation of 0.5 ml of 0.08 N nitric, hydrochloric, or sulfuric acid to determine their airway epithelial response. Three weeks after exposure, the left intrapulmonary bronchi in Alcian blue/PAS-strained paraffin sections were evaluated for the amount of secretory product in the airway epithelium as a measure of secretory cell metaplasia (SCM). Compared to saline-treated control animals, all three acids caused statistically significant SCM. In addition to the bronchial lesion, all three acids caused similar interstitial fibrosis, bronchiolectasis, and bronchiolization of alveoli that varied in individual animals from mild to severe. In a separate experiment to study the persistence of the SCM, hamsters treated with a single instillation of 0.1 N nitric acid showed significant SCM 3, 7, and 17 weeks after exposure. There was a high correlation (r = 0.96) between a subjective assessment of SCM and objective assessment using a digital image-analysis system. We conclude that protons induce SCM independently of the associated anion; the SCM persists at least 17 weeks. Sulfuric acid is an atmospheric pollutant and nitric acid may form locally on the mucosa of lungs exposed to nitrogen dioxide. These acids may contribute to the development of maintenance of the SCM seen in the conducting airways of humans with chronic obstructive pulmonary disease.

  17. Hypotonic swelling of salicylate-treated cochlear outer hair cells.

    PubMed

    Zhi, Man; Ratnanather, J Tilak; Ceyhan, Elvan; Popel, Aleksander S; Brownell, William E

    2007-06-01

    The outer hair cell (OHC) is a hydrostat with a low hydraulic conductivity of Pf=3x10(-4) cm/s across the plasma membrane (PM) and subsurface cisterna that make up the OHC's lateral wall. The SSC is structurally and functionally a transport barrier in normal cells that is known to be disrupted by salicylate. The effect of sodium salicylate on Pf is determined from osmotic experiments in which isolated, control and salicylate-treated OHCs were exposed to hypotonic solutions in a constant flow chamber. The value of Pf=3.5+/-0.5x10(-4) cm/s (mean+/-s.e.m., n=34) for salicylate-treated OHCs was not significantly different from Pf=2.4+/-0.3x10(-4) cm/s (mean+/-s.e.m., n=31) for untreated OHCs (p=.3302). Thus Pf is determined by the PM and is unaffected by salicylate treatment. The ratio of longitudinal strain to radial strain epsilonz/epsilonc=-0.76 for salicylate-treated OHCs was significantly smaller (p=.0143) from -0.72 for untreated OHCs, and is also independent of the magnitude of the applied osmotic challenge. Salicylate-treated OHCs took longer to attain a steady-state volume which is larger than that for untreated OHCs and increased in volume by 8-15% prior to hypotonic perfusion unlike sodium alpha-ketoglutarate-treated OHCs. It is suggested that depolymerization of cytoskeletal proteins and/or glycogen may be responsible for the large volume increase in salicylate-treated OHCs as well as the different responses to different modes of application of the hypotonic solution. PMID:17400411

  18. Dendritic Cells: A Spot on Sialic Acid

    PubMed Central

    Crespo, Hélio J.; Lau, Joseph T. Y.; Videira, Paula A.

    2013-01-01

    Glycans decorating cell surface and secreted proteins and lipids occupy the juncture where critical host–host and host-pathogen interactions occur. The role of glycan epitopes in cell–cell and cell-pathogen adhesive events is already well-established, and cell surface glycan structures change rapidly in response to stimulus and inflammatory cues. Despite the wide acceptance that glycans are centrally implicated in immunity, exactly how glycans and their changes contribute to the overall immune response remains poorly defined. Sialic acids are unique sugars that usually occupy the terminal position of the glycan chains and may be modified by external factors, such as pathogens, or upon specific physiological cellular events. At cell surface, sialic acid-modified structures form the key fundamental determinants for a number of receptors with known involvement in cellular adhesiveness and cell trafficking, such as the Selectins and the Siglec families of carbohydrate recognizing receptors. Dendritic cells (DCs) preside over the transition from innate to the adaptive immune repertoires, and no other cell has such relevant role in antigen screening, uptake, and its presentation to lymphocytes, ultimately triggering the adaptive immune response. Interestingly, sialic acid-modified structures are involved in all DC functions, such as antigen uptake, DC migration, and capacity to prime T cell responses. Sialic acid content changes along DC differentiation and activation and, while, not yet fully understood, these changes have important implications in DC functions. This review focuses on the developmental regulation of DC surface sialic acids and how manipulation of DC surface sialic acids can affect immune-critical DC functions by altering antigen endocytosis, pathogen and tumor cell recognition, cell recruitment, and capacity for T cell priming. The existing evidence points to a potential of DC surface sialylation as a therapeutic target to improve and diversify DC

  19. Modification of growth of neuroblastoma cells in syngeneic mice by aldehyde-treated neuroblastoma cells.

    PubMed

    Bertolini, L; Diamond, L; Revoltella, R

    1976-06-01

    Pretreatment of syngeneic strain A mice with aldehyde-fixed neuroblastoma cells (clone NB6R) almost completely protected the mice against challenge with viable NB6R cells. In contrast, tumor growth was enhanced in mice treated with fixed cells after challenge with viable cells.

  20. Inactivation of metalloenzymes by lysinoalanine, phenylethylaminoalanine, alkali-treated food proteins, and sulfur amino acids.

    PubMed

    Friedman, M; Grosjean, O K; Zahnley, J C

    1986-01-01

    Synthetic lysinoalanine (LAL) may be a more effective inhibitor of the zinc-containing enzyme carboxypeptidase A than is ethylenediamine tetraacetic acid (EDTA). The enzyme is also inactivated by alkali-treated, lysinoalanine-containing food proteins such as casein, high-lysine corn protein, lactalbumin, soy protein isolate, and wheat gluten, and by alkali-treated zein, which contains no lysinoalanine. Zinc sulfate regenerates only part of the enzymatic activity after exposure to the treated proteins. The extent of inhibition increases with protein concentration and time of treatment. Any inhibition due to phytate is distinct from that due to the treatment. Phenylethylaminoalanine (PEAA), derived from biogenic phenylethylamine, inhibited enzymatic activity of the metalloenzyme carboxypeptidase A (CPA). The inhibition was maximal at pH 7.0 in the pH range 7 to 8.5. The extent of inhibition increased with time of treatment and PEAA concentration. N-acetyl-PEAA did not inhibit the enzyme, suggesting that the free alpha-NH2 group is required for inhibition. PEAA, LAL, sodium phytate, and cysteine also inactivated the copper enzyme, polyphenol, oxidase (tyrosinase) which plays a major role in enzymatic (oxidative) browning of foods. Analogous comparative studies with LAL, EDTA, and sodium phytate suggest that the potency of PEAA as an inhibitor of CPA is similar to that of sodium phytate, and that of the four compounds tested, PEAA is least effective against tyrosinase. Related studies of the iron and copper containing enzyme cytochrome C oxidase showed that EDTA was not inhibitory, PEAA was slightly inhibitory, and LAL and sodium phytate were stronger inhibitors. Mechanistic explanations are offered to account for some of these observations. The possible relevance of these findings to in vivo protein digestion, enzymatic (oxidative) browning of foods, and the mechanism of the lysinoalanine effect on kidney cells are also discussed.

  1. Okadaic acid inhibits cell multiplication and induces apoptosis in a549 cells, a human lung adenocarcinoma cell line

    PubMed Central

    Wang, Renjun; Lv, Lili; Zhao, Yunfeng; Yang, Nana

    2014-01-01

    This essay aims to research the effect of okadaic acid (OA) on A549 cell multiplication, and cell apoptosis induced by OA was observed by cell morphology. MTT assay, trypan blue exclusion test (TBET), Giemsa staining method and acridine orange (AO) fluorescence staining assay were applied. The results of cell survival evaluated by TBET and colorimetric assay with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) showed: The number of A549 cells was decreased in a dose-dependent manner. Cytomorphology observation of okadaic acid-treated cells showed that cells became shrinkage and turned round, some cells floated in the nutrient medium with nucleus agglutination broken, resulting in apoptotic bodies. Above-mentioned results indicated that OA exerted significantly inhibitory effect on A549 cell multiplication due to the apoptosis induced by OA. PMID:25232383

  2. Anacardic Acid, Salicylic Acid, and Oleic Acid Differentially Alter Cellular Bioenergetic Function in Breast Cancer Cells.

    PubMed

    Radde, Brandie N; Alizadeh-Rad, Negin; Price, Stephanie M; Schultz, David J; Klinge, Carolyn M

    2016-11-01

    Anacardic acid is a dietary and medicinal phytochemical that inhibits breast cancer cell proliferation and uncouples oxidative phosphorylation (OXPHOS) in isolated rat liver mitochondria. Since mitochondrial-targeted anticancer therapy (mitocans) may be useful in breast cancer, we examined the effect of anacardic acid on cellular bioenergetics and OXPHOS pathway proteins in breast cancer cells modeling progression to endocrine-independence: MCF-7 estrogen receptor α (ERα)+ endocrine-sensitive; LCC9 and LY2 ERα+, endocrine-resistant, and MDA-MB-231 triple negative breast cancer (TNBC) cells. At concentrations similar to cell proliferation IC50 s, anacardic acid reduced ATP-linked oxygen consumption rate (OCR), mitochondrial reserve capacity, and coupling efficiency while increasing proton leak, reflecting mitochondrial toxicity which was greater in MCF-7 compared to endocrine-resistant and TNBC cells. These results suggest tolerance in endocrine-resistant and TNBC cells to mitochondrial stress induced by anacardic acid. Since anacardic acid is an alkylated 2-hydroxybenzoic acid, the effects of salicylic acid (SA, 2-hydroxybenzoic acid moiety) and oleic acid (OA, monounsaturated alkyl moiety) were tested. SA inhibited whereas OA stimulated cell viability. In contrast to stimulation of basal OCR by anacardic acid (uncoupling effect), neither SA nor OA altered basal OCR- except OA inhibited basal and ATP-linked OCR, and increased ECAR, in MDA-MB-231 cells. Changes in OXPHOS proteins correlated with changes in OCR. Overall, neither the 2-hydroxybenzoic acid moiety nor the monounsaturated alky moiety of anacardic acid is solely responsible for the observed mitochondria-targeted anticancer activity in breast cancer cells and hence both moieties are required in the same molecule for the observed effects. J. Cell. Biochem. 117: 2521-2532, 2016. © 2016 Wiley Periodicals, Inc. PMID:26990649

  3. Therapeutic approaches for treating hemophilia A using embryonic stem cells.

    PubMed

    Kasuda, Shogo; Tatsumi, Kohei; Sakurai, Yoshihiko; Shima, Midori; Hatake, Katsuhiko

    2016-06-01

    Hemophilia A is an X-linked rescessive bleeding disorder that results from F8 gene aberrations. Previously, we established embryonic stem (ES) cells (tet-226aa/N6-Ainv18) that secrete human factor VIII (hFVIII) by introducing the human F8 gene in mouse Ainv18 ES cells. Here, we explored the potential of cell transplantation therapy for hemophilia A using the ES cells. Transplant tet-226aa/N6-Ainv18 ES cells were injected into the spleens of severe combined immunodeficiency (SCID) mice, carbon tetrachloride (CCl4)-pretreated wild-type mice, and CCl4-pretreated hemophilia A mice. F8 expression was induced by doxycycline in drinking water, and hFVIII-antigen production was assessed in all cell transplantation experiments. Injecting the ES cells into SCID mice resulted in an enhanced expression of the hFVIII antigen; however, teratoma generation was confirmed in the spleen. Transplantation of ES cells into wild-type mice after CCl4-induced liver injury facilitated survival and engraftment of transplanted cells without teratoma formation, resulting in hFVIII production in the plasma. Although CCl4 was lethal to most hemophilia A mice, therapeutic levels of FVIII activity, as well as the hFVIII antigen, were detected in surviving hemophilia A mice after cell transplantation. Immunolocalization results for hFVIII suggested that transplanted ES cells might be engrafted at the periportal area in the liver. Although the development of a safer induction method for liver regeneration is required, our results suggested the potential for developing an effective ES-cell transplantation therapeutic model for treating hemophilia A in the future. PMID:27131224

  4. Therapeutic approaches for treating hemophilia A using embryonic stem cells.

    PubMed

    Kasuda, Shogo; Tatsumi, Kohei; Sakurai, Yoshihiko; Shima, Midori; Hatake, Katsuhiko

    2016-06-01

    Hemophilia A is an X-linked rescessive bleeding disorder that results from F8 gene aberrations. Previously, we established embryonic stem (ES) cells (tet-226aa/N6-Ainv18) that secrete human factor VIII (hFVIII) by introducing the human F8 gene in mouse Ainv18 ES cells. Here, we explored the potential of cell transplantation therapy for hemophilia A using the ES cells. Transplant tet-226aa/N6-Ainv18 ES cells were injected into the spleens of severe combined immunodeficiency (SCID) mice, carbon tetrachloride (CCl4)-pretreated wild-type mice, and CCl4-pretreated hemophilia A mice. F8 expression was induced by doxycycline in drinking water, and hFVIII-antigen production was assessed in all cell transplantation experiments. Injecting the ES cells into SCID mice resulted in an enhanced expression of the hFVIII antigen; however, teratoma generation was confirmed in the spleen. Transplantation of ES cells into wild-type mice after CCl4-induced liver injury facilitated survival and engraftment of transplanted cells without teratoma formation, resulting in hFVIII production in the plasma. Although CCl4 was lethal to most hemophilia A mice, therapeutic levels of FVIII activity, as well as the hFVIII antigen, were detected in surviving hemophilia A mice after cell transplantation. Immunolocalization results for hFVIII suggested that transplanted ES cells might be engrafted at the periportal area in the liver. Although the development of a safer induction method for liver regeneration is required, our results suggested the potential for developing an effective ES-cell transplantation therapeutic model for treating hemophilia A in the future.

  5. Effect of PDT-treated apoptotic cells on macrophages

    NASA Astrophysics Data System (ADS)

    Song, Sheng; Xing, Da; Zhou, Fei-fan; Chen, Wei R.

    2009-02-01

    Recently, the long-term immunological effects of photodynamic therapy have attracted much attention. PDT induced immune response was mainly initiated through necrotic cells and apoptotic cells, as well as immune cells such as macrophages. Nitric oxide (NO) as an important regulatory factor in signal transfer between cells has been wildly studied for generation, development, and metastasis of tumors. NO synthase is a key enzyme in nitric oxide synthesis. However, inducible nitric oxide synthase (iNOS) is usually activated under pathological conditions, such as stress and cancer, which can produce high levels of nitric oxide and contribute to tumor cytotoxicity. In addition, increased NO production by iNOS has been associated with the host immune response and cell apoptosis, which play an important role in many carcinogenesis and anti-carcinoma mechanisms. This study focuses on the NO production in macrophages, induced by mouse breast carcinoma apoptotic cells treated by PDT in vitro, and on the effects of immune response induced by apoptotic cells in tumor cells growth.

  6. Fetal progenitor cell transplantation treats methylmalonic aciduria in a mouse model

    SciTech Connect

    Buck, Nicole E.; Pennell, Samuel D.; Wood, Leonie R.; Pitt, James J.; Allen, Katrina J.; Peters, Heidi L.

    2012-10-12

    Highlights: Black-Right-Pointing-Pointer Fetal cells were transplanted into a methylmalonic acid mouse model. Black-Right-Pointing-Pointer Cell engraftment was detected in liver, spleen and bone marrow. Black-Right-Pointing-Pointer Biochemical disease correction was measured in blood samples. Black-Right-Pointing-Pointer A double dose of 5 million cells (1 week apart) proved more effective. Black-Right-Pointing-Pointer Higher levels of engraftment may be required for greater disease correction. -- Abstract: Methylmalonic aciduria is a rare disorder caused by an inborn error of organic acid metabolism. Current treatment options are limited and generally focus on disease management. We aimed to investigate the use of fetal progenitor cells to treat this disorder using a mouse model with an intermediate form of methylmalonic aciduria. Fetal liver cells were isolated from healthy fetuses at embryonic day 15-17 and intravenously transplanted into sub-lethally irradiated mice. Liver donor cell engraftment was determined by PCR. Disease correction was monitored by urine and blood methylmalonic acid concentration and weight change. Initial studies indicated that pre-transplantation sub-lethal irradiation followed by transplantation with 5 million cells were suitable. We found that a double dose of 5 million cells (1 week apart) provided a more effective treatment. Donor cell liver engraftment of up to 5% was measured. Disease correction, as defined by a decrease in blood methylmalonic acid concentration, was effected in methylmalonic acid mice transplanted with a double dose of cells and who showed donor cell liver engraftment. Mean plasma methylmalonic acid concentration decreased from 810 {+-} 156 (sham transplanted) to 338 {+-} 157 {mu}mol/L (double dose of 5 million cells) while mean blood C3 carnitine concentration decreased from 20.5 {+-} 4 (sham transplanted) to 5.3 {+-} 1.9 {mu}mol/L (double dose of 5 million cells). In conclusion, higher levels of engraftment may

  7. Rapid characterization of the biomechanical properties of drug-treated cells in a microfluidic device

    NASA Astrophysics Data System (ADS)

    Zhang, Xiaofei; Chu, Henry K.; Zhang, Yang; Bai, Guohua; Wang, Kaiqun; Tan, Qiulin; Sun, Dong

    2015-10-01

    Cell mechanics is closely related to many cell functions. Recent studies have suggested that the deformability of cells can be an effective biomarker to indicate the onset and progression of diseases. In this paper, a microfluidic chip is designed for rapid characterization of the mechanics of drug-treated cells through stretching with dielectrophoresis (DEP) force. This chip was fabricated using PDMS and micro-electrodes were integrated and patterned on the ITO layer of the chip. Leukemia NB4 cells were considered and the effect of all-trans retinoic acid (ATRA) drug on NB4 cells were examined via the microfluidic chip. To induce a DEP force onto the cell, a relatively weak ac voltage was utilized to immobilize a cell at one side of the electrodes. The applied voltage was then increased to 3.5 V pp and the cell started to be stretched along the applied electric field lines. The elongation of the cell was observed using an optical microscope and the results showed that both types of cells were deformed by the induced DEP force. The strain of the NB4 cell without the drug treatment was recorded to be about 0.08 (time t = 180 s) and the drug-treated NB4 cell was about 0.21 (time t = 180 s), indicating a decrease in the stiffness after drug treatment. The elastic modulus of the cell was also evaluated and the modulus changed from 140 Pa to 41 Pa after drug treatment. This microfluidic chip can provide a simple and rapid platform for measuring the change in the biomechanical properties of cells and can potentially be used as the tool to determine the biomechanical effects of different drug treatments for drug discovery and development applications.

  8. Technology development for phosphoric acid fuel cell powerplant, phase 2

    NASA Technical Reports Server (NTRS)

    Christner, L.

    1981-01-01

    The development of materials, cell components, and reformers for on site integrated energy systems is described. Progress includes: (1) heat-treatment of 25 sq cm, 350 sq cm and 1200 sq cm cell test hardware was accomplished. Performance of fuel cells is improved by using this material; (2) electrochemical and chemical corrosion rates of heat-treated and as-molded graphite/phenolic resin composites in phosphoric acid were determined; (3) three cell, 5 in. x 15 in. stacks operated for up to 10,000 hours and 12 in. x 17 in. five cell stacks were tested for 5,000 hours; (4) a three cell 5 in. x 15 in. stack with 0.12 mg Pt/sq cm anodes and 0.25 mg Pt/sq cm cathodes was operated for 4,500 hours; and (5) an ERC proprietary high bubble pressure matrix, MAT-1, was tested for up to 10,000 hours.

  9. Natural killer (NK) activity of pit cells perfused from livers of rats treated with ethanol

    SciTech Connect

    Albornoz, L.; Jones, J.M.; Crutchfield, C.; Veech, R.L. Univ. of Arkansas Medical Sciences, Little Rock )

    1991-03-11

    The liver is the major site of ethanol (ETOH) metabolism. Liver sinusoids contain lymphocytes with NK activity. The authors treated LEW rats for 2 weeks with i.p. injection of 1.25 ml 25% ETOH/kg 3 times/week and 5% ETOH in drinking water. Livers were perfused at 5-fold physiological pressure and cells obtained were banded on 1.077 density Ficoll. Their cytotoxicity was tested against {sup 51}Cr-labeled YAC-1 or U937 and compared to spleen and blood lymphocytes. In untreated rats, pit cell NK activity was 2-fold that of splenic lymphocytes and 4-fold that of blood lymphocytes. Compared to controls, ETOH-treated rats exhibited a 30 to 90% rise in pit cell NK activity detected with YAC-1 or U937 targets. The pit cell enhanced NK activity in ETOH-treated rats was further increased if polyinosinicpolycytidilic acid was injection i.p. 18 hours before the assay. Blood and spleen lymphocyte NK activity of ETOH-treated rats was also greater than in controls. There was no evidence that ETOH merely redistributed lymphocytes among the tissues. Although ETOH acutely inhibits NK activity in vitro, chronic ETOH increases in vivo.

  10. Comparative Proteomic Study of Fatty Acid-treated Myoblasts Reveals Role of Cox-2 in Palmitate-induced Insulin Resistance

    PubMed Central

    Chen, Xiulan; Xu, Shimeng; Wei, Shasha; Deng, Yaqin; Li, Yiran; Yang, Fuquan; Liu, Pingsheng

    2016-01-01

    Accumulated studies demonstrate that saturated fatty acids (FAs) such as palmitic acid (PA) inhibit insulin signaling in skeletal muscle cells and monounsaturated fatty acids such as oleic acid (OA) reverse the effect of PA on insulin signaling. The detailed molecular mechanism of these opposite effects remains elusive. Here we provide a comparative proteomic study of skeletal myoblast cell line C2C12 that were untreated or treated with PA, and PA plus OA. A total of 3437 proteins were quantified using SILAC in this study and 29 proteins fall into the pattern that OA reverses PA effect. Expression of some these proteins were verified using qRT-PCR and Western blot. The most significant change was cyclooxygenase-2 (Cox-2). In addition to whole cell comparative proteomic study, we also compared lipid droplet (LD)-associated proteins and identified that Cox-2 was one of three major altered proteins under the FA treatment. This finding was then confirmed using immunofluorescence. Finally, Cox-2 selective inhibitor, celecoxib protected cells from PA-reduced insulin signaling Akt phosphorylation. Together, these results not only provide a dataset of protein expression change in FA treatment but also suggest that Cox-2 and lipid droplets (LDs) are potential players in PA- and OA-mediated cellular processes. PMID:26899878

  11. Intrinsic fluorescence biomarkers in cells treated with chemopreventive drugs

    NASA Astrophysics Data System (ADS)

    Kirkpatrick, Nathaniel D.; Brands, William R.; Zou, Changping; Brewer, Molly A.; Utzinger, Urs

    2005-03-01

    Non-invasive monitoring of cellular metabolism offers promising insights into areas ranging from biomarkers for drug activity to cancer diagnosis. Fluorescence spectroscopy can be utilized in order to exploit endogenous fluorophores, typically metabolic co-factors nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD), and estimate the redox status of the sample. Fluorescence spectroscopy was applied to follow metabolic changes in epithelial ovarian cells as well as bladder epithelial cancer cells during treatment with a chemopreventive drug that initiates cellular quiescence. Fluorescence signals consistent with NADH, FAD, and tryptophan were measured to monitor cellular activity, redox status, and protein content. Cells were treated with varying concentrations of N-4-(hydroxyphenyl) retinamide (4-HPR) and measured in a stable environment with a sensitive fluorescence spectrometer. A subset of measurements was completed on a low concentration of cells to demonstrate feasibility for medical application such as in bladder or ovary washes. Results suggest that all of the cells responded with similar dose dependence but started at different estimated redox ratio baseline levels correlating with cell cycle, growth inhibition, and apoptosis assays. NADH and tryptophan related fluorescence changed significantly while FAD related fluorescence remained unaltered. Fluorescence data collected from approximately 1000 - 2000 cells, comparable to a bladder or ovary wash, was measurable and useful for future experiments. This study suggests that future intrinsic biomarker measurements may need to be most sensitive to changes in NADH and tryptophan related fluorescence while using FAD related fluorescence to help estimate the baseline redox ratio and predict response to chemopreventive agents.

  12. PDT-treated apoptotic cells induce macrophage synthesis NO

    NASA Astrophysics Data System (ADS)

    Song, S.; Xing, D.; Zhou, F. F.; Chen, W. R.

    2009-11-01

    Nitric oxide (NO) is a biologically active molecule which has multi-functional in different species. As a second messenger and neurotransmitter, NO is not only an important regulatory factor between cells' information transmission, but also an important messenger in cell-mediated immunity and cytotoxicity. On the other side, NO is involving in some diseases' pathological process. In pathological conditions, the macrophages are activated to produce a large quantity of nitric oxide synthase (iNOS), which can use L-arginine to produce an excessive amount of NO, thereby killing bacteria, viruses, parasites, fungi, tumor cells, as well as in other series of the immune process. In this paper, photofrin-based photodynamic therapy (PDT) was used to treat EMT6 mammary tumors in vitro to induce apoptotic cells, and then co-incubation both apoptotic cells and macrophages, which could activate macrophage to induce a series of cytotoxic factors, especially NO. This, in turn, utilizes macrophages to activate a cytotoxic response towards neighboring tumor cells. These results provided a new idea for us to further study the immunological mechanism involved in damaging effects of PDT, also revealed the important function of the immune effect of apoptotic cells in PDT.

  13. Mobility of acid-treated carbon nanotubes in water-saturated porous media.

    PubMed

    Peng, X J; Du, C J; Liang, Z; Wang, J; Luan, Z K; Li, W J

    2011-01-01

    The production, use, and disposal of nanomaterials may inevitably lead to their appearance in water. With the development of new industries around nanomaterials, it seems necessary to be concerned about the transport of nanomaterials in the environment. In this paper, the transport of acid-treated carbon nanotubes (CNTs) in porous media was investigated. Before the mobility investigation, the stability of acid-treated CNT dispersions was studied using ultraviolet-visible spectra and it was indicated that, under the chemical conditions employed in this work, there was no apparent aggregation. The mobility investigation showed that transport of acid-treated CNTs increased with treatment time due to increase in particle zeta potential. Carbon nanotubes treated with nitric acid for 2, 6, and 12 h possessed measured zeta potentials of -30.0, -43.0, and -48.5 mV, respectively. Utilizing clean-bed filtration theory, we showed that acid-treated CNTs have the potential to migrate 3.28, 5.67, and 7.69 m in saturated glass beads, respectively. We showed that solution ionic strength and pH have important effects on the mobility of acid-treated CNTs. Increasing the pH from 6.0 to 7.9 resulted in an increase in migration potential from 2.96 to 10.86 m. Increasing the ionic strength from 0.005 to 0.020 M resulted in a decrease in CNT migration potential from 5.67 to 1.42 m.

  14. Corrosion free phosphoric acid fuel cell

    DOEpatents

    Wright, Maynard K.

    1990-01-01

    A phosphoric acid fuel cell with an electrolyte fuel system which supplies electrolyte via a wick disposed adjacent a cathode to an absorbent matrix which transports the electrolyte to portions of the cathode and an anode which overlaps the cathode on all sides to prevent corrosion within the cell.

  15. Ferulic acid is esterified to glucuronoarabinoxylans in pineapple cell walls.

    PubMed

    Smith, B G; Harris, P J

    2001-03-01

    The ester-linkage of ferulic acid (mainly E) to polysaccharides in primary cell walls of pineapple fruit (Ananas comosus) (Bromeliaceae) was investigated by treating a cell-wall preparation with 'Driselase' which contains a mixture of endo- and exo-glycanases, but no hydroxycinnamoyl esterase activity. The most abundant feruloyl oligosaccharide released was O-[5-O-(E-feruloyl)-alpha-L-arabinofuranosyl](1-->3)-O-beta-D-xylopyranosyl-(1-->4)-D-xylopyranose (FAXX). This indicated that the ferulic acid is ester-linked to glucuronoarabinoxylans in the same way as in the primary walls of grasses and cereals (Poaceae). Glucuronoarabinoxylans are the major non-cellulosic polysaccharides in the pineapple cell walls.

  16. A role for TLR signaling during B cell activation in antiretroviral-treated HIV individuals.

    PubMed

    Siewe, Basile; Keshavarzian, Ali; French, Audrey; Demarais, Patricia; Landay, Alan

    2013-10-01

    The mechanisms underlying B cell activation that persists during antiretroviral therapy (ART) are unknown. Toll-like receptor (TLR) signaling is a critical mediator of innate cell activation and though B cells express TLRs, few studies have investigated a role for TLR signaling in B cell activation during HIV infection. We addressed this question by assessing the activated phenotype and TLR expression/responsiveness of B cells from ART-treated HIV-infected subjects (HIVART(+)). We evaluated activation markers implicated in B cell-mediated T cell trans infection during HIV pathogenesis. We found no significant difference in TLR expression between B cells of HIVART(+) and HIV(-) subjects. However, B cells of HIVART(+) subjects exhibited heightened endogenous expression levels of IL-6 (p=0.0051), T cell cognate ligands CD40 (p=0.0475), CD54 (p=0.0229), and phosphorylated p38 (p<0.0001), a marker of TLR signaling. In vitro, B cells of HIVART(+) individuals were less responsive to TLR stimulation compared to B cells of HIV(-) subjects. The activated phenotype of in vitro TLR-stimulated B cells of HIV(-) subjects was similar to ex vivo B cells from HIVART(+) individuals. TLR2 stimulation was a potent mediator of B cell activation, whereas B cells were least responsive to TLR4 stimulation. Compared to HIV(-) subjects, the serum level of lipoteichoic acid (TLR2 ligand) in HIVART(+) subjects was significantly higher (p=0.0207), correlating positively with viral load (p=0.0127, r=0.6453). Our data suggest that during HIV infection TLR-activated B cells may exert a pathogenic role and B cells from HIVART(+) subjects respond to in vitro TLR stimulation, yet exhibit a TLR tolerant phenotype suggesting prior in vivo TLR stimulation. PMID:23763346

  17. A Role for TLR Signaling During B Cell Activation in Antiretroviral-Treated HIV Individuals

    PubMed Central

    Keshavarzian, Ali; French, Audrey; Demarais, Patricia; Landay, Alan

    2013-01-01

    Abstract The mechanisms underlying B cell activation that persists during antiretroviral therapy (ART) are unknown. Toll-like receptor (TLR) signaling is a critical mediator of innate cell activation and though B cells express TLRs, few studies have investigated a role for TLR signaling in B cell activation during HIV infection. We addressed this question by assessing the activated phenotype and TLR expression/responsiveness of B cells from ART-treated HIV-infected subjects (HIVART+). We evaluated activation markers implicated in B cell-mediated T cell trans infection during HIV pathogenesis. We found no significant difference in TLR expression between B cells of HIVART+ and HIV− subjects. However, B cells of HIVART+ subjects exhibited heightened endogenous expression levels of IL-6 (p=0.0051), T cell cognate ligands CD40 (p=0.0475), CD54 (p=0.0229), and phosphorylated p38 (p<0.0001), a marker of TLR signaling. In vitro, B cells of HIVART+ individuals were less responsive to TLR stimulation compared to B cells of HIV− subjects. The activated phenotype of in vitro TLR-stimulated B cells of HIV− subjects was similar to ex vivo B cells from HIVART+ individuals. TLR2 stimulation was a potent mediator of B cell activation, whereas B cells were least responsive to TLR4 stimulation. Compared to HIV− subjects, the serum level of lipoteichoic acid (TLR2 ligand) in HIVART+ subjects was significantly higher (p=0.0207), correlating positively with viral load (p=0.0127, r=0.6453). Our data suggest that during HIV infection TLR-activated B cells may exert a pathogenic role and B cells from HIVART+ subjects respond to in vitro TLR stimulation, yet exhibit a TLR tolerant phenotype suggesting prior in vivo TLR stimulation. PMID:23763346

  18. Benzaldehyde dehydrogenase from chitosan-treated Sorbus aucuparia cell cultures.

    PubMed

    Gaid, Mariam M; Sircar, Debabrata; Beuerle, Till; Mitra, Adinpunya; Beerhues, Ludger

    2009-09-01

    Cell cultures of Sorbus aucuparia respond to the addition of chitosan with the accumulation of the biphenyl phytoalexin aucuparin. The carbon skeleton of this inducible defense compound is formed by biphenyl synthase (BIS) from benzoyl-CoA and three molecules of malonyl-CoA. The formation of benzoyl-CoA proceeds via benzaldehyde as an intermediate. Benzaldehyde dehydrogenase (BD), which converts benzaldehyde into benzoic acid, was detected in cell-free extracts from S. aucuparia cell cultures. BD and BIS were induced by chitosan treatment. The preferred substrate for BD was benzaldehyde (K(m)=49 microM). Cinnamaldehyde and various hydroxybenzaldehydes were relatively poor substrates. BD activity was strictly dependent on the presence of NAD(+) as a cofactor (K(m)=67 microM).

  19. Process strategies to maximize lipid accumulations of novel yeast in acid and base treated hydrolyzates

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Oleaginous yeasts can accumulate up to 70% of cell biomass as lipids, predominantly as triacylglycerols. Yeast lipid fatty acid profiles have been reported to be similar to that of vegetable oils and consist primarily of oleic, palmitic, stearic, and linoleic acids. This capability provides the oppo...

  20. Dielectrophoretic characterization of antibiotic-treated Mycobacterium tuberculosis complex cells.

    PubMed

    Inoue, Shinnosuke; Lee, Hyun-Boo; Becker, Annie L; Weigel, Kris M; Kim, Jong-Hoon; Lee, Kyong-Hoon; Cangelosi, Gerard A; Chung, Jae-Hyun

    2015-10-01

    Multi-drug resistant tuberculosis (MDR-TB) has become a serious concern for proper treatment of patients. As a phenotypic method, dielectrophoresis can be useful but is yet to be attempted to evaluate Mycobacterium tuberculosis complex cells. This paper investigates the dielectrophoretic behavior of Mycobacterium bovis (Bacillus Calmette-Guérin, BCG) cells that are treated with heat or antibiotics rifampin (RIF) or isoniazid (INH). The experimental parameters are designed on the basis of our sensitivity analysis. The medium conductivity (σ(m)) and the frequency (f) for a crossover frequency (f(xo1)) test are decided to detect the change of σ(m)-f(xo1) in conjunction with the drug mechanism. Statistical modeling is conducted to estimate the distributions of viable and nonviable cells from the discrete measurement of f (xo1). Finally, the parameters of the electrophysiology of BCG cells, C(envelope) and σ(cyto), are extracted through a sampling algorithm. This is the first evaluation of the dielectrophoresis (DEP) approach as a means to assess the effects of antimicrobial drugs on M. tuberculosis complex cells.

  1. Nucleic Acid Aptamers for Living Cell Analysis

    NASA Astrophysics Data System (ADS)

    Xiong, Xiangling; Lv, Yifan; Chen, Tao; Zhang, Xiaobing; Wang, Kemin; Tan, Weihong

    2014-06-01

    Cells as the building blocks of life determine the basic functions and properties of a living organism. Understanding the structure and components of a cell aids in the elucidation of its biological functions. Moreover, knowledge of the similarities and differences between diseased and healthy cells is essential to understanding pathological mechanisms, identifying diagnostic markers, and designing therapeutic molecules. However, monitoring the structures and activities of a living cell remains a challenging task in bioanalytical and life science research. To meet the requirements of this task, aptamers, as “chemical antibodies,” have become increasingly powerful tools for cellular analysis. This article reviews recent advances in the development of nucleic acid aptamers in the areas of cell membrane analysis, cell detection and isolation, real-time monitoring of cell secretion, and intracellular delivery and analysis with living cell models. Limitations of aptamers and possible solutions are also discussed.

  2. Micro-electro-mechanical systems phosphoric acid fuel cell

    DOEpatents

    Sopchak, David A.; Morse, Jeffrey D.; Upadhye, Ravindra S.; Kotovsky, Jack; Graff, Robert T.

    2010-08-17

    A phosphoric acid fuel cell system comprising a porous electrolyte support, a phosphoric acid electrolyte in the porous electrolyte support, a cathode electrode contacting the phosphoric acid electrolyte, and an anode electrode contacting the phosphoric acid electrolyte.

  3. Micro-electro-mechanical systems phosphoric acid fuel cell

    DOEpatents

    Sopchak, David A.; Morse, Jeffrey D.; Upadhye, Ravindra S.; Kotovsky, Jack; Graff, Robert T.

    2010-12-21

    A phosphoric acid fuel cell system comprising a porous electrolyte support, a phosphoric acid electrolyte in the porous electrolyte support, a cathode electrode contacting the phosphoric acid electrolyte, and an anode electrode contacting the phosphoric acid electrolyte.

  4. Conversion of Aqueous Ammonia-Treated Corn Stover to Lactic Acid by Simultaneous Saccharification and Cofermentation

    NASA Astrophysics Data System (ADS)

    Zhu, Yongming; Lee, Y. Y.; Elander, Richard T.

    Treatment of corn stover with aqueous ammonia removes most of the structural lignin, whereas retaining the majority of the carbohydrates in the solids. After treatment, both the cellulose and hemicellulose in corn stover become highly susceptible to enzymatic digestion. In this study, corn stover treated by aqueous ammonia was investigated as the substrate for lactic acid production by simultaneous saccharification and cofermentation (SSCF). A commercial cellulase (Spezyme-CP) and Lactobacillus pentosus American Type Culture Collection (ATCC) 8041 (Spanish Type Culture Collection [CECT]-4023) were used for hydrolysis and fermentation, respectively. In batch SSCF operation, the carbohydrates in the treated corn stover were converted to lactic acid with high yields, the maximum lactic acid yield reaching 92% of the stoichiometric maximum based on total fermentable carbohydrates (glucose, xylose, and arabinose). A small amount of acetic acid was also produced from pentoses through the phosphoketolase pathway. Among the major process variables for batch SSCF, enzyme loading and the amount of yeast extract were found to be the key factors affecting lactic acid production. Further tests on nutrients indicated that corn steep liquor could be substituted for yeast extract as a nitrogen source to achieve the same lactic acid yield. Fed-batch operation of the SSCF was beneficial in raising the concentration of lactic acid to a maximum value of 75.0 g/L.

  5. NRMRL EVALUATES ACTIVE AND SEMI-PASSIVE TECHNOLOGIES FOR TREATING ACID MINE DRAINAGE

    EPA Science Inventory

    Two-page article describing three SITE demonstration projects underway on the Leviathan mine site in California. BiPhasic lime treatment, lime treatment lagoons and compost free BioReactors are being evaluated as innovative technologies for treating acid mine drainage.

  6. Prenatal transplantation of mesenchymal stem cells to treat osteogenesis imperfecta

    PubMed Central

    Chan, Jerry K. Y.; Götherström, Cecilia

    2014-01-01

    Osteogenesis imperfecta (OI) can be a severe disorder that can be diagnosed before birth. Transplantation of mesenchymal stem cells (MSC) has the potential to improve the bone structure, growth, and fracture healing. In this review, we give an introduction to OI and MSC, and the basis for pre- and postnatal transplantation in OI. We also summarize the two patients with OI who have received pre- and postnatal transplantation of MSC. The findings suggest that prenatal transplantation of allogeneic MSC in OI is safe. The cell therapy is of likely clinical benefit with improved linear growth, mobility, and reduced fracture incidence. Unfortunately, the effect is transient. For this reason, postnatal booster infusions using same-donor MSC have been performed with clinical benefit, and without any adverse events. So far there is limited experience in this specific field and proper studies are required to accurately conclude on clinical benefits of MSC transplantation to treat OI. PMID:25346689

  7. Genomic instability of gold nanoparticle treated human lung fibroblast cells.

    PubMed

    Li, Jasmine J; Lo, Soo-Ling; Ng, Cheng-Teng; Gurung, Resham Lal; Hartono, Deny; Hande, Manoor Prakash; Ong, Choon-Nam; Bay, Boon-Huat; Yung, Lin-Yue Lanry

    2011-08-01

    Gold nanoparticles (AuNPs) are one of the most versatile and widely researched materials for novel biomedical applications. However, the current knowledge in their toxicological profile is still incomplete and many on-going investigations aim to understand the potential adverse effects in human body. Here, we employed two dimensional gel electrophoresis to perform a comparative proteomic analysis of AuNP treated MRC-5 lung fibroblast cells. In our findings, we identified 16 proteins that were differentially expressed in MRC-5 lung fibroblasts following exposure to AuNPs. Their expression levels were also verified by western blotting and real time RT-PCR analysis. Of interest was the difference in the oxidative stress related proteins (NADH ubiquinone oxidoreductase (NDUFS1), protein disulfide isomerase associate 3 (PDIA3), heterogeneous nuclear ribonucleus protein C1/C2 (hnRNP C1/C2) and thioredoxin-like protein 1 (TXNL1)) as well as proteins associated with cell cycle regulation, cytoskeleton and DNA repair (heterogeneous nuclear ribonucleus protein C1/C2 (hnRNP C1/C2) and Secernin-1 (SCN1)). This finding is consistent with the genotoxicity observed in the AuNP treated lung fibroblasts. These results suggest that AuNP treatment can induce oxidative stress-mediated genomic instability.

  8. Formic acid fuel cells and catalysts

    DOEpatents

    Masel, Richard I.; Larsen, Robert; Ha, Su Yun

    2010-06-22

    An exemplary fuel cell of the invention includes a formic acid fuel solution in communication with an anode (12, 134), an oxidizer in communication with a cathode (16, 135) electrically linked to the anode, and an anode catalyst that includes Pd. An exemplary formic acid fuel cell membrane electrode assembly (130) includes a proton-conducting membrane (131) having opposing first (132) and second surfaces (133), a cathode catalyst on the second membrane surface, and an anode catalyst including Pd on the first surface.

  9. Treating hearing disorders with cell and gene therapy

    NASA Astrophysics Data System (ADS)

    Gillespie, Lisa N.; Richardson, Rachael T.; Nayagam, Bryony A.; Wise, Andrew K.

    2014-12-01

    Hearing loss is an increasing problem for a substantial number of people and, with an aging population, the incidence and severity of hearing loss will become more significant over time. There are very few therapies currently available to treat hearing loss, and so the development of new therapeutic strategies for hearing impaired individuals is of paramount importance to address this unmet clinical need. Most forms of hearing loss are progressive in nature and therefore an opportunity exists to develop novel therapeutic approaches to slow or halt hearing loss progression, or even repair or replace lost hearing function. Numerous emerging technologies have potential as therapeutic options. This paper details the potential of cell- and gene-based therapies to provide therapeutic agents to protect sensory and neural cells from various insults known to cause hearing loss; explores the potential of replacing lost sensory and nerve cells using gene and stem cell therapy; and describes the considerations for clinical translation and the challenges that need to be overcome.

  10. Phosphoric Acid Fuel Cell Technology Status

    NASA Technical Reports Server (NTRS)

    Simons, S. N.; King, R. B.; Prokopius, P. R.

    1981-01-01

    A review of the current phosphoric acid fuel cell system technology development efforts is presented both for multimegawatt systems for electric utility applications and for multikilowatt systems for on-site integrated energy system applications. Improving fuel cell performance, reducing cost, and increasing durability are the technology drivers at this time. Electrodes, matrices, intercell cooling, bipolar/separator plates, electrolyte management, and fuel selection are discussed.

  11. Solid acids as fuel cell electrolytes.

    PubMed

    Haile, S M; Boysen, D A; Chisholm, C R; Merle, R B

    2001-04-19

    Fuel cells are attractive alternatives to combustion engines for electrical power generation because of their very high efficiencies and low pollution levels. Polymer electrolyte membrane fuel cells are generally considered to be the most viable approach for mobile applications. However, these membranes require humid operating conditions, which limit the temperature of operation to less than 100 degrees C; they are also permeable to methanol and hydrogen, which lowers fuel efficiency. Solid, inorganic, acid compounds (or simply, solid acids) such as CsHSO4 and Rb3H(SeO4)2 have been widely studied because of their high proton conductivities and phase-transition behaviour. For fuel-cell applications they offer the advantages of anhydrous proton transport and high-temperature stability (up to 250 degrees C). Until now, however, solid acids have not been considered viable fuel-cell electrolyte alternatives owing to their solubility in water and extreme ductility at raised temperatures (above approximately 125 degrees C). Here we show that a cell made of a CsHSO4 electrolyte membrane (about 1.5 mm thick) operating at 150-160 degrees C in a H2/O2 configuration exhibits promising electrochemical performances: open circuit voltages of 1.11 V and current densities of 44 mA cm-2 at short circuit. Moreover, the solid-acid properties were not affected by exposure to humid atmospheres. Although these initial results show promise for applications, the use of solid acids in fuel cells will require the development of fabrication techniques to reduce electrolyte thickness, and an assessment of possible sulphur reduction following prolonged exposure to hydrogen.

  12. Detection of methylglyoxal as a degradation product of DNA and nucleic acid components treated with strong acid.

    PubMed

    Chaplen, F W; Fahl, W E; Cameron, D C

    1996-05-01

    The 1,2-diaminobenzene derivation assay for methylglyoxal in biological systems involves the use of perchloric acid, both as a deproteinizing agent and to prevent the spontaneous formation of methylglyoxal from glycolytic pathway intermediates. However, while using a modification of the standard literature assay to measure methylglyoxal in Chinese hamster ovary cells, we found that oxidation of nucleic acids and related compounds by perchloric or trichloroacetic acid results in the formation of methylglyoxal. Compounds containing 2-deoxyribose gave higher levels of methylglyoxal than those containing ribose; purine nucleotides and deoxynucleotides gave more methylglyoxal than did the pyrimidines. Nucleic acids were the most susceptible to degradation, with 12-fold more methylglyoxal being formed from DNA than RNA. Oxidation of nucleic acids increased with higher temperatures and with decreasing nucleic acid fragment size. Another product of nucleic acid oxidation was 2,3-butanedione, the 1,2-diaminobenzene derivative of which is sometimes used as an internal standard during methylglyoxal measurement. Unless accounted for during the assay procedure, the generation of methylglyoxal and 2,3-butanedione due to the oxidation of nucleic acids may lead to substantial errors in the determination of methylglyoxal concentrations in biological systems.

  13. Degradation of 3-chloro-4-hydroxybenzoic acid in biological treated effluent by gamma irradiation

    NASA Astrophysics Data System (ADS)

    Chu, Libing; Wang, Jianlong

    2016-02-01

    Gamma irradiation-induced degradation of a chlorinated aromatic compound, 3-chloro-4-hydroxybenzoic acid (CHBA) in biological treated effluent was studied and the results were compared with those obtained in deionized water. Gamma irradiation led to a complete decomposition of CHBA and a partial mineralization in the treated effluent. The removal of CHBA followed the pseudo first-order reaction kinetic model and the rate constant in the treated effluent was 1.7-3.5 times lower than that in deionized water. The CHBA degradation rate was higher at acidic condition than at neutral and alkaline conditions. The radiolytic yield, G-value for CHBA degradation was lower in the treated effluent, which decreased with increase in absorbed doses and increased with increase in initial concentrations of CHBA. The degradation mechanism of CHBA using gamma irradiation was proposed through the oxidation by -OH and reduction by eaq- and H- radicals. As exposed to gamma irradiation, dechlorination takes place rapidly and combines with the oxidation and cleavage of the aromatic ring, producing chloride ions, small carboxylic acids, acetaldehyde and other intermediates into the solution.

  14. Depigmenting Effect of Kojic Acid Esters in Hyperpigmented B16F1 Melanoma Cells

    PubMed Central

    Lajis, Ahmad Firdaus B.; Hamid, Muhajir; Ariff, Arbakariya B.

    2012-01-01

    The depigmenting effect of kojic acid esters synthesized by the esterification of kojic acid using Rhizomucor miehei immobilized lipase was investigated in B16F1 melanoma cells. The depigmenting effect of kojic acid and kojic acid esters was evaluated by the inhibitory effect of melanin formation and tyrosinase activity on alpha-stimulating hormone- (α-MSH-) induced melanin synthesis in B16F1 melanoma cells. The cellular tyrosinase inhibitory effect of kojic acid monooleate, kojic acid monolaurate, and kojic acid monopalmitate was found similar to kojic acid at nontoxic doses ranging from 1.95 to 62.5 μg/mL. However, kojic acid monopalmitate gave slightly higher inhibition to melanin formation compared to other inhibitors at doses ranging from 15.63 to 62.5 μg/mL. Kojic acid and kojic acid esters also show antioxidant activity that will enhance the depigmenting effect. The cytotoxicity of kojic acid esters in B16F1 melanoma cells was significantly lower than kojic acid at high doses, ranging from 125 and 500 μg/mL. Since kojic acid esters have lower cytotoxic effect than kojic acid, it is suggested that kojic acid esters can be used as alternatives for a safe skin whitening agent and potential depigmenting agents to treat hyperpigmentation. PMID:23091364

  15. Inhibitory effect of CGRP on osteoclast formation by mouse bone marrow cells treated with isoproterenol.

    PubMed

    Ishizuka, Kyoko; Hirukawa, Koji; Nakamura, Hiroshi; Togari, Akifumi

    2005-04-29

    The present study was designed to elucidate the mode of action of isoproterenol (Isp; adrenergic beta-agonist) and to characterize the effect of the calcitonin gene-related peptide (CGRP; sensory neuropeptide) on osteoclast formation induced by Isp in a mouse bone marrow culture system. Treatment of mouse bone marrow cells with Isp generated tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells (MNCs) capable of excavating resorptive pits on dentine slices, and caused an increase in receptor activator of NF-kappaB ligand (RANKL) and a decrease in osteoprotegerin (OPG) production by the marrow cells. The osteoclast formation was significantly inhibited by OPG, suggesting the involvement of the RANKL-RANK system. CGRP inhibited the osteoclast formation caused by Isp or soluble RANKL (s-RANKL) but had no influence on RANKL or OPG production by the bone marrow cells treated with Isp, suggesting that CGRP inhibited the osteoclast formation by interfering with the action of RANKL produced by the Isp-treated bone marrow cells without affecting RANKL or OPG production. This in vitro data suggest the physiological interaction of sympathetic and sensory nerves in osteoclastogenesis in vivo. PMID:15814197

  16. [Isolation and in vitro translation of polysomes and the RNA matrix from gibberellic acid-treated etiolated dwarf pea shoots].

    PubMed

    Kilev, S N; Evtushenko, E V; Chekurov, V M; Mertvetsov, N P

    1983-08-01

    The effect of gibberellic acid (GA) on the size of polysomes (PS) and on the specific translation activity of epicotyl PS of two dwarf pea varieties was studied. It was shown that GA does not significantly alter the specific translation activity of PS and of mRNA isolated from dwarf pea epicotyl PS. Electrophoretic separation of the polypeptides synthesized in a cell-free protein-synthesizing system in PS of control and GA-treated shoots revealed no differences between them. Some minor qualitative and quantitative differences in the protein composition of the cytoplasm of control and hormone-treated shoots were found. Possible influence of GA on the composition of a definite class of mRNA and on posttranslational processing of plant proteins is discussed. PMID:6194827

  17. Omega-3 fatty acids differentially modulate enzymatic anti-oxidant systems in skeletal muscle cells.

    PubMed

    da Silva, E P; Nachbar, R T; Levada-Pires, A C; Hirabara, S M; Lambertucci, R H

    2016-01-01

    During physical activity, increased reactive oxygen species production occurs, which can lead to cell damage and in a decline of individual's performance and health. The use of omega-3 polyunsaturated fatty acids as a supplement to protect the immune system has been increasing; however, their possible benefit to the anti-oxidant system is not well described. Thus, the aim of this study was to evaluate whether the omega-3 fatty acids (docosahexaenoic acid and eicosapentaenoic acid) can be beneficial to the anti-oxidant system in cultured skeletal muscle cells. C2C12 myocytes were differentiated and treated with either eicosapentaenoic acid or docosahexaenoic acid for 24 h. Superoxide content was quantified using the dihydroethidine oxidation method and superoxide dismutase, catalase, and glutathione peroxidase activity, and expression was quantified. We observed that the docosahexaenoic fatty acids caused an increase in superoxide production. Eicosapentaenoic acid induced catalase activity, while docosahexaenoic acid suppressed superoxide dismutase activity. In addition, we found an increased protein expression of the total manganese superoxide dismutase and catalase enzymes when cells were treated with eicosapentaenoic acid. Taken together, these data indicate that the use of eicosapentaenoic acid may present both acute and chronic benefits; however, the treatment with DHA may not be beneficial to muscle cells.

  18. Omega-3 fatty acids differentially modulate enzymatic anti-oxidant systems in skeletal muscle cells.

    PubMed

    da Silva, E P; Nachbar, R T; Levada-Pires, A C; Hirabara, S M; Lambertucci, R H

    2016-01-01

    During physical activity, increased reactive oxygen species production occurs, which can lead to cell damage and in a decline of individual's performance and health. The use of omega-3 polyunsaturated fatty acids as a supplement to protect the immune system has been increasing; however, their possible benefit to the anti-oxidant system is not well described. Thus, the aim of this study was to evaluate whether the omega-3 fatty acids (docosahexaenoic acid and eicosapentaenoic acid) can be beneficial to the anti-oxidant system in cultured skeletal muscle cells. C2C12 myocytes were differentiated and treated with either eicosapentaenoic acid or docosahexaenoic acid for 24 h. Superoxide content was quantified using the dihydroethidine oxidation method and superoxide dismutase, catalase, and glutathione peroxidase activity, and expression was quantified. We observed that the docosahexaenoic fatty acids caused an increase in superoxide production. Eicosapentaenoic acid induced catalase activity, while docosahexaenoic acid suppressed superoxide dismutase activity. In addition, we found an increased protein expression of the total manganese superoxide dismutase and catalase enzymes when cells were treated with eicosapentaenoic acid. Taken together, these data indicate that the use of eicosapentaenoic acid may present both acute and chronic benefits; however, the treatment with DHA may not be beneficial to muscle cells. PMID:26386577

  19. Live cell imaging of actin dynamics in dexamethasone-treated porcine trabecular meshwork cells.

    PubMed

    Fujimoto, Tomokazu; Inoue, Toshihiro; Inoue-Mochita, Miyuki; Tanihara, Hidenobu

    2016-04-01

    The regulation of the actin cytoskeleton in trabecular meshwork (TM) cells is important for controlling outflow of the aqueous humor. In some reports, dexamethasone (DEX) increased the aqueous humor outflow resistance and induced unusual actin structures, such as cross-linked actin networks (CLAN), in TM cells. However, the functions and dynamics of CLAN in TM cells are not completely known, partly because actin stress fibers have been observed only in fixed cells. We conducted live-cell imaging of the actin dynamics in TM cells with or without DEX treatment. An actin-green fluorescent protein (GFP) fusion construct with a modified insect virus was transfected into porcine TM cells. Time-lapse imaging of live TM cells treated with 25 μM Y-27632 and 100 nM DEX was performed using an inverted fluorescence microscope. Fluorescent images were recorded every 15 s for 30 min after Y-27632 treatment or every 30 min for 72 h after DEX treatment. The GFP-actin was expressed in 22.7 ± 10.9% of the transfected TM cells. In live TM cells, many actin stress fibers were observed before the Y-27632 treatment. Y-27632 changed the cell shape and decreased stress fibers in a time-dependent manner. In fixed cells, CLAN-like structures were seen in 26.5 ± 1.7% of the actin-GFP expressed PTM cells treated with DEX for 72 h. In live imaging, there was 28% CLAN-like structure formation at 72 h after DEX treatment, and the lifetime of CLAN-like structures increased after DEX treatment. The DEX-treated cells with CLAN-like structures showed less migration than DEX-treated cells without CLAN-like structures. Furthermore, the control cells (without DEX treatment) with CLAN-like structures also showed less migration than the control cells without CLAN-like structures. These results suggested that CLAN-like structure formation was correlated with cell migration in TM cells. Live cell imaging of the actin cytoskeleton provides valuable information on the actin dynamics in TM

  20. Microarray-based mRNA expression profiling of leukemia cells treated with the flavonoid, casticin.

    PubMed

    Righeschi, Chiara; Eichhorn, Tolga; Karioti, Anastasia; Bilia, Anna Rita; Efferth, Thomas

    2012-01-01

    Natural polyphenols play an important role in tumor inhibition. We used a doxorubicin-sensitive acute T-lymphoblastic leukemia cell line (CCRF-CEM) and its multidrug-resistant subline (CEM/ADR5000) to evaluate the activity of 15 plant polyphenols isolated in our laboratory (hypericin and pseudohypericin, verbascoside, ellagic acid, casticin, kaempferol-3-O-(2'',6''-di-E-p-coumaroyl)-glucopyranoside, kaempferol-3-O-(3,4-diacetyl-2,6-di-E-p-coumaroyl) -glucopyranoside, tiliroside, salvianolic acid B, oleuropein, rosmarinic acid, bergenin) or of others from commercial sources (curcumin, epigallocatechin-3-gallate, silymarin). Casticin was the most potent compound (IC50 values of 0.28 ± 0.02 μM in CCRF-CEM and 0.44 ± 0.17 μM in CEM/ADR5000 cells. The IC50 values of the other compounds tested ranged from 1.52 μM to 164.1 μM. A microarray-based mRNA expression profiling of CCRF-CEM cells treated with casticin was performed in order to identify genes with altered expression following casticin treatment. Networks related to NF-κB, p38MAPK, histones H3 and H4, and follicle stimulating hormone were identified.

  1. Cell proliferation, apoptosis and accumulation of lipid droplets in U937-1 cells incubated with eicosapentaenoic acid.

    PubMed Central

    Finstad, H S; Drevon, C A; Kulseth, M A; Synstad, A V; Knudsen, E; Kolset, S O

    1998-01-01

    The monocytic cell line U937-1 was cultured in the presence of eicosapentaenoic acid (20:5, n-3) (EPA) or oleic acid (18:1, n-9) (OA). EPA caused a dose-dependent inhibition of cell proliferation, whereas OA had no effect. At the highest EPA concentrations, 120 and 240 microM, inhibition of cell proliferation was accompanied by initiation of apoptosis. A concentration of 60 microM EPA caused a 35% reduction in cell proliferation without inducing apoptosis, and was therefore used for further studies. Addition of antioxidants or inhibitors of eicosanoid synthesis had no influence on the reduced cell proliferation after EPA treatment. The inhibition required continuous presence of EPA in the incubation medium as the cells resumed a normal proliferation rate when they were placed in EPA-free medium. The inhibition of proliferation was not accompanied by differentiation into macrophage-like cells, as expression of serglycin and the ability to perform respiratory burst was unaffected by EPA. Expression of CD23 mRNA increased when the cells were incubated with EPA, but to a smaller extent than after retinoic acid (RA) or PMA treatment. Furthermore, expression of the monocytic differentiation markers CD36 and CD68 was lower in cells treated with EPA or OA when compared with untreated cells. The cell cycle distribution of U937-1 cells was similar in cells incubated with EPA or PMA, whereas RA-treated cells accumulated in the G1 phase. Side scatter increased in cells incubated with EPA and OA, which was ascribed to an accumulation of lipid droplets after examination of the cells by electron microscopy. The number of droplets per cell was higher in cells exposed to EPA than OA. The cellular triacylglycerol (TAG) increased 5.5- and 15.5-fold after incubation with OA and EPA respectively. No difference in the cellular content of cholesterol compared with untreated cells was observed. The TAG fraction in EPA-treated cells contained high amounts of EPA and docosapentaenoic acid

  2. All-Trans-Retinoic Acid Improves Cholestasis in α-Naphthylisothiocyanate–Treated Rats and Mdr2−/− Mice

    PubMed Central

    Mennone, Albert; Soroka, Carol J.

    2014-01-01

    Chronic cholestasis results in liver injury and eventually liver failure. Although ursodeoxycholic acid (UDCA) showed limited benefits in primary biliary cirrhosis, there is an urgent need to develop alternative therapy for chronic cholestatic disorders. Previous studies from our laboratory demonstrated that all-trans-retinoic acid (atRA) is a potent suppressor of CYP7A1, the rate-limiting enzyme in bile acid synthesis. atRA also repressed the expression of tumor growth factor-β and collagen 1A1 in activated primary human stellate cells and LX2 cells. When administered together with UDCA to bile duct–ligated rats, this combined therapy significantly reduced the bile acid pool size and improved liver conditions. To further examine whether atRA alone or in combination with UDCA has greater beneficial effects than UDCA treatment alone, we assessed this treatment in two additional chronic cholestatic rodent models: α-naphthylisothiocyanate (ANIT)–treated rats and the Mdr2−/− (Abcb4−/−) knockout mouse. atRA alone significantly reduced bile duct proliferation, inflammation, and hydroxyproline levels in ANIT-treated rats, whereas the combination of atRA and UDCA significantly reduced plasma bile salt level compared with UDCA treatment. atRA alone or in combination with UDCA significantly reduced plasma levels of alkaline phosphatase and bile salts in 12-week-old Mdr2−/− mice. Reduced bile duct proliferation and inflammation were also observed in the livers of these mice. Together, atRA alone or in combination with UDCA significantly reduced the severity of liver injury in these two animal models, further supporting the combination treatment of atRA and UDCA as a potential new therapy for patients with chronic cholestatic liver disease who have not responded fully to UDCA. PMID:24492652

  3. [Cd uptake in rice cultivars and Cd fractions in soil treated with organic acids and EDTA].

    PubMed

    Zhang, Hai-Bo; Li, Yang-Rui; Xu, Wei-Hong; Chen, Gui-Qing; Wang, Hui-Xian; Han, Gui-Qi; Zhang, Xiao-Jing; Xiong, Zhi-Ting; Zhang, Jin-Zhong; Xie, De-Ti

    2011-09-01

    A pot experiment was conducted to examine the yield, quality and cadmium (Cd) uptake in different rice cultivars, and Cd speciation in soil after exposing to Cd (0, 1 and 5 mg x kg(-1)) in the presence of organic acids and ethylenediamine tetraacetic acid (EDTA). The results showed that general increase in the yield for cultivars Xiushui63 and II you527 was observed. Yield of two rice cultivars were in order of organic acids treatment or organic acids + 1/2EDTA treatment > EDTA treatment. The exchangeable, carbonate related and ferric-manganese oxidation related Cd increased; while organic complexation Cd and residules decreased in the presence of organic acids and EDTA. Cadmium concentrations in grain, straw and roots of both cultivars markedly reduced in the presence of organic acids and EDTA. Grain Cd concentration was the lowest for plants treated with EDTA, followed by organic acids + 1/2EDTA, and the highest Cd concentration in grain was found in the treatment with organic acids. Grain Cd concentration decreased by 9.0% to 49.3% and 16.5% to 30.6% at 1 mg x kg(-1) Cd in the presence of organic acids and EDTA, and by 12.7% to 28.5% and 4.3% to 19.1% at 5 mg x kg(-1) Cd. Cadmium concentration and accumulation in plants and total Cd content in soil were higher in Xiushui63 than in that in II you527. Grain Cd concentration decreased, and yield and quality of two rice cultivars increased at the same time in the presence of organic acids + 1/2EDTA.

  4. 5-aminolevulinic acid for quantitative seek-and-treat of high-grade dysplasia in Barrett's esophagus cellular models

    NASA Astrophysics Data System (ADS)

    Yeh, Shu-Chi Allison; Ling, Celine S. N.; Andrews, David W.; Patterson, Michael S.; Diamond, Kevin R.; Hayward, Joseph E.; Armstrong, David; Fang, Qiyin

    2015-02-01

    High-grade dysplasia (HGD) in Barrett's esophagus (BE) poses increased risk for developing esophageal adenocarcinoma. To date, early detection and treatment of HGD regions are still challenging due to the sampling error from tissue biopsy and relocation error during the treatment after histopathological analysis. In this study, CP-A (metaplasia) and CP-B (HGD) cell lines were used to investigate the "seek-and-treat" potential using 5-aminolevulinic acid-induced protoporphyrin IX (PpIX). The photodynamic therapy photosensitizer then provides both a phototoxic effect and additional image contrast for automatic detection and real-time laser treatment. Complementary to our studies on automatic classification, this work focused on characterizing subcellular irradiation and the potential phototoxicity on both metaplasia and HGD. The treatment results showed that the HGD cells are less viable than metaplastic cells due to more PpIX production at earlier times. Also, due to mitochondrial localization of PpIX, a better killing effect was achieved by involving mitochondria or whole cells compared with just nucleus irradiation in the detected region. With the additional toxicity given by PpIX and potential morphological/textural differences for pattern recognition, this cellular platform serves as a platform to further investigate real-time "seek-and-treat" strategies in three-dimensional models for improving early detection and treatment of BE.

  5. Adsorption of Crystal violet on raw and acid-treated montmorillonite, K10, in aqueous suspension.

    PubMed

    Sarma, Gautam Kumar; Sen Gupta, Susmita; Bhattacharyya, Krishna G

    2016-04-15

    Crystal violet is used as a dye in cotton and silk textiles, paints and printing ink. The dye is hazardous and exposure to it may cause permanent injury to the cornea and conjunctiva including permanent blindness, and in severe cases, may lead to respiratory and kidney failure. The present work describes removal of Crystal violet from aqueous solution by adsorption on raw and acid-treated montmorillonite, K10. The clay mineral was treated with 0.25 and 0.50 M sulfuric acid and the resulting materials were characterized by XRD, zeta potential, SEM, FTIR, cation exchange capacity, BET surface area and pore volume measurements. The influences of pH, interaction time, adsorbent amount, and temperature on adsorption were monitored and explained on the basis of physico-chemical characteristics of the materials. Basic pH generally favors adsorption but considerable removal was possible even under neutral conditions. Adsorption was very rapid and equilibrium could be attained in 180 min. The kinetics conformed to second order model. Langmuir monolayer adsorption capacity of raw montmorillonite K10 was 370.37 mg g(-1) whereas 0.25 M and 0.50 M acid treated montmorillonite K10 had capacities of 384.62 and 400.0 mg g(-1) respectively at 303 K. Adsorption was exothermic and decreased in the temperature range of 293-323 K. Thermodynamically, the process was spontaneous with Gibbs energy decreasing with rise in temperature. The results suggest that montmorillonite K10 and its acid treated forms would be suitable for removing Crystal violet from aqueous solution.

  6. Proteomic analysis of the molecular response of Raji cells to maslinic acid treatment.

    PubMed

    Yap, W H; Khoo, K S; Lim, S H; Yeo, C C; Lim, Y M

    2012-01-15

    Maslinic acid, a natural pentacyclic triterpene has been shown to inhibit growth and induce apoptosis in some tumour cell lines. We studied the molecular response of Raji cells towards maslinic acid treatment. A proteomics approach was employed to identify the target proteins. Seventeen differentially expressed proteins including those involved in DNA replication, microtubule filament assembly, nucleo-cytoplasmic trafficking, cell signaling, energy metabolism and cytoskeletal organization were identified by MALDI TOF-TOF MS. The down-regulation of stathmin, Ran GTPase activating protein-1 (RanBP1), and microtubule associated protein RP/EB family member 1 (EB1) were confirmed by Western blotting. The study of the effect of maslinic acid on Raji cell cycle regulation showed that it induced a G1 cell cycle arrest. The differential proteomic changes in maslinic acid-treated Raji cells demonstrated that it also inhibited expression of dUTPase and stathmin which are known to induce early S and G2 cell cycle arrests. The mechanism of maslinic acid-induced cell cycle arrest may be mediated by inhibiting cyclin D1 expression and enhancing the levels of cell cycle-dependent kinase (CDK) inhibitor p21 protein. Maslinic acid suppressed nuclear factor-kappa B (NF-κB) activity which is known to stimulate expression of anti-apoptotic and cell cycle regulatory gene products. These results suggest that maslinic acid affects multiple signaling molecules and inhibits fundamental pathways regulating cell growth and survival in Raji cells. PMID:21893403

  7. Exciton-blocking phosphonic acid-treated anode buffer layers for organic photovoltaics

    NASA Astrophysics Data System (ADS)

    Zimmerman, Jeramy D.; Song, Byeongseop; Griffith, Olga; Forrest, Stephen R.

    2013-12-01

    We demonstrate significant improvements in power conversion efficiency of bilayer organic photovoltaics by replacing the exciton-quenching MoO3 anode buffer layer with an exciton-blocking benzylphosphonic acid (BPA)-treated MoO3 or NiO layer. We show that the phosphonic acid treatment creates buffers that block up to 70% of excitons without sacrificing the hole extraction efficiency. Compared to untreated MoO3 anode buffers, BPA-treated NiO buffers exhibit a ˜ 25% increase in the near-infrared spectral response in diphenylanilo functionalized squaraine (DPSQ)/C60-based bilayer devices, increasing the power conversion efficiency under 1 sun AM1.5G simulated solar illumination from 4.8 ± 0.2% to 5.4 ± 0.3%. The efficiency can be further increased to 5.9 ± 0.3% by incorporating a highly conductive exciton blocking bathophenanthroline (BPhen):C60 cathode buffer. We find similar increases in efficiency in two other small-molecule photovoltaic systems, indicating the generality of the phosphonic acid-treated buffer approach to enhance exciton blocking.

  8. Hyponatremic Chloride-depletion Metabolic Alkalosis Successfully Treated with High Cation-gap Amino Acid.

    PubMed

    Ryuge, Akihiro; Matsui, Katsuomi; Shibagaki, Yugo

    2016-01-01

    Chloride (Cl)-depletion alkalosis (CDA) develops due to the loss of Cl-rich body fluid, i.e., vomiting or diuretics use, and is typically treated with a chloride-rich solution such as normal saline (NS). Although NS is one of the most utilized Cl-rich solutions, high cation-gap amino acid (HCG-AA) predominantly comprises Cl and less sodium, making HCG-AA more efficient in correcting CDA. We herein report a case of CDA with chronic hyponatremia after frequent vomiting, which was successfully treated with HCG-AA without overcorrecting hyponatremia or causing hypervolemia. HCG-AA may be more beneficial than NS for treating hyponatremic or hypervolemic metabolic alkalosis. PMID:27374680

  9. Clavulanic acid inhibits MPP⁺-induced ROS generation and subsequent loss of dopaminergic cells.

    PubMed

    Kost, Gina Chun; Selvaraj, Senthil; Lee, Young Bok; Kim, Deog Joong; Ahn, Chang-Ho; Singh, Brij B

    2012-08-21

    Clavulanic acid is a psychoactive compound that has been shown to modulate central nervous system activity. Importantly, in neurotoxin-induced animal models, clavulanic acid has been shown to improve motor function (Huh et al., 2010) suggesting that it can be neuroprotective; however, the mechanism as how clavulanic acid can induce neuroprotection is not known. We demonstrate here that clavulanic acid abrogates the effects of the neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)) which mimics Parkinson's disease (PD) by inducing neurodegeneration. To further establish the mechanism we identified that clavulanic acid inhibits neurotoxin-induced loss of mitochondrial membrane potential and ROS production. Consistent with these results, neurotoxin-induced increase in Bax levels was also decreased in clavulanic acid treated cells. Importantly, neurotoxin-induced release of cytochrome c levels as well as caspase activation was also inhibited in clavulanic acid treated cells. In addition, Bcl-xl levels were also restored and the Bcl-xl/Bax ratio that is critical for inducing apoptosis was increased in clavulanic acid treated cells. Overall, these results suggest that clavulanic acid is intimately involved in inhibiting neurotoxin-induced loss of mitochondrial function and induction of apoptosis that contributes towards neuronal survival.

  10. Acetylsalicylic acid induces programmed cell death in Arabidopsis cell cultures.

    PubMed

    García-Heredia, José M; Hervás, Manuel; De la Rosa, Miguel A; Navarro, José A

    2008-06-01

    Acetylsalicylic acid (ASA), a derivative from the plant hormone salicylic acid (SA), is a commonly used drug that has a dual role in animal organisms as an anti-inflammatory and anticancer agent. It acts as an inhibitor of cyclooxygenases (COXs), which catalyze prostaglandins production. It is known that ASA serves as an apoptotic agent on cancer cells through the inhibition of the COX-2 enzyme. Here, we provide evidences that ASA also behaves as an agent inducing programmed cell death (PCD) in cell cultures of the model plant Arabidopsis thaliana, in a similar way than the well-established PCD-inducing agent H(2)O(2), although the induction of PCD by ASA requires much lower inducer concentrations. Moreover, ASA is herein shown to be a more efficient PCD-inducing agent than salicylic acid. ASA treatment of Arabidopsis cells induces typical PCD-linked morphological and biochemical changes, namely cell shrinkage, nuclear DNA degradation, loss of mitochondrial membrane potential, cytochrome c release from mitochondria and induction of caspase-like activity. However, the ASA effect can be partially reverted by jasmonic acid. Taking together, these results reveal the existence of common features in ASA-induced animal apoptosis and plant PCD, and also suggest that there are similarities between the pathways of synthesis and function of prostanoid-like lipid mediators in animal and plant organisms.

  11. Tissue distribution and urinary excretion of dimethylated arsenic and its metabolites in dimethylarsinic acid- or arsenate-treated rats

    SciTech Connect

    Adair, Blakely M.; Moore, Tanya; Conklin, Sean D.; Creed, John T.; Wolf, Douglas C.; Thomas, David J. . E-mail: thomas.david@epa.gov

    2007-07-15

    Adult female Fisher 344 rats received drinking water containing 0, 4, 40, 100, or 200 parts per million of dimethylarsinic acid or 100 parts per million of arsenate for 14 days. Urine was collected during the last 24 h of exposure. Tissues were then taken for analysis of dimethylated and trimethylated arsenicals; urines were analyzed for these arsenicals and their thiolated derivatives. In dimethylarsinic acid-treated rats, highest concentrations of dimethylated arsenic were found in blood. In lung, liver, and kidney, concentrations of dimethylated arsenic exceeded those of trimethylated species; in urinary bladder and urine, trimethylated arsenic predominated. Dimethylthioarsinic acid and trimethylarsine sulfide were present in urine of dimethylarsinic acid-treated rats. Concentrations of dimethylated arsenicals were similar in most tissues of dimethylarsinic acid- and arsenate-treated rats, including urinary bladder which is the target for dimethylarsinic acid-induced carcinogenesis in the rat. Mean concentration of dimethylated arsenic was significantly higher (P < 0.05) in urine of dimethylarsinic acid-treated rats than in arsenate-treated rats, suggesting a difference between treatment groups in the flux of dimethylated arsenic through urinary bladder. Concentrations of trimethylated arsenic concentrations were consistently higher in dimethylarsinic acid-treated rats than in arsenate-treated rats; these differences were significant (P < 0.05) in liver, urinary bladder, and urine. Concentrations of dimethylthioarsinic acid and trimethylarsine sulfide were higher in urine from dimethylarsinic acid-treated rats than from arsenate-treated rats. Dimethylarsinic acid is extensively metabolized in the rat, yielding significant concentrations of trimethylated species and of thiolated derivatives. One or more of these metabolites could be the species causing alterations of cellular function that lead to tumors in the urinary bladder.

  12. Cell density-dependent linoleic acid toxicity to Saccharomyces cerevisiae.

    PubMed

    Ferreira, Túlio César; de Moraes, Lídia Maria Pepe; Campos, Elida Geralda

    2011-08-01

    Since the discovery of the apoptotic pathway in Saccharomyces cerevisiae, several compounds have been shown to cause apoptosis in this organism. While the toxicity of polyunsaturated fatty acids (PUFA) peroxides towards S. cerevisiae has been known for a long time, studies on the effect of nonoxidized PUFA are scarce. The present study deals specifically with linoleic acid (LA) in its nonoxidized form and investigates its toxicity to yeast. Saccharomyces cerevisiae is unable to synthesize PUFA, but can take up and incorporate them into its membranes. Reports from the literature indicate that LA is not toxic to yeast cells. However, we demonstrated that yeast cell growth decreased in cultures treated with 0.1 mM LA for 4 h, and 3-(4,5 dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide reduction (a measure of respiratory activity) decreased by 47%. This toxicity was dependent on the number of cells used in the experiment. We show apoptosis induction by LA concomitant with increases in malondialdehyde, glutathione content, activities of catalase and cytochrome c peroxidase, and decreases in two metabolic enzyme activities. While the main purpose of this study was to show that LA causes cell death in yeast, our results indicate some of the molecular mechanisms of the cell toxicity of PUFA. PMID:21457450

  13. Reducing and verifying haloacetic acids in treated drinking water using a biological filter system.

    PubMed

    Lou, Jie C; Chan, Hung Y; Yang, Chih Y; Tseng, Wei B; Han, Jia Y

    2014-01-01

    This study focused on reducing the haloacetic acid (HAA) concentrations in treated drinking water. HAA has been thought to be one possible nutrient supporting heterotrophic bacteria regrowth in drinking water. In this study, experiments were conducted using a pilot-scale system to evaluate the efficiency of biological filters (BF) for reducing excess HAA concentrations in water. The BF system reduced the total HAA concentration and the concentrations of five HAA species in the water. Dichloroacetic acid (DCAA), monobromoacetic acid (MBAA) and dibromoacetic acid (DBAA) were the three main HAA5 species that were present in the treated drinking water in this investigation. Combined, these three species represent approximately 77% of the HAA5 in the finished water after BF. The verification of the empirical HAA equation for the outlet in the BF system indicated linear relationships with high correlation coefficients. The empirical equation for the HAA5 concentrations in the finished water was established by examining other nutrients (e.g., dissolved organic carbon (DOC), ultraviolet absorbance at 254 nm wavelength (UV254), and ammonia nitrogen) that can reduce pathogenic contamination. These findings may be useful for designing advanced processes for conventional water treatment plants or for managing water treatment and distribution systems for providing high-quality drinking water.

  14. Zinc recovery by ultrasound acid leaching of double kiln treated electric arc furnace dust

    SciTech Connect

    Barrera Godinez, J.A.

    1989-01-01

    The need to convert 70,000 tons a year of electric arc furnace (EAF) dust into an environmentally safe or recyclable product has encouraged studies to reclaim zinc from this waste material. Successful characterization of a double-kiln calcine, produced from EAF dust, has shown that the calcine pellets consisted mainly of zinc oxide plates with some iron oxide particles. Preliminary leaching tests using hydrochloric and sulfuric acids indicated that this calcine is suitable for selective ultrasound leaching of zinc. A factorially designed screening test using hydrochloric acid showed that ultrasound significantly lowered iron dissolution and increased zinc dissolution, thus enhancing the selective leaching of zinc. Ultrasound, temperature, air bubbling rate and acidity increased the sulfuric acid selectivity, while fluorosilicic acid was not selective. Reactor characterization through ultrasonic field measurements led to the selection of reactor and ultrasound bath, which were utilized to enhance the selectivity of a laboratory scale sulfuric acid leaching of a double-kiln treated electric arc furnace dust. Results indicated that ultrasonic leaching of this calcine is a satisfactory technique to selectively separate zinc from iron. After further iron removal by precipitation and cementation of nickel, it was possible to electrowin zinc from the leach liquor under common industrial conditions, with current efficiencies from 86% through 92% being observed. Calcine washing showed that a substantial chloride removal is possible, but fluoride ion in the electrolyte caused deposit sticking during electrowinning.

  15. A novel cleaner production process of citric acid by recycling its treated wastewater.

    PubMed

    Xu, Jian; Su, Xian-Feng; Bao, Jia-Wei; Zhang, Hong-Jian; Zeng, Xin; Tang, Lei; Wang, Ke; Zhang, Jian-Hua; Chen, Xu-Sheng; Mao, Zhong-Gui

    2016-07-01

    In this study, a novel cleaner production process of citric acid was proposed to completely solve the problem of wastewater management in citric acid industry. In the process, wastewater from citric acid fermentation was used to produce methane through anaerobic digestion and then the anaerobic digestion effluent was further treated with air stripping and electrodialysis before recycled as process water for the later citric acid fermentation. This proposed process was performed for 10 batches and the average citric acid production in recycling batches was 142.4±2.1g/L which was comparable to that with tap water (141.6g/L). Anaerobic digestion was also efficient and stable in operation. The average chemical oxygen demand (COD) removal rate was 95.1±1.2% and methane yield approached to 297.7±19.8mL/g TCODremoved. In conclusion, this novel process minimized the wastewater discharge and achieved the cleaner production in citric acid industry.

  16. In vivo study of ALA PLGA nanoparticles-mediated PDT for treating cutaneous squamous cell carcinoma

    NASA Astrophysics Data System (ADS)

    Wang, Xiaojie; Shi, Lei; Huang, Zheng; Wang, Xiuli

    2014-09-01

    Background: Squamous cell carcinoma (SCC) is a common skin cancer and its treatment is still a challenge. Although topical photodynamic therapy (PDT) is effective for treating in situ and superficial SCC, the effectiveness of topical ALA delivery to thick SCC can be limited by its bioavailability. Polylactic-co-glycolic acid nanopartieles (PLGA NPs) might provide a promising ALA delivery strategy. The aim of this study was to evaluate the efficacy of ALA PLGA NPs PDT for the treatment of cutaneous SCC in a mouse model. Methods: ALA loaded PLGA NPs were prepared and characterized. The therapeutic efficacy of ALA PLGA NP mediated PDT in treating UV-induced cutaneous SCC in the mice model were examined. Results: In vivo study showed that ALA PLGA NPs PDT were more effective than free ALA of the same concentration in treating mouse cutaneous SCC. Conclusion: ALA PLGA NPs provides a promising strategy for delivering ALA and treating cutaneous SCC.

  17. Laser restoring the glass surface treated with acid-based paint

    NASA Astrophysics Data System (ADS)

    Strusevich, Anastasia V.; Poltaev, Yuriy A.; Sinev, Dmitrii A.

    2013-11-01

    The modern city facilities are often being attacked by graffiti artists, and increasingly vandals leave "tags" using paints, which compound based on acids, hydrofluoric or acetic commonly. These paints not only ink the surface, but also increase the surface roughness, and such impact can not be corrected by conventional cleaning. Thus, it was requested to develop technology that would not only clean the surface, but also to restore its structure by smoothing out irregularities and roughness formed after exposure in acid. In this work we investigated the effect of restoring the surface of the glass, spoiled by acid-based paint and then treated with CO2-laser. During the experiments, it was found that it is real to create the single-step laser surface restoring technology.

  18. Safety in use of cryotherapy and topical salicylic acid with lactic acid combination in treating verruca vulgaris.

    PubMed

    Sultana, R; Alam, M; Khondker, L; Ahamed, R S

    2012-10-01

    An interventional study in the treatment of verruca vulgaris was conducted in sixty patients. This study conducted in the out-patient Department of Dermatology and Venereology, Chittagong Medical College Hospital, Chittagong, Bangladesh for duration of eight months (From January 2009 to September 2009). Thirty patients treated with cryotherapy, belonged to Group C and rest thirty patients treated with topical salicylic acid with lactic acid, belonged to Group D. The result showed that the highest side effects immediately after therapy for Group C was burning 30(100%), then irritation 29(96.7%), erythema 28(93.7%), blister formation 28(93.7%) and pain 23(76.7%). On the other hand, highest side effect for Group D is irritation 29(96.7%), then burning 22(73.3%), pain 11(36.7%), pruritus 06(20%), blister formation 04(13%) and erythema 01(3.3%). Statistical significant difference was observed between Group C & Group D patients other than irritation. At 2nd visit, erythema 26(86.7%) was evidenced for Group C, whereas in Group D, there was irritation 16(53.3%). After 3rd visit in 4th week for Group C patients, there was burning 13(43.3%) but in Group D patients, hypo-pigmentation 13(43.3%) was evidenced. On 4th visit in 6th week, hypo-pigmentation 09(30%) was seen in Group C, while in Group D, pruritus and irritation were found. Statistical significant difference was observed between Group C & Group D respondents. Both treatments were associated with side-effects but these were higher with cryotherapy. The study recommends the combination of topical salicylic acid with lactic acid is safer than cryotherapy.

  19. Mild hypothermia combined with a scaffold of NgR-silenced neural stem cells/Schwann cells to treat spinal cord injury.

    PubMed

    Wang, Dong; Liang, Jinhua; Zhang, Jianjun; Liu, Shuhong; Sun, Wenwen

    2014-12-15

    Because the inhibition of Nogo proteins can promote neurite growth and nerve cell differentiation, a cell-scaffold complex seeded with Nogo receptor (NgR)-silenced neural stem cells and Schwann cells may be able to improve the microenvironment for spinal cord injury repair. Previous studies have found that mild hypothermia helps to attenuate secondary damage in the spinal cord and exerts a neuroprotective effect. Here, we constructed a cell-scaffold complex consisting of a poly(D,L-lactide-co-glycolic acid) (PLGA) scaffold seeded with NgR-silenced neural stem cells and Schwann cells, and determined the effects of mild hypothermia combined with the cell-scaffold complexes on the spinal cord hemi-transection injury in the T9 segment in rats. Compared with the PLGA group and the NgR-silencing cells + PLGA group, hindlimb motor function and nerve electrophysiological function were clearly improved, pathological changes in the injured spinal cord were attenuated, and the number of surviving cells and nerve fibers were increased in the group treated with the NgR-silenced cell scaffold + mild hypothermia at 34°C for 6 hours. Furthermore, fewer pathological changes to the injured spinal cord and more surviving cells and nerve fibers were found after mild hypothermia therapy than in injuries not treated with mild hypothermia. These experimental results indicate that mild hypothermia combined with NgR gene-silenced cells in a PLGA scaffold may be an effective therapy for treating spinal cord injury.

  20. Stabilizing platinum in phosphoric acid fuel cells

    NASA Technical Reports Server (NTRS)

    Remick, R. J.

    1981-01-01

    The cathode of the phosphoric acid fuel cell uses a high surface area platinum catalyst supported on a carbon substrate. During operation, the small platinum crystallites sinter, causing loss in cell performance. A support was developed that stabilizes platinum in the high surface area condition by retarding or preventing the sintering process. The approach is to form etch pits in the carbon by oxidizing the carbon in the presence of a metal oxide catalyst, remove the metal oxide by an acid wash, and then deposit platinum in these pits. Results confirm the formation of etch pits in each of the three supports chosen for investigation: Vulcan XC-72R, Vulcan XC-72 that was graphized at 2500 C, and Shawinigan Acetylene Black.

  1. Hydrochloric acid alters the effect of L-glutamic acid on cell viability in human neuroblastoma cell cultures.

    PubMed

    Croce, Nicoletta; Bernardini, Sergio; Di Cecca, Stefano; Caltagirone, Carlo; Angelucci, Francesco

    2013-07-15

    l-Glutamic acid (l-glutamate) is used to induce excitotoxicity and test neuroprotective compounds in cell cultures. However, because l-glutamate powder is nearly insoluble in water, many manufacturers recommend reconstituting l-glutamate in hydrochloric acid (HCl) prior to successive dilutions. Nevertheless, HCl, even at low concentrations, may alter the pH of the cell culture medium and interfere with cell activity. Thus, the aim of this study was to evaluate whether the reconstitution of l-glutamate powder in HCl alters its capacity to induce neurotoxicity in different human neuroblastoma cell lines. SH-SY5Y, IMR-32 and SK-N-BE(2) cells were exposed to various concentrations of l-glutamate, which was either reconstituted in HCl (1M) or post re-equilibrated to the pH of the culture medium (7.5). After 24 and 48h of incubation, changes in the cell viability of treated versus untreated cells were evaluated. The effect of an identical amount of HCl present in the l-glutamate dilutions on neuroblastoma cell survival was also investigated. Our data showed that the neurotoxicity of glutamate reconstituted in HCl was comparable to that of HCl alone. Moreover, the pH variations induced by glutamate or HCl in the culture medium were similar. When the pH of the glutamate stock solution was re-equilibrated, l-glutamate induced variation in cell viability to a lower extent and after a longer incubation time. This study demonstrated that HCl used to reconstitute l-glutamate powder might alter the effect of glutamate itself in neuroblastoma cell cultures. Thus, this information might be useful to scientists who use l-glutamate to induce excitotoxicity or to test neuroprotective agents.

  2. Chemical, sensory and shelf life evaluation of sliced salmon treated with salts of organic acids

    PubMed Central

    Sallam, Khalid Ibrahim

    2007-01-01

    This study was carried out to evaluate the shelf life, chemical quality and sensory attributes of salmon slices treated by dipping in 2.5% aqueous solution of sodium acetate (NaA), sodium lactate (NaL), or sodium citrate (NaC) during refrigerated storage at 1 °C. The chemical analyses demonstrated significant reduction in K value, hypoxanthine (Hx) concentration, total volatile base nitrogen (TVB-N), and trimethylamine (TMA) in treated salmon slices when compared with the control. Sensory scores of treated salmon were in a typical category for appearance, juiciness and tenderness compared with the control. Only minor changes in the sensory attributes were recognized by few panellists in NaA- and NaL-treated samples. A shelf life of 12, 12 and 15 days has been estimated for salmon treated with NaL, NaC, and NaA, respectively, versus 8 days for control. The salts of organic acids can therefore be used as safe preservatives for fish under refrigerated storage. PMID:17245440

  3. Palifosfamide in Treating Patients With Recurrent Germ Cell Tumors

    ClinicalTrials.gov

    2015-06-11

    Adult Central Nervous System Germ Cell Tumor; Adult Teratoma; Malignant Extragonadal Germ Cell Tumor; Malignant Extragonadal Non-Seminomatous Germ Cell Tumor; Extragonadal Seminoma; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Ovarian Germ Cell Tumor; Stage IV Extragonadal Non-Seminomatous Germ Cell Tumor; Stage IV Extragonadal Seminoma; Stage IV Ovarian Germ Cell Tumor

  4. World wide IFC phosphoric acid fuel cell implementation

    SciTech Connect

    King, J.M. Jr

    1996-04-01

    International Fuel Cells, a subsidary of United technologies Corporation, is engaged in research and development of all types of fuel cell technologies and currently manufactures alkaline fuel cell power plants for the U.S. manned space flight program and natural gas fueled stationary power plants using phosphoric acid fuel cells. This paper describes the phosphoric acid fuel cell power plants.

  5. Promise of Retinoic Acid-Triazolyl Derivatives in Promoting Differentiation of Neuroblastoma Cells.

    PubMed

    Lone, Ali Mohd; Dar, Nawab John; Hamid, Abid; Shah, Wajaht Amin; Ahmad, Muzamil; Bhat, Bilal A

    2016-01-20

    Retinoic acid induces differentiation in various types of cells including skeletal myoblasts and neuroblasts and maintains differentiation of epithelial cells. The present study demonstrates synthesis and screening of a library of retinoic acid-triazolyl derivatives for their differentiation potential on neuroblastoma cells. Click chemistry approach using copper(I)-catalyzed azide-alkyne cycloaddition was adopted for the preparation of these derivatives. The neurite outgrowth promoting potential of retinoic acid-triazolyl derivatives was studied on neuroblastoma cells. Morphological examination revealed that compounds 8a, 8e, 8f, and 8k, among the various derivatives screened, exhibited promising neurite-outgrowth inducing activity at a concentration of 10 μM compared to undifferentiated and retinoic acid treated cells. Further on, to confirm this differentiation potential of these compounds, neuroblastoma cells were probed for expression of neuronal markers such as NF-H and NeuN. The results revealed a marked increase in the NF-H and NeuN protein expression when treated with 8a, 8e, 8f, and 8k compared to undifferentiated and retinoic acid treated cells. Thus, these compounds could act as potential leads in inducing neuronal differentiation for future studies.

  6. p38 mitogen-activated protein kinase interacts with vinculin at focal adhesions during fatty acid-stimulated cell adhesion

    PubMed Central

    George, Margaret D.; Wine, Robert N.; Lackford, Brad; Kissling, Grace E.; Akiyama, Steven K.; Olden, Kenneth; Roberts, John D.

    2014-01-01

    Arachidonic acid stimulates cell adhesion by activating α2β1 integrins in a process that depends on protein kinases, including p38 mitogen activated protein kinase. Here, we describe the interaction of cytoskeletal components with key signaling molecules that contribute to spreading of, and morphological changes in, arachidonic acid-treated MDA-MB-435 human breast carcinoma cells. Arachidonic acid-treated cells showed increased attachment and spreading on collagen type IV as measured by electric cell-substrate impedance sensing. Fatty acid-treated cells displayed short cortical actin filaments associated with an increased number of β1 integrin-containing pseudopodia whereas untreated cells displayed elongated stress fibers and fewer clusters of β1 integrins. Confocal microscopy of arachidonic acid-treated cells showed that vinculin and phospho-p38 both appeared enriched in pseudopodia and at the tips of actin filaments, and fluorescence ratio imaging indicated the increase was specific for the phospho-(active) form of p38. Immunoprecipitates of phospho-p38 from extracts of arachidonic acid-treated cells contained vinculin, and GST-vinculin fusion proteins carrying the central region of vinculin bound phospho-p38, whereas fusion proteins expressing the terminal portions of vinculin did not. These data suggest that phospho-p38 associates with particular domains on critical focal adhesion proteins that are involved in tumor cell adhesion and spreading and that this association can be regulated by factors in the tumor microenvironment. PMID:24219282

  7. Blood Stem Cell Transplant in Treating Patients With Hematologic Cancer

    ClinicalTrials.gov

    2014-06-05

    Adult Langerhans Cell Histiocytosis; Childhood Langerhans Cell Histiocytosis; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms

  8. MTHFR C677T polymorphism, folic acid and hyperhomocysteinemia in levodopa treated patients with Parkinson's disease.

    PubMed

    Woitalla, D; Kuhn, W; Müller, T

    2004-01-01

    Certain mutations (TT homozygous; CT heterozygous; CC wild-type) of the methylenetetrahydrofolate (MTHFR) gene and long-term levodopa application in patients with Parkinson's disease (PD) support onset of hyperhomocysteinemia. Total plasma homocysteine (t-hcys) depends on B6, B12, folic acid, all of which support remyelination from t-hcys to methionine. Objective of this trial were to compare B6, B12, folic acid and t-hcys levels in plasma of 83 levodopa treated PD patients and 44 controls. PD patients with the CT or TT genotype had significant higher t-hcys levels than controls or PD patients with the CC allele. Concentrations of B6 or B12 did not differ, but folic acid was significant higher in PD patients with the CT mutation. We recommend MTHFR genotyping, t-hcys monitoring and early vitamin supplementation in PD patients. The folic acid increase in PD patients with the CT allele is hypothetically due to an endogenous upregulation of folic acid absorption to decrease t-hcys. PMID:15354385

  9. Effect of losartan on serum uric acid in hypertension treated with a diuretic: the COMFORT study.

    PubMed

    Matsumura, Kiyoshi; Arima, Hisatomi; Tominaga, Mitsuhiro; Ohtsubo, Toshio; Sasaguri, Toshiyuki; Fujii, Koji; Fukuhara, Masayo; Uezono, Keiko; Morinaga, Yuki; Ohta, Yuko; Otonari, Takatoshi; Kawasaki, Junya; Kato, Isao; Tsuchihashi, Takuya

    2015-01-01

    It has been shown that losartan, an angiotensin II receptor blocker (ARB), reduces serum uric acid levels. However, the effects of losartan on serum uric acid levels in the patients treated with a thiazide diuretic have not been fully elucidated. We have investigated the effects of losartan compared with other ARBs on blood variables and blood pressure control in hypertensive patients treated with a thiazide diuretic using data from the COMFORT study. The present analysis included a total of 118 hypertensive subjects on combination treatment with ARBs except for losartan and a diuretic who were randomly assigned to a daily regimen of a combination pill (losartan 50 mg/hydrochlorothiazide 12.5 mg) or to continuation of two pills, an ARB except for losartan and a diuretic. Blood pressures were evaluated at 1, 3, and 6 months after randomization and changes in blood variables including serum uric acid were evaluated during 6 months treatment period. Mean follow-up blood pressure levels were not different between the combination pill (losartan treatment) group and the control (ARBs except for losartan) group. On the other hand, serum uric acid significantly decreased in the combination pill group compared with the control group (-0.44 versus + 0.10 mg/dl; p = 0.01), although hematocrit, serum creatinine, sodium and potassium were not different between the groups. These results suggest that the treatment regimen switched from a combination therapy of ARBs except for losartan and a diuretic to a combination pill (losartan/ hydrochlorothiazide) decreases serum uric acid without affecting blood pressure control.

  10. Macronutrients, fatty acids, cholesterol and renal cell cancer risk.

    PubMed

    Bidoli, Ettore; Talamini, Renato; Zucchetto, Antonella; Polesel, Jerry; Bosetti, Cristina; Negri, Eva; Maruzzi, Daniele; Montella, Maurizio; Franceschi, Silvia; La Vecchia, Carlo

    2008-06-01

    The role of selected macronutrients, fatty acids and cholesterol in the etiology of renal cell carcinoma (RCC) was analyzed using data from a case-control study conducted in 4 Italian areas between 1992 and 2004. Cases were 767 patients with incident, histologically confirmed RCC, admitted to major teaching and general hospitals of the study areas. Controls were 1,534 subjects admitted for acute, nonneoplastic conditions to the same hospitals. Information on dietary habits and nutrient intake was elicited using a validated food frequency questionnaire including 78 food groups and recipes. Odds ratios (OR) and 95% confidence intervals (CI) for increasing levels of nutrient intake were estimated after allowance for total energy intake and other potential confounding factors. A direct association with RCC was found for starch intake (OR = 1.9 for highest versus lowest quintile of intake; 95% CI: 1.4-2.6, p-value for trend = 0.001), while an inverse association was found for fats from vegetable sources (OR = 0.6; 95% CI: 0.5-0.8; p-value for trend = 0.002), unsaturated fatty acids (OR = 0.5; 95% CI: 0.4-0.7; p-value for trend = 0.0002), and polyunsaturated fatty acids (OR = 0.5; 95% CI: 0.4-0.7; p-value for trend = 0.001). Among polyunsaturated fatty acids, linoleic acid (OR = 0.5; 95% CI: 0.4-0.7; p-value for trend = 0.0001) and linolenic acid (OR = 0.7; 95% CI: 0.5-1.0; p-value for trend = 0.01) were inversely related to RCC. When 6 major macronutrients were included in the same model, the adverse effect of high intake of starch remained statistically significant, together with the protective effect of polyunsaturated fatty acids. Results were consistent in strata of age, body mass index, treated hypertension, energy intake, stage and family history of RCC. PMID:18224688

  11. Biosensors for liquid biopsy: circulating nucleic acids to diagnose and treat cancer.

    PubMed

    Bellassai, Noemi; Spoto, Giuseppe

    2016-10-01

    The detection of cancer biomarkers freely circulating in blood offers new opportunities for cancer early diagnosis, patient follow-up, and therapy efficacy assessment based on liquid biopsy. In particular, circulating cell-free nucleic acids released from tumor cells have recently attracted great attention also because they become detectable in blood before the appearance of other circulating biomarkers, such as circulating tumor cells. The detection of circulating nucleic acids poses several technical challenges that arise from their low concentration and relatively small size. Here, possibilities offered by innovative biosensing approaches for the detection of circulating DNA in peripheral blood and blood-derived products such as plasma and serum blood are discussed. Different transduction principles are used to detect circulating DNAs and great advantages are derived from the combined use of nanostructured materials.

  12. Ultrastructural Analysis of Leishmania infantum chagasi Promastigotes Forms Treated In Vitro with Usnic Acid

    PubMed Central

    da Luz, João S. B.; de Oliveira, Erwelly B.; Martins, Monica C. B.; da Silva, Nicácio H.; Alves, Luiz C.; dos Santos, Fábio A. B.; da Silva, Luiz L. S.; Silva, Eliete C.; de Medeiros, Paloma L.

    2015-01-01

    Leishmaniasis is considered by the World Health Organization as one of the infectious parasitic diseases endemic of great relevance and a global public health problem. Pentavalent antimonials used for treatment of this disease are limited and new phytochemicals emerge as an alternative to existing treatments, due to the low toxicity and cost reduction. Usnic acid is uniquely found in lichens and is especially abundant in genera such as Alectoria, Cladonia, Evernia, Lecanora, Ramalina, and Usnea. Usnic acid has been shown to exhibit antiviral, antiprotozoal, antiproliferative, anti-inflammatory, and analgesic activity. The aim of this study was to evaluate the antileishmanial activity of usnic acid on Leishmania infantum chagasi promastigotes and the occurrence of drug-induced ultrastructural damage in the parasite. Usnic acid was effective against the promastigote forms (IC50 = 18.30 ± 2.00 µg/mL). Structural and ultrastructural aspects of parasite were analyzed. Morphological alterations were observed as blebs in cell membrane and shapes given off, increasing the number of cytoplasmic vacuoles, and cellular and mitochondrial swelling, with loss of cell polarity. We concluded that the usnic acid presented antileishmanial activity against promastigote forms of Leishmania infantum chagasi and structural and ultrastructural analysis reinforces its cytotoxicity. Further, in vitro studies are warranted to further evaluate this potential. PMID:25767824

  13. Microbial shelf life determination of vacuum-packaged fresh beef treated with polylactic acid, lactic acid, and nisin solutions.

    PubMed

    Ariyapitipun, T; Mustapha, A; Clarke, A D

    1999-08-01

    The effectiveness of polylactic acid, lactic acid, nisin, and combinations of the acids and nisin on extending the shelf-life of raw beef was determined. Fresh beef pieces (5 by 5 by 2.5 cm) were dipped in a solution of 2% low molecular weight polylactic acid (LMW-PLA), 2% lactic acid (LA), 200 IU of nisin per ml, or the combinations of nisin in either 2% LMW-PLA or 2% LA. The samples were then drip-dried, vacuum-packaged, and stored at 4 degrees C for up to 56 days. The beef surface pH values and numbers of psychrotrophic aerobic bacteria, psychrotrophic and mesophilic Enterobacteriaceae, Pseudomonas, and Lactobacillus were determined weekly for 56 days. The average surface pH values of the beef samples treated with 2% LMW-PLA or the combination of 200 IU of nisin per ml and 2% LMW-PLA were significantly reduced to 5.19 and 5.17, respectively, at day 0 (P < or = 0.05), while those decontaminated with 2% LA or 200 IU of nisin per ml in 2% LA solution were significantly decreased from 5.62 to 4.98 and 4.96, respectively. The 2% LMW-PLA, 2% LA, or the combinations of each acid and nisin showed immediate inhibitory effects on psychrotrophic aerobic bacteria (1.94, 2.36, 2.59, and 1.76 log reduction, respectively), psychrotrophic Enterobacteriaceae (1.37, 1.86, 1.77, and 1.35 log reduction, respectively), mesophilic Enterobacteriaceae (1.00, 1.00, 0.82, and 0.68 log reduction, respectively), and Pseudomonas (1.77, 1.57, 1.76, and 1.41 log reduction, respectively) on fresh beef (P < or = 0.05). The reduction was evident up to 56 days as seen by the numbers of Enterobacteriaceae and Pseudomonas (P < or = 0.05). Because there was no interaction between treatments and storage times, the data in each period were combined and presented as effect of treatments on overall microbial counts of fresh beef. It was found that 2% LMW-PLA, 2% LA, and the combinations of each acid and nisin significantly lowered the population of the above organisms compared with the untreated control

  14. [Basal cell carcinoma, squamous cell carcinoma and premalignant skin lesions--how to treat?].

    PubMed

    Pitkänen, Sari; Jeskanen, Leila; Ylitalo, Leea

    2014-01-01

    Increasing exposure to UV radiation is considered the most important etiologic factor of nonmelanoma skin cancers. Consequently, exposed areas such as the scalp and face, are the primary areas for developing non-melanoma skin cancers. Once a patient has presented with one tumor, additional lesions are common. The diagnosis is based on typical clinical picture and biopsy or excision for histopathological analysis. Various non-surgical treatment options have been established. Superficial basal cell carcinoma, superficial carcinoma in situ and all actinic keratoses are preferentially treated non-surgically. Most other basal cell and squamous cell carcinomas should be surgically removed. PMID:24724463

  15. Effectiveness of hyaluronic acid for treating diabetic foot: a systematic review and meta-analysis.

    PubMed

    Chen, Chao-Pen; Hung, Wei; Lin, Sheng-Hsuan

    2014-01-01

    Diabetic foot ulceration is a major complication of diabetes mellitus. Hyaluronic acid (HA) is used in the treatment of diabetic foot. This meta-analysis was designed to evaluate if HA increased the complete healing rate of diabetic foot compared with controls. We searched Medline, Cochrane, EMBASE, Google Scholar (until January 31, 2014) databases for prospective randomized controlled trials that assessed the effectiveness of HA in treating foot ulcers resulting from diabetes. The primary outcome for the study was complete healing rate of the ulcer at 12 weeks. Three hundred twenty-eight patients were identified from four studies that evaluated the rate of healing of diabetic foot that were treated with HA or controls. Among the four studies, odd ratios (OR) ranged from 1.19 to 8.86, with the overall OR being 1.71 (p = 0.047; 95% confidence interval = 1.01 to 2.90). In summary, our meta-analysis strengthens the findings that HA is beneficial in treating diabetic foot by increasing the rate of wound healing. These findings support the use of HA in treating diabetic foot.

  16. Bioavailability of heavy metals in strongly acidic soils treated with exceptional quality biosolids

    SciTech Connect

    Basta, N.T.; Sloan, J.J.

    1999-03-01

    New federal regulations may increase application of exceptional quality (EQ) biosolids to acidic soils, and information on the effect of this practice on bioavailability of heavy metal is limited. The objective of this study was to compare bioavailability of heavy metal in soil treated with nonalkaline or alkaline EQ biosolids with limestone-treated soils. Three acidic soils (pH 3.7--4.3) were treated with three amounts of lime-stabilized biosolids (LS), anaerobic-digested biosolids (AN), or agricultural limestone (L), and incubated at 25 C. Soil solution Cd, Zn, and other chemical constituents were measured at 1, 30, 90, and 180 d incubation. Soil solution Cd and Zn were AN > LS {ge} L, C. Soil solution Cd and Zn increased with AN applied but decreased wit h LS applied. The high application of LS had soil solution Zn dramatically decreased at soil pH > 5.5 and >5.1, respectively. Soil solution Cd and Zn increases were AN > LS with incubation time. Biosolids treatments increased heavy metal in Ca(NO{sub 3}){sub 2} and NaOAc fractions. Except for Cd, most metal from biosolids were in EDTA and HNO{sub 3} fractions. Heavy metal bioavailability, measured using lettuce (Latuca sativa L.), was AN > LS {ge} L, C. Although state regulations prohibiting application of nonalkaline EQ biosolids to acidic soil is a prudent practice, application of EQ alkaline biosolids that achieves soil pH > 5 minimizes risk from soil solution Cd and Zn and plant uptake of heavy metal.

  17. Orexin A attenuates palmitic acid-induced hypothalamic cell death.

    PubMed

    Duffy, Cayla M; Nixon, Joshua P; Butterick, Tammy A

    2016-09-01

    Palmitic acid (PA), an abundant dietary saturated fatty acid, contributes to obesity and hypothalamic dysregulation in part through increase in oxidative stress, insulin resistance, and neuroinflammation. Increased production of reactive oxygen species (ROS) as a result of PA exposure contributes to the onset of neuronal apoptosis. Additionally, high fat diets lead to changes in hypothalamic gene expression profiles including suppression of the anti-apoptotic protein B cell lymphoma 2 (Bcl-2) and upregulation of the pro-apoptotic protein B cell lymphoma 2 associated X protein (Bax). Orexin A (OXA), a hypothalamic peptide important in obesity resistance, also contributes to neuroprotection. Prior studies have demonstrated that OXA attenuates oxidative stress induced cell death. We hypothesized that OXA would be neuroprotective against PA induced cell death. To test this, we treated an immortalized hypothalamic cell line (designated mHypoA-1/2) with OXA and PA. We demonstrate that OXA attenuates PA-induced hypothalamic cell death via reduced caspase-3/7 apoptosis, stabilization of Bcl-2 gene expression, and reduced Bax/Bcl-2 gene expression ratio. We also found that OXA inhibits ROS production after PA exposure. Finally, we show that PA exposure in mHypoA-1/2 cells significantly reduces basal respiration, maximum respiration, ATP production, and reserve capacity. However, OXA treatment reverses PA-induced changes in intracellular metabolism, increasing basal respiration, maximum respiration, ATP production, and reserve capacity. Collectively, these results support that OXA protects against PA-induced hypothalamic dysregulation, and may represent one mechanism through which OXA can ameliorate effects of obesogenic diet on brain health. PMID:27449757

  18. Induction of apoptosis by gallic acid in human stomach cancer KATO III and colon adenocarcinoma COLO 205 cell lines.

    PubMed

    Yoshioka, K; Kataoka, T; Hayashi, T; Hasegawa, M; Ishi, Y; Hibasami, H

    2000-01-01

    Antitumor effects of gallic acid on human stomach cancer KATO III cells and human colon adenocarcinoma COLO 205 cells were investigated. The exposures of KATO III and COLO 205 cells to gallic acid led to both growth inhibition and induction of apoptosis. Morphological changes showing apoptotic bodies were observed in both the cell lines treated with gallic acid. The fragmentations by gallic acid of DNA to oligonucleosomal-sized fragments, that are characteristics of apoptosis, were observed to be concentration- and time-dependent. These findings suggest that growth inhibitions by gallic acid of KATO III cells and COLO 205 cells result from the apoptosis induced by gallic acid. Thus, gallic acid might be a candidate drug for digestive gut cancer treatment to overcome the resistance to chemotherapeutic drugs. PMID:11032918

  19. The study of aluminum loss and consequent phase transformation in heat-treated acid-leached kaolin

    SciTech Connect

    Foo, Choo Thye; Mahmood, Che Seman; Mohd Salleh, Mohamad Amran

    2011-04-15

    This study investigates the effect of Al leaching during Fe removal from kaolin to mullite. Heat-treated kaolin was obtained by heating natural kaolin at 400, 500, 600, 700, 800 and 900 deg. C. The heat-treated kaolin was then leached at 100 deg. C with 4 M, 3 M, 2 M, 1 M, 0.2 M solution of H{sub 2}SO{sub 4} and 0.2 M solution of oxalic acid. The dried samples were sintered to 1300 deg. C for 4 h at a heating rate of 10 deg. C min{sup -1}. X-ray diffractometry and differential thermal analysis were used to study the phase transformation of kaolin to mullite. It was found that 700 deg. C is the optimum preheat-treatment temperature to leach out Fe and also Al for both types of the acids used. The majority of the 4 M sulfuric acid-treated kaolins formed the cristobalite phase when sintered. On the other hand, 1 M, 0.2 M sulfuric acid and 0.2 M oxalic acid leached heat-treated kaolin formed mullite and quartz phase after sintering. - Research Highlights: {yields} Preheat-treatment of kaolin improves the leachability of unwanted iron. {yields} The optimum preheat-treatment temperature is 700 deg. C. {yields} Sintered 4 M sulfuric acid-treated kaolin majorly formed the cristobalite phase. {yields} Sintered 0.2 M oxalic acid-treated kaolin formed lesser amorphous silicate phase.

  20. Uric acid plasma level and urine pH in rats treated with ambroxol.

    PubMed

    Drewa, Tomasz; Wolski, Zbigniew; Gruszka, Marzena; Misterek, Bartosz; Lysik, Joanna

    2007-01-01

    It was a chance discovery that ambroxol parenteral administration led to urinary bladder stone formation in rats. This study was undertaken to examine the serum uric acid levels and urine pH in rats after ambroxol parenteral treatment. Ambroxol influence on the uric acid level was measured in 5 rats (Rattus sp.) treated with 60 mg/kg (dissolved in injection water, sc, daily) during 2 weeks. Ambroxol influence on urine pH was examined on 45 rats divided into 3 groups. Rats from the 1st and 2nd group received 30 and 60 mg/kg/24h ambroxol, respectively. Urine was collected once daily and measured with strip kit. All values were presented as the means with standard deviations. The Student t test was used to compare the means, p < 0.05 was considered as significant. Dynamics of pH changes was measured in 4 rats treated with 60 mg/kg/24h of ambroxol. Controls received 1 mL of injection water sc. Serum uric acid level increased up to 8.7 +/- 1.0 mg/dL vs. 5.7 +/- 1.0 mg/dL in control (p < 0.002). In the 1st and 2nd group urine pH increased up to 7.5 +/- 0.5 and 7.6 +/- 0.5 vs. 6.7 +/- 0.4 (p < 0.05). Ambroxol withdrawal resulted in sequential urine pH decrease. 11 days after interruption of ambroxol therapy pH reached the starting value. Urine pH changes and possible disturbances in uric acid metabolic pathway may influence on the stone formation in rats after ambroxol parenteral treatment. The influence of ambroxol on urinary tract GAG layer and the balance between xanthine and CaOx in the urine should be checked.

  1. Mucosal acid causes gastric mucosal microcirculatory disturbance in nonsteroidal anti-inflammatory drug-treated rats.

    PubMed

    Funatsu, Toshiyuki; Chono, Koji; Hirata, Takuya; Keto, Yoshihiro; Kimoto, Aishi; Sasamata, Masao

    2007-01-01

    The mechanism by which nonsteroidal anti-inflammatory drugs (NSAIDs) suppress gastric mucosal blood flow is not fully understood, although the depletion of mucosal prostaglandin E2 has been proposed as one possible explanation. We investigated the role of gastric acid on gastric mucosal blood flow in NSAID-treated rats. A rat stomach was mounted in an ex vivo chamber, and gastric mucosal blood flow was measured sequentially in a 5-mm2 area of the gastric corpus using a scanning laser Doppler perfusion image system. Results showed that diclofenac (5 mg/kg s.c.) and indomethacin (10 mg/kg s.c.) did not affect gastric mucosal blood flow, although both strongly decreased mucosal prostaglandin E2 when saline was instilled into the gastric chamber. On replacement of the saline in the chamber with 100 mM hydrochloric acid, these drugs caused a decrease in gastric mucosal blood flow levels within 30 min. The specific cyclooxygenase (COX)-2 inhibitors celecoxib (50 mg/kg s.c.) and rofecoxib (25 mg/kg s.c.) did not affect mucosal prostaglandin E2 level, nor did they decrease gastric mucosal blood flow, even when hydrochloric acid was added to the chamber. Furthermore, measurement of vasoconstrictive factors present in the mucosa showed that endothelin-1 levels increased after administration of diclofenac s.c. in the presence of intragastric hydrochloric acid. This indicates that the presence of mucosal hydrochloric acid plays an important role in the NSAID-induced decrease in gastric mucosal blood flow, while the COX-1-derived basal prostaglandin E2, which is unlikely to control gastric mucosal blood flow itself, protects microcirculatory systems from mucosal hydrochloric acid.

  2. Donor T Cells After Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies

    ClinicalTrials.gov

    2016-07-20

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Blastic Phase Chronic Myelogenous Leukemia; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Phase Chronic Myelogenous Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood

  3. Lysophosphatidic acid enhances survival of human CD34+ cells in ischemic conditions

    PubMed Central

    Kostic, Ivana; Fidalgo-Carvalho, Isabel; Aday, Sezin; Vazão, Helena; Carvalheiro, Tiago; Grãos, Mário; Duarte, António; Cardoso, Carla; Gonçalves, Lino; Carvalho, Lina; Paiva, Artur; Ferreira, Lino

    2015-01-01

    Several clinical trials are exploring therapeutic effect of human CD34+ cells in ischemic diseases, including myocardial infarction. Unfortunately, most of the cells die few days after delivery. Herein we show that lysophosphatidic acid (LPA)-treated human umbilical cord blood-derived CD34+ cells cultured under hypoxic and serum-deprived conditions present 2.2-fold and 1.3-fold higher survival relatively to non-treated cells and prostaglandin E2-treated cells, respectively. The pro-survival effect of LPA is concentration- and time-dependent and it is mediated by the activation of peroxisome proliferator-activator receptor γ (PPARγ) and downstream, by the activation of pro-survival ERK and Akt signaling pathways and the inhibition of mitochondrial apoptotic pathway. In hypoxia and serum-deprived culture conditions, LPA induces CD34+ cell proliferation without maintaining the their undifferentiating state, and enhances IL-8, IL-6 and G-CSF secretion during the first 12 h compared to non-treated cells. LPA-treated CD34+ cells delivered in fibrin gels have enhanced survival and improved cardiac fractional shortening at 2 weeks on rat infarcted hearts as compared to hearts treated with placebo. We have developed a new platform to enhance the survival of CD34+ cells using a natural and cost-effective ligand and demonstrated its utility in the preservation of the functionality of the heart after infarction. PMID:26553339

  4. Polyunsaturated fatty acids trigger apoptosis of colon cancer cells through a mitochondrial pathway

    PubMed Central

    Zhang, Chengcheng; Yu, Haining; Shen, Yuzhen; Ni, Xiaofeng; Das, Undurti N.

    2015-01-01

    Introduction Colorectal cancer is common in developed countries. Polyunsaturated fatty acids (PUFAs) have been reported to possess tumoricidal action, but the exact mechanism of their action is not clear. Material and methods In the present study, we studied the effect of various n-6 and n-3 fatty acids on the survival of the colon cancer cells LoVo and RKO and evaluated the possible involvement of a mitochondrial pathway in their ability to induce apoptosis. Results It was observed that n-3 α-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid (ALA, EPA and DHA respectively) and n-6 linoleic acid, gamma-linolenic acid and arachidonic acid (LA, GLA and AA respectively) induced apoptosis of the colon cancer cells LoVo and RKO at concentrations above 120 μM (p < 0.01 compared to control). The semi-differentiated colon cancer cell line RKO was more sensitive to the cytotoxic action of PUFAs compared to the undifferentiated colon cancer cell line LoVo. PUFA-treated cells showed an increased number of lipid droplets in their cytoplasm. PUFA-induced apoptosis of LoVo and RKO cells is mediated through a mitochondria-mediated pathway as evidenced by loss of mitochondrial membrane potential, generation of ROS, accumulation of intracellular Ca2+, activation of caspase-9 and caspase-3, decreased ATP level and increase in the Bax/Bcl2 expression ratio. Conclusions PUFAs induced apoptosis of colon cancer cells through a mitochondrial dependent pathway. PMID:26528354

  5. Complexing of amino acids to DNA by chromate in intact cells.

    PubMed Central

    Voitkun, V; Zhitkovich, A; Costa, M

    1994-01-01

    Using o-pthaldialdehyde (OPT) fluorescence, the amino acids associated with DNA were studied following exposure of intact Chinese hamster ovary cells to chromate. Rigorous extraction with EDTA, acid, or base was required to release the amino acids cross-linked to the DNA isolated from control or chromate-treated cells by standard procedures (i.e., proteinase K, phenol, etc.). Amino acids resisting extraction from DNA were not studied since analysis was limited to those that could be released by these procedures. There was a chromate dose-dependent increase in amino acids complexed with the DNA that could be released by EDTA, acid, and base, and these amino acids were separated by HPLC and identified. Substantial increases in cysteine, glutamine, glutamic acid, histidine, threonine, and tyrosine were found as a function of increasing concentrations of chromate. There was also a time-dependent increase in complexing of these amino acids to the DNA by chromate. The amino acids found complexed to DNA in intact cells by chromate were thought to originate from reactions of free amino acids or small peptides with the DNA rather than being proteolytic products derived from larger proteins that were cross-linked to the DNA. This was supported by a number of experiments: a) free amino acids or bovine serum albumin (BSA) were cross-linked by chromium to DNA in vitro and the DNA was isolated by standard procedures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7843108

  6. Uptake of barbituric acid derivatives in small intestinal brush border membrane vesicles from retinyl palmitate-treated rats.

    PubMed

    Tanii, H; Horie, T

    2000-08-01

    Brush border membrane was prepared from the small intestinal (jejunum) cells along the crypt-villus axis. The fluorescence spectra of 1,8-anilinonaphthalene sulfonic acid and the steady-state fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene were measured in the brush border membrane vesicle suspension. The hydrophobicity of brush border membrane was found to be in the order villus tip >mid villus >lower villus. The fluidity of brush border membrane was in the order villus tip acid derivatives by brush border membrane vesicles was well correlated with their partition coefficients (isopentyl acetate/water). No significant difference was observed between the uptake of hexobarbital by brush border membrane vesicles from the villus tip and lower villus. When retinyl palmitate was administered to rats, the fluidity of brush border membrane was found to be higher in the retinyl palmitate-treated rats than in the control rats. However, no significant difference in the uptake of hexobarbital by brush border membrane vesicles was observed between the retinyl palmitate-administered rats and the control rats. Thus, the retinyl palmitate treatment seems unlikely to affect the passively transported ligands like barbituric acid derivatives in brush border membrane vesicles. PMID:10989945

  7. Asiatic Acid Prevents the Deleterious Effects of Valproic Acid on Cognition and Hippocampal Cell Proliferation and Survival

    PubMed Central

    Umka Welbat, Jariya; Sirichoat, Apiwat; Chaijaroonkhanarak, Wunnee; Prachaney, Parichat; Pannangrong, Wanassanun; Pakdeechote, Poungrat; Sripanidkulchai, Bungorn; Wigmore, Peter

    2016-01-01

    Valproic acid (VPA) is commonly prescribed as an anticonvulsant and mood stabilizer used in the treatment of epilepsy and bipolar disorder. A recent study has demonstrated that VPA reduces histone deacetylase (HDAC) activity, an action which is believed to contribute to the effects of VPA on neural stem cell proliferation and differentiation which may explain the cognitive impairments produced in rodents and patients. Asiatic acid is a triterpenoid derived from the medicinal plant Centella asiatica. Our previous study has shown that Asiatic acid improves working spatial memory and increases cell proliferation in the sub granular zone of the hippocampal dentate gyrus. In the present study we investigate the effects of Asiatic acid in preventing the memory and cellular effects of VPA. Male Spraque-Dawley rats were orally administered Asiatic acid (30 mg/kg/day) for 28 days, while VPA-treated animals received injections of VPA (300 mg/kg) twice a day from Day 15 to Day 28 for 14 days. Spatial memory was determined using the novel object location (NOL) test and hippocampal cell proliferation and survival was quantified by immuostaining for Ki-67 and Bromodeoxyuridine (BrdU), respectively. The results showed that VPA-treated animals were unable to discriminate between objects in familiar and novel locations. Moreover, VPA significantly reduced numbers of Ki-67 and BrdU positive cells. These results indicate that VPA treatment caused impairments of spatial working memory, cell proliferation and survival in the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG). However, these abnormalities were restored to control levels by co-treatment with Asiatic acid. These data demonstrate that Asiatic acid could prevent the spatial memory and neurogenesis impairments caused by VPA. PMID:27213437

  8. Asiatic Acid Prevents the Deleterious Effects of Valproic Acid on Cognition and Hippocampal Cell Proliferation and Survival.

    PubMed

    Umka Welbat, Jariya; Sirichoat, Apiwat; Chaijaroonkhanarak, Wunnee; Prachaney, Parichat; Pannangrong, Wanassanun; Pakdeechote, Poungrat; Sripanidkulchai, Bungorn; Wigmore, Peter

    2016-01-01

    Valproic acid (VPA) is commonly prescribed as an anticonvulsant and mood stabilizer used in the treatment of epilepsy and bipolar disorder. A recent study has demonstrated that VPA reduces histone deacetylase (HDAC) activity, an action which is believed to contribute to the effects of VPA on neural stem cell proliferation and differentiation which may explain the cognitive impairments produced in rodents and patients. Asiatic acid is a triterpenoid derived from the medicinal plant Centella asiatica. Our previous study has shown that Asiatic acid improves working spatial memory and increases cell proliferation in the sub granular zone of the hippocampal dentate gyrus. In the present study we investigate the effects of Asiatic acid in preventing the memory and cellular effects of VPA. Male Spraque-Dawley rats were orally administered Asiatic acid (30 mg/kg/day) for 28 days, while VPA-treated animals received injections of VPA (300 mg/kg) twice a day from Day 15 to Day 28 for 14 days. Spatial memory was determined using the novel object location (NOL) test and hippocampal cell proliferation and survival was quantified by immuostaining for Ki-67 and Bromodeoxyuridine (BrdU), respectively. The results showed that VPA-treated animals were unable to discriminate between objects in familiar and novel locations. Moreover, VPA significantly reduced numbers of Ki-67 and BrdU positive cells. These results indicate that VPA treatment caused impairments of spatial working memory, cell proliferation and survival in the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG). However, these abnormalities were restored to control levels by co-treatment with Asiatic acid. These data demonstrate that Asiatic acid could prevent the spatial memory and neurogenesis impairments caused by VPA. PMID:27213437

  9. Lactic acid bacterial cell factories for gamma-aminobutyric acid.

    PubMed

    Li, Haixing; Cao, Yusheng

    2010-11-01

    Gamma-aminobutyric acid is a non-protein amino acid that is widely present in organisms. Several important physiological functions of gamma-aminobutyric acid have been characterized, such as neurotransmission, induction of hypotension, diuretic effects, and tranquilizer effects. Many microorganisms can produce gamma-aminobutyric acid including bacteria, fungi and yeasts. Among them, gamma-aminobutyric acid-producing lactic acid bacteria have been a focus of research in recent years, because lactic acid bacteria possess special physiological activities and are generally regarded as safe. They have been extensively used in food industry. The production of lactic acid bacterial gamma-aminobutyric acid is safe and eco-friendly, and this provides the possibility of production of new naturally fermented health-oriented products enriched in gamma-aminobutyric acid. The gamma-aminobutyric acid-producing species of lactic acid bacteria and their isolation sources, the methods for screening of the strains and increasing their production, the enzymatic properties of glutamate decarboxylases and the relative fundamental research are reviewed in this article. And the potential applications of gamma-aminobutyric acid-producing lactic acid bacteria were also referred to.

  10. Selective apoptotic cell death effects of oral cancer cells treated with destruxin B

    PubMed Central

    2014-01-01

    Background Recent studies have revealed that destruxins (Dtx) have potent cytotoxic activities on individual cancer cells, however, data on oral cancer cells especial human are absent. Methods Destruxin B (DB) was isolated and used to evaluate the selective cytotoxicity with human oral cancer cell lines, GNM (Neck metastasis of gingival carcinoma) and TSCCa (Tongue squamous cell carcinoma) cells, and normal gingival fibroblasts (GF) were also included as controls. Cells were tested with different concentrations of DB for 24, 48, and 72 h by MTT assay. Moreover, the mechanism of cytotoxicity was investigated using caspase-3 Immunofluorescence, annexin V/PI staining, and the expression of caspase-3, Bax, and Bcl-2 by western blotting after treated with different concentrations of DB for 72 h as parameters for apoptosis analyses. Results The results show that DB exhibited significant (p < 0.01) and selective time- and dose-dependent inhibitory effects on GNM and TSCCa cells viability but not on GF cells. The data suggested that DB is capable to induce tumor specific growth inhibition in oral GNM and TSCCa cancer cells via Bax/Bcl-2-mediated intrinsic mitochondrial apoptotic pathway in time- and dose-dependent manners. Conclusions This is the first report on the anti-proliferation effect of DB in oral cancer cells. The results reported here may offer further evidences to the development of DB as a potential complementary chemotherapeutic target for oral cancer complications. PMID:24972848

  11. Essential Role of Lysophosphatidylcholine Acyltransferase 3 in the Induction of Macrophage Polarization in PMA-Treated U937 Cells.

    PubMed

    Taniguchi, Kosuke; Hikiji, Hisako; Okinaga, Toshinori; Hashidate-Yoshida, Tomomi; Shindou, Hideo; Ariyoshi, Wataru; Shimizu, Takao; Tominaga, Kazuhiro; Nishihara, Tatsuji

    2015-12-01

    Lysophospholipid acyltransferases (LPLATs) regulate the diversification of fatty acid composition in biological membranes. Lysophosphatidylcholine acyltransferases (LPCATs) are members of the LPLATs that play a role in inflammatory responses. M1 macrophages differentiate in response to lipopolysaccharide (LPS) and are pro-inflammatory, whereas M2 macrophages, which differentiate in response to interleukin-4 (IL-4), are anti-inflammatory and involved in homeostasis and wound healing. In the present study, we showed that LPCATs play an important role in M1/M2-macrophage polarization. LPS changed the shape of PMA-treated U937 cells from rounded to spindle shaped and upregulated the mRNA and protein expression of the M1 macrophage markers CXCL10, TNF-α, and IL-1β. IL-4 had no effect on the shape of PMA-treated U937 cells and upregulated the M2 macrophage markers CD206, IL-1ra, and TGF-β in PMA-treated U937 cells. These results suggest that LPS and IL-4 promote the differentiation of PMA-treated U937 cells into M1- and M2-polarized macrophages, respectively. LPS significantly downregulated the mRNA expression of LPCAT3, one of four LPCAT isoforms, and suppressed its enzymatic activity toward linoleoyl-CoA and arachidonoyl-CoA in PMA-treated U937 cells. LPCAT3 knockdown induced a spindle-shaped morphology typical of M1-polarized macrophages, and increased the secretion of CXCL10 and decreased the levels of CD206 in IL-4-activated U937 cells. This indicates that knockdown of LPCAT3 shifts the differentiation of PMA-treated U937 cells to M1-polarized macrophages. Our findings suggest that LPCAT3 plays an important role in M1/M2-macrophage polarization, providing novel potential therapeutic targets for the regulation of immune and inflammatory disorders.

  12. Fluroide concentration in enamel treated with 50% phosphoric acid and NaF with subsequent decalcification in "acid-gel".

    PubMed

    Bohrer, J; Gedalia, I

    1980-06-01

    Fluoride concentration of enamel surfaces treated with 50% H3PO4, together with high NaF contents or etched with 50% H3PO4 followed by application with a water solution of high NaF content, was examined. In addition, the degree of decalcification and the fluoride content of subsequently incubated enamel samples in acid-gel at 37 degrees C were determined. Generally, incubation highly increased the fluoride contents of the etched and fluoridated (experimental), control (etched only), and untreated (vaseline) enamel samples. An increasing demineralization effect was observed in the samples of the following order: experimental, control, and baseline. It appears does not predispose to an increased caries challenge in vitro.

  13. Chemical surface modification of calcium carbonate particles with stearic acid using different treating methods

    NASA Astrophysics Data System (ADS)

    Cao, Zhi; Daly, Michael; Clémence, Lopez; Geever, Luke M.; Major, Ian; Higginbotham, Clement L.; Devine, Declan M.

    2016-08-01

    Calcium carbonate (CaCO3) is often treated with stearic acid (SA) to decrease its polarity. However, the method of application of the SA treatments has a strong influence on CaCO3 thermoplastic composite's interfacial structure and distribution. Several of papers describe the promising effects of SA surface treatment, but few compare the treatment process and its effect on the properties of the final thermoplastic composite. In the current study, we assessed a new SA treatment method, namely, complex treatment for polymer composite fabrication with HDPE. Subsequently, a comparative study was performed between the "complex" process and the other existing methods. The composites were assessed using different experiments included scanning electron microscopy (SEM), void content, density, wettability, differential scanning calorimetry (DSC), and tensile tests. It was observed that the "complex" surface treatment yielded composites with a significantly lower voids content and higher density compared to other surface treatments. This indicates that after the "complex" treatment process, the CaCO3 particles and HDPE matrix are more tightly packed than other methods. DSC and wettability results suggest that the "wet" and "complex" treated CaCO3 composites had a significantly higher heat of fusion and moisture resistance compared to the "dry" treated CaCO3 composites. Furthermore, "wet" and "complex" treated CaCO3 composites have a significantly higher tensile strength than the composites containing untreated and "dry" treated CaCO3. This is mainly because the "wet" and "complex" treatment processes have increased adsorption density of stearate, which enhances the interfacial interaction between matrix and filler. These results confirm that the chemical adsorption of the surfactant ions at the solid-liquid interface is higher than at other interface. From this study, it was concluded that the utilization of the "complex" method minimised the negative effects of void

  14. Satellite glial cells in dorsal root ganglia are activated in streptozotocin-treated rodents

    PubMed Central

    Hanani, Menachem; Blum, Erez; Liu, Shuangmei; Peng, Lichao; Liang, Shangdong

    2014-01-01

    Neuropathic pain is a very common complication in diabetes mellitus (DM), and treatment for it is limited. As DM is becoming a global epidemic it is important to understand and treat this problem. The mechanisms of diabetic neuropathic pain are largely obscure. Recent studies have shown that glial cells are important for a variety of neuropathic pain types, and we investigated what are the changes that satellite glial cells (SGCs) in dorsal root ganglia undergo in a DM type 1 model, induced by streptozotocin (STZ) in mice and rats. We carried out immunohistochemical studies to learn about changes in the activation marker glial fibrillary acidic protein (GFAP) in SGCs. We found that after STZ-treatment the number of neurons surrounded with GFAP-positive SGCs in dorsal root ganglia increased 4-fold in mice and 5-fold in rats. Western blotting for GFAP, which was done only on rats because of the larger size of the ganglia, showed an increase of about 2-fold in STZ-treated rats, supporting the immunohistochemical results. These results indicate for the first time that SGCs are activated in rodent models of DM1. As SGC activation appears to contribute to chronic pain, these results suggest that SGCs may participate in the generation and maintenance of diabetic neuropathic pain, and can serve as a potential therapeutic target. PMID:25312986

  15. Isogambogenic acid induces apoptosis-independent autophagic cell death in human non-small-cell lung carcinoma cells.

    PubMed

    Yang, Jianhong; Zhou, Yongzhao; Cheng, Xia; Fan, Yi; He, Shichao; Li, Shucai; Ye, Haoyu; Xie, Caifeng; Wu, Wenshuang; Li, Chunyan; Pei, Heying; Li, Luyuan; Wei, Zhe; Peng, Aihua; Wei, Yuquan; Li, Weimin; Chen, Lijuan

    2015-01-09

    To overcome drug resistance caused by apoptosis deficiency in patients with non-small cell lung carcinoma (NSCLC), there is a need to identify other means of triggering apoptosis-independent cancer cell death. We are the first to report that isogambogenic acid (iso-GNA) can induce apoptosis-independent autophagic cell death in human NSCLC cells. Several features of the iso-GNA-treated NSCLC cells indicated that iso-GNA induced autophagic cell death. First, there was no evidence of apoptosis or cleaved caspase 3 accumulation and activation. Second, iso-GNA treatment induced the formation of autophagic vacuoles, increased LC3 conversion, caused the appearance of autophagosomes and increased the expression of autophagy-related proteins. These findings provide evidence that iso-GNA induces autophagy in NSCLC cells. Third, iso-GNA-induced cell death was inhibited by autophagic inhibitors or by selective ablation of Atg7 and Beclin 1 genes. Furthermore, the mTOR inhibitor rapamycin increased iso-GNA-induced cell death by enhancing autophagy. Finally, a xenograft model provided additional evidence that iso-GNA exhibited anticancer effect through inducing autophagy-dependent cell death in NSCLC cells. Taken together, our results demonstrated that iso-GNA exhibited an anticancer effect by inducing autophagy-dependent cell death in NSCLC cells, which may be an effective chemotherapeutic agent that can be used against NSCLC in a clinical setting.

  16. Isogambogenic acid induces apoptosis-independent autophagic cell death in human non-small-cell lung carcinoma cells

    PubMed Central

    Yang, Jianhong; Zhou, Yongzhao; Cheng, Xia; Fan, Yi; He, Shichao; Li, Shucai; Ye, Haoyu; Xie, Caifeng; Wu, Wenshuang; Li, Chunyan; Pei, Heying; Li, Luyuan; Wei, Zhe; Peng, Aihua; Wei, Yuquan; Li, Weimin; Chen, Lijuan

    2015-01-01

    To overcome drug resistance caused by apoptosis deficiency in patients with non-small cell lung carcinoma (NSCLC), there is a need to identify other means of triggering apoptosis-independent cancer cell death. We are the first to report that isogambogenic acid (iso-GNA) can induce apoptosis-independent autophagic cell death in human NSCLC cells. Several features of the iso-GNA-treated NSCLC cells indicated that iso-GNA induced autophagic cell death. First, there was no evidence of apoptosis or cleaved caspase 3 accumulation and activation. Second, iso-GNA treatment induced the formation of autophagic vacuoles, increased LC3 conversion, caused the appearance of autophagosomes and increased the expression of autophagy-related proteins. These findings provide evidence that iso-GNA induces autophagy in NSCLC cells. Third, iso-GNA-induced cell death was inhibited by autophagic inhibitors or by selective ablation of Atg7 and Beclin 1 genes. Furthermore, the mTOR inhibitor rapamycin increased iso-GNA-induced cell death by enhancing autophagy. Finally, a xenograft model provided additional evidence that iso-GNA exhibited anticancer effect through inducing autophagy-dependent cell death in NSCLC cells. Taken together, our results demonstrated that iso-GNA exhibited an anticancer effect by inducing autophagy-dependent cell death in NSCLC cells, which may be an effective chemotherapeutic agent that can be used against NSCLC in a clinical setting. PMID:25571970

  17. Activation of AMP-Activated Protein Kinase and Stimulation of Energy Metabolism by Acetic Acid in L6 Myotube Cells.

    PubMed

    Maruta, Hitomi; Yoshimura, Yukihiro; Araki, Aya; Kimoto, Masumi; Takahashi, Yoshitaka; Yamashita, Hiromi

    2016-01-01

    Previously, we found that orally administered acetic acid decreased lipogenesis in the liver and suppressed lipid accumulation in adipose tissue of Otsuka Long-Evans Tokushima Fatty rats, which exhibit hyperglycemic obesity with hyperinsulinemia and insulin resistance. Administered acetic acid led to increased phosphorylation of AMP-activated protein kinase (AMPK) in both liver and skeletal muscle cells, and increased transcripts of myoglobin and glucose transporter 4 (GLUT4) genes in skeletal muscle of the rats. It was suggested that acetic acid improved the lipid metabolism in skeletal muscles. In this study, we examined the activation of AMPK and the stimulation of GLUT4 and myoglobin expression by acetic acid in skeletal muscle cells to clarify the physiological function of acetic acid in skeletal muscle cells. Acetic acid added to culture medium was taken up rapidly by L6 cells, and AMPK was phosphorylated upon treatment with acetic acid. We observed increased gene and protein expression of GLUT4 and myoglobin. Uptake of glucose and fatty acids by L6 cells were increased, while triglyceride accumulation was lower in treated cells compared to untreated cells. Furthermore, treated cells also showed increased gene and protein expression of myocyte enhancer factor 2A (MEF2A), which is a well-known transcription factor involved in the expression of myoglobin and GLUT4 genes. These results indicate that acetic acid enhances glucose uptake and fatty acid metabolism through the activation of AMPK, and increases expression of GLUT4 and myoglobin.

  18. Activation of AMP-Activated Protein Kinase and Stimulation of Energy Metabolism by Acetic Acid in L6 Myotube Cells.

    PubMed

    Maruta, Hitomi; Yoshimura, Yukihiro; Araki, Aya; Kimoto, Masumi; Takahashi, Yoshitaka; Yamashita, Hiromi

    2016-01-01

    Previously, we found that orally administered acetic acid decreased lipogenesis in the liver and suppressed lipid accumulation in adipose tissue of Otsuka Long-Evans Tokushima Fatty rats, which exhibit hyperglycemic obesity with hyperinsulinemia and insulin resistance. Administered acetic acid led to increased phosphorylation of AMP-activated protein kinase (AMPK) in both liver and skeletal muscle cells, and increased transcripts of myoglobin and glucose transporter 4 (GLUT4) genes in skeletal muscle of the rats. It was suggested that acetic acid improved the lipid metabolism in skeletal muscles. In this study, we examined the activation of AMPK and the stimulation of GLUT4 and myoglobin expression by acetic acid in skeletal muscle cells to clarify the physiological function of acetic acid in skeletal muscle cells. Acetic acid added to culture medium was taken up rapidly by L6 cells, and AMPK was phosphorylated upon treatment with acetic acid. We observed increased gene and protein expression of GLUT4 and myoglobin. Uptake of glucose and fatty acids by L6 cells were increased, while triglyceride accumulation was lower in treated cells compared to untreated cells. Furthermore, treated cells also showed increased gene and protein expression of myocyte enhancer factor 2A (MEF2A), which is a well-known transcription factor involved in the expression of myoglobin and GLUT4 genes. These results indicate that acetic acid enhances glucose uptake and fatty acid metabolism through the activation of AMPK, and increases expression of GLUT4 and myoglobin. PMID:27348124

  19. Activation of AMP-Activated Protein Kinase and Stimulation of Energy Metabolism by Acetic Acid in L6 Myotube Cells

    PubMed Central

    Maruta, Hitomi; Yoshimura, Yukihiro; Araki, Aya; Kimoto, Masumi; Takahashi, Yoshitaka; Yamashita, Hiromi

    2016-01-01

    Previously, we found that orally administered acetic acid decreased lipogenesis in the liver and suppressed lipid accumulation in adipose tissue of Otsuka Long-Evans Tokushima Fatty rats, which exhibit hyperglycemic obesity with hyperinsulinemia and insulin resistance. Administered acetic acid led to increased phosphorylation of AMP-activated protein kinase (AMPK) in both liver and skeletal muscle cells, and increased transcripts of myoglobin and glucose transporter 4 (GLUT4) genes in skeletal muscle of the rats. It was suggested that acetic acid improved the lipid metabolism in skeletal muscles. In this study, we examined the activation of AMPK and the stimulation of GLUT4 and myoglobin expression by acetic acid in skeletal muscle cells to clarify the physiological function of acetic acid in skeletal muscle cells. Acetic acid added to culture medium was taken up rapidly by L6 cells, and AMPK was phosphorylated upon treatment with acetic acid. We observed increased gene and protein expression of GLUT4 and myoglobin. Uptake of glucose and fatty acids by L6 cells were increased, while triglyceride accumulation was lower in treated cells compared to untreated cells. Furthermore, treated cells also showed increased gene and protein expression of myocyte enhancer factor 2A (MEF2A), which is a well-known transcription factor involved in the expression of myoglobin and GLUT4 genes. These results indicate that acetic acid enhances glucose uptake and fatty acid metabolism through the activation of AMPK, and increases expression of GLUT4 and myoglobin. PMID:27348124

  20. [Progress in treating diabetes mellitus with adult stem cells].

    PubMed

    Zhang, Lixin; Teng, Chunbo; An, Tiezhu

    2008-02-01

    Diabetes mellitus is a metabolic diseases, mainly including type 1 and type 2 diabetes. Treatment for type 1 and part of type 2 often involves regular insulin injection. However, this treatment neither precisely controls the blood sugar levels, nor prevents the diabetes complications. Transplantation of islets of Langerhans offers an attractive strategy for diabetes therapies, but its wide application has been limited by donor shortage and immunological rejection after transplantation. Stem cells with strong proliferation capacity and multipotential may be potential cell sources in diabetes therapies. For this, adult stem cells are interesting because of absence of teratoma formation and ethnical problems. Adult pancreatic stem cells (PSCs) really exist and could produce insulin-secreting cells both under the condition of pancreatic injury and in vitro culture, but lack of effective markers to enrich PSCs hampers the studies of exploring the expanding and differentiating conditions in vitro. Some other adult stem cells, such as hepatic stem cells, marrow stem cells or intestine stem cells, were also suggested to transdifferentiate into insulin-producing cells under special culture conditions in vitro or by genetic modifications. Moreover, transplanting these adult stem cells-derived insulin-secreting cells into the diabetic mouse could cure diabetes. Thus, adult stem cells would supply the abundant beta-cell sources for cell replacement therapy of diabetes. PMID:18464596

  1. [Progress in treating diabetes mellitus with adult stem cells].

    PubMed

    Zhang, Lixin; Teng, Chunbo; An, Tiezhu

    2008-02-01

    Diabetes mellitus is a metabolic diseases, mainly including type 1 and type 2 diabetes. Treatment for type 1 and part of type 2 often involves regular insulin injection. However, this treatment neither precisely controls the blood sugar levels, nor prevents the diabetes complications. Transplantation of islets of Langerhans offers an attractive strategy for diabetes therapies, but its wide application has been limited by donor shortage and immunological rejection after transplantation. Stem cells with strong proliferation capacity and multipotential may be potential cell sources in diabetes therapies. For this, adult stem cells are interesting because of absence of teratoma formation and ethnical problems. Adult pancreatic stem cells (PSCs) really exist and could produce insulin-secreting cells both under the condition of pancreatic injury and in vitro culture, but lack of effective markers to enrich PSCs hampers the studies of exploring the expanding and differentiating conditions in vitro. Some other adult stem cells, such as hepatic stem cells, marrow stem cells or intestine stem cells, were also suggested to transdifferentiate into insulin-producing cells under special culture conditions in vitro or by genetic modifications. Moreover, transplanting these adult stem cells-derived insulin-secreting cells into the diabetic mouse could cure diabetes. Thus, adult stem cells would supply the abundant beta-cell sources for cell replacement therapy of diabetes.

  2. Detection of bacterial aggregation in cell suspensions treated with pathogenic bacteria

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The early interaction between plant cells and pathogenic bacteria were studied using tobacco cell suspensions treated with pathogenic and nonpathogenic Pseudomonas species. Previous studies of this system have documented that interactions with pathogens that cause a hypersensitive response on whole...

  3. Comparative biomechanical and microstructural analysis of native versus peracetic acid-ethanol treated cancellous bone graft.

    PubMed

    Rauh, Juliane; Despang, Florian; Baas, Jorgen; Liebers, Cornelia; Pruss, Axel; Gelinsky, Michael; Günther, Klaus-Peter; Stiehler, Maik

    2014-01-01

    Bone transplantation is frequently used for the treatment of large osseous defects. The availability of autologous bone grafts as the current biological gold standard is limited and there is a risk of donor site morbidity. Allogenic bone grafts are an appealing alternative, but disinfection should be considered to reduce transmission of infection disorders. Peracetic acid-ethanol (PE) treatment has been proven reliable and effective for disinfection of human bone allografts. The purpose of this study was to evaluate the effects of PE treatment on the biomechanical properties and microstructure of cancellous bone grafts (CBG). Forty-eight human CBG cylinders were either treated by PE or frozen at -20 °C and subjected to compression testing and histological and scanning electron microscopy (SEM) analysis. The levels of compressive strength, stiffness (Young's modulus), and fracture energy were significantly decreased upon PE treatment by 54%, 59%, and 36%, respectively. Furthermore, PE-treated CBG demonstrated a 42% increase in ultimate strain. SEM revealed a modified microstructure of CBG with an exposed collagen fiber network after PE treatment. We conclude that the observed reduced compressive strength and reduced stiffness may be beneficial during tissue remodeling thereby explaining the excellent clinical performance of PE-treated CBG.

  4. Compromised Osseous Healing of Dental Extraction Sites in Zoledronic Acid-Treated Dogs

    PubMed Central

    Allen, Matthew R.; Kubek, Daniel J.; Burr, David B.; Ruggiero, Salvatore L.; Chu, Tien-Min Gabriel

    2010-01-01

    PURPOSE The goal of this study was to document how treatment with a bisphosphonate affects the bone tissue following dental extraction. METHODS Skeletally mature female beagle dogs were either untreated controls (CON) or treated with intravenous zoledronic acid (ZOL). Following the extraction of the 4th premolars, healing was allowed for 4 or 8 weeks. Properties of the extraction site were assessed using micro-computed tomography (micro-CT) and dynamic histomorphometry. RESULTS The initial infilling of the extraction socket with bone was not affected by ZOL but subsequent removal of this bone was significantly suppressed compared to CON. After 8-weeks of healing, the alveolar cortical bone adjacent to the extraction socket had a remodeling rate of ~50%/year in CON animals while ZOL-treated animals had a rate of < 1%/year. One ZOL-treated animal developed exposed bone post-extraction which eventually led to the formation of a sequestrum. Assessment of the sequestrum with micro-CT and histology showed that it had features consistent with those reported in humans with osteonecrosis of the jaw. CONCLUSIONS These results, showing significantly compromised post-extraction osseous healing as well as presence of exposed bone and development of a sequestrum in one ZOL animal, provide a building block toward understanding the pathophysiology of osteonecrosis of the jaw. PMID:20458574

  5. Comparative biomechanical and microstructural analysis of native versus peracetic acid-ethanol treated cancellous bone graft.

    PubMed

    Rauh, Juliane; Despang, Florian; Baas, Jorgen; Liebers, Cornelia; Pruss, Axel; Gelinsky, Michael; Günther, Klaus-Peter; Stiehler, Maik

    2014-01-01

    Bone transplantation is frequently used for the treatment of large osseous defects. The availability of autologous bone grafts as the current biological gold standard is limited and there is a risk of donor site morbidity. Allogenic bone grafts are an appealing alternative, but disinfection should be considered to reduce transmission of infection disorders. Peracetic acid-ethanol (PE) treatment has been proven reliable and effective for disinfection of human bone allografts. The purpose of this study was to evaluate the effects of PE treatment on the biomechanical properties and microstructure of cancellous bone grafts (CBG). Forty-eight human CBG cylinders were either treated by PE or frozen at -20 °C and subjected to compression testing and histological and scanning electron microscopy (SEM) analysis. The levels of compressive strength, stiffness (Young's modulus), and fracture energy were significantly decreased upon PE treatment by 54%, 59%, and 36%, respectively. Furthermore, PE-treated CBG demonstrated a 42% increase in ultimate strain. SEM revealed a modified microstructure of CBG with an exposed collagen fiber network after PE treatment. We conclude that the observed reduced compressive strength and reduced stiffness may be beneficial during tissue remodeling thereby explaining the excellent clinical performance of PE-treated CBG. PMID:24678514

  6. Comparative Biomechanical and Microstructural Analysis of Native versus Peracetic Acid-Ethanol Treated Cancellous Bone Graft

    PubMed Central

    Rauh, Juliane; Despang, Florian; Baas, Jorgen; Liebers, Cornelia; Pruss, Axel; Günther, Klaus-Peter; Stiehler, Maik

    2014-01-01

    Bone transplantation is frequently used for the treatment of large osseous defects. The availability of autologous bone grafts as the current biological gold standard is limited and there is a risk of donor site morbidity. Allogenic bone grafts are an appealing alternative, but disinfection should be considered to reduce transmission of infection disorders. Peracetic acid-ethanol (PE) treatment has been proven reliable and effective for disinfection of human bone allografts. The purpose of this study was to evaluate the effects of PE treatment on the biomechanical properties and microstructure of cancellous bone grafts (CBG). Forty-eight human CBG cylinders were either treated by PE or frozen at −20°C and subjected to compression testing and histological and scanning electron microscopy (SEM) analysis. The levels of compressive strength, stiffness (Young's modulus), and fracture energy were significantly decreased upon PE treatment by 54%, 59%, and 36%, respectively. Furthermore, PE-treated CBG demonstrated a 42% increase in ultimate strain. SEM revealed a modified microstructure of CBG with an exposed collagen fiber network after PE treatment. We conclude that the observed reduced compressive strength and reduced stiffness may be beneficial during tissue remodeling thereby explaining the excellent clinical performance of PE-treated CBG. PMID:24678514

  7. New applications for phosphoric acid fuel cells

    NASA Technical Reports Server (NTRS)

    Stickles, R. P.; Breuer, C. T.

    1983-01-01

    New applications for phosphoric acid fuel cells were identified and evaluated. Candidates considered included all possibilities except grid connected electric utility applications, on site total energy systems, industrial cogeneration, opportunistic use of waste hydrogen, space and military applications, and applications smaller than 10 kW. Applications identified were screened, with the most promising subjected to technical and economic evaluation using a fuel cell and conventional power system data base developed in the study. The most promising applications appear to be the underground mine locomotive and the railroad locomotive. Also interesting are power for robotic submersibles and Arctic villages. The mine locomotive is particularly attractive since it is expected that the fuel cell could command a very high price and still be competitive with the conventionally used battery system. The railroad locomotive's attractiveness results from the (smaller) premium price which the fuel cell could command over the conventional diesel electric system based on its superior fuel efficiency, and on the large size of this market and the accompanying opportunities for manufacturing economy.

  8. New applications for phosphoric acid fuel cells

    SciTech Connect

    Stickles, R.P.; Breuer, C.T.

    1983-11-01

    New applications for phosphoric acid fuel cells were identified and evaluated. Candidates considered included all possibilities except grid connected electric utility applications, on-site total energy systems, industrial co-generation, opportunistic use of waste hydrogen, space and military applications, and applications smaller than 10 kW. Applications identified were screened, with the most promising subjected to technical and economic evaluation using a fuel cell and conventional power system data base developed in the study. The most promising applications appear to be the underground mine locomotive and the railroad locomotive. Also interesting is power for robotic submersibles and Arctic villages. The mine locomotive is particularly attractive since it is expected that the fuel cell could command a very high price and still be competitive with the conventionally used battery system. The railroad locomotive's attractiveness results from the (smaller) premium price which the fuel cell could command over the conventional diesel electric system based on its superior fuel efficiency, and on the large size of this market and the accompanying opportunities for manufacturing economy.

  9. Inhibition of Fatty Acid Synthesis Induces Apoptosis of Human Pancreatic Cancer Cells.

    PubMed

    Nishi, Koji; Suzuki, Kenta; Sawamoto, Junpei; Tokizawa, Yuma; Iwase, Yumiko; Yumita, Nagahiko; Ikeda, Toshihiko

    2016-09-01

    Cancer cells tend to have a high requirement for lipids, including fatty acids, cholesterol and triglyceride, because of their rapid proliferative rate compared to normal cells. In this study, we investigated the effects of inhibition of lipid synthesis on the proliferation and viability of human pancreatic cancer cells. Of the inhibitors of lipid synthesis that were tested, 5-(tetradecyloxy)-2-furoic acid (TOFA), which is an inhibitor of acetyl-CoA carboxylase, and the fatty acid synthase (FAS) inhibitors cerulenin and irgasan, significantly suppressed the proliferation of MiaPaCa-2 and AsPC-1 cells. Treatment of MiaPaCa-2 cells with these inhibitors significantly increased the number of apoptotic cells. In addition, TOFA increased caspase-3 activity and induced cleavage of poly (ADP-ribose) polymerase in MiaPaCa-2 cells. Moreover, addition of palmitate to MiaPaCa-2 cells treated with TOFA rescued cells from apoptotic cell death. These results suggest that TOFA induces apoptosis via depletion of fatty acids and that, among the various aspects of lipid metabolism, inhibition of fatty acid synthesis may be a notable target for the treatment of human pancreatic cancer cells. PMID:27630308

  10. A Novel Peptide to Treat Oral Mucositis Blocks Endothelial and Epithelial Cell Apoptosis

    SciTech Connect

    Wu Xiaoyan; Chen Peili; Sonis, Stephen T.; Lingen, Mark W.; Berger, Ann; Toback, F. Gary

    2012-07-01

    Purpose: No effective agents currently exist to treat oral mucositis (OM) in patients receiving chemoradiation for the treatment of head-and-neck cancer. We identified a novel 21-amino acid peptide derived from antrum mucosal protein-18 that is cytoprotective, mitogenic, and motogenic in tissue culture and animal models of gastrointestinal epithelial cell injury. We examined whether administration of antrum mucosal protein peptide (AMP-p) could protect against and/or speed recovery from OM. Methods and Materials: OM was induced in established hamster models by a single dose of radiation, fractionated radiation, or fractionated radiation together with cisplatin to simulate conventional treatments of head-and-neck cancer. Results: Daily subcutaneous administration of AMP-p reduced the occurrence of ulceration and accelerated mucosal recovery in all three models. A delay in the onset of erythema after irradiation was observed, suggesting that a protective effect exists even before injury to mucosal epithelial cells occurs. To test this hypothesis, the effects of AMP-p on tumor necrosis factor-{alpha}-induced apoptosis were studied in an endothelial cell line (human dermal microvascular endothelial cells) as well as an epithelial cell line (human adult low-calcium, high-temperature keratinocytes; HaCaT) used to model the oral mucosa. AMP-p treatment, either before or after cell monolayers were exposed to tumor necrosis factor-{alpha}, protected against development of apoptosis in both cell types when assessed by annexin V and propidium iodide staining followed by flow cytometry or ligase-mediated polymerase chain reaction. Conclusions: These observations suggest that the ability of AMP-p to attenuate radiation-induced OM could be attributable, at least in part, to its antiapoptotic activity.

  11. Lactobionic and cellobionic acid production profiles of the resting cells of acetic acid bacteria.

    PubMed

    Kiryu, Takaaki; Kiso, Taro; Nakano, Hirofumi; Murakami, Hiromi

    2015-01-01

    Lactobionic acid was produced by acetic acid bacteria to oxidize lactose. Gluconobacter spp. and Gluconacetobacter spp. showed higher lactose-oxidizing activities than Acetobacter spp. Gluconobacter frateurii NBRC3285 produced the highest amount of lactobionic acid per cell, among the strains tested. This bacterium assimilated neither lactose nor lactobionic acid. At high lactose concentration (30%), resting cells of the bacterium showed sufficient oxidizing activity for efficient production of lactobionic acid. These properties may contribute to industrial production of lactobionic acid by the bacterium. The bacterium showed higher oxidizing activity on cellobiose than that on lactose and produced cellobionic acid. PMID:25965080

  12. Induced accumulation of oleanolic acid and ursolic acid in cell suspension cultures of Uncaria tomentosa.

    PubMed

    Feria-Romero, Iris; Lazo, Elizabeth; Ponce-Noyola, Teresa; Cerda-García-Rojas, Carlos M; Ramos-Valdivia, Ana C

    2005-06-01

    Increasing sucrose from 20 to 50 g l(-1) in Uncaria tomentosa cell suspension cultures enhanced ursolic acid and oleanolic acid production from 129 +/- 61 to 553 +/- 193 microg g(-1) cell dry wt. The maximal concentration of both triterpenes (1680 +/- 39 microg g(-1) cell dry wt) was 8 days after elicitation by jasmonic acid, while yeast extract or citrus pectin treatments produced 1189 +/- 20 or 1120 +/- 26 microg g(-1) cell dry wt, respectively. The ratio of ursolic acid:oleanolic acid was constant at 70:30.

  13. Extension of UNRES force field to treat polypeptide chains with D-amino-acid residues

    PubMed Central

    Sieradzan, Adam K.; Hansmann, Ulrich H.E.; Scheraga, Harold A.; Liwo, Adam

    2013-01-01

    Coarse-grained force fields for protein simulations are usually designed and parameterized to treat proteins composed of natural L-amino-acid residues. However, D-amino-acid residues occur in bacterial, fungal (e.g., gramicidins), as well as human-designed proteins. For this reason, we have extended the UNRES coarse-grained force field developed in our laboratory to treat systems with D-amino-acid residues. We developed the respective virtual-bond-torsional and double-torsional potentials for rotation about the Cα · · · Cα virtual-bond axis and two consecutive Cα · · · Cα virtual-bond axes, respectively, as functions of virtual-bond-dihedral angles γ. In turn, these were calculated as potentials of mean force (PMFs) from the diabatic energy surfaces of terminally-blocked model compounds for glycine, alanine, and proline. The potential-energy surfaces were calculated by using the ab initio method of molecular quantum mechanics at the Møller-Plesset (MP2) level of theory and the 6-31G(d,p) basis set, with the rotation angles of the peptide groups about Ci-1α⋯Ciα(λ(1)) and Ciα⋯Ci+1α(λ(2)) used as variables, and the energy was minimized with respect to the remaining degrees of freedom. The PMFs were calculated by numerical integration for all pairs and triplets with all possible combinations of types (glycine, alanine, and proline) and chirality (D or L); however, symmetry relations reduce the number of non-equivalent torsional potentials to 13 and the number of double-torsional potentials to 63 for a given C-terminal blocking group. Subsequently, one- (for torsional) and two-dimensional (for double-torsional potentials) Fourier series were fitted to the PMFs to obtain analytical expressions. It was found that the torsional potentials of the x-Y and X-y types, where X and Y are Ala or Pro, respectively, and a lowercase letter denotes D-chirality, have global minima for small absolute values of γ, accounting for the double-helical structure of

  14. Lactic acid production from lime-treated wheat straw by Bacillus coagulans: neutralization of acid by fed-batch addition of alkaline substrate

    PubMed Central

    Maas, Ronald H. W.; Bakker, Robert R.; Jansen, Mickel L. A.; Visser, Diana; de Jong, Ed; Eggink, Gerrit

    2008-01-01

    Conventional processes for lignocellulose-to-organic acid conversion requires pretreatment, enzymatic hydrolysis, and microbial fermentation. In this study, lime-treated wheat straw was hydrolyzed and fermented simultaneously to lactic acid by an enzyme preparation and Bacillus coagulans DSM 2314. Decrease in pH because of lactic acid formation was partially adjusted by automatic addition of the alkaline substrate. After 55 h of incubation, the polymeric glucan, xylan, and arabinan present in the lime-treated straw were hydrolyzed for 55%, 75%, and 80%, respectively. Lactic acid (40.7 g/l) indicated a fermentation efficiency of 81% and a chiral l(+)-lactic acid purity of 97.2%. In total, 711 g lactic acid was produced out of 2,706 g lime-treated straw, representing 43% of the overall theoretical maximum yield. Approximately half of the lactic acid produced was neutralized by fed-batch feeding of lime-treated straw, whereas the remaining half was neutralized during the batch phase with a Ca(OH)2 suspension. Of the lime added during the pretreatment of straw, 61% was used for the neutralization of lactic acid. This is the first demonstration of a process having a combined alkaline pretreatment of lignocellulosic biomass and pH control in fermentation resulting in a significant saving of lime consumption and avoiding the necessity to recycle lime. PMID:18247027

  15. Decontamination of CCA-treated eucalyptus wood waste by acid leaching.

    PubMed

    Ferrarini, Suzana Frighetto; dos Santos, Heldiane Souza; Miranda, Luciana Gampert; Azevedo, Carla Maria Nunes; Maia, Sandra Maria; Pires, Marçal

    2016-03-01

    Preservatives such as chromated copper arsenate (CCA) are used to increase the resistance of wood to deterioration. The components of CCA are highly toxic, resulting in growing concern over the disposal of the waste generated. The aim of this study was to investigate the removal of Cu, Cr and As present in CCA-treated eucalyptus wood from utility poles removed from service in southern Brazil, in order to render them non-hazardous waste. The removal was carried out by acid leaching in bench-scale and applying optimal extractor concentration, total solid content, reactor volume, temperature and reaction time obtained by factorial experiments. The best working conditions were achieved using three extraction steps with 0.1 mol L(-1) H2SO4 at 75°C for 2h each (total solid content of 15%), and 3 additional 1h-long washing steps using water at ambient temperature. Under these conditions, removal of 97%, 85% and 98% were obtained for Cu, Cr and As, respectively, rendering the decontaminated wood non-hazardous waste. The wastewater produced by extraction showed acid pH, high organic loading as well as high concentrations of the elements, needing prior treatment to be discarded. However, rinsing water can be recycled in the extraction process without compromising its efficiency. The acid extraction is a promising alternative for CCA removal from eucalyptus wood waste in industrial scale. PMID:26856447

  16. Role of the p70 S6 kinase cascade in neutrophilic differentiation and proliferation of HL-60 cells-a study of transferrin receptor-positive and -negative cells obtained from dimethyl sulfoxide- or retinoic acid-treated HL-60 cells.

    PubMed

    Kanayasu-Toyoda, Toshie; Yamaguchi, Teruhide; Oshizawa, Tadashi; Kogi, Mieko; Uchida, Eriko; Hayakawa, Takao

    2002-09-01

    Previously, we suggested that p70 S6 kinase (p70 S6K) plays an important role in the regulation of neutrophilic differentiation of HL-60 cells; this conclusion was based on our analysis of transferrin receptor (Trf-R) positive (Trf-R(+)) and negative (Trf-R(-)) cells that appeared after treatment with dimethyl sulfoxide (Me(2)SO). In this study, we analyzed the upstream of p70 S6K in relation to the differentiation and proliferation of both cell types. The granulocyte colony-stimulating factor (G-CSF)-induced enhancement of phosphatidylinositol 3-kinase (PI3K) activity in Trf-R(+) cells was markedly higher than that in Trf-R(-) cells. Wortmannin, a specific inhibitor of PI3K, partially inhibited G-CSF-induced p70 S6K activity and G-CSF-dependent proliferation, whereas rapamycin, an inhibitor of p70 S6K, completely inhibited these activities. The wortmannin-dependent enhancement of neutrophilic differentiation was similar to that induced by rapamycin. From these results, we conclude that the PI3K/p70 S6K cascade may play an important role in negative regulation of neutrophilic differentiation in HL-60 cells. For the G-CSF-dependent proliferation, however, p70 S6K appears to be a highly important pathway through not only a PI3K-dependent but also possibly an independent cascade.

  17. Acetylsalicylic Acid and Eflornithine in Treating Patients at High Risk for Colorectal Cancer | Division of Cancer Prevention

    Cancer.gov

    This phase II trial is studying how well giving acetylsalicylic acid together with eflornithine works in treating patients at high risk for colorectal cancer. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of acetylsalicylic acid and eflornithine may prevent colorectal cancer. |

  18. Effect of nerve growth factor on the synthesis of amino acids in PC12 cells

    SciTech Connect

    Zielke, H.R.; Tildon, J.T.; Kauffman, F.C.; Baab, P.J. )

    1989-04-01

    Radioactive short-chain fatty acids preferentially label glutamine relative to glutamate in brain due to compartmentation of glutamine and glutamate. To determine whether this phenomenon occurs in a single cell culture model, we examined the effect of fatty acid chain length on the synthesis as well as pool size of selected amino acids in rat pheochromocytoma PC12 cells, a cell culture model of the large glutamate compartment in neurons. Intracellular 14C-amino acids were quantitated by HPLC, and the incorporation of (U-14C)-glucose, (1-14C)-butyrate, (1-14C)-octanoate, and (1-14C)-palmitate into five amino acids was measured in native and NGF-treated PC12 cells. NGF pretreatment decreased the intracellular concentration of amino acids as did addition of fatty acids but these effects were not additive. Specific activities of amino acids in native cells labelled by 14C-octanoate were 1,300 DPM/nmol, 490 DPM/nmol, 200 DPM/nmol, and 110 DPM/nmol for glutamate, aspartate, glutamine, and serine, respectively. No radioactivity was detected in alanine. Similar specific activities were noted when 14C-butyrate was the precursor; however, there was at least 5-fold less if 14C-palmitate was the precursor. Pretreatment of cells with NGF decreased the specific activity of amino acids by 25-65%. Specific activities of amino acids synthesized from 14C-glucose decreased in the following order: glutamate, 1,640 DPM/nmol; aspartate, 1,210 DPM/nmol; alanine, 580 DPM/nmol; glutamine, 275 DPM/nmol; and serine, 80 DPM/nmol for native cells. NGF pretreatment decreased the specific activities of glutamate and glutamine, but not of the other 3 amino acids. The preferred precursor for glutamate synthesis in native PC12 cells was glucose followed by octanoate, butyrate and palmitate (16:6:3:1).

  19. Lactobacillus casei combats acid stress by maintaining cell membrane functionality.

    PubMed

    Wu, Chongde; Zhang, Juan; Wang, Miao; Du, Guocheng; Chen, Jian

    2012-07-01

    Lactobacillus casei strains have traditionally been recognized as probiotics and frequently used as adjunct culture in fermented dairy products where lactic acid stress is a frequently encountered environmental condition. We have investigated the effect of lactic acid stress on the cell membrane of L. casei Zhang [wild type (WT)] and its acid-resistant mutant Lbz-2. Both strains were grown under glucose-limiting conditions in chemostats; following challenge by low pH, the cell membrane stress responses were investigated. In response to acid stress, cell membrane fluidity decreased and its fatty acid composition changed to reduce the damage caused by lactic acid. Compared with the WT, the acid-resistant mutant exhibited numerous survival advantages, such as higher membrane fluidity, higher proportions of unsaturated fatty acids, and higher mean chain length. In addition, cell integrity analysis showed that the mutant maintained a more intact cellular structure and lower membrane permeability after environmental acidification. These results indicate that alteration in membrane fluidity, fatty acid distribution, and cell integrity are common mechanisms utilized by L. casei to withstand severe acidification and to reduce the deleterious effect of lactic acid on the cell membrane. This detailed comparison of cell membrane responses between the WT and mutant add to our knowledge of the acid stress adaptation and thus enable new strategies to be developed aimed at improving the industrial performance of this species under acid stress. PMID:22366811

  20. Luteolin prevents uric acid-induced pancreatic β-cell dysfunction

    PubMed Central

    Ding, Ying; Shi, Xuhui; Shuai, Xuanyu; Xu, Yuemei; Liu, Yun; Liang, Xiubin; Wei, Dong; Su, Dongming

    2014-01-01

    Abstract Elevated uric acid causes direct injury to pancreatic β-cells. In this study, we examined the effects of luteolin, an important antioxidant, on uric acid-induced β-cell dysfunction. We first evaluated the effect of luteolin on nitric oxide (NO) formation in uric acid-stimulated Min6 cells using the Griess method. Next, we performed transient transfection and reporter assays to measure transcriptional activity of nuclear factor (NF)-κB. Western blotting assays were also performed to assess the effect of luteolin on the expression of MafA and inducible NO synthase (iNOS) in uric acid-treated cells. Finally, we evaluated the effect of luteolin on uric acid-induced inhibition of glucose-stimulated insulin secretion (GSIS) in Min6 cells and freshly isolated mouse pancreatic islets. We found that luteolin significantly inhibited uric acid-induced NO production, which was well correlated with reduced expression of iNOS mRNA and protein. Furthermore, decreased activity of NF-κB was implicated in inhibition by luteolin of increased iNOS expression induced by uric acid. Besides, luteolin significantly increased MafA expression in Min6 cells exposed to uric acid, which was reversed by overexpression of iNOS. Moreover, luteolin prevented uric acid-induced inhibition of GSIS in both Min6 cells and mouse islets. In conclusion, luteolin protects pancreatic β-cells from uric acid-induced dysfunction and may confer benefit on the protection of pancreatic β-cells in hyperuricemia-associated diabetes. PMID:25050113

  1. Culture of Oral Mucosal Epithelial Cells for the Purpose of Treating Limbal Stem Cell Deficiency.

    PubMed

    Utheim, Tor Paaske; Utheim, Øygunn Aass; Khan, Qalb-E-Saleem; Sehic, Amer

    2016-01-01

    The cornea is critical for normal vision as it allows allowing light transmission to the retina. The corneal epithelium is renewed by limbal epithelial cells (LEC), which are located in the periphery of the cornea, the limbus. Damage or disease involving LEC may lead to various clinical presentations of limbal stem cell deficiency (LSCD). Both severe pain and blindness may result. Transplantation of cultured autologous oral mucosal epithelial cell sheet (CAOMECS) represents the first use of a cultured non-limbal autologous cell type to treat this disease. Among non-limbal cell types, CAOMECS and conjunctival epithelial cells are the only laboratory cultured cell sources that have been explored in humans. Thus far, the expression of p63 is the only predictor of clinical outcome following transplantation to correct LSCD. The optimal culture method and substrate for CAOMECS is not established. The present review focuses on cell culture methods, with particular emphasis on substrates. Most culture protocols for CAOMECS used amniotic membrane as a substrate and included the xenogeneic components fetal bovine serum and murine 3T3 fibroblasts. However, it has been demonstrated that tissue-engineered epithelial cell sheet grafts can be successfully fabricated using temperature-responsive culture surfaces and autologous serum. In the studies using different substrates for culture of CAOMECS, the quantitative expression of p63 was generally poorly reported; thus, more research is warranted with quantification of phenotypic data. Further research is required to develop a culture system for CAOMECS that mimics the natural environment of oral/limbal/corneal epithelial cells without the need for undefined foreign materials such as serum and feeder cells. PMID:26938569

  2. Culture of Oral Mucosal Epithelial Cells for the Purpose of Treating Limbal Stem Cell Deficiency

    PubMed Central

    Paaske Utheim, Tor; Aass Utheim, Øygunn; Khan, Qalb-E-Saleem; Sehic, Amer

    2016-01-01

    The cornea is critical for normal vision as it allows allowing light transmission to the retina. The corneal epithelium is renewed by limbal epithelial cells (LEC), which are located in the periphery of the cornea, the limbus. Damage or disease involving LEC may lead to various clinical presentations of limbal stem cell deficiency (LSCD). Both severe pain and blindness may result. Transplantation of cultured autologous oral mucosal epithelial cell sheet (CAOMECS) represents the first use of a cultured non-limbal autologous cell type to treat this disease. Among non-limbal cell types, CAOMECS and conjunctival epithelial cells are the only laboratory cultured cell sources that have been explored in humans. Thus far, the expression of p63 is the only predictor of clinical outcome following transplantation to correct LSCD. The optimal culture method and substrate for CAOMECS is not established. The present review focuses on cell culture methods, with particular emphasis on substrates. Most culture protocols for CAOMECS used amniotic membrane as a substrate and included the xenogeneic components fetal bovine serum and murine 3T3 fibroblasts. However, it has been demonstrated that tissue-engineered epithelial cell sheet grafts can be successfully fabricated using temperature-responsive culture surfaces and autologous serum. In the studies using different substrates for culture of CAOMECS, the quantitative expression of p63 was generally poorly reported; thus, more research is warranted with quantification of phenotypic data. Further research is required to develop a culture system for CAOMECS that mimics the natural environment of oral/limbal/corneal epithelial cells without the need for undefined foreign materials such as serum and feeder cells. PMID:26938569

  3. Practical application of acid dissociation in monitoring patients treated with adalimumab.

    PubMed

    Llinares-Tello, Francisca; Rosas-Gómez de Salazar, José; Senabre-Gallego, José Miguel; Santos-Soler, Gregorio; Santos-Ramírez, Carlos; Salas-Heredia, Esteban; Barber-Vallés, Xavier; Molina-García, Juan

    2014-12-01

    Patients treated with adalimumab (ADL) can induce anti-ADL antibodies (AAA) formation that is associated with low drug levels and clinical non-response. But, in the majority of the assays, the measurement of AAA is hampered by the presence of the drug itself. In support of immunogenicity assessment in clinical samples with subtherapeutic ADL levels, we proved acid pre-treatment for AAA detection with the Promonitor-enzyme-linked immunosorbent assay (ELISA). Were measured AAA after acidification in 32 serum samples with a subtherapeutic ADL trough level. ADL and AAA concentrations were measured by ELISA (Promonitor). The impact of drug concentration on AAA recovery (with or without acidification) was also evaluated by mixing known amounts of ADL (0.25, 0.5 and 1 mg/L) and AAA (100, 200, 300 and 400 AU/mL) from clinical samples in pooled serum. The drug significantly inhibited the detection of AAA in untreated samples. And progressively higher levels of ADL cause increasing inhibition of signal. Acid pre-treatment carried a significant increase in assay response, particularly at lower free ADL concentrations. AAA were detected in the 53 % of the samples after acid dissociation. In seven patients, the positive AAA after dissociation was detected in the first monitoring of ADL and five patients were positive 3 months later for AAA with the standard assay. Monitoring AAA using acid dissociation in patients with subtherapeutic circulating level of ADL could detect precocious problems of bioavailability, assess the immunogenicity of ADL and may be used to optimise dose regimens, thereby preventing prolonged use of inadequate therapy and guide change of treatment.

  4. Corrosion-resistant catalyst supports for phosphoric acid fuel cells

    SciTech Connect

    Kosek, J.A.; Cropley, C.C.; LaConti, A.B.

    1990-01-01

    High-surface-area carbon blacks such as Vulcan XC-72 (Cabot Corp.) and graphitized carbon blacks such as 2700{degree}C heat-treated Black Pearls 2000 (HTBP) (Cabot Corp.) have found widespread applications as catalyst supports in phosphoric acid fuel cells (PAFCs). However, due to the operating temperatures and pressures being utilized in PAFCs currently under development, the carbon-based cathode catalyst supports suffer from corrosion, which decreases the performance and life span of a PAFC stack. The feasibility of using alternative, low-cost, corrosion-resistant catalyst support (CRCS) materials as replacements for the cathode carbon support materials was investigated. The objectives of the program were to prepare high-surface-area alternative supports and to evaluate the physical characteristics and the electrochemical stability of these materials. The O{sub 2} reduction activity of the platinized CRCS materials was also evaluated. 2 refs., 3 figs.

  5. Immunomodulatory activity of mefenamic acid in mice models of cell-mediated and humoral immunity

    PubMed Central

    Shabbir, Arham; Arshad, Hafiza Maida; Shahzad, Muhammad; Shamsi, Sadia; Ashraf, Muhammad Imran

    2016-01-01

    Objectives: Previously, different nonsteroidal anti-inflammatory drugs (NSAIDs) have been evaluated for their potential immunomodulatory activities. Mefenamic acid is a well-known NSAID and is used in the treatment of musculoskeletal disorders, inflammation, fever, and pain. To the best of our knowledge, promising data regarding the immunomodulatory activity of mefenamic acid is scarce. Current study investigates the immunomodulatory activity of mefenamic acid in different models of cell-mediated and humoral immunity. Materials and Methods: Immunomodulatory effects on cell-mediated immunity were evaluated using dinitrochlorobenzene-induced delayed type hypersensitivity (DTH) and cyclophosphamide-induce myelosuppression assays. While effects on humoral immunity were evaluated using hemagglutination assay and mice lethality test. Results: Hematological analysis showed that mefenamic acid significantly reduced white blood cell count, red blood cell (RBC) count, hemoglobin content, lymphocytes levels, and neutrophils levels in healthy mice as compared with control, suggesting the immunosuppressive activity of mefenamic acid. Treatment with mefenamic acid also significantly reduced all the hematological parameters in cyclophosphamide-induced neutropenic mice, as compared with positive control group. We found that treatment with mefenamic acid significantly suppressed DTH after 24 h, 48 h, and 72 h, as compared with positive control group. Mefenamic acid treated groups showed a significant reduction in antibody titer against sheep RBCs as compared to control group, similar to the effect of cyclophosphamide. We also found increased mice lethality rate in mefenamic acid treated groups, as compared with positive control group. Conclusions: The results provided basic information of immunosuppression of mefenamic acid on both cell-mediated and humoral immunity. PMID:27127320

  6. Stromal uptake and transmission of acid is a pathway for venting cancer cell-generated acid.

    PubMed

    Hulikova, Alzbeta; Black, Nicholas; Hsia, Lin-Ting; Wilding, Jennifer; Bodmer, Walter F; Swietach, Pawel

    2016-09-01

    Proliferation and invasion of cancer cells require favorable pH, yet potentially toxic quantities of acid are produced metabolically. Membrane-bound transporters extrude acid from cancer cells, but little is known about the mechanisms that handle acid once it is released into the poorly perfused extracellular space. Here, we studied acid handling by myofibroblasts (colon cancer-derived Hs675.T, intestinal InMyoFib, embryonic colon-derived CCD-112-CoN), skin fibroblasts (NHDF-Ad), and colorectal cancer (CRC) cells (HCT116, HT29) grown in monoculture or coculture. Expression of the acid-loading transporter anion exchanger 2 (AE2) (SLC4A2 product) was detected in myofibroblasts and fibroblasts, but not in CRC cells. Compared with CRC cells, Hs675.T and InMyoFib myofibroblasts had very high capacity to absorb extracellular acid. Acid uptake into CCD-112-CoN and NHDF-Ad cells was slower and comparable to levels in CRC cells, but increased alongside SLC4A2 expression under stimulation with transforming growth factor β1 (TGFβ1), a cytokine involved in cancer-stroma interplay. Myofibroblasts and fibroblasts are connected by gap junctions formed by proteins such as connexin-43, which allows the absorbed acid load to be transmitted across the stromal syncytium. To match the stimulatory effect on acid uptake, cell-to-cell coupling in NHDF-Ad and CCD-112-CoN cells was strengthened with TGFβ1. In contrast, acid transmission was absent between CRC cells, even after treatment with TGFβ1. Thus, stromal cells have the necessary molecular apparatus for assembling an acid-venting route that can improve the flow of metabolic acid through tumors. Importantly, the activities of stromal AE2 and connexin-43 do not place an energetic burden on cancer cells, allowing resources to be diverted for other activities. PMID:27543333

  7. Stromal uptake and transmission of acid is a pathway for venting cancer cell-generated acid

    PubMed Central

    Hulikova, Alzbeta; Black, Nicholas; Hsia, Lin-Ting; Wilding, Jennifer; Bodmer, Walter F.; Swietach, Pawel

    2016-01-01

    Proliferation and invasion of cancer cells require favorable pH, yet potentially toxic quantities of acid are produced metabolically. Membrane-bound transporters extrude acid from cancer cells, but little is known about the mechanisms that handle acid once it is released into the poorly perfused extracellular space. Here, we studied acid handling by myofibroblasts (colon cancer-derived Hs675.T, intestinal InMyoFib, embryonic colon-derived CCD-112-CoN), skin fibroblasts (NHDF-Ad), and colorectal cancer (CRC) cells (HCT116, HT29) grown in monoculture or coculture. Expression of the acid-loading transporter anion exchanger 2 (AE2) (SLC4A2 product) was detected in myofibroblasts and fibroblasts, but not in CRC cells. Compared with CRC cells, Hs675.T and InMyoFib myofibroblasts had very high capacity to absorb extracellular acid. Acid uptake into CCD-112-CoN and NHDF-Ad cells was slower and comparable to levels in CRC cells, but increased alongside SLC4A2 expression under stimulation with transforming growth factor β1 (TGFβ1), a cytokine involved in cancer–stroma interplay. Myofibroblasts and fibroblasts are connected by gap junctions formed by proteins such as connexin-43, which allows the absorbed acid load to be transmitted across the stromal syncytium. To match the stimulatory effect on acid uptake, cell-to-cell coupling in NHDF-Ad and CCD-112-CoN cells was strengthened with TGFβ1. In contrast, acid transmission was absent between CRC cells, even after treatment with TGFβ1. Thus, stromal cells have the necessary molecular apparatus for assembling an acid-venting route that can improve the flow of metabolic acid through tumors. Importantly, the activities of stromal AE2 and connexin-43 do not place an energetic burden on cancer cells, allowing resources to be diverted for other activities. PMID:27543333

  8. Retinol metabolism in LLC-PK1 Cells. Characterization of retinoic acid synthesis by an established mammalian cell line.

    PubMed

    Napoli, J L

    1986-10-15

    Specific assays, based on gas chromatography-mass spectrometry and high-performance liquid chromatography, were used to quantify the conversion of retinol and retinal into retinoic acid by the pig kidney cell line LLC-PK1. Retinoic acid synthesis was linear for 2-4 h as well as with graded amounts of either substrate to at least 50 microM. Retinoic acid concentrations increased through 6-8 h, but decreased thereafter because of substrate depletion (t1/2 of retinol = 13 h) and product metabolism (1/2 = 2.3 h). Retinoic acid metabolism was accelerated by treating cells with 100 nM retinoic acid for 10 h (t1/2 = 1.7 h) and was inhibited by the antimycotic imidazole ketoconazole. Feedback inhibition was not indicated since retinoic acid up to 100 nM did not inhibit its own synthesis. Retinol dehydrogenation was rate-limiting. The reduction and dehydrogenation of retinal were 4-8-fold and 30-60-fold faster, respectively. Greater than 95% of retinol was converted into metabolites other than retinoic acid, whereas the major metabolite of retinal was retinoic acid. The synthetic retinoid 13-cis-N-ethylretinamide inhibited retinoic acid synthesis, but 4-hydroxylphenylretinamide did not. 4'-(9-Acridinylamino)methanesulfon-m-anisidide, an inhibitor of aldehyde oxidase, and ethanol did not inhibit retinoic acid synthesis. 4-Methylpyrazole was a weak inhibitor: disulfiram was a potent inhibitor. These data indicate that retinol dehydrogenase is a sulfhydryl group-dependent enzyme, distinct from ethanol dehydrogenase. Homogenates of LLC-PK1 cells converted retinol into retinoic acid and retinyl palmitate and hydrolyzed retinyl palmitate. This report suggests that substrate availability, relative to enzyme activity/amount, is a primary determinant of the rate of retinoic acid synthesis, identifies inhibitors of retinoic acid synthesis, and places retinoic acid synthesis into perspective with several other known pathways of retinoid metabolism. PMID:3759984

  9. Bioaugmentation for treating transient 4-fluorocinnamic acid shock loads in a rotating biological contactor.

    PubMed

    Amorim, Catarina L; Duque, Anouk F; Afonso, Carlos M M; Castro, Paula M L

    2013-09-01

    A rotating biological contactor (RBC) was used to treat shock loadings of 4-fluorocinnamic acid (4-FCA). Intermittent 4-FCA shocks of 35 mg L(-1) were applied (ca. 3 months) with only limited mineralization occurring and accumulation of 4-fluorobenzoate (4-FBA) as an intermediate. After bioaugmentation with a degrading bacterium the RBC was able to deal with 4-FCA intermittent loading of 80 mg L(-1) however, a gradual decline in RBC performance occurred, leading to 4-FBA accumulation. The degrading strain was recovered from the biofilm during 2 months but intermittent feeding may have led to diminishing strain numbers. Distinct bacterial communities in the 1st and the 5th and 10th stages of the RBC were revealed by denaturating gradient gel electrophoresis. Several isolates retrieved from the RBC transformed 4-FCA into 4-FBA but only two strains mineralized the compound. Bioaugmentation allowed removal of the fluorinated compound however intermittent feeding may have compromised the bioreactor efficiency.

  10. Stem Cell Transplantation in Treating Patients With Hematologic Cancer

    ClinicalTrials.gov

    2012-05-31

    Chronic Myeloproliferative Disorders; Graft Versus Host Disease; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Precancerous/Nonmalignant Condition; Small Intestine Cancer

  11. Effectiveness of Glycyrrhizinic Acid (Glizigen) and an Immunostimulant (Viusid) to Treat Anogenital Warts

    PubMed Central

    Domínguez Gómez, José; Simón, Ramón Daniel; Abreu Daniel, Alfredo; Zelenkova, Hana

    2012-01-01

    Genital warts are benign proliferations of skin and mucosa caused by the human papillomavirus infection (hereinafter referred to as HPV). It is one of the most common sexually transmitted diseases in the world, whose incidence rate has increased in the last three decades. Current treatment involves the physical destruction of the infected cells. The fact that there are many different types of treatment goes to show that none of them are uniformly effective or directly antiviral. Objective. Demonstrate the efficacy of Glizigen in the III-phase clinical trial combined with a food supplement (VIUSID) formulated to boost the immune system when treating external anogenital warts. Design. 100 patients clinically diagnosed with anogenital lesions were included in the trial and assigned to two groups of 50 individuals. Those from one group where treated with Glizigen and Viusid and those from the other group with 25% podophyllin in alcohol, the results from each were then compared. Results. The combined Glizigen-Viusid treatment was seen to have an 87.5% efficacy rate, which was slightly more than that of the treatment with podophyllin, and there were hardly any adverse reactions reported during the treatment. Conclusions. the combined Glizigen-Viusid treatment was effective in treating genital warts. PMID:22957266

  12. Fed-batch production of gluconic acid by terpene-treated Aspergillus niger spores.

    PubMed

    Ramachandran, Sumitra; Fontanille, Pierre; Pandey, Ashok; Larroche, Christian

    2008-12-01

    Aspergillus niger spores were used as catalyst in the bioconversion of glucose to gluconic acid. Spores produced by solid-state fermentation were treated with 15 different terpenes including monoterpenes and monoterpenoids to permeabilize and inhibit spore germination. It was found that spore membrane permeability is significantly increased by treatment with terpenoids when compared to monoterpenes. Best results were obtained with citral and isonovalal. Studies were carried out to optimize spores concentration (10(7)-10(10) spores/mL), terpene concentrations in the bioconversion medium and time of exposure (1-18 h) needed for permeabilization of spores. Fed-batch production of gluconate was done in a bioreactor with the best conditions [10(9) spores/mL of freeze-thawed spores treated with citral (3% v/v) for 5 h] followed by sequential additions of glucose powder and pH-regulated with a solution containing 2 mol/L of either NaOH or KOH. Bioconversion performance of the spore enzyme was compared with the commercial glucose oxidase at 50, 60, and 70 degrees C. Results showed that the spore enzyme was comparatively stable at 60 degrees C. It was also found that the spores could be reutilized for more than 14 cycles with almost similar reaction rate. Similar biocatalytic activity was rendered by spores even after its storage of 1 year at -20 degrees C. This study provided an experimental evidence of the significant catalytic role played by A. niger spore in bioconversion of glucose to gluconic acid with high yield and stability, giving protection to glucose oxidase.

  13. Study on removal of elemental mercury from simulated flue gas over activated coke treated by acid

    NASA Astrophysics Data System (ADS)

    Ma, Jinfeng; Li, Caiting; Zhao, Lingkui; Zhang, Jie; Song, Jingke; Zeng, Guangming; Zhang, Xunan; Xie, Yine

    2015-02-01

    This work addressed the investigation of activated coke (AC) treated by acids. Effects of AC samples, modified by ether different acids (H2SO4, HNO3 and HClO4) or HClO4 of varied concentrations, on Hg0 removal were studied under simulated flue gas conditions. In addition, effects of reaction temperature and individual flue gas components including O2, NO, SO2 and H2O were discussed. In the experiments, Brunauer-Emmett-Teller (BET), X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR) were applied to explore the surface properties of sorbents and possible mechanism of Hg0 oxidation. Results showed that AC sample treated by HClO4 of 4.5 mol/L exhibited maximum promotion of efficiency on Hg0 removal at 160 °C. NO was proved to be positive in the removal of Hg0. And SO2 displayed varied impact in capturing Hg0 due to the integrated reactions between SO2 and modified AC. The addition of O2 could improve the advancement further to some extent. Besides, the Hg0 removal capacity had a slight declination when H2O was added in gas flow. Based on the analysis of XPS and FTIR, the selected sample absorbed Hg0 mostly in chemical way. The reaction mechanism, deduced from results of characterization and performance of AC samples, indicated that Hg0 could firstly be absorbed on sorbent and then react with oxygen-containing (Csbnd O) or chlorine-containing groups (Csbnd Cl) on the surface of sorbent. And the products were mainly in forms of mercuric chloride (HgCl2) and mercuric oxide (HgO).

  14. Chromate adsorption on acid-treated and amines-modified clay

    NASA Astrophysics Data System (ADS)

    Hajjaji, M.; Beraa, A.

    2015-03-01

    Acid-treated montmorillonite-rich clay and amines (methylamine, morpholine, and aniline)-modified clay adsorbents were investigated and their abilities to remove chromate from aqueous solution were studied. For the later purpose, kinetic studies were carried out under different operating conditions (chromate concentration, adsorbent content, and temperature), and adsorption isotherm measurements were performed. It was found that the kinetic of adsorption was fast and the data followed the pseudo-second rate equation. The rate of adsorption was controlled by the intra-particle diffusion and mass transfer through the liquid film, and the relative importance of these limiting steps depended on the operating conditions. Chromate adsorption was an endothermic process and took place spontaneously by physisorption. The free energy at 25 ≤ T ≤ 40 °C varied from -1.5 to -46 kJ/mol. Adsorption isotherms of Na+-saturated clay (AN), acid-treated clay (AA), and methylamine-clay and morpholine-clay (A-Me, A-Mo) were type V, whereas those of aniline-clay (A-An) were type III. The estimated maximum uptakes were 105, 29, 15, 11, and 10 mmol/kg for A-An, AN, A-Mo, AA, and A-Me, respectively. The mechanism of chromate adsorption was discussed based on the shape of the isotherms. Considering for instance the most efficient absorbent (A-An), the isotherm followed the Freundlich equation and hydrogen chromate (the main stable form at working pH) adsorbed to solid particles once aniline species were entirely desorbed.

  15. Untreated or drug-treated tumor cells are differentially recognized by allogeneic lymphocytes.

    PubMed

    D'Atri, S; Romani, L; Bonmassar, E; Grohmann, U; Tricarico, M; Christmas, S E; Moore, M

    1994-07-01

    Murine tumor cells treated with triazene compounds (TZC), in vivo or in vitro, are capable of eliciting specific transplantation resistance in syngeneic hosts, and T-cell-mediated proliferative and cytotoxic responses, directed against novel drug-induced antigen(s). Since this phenomenon, referred to as chemical xenogenization (CX) could open up new perspectives in the immunochemotherapy of human neoplasias, it was of interest to investigate whether CX could also occur in human tumors. However, established human tumor cell lines along with fully immunocompetent autologous lymphocytes, are seldom available. Therefore studies were carried out to test whether parental or TZC-treated tumor cells could be differentially recognized by allogeneic lymphocytes. Experiments were performed in both human and murine models, using a lung adenocarcinoma line treated in vitro with TZC, or an established xenogenized mouse lymphoma, respectively. The results indicate that allogeneic cytotoxic T-lymphocytes (CTL) recognize specifically murine TZC-treated tumor cells. This was supported by the finding that antisera directed against the drug-treated cells abrogated the generation and the cytolytic activity of allogeneic CTL reactive against the TZC-treated tumor. In addition it was found that changes of the antigenic pattern of cell membrane recognizable by cloned allogeneic CTL occur in the TZC-treated human carcinoma cell line.

  16. Cell cycle nucleic acids, polypeptides and uses thereof

    DOEpatents

    Gordon-Kamm, William J.; Lowe, Keith S.; Larkins, Brian A.; Dilkes, Brian R.; Sun, Yuejin

    2007-08-14

    The invention provides isolated nucleic acids and their encoded proteins that are involved in cell cycle regulation. The invention further provides recombinant expression cassettes, host cells, transgenic plants, and antibody compositions. The present invention provides methods and compositions relating to altering cell cycle protein content, cell cycle progression, cell number and/or composition of plants.

  17. New use for an old reagent: Cell cycle analysis of DNA content using flow cytometry in formamide treated cells.

    PubMed

    Carbonari, Maurizio

    2016-05-01

    Formamide has long been one of the most widely used reagents in the study of nucleic acids. However, the use of formamide for treating cells to be analyzed by flow cytometry is a recent development and is restricted to measuring telomere lengths by flow-FISH. In this field, we have published several papers in order to observe the effects of formamide treatment on cells at room temperature. We therefore discovered that, with suitable modifications, a short and simple incubation in this ionizing solvent facilitates cell cycle analysis by flow cytometry, equivalent or superior to that obtained with treatments in alcohol, acetone or detergent in hypotonic solution. Even using a bulky and problematic stain (low quantum efficiency and G-C base preference), such as 7-aminoactinomycin D (7-AAD) which, on the other hand, has the advantage of being excited at 488 nm and does not bind to the RNA, it is possible to obtain excellent coefficients of variation and (G2-M) mode/(G0-G1) mode ratios. These parameters, especially if stained cells are washed before acquisition, arrive at optimal values. It is noteworthy that the ability to wash the cells stained for DNA content analysis without affecting the stoichiometry of the staining has not been described elsewhere in the literature. With formamide treatment the doublets are practically absent, sample recovery is efficient, as well as the preservation of physical parameters, and the stained cells can be stored for at least 10 days at room temperature before acquisition. © 2016 International Society for Advancement of Cytometry. PMID:26866418

  18. Effects of the food additive, citric acid, on kidney cells of mice.

    PubMed

    Chen, Xg; Lv, Qx; Liu, Ym; Deng, W

    2015-01-01

    Citric acid is a food additive that is widely used in the food and drink industry. We investigated the effects of citric acid injection on mouse kidney. Forty healthy mice were divided into four groups of 10 including one control group and three citric acid-treated groups. Low dose, middle dose and high dose groups were given doses of 120, 240 and 480 mg/kg of citric acid, respectively. On day 7, kidney tissues were collected for histological, biochemical and molecular biological examination. We observed shrinkage of glomeruli, widened urinary spaces and capillary congestion, narrowing of the tubule lumen, edema and cytoplasmic vacuolated tubule cells, and appearance of pyknotic nuclei. The relation between histopathological changes and citric acid was dose dependent. Compared to the control, T-SOD and GSH-Px activities in the treated groups decreased with increasing doses of citric acid, NOS activity tended to increase, and H2O2 and MDA contents gradually decreased, but the differences between any treated group and the control were not statistically significant. The apoptosis assay showed a dose-dependent increase of caspase-3 activity after administering citrate that was statistically significant. DNA ladder formation occurred after treatment with any dose of citric acid. We concluded that administration of citric acid may cause renal toxicity in mice.

  19. Cancellous bone healing around strontium-doped hydroxyapatite in osteoporotic rats previously treated with zoledronic acid.

    PubMed

    Li, Yunfeng; Shui, Xueping; Zhang, Li; Hu, Jing

    2016-04-01

    Bisphosphonates (BPs) are potent anti-osteoporotic agents. Strontium-doped hydroxyapatite (HA) (SrHA) has been reported to increase bone density and improve trabecular microarchitecture in osteoporotic animals. But information about the effect of SrHA on the surrounding bone tissue in osteoporotic animals previously on BPs treatment is limited. We hypothesize that SrHA will induce increased bone density in the vicinity of the material when compared to HA, even in osteoporotic animals previously treated with BPs. HA and 10%SrHA (HA with 10 mol % calcium substituted by strontium) implants were prepared and characterized by scanning electronic microscopy (SEM), X-ray photoemission spectroscopy (XPS), and X-ray diffraction (XRD). Osteoporotic animal model was established by bilateral ovariectomy. Twelve weeks later, all OVX rats accepted subcutaneous injection of zoledronic acid (ZOL) at the dose of 1.5 μg/kg weekly for another twelve weeks. Subsequently, rod-shaped HA and SrHA implants were inserted in the distal femur of the OVX animals previously treated with ZOL. Eight weeks after implantation, specimens were harvested for histological and micro-computed tomography (micro-CT) analysis. Compared to HA, 10%SrHA raised the percent bone volume by 32.7%, the mean trabecular thickness by 36.5%, the mean trabecular number by 34.3%, the mean connectivity density by 38.4%, while the mean trabecular separation showed no significant difference. 10%SrHA also increased the bone area density by 36.3% in histological analysis. Results from this study indicated that 10%SrHA increased bone density and improved trabecular microarchitecture around implants in osteoporotic animals previously treated with ZOL when compared to HA. PMID:25891947

  20. Lysophosphatidic acid-induced chemotaxis of bone cells.

    SciTech Connect

    Karagiosis, Sue A.; Masiello, Lisa M.; Bollinger, Nikki; Karin, Norm J.

    2006-07-01

    Lysophosphatidic acid (LPA) is a platelet-derived bioactive lipid that is postulated to regulate wound healing. LPA activates G protein-coupled receptors to induce Ca2+ signaling in MC3T3-E1 pre-osteoblasts, and is a potent chemotactic stimulus for these cells. Since bone fracture healing requires the migration of osteoblast progenitors, we postulate that LPA is among the factors that stimulate bone repair. UMR 106-01 cells, which express a more mature osteoblastic phenotype than MC3T3-E1 cells, did not migrate in response to LPA, although they express LPA receptors and exhibit LPA-induced Ca2+ signals. This suggests that LPA differentially induces pre-osteoblast chemotaxis, consistent with our hypothesis that LPA stimulates the motility of osteoblast progenitors during bone healing. LPA-stimulated MC3T3-E1 cells exhibit striking changes in morphology and F-actin architecture, and phosphatidylinositol-3 kinase (PI3K) is required for motility-associated cytoskeletal rearrangements in many cell types. We found a dose-dependent reduction in LPA-induced osteoblast migration when cells also were treated with the PI3K inhibitor, LY294002. Treatment of many cell types with LPA is associated with an autocrine/paracrine transactivation of the EGF receptor (EGFR) via shedding of surface-tethered EGFR ligands, a phenomenon often required for LPA-induced chemotaxis. MC3T3-E1 cells express multiple EGFR ligands (epigen, epiregulin, HB-EGF and amphiregulin) and migrated in response to EGF. However, while EGF-stimulated motility in MC3T3-E1 cells was blocked by an EGFR inhibitor, there was no significant effect on LPA-induced chemotaxis. Activation of MAP kinases is a hallmark of EGFR-mediated signaling, and EGF treatment of MC3T3-E1 cells led to a strong stimulation of ERK1/2 kinase. In contrast, LPA induced only a minor elevation in ERK activity. Thus, it is likely that the increase in ERK activity by LPA is related to cell proliferation associated with lipid treatment. We

  1. Molecular Determinants of the Response of Tumor Cells to Boswellic Acids

    PubMed Central

    Eichhorn, Tolga; Greten, Henry Johannes; Efferth, Thomas

    2011-01-01

    Frankincense (Boswellia serrata, B. carterii) is used as traditional remedy to treat inflammatory diseases. The molecular effects of the active ingredients, the boswellic acids, on the immune system have previously been studied and verified in several clinical studies. Boswellic acids also inhibit cancer cell growth in vitro and in vivo. The molecular basis of the cytotoxicity of boswellic acids is, however, not fully understood as yet. By mRNA-based microarray, COMPARE, and hierarchical cluster analyses, we identified a panel of genes from diverse functional groups, which were significantly associated with sensitivity or resistance of α- or β-boswellic acids, such as transcription factors, signal transducers, growth regulating genes, genes involved in RNA and protein metabolism and others. This indicates that boswellic acids exert profound cytotoxicity on cancer cells by a multiplicity of molecular mechanisms.

  2. Counter-current acid leaching process for copper azole treated wood waste.

    PubMed

    Janin, Amélie; Riche, Pauline; Blais, Jean-François; Mercier, Guy; Cooper, Paul; Morris, Paul

    2012-09-01

    This study explores the performance of a counter-current leaching process (CCLP) for copper extraction from copper azole treated wood waste for recycling of wood and copper. The leaching process uses three acid leaching steps with 0.1 M H2SO4 at 75degrees C and 15% slurry density followed by three rinses with water. Copper is recovered from the leachate using electrodeposition at 5 amperes (A) for 75 min. Ten counter-current remediation cycles were completed achieving > or = 94% copper extraction from the wood during the 10 cycles; 80-90% of the copper was recovered from the extract solution by electrodeposition. The counter-current leaching process reduced acid consumption by 86% and effluent discharge volume was 12 times lower compared with the same process without use of counter-current leaching. However, the reuse of leachates from one leaching step to another released dissolved organic carbon and caused its build-up in the early cycles. PMID:23240206

  3. Electrochemical characteristics of acid electrolytes for fuel cells

    NASA Astrophysics Data System (ADS)

    Adzic, R.; Gervasio, D.; Kanamura, K.; Razaq, A.; Razaq, M.; Yeager, Ernest B.

    1990-01-01

    Five topics investigated by the Gas Research Institute (GRI) contractors at Case Western Reserve University (CWRU) during the past year included: (1) electrochemical evaluation of perfluorinated electrolyte, (2) the Nafion solid polymer electrolyte (SPE) fuel cell, (3) electrochemistry of single crystal Pt electrodes in acid solution, (4) catalytic effects of adatoms entrapped on electrode surfaces by bipolar or monopolar ion exchange membrane layers, (5) investigations of the Fleischmann-Pons phenomenon. The principal objective of the project is to evaluate new acid electrolytes. Electrochemical evaluation was made for two bisphosphonic acids as a replacement for phosphoric acid as a fuel cell electrolyte, and also a bis-sulfonyl carbon acid as an additive to concentrated phosphoric acid electrolyte for acid H2-O2 fuel cells. Electrochemical characteristics were found for these new perfluorinated acids.

  4. Rhabdovirus-induced apoptosis in a fish cell line is inhibited by a human endogenous acid cysteine proteinase inhibitor.

    PubMed

    Björklund, H V; Johansson, T R; Rinne, A

    1997-07-01

    To determine the mechanisms of cell death in rhabdovirus-infected cells, we studied the infection of the epithelial papilloma of carp cell line with spring viremia of carp virus. Studies using electron microscopy, confocal microscopy, and agarose gel electrophoresis revealed changes in cell morphology and DNA fragmentation indicative of apoptosis. The virus-induced apoptosis was inhibited in cells treated with a human endogenous acid cysteine proteinase inhibitor. PMID:9188644

  5. Gallic acid induced apoptotic events in HCT-15 colon cancer cells

    PubMed Central

    Subramanian, Aruna Priyadharshni; Jaganathan, Saravana Kumar; Mandal, Mahitosh; Supriyanto, Eko; Muhamad, Ida Idayu

    2016-01-01

    AIM: To investigate the inhibitory action of diet-derived phenolic compound gallic acid (GA) against HCT-15 colon cancer cells. METHODS: The antiproliferative effect of GA against colon cancer cells was determined by performing thiazolyl blue tetrazolium bromide (MTT) assay. The colony forming ability of GA treated colon cancer cells was evaluated using the colony forming assay. The cell cycle changes induced by GA in HCT-15 cells were analyzed by propidium iodide staining. Levels of reactive oxygen species (ROS) and mitochondrial membrane potential of HCT-15 exposed to GA was assessed using 2’,7’-dichlorfluorescein-diacetate and rhodamine-123 respectively, with the help of flow cytometry. Morphological changes caused by GA treatment in the colon cancer cells were identified by scanning electron microscope and photomicrograph examination. Apoptosis was confirmed using flow cytometric analysis of GA treated HCT-15 cells after staining with Yo-Pro-1. RESULTS: MTT assay results illustrated that GA has an inhibitory effect on HCT-15 cells with IC50 value of 740 μmol/L. A time-dependent inhibition of colony formation was evident with GA treatment. Cell cycle arrest was evident from the accumulation of GA treated HCT-15 cells at sub-G1 phase (0.98 ± 1.03 vs 58.01 ± 2.05) with increasing exposure time. Flow cytometric analysis of GA treated HCT-15 cells depicted early events associated with apoptosis like lipid layer breakage and fall in mitochondrial membrane potential apart from an increase in the generation of ROS which were in a time dependent manner. SEM and photomicrograph images of the GA-treated cells displayed membrane blebbing and cell shrinking characteristics of apoptosis. Further apoptosis confirmation by Yo-Pro-1 staining also showed the time-dependent increase of apoptotic cells after treatment. CONCLUSION: These results show that GA induced ROS dependent apoptosis and inhibited the growth of colon cancer cells. PMID:27099438

  6. Growth modulating effects of chlorinated oleic acid in cell cultures.

    PubMed

    Høstmark, A T; Lystad, E; Jebens, E; Skramstad, J; Frøyen, P

    1998-07-01

    Chlorinated fatty acids represent a major fraction of extractable, organically bound chlorine in fish. After dietary intake such fatty acids may be transferred from the mother to the foetus through the placenta, and via breast milk to the child. In the present work we have studied the effect of chlorinated oleic acid on the growth of three widely differing types of cells in culture. Chlorinated oleic acid inhibited growth of Human Microvascular Endothelial Cells (HMVEC), Immortilized Human Kidney Epithelial (IHKE) cells, and human Hepatoma cells (HepG2). The order of potency was: HMVEC > IHKE > HepG2. Vitamin E counteracted the inhibitory effect of chlorinated oleic acid on HepG2 cells, but did not significantly affect the fatty acid effect on HMVEC or IHKE. Defatted serum albumin stimulated the growth of HMVEC and IHKE. With HMVEC there was no major interaction between the effect of albumin and chlorinated oleic acid on cell growth. In contrast, with IHKE albumin at low concentration abolished the growth inhibiting effect of chlorinated oleic acid and appreciably counteracted growth inhibition by the fatty acid of HepG2. We conclude that the growth modulation by chlorinated oleic acid and its interaction with vitamin E and albumin are cell specific.

  7. Treating Multiply Relapsed or Refractory Hairy Cell Leukemia

    Cancer.gov

    In this trial, patients with hairy cell leukemia who have not responded or relapsed after initial chemotherapy will be randomly assigned to receive rituximab combined with either pentostatin or bendamustine.

  8. Can spherical eukaryotic microalgae cells be treated as optically homogeneous?

    PubMed

    Bhowmik, Arka; Pilon, Laurent

    2016-08-01

    This study aims to answer the question of whether spherical unicellular photoautotrophic eukaryotic microalgae cells, consisting of various intracellular compartments with their respective optical properties, can be modeled as homogeneous spheres with some effective complex index of refraction. The spectral radiation characteristics in the photosynthetically active region of a spherical heterogeneous microalgae cell, representative of Chlamydomonas reinhardtii and consisting of spherical compartments corresponding to the cell wall, cytoplasm, chloroplast, nucleus, and mitochondria, were estimated using the superposition T-matrix method. The effects of the presence of intracellular lipids and/or starch accumulation caused by stresses, such as nitrogen limitation, were explored. Predictions by the T-matrix method were qualitatively and quantitatively consistent with experimental measurements for various microalgae species. The volume-equivalent homogeneous sphere approximation with volume-averaged effective complex index of refraction gave accurate estimates of the spectral (i) absorption and (ii) scattering cross sections of the heterogeneous cells under both nitrogen-replete and nitrogen-limited conditions. In addition, the effect of a strongly refracting cell wall, representative of Chlorella vulgaris, was investigated. In this case, for the purpose of predicting their integral radiation characteristics, the microalgae should be represented as a coated sphere with a coating corresponding to the cell wall and a homogeneous core with volume-averaged complex index of refraction for the rest of the cell. However, both homogeneous sphere and coated sphere approximations predicted strong resonances in the scattering phase function and spectral backscattering cross section that were not observed in that of the heterogeneous cells. PMID:27505647

  9. Amino acids in the cultivation of mammalian cells.

    PubMed

    Salazar, Andrew; Keusgen, Michael; von Hagen, Jörg

    2016-05-01

    Amino acids are crucial for the cultivation of mammalian cells. This importance of amino acids was realized soon after the development of the first cell lines, and a solution of a mixture of amino acids has been supplied to cultured cells ever since. The importance of amino acids is further pronounced in chemically defined mammalian cell culture media, making the consideration of their biological and chemical properties necessary. Amino acids concentrations have been traditionally adjusted to their cellular consumption rates. However, since changes in the metabolic equilibrium of amino acids can be caused by changes in extracellular concentrations, metabolomics in conjunction with flux balance analysis is being used in the development of culture media. The study of amino acid transporters is also gaining importance since they control the intracellular concentrations of these molecules and are influenced by conditions in cell culture media. A better understanding of the solubility, stability, dissolution kinetics, and interactions of these molecules is needed for an exploitation of these properties in the development of dry powdered chemically defined media for mammalian cells. Due to the complexity of these mixtures however, this has proven to be challenging. Studying amino acids in mammalian cell culture media will help provide a better understanding of how mammalian cells in culture interact with their environment. It would also provide insight into the chemical behavior of these molecules in solutions of complex mixtures, which is important in the understanding of the contribution of individual amino acids to protein structure. PMID:26832172

  10. Amino acids in the cultivation of mammalian cells.

    PubMed

    Salazar, Andrew; Keusgen, Michael; von Hagen, Jörg

    2016-05-01

    Amino acids are crucial for the cultivation of mammalian cells. This importance of amino acids was realized soon after the development of the first cell lines, and a solution of a mixture of amino acids has been supplied to cultured cells ever since. The importance of amino acids is further pronounced in chemically defined mammalian cell culture media, making the consideration of their biological and chemical properties necessary. Amino acids concentrations have been traditionally adjusted to their cellular consumption rates. However, since changes in the metabolic equilibrium of amino acids can be caused by changes in extracellular concentrations, metabolomics in conjunction with flux balance analysis is being used in the development of culture media. The study of amino acid transporters is also gaining importance since they control the intracellular concentrations of these molecules and are influenced by conditions in cell culture media. A better understanding of the solubility, stability, dissolution kinetics, and interactions of these molecules is needed for an exploitation of these properties in the development of dry powdered chemically defined media for mammalian cells. Due to the complexity of these mixtures however, this has proven to be challenging. Studying amino acids in mammalian cell culture media will help provide a better understanding of how mammalian cells in culture interact with their environment. It would also provide insight into the chemical behavior of these molecules in solutions of complex mixtures, which is important in the understanding of the contribution of individual amino acids to protein structure.

  11. Transepithelial transport of ferulic acid by monocarboxylic acid transporter in Caco-2 cell monolayers.

    PubMed

    Konishi, Yutaka; Shimizu, Makoto

    2003-04-01

    Our previous study (Biosci. Biotechnol. Biochem., 66, 2449-2457 (2002)), suggested that ferulic acid was transported via a monocarboxylic acid transporter (MCT). Transepithelial transport of ferulic acid was examined in this study by directly measuring the rate of its transport across Caco-2 cell monolayers. Ferulic acid transport was dependent on pH, and in a vectorical way in the apical-basolateral direction. The permeation of ferulic acid was concentration-dependent and saturable; the Michaelis constant was 16.2 mM and the maximum velocity was 220.4 nmol min-1 (mg protein)-1. Various substrates for MCTs, such as benzoic acid and acetic acid, strongly inhibited the permeation of ferulic acid, demonstrating that ferulic acid is obviously transported by MCT. Antioxidative phenolic acid compounds from dietary sources like ferulic acid would be recognized and transported by MCT by intestinal absorption.

  12. Strategies for recruitment of stem cells to treat myocardial infarction.

    PubMed

    Shafiq, Muhammad; Lee, Sang-Hoon; Jung, Youngmee; Kim, Soo Hyun

    2015-01-01

    Heart failure is one of the most prominent causes of morbidity and mortality worldwide. According to the World Health Organization, coronary artery disease and myocardial infarction (MI) are responsible for 29% of deaths worldwide. MI results in obstruction of the blood supply to the heart and scar formation, and causes substantial death of cardiomyocytes in the infarct zone followed by an inflammatory response. Current treatment methodologies of MI and heart failure include organ transplantation, coronary artery bypass grafting, ventricular remodeling, cardiomyoplasty, and cellular therapy. Each of these methodologies has associated risks and benefits. Cellular cardiomyoplasty is a viable option to decrease the fibrosis of infarct scars, adverse post-ischemic remodeling, and improve heart function. However, the low rate of cell survival, shortage of cell sources and donors, tumorigenesis, and ethical issues hamper full exploitation of cell therapy for MI treatment. Consequently, the mobilization and recruitment of endogenous stem/progenitor cells from bone marrow, peripheral circulation, and cardiac tissues has immense potential through harnessing the host's own reparative capacities that result from interplay among cytokines, chemokines, and adhesion molecules. Therapeutic treatments to enhance the mobilization and homing of stem cells are under development. In this review, we present state-of-the-art approaches that are being pursued for stem cell mobilization and recruitment to regenerate infarcted myocardium. Potential therapeutic interventions and delivery strategies are discussed in detail.

  13. Strategies for recruitment of stem cells to treat myocardial infarction.

    PubMed

    Shafiq, Muhammad; Lee, Sang-Hoon; Jung, Youngmee; Kim, Soo Hyun

    2015-01-01

    Heart failure is one of the most prominent causes of morbidity and mortality worldwide. According to the World Health Organization, coronary artery disease and myocardial infarction (MI) are responsible for 29% of deaths worldwide. MI results in obstruction of the blood supply to the heart and scar formation, and causes substantial death of cardiomyocytes in the infarct zone followed by an inflammatory response. Current treatment methodologies of MI and heart failure include organ transplantation, coronary artery bypass grafting, ventricular remodeling, cardiomyoplasty, and cellular therapy. Each of these methodologies has associated risks and benefits. Cellular cardiomyoplasty is a viable option to decrease the fibrosis of infarct scars, adverse post-ischemic remodeling, and improve heart function. However, the low rate of cell survival, shortage of cell sources and donors, tumorigenesis, and ethical issues hamper full exploitation of cell therapy for MI treatment. Consequently, the mobilization and recruitment of endogenous stem/progenitor cells from bone marrow, peripheral circulation, and cardiac tissues has immense potential through harnessing the host's own reparative capacities that result from interplay among cytokines, chemokines, and adhesion molecules. Therapeutic treatments to enhance the mobilization and homing of stem cells are under development. In this review, we present state-of-the-art approaches that are being pursued for stem cell mobilization and recruitment to regenerate infarcted myocardium. Potential therapeutic interventions and delivery strategies are discussed in detail. PMID:25594408

  14. Amino acid conjugated self assembling molecules for enhancing surface wettability of fiber laser treated titanium surfaces

    NASA Astrophysics Data System (ADS)

    Akkan, Cagri K.; Hür, Deniz; Uzun, Lokman; Garipcan, Bora

    2016-03-01

    Surface wetting properties of implants are one of the most critical parameter, which determine the interaction of proteins and cells with the implant surface. In this regards, acid etching and sand blasting are the mostly used methods at surface modification of Titanium (Ti) for enhanced surface wettability. Besides, these kinds of modifications may cause a conflict whether the surface wettability is influenced by the process related surface contaminations or by the surface roughness. In contrast, lasers might be an option for the alteration of surface wetting properties via supporting micro and/or nano surface topographies while preventing surface chemical contaminations. In this work, we focused on two steps of surface processing approaches of Ti surface: physical and chemical modifications. Herein, we hierarchically structured Ti surfaces by using microsecond modulated pulsed fiber laser. Subsequently, laser structured and non-structured Ti surfaces were further modified with novel histidine and leucine Amino Acid conjugated Self-Assembled Molecules (His1-SAMs2 and Leu3-SAMs) to alter the surface wettability by introducing biologically hydrophilic and hydrophobic groups. Modification of Ti surfaces with His-SAMs and Leu-SAMs ended up with stable wetting properties when compared to non-modified surfaces after 7 days which may enhances the cell-surface interaction.

  15. HF-LPLI-treated tumor cells induce NO production in macrophage

    NASA Astrophysics Data System (ADS)

    Lu, Cuixia; Zhou, Feifan; Wu, Shengnan; Xing, Da

    2013-02-01

    High fluence low-power laser irradiation (HF-LPLI) provides a new stimulator to trigger cell apoptosis, and it is well known that apoptotic cells provide antigens to effectively trigger recognition by the immune system. In order to investigate the effect of HF-LPLI on the professional antigen-presenting cell (APC) function, in our primary study, we focused our attention on the effect of HF-LPLI-treated tumor cells on macrophages phagocytosis and NO production. Both confocal microscopy and flowcytometry analysis showed that HF-LPLI (120 J/cm2) induced significantly EMT6 death. Further experiments showed that HF-LPLI-treated EMT6 cells could be phagocyted by the murine macrophage cells RAW264.7, and could induce NO production in macrophages. Taken together, our results indicate that HF-LPLI-treated tumor cells effectively regulated the immune system. The HF-LPLI effect on the APC function needs to be further studied.

  16. Formic acid and acetic acid induce a programmed cell death in pathogenic Candida species.

    PubMed

    Lastauskienė, Eglė; Zinkevičienė, Auksė; Girkontaitė, Irutė; Kaunietis, Arnoldas; Kvedarienė, Violeta

    2014-09-01

    Cutaneous fungal infections are common and widespread. Antifungal agents used for the treatment of these infections often have undesirable side effects. Furthermore, increased resistance of the microorganisms to the antifungal drugs becomes the growing problem. Accordingly, the search for natural antifungal compounds continues to receive attention. Apoptosis is highly regulated programmed cell death. During yeast cell apoptosis, amino acids and peptides are released and can stimulate regeneration of human epithelium cells. Thus, detection of chemical compounds inducing apoptosis in yeast and nontoxic for humans is of great medical relevance. The aim of this study was to detect chemical compound inducing apoptosis in pathogenic Candida species with the lowest toxicity to the mammalian cells. Five chemical compounds--acetic acid, sodium bicarbonate, potassium carbonate, lithium acetate, and formic acid--were tested for evaluation of antifungal activity on C. albicans, C. guilliermondii, and C. lusitaniae. The results showed that acetic acid and formic acid at the lowest concentrations induced yeast cells death. Apoptosis analysis revealed that cells death was accompanied by activation of caspase. Minimal inhibitory concentrations of potassium carbonate and sodium bicarbonate induced Candida cells necrosis. Toxicity test with mammalian cell cultures showed that formic acid has the lowest effect on the growth of Jurkat and NIH 3T3 cells. In conclusion, our results show that a low concentration of formic acid induces apoptosis-like programmed cell death in the Candida yeast and has a minimal effect on the survivability of mammalian cells, suggesting potential applications in the treatment of these infections. PMID:24752490

  17. Production of citric acid using its extraction wastewater treated by anaerobic digestion and ion exchange in an integrated citric acid-methane fermentation process.

    PubMed

    Xu, Jian; Chen, Yang-Qiu; Zhang, Hong-Jian; Tang, Lei; Wang, Ke; Zhang, Jian-Hua; Chen, Xu-Sheng; Mao, Zhong-Gui

    2014-08-01

    In order to solve the problem of extraction wastewater pollution in citric acid industry, an integrated citric acid-methane fermentation process is proposed in this study. Extraction wastewater was treated by mesophilic anaerobic digestion and then used to make mash for the next batch of citric acid fermentation. The recycling process was done for seven batches. Citric acid production (82.4 g/L on average) decreased by 34.1 % in the recycling batches (2nd-7th) compared with the first batch. And the residual reducing sugar exceeded 40 g/L on average in the recycling batches. Pigment substances, acetic acid, ammonium, and metal ions in anaerobic digestion effluent (ADE) were considered to be the inhibitors, and their effects on the fermentation were studied. Results indicated that ammonium, Na(+) and K(+) in the ADE significantly inhibited citric acid fermentation. Therefore, the ADE was treated by acidic cation exchange resin prior to reuse to make mash for citric acid fermentation. The recycling process was performed for ten batches, and citric acid productions in the recycling batches were 126.6 g/L on average, increasing by 1.7 % compared with the first batch. This process could eliminate extraction wastewater discharge and reduce water resource consumption.

  18. Brown but not white adipose cells synthesize omega-3 docosahexaenoic acid in culture.

    PubMed

    Qin, Xia; Park, Hui Gyu; Zhang, Ji Yao; Lawrence, Peter; Liu, Guowen; Subramanian, Nivetha; Kothapalli, Kumar S D; Brenna, J Thomas

    2016-01-01

    Adipose tissue is a complex endocrine organ which coordinates several crucial biological functions including fatty acid metabolism, glucose metabolism, energy homeostasis, and immune function. Brown adipose tissue (BAT) is most abundant in young infants during the brain growth spurt when demands for omega-3 docosahexaenoic acid (DHA, 22:6n-3) is greatest for brain structure. Our aim was to characterize relative biosynthesis of omega-3 long chain polyunsaturated fatty acids (LCPUFA) from precursors in cultured white (WAT) and brown (BAT) cells and study relevant gene expression. Mouse WAT and BAT cells were grown in regular DMEM media to confluence, and differentiation was induced. At days 0 and 8 cells were treated with albumin bound d5-18:3n-3 (d5-ALA) and analyzed 24h later. d5-ALA increased cellular eicosapentaenoic acid (EPA, 20:5n-3) and docosapentaenoic acid (DPA, 22:5n-3) in undifferentiated BAT cells, whereas differentiated BAT cells accumulated 20:4n-3, EPA and DPA. DHA as a fraction of total omega-3 LCPUFA was greatest in differentiated BAT cells compared to undifferentiated cells. Undifferentiated WAT cells accumulated EPA, whereas differentiated cells accumulated DPA. WAT accumulated trace newly synthesized DHA. Zic1 a classical brown marker and Prdm16 a key driver of brown fat cell fate are expressed only in BAT cells. Ppargc1a is 15 fold higher in differentiated BAT cells. We conclude that in differentiated adipose cells accumulating fat, BAT cells but not WAT cells synthesize DHA, supporting the hypothesis that BAT is a net producer of DHA.

  19. Factors secreted from dental pulp stem cells show multifaceted benefits for treating experimental rheumatoid arthritis.

    PubMed

    Ishikawa, Jun; Takahashi, Nobunori; Matsumoto, Takuya; Yoshioka, Yutaka; Yamamoto, Noriyuki; Nishikawa, Masaya; Hibi, Hideharu; Ishigro, Naoki; Ueda, Minoru; Furukawa, Koichi; Yamamoto, Akihito

    2016-02-01

    Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial hyperplasia and chronic inflammation, which lead to the progressive destruction of cartilage and bone in the joints. Numerous studies have reported that administrations of various types of MSCs improve arthritis symptoms in animal models, by paracrine mechanisms. However, the therapeutic effects of the secreted factors alone, without the cell graft, have been uncertain. Here, we show that a single intravenous administration of serum-free conditioned medium (CM) from human deciduous dental pulp stem cells (SHED-CM) into anti-collagen type II antibody-induced arthritis (CAIA), a mouse model of rheumatoid arthritis (RA), markedly improved the arthritis symptoms and joint destruction. The therapeutic efficacy of SHED-CM was associated with an induction of anti-inflammatory M2 macrophages in the CAIA joints and the abrogation of RANKL expression. SHED-CM specifically depleted of an M2 macrophage inducer, the secreted ectodomain of sialic acid-binding Ig-like lectin-9 (ED-Siglec-9), exhibited a reduced ability to induce M2-related gene expression and attenuate CAIA. SHED-CM also inhibited the RANKL-induced osteoclastogenesis in vitro. Collectively, our findings suggest that SHED-CM provides multifaceted therapeutic effects for treating CAIA, including the ED-Siglec-9-dependent induction of M2 macrophage polarization and inhibition of osteoclastogenesis. Thus, SHED-CM may represent a novel anti-inflammatory and reparative therapy for RA. PMID:26603475

  20. Factors secreted from dental pulp stem cells show multifaceted benefits for treating experimental rheumatoid arthritis.

    PubMed

    Ishikawa, Jun; Takahashi, Nobunori; Matsumoto, Takuya; Yoshioka, Yutaka; Yamamoto, Noriyuki; Nishikawa, Masaya; Hibi, Hideharu; Ishigro, Naoki; Ueda, Minoru; Furukawa, Koichi; Yamamoto, Akihito

    2016-02-01

    Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial hyperplasia and chronic inflammation, which lead to the progressive destruction of cartilage and bone in the joints. Numerous studies have reported that administrations of various types of MSCs improve arthritis symptoms in animal models, by paracrine mechanisms. However, the therapeutic effects of the secreted factors alone, without the cell graft, have been uncertain. Here, we show that a single intravenous administration of serum-free conditioned medium (CM) from human deciduous dental pulp stem cells (SHED-CM) into anti-collagen type II antibody-induced arthritis (CAIA), a mouse model of rheumatoid arthritis (RA), markedly improved the arthritis symptoms and joint destruction. The therapeutic efficacy of SHED-CM was associated with an induction of anti-inflammatory M2 macrophages in the CAIA joints and the abrogation of RANKL expression. SHED-CM specifically depleted of an M2 macrophage inducer, the secreted ectodomain of sialic acid-binding Ig-like lectin-9 (ED-Siglec-9), exhibited a reduced ability to induce M2-related gene expression and attenuate CAIA. SHED-CM also inhibited the RANKL-induced osteoclastogenesis in vitro. Collectively, our findings suggest that SHED-CM provides multifaceted therapeutic effects for treating CAIA, including the ED-Siglec-9-dependent induction of M2 macrophage polarization and inhibition of osteoclastogenesis. Thus, SHED-CM may represent a novel anti-inflammatory and reparative therapy for RA.

  1. Recombinant T Cell Receptor Ligand (RTL) Treats Experimental Stroke

    PubMed Central

    Subramanian, Sandhya; Zhang, Bing; Kosaka, Yasuharu; Burrows, Gregory G.; Grafe, Marjorie R.; Vandenbark, Arthur A.; Hurn, Patricia D.; Offner, Halina

    2009-01-01

    Background and Purpose Experimental stroke induces a biphasic effect on the immune response that involves early activation of peripheral leukocytes followed by severe immunodepression and atrophy of spleen and thymus. In tandem, the developing infarct is exacerbated by influx of numerous inflammatory cell types, including T and B lymphocytes. These features of stroke prompted our use of Recombinant T Cell Receptor Ligands (RTL), partial MHC class II molecules covalently bound to myelin peptides. We tested the hypothesis that RTL would improve ischemic outcome in brain without exacerbating defects in peripheral immune system function. Methods Four daily doses of RTL were administered subcutaneously to C57BL/6 mice after middle cerebral artery occlusion (MCAO), and lesion size and cellular composition were assessed in brain, and cell numbers were assessed in spleen and thymus. Results Treatment with RTL551 (I-Ab molecule linked to MOG-35−55 peptide) reduced cortical and total stroke lesion size by ∼50%, inhibited the accumulation of inflammatory cells, particularly macrophages/activated microglial cells and dendritic cells, and mitigated splenic atrophy. Treatment with RTL1000 (HLA-DR2 moiety linked to human MOG-35−55 peptide) similarly reduced the stroke lesion size in HLA-DR2 transgenic mice. In contrast, control RTL with a non-neuroantigen peptide or a mismatched MHC class II moiety had no effect on stroke lesion size. Conclusions These data are the first to demonstrate successful treatment of experimental stroke using a neuroantigen specific immunomodulatory agent administered after ischemia, suggesting therapeutic potential in human stroke. PMID:19443805

  2. Targeting cancer cells with folic acid-iminoboronate fluorescent conjugates.

    PubMed

    Cal, Pedro M S D; Frade, Raquel F M; Chudasama, Vijay; Cordeiro, Carlos; Caddick, Stephen; Gois, Pedro M P

    2014-05-25

    Herein we present the synthesis of fluorescent 2-acetylbenzeneboronic acids that undergo B-N promoted conjugation with lysozyme and N-(2-aminoethyl) folic acid (EDA-FA), generating conjugates that are selectively recognized and internalized by cancer cells that over-express folic acid receptors.

  3. Retinol oxidation to retinoic acid in human thyroid glandular cells.

    PubMed

    Taibi, Gennaro; Gueli, Maria Concetta; Nicotra, Concetta M A; Cocciadiferro, Letizia; Carruba, Giuseppe

    2014-12-01

    Abstract Retinoic acid is regarded as the retinol metabolite that controls proliferation and differentiation of epithelial cells. In the present study, we investigated the potential role of xanthine dehydrogenase (XDH) in retinoic acid biosynthesis in human thyroid glandular cells (HTGC). In particular, we observed that cellular retinoids binding proteins (CRBPs) are also implicated in the biosynthetic pathway leading to retinoic acid formation in primary cultures of HTGC, as we have already reported for human mammary epithelial cells (HMEC). After partial protein purification, the enzyme responsible for retinoic acid biosynthesis was identified and quantified as XDH by immunoassay, by its ability to oxidize xanthine to uric acid and its sensitivity to the inhibitory effect of oxypurinol. The evidence of XDH-driven formation of retinoic acid in HTGC cultures further corroborates the potential role of XDH in retinoic acid biosynthesis in the epithelia. PMID:24506204

  4. Postnatal Neural Stem Cells in Treating Traumatic Brain Injury.

    PubMed

    Gazalah, Hussein; Mantash, Sarah; Ramadan, Naify; Al Lafi, Sawsan; El Sitt, Sally; Darwish, Hala; Azari, Hassan; Fawaz, Lama; Ghanem, Noël; Zibara, Kazem; Boustany, Rose-Mary; Kobeissy, Firas; Soueid, Jihane

    2016-01-01

    Traumatic brain injury (TBI) is one of the leading causes of death and disabilities worldwide. It affects approximately 1.5 million people each year and is associated with severe post-TBI symptoms such as sensory and motor deficits. Several neuro-therapeutic approaches ranging from cell therapy interventions such as the use of neural stem cells (NSCs) to drug-based therapies have been proposed for TBI management. Successful cell-based therapies are tightly dependent on reproducible preclinical animal models to ensure safety and optimal therapeutic benefits. In this chapter, we describe the isolation of NSCs from neonatal mouse brain using the neurosphere assay in culture. Subsequently, dissociated neurosphere-derived cells are used for transplantation into the ipsilateral cortex of a controlled cortical impact (CCI) TBI model in C57BL/6 mice. Following intra-cardiac perfusion and brain removal, the success of NSC transplantation is then evaluated using immunofluorescence in order to assess neurogenesis along with gliosis in the ipsilateral coronal brain sections. Behavioral tests including rotarod and pole climbing are conducted to evaluate the motor activity post-treatment intervention. PMID:27604746

  5. Chrysophanic Acid Induces Necrosis but not Necroptosis in Human Renal Cell Carcinoma Caki-2 Cells

    PubMed Central

    Choi, Joon-Seok

    2016-01-01

    Background: Chrysophanic acid, also known as chrysophanol, has a number of biological activities. It enhances memory and learning abilities, raises superoxide dismutase activity, and has anti-cancer effects in several model systems. According to previous reports, chrysophanic acid-induced cell death shares features of necrotic cell death. However, the molecular and cellular processes underlying chrysophanic acid-induced cell death remain poorly understood. Methods: Chrysophanic acid-induced cell death was monitored by cell viability assay and Annexin V-propidium iodide (PI) staining of renal cell carcinoma Caki-2 cells. The induction of intracellular reactive oxygen species (ROS) by chrysophanic acid and the suppression of ROS by anti-oxidants were evaluated by 2′,7′-dichlorofluorescin diacetate staining. The expression and phosphorylation of proteins that are involved in apoptosis and necroptosis were detected by immunoblotting. Results: The extent of chrysophanic acid-induced cell death was concentration and time dependent, and dead cells mainly appeared in the PI-positive population, which is a major feature of necrosis, upon fluorescence-activated cell sorting analysis. Chrysophanic acid-induced cell death was associated with the generation of intracellular ROS, and this effect was reversed by pretreatment with N-acetyl cysteine. Chrysophanic acid-induced cell death was not associated with changes in apoptotic or necroptotic marker proteins. Conclusions: The cell death induced by chrysophanic acid resembled neither apoptotic nor necroptotic cell death in human renal cell carcinoma Caki-2 cells. PMID:27390736

  6. Cleaner production of citric acid by recycling its extraction wastewater treated with anaerobic digestion and electrodialysis in an integrated citric acid-methane production process.

    PubMed

    Xu, Jian; Su, Xian-Feng; Bao, Jia-Wei; Chen, Yang-Qiu; Zhang, Hong-Jian; Tang, Lei; Wang, Ke; Zhang, Jian-Hua; Chen, Xu-Sheng; Mao, Zhong-Gui

    2015-01-01

    To solve the pollution problem of extraction wastewater in citric acid production, an integrated citric acid-methane production process was proposed. Extraction wastewater was treated through anaerobic digestion and the anaerobic digestion effluent (ADE) was recycled for the next batch of citric acid fermentation, thus eliminating wastewater discharge and reducing water consumption. Excessive Na(+) contained in ADE could significantly inhibit citric acid fermentation in recycling and was removed by electrodialysis in this paper. Electrodialysis performance was improved after pretreatment of ADE with air stripping and activated carbon adsorption to remove precipitable metal ions and pigments. Moreover, the concentrate water was recycled and mixed with feed to improve the water recovery rate above 95% in electrodialysis treatment, while the dilute water was collected for citric acid fermentation. The removal rate of Na(+) in ADE was above 95% and the citric acid production was even higher than that with tap water.

  7. Denosumab or Zoledronic Acid in Postmenopausal Women With Osteoporosis Previously Treated With Oral Bisphosphonates

    PubMed Central

    Pannacciulli, N.; Brown, J. P.; Czerwinski, E.; Nedergaard, B. S.; Bolognese, M. A.; Malouf, J.; Bone, H. G.; Reginster, J.-Y.; Singer, A.; Wang, C.; Wagman, R. B.; Cummings, S. R.

    2016-01-01

    Context: Denosumab and zoledronic acid (ZOL) are parenteral treatments for patients with osteoporosis. Objective: The objective of the study was to compare the effect of transitioning from oral bisphosphonates to denosumab or ZOL on bone mineral density (BMD) and bone turnover. Design and Setting: This was an international, multicenter, randomized, double-blind trial. Participants: A total of 643 postmenopausal women with osteoporosis previously treated with oral bisphosphonates participated in the study. Interventions: Subjects were randomized 1:1 to sc denosumab 60 mg every 6 months plus iv placebo once or ZOL 5 mg iv once plus sc placebo every 6 months for 12 months. Main Outcome Measures: Changes in BMD and bone turnover markers were measured. Results: BMD change from baseline at month 12 was significantly greater with denosumab compared with ZOL at the lumbar spine (primary end point; 3.2% vs 1.1%; P < .0001), total hip (1.9% vs 0.6%; P < .0001), femoral neck (1.2% vs −0.1%; P < .0001), and one-third radius (0.6% vs 0.0%; P < .05). The median decrease from baseline was greater with denosumab than ZOL for serum C-telopeptide of type 1 collagen at all time points after day 10 and for serum procollagen type 1 N-terminal propeptide at month 1 and at all time points after month 3 (all P < .05). Median percentage changes from baseline in serum intact PTH were significantly greater at months 3 and 9 with denosumab compared with ZOL (all P < .05). Adverse events were similar between groups. Three events consistent with the definition of atypical femoral fracture were observed (two denosumab and one ZOL). Conclusions: In postmenopausal women with osteoporosis previously treated with oral bisphosphonates, denosumab was associated with greater BMD increases at all measured skeletal sites and greater inhibition of bone remodeling compared with ZOL. PMID:27270237

  8. Toxicity and metal speciation in acid mine drainage treated by passive bioreactors

    SciTech Connect

    Neculita, C.M.; Vigneaul, B.; Zagury, G.J.

    2008-08-15

    Sulfate-reducing passive bioreactors treat acid mine drainage (AMD) by increasing its pH and alkalinity and by removing metals as metal sulfide precipitates. In addition to discharge limits based on physicochemical parameters, however, treated effluent is required to be nontoxic. Acute and sublethal toxicity was assessed for effluent from 3.5-L column bioreactors filled with mixtures of natural organic carbon sources and operated at different hydraulic retention times (HRTs) for the treatment of a highly contaminated AMD. Effluent was first tested for acute (Daphnia magna and Oncorhynchus mykiss) and sublethal (Pseudokirchneriella subcapitata, Ceriodaphnia dabia, and Lemna minor) toxicity. Acute toxicity was observed for D. magna, and a toxicity identification evaluation (TIE) procedure was then performed to identify potential toxicants. Finally, metal speciation in the effluent was determined using ultrafiltration and geochemical modeling for the interpretation of the toxicity results. The 10-d HRT effluent was nonacutely lethal for 0. mykiss but acutely lethal for D. magna. The toxicity to D. magna, however, was removed by 2 h of aeration, and the TIE procedure suggested iron as a cause of toxicity. Sublethal toxicity of the 10-d HRT effluent was observed for all test species, but it was reduced compared to the raw AMD and to a 7.3-d HRT effluent. Data regarding metal speciation indicated instability of both effluents during aeration and were consistent with the toxicity being caused by iron. Column bioreactors in operation for more than nine months efficiently improved the physicochemical quality of highly contaminated AMD at different HRTs.

  9. Colorimetric determination of phosphoric acid leakage for phosphoric acid-doped polybenzimidazole membrane fuel cell applications

    NASA Astrophysics Data System (ADS)

    Jeong, Yeon Hun; Jung, Ju Hae; Choi, Euiji; Han, Seungyoon; Begley, Alina Irene; Yoo, Sung Jong; Jang, Jong Hyun; Kim, Hyoung-Juhn; Nam, Suk Woo; Lee, Kwan-Young; Kim, Jin Young

    2015-12-01

    A simple and precise colorimetric method for analyzing phosphoric acid leakage in phosphoric acid-doped polybenzimidazole membrane fuel cells is described. The developed method is based on the colorimetric determination from a rapid formation of molybdenum blue color by the reduction reaction of molybdate ions in the presence of phosphoric acid in the acidic medium. The color is stable up to a few months and can be used for the sensitive and accurate detection of phosphoric acid electrolyte which is discharged from the fuel cell during operation. Tests with a wide concentration range of phosphate compounds showed that it permits determination of phosphoric acid up to nanogram quantities. The developed detection method assists monitoring the phosphoric acid contents and developing stable operation strategies of fuel cells.

  10. Enhanced Fischer-Tropsch synthesis performance of iron-based catalysts supported on nitric acid treated N-doped CNTs

    NASA Astrophysics Data System (ADS)

    Li, Zhenhua; Liu, Renjie; Xu, Yan; Ma, Xinbin

    2015-08-01

    Iron-based catalysts supported on N-doped CNTs (NCNTs) treated by various concentrations of nitric acid for Fischer-Tropsch synthesis (FTS) were investigated. An improved catalytic performance for the iron catalyst supported on acid treated NCNTs was obtained and the suitable nitric acid concentration was 10 M. The physiochemical properties of the NCNTs and the corresponding catalysts were characterized by BET, TEM, XRD, XPS, TGA and H2-TPR. The acid treatment removed the impurity and amorphous carbon, damaged the bamboo-like structure and increased the number of oxygen-containing functional groups and graphitization degree on the NCNTs. The more iron particles located inside the channels of NCNTs, the better catalytic FTS performance due to high dispersion and reducibility.

  11. Proteomic investigation into betulinic acid-induced apoptosis of human cervical cancer HeLa cells.

    PubMed

    Xu, Tao; Pang, Qiuying; Zhou, Dong; Zhang, Aiqin; Luo, Shaman; Wang, Yang; Yan, Xiufeng

    2014-01-01

    Betulinic acid is a pentacyclic triterpenoid that exhibits anticancer functions in human cancer cells. This study provides evidence that betulinic acid is highly effective against the human cervical cancer cell line HeLa by inducing dose- and time-dependent apoptosis. The apoptotic process was further investigated using a proteomics approach to reveal protein expression changes in HeLa cells following betulinic acid treatment. Proteomic analysis revealed that there were six up- and thirty down-regulated proteins in betulinic acid-induced HeLa cells, and these proteins were then subjected to functional pathway analysis using multiple analysis software. UDP-glucose 6-dehydrogenase, 6-phosphogluconate dehydrogenase decarboxylating, chain A Horf6-a novel human peroxidase enzyme that involved in redox process, was found to be down-regulated during the apoptosis process of the oxidative stress response pathway. Consistent with our results at the protein level, an increase in intracellular reactive oxygen species was observed in betulinic acid-treated cells. The proteins glucose-regulated protein and cargo-selection protein TIP47, which are involved in the endoplasmic reticulum pathway, were up-regulated by betulinic acid treatment. Meanwhile, 14-3-3 family proteins, including 14-3-3β and 14-3-3ε, were down-regulated in response to betulinic acid treatment, which is consistent with the decrease in expression of the target genes 14-3-3β and 14-3-3ε. Furthermore, it was found that the antiapoptotic bcl-2 gene was down-regulated while the proapoptotic bax gene was up-regulated after betulinic acid treatment in HeLa cells. These results suggest that betulinic acid induces apoptosis of HeLa cells by triggering both the endoplasmic reticulum pathway and the ROS-mediated mitochondrial pathway.

  12. Autophagy Regulates Formation of Primary Cilia in Mefloquine-Treated Cells

    PubMed Central

    Shin, Ji Hyun; Bae, Dong-Jun; Kim, Eun Sung; Kim, Han Byeol; Park, So Jung; Jo, Yoon Kyung; Jo, Doo Sin; Jo, Dong-Gyu; Kim, Sang-Yeob; Cho, Dong-Hyung

    2015-01-01

    Primary cilia have critical roles in coordinating multiple cellular signaling pathways. Dysregulation of primary cilia is implicated in various ciliopathies. To identify specific regulators of autophagy, we screened chemical libraries and identified mefloquine, an anti-malaria medicine, as a potent regulator of primary cilia in human retinal pigmented epithelial (RPE) cells. Not only ciliated cells but also primary cilium length was increased in mefloquine-treated RPE cells. Treatment with mefloquine strongly induced the elongation of primary cilia by blocking disassembly of primary cilium. In addition, we found that autophagy was increased in mefloquine-treated cells by enhancing autophagic flux. Both chemical and genetic inhibition of autophagy suppressed ciliogenesis in mefloquine-treated RPE cells. Taken together, these results suggest that autophagy induced by mefloquine positively regulates the elongation of primary cilia in RPE cells. PMID:26157548

  13. Modulation of drug release rate of diltiazem-HCl from hydrogel matrices of succinic acid-treated ispaghula husk.

    PubMed

    Gohel, M C; Amin, A F; Chhabaria, M T; Panchal, M K; Lalwani, A N

    2000-01-01

    The feasibility of using succinic acid-treated ispaghula husk in matrix-based tablets of diltiazem-HCl was investigated. The sample prepared using 4:1 weight ratio of ispaghula husk to succinic acid showed improved swelling and gelling. A 3(2) factorial design was employed to investigate the effect of amount of succinic acid-treated ispaghula husk and dicalcium phosphate (DCP) on the percentage of the drug dissolved in 60, 300, and 480 min from the compressed tablets. The results of multiple linear regression analysis revealed that the significance of the amount of succinic acid-treated ispaghula husk was greater in magnitude than that of the amount of DCP in controlling the drug release. Acceptable batches were identified from a contour plot with constraints on the percentage drug released at the three sampling times. A mathematical model was also evolved to describe the entire dissolution profile. The results of F-test revealed that the Higuchi model fits well to the in vitro dissolution data. The tablets showed considerable radial and axial swelling in distilled water. Succinic acid-treated ispaghula husk can be used as an economical hydrophilic matrixing agent.

  14. Phosphoric acid fuel cell platinum use study

    NASA Technical Reports Server (NTRS)

    Lundblad, H. L.

    1983-01-01

    The U.S. Department of Energy is promoting the private development of phosphoric acid fuel cell (PAFC) power plants for terrestrial applications. Current PAFC technology utilizes platinum as catalysts in the power electrodes. The possible repercussions that the platinum demand of PAFC power plant commercialization will have on the worldwide supply and price of platinum from the outset of commercialization to the year 2000 are investigated. The platinum demand of PAFC commercialization is estimated by developing forecasts of platinum use per unit of generating capacity and penetration of PAFC power plants into the electric generation market. The ability of the platinum supply market to meet future demands is gauged by assessing the size of platinum reserves and the capability of platinum producers to extract, refine and market sufficient quantities of these reserves. The size and timing of platinum price shifts induced by the added demand of PAFC commercialization are investigated by several analytical methods. Estimates of these price shifts are then used to calculate the subsequent effects on PAFC power plant capital costs.

  15. Phosphoric acid fuel cell platinum use study

    NASA Astrophysics Data System (ADS)

    Lundblad, H. L.

    1983-05-01

    The U.S. Department of Energy is promoting the private development of phosphoric acid fuel cell (PAFC) power plants for terrestrial applications. Current PAFC technology utilizes platinum as catalysts in the power electrodes. The possible repercussions that the platinum demand of PAFC power plant commercialization will have on the worldwide supply and price of platinum from the outset of commercialization to the year 2000 are investigated. The platinum demand of PAFC commercialization is estimated by developing forecasts of platinum use per unit of generating capacity and penetration of PAFC power plants into the electric generation market. The ability of the platinum supply market to meet future demands is gauged by assessing the size of platinum reserves and the capability of platinum producers to extract, refine and market sufficient quantities of these reserves. The size and timing of platinum price shifts induced by the added demand of PAFC commercialization are investigated by several analytical methods. Estimates of these price shifts are then used to calculate the subsequent effects on PAFC power plant capital costs.

  16. Strategies for Treating Cutaneous T-Cell Lymphoma

    PubMed Central

    Heald, Peter

    2009-01-01

    In this article, the management of cutaneous T-cell lymphoma will be presented in terms of the strategies that guide treatment. With the strategies and goals in mind, treatment options to achieve a measurable goal will be presented. The treatments presented in this article are those utilized to reliably achieve a remission. If remission is not achieved, a patient’s management plan must be changed. The landmarks that help guide the therapy plan will be discussed. PMID:20729945

  17. Acetylsalicylic Acid Compared to Placebo in Treating High-Risk Patients With Subsolid Lung Nodules | Division of Cancer Prevention

    Cancer.gov

    This randomized phase II trial studies acetylsalicylic acid compared to placebo in treating high-risk patients with subsolid lung nodules. A nodule is a growth or lump that may be malignant (cancer) or benign (not cancer). Chemoprevention is the use of drugs to keep cancer from forming or coming back. The use of acetylsalicylic acid may keep cancer from forming in patients with subsolid lung nodules. |

  18. How I treat and manage strokes in sickle cell disease

    PubMed Central

    Kassim, Adetola A.; Galadanci, Najibah A.; Pruthi, Sumit

    2015-01-01

    Neurologic complications are a major cause of morbidity and mortality in sickle cell disease (SCD). In children with sickle cell anemia, routine use of transcranial Doppler screening, coupled with regular blood transfusion therapy, has decreased the prevalence of overt stroke from ∼11% to 1%. Limited evidence is available to guide acute and chronic management of individuals with SCD and strokes. Current management strategies are based primarily on single arm clinical trials and observational studies, coupled with principles of neurology and hematology. Initial management of a focal neurologic deficit includes evaluation by a multidisciplinary team (a hematologist, neurologist, neuroradiologist, and transfusion medicine specialist); prompt neuro-imaging and an initial blood transfusion (simple followed immediately by an exchange transfusion or only exchange transfusion) is recommended if the hemoglobin is >4 gm/dL and <10 gm/dL. Standard therapy for secondary prevention of strokes and silent cerebral infarcts includes regular blood transfusion therapy and in selected cases, hematopoietic stem cell transplantation. A critical component of the medical care following an infarct is cognitive and physical rehabilitation. We will discuss our strategy of acute and long-term management of strokes in SCD. PMID:25824688

  19. Murine cytomegalovirus stimulates natural killer cell function but kills genetically resistant mice treated with radioactive strontium

    SciTech Connect

    Masuda, A.; Bennett, M.

    1981-12-01

    Treatment of C3H/St mice with 100 microCi of 89Sr weakened their genetic resistance to murine cytomegalovirus (MCMV) infection. The criteria utilized to detect increased susceptibility were: (i) survival of mice; (ii) numbers of MCMV-infected cells in the spleens and liver; and (iii) serum glutamic pyruvic transaminase levels. The natural killer (NK) cell activity of spleen cells from mice treated with 89Sr is very low. However, the NK activities of spleen cells of both normal and 89Sr-treated mice were greatly augmented 3 days after infection with MCMV. These NK cells lysed a variety of tumor cells and shared several features with conventional NK cells, but were not lysed by anti-Nk-1.2 serum (specific for NK cells) plus complement. Splenic adherent cells did not lyse tumor cells themselves but were necessary for the stimulation of NK cells by MCMV. The paradox of high NK cell function and poor survival in 89Sr-treated mice infected with MCMV was a surprise. We conclude that these augmented NK cells, of themselves, cannot account for the genetic resistance of C3H/St mice to infection with MCMV.

  20. Clavulanic acid increases dopamine release in neuronal cells through a mechanism involving enhanced vesicle trafficking.

    PubMed

    Kost, Gina Chun; Selvaraj, Senthil; Lee, Young Bok; Kim, Deog Joong; Ahn, Chang-Ho; Singh, Brij B

    2011-10-24

    Clavulanic acid is a CNS-modulating compound with exceptional blood-brain barrier permeability and safety profile. Clavulanic acid has been proposed to have anti-depressant activity and is currently entering Phase IIb clinical trials for the treatment of Major Depressive Disorder (MDD). Studies have also shown that clavulanic acid suppresses anxiety and enhances sexual functions in rodent and primate models by a mechanism involving central nervous system (CNS) modulation, although its detailed mechanism of action has yet to be elucidated. To further examine its potential as a CNS modulating agent as well as its mechanism of action, we investigated the effects of clavulanic acid in neuronal cells. Our results indicate that clavulanic acid enhances dopamine release in PC12 and SH-SY5Y cells without affecting dopamine synthesis. Furthermore, using affinity chromatography we were able to identify two proteins, Munc18-1 and Rab4 that potentially bind to clavulanic acid and play a critical role in neurosecretion and the vesicle trafficking process. Consistent with this result, an increase in the translocation of Munc18-1 and Rab4 from the cytoplasm to the plasma membrane was observed in clavulanic acid treated cells. Overall, these data suggest that clavulanic acid enhances dopamine release in a mechanism involving Munc18-1 and Rab4 modulation and warrants further investigation of its therapeutic use in CNS disorders, such as depression.

  1. Clavulanic acid increases dopamine release in neuronal cells through a mechanism involving enhanced vesicle trafficking

    PubMed Central

    Kost, Gina Chun; Selvaraj, Senthil; Lee, Young Bok; Kim, Deog Joong; Ahn, Chang-Ho; Singh, Brij B

    2011-01-01

    Clavulanic acid is a CNS-modulating compound with exceptional blood-brain barrier permeability and safety profile. Clavulanic acid has been proposed to have anti-depressant activity and is currently entering Phase IIb clinical trials for the treatment of Major Depressive Disorder (MDD). Studies have also shown that clavulanic acid suppresses anxiety and enhances sexual functions in rodent and primate models by a mechanism involving central nervous system (CNS) modulation, although its detailed mechanism of action has yet to be elucidated. To further examine its potential as a CNS modulating agent as well as its mechanism of action, we investigated the effects of clavulanic acid in neuronal cells. Our results indicate that clavulanic acid enhances dopamine release in PC12 and SH-SY5Y cells without affecting dopamine synthesis. Furthermore, using affinity chromatography we were able to identify two proteins, Munc18-1 and Rab4 that potentially bind to clavulanic acid and play a critical role in neurosecretion and the vesicle trafficking process. Consistent with this result, an increase in the translocation of Munc18-1 and Rab4 from the cytoplasm to the plasma membrane was observed in clavulanic acid treated cells. Overall, these data suggest that clavulanic acid enhances dopamine release in a mechanism involving Munc18-1 and Rab4 modulation and warrants further investigation of its therapeutic use in CNS disorders, such as depression. PMID:21964384

  2. Fusaric acid induction of programmed cell death modulated through nitric oxide signalling in tobacco suspension cells.

    PubMed

    Jiao, Jiao; Zhou, Benguo; Zhu, Xiaoping; Gao, Zhengliang; Liang, Yuancun

    2013-10-01

    Fusaric acid (FA) is a nonhost-selective toxin mainly produced by Fusarium oxysporum, the causal agent of plant wilt diseases. We demonstrate that FA can induce programmed cell death (PCD) in tobacco suspension cells and the FA-induced PCD is modulated by nitric oxide (NO) signalling. Cells undergoing cell death induced by FA treatment exhibited typical characteristics of PCD including cytoplasmic shrinkage, chromatin condensation, DNA fragmentation, membrane plasmolysis, and formation of small cytoplasmic vacuoles. In addition, caspase-3-like activity was activated upon the FA treatment. The process of FA-induced PCD was accompanied by a rapid accumulation of NO in a FA dose-dependent manner. Pre-treatment of cells with NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) or NO synthase inhibitor N(G)-monomethyl-arginine monoacetate (L-NMMA) significantly reduced the rate of FA-induced cell death. Furthermore, the caspase-3-like activity and the expression of PAL and Hsr203J genes were alleviated by application of cPTIO or L-NMMA to FA-treated tobacco cells. This indicates that NO is an important factor involved in the FA-induced PCD. Our results also show that pre-treatment of tobacco cells with a caspase-3-specific inhibitor, Ac-DEVD-CHO, can reduce the rate of FA-induced cell death. These results demonstrate that the FA-induced cell death is a PCD and is modulated by NO signalling through caspase-3-like activation. PMID:23838885

  3. Removal of chromium(VI) from wastewater using phosphoric acid treated activated carbon

    NASA Astrophysics Data System (ADS)

    Suganthi, N.

    2013-06-01

    Activated carbon prepared by phosphoric acid treatment of tamarind nuts (seeds) was investigated for the removal of Cr(VI) from aqueous solutions. The characteristics of phosphorylated tamarind nut carbon (PTNC) were evaluated for porosity and surface area. The effect of contact time, pH, adsorbent dose and particle size variation were studied to evaluate the potential applicability of carbon for treating Cr(VI) containing wastewater. The adsorbent data were modeled by Langmiur and Freundlich classical adsorption isotherms. The kinetic studies showed that Cr(VI) adsorption on PTNC was in compliance with the pseudo-second-order kinetic model. Desorption studies indicated that ion-exchange mechanism was operating. The continuous adsorption was studied in glass columns of 2.5 cm diameter using electroplating wastewater to ascertain the practical applicability of PTNC in large scale. The mechanism of adsorption was found to be ion-exchange process and was supported by FTIR spectroscopy. The surface modification after adsorption was confirmed by SEM studies.

  4. Kinetics of phenolic and phthalic acid esters biodegradation in membrane bioreactor (MBR) treating municipal landfill leachate.

    PubMed

    Boonnorat, Jarungwit; Chiemchaisri, Chart; Chiemchaisri, Wilai; Yamamoto, Kazuo

    2016-05-01

    The kinetic of phenolic and phthalic acid esters (PAEs) biodegradation in membrane bioreactor (MBR) treating municipal landfill leachate was investigated. Laboratory-scale MBR was fed with mixture of fresh and stabilized landfill leachate containing carbon to nitrogen (C/N) ratio of 10, 6, 3 and operated under different solid retention time (SRT) of 90, 15 and 5 d. Batch experiments using MBR sludge obtained from each steady-state operating condition revealed highest biodegradation rate constant (k) of 0.059-0.092 h(-1) of the phenolic and PAEs compounds at C/N of 6. Heterotrophic bacteria were the major group responsible for biodegradation of compounds whereas the presence of ammonia-oxidizing bacteria (AOB) helped accelerating their removals. Heterotrophic nitrifying bacteria found under high ammonia condition had an important role in enhancing the biodegradation of phenols and PAEs by releasing phenol hydroxylase (PH), esterase (EST) and phthalate dioxygenase (PDO) enzymes and the presence of AOB helped improving biodegradation of phenolic and PAEs compounds through their co-metabolism. PMID:26908045

  5. Designing Novel Nanoformulations Targeting Glutamate Transporter Excitatory Amino Acid Transporter 2: Implications in Treating Drug Addiction

    PubMed Central

    Rao, PSS; Yallapu, Murali M.; Sari, Youssef; Fisher, Paul B.; Kumar, Santosh

    2015-01-01

    Chronic drug abuse is associated with elevated extracellular glutamate concentration in the brain reward regions. Deficit of glutamate clearance has been identified as a contributing factor that leads to enhanced glutamate concentration following extended drug abuse. Importantly, normalization of glutamate level through induction of glutamate transporter 1 (GLT1)/ excitatory amino acid transporter 2 (EAAT2) expression has been described in several in vivo studies. GLT1 upregulators including ceftriaxone, a beta-lactam antibiotic, have been effective in attenuating drug-seeking and drug-consumption behavior in rodent models. However, potential obstacles toward clinical translation of GLT1 (EAAT2) upregulators as treatment for drug addiction might include poor gastrointestinal absorption, serious peripheral adverse effects, and/or suboptimal CNS concentrations. Given the growing success of nanotechnology in targeting CNS ailments, nanoformulating known GLT1 (EAAT2) upregulators for selective uptake across the blood brain barrier presents an ideal therapeutic approach for treating drug addiction. In this review, we summarize the results obtained with promising GLT1 (EAAT2) inducing compounds in animal models recapitulating drug addiction. Additionally, the various nanoformulations that can be employed for selectively increasing the CNS bioavailability of GLT1 (EAAT2) upregulators are discussed. Finally, the applicability of GLT1 (EAAT2) induction via central delivery of drug-loaded nanoformulations is described. PMID:26635971

  6. Methane Production from Rice Straw Hydrolysate Treated with Dilute Acid by Anaerobic Granular Sludge.

    PubMed

    Cheng, Jing-Rong; Liu, Xue-Ming; Chen, Zhi-Yi

    2016-01-01

    The traditional anaerobic digestion process of straw to biogas faces bottlenecks of long anaerobic digestion time, low digestion rate, less gas production, etc., while straw hydrolysate has the potential to overcome these drawbacks. In this study, the dilute sulphuric acid-treated hydrolysate of rice straw (DSARSH) containing high sulfate was firstly proved to be a feasible substrate for methane production under mesophilic digestion by granular sludge within a short digestion time. Batch anaerobic digestion process was operated under different initial chemical oxygen demand (COD) values at temperature of 37 °C with the pH of 8.5. Among the initial COD values ranging from 3000 to 11,000 mg/L, 5000 mg/L was proved to be the most appropriate considering high COD removal efficiency (94.17 ± 1.67 %), CH4 content (65.52 ± 3.12 %), and CH4 yield (0.346 ± 0.008 LCH4/g COD removed) within 120 h. Furthermore, when the studied system operated at the initial COD of 5000 mg/L, the sulfate removal ratio could reach 56.28 %.

  7. Ascorbic acid protects against cadmium-induced endoplasmic reticulum stress and germ cell apoptosis in testes.

    PubMed

    Ji, Yan-Li; Wang, Zhen; Wang, Hua; Zhang, Cheng; Zhang, Ying; Zhao, Mei; Chen, Yuan-Hua; Meng, Xiu-Hong; Xu, De-Xiang

    2012-11-01

    Cadmium (Cd) is a testicular toxicant which induces endoplasmic reticulum (ER) stress and germ cell apoptosis in testes. This study investigated the effects of ascorbic acid on Cd-evoked ER stress and germ cell apoptosis in testes. Male mice were intraperitoneally injected with CdCl(2) (2.0 mg/kg). As expected, a single dose of Cd induced testicular germ cell apoptosis. Interestingly, Cd-triggered testicular germ cell apoptosis was almost completely inhibited in mice treated with ascorbic acid. Interestingly, ascorbic acid significantly attenuated Cd-induced upregulation of GRP78 in testes. In addition, ascorbic acid significantly attenuated Cd-triggered testicular IRE1α and eIF2α phosphorylation and XBP-1 activation, indicating that this antioxidant counteracts Cd-induced unfolded protein response (UPR) in testes. Finally, ascorbic acid significantly attenuated Cd-evoked upregulation of CHOP and JNK phosphorylation, two components in ER stress-mediated apoptotic pathway. In conclusion, ascorbic acid protects mice from Cd-triggered germ cell apoptosis via inhibiting ER stress and UPR in testes. PMID:22569276

  8. Inhibitory effect of ursolic acid and oleanolic acid from Eriobotrya fragrans on A549 cell viability in vivo.

    PubMed

    Gao, Y S; Yuan, Y; Song, G; Lin, S Q

    2016-01-01

    Loquat [Eriobotrya japonica (Lindl.)] is a traditional Chinese medicine, which has been used as an anti-inflammatory and for curing chronic bronchitis among other potential applications. Extracted ursolic acid (UA) and oleanolic acid (OA) from wild loquat were previously found capable of suppressing the proliferation of A549 cells in vitro. In the current study, nude mice were used to determine the inhibitory effect of UA and OA on tumor formation in vivo. The results demonstrate that UA and OA reduced the proliferation of A549 cells in nude mice, and increased the expression of Bid while decreasing the protein levels of MMP-2, Ki-67, and CD34. In this study, we identified potential antitumor activity in a wild loquat extract containing UA and OA, which demonstrates that traditional Chinese medicine may have a role in treating certain types of cancer. PMID:27323036

  9. Inhibitory effect of ursolic acid and oleanolic acid from Eriobotrya fragrans on A549 cell viability in vivo.

    PubMed

    Gao, Y S; Yuan, Y; Song, G; Lin, S Q

    2016-05-13

    Loquat [Eriobotrya japonica (Lindl.)] is a traditional Chinese medicine, which has been used as an anti-inflammatory and for curing chronic bronchitis among other potential applications. Extracted ursolic acid (UA) and oleanolic acid (OA) from wild loquat were previously found capable of suppressing the proliferation of A549 cells in vitro. In the current study, nude mice were used to determine the inhibitory effect of UA and OA on tumor formation in vivo. The results demonstrate that UA and OA reduced the proliferation of A549 cells in nude mice, and increased the expression of Bid while decreasing the protein levels of MMP-2, Ki-67, and CD34. In this study, we identified potential antitumor activity in a wild loquat extract containing UA and OA, which demonstrates that traditional Chinese medicine may have a role in treating certain types of cancer.

  10. Resin–dentin bonds to EDTA-treated vs. acid-etched dentin using ethanol wet-bonding

    PubMed Central

    Sauro, Salvatore; Toledano, Manuel; Aguilera, Fatima Sánchez; Mannocci, Francesco; Pashley, David H.; Tay, Franklin R.; Watson, Timothy F.; Osorio, Raquel

    2013-01-01

    Objective To compare resin–dentin bond strengths and the micropermeability of hydrophobic vs. hydrophilic resins bonded to acid-etched or EDTA-treated dentin, using the ethanol wet-bonding technique. Methods Flat dentin surfaces from extracted human third molars were conditioned before bonding with: 37% H3PO4 (15 s) or 0.1 M EDTA (60 s). Five experimental resin blends of different hydrophilicities and one commercial adhesive (SBMP: Scotchbond Multi-Purpose) were applied to ethanol wet-dentin (1 min) and light-cured (20 s). The solvated resins were used as primers (50% ethanol/50% comonomers) and their respective neat resins were used as the adhesive. The resin-bonded teeth were stored in distilled water (24 h) and sectioned in beams for microtensile bond strength testing. Modes of failure were examined by stereoscopic light microscopy and SEM. Confocal tandem scanning microscopy (TSM) interfacial characterization and micropermeability were also performed after filling the pulp chamber with 1 wt% aqueous rhodamine-B. Results The most hydrophobic resin 1 gave the lowest bond strength values to acid-etched dentin and all beams failed prematurely when the resin was applied to EDTA-treated dentin. Resins 2 and 3 gave intermediate bond strengths to both conditioned substrates. Resin 4, an acidic hydrophilic resin, gave the highest bond strengths to both EDTA-treated and acid-etched dentin. Resin 5 was the only hydrophilic resin showing poor resin infiltration when applied on acid-etched dentin. Significance The ethanol wet-bonding technique may improve the infiltration of most of the adhesives used in this study into dentin, especially when applied to EDTA-treated dentin. The chemical composition of the resin blends was a determining factor influencing the ability of adhesives to bond to EDTA-treated or 37% H3PO4 acid-etched dentin, when using the ethanol wet-bonding technique in a clinically relevant time period. PMID:20074787

  11. Lauric Acid Stimulates Ketone Body Production in the KT-5 Astrocyte Cell Line.

    PubMed

    Nonaka, Yudai; Takagi, Tetsuo; Inai, Makoto; Nishimura, Shuhei; Urashima, Shogo; Honda, Kazumitsu; Aoyama, Toshiaki; Terada, Shin

    2016-08-01

    Coconut oil has recently attracted considerable attention as a potential Alzheimer's disease therapy because it contains large amounts of medium-chain fatty acids (MCFAs) and its consumption is thought to stimulate hepatic ketogenesis, supplying an alternative energy source for brains with impaired glucose metabolism. In this study, we first reevaluated the responses of plasma ketone bodies to oral administration of coconut oil to rats. We found that the coconut oil-induced increase in plasma ketone body concentration was negligible and did not significantly differ from that observed after high-oleic sunflower oil administration. In contrast, the administration of coconut oil substantially increased the plasma free fatty acid concentration and lauric acid content, which is the major MCFA in coconut oil. Next, to elucidate whether lauric acid can activate ketogenesis in astrocytes with the capacity to generate ketone bodies from fatty acids, we treated the KT-5 astrocyte cell line with 50 and 100 μM lauric acid for 4 h. The lauric acid treatments increased the total ketone body concentration in the cell culture supernatant to a greater extent than oleic acid, suggesting that lauric acid can directly and potently activate ketogenesis in KT-5 astrocytes. These results suggest that coconut oil intake may improve brain health by directly activating ketogenesis in astrocytes and thereby by providing fuel to neighboring neurons.

  12. Lauric Acid Stimulates Ketone Body Production in the KT-5 Astrocyte Cell Line.

    PubMed

    Nonaka, Yudai; Takagi, Tetsuo; Inai, Makoto; Nishimura, Shuhei; Urashima, Shogo; Honda, Kazumitsu; Aoyama, Toshiaki; Terada, Shin

    2016-08-01

    Coconut oil has recently attracted considerable attention as a potential Alzheimer's disease therapy because it contains large amounts of medium-chain fatty acids (MCFAs) and its consumption is thought to stimulate hepatic ketogenesis, supplying an alternative energy source for brains with impaired glucose metabolism. In this study, we first reevaluated the responses of plasma ketone bodies to oral administration of coconut oil to rats. We found that the coconut oil-induced increase in plasma ketone body concentration was negligible and did not significantly differ from that observed after high-oleic sunflower oil administration. In contrast, the administration of coconut oil substantially increased the plasma free fatty acid concentration and lauric acid content, which is the major MCFA in coconut oil. Next, to elucidate whether lauric acid can activate ketogenesis in astrocytes with the capacity to generate ketone bodies from fatty acids, we treated the KT-5 astrocyte cell line with 50 and 100 μM lauric acid for 4 h. The lauric acid treatments increased the total ketone body concentration in the cell culture supernatant to a greater extent than oleic acid, suggesting that lauric acid can directly and potently activate ketogenesis in KT-5 astrocytes. These results suggest that coconut oil intake may improve brain health by directly activating ketogenesis in astrocytes and thereby by providing fuel to neighboring neurons. PMID:27430387

  13. Designer nucleic acids to probe and program the cell.

    PubMed

    Krishnan, Yamuna; Bathe, Mark

    2012-12-01

    Recent advances in nucleic acid sequencing, structural, and computational technologies have resulted in dramatic progress in our understanding of nucleic acid structure and function in the cell. This knowledge, together with the predictable base-pairing of nucleic acids and powerful synthesis and expression capabilities now offers the unique ability to program nucleic acids to form precise 3D architectures with diverse applications in synthetic and cell biology. The unique modularity of structural motifs that include aptamers, DNAzymes, and ribozymes, together with their well-defined construction rules, enables the synthesis of functional higher-order nucleic acid complexes from these subcomponents. As we illustrate here, these highly programmable, smart complexes are increasingly enabling researchers to probe and program the cell in a sophisticated manner that moves well beyond the use of nucleic acids for conventional genetic manipulation alone.

  14. Effects of ozone, ultraviolet and peracetic acid disinfection of a primary-treated municipal effluent on the immune system of rainbow trout (Oncorhynchus mykiss).

    PubMed

    Hébert, N; Gagné, F; Cejka, P; Bouchard, B; Hausler, R; Cyr, D G; Blaise, C; Fournier, M

    2008-08-01

    Municipal sewage effluents are complex mixtures that are known to compromise the health condition of aquatic organisms. The aim of this study was to evaluate the impacts of various wastewater disinfection processes on the immune system of juvenile rainbow trout (Oncorhynchus mykiss). The trout were exposed to a primary-treated effluent for 28 days before and after one of each of the following treatments: ultraviolet (UV) radiation, ozonation and peracetic acid. Immune function was characterized in leucocytes from the anterior head kidney by the following three parameters: phagocytosis activity, natural cytotoxic cells (NCC) function and lymphocyte (B and T) proliferation assays. The results show that the fish mass to length ratio was significantly decreased for the primary-treated and all three disinfection processes. Exposure to the primary-treated effluent led to a significant increase in macrophage-related phagocytosis; the addition of a disinfection step was effective in removing this effect. Both unstimulated and mitogen-stimulated T lymphocyte proliferation in fish decreased dramatically in fish exposed to the ozonated effluent compared to fish exposed to either the primary-treated effluent or to aquarium water. Stimulation of T lymphocytes proliferation was observed with the peracetic acid treatment group. In conclusion, the disinfection strategy used can modify the immune system in fish at the level of T lymphocyte proliferation but was effective to remove the effects on phagocytosis activity.

  15. Study of urinary 2-{[2-(acetylamino-2-carboxyethyl]sulfanyl}butanedioic acid, a mercapturic acid of rats treated with maleic acid.

    PubMed

    Luo, Yu-Syuan; Tsai, Hsin-Yun; Chen, Hsin-Chang; Wu, Charlene; Shen, Li-Ching; Chung, Wen-Sheng; Chiang, Su-Yin; Wu, Kuen-Yuh

    2015-08-01

    Maleic anhydride was reported illegally adulterated into starch to prepare traditional foods for decades in Taiwan. Maleic acid (MA), hydrolyzed from maleic anhydride, could cause kidney damages to animals. The potential health effects due to long-term MA exposures through food consumption have been of great concerns. Assessment of the dietary MA exposures could be very difficult and complicated. One of the alternatives is to analyze an MA-specific biomarker to assess the daily total MA intake. Therefore, this paper aimed to study the mercapturic acid of MA, 2-{[2-(acetylamino)-2-carboxyethyl]sulfanyl}butanedioic acid (MAMA), with our newly-developed isotope-dilution online solid-phase extraction liquid chromatography tandem mass spectrometry (ID-SPE-LC-MS/MS) method. MAMA was first synthesized, purified, and characterized with NMR to reveal two diastereomers and used for developing the analytical method. The method was validated to reveal excellent sensitivity with a LOD at 16.3ng/mL and a LOQ at 20.6ng/mL and used to analyze MAMA in urine samples collected from Sprague-Dawley rats treated with a single dose of 0mg/kg, 6mg/kg, and 60mg/kg (n=5) of MA through gavage. Our results show dose-dependent increases in urinary MAMA contents, and 70% MAMA was excreted within 12h with no gender differences (p>0.05). A half life of urinary MAMA was estimated at 6.8h for rat. The formation of urinary MAMA validates it as a chemically-specific biomarker for current MA exposure. Future study of MA metabolism in vivo will elucidate mechanisms of MAMA formation, and analysis of this marker in epidemiology studies could help to shed light on the causal effects of MA on human.

  16. Induction of karyopherin α1 expression by indole-3-acetic acid in auxin-treated or overproducing tobacco plants.

    PubMed

    Rand, Karin; Kobrinsky-Aaronowitz, Irina; Levy, Yael; Shaul, Orit; Aloni, Roni; Gafni, Yedidya

    2011-06-01

    Macromolecules may transfer between the cytoplasm and the nucleus only through specific gates - the nuclear pore complexes (NPCs). Translocation of nucleic acids and large proteins requires the presence of a nuclear localization signal (NLS) within the transported molecule. This NLS is recognized by a class of soluble transport receptors termed karyopherins α and beta. We previously characterized the expression pattern of the tomato karyopherin α 1 (LeKAPα1) promoter in transformed tobacco plants. Expression of LeKAPα1 was mainly observed in growing tissues where cell division and extension is rapid. The expression pattern of LeKAPα1 resembled that of auxin-responsive genes. This led us to suggest that auxin participates in the regulation of LeKAPα1 expression. Here we characterized the correlation between auxin level and the activity of the LeKAPα1 promoter. To this end, transgenic tobacco plants carrying the GUS reporter gene under the control of the LeKAPα1 promoter were treated with various levels of exogenous auxin. We also studied transgenic plants in which we increased the endogenous levels of auxin. For this, we expressed in plants both the LeKAPα1 promoter-GUS reporter and the Agrobacterium tumefaciens iaaM gene, which increases the endogenous levels of auxin. The results indicate that the auxin indole-3-acetic acid (IAA) can induce LeKAPα1 expression. We also identified that the sites and levels of LeKAPα1 expression correlated with the endogenous pathways of polar auxin transport.

  17. Gallic acid reduces cell viability, proliferation, invasion and angiogenesis in human cervical cancer cells

    PubMed Central

    ZHAO, BING; HU, MENGCAI

    2013-01-01

    Gallic acid is a trihydroxybenzoic acid, also known as 3,4,5-trihydroxybenzoic acid, which is present in plants worldwide, including Chinese medicinal herbs. Gallic acid has been shown to have cytotoxic effects in certain cancer cells, without damaging normal cells. The objective of the present study was to determine whether gallic acid is able to inhibit human cervical cancer cell viability, proliferation and invasion and suppress cervical cancer cell-mediated angiogenesis. Treatment of HeLa and HTB-35 human cancer cells with gallic acid decreased cell viability in a dose-dependent manner. BrdU proliferation and tube formation assays indicated that gallic acid significantly decreased human cervical cancer cell proliferation and tube formation in human umbilical vein endothelial cells, respectively. Additionally, gallic acid decreased HeLa and HTB-35 cell invasion in vitro. Western blot analysis demonstrated that the expression of ADAM17, EGFR, p-Akt and p-Erk was suppressed by gallic acid in the HeLa and HTB-35 cell lines. These data indicate that the suppression of ADAM17 and the downregulation of the EGFR, Akt/p-Akt and Erk/p-Erk signaling pathways may contribute to the suppression of cancer progression by Gallic acid. Gallic acid may be a valuable candidate for the treatment of cervical cancer. PMID:24843386

  18. Lactic acid fermentation in cell-recycle membrane bioreactor.

    PubMed

    Choudhury, B; Swaminathan, T

    2006-02-01

    Traditional lactic acid fermentation suffers from low productivity and low product purity. Cell-recycle fermentation has become one of the methods to obtain high cell density, which results in higher productivity. Lactic acid fermentation was investigated in a cell-recycle membrane bioreactor at higher substrate concentrations of 100 and 120 g/dm3. A maximum cell density of 145 g/dm3 and a maximum productivity of 34 g/(dm3.h) were achieved in cell-recycle fermentation. In spite of complete consumption of substrate, there was a continuous increase in cell density in cell-recycle fermentation. Control of cell density in cell-recycle fermentation was attempted by cell bleeding and reduction in yeast extract concentration.

  19. Single dose oral amoxycillin 3 g with either 125 mg or 250 mg clavulanic acid to treat uncomplicated anogenital gonorrhoea.

    PubMed Central

    Lawrence, A G; Shanson, D C

    1985-01-01

    A single supervised oral dose of amoxycillin 3 g combined with clavulanic acid 125 mg as a suspension (Augmentin 3.125G) plus probenecid 1 g, cured 97 of 100 assessable patients who had uncomplicated anogenital gonorrhoea. Thirteen of the 100 patients were infected with penicillinase producing strains of Neisseria gonorrhoeae (PPNG) and 11 (85%) of these patients were cured, including one infected with a PPNG strain that was also resistant to spectinomycin. Another group of 93 assessable patients was treated with ampicillin 3 g plus probenecid 1 g, and only 85 (91%) patients were cured. Of the eight treatment failures in this group, five were found to be infected with PPNG strains. In a second study 144 assessable patients were treated with amoxycillin 3 g combined with clavulanic acid 250 mg, (Augmentin 3.250G) plus probenecid 1 g, and a 97% cure rate was again obtained. Five of seven (71%) patients infected with PPNG strains were cured. Although both Augmentin regimens were effective for treating gonorrhoea caused by PPNG and non-PPNG strains, side effects were noted in more patients treated with 250 mg clavulanic acid (24%) than with 125 mg clavulanic acid (5%). In addition, a similar cure rate was obtained in the three primary sites of infection, the urethra, cervix, and rectum. PMID:4007860

  20. Cell wall integrity, genotoxic injury and PCD dynamics in alfalfa saponin-treated white poplar cells highlight a complex link between molecule structure and activity.

    PubMed

    Paparella, Stefania; Tava, Aldo; Avato, Pinarosa; Biazzi, Elisa; Macovei, Anca; Biggiogera, Marco; Carbonera, Daniela; Balestrazzi, Alma

    2015-03-01

    In the present work, eleven saponins and three sapogenins purified from Medicago sativa were tested for their cytotoxicity against highly proliferating white poplar (Populus alba L.) cell suspension cultures. After preliminary screening, four saponins with different structural features in terms of aglycone moieties and sugar chains (saponin 3, a bidesmoside of hederagenin; saponins 4 and 5, monodesmoside and bidesmoside of medicagenic acid respectively, and saponin 10, a bidesmoside of zanhic acid) and different cytotoxicity were selected and used for further investigation on their structure-activity relationship. Transmission Electron Microscopy (TEM) analyses provided for the first time evidence of the effects exerted by saponins on plant cell wall integrity. Exposure to saponin 3 and saponin 10 resulted into disorganization of the outer wall layer and the effect was even more pronounced in white poplar cells treated with the two medicagenic acid derivatives, saponins 4 and 5. Oxidative burst and nitric oxide accumulation were common hallmarks of the response of white poplar cells to saponins. When DNA damage accumulation and DNA repair profiles were evaluated by Single Cell Gel Electrophoresis, induction of single and double strand breaks followed by effective repair was observed within 24h. The reported data are discussed in view of the current issues dealing with saponin structure-activity relationship.

  1. A Phenolic Extract Obtained from Methyl Jasmonate-Treated Strawberries Enhances Apoptosis in a Human Cervical Cancer Cell Line.

    PubMed

    Spagnuolo, Carmela; Flores, Gema; Russo, Gian Luigi; Ruiz Del Castillo, Maria Luisa

    2016-10-01

    In the present study, we evaluated the effect of methyl jasmonate (MeJA) treatment on strawberry phenolic composition. Strawberry extracts contain a mixture of phenolic compounds possessing several biological properties. We demonstrated that these extracts were more effective in inducing apoptosis in HeLa cells compared to phenolic preparations derived from untreated strawberries. Treatment of strawberries with 0.5% MeJA resulted in increased polyphenols content (from 7.4 to 8.6 mM quercetin equivalents) and antioxidant properties (from 3.9 to 4.6 mM quercetin equivalents). The identification and quantification of phenolic compounds by liquid chromatography-mass spectrometry in the strawberry extracts showed that cyanidin glucoside, pelargonidin glucoside, and ellagic glucoside acid were significantly higher in strawberries treated with MeJA. Phenolic extracts from MeJA-treated strawberries significantly decreased the cell viability in HeLa cells, compared to extracts derived from untreated fruits. We hypothesized that the enhanced apoptotic activity of MeJA-treated strawberries was due to a synergistic or additive effect of different phenolic compounds present in the extract, rather than the activity of a single molecule.

  2. A Phenolic Extract Obtained from Methyl Jasmonate-Treated Strawberries Enhances Apoptosis in a Human Cervical Cancer Cell Line.

    PubMed

    Spagnuolo, Carmela; Flores, Gema; Russo, Gian Luigi; Ruiz Del Castillo, Maria Luisa

    2016-10-01

    In the present study, we evaluated the effect of methyl jasmonate (MeJA) treatment on strawberry phenolic composition. Strawberry extracts contain a mixture of phenolic compounds possessing several biological properties. We demonstrated that these extracts were more effective in inducing apoptosis in HeLa cells compared to phenolic preparations derived from untreated strawberries. Treatment of strawberries with 0.5% MeJA resulted in increased polyphenols content (from 7.4 to 8.6 mM quercetin equivalents) and antioxidant properties (from 3.9 to 4.6 mM quercetin equivalents). The identification and quantification of phenolic compounds by liquid chromatography-mass spectrometry in the strawberry extracts showed that cyanidin glucoside, pelargonidin glucoside, and ellagic glucoside acid were significantly higher in strawberries treated with MeJA. Phenolic extracts from MeJA-treated strawberries significantly decreased the cell viability in HeLa cells, compared to extracts derived from untreated fruits. We hypothesized that the enhanced apoptotic activity of MeJA-treated strawberries was due to a synergistic or additive effect of different phenolic compounds present in the extract, rather than the activity of a single molecule. PMID:27618150

  3. Autism-like behaviours with transient histone hyperacetylation in mice treated prenatally with valproic acid.

    PubMed

    Kataoka, Shunsuke; Takuma, Kazuhiro; Hara, Yuta; Maeda, Yuko; Ago, Yukio; Matsuda, Toshio

    2013-02-01

    Maternal use of valproic acid (VPA) during pregnancy has been implicated in the aetiology of autism spectrum disorders in children, and rodents prenatally exposed to VPA showed behavioural alterations similar to those observed in humans with autism. However, the exact mechanism for VPA-induced behavioural alterations is not known. To study this point, we examined the effects of prenatal exposure to VPA and valpromide, a VPA analog lacking histone deacetylase inhibition activity, on behaviours, cortical pathology and histone acetylation levels in mice. Mice exposed to VPA at embryonic day 12.5 (E12.5), but not at E9 and E14.5, displayed social interaction deficits, anxiety-like behaviour and memory deficits at age 4-8 wk. In contrast to male mice, the social interaction deficits (a decrease in sniffing behaviour) were not observed in female mice at age 8 wk. The exposure to VPA at E12.5 decreased the number of Nissl-positive cells in the middle and lower layers of the prefrontal cortex and in the lower layers of the somatosensory cortex at age 8 wk. Furthermore, VPA exposure caused a transient increase in acetylated histone levels in the embryonic brain, followed by an increase in apoptotic cell death in the neocortex and a decrease in cell proliferation in the ganglionic eminence. In contrast, prenatal exposure to valpromide at E12.5 did not affect the behavioural, biochemical and histological parameters. Furthermore, these findings suggest that VPA-induced histone hyperacetylation plays a key role in cortical pathology and abnormal autism-like behaviours in mice.

  4. Transformation and apoptosis of NIH/3T3 cells treated with nickel-smelting fumes.

    PubMed

    Jin, Yan-Tao; Wu, Yong-Hui; Hu, Fu-Lan; Hu, Xue-Ying

    2009-01-01

    The purpose of this study was to investigate the transformation and apoptosis of NIH/3T3 cells treated with nickel (Ni) smelting fumes. Cytotoxicity of NIH/3T3 cells was detected with a methyl thiazolyl tetrazolium (MTT) colorimetric assay. The cell translation model was established by cell focus translation using two types of Ni-smelting fumes from a Ni smelting plant in China. The transformed focus was determined by soft agar culture assay. The apoptotic characteristics of NIH/3T3 cells treated with Ni-smelting fumes were detected by flow cytometry using Annexin V-FITC and PI as markers. The DNA fragment of apoptosis in NIH/3T3 cells treated with nickel smelting fumes was detected by observing agarose electrophoresis and morphological characteristics of cells under electron microscopy. With increase in exposure time, growth of NIH/3T3 cells was inhibited. The NIH/3T3 cell transformation model was established successfully using two Ni-smelting fumes, and the transformed cells grow in soft agar. No apoptosis peak was detected by flow cytometry. Apoptotic cells characterized by necrosis were observed using electron microscopy. There was no apparent "ladder" observed by DNA fragment analysis. Data indicated that Ni-smelting fumes produced cytotoxicity by mechanisms associated with necrosis but not apoptosis. PMID:19492236

  5. Transformation and apoptosis of NIH/3T3 cells treated with nickel-smelting fumes.

    PubMed

    Jin, Yan-Tao; Wu, Yong-Hui; Hu, Fu-Lan; Hu, Xue-Ying

    2009-01-01

    The purpose of this study was to investigate the transformation and apoptosis of NIH/3T3 cells treated with nickel (Ni) smelting fumes. Cytotoxicity of NIH/3T3 cells was detected with a methyl thiazolyl tetrazolium (MTT) colorimetric assay. The cell translation model was established by cell focus translation using two types of Ni-smelting fumes from a Ni smelting plant in China. The transformed focus was determined by soft agar culture assay. The apoptotic characteristics of NIH/3T3 cells treated with Ni-smelting fumes were detected by flow cytometry using Annexin V-FITC and PI as markers. The DNA fragment of apoptosis in NIH/3T3 cells treated with nickel smelting fumes was detected by observing agarose electrophoresis and morphological characteristics of cells under electron microscopy. With increase in exposure time, growth of NIH/3T3 cells was inhibited. The NIH/3T3 cell transformation model was established successfully using two Ni-smelting fumes, and the transformed cells grow in soft agar. No apoptosis peak was detected by flow cytometry. Apoptotic cells characterized by necrosis were observed using electron microscopy. There was no apparent "ladder" observed by DNA fragment analysis. Data indicated that Ni-smelting fumes produced cytotoxicity by mechanisms associated with necrosis but not apoptosis.

  6. Salvianolic acid B stimulates osteogenesis in dexamethasone-treated zebrafish larvae

    PubMed Central

    Luo, Shi-ying; Chen, Jing-feng; Zhong, Zhi-guo; Lv, Xiao-hua; Yang, Ya-jun; Zhang, Jing-jing; Cui, Liao

    2016-01-01

    Aim: Our previous studies show that salvianolic acid B (Sal B) promotes osteoblast differentiation and matrix mineralization. In this study, we evaluated the protective effects of Sal B on the osteogenesis in dexamethasone (Dex)-treated larval zebrafish, and elucidated the underlying mechanisms. Methods: At 3 d post fertilization, wild-type AB zebrafish larvae or bone transgenic tg (sp7:egfp) zebrafish larvae were exposed to Sal B, Dex, or a mixture of Dex+Sal B for 6 d. Bone mineralization in AB strain larval zebrafish was assessed with alizarin red staining, and osteoblast differentiation in tg (sp7:egfp) larval zebrafish was examined with fluorescence scanning. The expression of osteoblast-specific genes in the larvae was detected using qRT-PCR assay. The levels of oxidative stress markers (ROS and MDA) in the larvae were also measured. Results: Exposure to Dex (5–20 μmol/L) dose-dependently decreased the bone mineralization area and integral optical density (IOD) in wild-type AB zebrafish larvae and the osteoblast fluorescence area and IOD in tg (sp7:egfp) zebrafish larvae. Exposure to Dex (10 μmol/L) significantly reduced the expression of osteoblast-specific genes, including runx2a, osteocalcin (OC), alkaline phosphatase (ALP) and osterix (sp7), and increased the accumulation of ROS and MDA in the larvae. Co-exposure to Sal B (0.2–2 μmol/L) dose-dependently increased the bone mineralization area and IOD in AB zebafish larvae and osteoblast fluorescence in tg (sp7:egfp) zebrafish larvae. Co-exposure to Sal B (2 μmol/L) significantly attenuated deleterious alterations in bony tissue and oxidative stress in both Dex-treated AB zebafish larvae and tg (sp7:egfp) zebrafish larvae. Conclusion: Sal B stimulates bone formation and rescues GC-caused inhibition on osteogenesis in larval zebrafish by counteracting oxidative stress and increasing the expression of osteoblast-specific genes. Thus, Sal B may have protective effects on bone loss trigged by GC. PMID

  7. Synthesis of novel acid electrolytes for phosphoric acid fuel cells

    NASA Astrophysics Data System (ADS)

    Adcock, James L.

    1988-11-01

    A 40 millimole per hour scale aerosol direct fluorination reactor was constructed. F-Methyl F-4-methoxybutanoate and F-4-methoxybutanoyl fluoride were synthesized by aerosol direct fluorination of methyl 4-methoxybutanoate. Basic hydrolysis of the perfluorinated derivatives produce sodium F-4 methoxybutanoate which was pyrolyzed to F-3-methoxy-1-propene. Purification and shipment of 33 grams of F-3-methoxy-1-propene followed. Syntheses by analogous methods allowed production and shipment of 5 grams of F-3-ethoxy 1-propene, 18 grams of F-3-(2-methoxy.ethoxy) 1-propene, and 37 grams of F-3,3-dimethyl 1-butene. Eighteen grams of F-2,2-dimethyl 1-chloropropane was produced directly and shipped. As suggested by other contractors, 5 grams of F-3-methoxy 1-iodopropane, and 5 grams of F-3-(2-methoxy.ethoxy) 1-iodopropane were produced by converting the respective precursor acid sodium salts produced for olefin synthesis to the silver salts and pyrolyzing them with iodine. Each of these compounds was prepared for the first time by the aerosol fluorination process during the course of the contract. These samples were provided to other Gas Research Institute (GRI) contractors for synthesis of perfluorinated sulfur (VI) and phosphorous (V) acids.

  8. CD73 protein as a source of extracellular precursors for sustained NAD+ biosynthesis in FK866-treated tumor cells.

    PubMed

    Grozio, Alessia; Sociali, Giovanna; Sturla, Laura; Caffa, Irene; Soncini, Debora; Salis, Annalisa; Raffaelli, Nadia; De Flora, Antonio; Nencioni, Alessio; Bruzzone, Santina

    2013-09-01

    NAD(+) is mainly synthesized in human cells via the "salvage" pathways starting from nicotinamide, nicotinic acid, or nicotinamide riboside (NR). The inhibition with FK866 of the enzyme nicotinamide phosphoribosyltransferase (NAMPT), catalyzing the first reaction in the "salvage" pathway from nicotinamide, showed potent antitumor activity in several preclinical models of solid and hematologic cancers. In the clinical studies performed with FK866, however, no tumor remission was observed. Here we demonstrate that low micromolar concentrations of extracellular NAD(+) or NAD(+) precursors, nicotinamide mononucleotide (NMN) and NR, can reverse the FK866-induced cell death, this representing a plausible explanation for the failure of NAMPT inhibition as an anti-cancer therapy. NMN is a substrate of both ectoenzymes CD38 and CD73, with generation of NAM and NR, respectively. In this study, we investigated the roles of CD38 and CD73 in providing ectocellular NAD(+) precursors for NAD(+) biosynthesis and in modulating cell susceptibility to FK866. By specifically silencing or overexpressing CD38 and CD73, we demonstrated that endogenous CD73 enables, whereas CD38 impairs, the conversion of extracellular NMN to NR as a precursor for intracellular NAD(+) biosynthesis in human cells. Moreover, cell viability in FK866-treated cells supplemented with extracellular NMN was strongly reduced in tumor cells, upon pharmacological inhibition or specific down-regulation of CD73. Thus, our study suggests that genetic or pharmacologic interventions interfering with CD73 activity may prove useful to increase cancer cell sensitivity to NAMPT inhibitors. PMID:23880765

  9. Transcriptomic and proteomic analysis of human hepatic stellate cells treated with natural taurine.

    PubMed

    Liang, Jian; Deng, Xin; Wu, Fa-Sheng; Tang, Yan-Fang

    2013-05-01

    The aim of this study was to investigate the differential expression of genes and proteins between natural taurine (NTau)‑treated hepatic stellate cells (HSCs) and control cells as well as the underlying mechanism of NTau in inhibiting hepatic fibrosis. A microculture tetrazolium (MTT) assay was used to analyze the proliferation of NTau‑treated HSCs. Flow cytometry was performed to compare the apoptosis rate between NTau-treated and non‑treated HSCs. Proteomic analysis using a combination of 2-dimensional gel electrophoresis (2DE) and mass spectrometry (MS) was conducted to identify the differentially expressed proteins. Microarray analysis was performed to investigate the differential expression of genes and real-time polymerase chain reaction (PCR) was used to validate the results. The experimental findings obtained demonstrated that NTau decreased HSC proliferation, resulting in an increased number of cells in the G0/G1 phase and a reduced number of cells in the S phase. Flow cytometric analysis showed that NTau-treated HSCs had a significantly increased rate of apoptosis when compared with the non‑treated control group. A total of 15 differentially expressed proteins and 658 differentially expressed genes were identified by 2DE and MS, and microarray analysis, respectively. Gene ontology (GO) functional analysis indicated that these genes and proteins were enriched in the function clusters and pathways related to cell proliferation, cellular apoptosis and oxidation. The transcriptome and proteome analyses of NTau-treated HSCs demonstrated that NTau is able to significantly inhibit cell proliferation and promote cell apoptosis, highlighting its potential therapeutic benefits in the treatment of hepatic fibrosis. PMID:23525364

  10. Transcriptomic and proteomic analysis of human hepatic stellate cells treated with natural taurine.

    PubMed

    Liang, Jian; Deng, Xin; Wu, Fa-Sheng; Tang, Yan-Fang

    2013-05-01

    The aim of this study was to investigate the differential expression of genes and proteins between natural taurine (NTau)‑treated hepatic stellate cells (HSCs) and control cells as well as the underlying mechanism of NTau in inhibiting hepatic fibrosis. A microculture tetrazolium (MTT) assay was used to analyze the proliferation of NTau‑treated HSCs. Flow cytometry was performed to compare the apoptosis rate between NTau-treated and non‑treated HSCs. Proteomic analysis using a combination of 2-dimensional gel electrophoresis (2DE) and mass spectrometry (MS) was conducted to identify the differentially expressed proteins. Microarray analysis was performed to investigate the differential expression of genes and real-time polymerase chain reaction (PCR) was used to validate the results. The experimental findings obtained demonstrated that NTau decreased HSC proliferation, resulting in an increased number of cells in the G0/G1 phase and a reduced number of cells in the S phase. Flow cytometric analysis showed that NTau-treated HSCs had a significantly increased rate of apoptosis when compared with the non‑treated control group. A total of 15 differentially expressed proteins and 658 differentially expressed genes were identified by 2DE and MS, and microarray analysis, respectively. Gene ontology (GO) functional analysis indicated that these genes and proteins were enriched in the function clusters and pathways related to cell proliferation, cellular apoptosis and oxidation. The transcriptome and proteome analyses of NTau-treated HSCs demonstrated that NTau is able to significantly inhibit cell proliferation and promote cell apoptosis, highlighting its potential therapeutic benefits in the treatment of hepatic fibrosis.

  11. Influence of decenylsuccinic Acid on water permeability of plant cells.

    PubMed

    Lee, O Y; Stadelmann, E J; Weiser, C J

    1972-11-01

    Decenylsuccinic acid altered permeability to water of epidermal cells of bulb scales of Allium cepa and of the leaf midrib of Rhoeo discolor. Water permeability, as determined by deplasmolysis time measurements, was related to the dose of undissociated decenylsuccinic acid (mm undissociated decenylsuccinic acid x minute). No relationship was found between permeability and total dose of decenylsuccinic acid, or dose of dissociated decenylsuccinic acid, suggesting that the undissociated molecule was the active factor in permeability changes and injury.At doses which did not damage cells (0.0008 to 0.6 [mm of the undissociated molecule x minute]) decenylsuccinic acid decreased water permeability. At higher doses (e.g., 4 to 8 [mm x minute]) injury to cells was common and decenylsuccinic acid increased permeability. Doses above the 10 to 20 (mm x minute) range were generally lethal. The plasmolysis form of uninjured cells was altered and protoplasmic swelling occasionally was observed. The dose-dependent reversal of water permeability changes (decreased to increased permeability) may reflect decenylsuccinic acid-induced changes in membrane structure. Reported effects of decenylsuccinic acid on temperature dependence of permeability and frost resistance were not verified. PMID:16658227

  12. Acitretin systemic and retinoic acid 0.1% cream supression of basal cell carcinoma

    PubMed Central

    Zhang, Xi-Bao; Zhang, San-Quan; Li, Chang-Xing; Huang, Zhen-Ming; Luo, Yu-Wu

    2010-01-01

    Retinoids have been used for years as monotherapy and/or in combination for treatment and suppression of cutaneous malignancies in patients with basal cell nevus syndrome, xeroderma pigmentosum, or cutaneous T-cell lymphoma (CTCL) basal cell carcinoma (BCC). We report 4 cases with BCC confirmed by histopathology who were treated by short-term systemic acitretin combined with retinoic acid 0.1% cream. The 4 cases with BCC showed good response to the treatment without severe adverse effects during treatment and follow-up. The finding suggests that acitretin may be an appropriate treatment option for elderly patients who require less invasive treatment for BCC. PMID:25386240

  13. Effects of Asiatic Acid on Spatial Working Memory and Cell Proliferation in the Adult Rat Hippocampus.

    PubMed

    Sirichoat, Apiwat; Chaijaroonkhanarak, Wunnee; Prachaney, Parichat; Pannangrong, Wanassanan; Leksomboon, Ratana; Chaichun, Amnart; Wigmore, Peter; Welbat, Jariya Umka

    2015-10-05

    Asiatic acid is a pentacyclic triterpene from Centella asiatica. Previous studies have reported that asiatic acid exhibits antioxidant and neuroprotective activities in cell culture. It also prevents memory deficits in animal models. The objective of this study was to investigate the relationship between spatial working memory and changes in cell proliferation within the hippocampus after administration of asiatic acid to male Spraque-Dawley rats. Control rats received vehicle (propylene glycol) while treated rats received asiatic acid (30 mg/kg) orally for 14 or 28 days. Spatial memory was determined using the novel object location (NOL) test. In animals administered asiatic acid for both 14 and 28 days, the number of Ki-67 positive cells in the subgranular zone of the dentate gyrus was significantly higher than in control animals. This was associated with a significant increase in their ability to discriminate between novel and familiar object locations in a novel object discrimination task, a hippocampus-dependent spatial memory test. Administration of asiatic acid also significantly increased doublecortin (DCX) and Notch1 protein levels in the hippocampus. These findings demonstrate that asiatic acid treatment may be a potent cognitive enhancer which improves hippocampal-dependent spatial memory, likely by increasing hippocampal neurogenesis.

  14. The Polyunsaturated Fatty Acids Arachidonic Acid and Docosahexaenoic Acid Induce Mouse Dendritic Cells Maturation but Reduce T-Cell Responses In Vitro

    PubMed Central

    Carlsson, Johan A.; Wold, Agnes E.; Sandberg, Ann-Sofie; Östman, Sofia M.

    2015-01-01

    Long-chain polyunsaturated fatty acids (PUFAs) might regulate T-cell activation and lineage commitment. Here, we measured the effects of omega-3 (n-3), n-6 and n-9 fatty acids on the interaction between dendritic cells (DCs) and naïve T cells. Spleen DCs from BALB/c mice were cultured in vitro with ovalbumin (OVA) with 50 μM fatty acids; α-linolenic acid, arachidonic acid (AA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), linoleic acid or oleic acid and thereafter OVA-specific DO11.10 T cells were added to the cultures. Fatty acids were taken up by the DCs, as shown by gas chromatography analysis. After culture with arachidonic acid or DHA CD11c+ CD11b+ and CD11c+ CD11bneg DCs expressed more CD40, CD80, CD83, CD86 and PDL-1, while IAd remained unchanged. However, fewer T cells co-cultured with these DCs proliferated (CellTrace Violetlow) and expressed CD69 or CD25, while more were necrotic (7AAD+). We noted an increased proportion of T cells with a regulatory T cell (Treg) phenotype, i.e., when gating on CD4+ FoxP3+ CTLA-4+, CD4+ FoxP3+ Helios+ or CD4+ FoxP3+ PD-1+, in co-cultures with arachidonic acid- or DHA-primed DCs relative to control cultures. The proportion of putative Tregs was inversely correlated to T-cell proliferation, indicating a suppressive function of these cells. With arachidonic acid DCs produced higher levels of prostaglandin E2 while T cells produced lower amounts of IL-10 and IFNγ. In conclusion arachidonic acid and DHA induced up-regulation of activation markers on DCs. However arachidonic acid- and DHA-primed DCs reduced T-cell proliferation and increased the proportion of T cells expressing FoxP3, indicating that these fatty acids can promote induction of regulatory T cells. PMID:26619195

  15. Use of Differentiated Pluripotent Stem Cells in Replacement Therapy for Treating Disease

    PubMed Central

    Fox, Ira J.; Daley, George Q.; Goldman, Steven A.; Huard, Johnny; Kamp, Timothy J.; Trucco, Massimo

    2015-01-01

    Patient-derived pluripotent stem cells (PSC) directed to various cell fates holds promise as source material for treating numerous disorders. The availability of precisely differentiated PSC-derived cells will dramatically impact blood component and hematopoietic stem cell therapies, and should facilitate treatment of diabetes, some forms of liver disease and neurologic disorders, retinal diseases, and possibly heart disease. Although an unlimited supply of specific cell types are needed, other barriers must be overcome. This review of the state of cell therapies highlights important challenges. Successful cell transplantation will require optimizing the best cell type and site for engraftment, overcoming limitations to cell migration and tissue integration, and occasionally needing to control immunologic reactivity. Collaboration among scientists, clinicians, and industry is critical for generating new stem cell-based therapies. PMID:25146295

  16. Gallic acid suppresses cell viability, proliferation, invasion and angiogenesis in human glioma cells

    PubMed Central

    Lu, Yong; Jiang, Feng; Jiang, Hao; Wu, Kalina; Zheng, Xuguang; Cai, Yizhong; Katakowski, Mark; Chopp, Michael; To, Shing-Shun Tony

    2010-01-01

    Gallic acid, an organic acid, also known as 3,4,5-trihydroxybenzoic acid, is cytotoxic against certain cancer cells, without harming normal cells. The objective of this study is to evaluate whether gallic acid can inhibit glioma cell viability, proliferation, invasion and reduce glioma cell mediated angiogenesis. Treatment of U87 and U251n glioma cells with gallic acid inhibited cell viability in a dose- and time-dependent manner. BrdU and tube formation assays indicated that gallic acid significantly decreased glioma cell proliferation and tube formation in mouse brain endothelial cells, respectively. In addition, gallic acid decreased U87 cell invasion in vitro. Western blot analysis showed that expression of ADAM17, p-Akt and p-Erk was suppressed by gallic acid in both U87 and U251n cell lines. These data suggest that suppression of ADAM17 and downregulation of PI3K/Akt and Ras/MAPK signaling pathways may contribute to gallic acid-induced decrease of invasiveness. Gallic acid may be a valuable candidate for treatment of brain tumor. PMID:20553913

  17. Gambogic acid sensitizes ovarian cancer cells to doxorubicin through ROS-mediated apoptosis.

    PubMed

    Wang, Jianxia; Yuan, Zhixiang

    2013-09-01

    Ovarian cancer is one human malignancy which has response portly to doxorubicin. The anti-cancer activity of gambogic acid has been tested in in vitro and in vivo studies. In this study, we showed that gambogic acid, a natural compound, could potentiate the anticancer activity of doxorubicin in ovarian cancer through ROS-mediated apoptosis. Platinum-resistant human ovarian cancer cell line (SKOV-3) was treated with gambogic acid, doxorubicin, or the combination of both to investigate cell proliferation and apoptosis. We found that the combination of gambogic acid and doxorubicin causes synergistic loss of cell viability in SKOV-3 cells and this synergistic effect correlated with increased cellular ROS accumulation. Moreover, in vivo results showed that gambogic acid and doxorubicin combination resulted in a synergistic suppressing effect on tumor growth in ovarian cancer mice model. Taken together, the results suggested that doxorubicin in combination with gambogic acid might provide a promising therapeutic strategy to enhance chemosensitivity of ovarian cancer to doxorubicin.

  18. Arachidonic acid release and prostaglandin synthesis in a macrophage-like cell line exposed to asbestos.

    PubMed

    Brown, R C; Poole, A

    1984-10-01

    A macrophage-like cell line (P388D1) has been treated with asbestos and the release of arachidonic acid and its metabolites has been studied using two methods. In the first monolayer cultures of the cells were labelled with tritiated arachidonic acid and the release of label into the medium was quantified: secondly the synthesis and release of prostaglandins E2 and F2 alpha were followed using radioimmune assay. Crocidolite asbestos caused the greatest release of tritium while the medium from chrysotile-treated cultures contained more of both prostaglandins. Both of the fibrous dusts were significantly more active in both test systems than were the two 'inert' materials--titanium dioxide and milled sample of crocidolite. It is suggested that these phenomena are due to the effect of mineral dusts on phospholipase activity and that differences in this activity are associated with differences in the pathogenicity of various mineral dusts. PMID:6098173

  19. Intestinal-fatty acid binding protein and lipid transport in human intestinal epithelial cells

    SciTech Connect

    Montoudis, Alain; Delvin, Edgard; Menard, Daniel

    2006-01-06

    Intestinal-fatty acid binding protein (I-FABP) is a 14-15 kDa cytoplasmic molecule highly expressed in the enterocyte. Although different functions have been proposed for various FABP family members, the specific function of I-FABP in human intestine remains unclear. Here, we studied the role of I-FABP in molecularly modified normal human intestinal epithelial cells (HIEC-6). cDNA transfection resulted in 90-fold I-FABP overexpression compared to cells treated with empty pQCXIP vector. The high-resolution immunogold technique revealed labeling mainly in the cytosol and confirmed the marked phenotype abundance of I-FABP in cDNA transfected cells. I-FABP overexpression was not associated with alterations in cell proliferation and viability. Studies using these transfected cells cultured with [{sup 14}C]oleic acid did not reveal higher efficiency in de novo synthesis or secretion of triglycerides, phospholipids, and cholesteryl esters compared to cells treated with empty pQCXIP vector only. Similarly, the incubation with [{sup 35}S]methionine did not disclose a superiority in the biogenesis of apolipoproteins (apo) A-I, A-IV, B-48, and B-100. Finally, cells transfected with I-FABP did not exhibit an increased production of chylomicrons, VLDL, LDL, and HDL. Our observations establish that I-FABP overexpression in normal HIEC-6 is not related to cell proliferation, lipid esterification, apo synthesis, and lipoprotein assembly, and, therefore, exclude its role in intestinal fat transport.

  20. Dehydroabietic Acid Derivative QC2 Induces Oncosis in Hepatocellular Carcinoma Cells

    PubMed Central

    Zhang, Guang; Jiang, Chunping; Wang, Zhongxia; Chen, Weibo; Gu, Wen; Ding, Yitao

    2014-01-01

    Aim. Rosin, the traditional Chinese medicine, is reported to be able to inhibit skin cancer cell lines. In this report, we investigate the inhibitory effect against HCC cells of QC2, the derivative of rosin's main components dehydroabietic acid. Methods. MTT assay was used to determine the cytotoxicity of QC2. Morphological changes were observed by time-lapse microscopy and transmission electron microscopy and the cytoskeleton changes were observed by laser-scanning confocal microscopy. Cytomembrane integrity and organelles damage were confirmed by detection of the reactive oxygen (ROS), lactate dehydrogenase (LDH), and mitochondrial membrane potential (Δψm). The underlying mechanism was manifested by Western blotting. The oncotic cell death was further confirmed by detection of oncosis related protein calpain. Results. Swelling cell type and destroyed cytoskeleton were observed in QC2-treated HCC cells. Organelle damage was visualized by transmission electron microscopy. The detection of ROS accumulation, increased LDH release, and decreased ATP and Δψm confirmed the cell death. The oncotic related protein calpain was found to increase time-dependently in QC2-treated HCC cells, while its inhibitor PD150606 attenuated the cytotoxicity. Conclusions. Dehydroabietic acid derivative QC2 activated oncosis related protein calpain to induce the damage of cytomembrane and organelles which finally lead to oncosis in HCC cells. PMID:25110686

  1. Rapid Formation of Cell Aggregates and Spheroids Induced by a "Smart" Boronic Acid Copolymer.

    PubMed

    Amaral, Adérito J R; Pasparakis, George

    2016-09-01

    Cell surface engineering has emerged as a powerful approach to forming cell aggregates/spheroids and cell-biomaterial ensembles with significant uses in tissue engineering and cell therapeutics. Herein, we demonstrate that cell membrane remodeling with a thermoresponsive boronic acid copolymer induces the rapid formation of spheroids using either cancer or cardiac cell lines under conventional cell culture conditions at minute concentrations. It is shown that the formation of well-defined spheroids is accelerated by at least 24 h compared to non-polymer-treated controls, and, more importantly, the polymer allows for fine control of the aggregation kinetics owing to its stimulus response to temperature and glucose content. On the basis of its simplicity and effectiveness to promote cellular aggregation, this platform holds promise in three-dimensional tissue/tumor modeling and tissue engineering applications. PMID:27571512

  2. Outcomes in patients with nonerosive reflux disease treated with a proton pump inhibitor and alginic acid ± glycyrrhetinic acid and anthocyanosides

    PubMed Central

    Di Pierro, Francesco; Gatti, Mario; Rapacioli, Giuliana; Ivaldi, Leandro

    2013-01-01

    Background The purpose of this study was to compare the efficacy of alginic acid alone versus alginic acid combined with low doses of pure glycyrrhetinic acid and bilberry anthocyanosides as an addon to conventional proton pump inhibitor therapy in relieving symptoms associated with nonerosive reflux disease. Methods This prospective, randomized, 8-week, open-label trial was conducted at two centers. Sixty-three patients with persistent symptoms of gastroesophageal reflux disease and normal upper gastrointestinal endoscopy were eligible for the study. Patients in group A (n = 31) were treated with pantoprazole and a formula (Mirgeal®) containing alginic acid and low doses of pure glycyrrhetinic acid + standardized Vaccinium myrtillus extract for 4 weeks, then crossed over to the multi-ingredient formula for a further 4 weeks. Patients in group B (n = 32) were treated pantoprazole and alginic acid alone twice daily, then crossed over to alginic acid twice daily for a further 4 weeks. Efficacy was assessed by medical evaluation of a symptom relief score, estimated using a visual analog scale (0–10). Side effects, tolerability, and compliance were also assessed. Results Of the 63 patients enrolled in the study, 58 (29 in group A and 29 in group B) completed the 8-week trial. The baseline characteristics were comparable between the two groups. During the study, significant differences were recorded in symptom scores for both groups. In group A, symptoms of chest pain, heartburn, and abdominal swelling were less serious than in group B. Treatment A was better tolerated, did not induce hypertension, and had fewer side effects than treatment B. No significant differences in compliance were found between the two groups. Conclusion Use of low doses of pure glycyrrhetinic acid + bilberry anthocyanosides, together with alginic acid as addon therapy, substantially improves symptoms in patients with nonerosive reflux disease without increasing side effects or worsening

  3. Retinoic Acid Stimulates Regeneration of Mammalian Auditory Hair Cells

    NASA Astrophysics Data System (ADS)

    Lefebvre, Philippe P.; Malgrange, Brigitte; Staecker, Hinrich; Moonen, Gustave; van de Water, Thomas R.

    1993-04-01

    Sensorineural hearing loss resulting from the loss of auditory hair cells is thought to be irreversible in mammals. This study provides evidence that retinoic acid can stimulate the regeneration in vitro of mammalian auditory hair cells in ototoxic-poisoned organ of Corti explants in the rat. In contrast, treatment with retinoic acid does not stimulate the formation of extra hair cells in control cultures of Corti's organ. Retinoic acid-stimulated hair cell regeneration can be blocked by cytosine arabinoside, which suggests that a period of mitosis is required for the regeneration of auditory hair cells in this system. These results provide hope for a recovery of hearing function in mammals after auditory hair cell damage.

  4. Nerve growth factor-treated, neurite-bearing PC12 cells continue to synthesize DNA

    SciTech Connect

    Ignatius, M.J.; Chandler, C.R.; Shooter, E.M.

    1985-02-01

    Cultures of rat pheochromocytoma (PC12) cells treated with beta-nerve growth factor (NGF) for up to 15 days continue to synthesize DNA. The present study compares the extent of maintained DNA synthesis in cells with and without processes and asks whether the observed DNA synthesis in differentiated PC12 cells reflects either the continued division of the cells or the formation of polyploid cells, or both. PC12 cells were grown on tissue coverslips for various lengths of time with or without 50 ng/ml of beta-NGF and then assayed for DNA synthesis by (/sup 3/H)thymidine labeling and autoradiography. In 8-day-old control cultures (no NGF), 30% of the cells had labeled nuclei after a 2-hr (/sup 3/H)thymidine pulse. In contrast, in cultures treated for 8 days with NGF, only 7% of the cells were labeled (i.e., still synthesizing DNA). The fractions of process-bearing and non-process-bearing cells with labeled nuclei were identical. Even after 14 days in NGF, 7% of the cells with neurites were still synthesizing DNA during any 2-hr period. With continuous (/sup 3/H)thymidine labeling in the presence of NGF from 8 to 13 days, nearly 70% of the cells with neurites were labeled. The presence of neurites induced by NGF does not preclude continued (albeit reduced) DNA synthesis in these PC12 cells. To determine the fate of this newly synthesized DNA, nuclei extracted from NGF-treated PC12 cells were analyzed for the cellular distribution of DNA by combined propidium iodine staining and flow microfluorimetry. NGF treatment resulted in a 3-fold increase in the number of G2+M/4N cells along with the appearance of 8N cells.

  5. Permeability of rosmarinic acid in Prunella vulgaris and ursolic acid in Salvia officinalis extracts across Caco-2 cell monolayers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rosmarinic acid (RA), a caffeic acid derivative found in high concentrations in Prunella vulgaris (self-heal), and ursolic acid (UA), a pentacyclic triterpene acid concentrated in Salvia officinalis (sage), have been traditionally used to treat inflammation in the mouth, and may also be of benefit t...

  6. Direct acid methylation for extraction of fatty acid content from microalgae cells.

    PubMed

    Frigo-Vaz, Benjamin D; Wang, Ping

    2014-08-01

    Direct acid methylation was examined as a means for both analysis of fatty acid content in microalgal cells and biodiesel production without pretreatment. Microalgal cells of Chlamydomonas reinhardtii and Dunaliella tertiolecta were prepared and examined. It appeared that direct acid methylation extracted higher fatty acid content than the solvent-based Soxhlet extraction process. It also revealed that the latter was prone to extract a significant amount of nonlipid hydrophobic impurities, including hydrophobic proteins and phytol-type compounds, while direct methylation produces essentially pure ester product. This work demonstrates that direct acid methylation provides superior fatty acid extraction, promising an efficient process for either quantification of lipid content or production of biodiesel. PMID:24838798

  7. Oxygen nano-bubble water reduces calcium oxalate deposits and tubular cell injury in ethylene glycol-treated rat kidney.

    PubMed

    Hirose, Yasuhiko; Yasui, Takahiro; Taguchi, Kazumi; Fujii, Yasuhiro; Niimi, Kazuhiro; Hamamoto, Shuzo; Okada, Atsushi; Kubota, Yasue; Kawai, Noriyasu; Itoh, Yasunori; Tozawa, Keiichi; Sasaki, Shoichi; Kohri, Kenjiro

    2013-08-01

    Renal tubular cell injury induced by oxalate plays an important role in kidney stone formation. Water containing oxygen nano-bubbles (nanometer-sized bubbles generated from oxygen micro-bubbles; ONB) has anti-inflammatory effects. Therefore, we investigated the inhibitory effects of ONB water on kidney stone formation in ethylene glycol (EG)-treated rats. We divided 60 rats, aged 4 weeks, into 5 groups: control, the water-fed group; 100 % ONB, the 100 % ONB water-fed group; EG, the EG treated water-fed group; EG + 50 % ONB and EG + 100 % ONB, water containing EG and 50 % or 100 % ONB, respectively. Renal calcium oxalate (CaOx) deposition, urinary excretion of N-acetyl-β-D-glucosaminidase (NAG), and renal expression of inflammation-related proteins, oxidative stress biomarkers, and the crystal-binding molecule hyaluronic acid were compared among the 5 groups. In the control and 100 % ONB groups, no renal CaOx deposits were detected. In the EG + 50 % ONB and EG + 100 % ONB groups, ONB water significantly decreased renal CaOx deposits, urinary NAG excretion, and renal monocyte chemoattractant protein-1, osteopontin, and hyaluronic acid expression and increased renal superoxide dismutase-1 expression compared with the EG group. ONB water substantially affected kidney stone formation in the rat kidney by reducing renal tubular cell injury. ONB water is a potential prophylactic agent for kidney stones.

  8. Full scale phosphoric acid fuel cell stack technology development

    NASA Technical Reports Server (NTRS)

    Christner, L.; Faroque, M.

    1984-01-01

    The technology development for phosphoric acid fuel cells is summarized. The preparation, heat treatment, and characterization of carbon composites used as bipolar separator plates are described. Characterization included resistivity, porosity, and electrochemical corrosion. High density glassy carbon/graphite composites performed well in long-term fuel cell endurance tests. Platinum alloy cathode catalysts and low-loaded platinum electrodes were evaluated in 25 sq cm cells. Although the alloys displayed an initial improvement, some of this improvement diminished after a few thousand hours of testing. Low platinum loading (0.12 mg/sq cm anodes and 0.3 mg/sq cm cathodes) performed nearly as well as twice this loading. A selectively wetproofed anode backing paper was tested in a 5 by 15 inch three-cell stack. This material may provide for acid volume expansion, acid storage, and acid lateral distribution.

  9. Effects of fatty acids on benzo[a]pyrene uptake and metabolism in human lung adenocarcinoma A549 cells.

    PubMed

    Barhoumi, Rola; Mouneimne, Youssef; Chapkin, Robert S; Burghardt, Robert C

    2014-01-01

    Dietary supplementation with natural chemoprotective agents is receiving considerable attention because of health benefits and lack of toxicity. In recent in vivo and in vitro experimental studies, diets rich in n-3 polyunsaturated fatty acids have been shown to provide significant anti-tumor action. In this investigation, the effects of control fatty acids (oleic acid (OA), linoleic acid (LA)) and n-3 PUFA, e.g., docosahexaenoic acid (DHA) on the uptake and metabolism of the carcinogenic polycyclic aromatic hydrocarbon, benzo[a]pyrene (BaP) was investigated in A549 cells, a human adenocarcinoma alveolar basal epithelial cell line. A549 cells activate BaP through the cytochrome P450 enzyme system to form reactive metabolites, a few of which covalently bind to DNA and proteins. Therefore, multiphoton microscopy spectral analysis combined with linear unmixing was used to identify the parent compound and BaP metabolites formed in cells, in the presence and absence of fatty acids. The relative abundance of select metabolites was associated with altered P450 activity as determined using ethoxyresorufin-O-deethylase activity in cells cultured in the presence of BSA-conjugated fatty acids. In addition, the parent compound within cellular membranes increases significantly in the presence of each of the fatty acids, with the greatest accumulation observed following DHA treatment. DHA treated cells exhibit significantly lower pyrene-like metabolites indicative of lower adducts including DNA adducts compared to control BSA, OA or LA treated cells. Further, DHA reduced the abundance of the proximate carcinogen BaP 7,8-dihydrodiol and the 3-hydroxybenzo[a]pyrene metabolites compared to other treatments. The significant changes in BaP metabolites in DHA treated cells may be mediated by the effects on the physicochemical properties of the membrane known to affect enzyme activity related to phase I and phase II metabolism. In summary, DHA is a highly bioactive chemo

  10. Technology development for phosphoric acid fuel cell powerplant (phase 2)

    NASA Technical Reports Server (NTRS)

    Christner, L.

    1979-01-01

    The status of technology for the manufacturing and testing of 1200 sq. cm cell materials, components, and stacks for on-site integrated energy systems is assessed. Topics covered include: (1) preparation of thin layers of silicon carbide; (2) definition and control schemes for volume changes in phosphoric acid fuel cells; (3) preparation of low resin content graphite phenolic resin composites; (4) chemical corrosion of graphite-phenolic resin composites in hot phosphoric acid; (5) analysis of electrical resistance of composite materials for fuel cells; and (6) fuel cell performance and testing.

  11. Novel efficient methods for measuring mesophyll anatomical characteristics from fresh thick sections using stereology and confocal microscopy: application on acid rain-treated Norway spruce needles.

    PubMed

    Albrechtová, Jana; Janácek, Jirí; Lhotáková, Zuzana; Radochová, Barbora; Kubínová, Lucie

    2007-01-01

    Recent design-based stereological methods that can be applied to thick sections cut in an arbitrary direction are presented and their implementation for measuring mesophyll anatomical characteristics is introduced. These methods use software-randomized virtual 3D probes, such as disector and fakir test probes, in stacks of optical sections acquired using confocal microscopy. They enable unbiased estimations of the mean mesophyll cell volume, mesophyll cell number in a needle, and for the first time an internal surface area of needles or other narrow leaves directly from the fresh tissue cross-sections cut using a hand microtome. Therefore, reliable results can be obtained much faster than when using a standard microtechnical preparation. The proposed methods were tested on Norway spruce needles affected for 1 year by acid rain treatment. The effect of acid rain resulted in changes of mesophyll parameters: the ratio of intercellular spaces per mesophyll cell volume increased, while needle internal surface area, total number of mesophyll cells, and number of mesophyll cells per unit volume of a needle decreased in the treated needles.

  12. Effects of oral eicosapentaenoic acid versus docosahexaenoic acid on human peripheral blood mononuclear cell gene expression

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have beneficial effects on inflammation and cardiovascular disease (CVD). Our aim was to assess the effect of a six-week supplementation with either olive oil, EPA, or DHA on gene expression in peripheral blood mononuclear cells (...

  13. Optical, morphology and electrical properties of In2O3 incorporating acid-treated single-walled carbon nanotubes based DSSC

    NASA Astrophysics Data System (ADS)

    Mahalingam, S.; Abdullah, H.; Ashaari, I.; Shaari, S.; Muchtar, A.

    2016-02-01

    This study focuses on the influence of an acid treatment process of single-walled carbon nanotubes (SWCNTs) in In2O3-based dye-sensitized solar cells (DSSCs). Pure In2O3, In2O3-SWCNTs with acid treatment and In2O3-SWCNTs without acid treatment were prepared using the sol-gel method via a spin coating technique annealed at 450 °C. The optical, morphology and electrical properties of the photoanodes were characterized by means of UV-Vis analysis, atomic force microscopy and field-emission scanning electron microscopy, and J-V curve measurements, respectively. The optical band gap obtained through UV-Vis analysis showed that the acid treatment process modified the band gap of the photoanode, which enhances the V oc of the DSSCs. In addition, In2O3-SWCNTs with acid treatment possess a porous structure that improves the power conversion efficiency (PCE) of the DSSCs. In addition, the diameter of acid-treated SWCNTs was reduced compared to pristine SWCNTs. In2O3-SWCNTs with acid treatment exhibited the highest PCE of 1.40% with J sc of 7.6 mA cm-2, V oc of 0.51 V, and fill factor of 0.36. The increment in V oc is due to the higher band gap obtained through the UV-Vis absorption spectrum. Moreover, In2O3-SWCNTs with acid treatment has a higher electron lifetime with a higher effective diffusion coefficient that slows down the recombination rate and speeds up the electron transport process.

  14. Regulation of vitamin D receptor expression by retinoic acid receptor alpha in acute myeloid leukemia cells.

    PubMed

    Marchwicka, Aleksandra; Cebrat, Małgorzata; Łaszkiewicz, Agnieszka; Śnieżewski, Łukasz; Brown, Geoffrey; Marcinkowska, Ewa

    2016-05-01

    Acute myeloid leukemia (AML) is the predominant acute leukemia among adults, characterized by an accumulation of malignant immature myeloid precursors. A very promising way to treat AML is differentiation therapy using either all-trans-retinoic acid (ATRA) or 1,25-dihydroxyvitamin D3 (1,25D), or the use of both these differentiation-inducing agents. However, the effect of combination treatment varies in different AML cell lines, and this is due to ATRA either down- or up-regulating transcription of vitamin D receptor (VDR) in the cells examined. The mechanism of transcriptional regulation of VDR in response to ATRA has not been fully elucidated. Here, we show that the retinoic acid receptor α (RARα) is responsible for regulating VDR transcription in AML cells. We have shown that a VDR transcriptional variant, originating in exon 1a, is regulated by RARα agonists in AML cells. Moreover, in cells with a high basal level of RARα protein, the VDR gene is transcriptionally repressed as long as RARα agonist is absent. In these cells down-regulation of the level of RARα leads to increased expression of VDR. We consider that our findings provide a mechanistic background to explain the different outcomes from treating AML cell lines with a combination of ATRA and 1,25D. PMID:26969398

  15. Retinoic acid synergizes ATO-mediated cytotoxicity by precluding Nrf2 activity in AML cells

    PubMed Central

    Valenzuela, M; Glorieux, C; Stockis, J; Sid, B; Sandoval, J M; Felipe, K B; Kviecinski, M R; Verrax, J; Calderon, P Buc

    2014-01-01

    Background: Standard therapy for acute promyelocytic leukaemia (APL) includes retinoic acid (all-trans retinoic acid (ATRA)), which promotes differentiation of promyelocytic blasts. Although co-administration of arsenic trioxide (ATO) with ATRA has emerged as an effective option to treat APL, the molecular basis of this effect remains unclear. Methods: Four leukaemia cancer human models (HL60, THP-1, NBR4 and NBR4-R2 cells) were treated either with ATO alone or ATO plus ATRA. Cancer cell survival was monitored by trypan blue exclusion and DEVDase activity assays. Gene and protein expression changes were assessed by RT-PCR and western blot. Results: ATO induced an antioxidant response characterised by Nrf2 nuclear translocation and enhanced transcription of downstream target genes (that is, HO-1, NQO1, GCLM, ferritin). In cells exposed to ATO plus ATRA, the Nrf2 nuclear translocation was prevented and cytotoxicity was enhanced. HO-1 overexpression reversed partially the cytotoxicity by ATRA-ATO in HL60 cells. The inhibitory effects of ATRA on ATO-mediated responses were not observed in either the ATRA-resistant NB4-R2 cells or in NB4 cells pre-incubated with the RARα antagonist Ro-41-52-53. Conclusions: The augmented cytotoxicity observed in leukaemia cells following combined ATO-ATRA treatment is likely due to inhibition of Nrf2 activity, thus explaining the efficacy of combined ATO-ATRA treatment in the APL therapy. PMID:25003661

  16. Identification of sialic acids on the cell surface of Candida albicans.

    PubMed

    Soares, R M; de A Soares, R M; Alviano, D S; Angluster, J; Alviano, C S; Travassos, L R

    2000-04-01

    The cell-surface expression of sialic acids in two isolates of Candida albicans was analyzed by thin-layer and gas chromatography, binding of lectins, colorimetry, sialidase treatment and flow cytofluorimetry with fluorescein-labeled lectins. N-acetylneuraminic acid (NANA) was the only derivative found in both strains of C. albicans grown in a chemically defined medium. Its identification was confirmed by mass spectrometry in comparison with an authentic standard. The density of sialic acid residues per cell ranged from 1. 6x10(6) to 2.8x10(6). The surface distribution of sialic acids over the entire C. albicans was inferred from labeling with fluorescein-Limulus polyphemus and Limax flavus agglutinins and directly observed by optical microscopy with (FITC)-Sambucus nigra agglutinin (SNA), abrogated by previous treatment of yeasts with bacterial sialidase. Sialidase-treated yeasts generated beta-galactopyranosyl terminal residues that reacted with peanut agglutinin. In C. albicans N-acetyl-neuraminic acids are alpha2,6- and alpha2,3-linked as indicated by yeast binding to SNA and Maackia amurensis agglutinin. The alpha2,6-linkage clearly predominated in both strains. We also investigated the contribution of sialic acids to the electronegativity of C. albicans, an important factor determining fungal interactions in vivo. Adhesion of yeast cells to a cationic solid phase substrate (poly-L-lysine) was mediated in part by sialic acids, since the number of adherent cells was significantly reduced after treatment with bacterial sialidase. The present evidence adds C. albicans to the list of pathogenic fungi that synthesize sialic acids, which contribute to the negative charge of fungal cells and have a role in their specific interaction with the host tissue.

  17. The effect of propionic acid and valeric acid on the cell cycle in root meristems of Pisum sativum

    SciTech Connect

    Tramontano, W.A.; Yang, Shauyu; Delillo, A.R. )

    1990-01-01

    Propionic acid and valeric acid at 1mM reduced the mitotic index of root meristem cells of Pisum sativum to < 1% after 12 hr in aerated White's medium. This effect varied with different acid concentrations. After a 12 hr exposure to either acid, seedlings transferred to fresh medium without either acid, resumed their normal mitotic index after 12 hr, with a burst of mitosis 8 hr post-transfer. Exposure of root meristem cells to either acid also inhibited ({sup 3}H)-TdR incorporation. Neither acid significantly altered the distribution of meristematic cells in G1 and G2 after 12 hr. The incorporation of ({sup 3}H) - uridine was also unaltered by the addition of either acid. This information suggests that propionic acid and valeric acid, limit progression through the cell cycle by inhibiting DNA synthesis and arresting cells in G1 and G2. These results were consistent with previous data which utilized butyric acid.

  18. Enhanced replication of UV-damaged Simian virus 40 DNA in carcinogen-treated mammalian cells

    SciTech Connect

    Maga, J.A.

    1983-01-01

    The replication of UV-damaged Simian virus 40 (SV40) in carcinogen-treated monkey cells has been studied to elucidate the mechanism of carcinogen-enhanced reactivation. Carcinogen enhanced reactivation is the observed increase in UV-irradiated virus survival in host cells treated with low doses of carcinogen compared to UV-irradiated virus survival in untreated hosts. Carcinogen treatment of monkey kidney cells with either N-acetoxy-2-acetylaminofluorene (AAAF) or UV radiation leads to an enhanced capacity to replicate UV-damaged virus during the first round of infection. To further define the mechanism leading to enhanced replication, a detailed biochemical analysis of replication intermediates in carcinogen-treated cells was performed. Several conclusions can be drawn. First enhanced replication can be observed in the first four rounds of replication after UV irradiation of viral templates. The second major finding is that the relaxed circular intermediate model proposed for the replication of UV-damaged templates in untreated cells appears valid for replication of UV-damaged templates in carcinogen-treated cells. Possible mechanisms and the supporting evidence are discussed and future experiments outlined.

  19. The serologic behaviour of neuraminidase-treated lymphoid cells: alloantigenicity and complement sensitivity

    PubMed Central

    Ray, P. K.; Gewurz, H.; Simmons, R. L.

    1972-01-01

    Vibrio cholerae neuraminidase (VCN) renders mouse lymphoid cells highly susceptible to the cytolytic effects of alloantibody and complement (C). This increased susceptibility to lysis is not due to unmasking of alloantigens since no increase in alloantibody-binding capacity of VCN-treated cells could be detected. However, VCN-treated cells can be lysed by normal rabbit serum, human serum, and guinea-pig serum even if specific antibody is not added to the incubation mixture. VCN, therefore, while not unmasking strong H-2 histocompatibility antigens, may be capable of unmasking other antigens with which heterologous sera can react. The increased susceptibility to immune cytolysis of VCN-treated cells appears to be related, at least partially, to its extreme susceptibility to C. Complement inactivation by heat totally abrogated the lytic effect, as did C inactivation by ammonium hydroxide, viscarin, and zymosan. In addition, activation of the autologous serum C within the fluid phase by cobra venom factor produced cytolysis only in VCN-treated cells. Thus, VCN renders nucleated cells highly susceptible to lysis by C. PMID:5042921

  20. Decreased platelet membrane anisotropy in patients with adrenoleukodystrophy treated with erucic acid (22:1)-rich triglycerides.

    PubMed

    Stöckler, S; Opper, C; Greinacher, A; Hunneman, D H; Korenke, G C; Unkrig, C J; Hanefeld, F

    1997-03-01

    Low platelet count and bleeding diathesis have been observed in patients with adrenoleukodystrophy (ALD) treated with erucic acid (22:1)-rich triglycerides ("Lorenzo's oil'). To investigate possible alterations of biophysical membrane properties, we measured platelet membrane anisotropy, which is inversely related to membrane fluidity, in 16 patients with and in 3 patients without treatment. In patients on treatment, platelet membrane anisotropy was significantly decreased. Additionally, we found increased platelet concentrations of 22:1 and compromised in vitro platelet aggregation response. The decrease of platelet membrane anisotropy is probably a main cause of bleeding diathesis. Long-term haematological side-effects must be considered in ALD patients treated with Lorenzo's oil.

  1. Evaluation of STAT5A Gene Expression in Aflatoxin B1 Treated Bovine Mammary Epithelial Cells

    PubMed Central

    Forouharmehr, Ali; Harkinezhad, Taher; Qasemi-Panahi, Babak

    2013-01-01

    Purpose: Aflatoxin B1 (AFB1) is a potent mycotoxin which has been produced by fungi such as Aspergillus flavus and Aspergillus parasiticus as secondary metabolites due to their growth on food stuffs and induces hepatocellular carcinoma in many animal species, including humans. In the present study, the effect of AFB1 on STAT5A gene expression was investigated in bovine mammary epithelial cells using real time RT-PCR. Methods: Bovine mammary epithelial cells were seeded in a 24-well culture plate for three-dimensional (3D) culture in Matrigel matrix. After 21 days of 3D culture and reaching the required number of cells, cells were treated with AFB1 and incubated for 8 h. For real time PCR reaction, total RNA from the cultured and treated cells was extracted and used for complementary DNA synthesis. Results: The expression of STAT5A gene was significantly down regulated by AFB1 in dose- dependent manner and led to the reduction of proliferation and differentiation of epithelial cells, which has direct effect in milk protein quantity and quality. Conclusion: According to the results, it seems that down regulation of STAT5A gene in AFB1-treated cells maybe due to DNA damage induced by AFB1 in bovine mammary epithelial cells. PMID:24312879

  2. Immobilization of bioluminescent Escherichia coli cells using natural and artificial fibers treated with polyethyleneimine.

    PubMed

    Chu, Yi-Fang; Hsu, Chia-Hua; Soma, Pavan K; Lo, Y Martin

    2009-07-01

    Biosensors based on whole-cell bioluminescence have the potential to become a cost-effective alternative to conventional detection methods upon validation of target selectivity and sensitivity. However, quantitative analysis of bioluminescence is greatly hindered due to lack of control over the total number of cells in a suspending culture. In this study, the effect of surface properties of genetically engineered luminous E. coli cells and fibrous matrices on the immobilization capacity and effectiveness under various environmental conditions were characterized. Four different fibers, including cotton, polyester, viscose rayon, and silk, were investigated. Although cell adhesion was observed on untreated viscose and cotton fibers, viscose fiber pretreated with 0.667% polyethyleneimine (PEI) was found capable of immobilizing the most viable E. coli DPD2234 cells, followed by viscose treated with 0.33% and 1% PEI. The cells immobilized on PEI-treated viscose remained viable and yielded 20% or more bioluminescence signals immediately upon contact with the inducer up to 72 h without feeding nutrients to the cells, suggesting that viscose treated with 0.667% PEI could provide a stable immobilization mechanism for bioluminescent E. coli cells with long sensing period, quick response time, and good signal reproducibility.

  3. Carnosic Acid Inhibits the Epithelial-Mesenchymal Transition in B16F10 Melanoma Cells: A Possible Mechanism for the Inhibition of Cell Migration

    PubMed Central

    Park, So Young; Song, Hyerim; Sung, Mi-Kyung; Kang, Young-Hee; Lee, Ki Won; Park, Jung Han Yoon

    2014-01-01

    Carnosic acid is a natural benzenediol abietane diterpene found in rosemary and exhibits anti-inflammatory, antioxidant, and anti-carcinogenic activities. In this study, we evaluated the effects of carnosic acid on the metastatic characteristics of B16F10 melanoma cells. When B16F10 cells were cultured in an in vitro Transwell system, carnosic acid inhibited cell migration in a dose-dependent manner. Carnosic acid suppressed the adhesion of B16F10 cells, as well as the secretion of matrix metalloproteinase (MMP)-9, tissue inhibitor of metalloproteinase (TIMP)-1, urokinase plasminogen activator (uPA), and vascular cell adhesion molecule (VCAM)-1. Interestingly, secretion of TIMP-2 increased significantly in B16F10 cells treated with 10 μmol/L carnosic acid. Additionally, carnosic acid suppressed the mesenchymal markers snail, slug, vimentin, and N-cadherin and induced epithelial marker E-cadherin. Furthermore, carnosic acid suppressed phosphorylation of Src, FAK, and AKT. These results indicate that inhibition of the epithelial-mesenchymal transition may be important for the carnosic acid-induced inhibition of B16F10 cell migration. PMID:25036034

  4. Valproic acid affects the engraftment of TPO-expanded cord blood cells in NOD/SCID mice.

    PubMed

    Vulcano, Francesca; Milazzo, Luisa; Ciccarelli, Carmela; Barca, Alessandra; Agostini, Francesca; Altieri, Ilaria; Macioce, Giampiero; Di Virgilio, Antonio; Screnci, Maria; De Felice, Lidia; Giampaolo, Adele; Hassan, Hamisa Jane

    2012-02-15

    Hematopoietic stem and progenitor cells (HSPC) can improve the long-term outcome of transplanted individuals and reduce the relapse rate. Valproic acid (VPA), an inhibitor of histone deacetylase, when combined with different cytokine cocktails, induces the expansion of CD34+ cell populations derived from cord blood (CB) and other sources. We evaluated the effect of VPA, in combination with thrombopoietin (TPO), on the viability and expansion of CB-HSPCs and on short- and long-term engraftability in the NOD/SCID mouse model. In vitro, VPA+TPO inhibited HSPC differentiation and preserved the CD34+ cell fraction; the self-renewal of the CD34+ TPO+VPA-treated cells was suggested by the increased replating efficiency. In vivo, short- and long-term engraftment was determined after 6 and 20 weeks. After 6 weeks, the median chimerism percentage was 13.0% in mice transplanted with TPO-treated cells and only 1.4% in those transplanted with TPO+VPA-treated cells. By contrast, after 20 weeks, the engraftment induced by the TPO+VPA-treated cells was three times more effective than that induced by TPO alone, and over ten times more effective compared to the short-term engraftment induced by the TPO+VPA-treated cells. The in vivo results are consistent with the higher secondary plating efficiency of the TPO+VPA-treated cells in vitro. PMID:22166516

  5. Eicosapentaenoic acid inhibits voltage-gated sodium channels and invasiveness in prostate cancer cells

    PubMed Central

    Nakajima, T; Kubota, N; Tsutsumi, T; Oguri, A; Imuta, H; Jo, T; Oonuma, H; Soma, M; Meguro, K; Takano, H; Nagase, T; Nagata, T

    2009-01-01

    Background and purpose: The voltage-gated Na+ channels (Nav) and their corresponding current (INa) are involved in several cellular processes, crucial to metastasis of cancer cells. We investigated the effects of eicosapentaenoic (EPA), an omega-3 polyunsaturated fatty acid, on INa and metastatic functions (cell proliferation, endocytosis and invasion) in human and rat prostate cancer cell lines (PC-3 and Mat-LyLu cells). Experimental approach: The whole-cell voltage clamp technique and conventional/quantitative real-time reverse transcriptase polymerase chain reaction analysis were used. The presence of Nav proteins was shown by immunohistochemical methods. Alterations in the fatty acid composition of phospholipids after treatment with EPA and metastatic functions were also examined. Key results: A transient inward Na+ current (INa), highly sensitive to tetrodotoxin, and NaV proteins were found in these cells. Expression of NaV1.6 and NaV1.7 transcripts (SCN8A and SCN9A) was predominant in PC-3 cells, while NaV1.7 transcript (SCN9A) was the major component in Mat-LyLu cells. Tetrodotoxin or synthetic small interfering RNA targeted for SCN8A and SCN9A inhibited metastatic functions (endocytosis and invasion), but failed to inhibit proliferation in PC-3 cells. Exposure to EPA produced a rapid and concentration-dependent suppression of INa. In cells chronically treated (up to 72h) with EPA, the EPA content of cell lipids increased time-dependently, while arachidonic acid content decreased. Treatment of PC-3 cells with EPA decreased levels of mRNA for SCN9A and SCN8A, cell proliferation, invasion and endocytosis. Conclusion and implications: Treatment with EPA inhibited INa directly and also indirectly, by down-regulation of Nav mRNA expression in prostate cancer cells, thus inhibiting their metastatic potential. PMID:19154441

  6. Involvement of calreticulin in cell proliferation, invasion and differentiation in diallyl disulfide-treated HL-60 cells

    PubMed Central

    Yi, Lan; Shan, Jian; Chen, Xin; Li, Guoqing; Li, Linwei; Tan, Hui; Su, Qi

    2016-01-01

    Diallyl disulfide (DADS) has shown potential as a therapeutic agent in various cancers. Previously, calreticulin (CRT) was found to be downregulated in differentiated HL-60 cells treated with DADS. The present study investigated the role of CRT proteins in DADS-induced proliferation, invasion and differentiation in HL-60 cells. The present study demonstrated that DADS treatment significantly changed the morphology of HL-60 cells and caused the significant time-dependent downregulation of CRT. Small interfering RNA (siRNA)-mediated knockdown of CRT expression significantly inhibited proliferation, decreased invasion ability, increased the expression of cluster of differentiation (CD)11b and reduced the expression of CD33 in DADS-treated HL-60 cells. DADS also significantly affected cell proliferation, invasion and differentiation in CRT-overexpressed HL-60 cells. Nitroblue tetrazolium (NBT) reduction assays showed decreased NBT reduction activity in the CRT overexpression group and increased NBT reduction in the CRT siRNA group. Following treatment with DADS, the NBT reduction abilities in all groups were increased. In conclusion, the present study clearly demonstrates the downregulation of CRT during DADS-induced differentiation in HL-60 cells and indicates that CRT is involved in cell proliferation, invasion and differentiation in DADS-treated HL-60 cells. PMID:27588133

  7. Data in support of the bone analysis of NOD-SCID mice treated with zoledronic acid and prednisolone.

    PubMed

    Hori, Naoko; Abe, Takahiro; Sato, Tsuyoshi; Kokabu, Shoichiro; Shimamura, Yumiko; Sato, Tomoya; Yoda, Tetsuya

    2016-06-01

    This paper reports data on the bone, specifically the tibia and mandible, of nonobese diabetic mice with severe combined immunodeficiency disease (NOD-SCID mice) treated with zoledronic acid (ZA) and prednisolone (PSL). The data described here are related to the research article titled "Zoledronic acid basically increases circulating soluble RANKL level in mice, and in glucocorticoid-administrated mice, more increases lymphocytes derived sRANKL by bacterial endotoxic stimuli" [1]. The present data and the NOD-SCID mice experiments described contain insights into the role of bone-remodeling factors induced by ZA treatment.

  8. [The role and limitations of litholytic therapy of cholesterin cholecystolithiasis. Results in 86 cases treated with chenic acid].

    PubMed

    Mortola, G P; Anfossi, A; Parodi, E; Cafiero, F; Pezzoli, F; Berti Riboli, E

    1980-09-01

    86 carefully selected patients with cholesterinic cholecystic lithiasis were submitted to litholytic treatment with chenodesoxycholic acid at a dose of 15 mg per kg of body weight as part of a multidisciplinary therapeutic approach to biliary lithiasis. Follow up of these patients up to 24 months showed the positive action of the drug on dyspeptic pain symptomatology, the absence of significant side effects, and the absence of hepatotoxic effects of chenic acid at therapeutic doses, as well as its effectiveness with respect to total or partial litholysis in 78% of patients. These data confirm the positive role of litholytic treatment as an alternative to cholecystectomy in highly selected patients treated at specialist centres.

  9. Generation and Feasibility Assessment of a New Vehicle for Cell-Based Therapy for Treating Corneal Endothelial Dysfunction.

    PubMed

    Okumura, Naoki; Kakutani, Kazuya; Inoue, Ryota; Matsumoto, Daiki; Shimada, Tomoki; Nakahara, Makiko; Kiyanagi, Yumiko; Itoh, Takehiro; Koizumi, Noriko

    2016-01-01

    The corneal endothelium maintains corneal transparency by its pump and barrier functions; consequently, its decompensation due to any pathological reason causes severe vision loss due to corneal haziness. Corneal transplantation is the only therapeutic choice for treating corneal endothelial dysfunction, but associated problems, such as a shortages of donor corneas, the difficulty of the surgical procedure, and graft failure, still need to be resolved. Regenerative medicine is attractive to researchers as a means of providing innovative therapies for corneal endothelial dysfunction, as it now does for other diseases. We previously demonstrated the successful regeneration of corneal endothelium in animal models by injecting cultured corneal endothelial cells (CECs) in combination with a Rho kinase (ROCK) inhibitor. The purpose of the present study was to optimize the vehicle for clinical use in cell-based therapy. Our screening of cell culture media revealed that RELAR medium promoted CEC adhesion. We then modified RELAR medium by removing hormones, growth factors, and potentially toxic materials to generate a cell therapy vehicle (CTV) composed of amino acid, salts, glucose, and vitamins. Injection of CECs in CTV enabled efficient engraftment and regeneration of the corneal endothelium in the rabbit corneal endothelial dysfunction model, with restoration of a transparent cornea. The CECs retained >85% viability after a 24 hour preservation as a cell suspension in CTV at 4°C and maintained their potency to regenerate the corneal endothelium in vivo. The vehicle developed here is clinically applicable for cell-based therapy aimed at treating the corneal endothelium. Our strategy involves the generation of vehicle from a culture medium appropriate for a given cell type by removing materials that are not favorable for clinical use. PMID:27355373

  10. Generation and Feasibility Assessment of a New Vehicle for Cell-Based Therapy for Treating Corneal Endothelial Dysfunction

    PubMed Central

    Okumura, Naoki; Kakutani, Kazuya; Inoue, Ryota; Matsumoto, Daiki; Shimada, Tomoki; Nakahara, Makiko; Kiyanagi, Yumiko; Itoh, Takehiro; Koizumi, Noriko

    2016-01-01

    The corneal endothelium maintains corneal transparency by its pump and barrier functions; consequently, its decompensation due to any pathological reason causes severe vision loss due to corneal haziness. Corneal transplantation is the only therapeutic choice for treating corneal endothelial dysfunction, but associated problems, such as a shortages of donor corneas, the difficulty of the surgical procedure, and graft failure, still need to be resolved. Regenerative medicine is attractive to researchers as a means of providing innovative therapies for corneal endothelial dysfunction, as it now does for other diseases. We previously demonstrated the successful regeneration of corneal endothelium in animal models by injecting cultured corneal endothelial cells (CECs) in combination with a Rho kinase (ROCK) inhibitor. The purpose of the present study was to optimize the vehicle for clinical use in cell-based therapy. Our screening of cell culture media revealed that RELAR medium promoted CEC adhesion. We then modified RELAR medium by removing hormones, growth factors, and potentially toxic materials to generate a cell therapy vehicle (CTV) composed of amino acid, salts, glucose, and vitamins. Injection of CECs in CTV enabled efficient engraftment and regeneration of the corneal endothelium in the rabbit corneal endothelial dysfunction model, with restoration of a transparent cornea. The CECs retained >85% viability after a 24 hour preservation as a cell suspension in CTV at 4°C and maintained their potency to regenerate the corneal endothelium in vivo. The vehicle developed here is clinically applicable for cell-based therapy aimed at treating the corneal endothelium. Our strategy involves the generation of vehicle from a culture medium appropriate for a given cell type by removing materials that are not favorable for clinical use. PMID:27355373

  11. Surface properties and early murine pre-osteoblastic cell responses of phosphoric acid modified titanium surface

    PubMed Central

    Osathanon, Thanaphum; Sawangmake, Chenphop; Ruangchainicom, Nanticha; Wutikornwipak, Pavitra; Kantukiti, Panisa; Nowwarote, Nunthawan; Pavasant, Prasit

    2015-01-01

    Aims The present study investigated the surface properties and murine pre-osteoblast cell (MC3T3-E1) responses of phosphoric acid (H3PO4) treated commercially pure titanium. Methods Titanium discs were treated with various concentration of H3PO4 (5%, 10%, and 20%; v/v) at 90 °C for 30 min. Surface properties were evaluated by profilometer, contact angle meter, and scanning electron microscopy (SEM) with energy dispersive X-rays. MC3T3-E1 attachment and spreading were evaluated by SEM and phalloidin immunohistochemistry staining. Results Surface roughness and wettability were not statistically difference among all experimental and control groups. Phosphate and oxygen were detected on H3PO4 treated surfaces. At 20 min, cell attachment was significantly higher in 10% and 20% H3PO4 treated groups compared to the control. Cells exhibited orientated-cytoskeleton fibers on 20% H3PO4 modified titanium surface. Though, there was no difference in cell spreading stage among all treatment groups. Conclusion H3PO4 treatment on titanium may influence early cell response, particularly on attachment and spreading. PMID:26937362

  12. Expanding the diversity of unnatural cell surface sialic acids

    SciTech Connect

    Luchansky, Sarah J.; Goon, Scarlett; Bertozzi, Carolyn R.

    2003-10-30

    Novel chemical reactivity can be introduced onto cell surfaces through metabolic oligosaccharide engineering. This technique exploits the substrate promiscuity of cellular biosynthetic enzymes to deliver unnatural monosaccharides bearing bioorthogonal functional groups into cellular glycans. For example, derivatives of N-acetylmannosamine (ManNAc) are converted by the cellular biosynthetic machinery into the corresponding sialic acids and subsequently delivered to the cell surface in the form of sialoglycoconjugates. Analogs of N-acetylglucosamine (GlcNAc) and N-acetylgalactosamine (GalNAc) are also metabolized and incorporated into cell surface glycans, likely through the sialic acid and GalNAc salvage pathways, respectively. Furthermore, GlcNAc analogs can be incorporated into nucleocytoplasmic proteins in place of {beta}-O-GlcNAc residues. These pathways have been exploited to integrate unique electrophiles such as ketones and azides into the target glycoconjugate class. These functional groups can be further elaborated in a chemoselective fashion by condensation with hydrazides and by Staudinger ligation, respectively, thereby introducing detectable probes onto the cell. In conclusion, sialic acid derivatives are efficient vehicles for delivery of bulky functional groups to cell surfaces and masking of their hydroxyl groups improves their cellular uptake and utilization. Furthermore, the successful introduction of photoactivatable aryl azides into cell surface glycans opens up new avenues for studying sialic acid-binding proteins and elucidating the role of sialic acid in essential processes such as signaling and cell adhesion.

  13. Subcellular SIMS imaging of isotopically labeled amino acids in cryogenically prepared cells

    NASA Astrophysics Data System (ADS)

    Chandra, Subhash

    2004-06-01

    Ion microscopy is a potentially powerful technique for localization of isotopically labeled molecules. In this study, L-arginine and phenylalanine amino acids labeled with stable isotopes 13C and 15N were localized in cultured cells with the ion microscope at 500 nm spatial resolution. Cells were exposed to the labeled amino acids and cryogenically prepared. SIMS analyses were made in fractured freeze-dried cells. A dynamic distribution was observed from labeled arginine-treated LLC-PK 1 kidney cells at mass 28 ( 13C15N) in negative secondaries, revealing cell-to-cell heterogeneity and preferential accumulation of the amino acid (or its metabolite) in the nucleus and nucleolus of some cells. The smaller nucleolus inside the nucleus was clearly resolved in SIMS images and confirmed by correlative light microscopy. The distribution of labeled phenylalanine contrasted with arginine as it was rather homogeneously distributed in T98G human glioblastoma cells. Images of 39K, 23Na and 40Ca were also recorded to confirm the reliability of sample preparation and authenticity of the observed amino acid distributions. These observations indicate that SIMS techniques can provide a valuable technology for subcellular localization of nitrogen-containing molecules in proteomics since nitrogen does not have a radionuclide tracer isotope. Amino acids labeled with stable isotopes can be used as tracers for studying their transport and metabolism in distinct subcellular compartments with SIMS. Further studies of phenylalanine uptake in human glioblastoma cells may have special significance in boron neutron capture therapy (BNCT) as a boron analogue of phenylalanine, boronophenylalanine is a clinically approved compound for the treatment of brain tumors.

  14. Virus-specific RNA synthesis in interferon-treated mouse cells productively infected with Moloney murine leukemia virus.

    PubMed Central

    Fan, H; MacIsaac, P

    1978-01-01

    Mouse cells productively infected with Moloney murine leukemia virus were treated with interferon, and intracellular virus-specific RNA was studied by hybridization with complementary DNA. The steady-state concentration of virus-specific RNA in interferon-treated cells was somewhat greater than that in untreated cells, and the rates of virus-specific RNA synthesis were approximately equal in treated and untreated cells. PMID:691118

  15. Anticarcinogenic properties of medium chain fatty acids on human colorectal, skin and breast cancer cells in vitro.

    PubMed

    Narayanan, Amoolya; Baskaran, Sangeetha Ananda; Amalaradjou, Mary Anne Roshni; Venkitanarayanan, Kumar

    2015-03-05

    Colorectal cancer, breast cancer and skin cancer are commonly-reported cancer types in the U.S. Although radiation and chemotherapy are routinely used to treat cancer, they produce side effects in patients. Additionally, resistance to chemotherapeutic drugs has been noticed in cancers. Thus, there is a need for effective and safe bioprophylactics and biotherapeutics in cancer therapy. The medicinal value of goat milk has been recognized for centuries and is primarily attributed to three fatty acids, namely capric, caprylic and caproic acids. This research investigates the anticancer property of these fatty acids on human colorectal, skin and mammary gland cancer cells. The cancer cells were treated with various concentrations of fatty acids for 48 h, and cell viability was monitored by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. Additionally, real-time quantitative PCR (RT-qPCR) was performed to elucidate the potential anti-cancer mechanisms of the three fatty acids under investigation. Capric, caprylic and caproic acids reduced cancer cell viability by 70% to 90% (p < 0.05) compared to controls. RT-qPCR data indicated that these natural molecules produced anticancer effects by down-regulating cell cycle regulatory genes and up-regulating genes involved in apoptosis. Future research will validate the anticancer effect of these fatty acids in an appropriate in vivo model.

  16. Anticarcinogenic Properties of Medium Chain Fatty Acids on Human Colorectal, Skin and Breast Cancer Cells in Vitro

    PubMed Central

    Narayanan, Amoolya; Ananda Baskaran, Sangeetha; Amalaradjou, Mary Anne Roshni; Venkitanarayanan, Kumar

    2015-01-01

    Colorectal cancer, breast cancer and skin cancer are commonly-reported cancer types in the U.S. Although radiation and chemotherapy are routinely used to treat cancer, they produce side effects in patients. Additionally, resistance to chemotherapeutic drugs has been noticed in cancers. Thus, there is a need for effective and safe bioprophylactics and biotherapeutics in cancer therapy. The medicinal value of goat milk has been recognized for centuries and is primarily attributed to three fatty acids, namely capric, caprylic and caproic acids. This research investigates the anticancer property of these fatty acids on human colorectal, skin and mammary gland cancer cells. The cancer cells were treated with various concentrations of fatty acids for 48 h, and cell viability was monitored by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. Additionally, real-time quantitative PCR (RT-qPCR) was performed to elucidate the potential anti-cancer mechanisms of the three fatty acids under investigation. Capric, caprylic and caproic acids reduced cancer cell viability by 70% to 90% (p < 0.05) compared to controls. RT-qPCR data indicated that these natural molecules produced anticancer effects by down-regulating cell cycle regulatory genes and up-regulating genes involved in apoptosis. Future research will validate the anticancer effect of these fatty acids in an appropriate in vivo model. PMID:25749477

  17. Nuclear CD38 in retinoic acid-induced HL-60 cells

    SciTech Connect

    Yalcintepe, Leman . E-mail: lemany@istanbul.edu.tr; Albeniz, Isil; Adin-Cinar, Suzan; Tiryaki, Demir; Bermek, Engin; Graeff, Richard M.; Lee, Hon Cheung

    2005-02-01

    The cell surface antigen, CD38, is a 45-kDa transmembrane protein which is predominantly expressed on hematopoietic cells during differentiation. As a bifunctional ectoenzyme, it catalyzes the synthesis of cyclic ADP-ribose (cADPR) from NAD{sup +} and hydrolysis of either NAD{sup +} or cADPR to ADP-ribose. All-trans-retinoic acid (RA) is a potent and specific inducer of CD38 in myeloid cells. In this report, we demonstrate that the nuclei of RA-treated human HL-60 myeloblastic cells reveal enzymatic activities inherent to CD38. Thus, GDP-ribosyl cyclase and NAD{sup +} glycohydrolase activities in the nuclear fraction increased very significantly in response to incubation with RA. With Western blotting, we detected in the nuclear protein fraction from RA-treated cells a {approx}43-kDa protein band which was reactive with the CD38-specific monoclonal antibody OKT10. The expression of CD38 in HL-60 nuclei was also shown with FACScan analysis. RA treatment gave rise to an increase in in vitro ADP ribosylation of the {approx}43-kDa nuclear protein. Moreover, nuclei isolated from RA-treated HL-60 cells revealed calcium release in response to cADPR, whereas a similar response was not observed in control nuclei. These results suggest that CD38 is expressed in HL-60 cell nuclei during RA-induced differentiation.

  18. Technology Development for Phosphoric Acid Fuel Cell Powerplant, Phase 2

    NASA Technical Reports Server (NTRS)

    Christner, L.

    1980-01-01

    The technology development for materials, cells, and reformers for on site integrated energy systems is described. The carbonization of 25 cu cm, 350 cu cm, and 1200 cu cm cell test hardware was accomplished and the performance of 25 cu cm fuel cells was improved. Electrochemical corrosion rates of graphite/phenolic resin composites in phosphoric acid were determined. Three cells (5 in by 15 in stacks) were operated for longer than 7000 hours. Specified endurance stacks completed a total of 4000 hours. An electrically heated reformer was tested and is to provide hydrogen for 23 cell fuel cell stack.

  19. Etanercept in Treating Young Patients With Idiopathic Pneumonia Syndrome After Undergoing a Donor Stem Cell Transplant

    ClinicalTrials.gov

    2016-02-23

    Accelerated Phase Chronic Myelogenous Leukemia; Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Disseminated Neuroblastoma; Juvenile Myelomonocytic Leukemia; Previously Treated Childhood Rhabdomyosarcoma; Previously Treated Myelodysplastic Syndromes; Pulmonary Complications; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Neuroblastoma; Recurrent Wilms Tumor and Other Childhood Kidney Tumors; Recurrent/Refractory Childhood Hodgkin Lymphoma; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

  20. Improvement of Liver Cell Therapy in Rats by Dietary Stearic Acid

    PubMed Central

    Goradel, Nasser Hashemi; Eghbal, Mohammad Ali; Darabi, Masoud; Roshangar, Leila; Asadi, Maryam; Zarghami, Nosratollah; Nouri, Mohammad

    2016-01-01

    Background: Stearic acid is known as a potent anti-inflammatory lipid. This fatty acid has profound and diverse effects on liver metabolism. The aim of this study was to investigate the effect of stearic acid on markers of hepatocyte transplantation in rats with acetaminophen (APAP)-induced liver damage. Methods: Wistar rats were randomly assigned to 10-day treatment. Stearic acid was administered to the rats with APAP-induced liver damage. The isolated liver cells were infused intraperitoneally into rats. Blood samples were obtained to evaluate the changes in the serum liver enzymes, including activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) and the level of serum albumin. To assess the engraftment of infused hepatocytes, rats were euthanized, and the liver DNA was used for PCR using sex-determining region Y (SRY) primers. Results: The levels of AST, ALT and ALP in the serum of rats with APAP-induced liver injury were significantly increased and returned to the levels in control group by day six. The APAP-induced decrease in albumin was significantly improved in rats through cell therapy, when compared with that in the APAP-alone treated rats. SRY PCR analysis showed the presence of the transplanted cells in the liver of transplanted rats. Conclusion: Stearic acid-rich diet in combination with cell therapy accelerates the recovering of hepatic dysfunction in a rat model of liver injury. PMID:27090202

  1. Epoxyeicosatrienoic Acids Affect Electrolyte Transport in Renal Tubular Epithelial Cells: Dependence on Cyclooxygenase and Cell Polarity

    PubMed Central

    Nüsing, Rolf M.; Schweer, Horst; Fleming, Ingrid; Zeldin, Darryl C.; Wegmann, Markus

    2007-01-01

    We investigated the effects of epoxyeicosatrienoic acids (EETs) on ion transport in the polarized renal distal tubular cell line, MDCK C7. Of the four EET regioisomers (5,6-EET, 8,9-EET, 11,12-EET, and 14,15-EET) studied, only apical, but not basolateral, application of 5,6-EET increased short circuit current (Isc) with kinetics similar to those of arachidonic acid. The ion transport was blocked by preincubation with the cyclooxygenase inhibitor indomethacin or with the chloride channel blocker NPPB. Further, both a Cl−-free bath solution and the Ca2+ antagonist verapamil blocked 5,6-EET-induced ion transport. Although the presence of the PGE2 receptors EP2, EP3, and EP4 was demonstrated, apically added PGE2 was ineffective and basolaterally added PGE2 caused a different kinetics in ion transport compared to 5,6-EET. Moreover, PGE2 sythesis in MDCK C7 cells was unaffected by 5,6-EET treatment. GC/MS/MS analysis of cell supernatants revealed the presence of the biologically inactive 5,6-dihydroxy-PGE1 in 5,6-EET-treated cells, but not in control cells. Indomethacin suppressed the formation of 5,6-dihydroxy-PGE1. 5,6-epoxy-PGE1 the precursor of 5,6-dihydroxy-PGE1, caused a similar ion transport as 5,6-EET. Cytochrome P450 enzymes homolog to human CYP2C8, CYP2C9, and CYP2J2 protein were detected immunologically in the MDCK C7 cells. Our findings suggest that 5,6-EET affects Cl-transport in renal distal tubular cells independent of PGE2 but by a mechanism, dependent on its conversion to 5,6-epoxy-PGE1 by cyclooxygenase. We suggest a role for this P450 epoxygenase product in the regulation of electrolyte transport, especially as a saluretic compound acting from the luminal side of tubular cells in the mammalian kidney. PMID:17494091

  2. Bile acids induce hepatic differentiation of mesenchymal stem cells

    PubMed Central

    Sawitza, Iris; Kordes, Claus; Götze, Silke; Herebian, Diran; Häussinger, Dieter

    2015-01-01

    Mesenchymal stem cells (MSC) have the potential to differentiate into multiple cell lineages and their therapeutic potential has become obvious. In the liver, MSC are represented by stellate cells which have the potential to differentiate into hepatocytes after stimulation with growth factors. Since bile acids can promote liver regeneration, their influence on liver-resident and bone marrow-derived MSC was investigated. Physiological concentrations of bile acids such as tauroursodeoxycholic acid were able to initiate hepatic differentiation of MSC via the farnesoid X receptor and transmembrane G-protein-coupled bile acid receptor 5 as investigated with knockout mice. Notch, hedgehog, transforming growth factor-β/bone morphogenic protein family and non-canonical Wnt signalling were also essential for bile acid-mediated differentiation, whereas β-catenin-dependent Wnt signalling was able to attenuate this process. Our findings reveal bile acid-mediated signalling as an alternative way to induce hepatic differentiaion of stem cells and highlight bile acids as important signalling molecules during liver regeneration. PMID:26304833

  3. Treating cancer stem cells and cancer metastasis using glucose-coated gold nanoparticles.

    PubMed

    Hu, Chenxia; Niestroj, Martin; Yuan, Daniel; Chang, Steven; Chen, Jie

    2015-01-01

    Cancer ranks among the leading causes of human mortality. Cancer becomes intractable when it spreads from the primary tumor site to various organs (such as bone, lung, liver, and then brain). Unlike solid tumor cells, cancer stem cells and metastatic cancer cells grow in a non-attached (suspension) form when moving from their source to other locations in the body. Due to the non-attached growth nature, metastasis is often first detected in the circulatory systems, for instance in a lymph node near the primary tumor. Cancer research over the past several decades has primarily focused on treating solid tumors, but targeted therapy to treat cancer stem cells and cancer metastasis has yet to be developed. Because cancers undergo faster metabolism and consume more glucose than normal cells, glucose was chosen in this study as a reagent to target cancer cells. In particular, by covalently binding gold nanoparticles (GNPs) with thio-PEG (polyethylene glycol) and thio-glucose, the resulting functionalized GNPs (Glu-GNPs) were created for targeted treatment of cancer metastasis and cancer stem cells. Suspension cancer cell THP-1 (human monocytic cell line derived from acute monocytic leukemia patients) was selected because it has properties similar to cancer stem cells and has been used as a metastatic cancer cell model for in vitro studies. To take advantage of cancer cells' elevated glucose consumption over normal cells, different starvation periods were screened in order to achieve optimal treatment effects. Cancer cells were then fed using Glu-GNPs followed by X-ray irradiation treatment. For comparison, solid tumor MCF-7 cells (breast cancer cell line) were studied as well. Our irradiation experimental results show that Glu-GNPs are better irradiation sensitizers to treat THP-1 cells than MCF-7 cells, or Glu-GNPs enhance the cancer killing of THP-1 cells 20% more than X-ray irradiation alone and GNP treatment alone. This finding can help oncologists to design

  4. Low contaminant formic acid fuel for direct liquid fuel cell

    DOEpatents

    Masel, Richard I.; Zhu, Yimin; Kahn, Zakia; Man, Malcolm

    2009-11-17

    A low contaminant formic acid fuel is especially suited toward use in a direct organic liquid fuel cell. A fuel of the invention provides high power output that is maintained for a substantial time and the fuel is substantially non-flammable. Specific contaminants and contaminant levels have been identified as being deleterious to the performance of a formic acid fuel in a fuel cell, and embodiments of the invention provide low contaminant fuels that have improved performance compared to known commercial bulk grade and commercial purified grade formic acid fuels. Preferred embodiment fuels (and fuel cells containing such fuels) including low levels of a combination of key contaminants, including acetic acid, methyl formate, and methanol.

  5. Gene therapy strategies using engineered stem cells for treating gynecologic and breast cancer patients (Review).

    PubMed

    Kim, Ye-Seul; Hwang, Kyung-A; Go, Ryeo-Eun; Kim, Cho-Won; Choi, Kyung-Chul

    2015-05-01

    There are three types of stem cells: embryonic stem (ES) cells, adult stem (AS) cells and induced pluripotent stem (iPS) cells. These stem cells have many benefits including the potential ability to differentiate into various organs. In addition, engineered stem cells (GESTECs) designed for delivering therapeutic genes may be capable of treating human diseases including malignant cancers. Stem cells have been found to possess the potential for serving as novel delivery vehicles for therapeutic or suicide genes to primary or metastatic cancer formation sites as a part of gene-directed enzyme/prodrug combination therapy (GEPT). Given the advantageous properties of stem cells, tissue-derived stem cells are emerging as a new tool for anticancer therapy combined with prodrugs. In this review, the effects of GESTECs with different origins, i.e., neural, amniotic membrane and amniotic fluid, introduced to treat patients with diverse types of gynecologic and breast cancers are discussed. Data from the literature indicate the therapeutic potential of these cells as a part of gene therapy strategies to selectively target malignancies in women at clinically terminal stages.

  6. Gibberellic-acid-induced cell elongation in pea epicotyls: Effect on polyploidy and DNA content.

    PubMed

    Boeken, G; Van Oostveldt, P

    1977-01-01

    In gibberellic-acid(GA3)-treated epicotyls of dwarf peas (Pisum sativum L.) grown in the light, DNA (per cell and per epicotyl) is followed. Histofluorometric DNA determinations show that GA3-promoted cell elongation is not accompanied by increased endomitosis, but chemical estimations show an increased DNA content per epicotyl. This difference must therefore be the result of increased mitotic activity in the GA3-treated tissue. Epicotyls of seedlings grown with or without cotyledons under continuous light with GA3 are tetraploid, as are those of ecotylized embryos grown in darkness. These epicotyls reach no more than half the length of octaploid epicotyls of seedlings grown in darkness. This result provides evidence for a relationship between polyploidy and final possible cell length. PMID:24419898

  7. A report of two cases of chronic serious manganese poisoning treated with sodium para-aminosalicylic acid.

    PubMed Central

    Ky, S Q; Deng, H S; Xie, P Y; Hu, W

    1992-01-01

    Two cases of chronic manganese poisoning were treated with sodium para-aminosalicylic acid (PAS-Na; 6 g/day in 500 ml of 10% glucose solution by intravenous drip). The results indicated that one had been clinically cured and that the other had obviously improved in clinical symptoms and signs. Thus PAS-Na appears to be an effective drug for treatment of serious chronic manganese poisoning. Images PMID:1733459

  8. Salvianolic Acid B Prevents Bone Loss in Prednisone-Treated Rats through Stimulation of Osteogenesis and Bone Marrow Angiogenesis

    PubMed Central

    Cui, Liao; Li, Ting; Liu, Yuyu; Zhou, Le; Li, Pinghua; Xu, Bilian; Huang, Lianfang; Chen, Yan; Liu, Yanzhi; Tian, Xiaoyan; Jee, Webster S. S.; Wu, Tie

    2012-01-01

    Glucocorticoid (GC) induced osteoporosis (GIO) is caused by the long-term use of GC for treatment of autoimmune and inflammatory diseases. The GC related disruption of bone marrow microcirculation and increased adipogenesis contribute to GIO development. However, neither currently available anti-osteoporosis agent is completely addressed to microcirculation and bone marrow adipogenesis. Salvianolic acid B (Sal B) is a polyphenolic compound from a Chinese herbal medicine, Salvia miltiorrhiza Bunge. The aim of this study was to determine the effects of Sal B on osteoblast bone formation, angiogenesis and adipogenesis-associated GIO by performing marrow adipogenesis and microcirculation dilation and bone histomorphometry analyses. (1) In vivo study: Bone loss in GC treated rats was confirmed by significantly decreased BMD, bone strength, cancellous bone mass and architecture, osteoblast distribution, bone formation, marrow microvessel density and diameter along with down-regulation of marrow BMPs expression and increased adipogenesis. Daily treatment with Sal B (40 mg/kg/d) for 12 weeks in GC male rats prevented GC-induced cancellous bone loss and increased adipogenesis while increasing cancellous bone formation rate with improved local microcirculation by capillary dilation. Treatment with Sal B at a higher dose (80 mg/kg/d) not only prevented GC-induced osteopenia, but also increased cancellous bone mass and thickness, associated with increase of marrow BMPs expression, inhibited adipogenesis and further increased microvessel diameters. (2) In vitro study: In concentration from 10−6 mol/L to 10−7 mol/L, Sal B stimulated bone marrow stromal cell (MSC) differentiation to osteoblast and increased osteoblast activities, decreased GC associated adipogenic differentiation by down-regulation of PPARγ mRNA expression, increased Runx2 mRNA expression without osteoblast inducement, and, furthermore, Sal B decreased Dickkopf-1 and increased β-catenin mRNA expression with

  9. Corrosion of graphite composites in phosphoric acid fuel cells

    NASA Technical Reports Server (NTRS)

    Christner, L. G.; Dhar, H. P.; Farooque, M.; Kush, A. K.

    1986-01-01

    Polymers, polymer-graphite composites and different carbon materials are being considered for many of the fuel cell stack components. Exposure to concentrated phosphoric acid in the fuel cell environment and to high anodic potential results in corrosion. Relative corrosion rates of these materials, failure modes, plausible mechanisms of corrosion and methods for improvement of these materials are investigated.

  10. Amino acid transporters: roles in amino acid sensing and signalling in animal cells.

    PubMed Central

    Hyde, Russell; Taylor, Peter M; Hundal, Harinder S

    2003-01-01

    Amino acid availability regulates cellular physiology by modulating gene expression and signal transduction pathways. However, although the signalling intermediates between nutrient availability and altered gene expression have become increasingly well documented, how eukaryotic cells sense the presence of either a nutritionally rich or deprived medium is still uncertain. From recent studies it appears that the intracellular amino acid pool size is particularly important in regulating translational effectors, thus, regulated transport of amino acids across the plasma membrane represents a means by which the cellular response to amino acids could be controlled. Furthermore, evidence from studies with transportable amino acid analogues has demonstrated that flux through amino acid transporters may act as an initiator of nutritional signalling. This evidence, coupled with the substrate selectivity and sensitivity to nutrient availability classically associated with amino acid transporters, plus the recent discovery of transporter-associated signalling proteins, demonstrates a potential role for nutrient transporters as initiators of cellular nutrient signalling. Here, we review the evidence supporting the idea that distinct amino acid "receptors" function to detect and transmit certain nutrient stimuli in higher eukaryotes. In particular, we focus on the role that amino acid transporters may play in the sensing of amino acid levels, both directly as initiators of nutrient signalling and indirectly as regulators of external amino acid access to intracellular receptor/signalling mechanisms. PMID:12879880

  11. Cellular distribution of cell cycle-related molecules in the renal tubules of rats treated with renal carcinogens for 28 days: relationship between cell cycle aberration and carcinogenesis.

    PubMed

    Taniai, Eriko; Hayashi, Hitomi; Yafune, Atsunori; Watanabe, Maiko; Akane, Hirotoshi; Suzuki, Kazuhiko; Mitsumori, Kunitoshi; Shibutani, Makoto

    2012-09-01

    Some renal carcinogens can induce karyomegaly, which reflects aberrant cell division in the renal tubules, from the early stages of exposure. To clarify the cell cycle-related changes during the early stages of renal carcinogenesis, we performed immunohistochemical analysis of tubular cells in male F344 rats treated with carcinogenic doses of representative renal carcinogens for 28 days. For this purpose, the karyomegaly-inducing carcinogens ochratoxin A (OTA), ferric nitrilotriacetic acid, and monuron, and the non-karyomegaly-inducing carcinogens tris(2-chloroethyl) phosphate and potassium bromate were examined. For comparison, a karyomegaly-inducing non-carcinogen, p-nitrobenzoic acid, and a non-carcinogenic non-karyomegaly-inducing renal toxicant, acetaminophen, were also examined. The outer stripe of the outer medulla (OSOM) and the cortex + OSOM were subjected to morphometric analysis of immunoreactive proximal tubular cells. Renal carcinogens, irrespective of their karyomegaly-inducing potential, increased proximal tubular cell proliferation accompanied by an increase in topoisomerase IIα-immunoreactive cells, suggesting a reflection of cell proliferation. Karyomegaly-inducing carcinogens increased nuclear Cdc2-, γH2AX-, and phosphorylated Chk2-immunoreactive cells in both areas, the former two acting in response to DNA damage and the latter one suggestive of sustained G₂. OTA, an OSOM-targeting carcinogen, could easily be distinguished from untreated controls and non-carcinogens by evaluation of molecules responding to DNA damage and G₂/M transition in the OSOM. Thus, all renal carcinogens examined facilitated proximal tubular proliferation by repeated short-term treatment. Among these, karyomegaly-inducing carcinogens may cause DNA damage and G₂ arrest in the target tubular cells.

  12. LABORATORY EVALUATION OF ZERO-VALENT IRON TO TREAT GROUNDWATER IMPACTED BY ACID MINE DRAINAGE

    EPA Science Inventory

    The generation and release of acidic, metal-rich water from mine wastes continues to be an intractable environmental problem. Although the effects of acid mine drainage (AMD) are most evident in surface waters, there is an obvious need for developing cost-effective approaches fo...

  13. Changes in tissue free amino acid pools in growing chickens fed thermally treated vetch diets.

    PubMed

    Fernández-Fígares, I; Nieto, R; Aguilera, J F; Lachica, M

    2014-04-01

    A three-day assay was developed to evaluate the effect of autoclaving on protein quality of vetch as an alternative to classical growth methods. Male chickens (n = 10/diet) were given approximately isonitrogenous diets based on raw or autoclaved vetch for 3 days. Samples of plasma, muscle and liver were obtained for free amino acid analysis. Heating vetch depressed growth (11.9 vs. 23.2 g/d; p < 0.05). Plasma methionine and histidine increased (0.05 < p < 0.06), while gluconeogenic amino acids tended to decrease (p < 0.10) after heating. Muscle free amino acids did not change except for a trend to increased methionine (p = 0.06) in birds fed autoclaved vetch. In liver, most essential amino acids, glycine, proline and tyrosine increased markedly with heated vetch diet. Correlations between plasma and muscle free amino acids were poor compared with those between plasma and liver free amino acids. Liver free amino acid pool was more sensitive than muscle or plasma pool to amino acid inflow modifications after vetch heating.

  14. Fuel and lubricant additives from acid treated mixtures of vegetable oil derived amides and esters

    SciTech Connect

    Bonazza, B.R.; Devault, A.N.

    1981-05-26

    Vegetable oils such as corn oil, peanut oil, and soy oil are reacted with polyamines to form a mixture containing amides, imides, half esters, and glycerol with subsequent treatment with a strong acid such as sulfonic acid to produce a product mix that has good detergent properties in fuels and lubricants.

  15. Gene-Expression Patterns and Levels of Jasmonic Acid in Rice Treated with the Resistance Inducer 2,6-Dichloroisonicotinic Acid.

    PubMed Central

    Schweizer, P.; Buchala, A.; Metraux, J. P.

    1997-01-01

    Acquired disease resistance can be induced in rice (Oryza sativa) by a number of synthetic or natural compounds, but the molecular mechanisms behind the phenomenon are poorly understood. One of the synthetic inducers of resistance, 2,6-dichloroisonicotinic acid (INA), efficiently protected rice leaves from infection by the rice blast fungus Magnaporthe grisea (Hebert) Barr. A comparison of gene-expression patterns in plants treated with INA versus plants inoculated with the compatible pathogen M. grisea or the incompatible pathogen Pseudomonas syringae pv syringae revealed only a marginal overlap: 6 gene products, including pathogenesis-related proteins (PR1-PR9), accumulated in both INA-treated and pathogen-attacked leaves, whereas 26 other gene products accumulated only in INA-treated or only in pathogen-attacked leaves. Lipoxygenase enzyme activity and levels of nonconjugated jasmonic acid (JA) were enhanced in leaves of plants treated with a high dose of INA (100 ppm). Exogenously applied JA enhanced the gene induction and plant protection caused by lower doses of INA (0.1 to 10 ppm) that by themselves did not give rise to enhanced levels of endogenous (-)-JA. These data suggest that INA, aside from activating a pathogen-induced signaling pathway, also induces events that are not related to pathogenesis. JA acts as an enhancer of both types of INA-induced reactions in rice. PMID:12223792

  16. Nucleic Acid Encoding A Lectin-Derived Progenitor Cell Preservation Factor

    SciTech Connect

    Colucci, M. Gabriella; Chrispeels, Maarten J.; Moore, Jeffrey G.

    2001-10-30

    The invention relates to an isolated nucleic acid molecule that encodes a protein that is effective to preserve progenitor cells, such as hematopoietic progenitor cells. The nucleic acid comprises a sequence defined by SEQ ID NO:1, a homolog thereof, or a fragment thereof. The encoded protein has an amino acid sequence that comprises a sequence defined by SEQ ID NO:2, a homolog thereof, or a fragment thereof that contains an amino acid sequence TNNVLQVT. Methods of using the encoded protein for preserving progenitor cells in vitro, ex vivo, and in vivo are also described. The invention, therefore, include methods such as myeloablation therapies for cancer treatment wherein myeloid reconstitution is facilitated by means of the specified protein. Other therapeutic utilities are also enabled through the invention, for example, expanding progenitor cell populations ex vivo to increase chances of engraftation, improving conditions for transporting and storing progenitor cells, and facilitating gene therapy to treat and cure a broad range of life-threatening hematologic diseases.

  17. Transport of ascorbic acid and dehydroascorbic acid by pancreatic islet cells from neonatal rats.

    PubMed Central

    Zhou, A; Nielsen, J H; Farver, O; Thorn, N A

    1991-01-01

    Several amidated biologically active peptides such as pancreastatin, thyrotropin-releasing hormone, pancreatic polypeptide and amylin are produced in endocrine pancreatic tissue which contains the enzyme necessary for their final processing, i.e. peptidylglycine alpha-amidating mono-oxygenase (EC 1.14.17.3). The enzyme needs ascorbic acid for activity as well as copper and molecular oxygen. The present work shows that pancreatic islet cells prepared from overnight cultures of isolated islets from 5-7-day-old rats accumulate 14C-labelled ascorbic acid by a Na(+)-dependent active transport mechanism which involves a saturable process (estimated Km 17.6 microM). Transport was inhibited by ouabain, phloridzin, cytochalasin B, amiloride and probenecid. Glucose inhibited or stimulated uptake, depending on the length of incubation time of the cells. The uptake of dehydroascorbic acid was linearly dependent on concentration. Dehydroascorbic acid was converted to ascorbic acid by an unknown mechanism after uptake. The uptake of both ascorbic acid and dehydroascorbic acid was inhibited by tri-iodothyronine, and uptake of ascorbic acid, but not of dehydroascorbic acid, was inhibited by glucocorticoids. Isolated secretory granules contained a fairly low concentration of iron but a high concentration of copper. Images Fig. 6. PMID:2012602

  18. Plasma and red blood cell fatty acids in peroxisomal disorders.

    PubMed

    Moser, A B; Jones, D S; Raymond, G V; Moser, H W

    1999-02-01

    The demonstration of abnormal levels of fatty acids or plasmalogens in plasma or red blood cells is key to the diagnosis of peroxisomal disorders. We report the levels of 62 fatty acids and plasmalogens in patients with X-linked adrenoleukodystrophy (X-ALD), Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD), and infantile Refsum disease (IRD), both at baseline and after dietary interventions. "Lorenzo's Oil" therapy in X-ALD normalizes the levels of saturated very long chain fatty acids in plasma, but leads to reduced levels of omega 6 and other omega 3 fatty acids, and requires monitoring and appropriate dietary supplements. Patients with ZS, NALD and IRD have reduced levels of docosahexaenoic acid (DHA) and arachidonic acid (AA) which can be normalized by the oral administration of microencapsulated DHA and AA.

  19. Citric acid effects on brain and liver oxidative stress in lipopolysaccharide-treated mice.

    PubMed

    Abdel-Salam, Omar M E; Youness, Eman R; Mohammed, Nadia A; Morsy, Safaa M Youssef; Omara, Enayat A; Sleem, Amany A

    2014-05-01

    Citric acid is a weak organic acid found in the greatest amounts in citrus fruits. This study examined the effect of citric acid on endotoxin-induced oxidative stress of the brain and liver. Mice were challenged with a single intraperitoneal dose of lipopolysaccharide (LPS; 200 μg/kg). Citric acid was given orally at 1, 2, or 4 g/kg at time of endotoxin injection and mice were euthanized 4 h later. LPS induced oxidative stress in the brain and liver tissue, resulting in marked increase in lipid peroxidation (malondialdehyde [MDA]) and nitrite, while significantly decreasing reduced glutathione, glutathione peroxidase (GPx), and paraoxonase 1 (PON1) activity. Tumor necrosis factor-alpha (TNF-α) showed a pronounced increase in brain tissue after endotoxin injection. The administration of citric acid (1-2 g/kg) attenuated LPS-induced elevations in brain MDA, nitrite, TNF-α, GPx, and PON1 activity. In the liver, nitrite was decreased by 1 g/kg citric acid. GPx activity was increased, while PON1 activity was decreased by citric acid. The LPS-induced liver injury, DNA fragmentation, serum transaminase elevations, caspase-3, and inducible nitric oxide synthase expression were attenuated by 1-2 g/kg citric acid. DNA fragmentation, however, increased after 4 g/kg citric acid. Thus in this model of systemic inflammation, citric acid (1-2 g/kg) decreased brain lipid peroxidation and inflammation, liver damage, and DNA fragmentation.

  20. Citric Acid Effects on Brain and Liver Oxidative Stress in Lipopolysaccharide-Treated Mice

    PubMed Central

    Youness, Eman R.; Mohammed, Nadia A.; Morsy, Safaa M. Youssef; Omara, Enayat A.; Sleem, Amany A.

    2014-01-01

    Abstract Citric acid is a weak organic acid found in the greatest amounts in citrus fruits. This study examined the effect of citric acid on endotoxin-induced oxidative stress of the brain and liver. Mice were challenged with a single intraperitoneal dose of lipopolysaccharide (LPS; 200 μg/kg). Citric acid was given orally at 1, 2, or 4 g/kg at time of endotoxin injection and mice were euthanized 4 h later. LPS induced oxidative stress in the brain and liver tissue, resulting in marked increase in lipid peroxidation (malondialdehyde [MDA]) and nitrite, while significantly decreasing reduced glutathione, glutathione peroxidase (GPx), and paraoxonase 1 (PON1) activity. Tumor necrosis factor-alpha (TNF-α) showed a pronounced increase in brain tissue after endotoxin injection. The administration of citric acid (1–2 g/kg) attenuated LPS-induced elevations in brain MDA, nitrite, TNF-α, GPx, and PON1 activity. In the liver, nitrite was decreased by 1 g/kg citric acid. GPx activity was increased, while PON1 activity was decreased by citric acid. The LPS-induced liver injury, DNA fragmentation, serum transaminase elevations, caspase-3, and inducible nitric oxide synthase expression were attenuated by 1–2 g/kg citric acid. DNA fragmentation, however, increased after 4 g/kg citric acid. Thus in this model of systemic inflammation, citric acid (1–2 g/kg) decreased brain lipid peroxidation and inflammation, liver damage, and DNA fragmentation. PMID:24433072

  1. Enhanced Performance and Stability in Polymer Photovoltaic Cells Using Ultraviolet-Treated PEDOT:PSS

    NASA Astrophysics Data System (ADS)

    Xu, Xue-Jian; Yang, Li-Ying; Tian, Hui; Qin, Wen-Jing; Yin, Shou-Gen; Zhang, Fengling

    2013-07-01

    We investigate the effects of ultraviolet (UV) irradiation treatment with varying irradiation intensities for different treatment times of poly(3, 4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) film on the performance and stability of polymer solar cells (PSCs) based on regioregular poly(3-hexylthiophene) (P3HT) and methanofullerene [6,6]-phenyl C61-butyric acid methyl ester (PCBM) blend. Ultraviolet-visible transmission spectra, x-ray photoelectron spectroscopy, contact angle measurement, atomic force microscopy and the Kelvin probe method are conducted to characterize the UV-treated PEDOT:PSS film. The results demonstrate that UV treatment can improve the power conversion efficiency (PCE) and stability of PSCs effectively. The best performance is achieved under 1200 μW/cm2 UV treatment for 50 min. Compared to the control device, the optimized device exhibits enhanced performance with a Voc of 0.59 V, Jsc of 12.3 mA/cm2, fill factor of 51%, and PCE of 3.64%, increased by 3.5%, 33%, 8.7% and 50%, respectively. The stability of the PSCs is enhanced by 2.5 times simply through the UV treatment on the PEDOT:PSS buffer layer. The improvement in the device performance and stability is attributed to the improvement in the wettability property and the increase in the work function of the PEDOT:PSS film by UV treatment, while the impact of UV treatment on the transparency of the PEDOT:PSS film is negligible. The strategy of using UV treatment to improve device performance and stability is attractive due to its simplicity, cost-effectiveness, and because it is suitable for large-scale commercial production.

  2. Inhibition of Interjacent Ribonucleic Acid (26S) Synthesis in Cells Infected by Sindbis Virus

    PubMed Central

    Scheele, Christina M.; Pfefferkorn, E. R.

    1969-01-01

    The interrelationship of viral ribonucleic acid (RNA) and protein synthesis in cells infected by Sindbis virus was investigated. When cultures were treated with puromycin early in the course of infection, the synthesis of interjacent RNA (26S) was preferentially inhibited. A similar result was obtained by shifting cells infected by one temperature-sensitive mutant defective in RNA synthesis from the permissive (29 C) to the nonpermissive (41.5 C) temperature. Under both conditions, the viral RNA produced appeared to be fully active biologically. Once underway, the synthesis of viral RNA in wild-type Sindbis infections did not require concomitant protein synthesis. PMID:5817400

  3. Prognostic biomarkers in patients with localized natural killer/T-cell lymphoma treated with concurrent chemoradiotherapy

    PubMed Central

    Yamaguchi, Motoko; Takata, Katsuyoshi; Yoshino, Tadashi; Ishizuka, Naoki; Oguchi, Masahiko; Kobayashi, Yukio; Isobe, Yasushi; Ishizawa, Kenichi; Kubota, Nobuko; Itoh, Kuniaki; Usui, Noriko; Miyazaki, Kana; Wasada, Izumi; Nakamura, Shigeo; Matsuno, Yoshihiro; Oshimi, Kazuo; Kinoshita, Tomohiro; Tsukasaki, Kunihiro; Tobinai, Kensei

    2014-01-01

    Concurrent chemoradiotherapy has become one of the standard management approaches for newly diagnosed localized nasal natural killer (NK)/T-cell lymphoma (NKTCL). Few data are available on the prognostic biomarkers of NKTCL among patients treated with concurrent chemoradiotherapy. To evaluate the prognostic significance of immunophenotypic biomarkers for patients treated with concurrent chemoradiotherapy, latent membrane protein 1 (LMP1), cutaneous lymphocyte antigen (CLA) and cell origin were examined in samples from 32 patients who were enrolled in the Japan Clinical Oncology Group 0211 trial and treated with concurrent chemoradiotherapy. LMP1 and CLA were positive in 66% (19/29) and 29% (9/31) of the cases examined, respectively. The median follow-up duration was 68 months (range, 61–94). The patients with LMP1-positive tumors showed a better overall survival (OS) than the patients with LMP1-negative tumors (hazard ratio, 0.240; 95% confidence interval [CI], 0.057–1.013; 80% CI, 0.093–0.615; P = 0.035). All five patients with LMP1-negative tumors who experienced disease progression died of lymphoma, and both patients with local failure had LMP1-negative tumors. There was no significant difference in OS according to CLA expression. A total of 27 (84%) cases were of NK-cell origin, two were of αβ T-cell origin and three were of γδ T-cell origin. In contrast to those with tumors of NK-cell origin, all five patients with NKTCL of T-cell origin were alive without relapse at the last follow up. Our results indicate that LMP1 expression is a favorable prognostic marker and suggest that a T-cell origin of the tumor may be a favorable prognostic marker for patients with localized NKTCL treated with concurrent chemoradiotherapy. PMID:25181936

  4. Ursolic acid from Trailliaedoxa gracilis induces apoptosis in medullary thyroid carcinoma cells

    PubMed Central

    AGUIRIANO-MOSER, VICTOR; SVEJDA, BERNHARD; LI, ZENG-XIA; STURM, SONJA; STUPPNER, HERMANN; INGOLIC, ELISABETH; HÖGER, HARALD; SIEGL, VERONIKA; MEIER-ALLARD, NATHALIE; SADJAK, ANTON; PFRAGNER, ROSWITHA

    2015-01-01

    Medullary thyroid carcinoma (MTC) originates from the C-cells of the thyroid and is not sensitive to radiation or chemotherapy. Therefore, surgical removal of the tumor tissue in its entirety is the only curative treatment for MTC. The present study aimed to examine the potential mechanisms of action of extracts of Trailliaedoxa gracilis (TG; WW Smith & Forrest), a plant from the province of Sichuan, China, and of ursolic acid (UA), a pentacyclic triterpen present in TG, on the MTC-SK MTC cell line. A total of 13 TG fractions and UA were examined in vitro for their effects on cell morphology, cell number, proliferation and rates of apoptosis. Reverse transcription-quantitative polymerase chain reaction of nuclear factor-κB essential modifier (NEMO) was performed to delineate the role of the apoptotic pathway following treatment with UA. TG and UA were examined in vivo in xenotransplanted MTC-bearing severe combined immunodeficient mice. The TG fractions exhibited antiproliferative effects, with inhibition of mitochondrial activity in the tumor cells at concentrations, which caused no impairment of the normal control cells. The apoptotic rates of the MTC-SK cells treated with the TG fractions and UA were determined, in which no marked tumor inhibition was observed in the treated MTC-mice, and no change in the expression of NEMO was detected in the treated MTC-SK cells. The observation of early-onset activation of caspase 8 suggested that the responsible factor was linked to NEMO, an anti-apoptotic protein. However, no differences in the mRNA transcription levels of NEMO were detected in MTC-SK cells treated with UA, suggesting that this protein was not associated with the signal transducer and activator of transcription 3 pathway. PMID:26151624

  5. Vaccination with epigenetically treated mesothelioma cells induces immunisation and blocks tumour growth.

    PubMed

    Guillot, Flora; Boutin, Benoît; Blanquart, Christophe; Fonteneau, Jean-François; Robard, Myriam; Grégoire, Marc; Pouliquen, Daniel

    2011-07-26

    Malignant mesothelioma (MM) is an aggressive tumour associated with poor outcome in patients. Current treatments for MM are of limited efficacy. Our recent findings suggest that epigenetic drugs may induce both cytotoxicity and an immune response against MM cells. Thus, we used a mouse model of MM (AK7) to analyse how epigenetic drugs could modulate MM development in vivo. The treatment of tumour-bearing mice with an epigenetic drug already tested in clinical MM treatments (SAHA/Vorinostat) reduced the tumour mass and induced a moderate lymphocytic infiltration. However, the treatment did not stop tumour development. In order to show the potential effect of this epigenetic drug on tumour immunogenicity, in addition to cell cytotoxicity, we immunised mice either with AK7 cells pre-treated with SAHA, or with one of two cytotoxic drugs (curcumin or selenite), prior to transplantation of live AK7 cells. A specific immune response was observed only in mice immunised with AK7 cells pre-treated with the epigenetic drug (SAHA) and the tumour growth was arrested. An increase in the proportion of CD3+ CD8+ lymphocytes occurred in the peritoneal cavity. We also observed large conglomerates of immune cells in the omentum with clusters of CD8+ T cells, together with lymphocytes directed against residual AK7 cells in the interlobular connective tissue of the pancreas. Our data demonstrate that epigenetic drugs, such as SAHA, can stimulate tumour immunogenicity and improve the recognition of aggressive MM cells by the immune system in vivo. PMID:21619908

  6. Tauroursodeoxycholic acid reduces glial cell activation in an animal model of acute neuroinflammation

    PubMed Central

    2014-01-01

    Background Bile acids are steroid acids found predominantly in the bile of mammals. The bile acid conjugate tauroursodeoxycholic acid (TUDCA) is a neuroprotective agent in different animal models of stroke and neurological diseases. However, the anti-inflammatory properties of TUDCA in the central nervous system (CNS) remain unknown. Methods The acute neuroinflammation model of intracerebroventricular (icv) injection with bacterial lipopolysaccharide (LPS) in C57BL/6 adult mice was used herein. Immunoreactivity against Iba-1, GFAP, and VCAM-1 was measured in coronal sections in the mice hippocampus. Primary cultures of microglial cells and astrocytes were obtained from neonatal Wistar rats. Glial cells were treated with proinflammatory stimuli to determine the effect of TUDCA on nitrite production and activation of inducible enzyme nitric oxide synthase (iNOS) and NFκB luciferase reporters. We studied the effect of TUDCA on transcriptional induction of iNOS and monocyte chemotactic protein-1 (MCP-1) mRNA as well as induction of protein expression and phosphorylation of different proteins from the NFκB pathway. Results TUDCA specifically reduces microglial reactivity in the hippocampus of mice treated by icv injection of LPS. TUDCA treatment reduced the production of nitrites by microglial cells and astrocytes induced by proinflammatory stimuli that led to transcriptional and translational diminution of the iNOS. This effect might be due to inhibition of the NFκB pathway, activated by proinflammatory stimuli. TUDCA decreased in vitro microglial migration induced by both IFN-γ and astrocytes treated with LPS plus IFN-γ. TUDCA inhibition of MCP-1 expression induced by proinflammatory stimuli could be in part responsible for this effect. VCAM-1 inmunoreactivity in the hippocampus of animals treated by icv LPS was reduced by TUDCA treatment, compared to animals treated with LPS alone. Conclusions We show a triple anti-inflammatory effect of TUDCA on glial cells: i

  7. Solid Acid Fuel Cell Stack for APU Applications

    SciTech Connect

    Duong, Hau H.

    2011-04-15

    Solid acid fuel cell technology affords the opportunity to operate at the 200-300 degree centigrade regime that would allow for more fuel flexibility, compared to polymer electrode membrane fuel cell, while avoiding the relatively more expensive and complex system components required by solid oxide fuel cell. This project addresses many factors such as MEA size scalability, fuel robustness, stability, etc., that are essential for successful commercialization of the technology.

  8. Silicon dioxide thin film mediated single cell nucleic acid isolation.

    PubMed

    Bogdanov, Evgeny; Dominova, Irina; Shusharina, Natalia; Botman, Stepan; Kasymov, Vitaliy; Patrushev, Maksim

    2013-01-01

    A limited amount of DNA extracted from single cells, and the development of single cell diagnostics make it necessary to create a new highly effective method for the single cells nucleic acids isolation. In this paper, we propose the DNA isolation method from biomaterials with limited DNA quantity in sample, and from samples with degradable DNA based on the use of solid-phase adsorbent silicon dioxide nanofilm deposited on the inner surface of PCR tube.

  9. Silicon Dioxide Thin Film Mediated Single Cell Nucleic Acid Isolation

    PubMed Central

    Bogdanov, Evgeny; Dominova, Irina; Shusharina, Natalia; Botman, Stepan; Kasymov, Vitaliy; Patrushev, Maksim

    2013-01-01

    A limited amount of DNA extracted from single cells, and the development of single cell diagnostics make it necessary to create a new highly effective method for the single cells nucleic acids isolation. In this paper, we propose the DNA isolation method from biomaterials with limited DNA quantity in sample, and from samples with degradable DNA based on the use of solid-phase adsorbent silicon dioxide nanofilm deposited on the inner surface of PCR tube. PMID:23874571

  10. Identification of sialylated glycoproteins in Doxorubicin-treated hepatoma cells with glycoproteomic analyses.

    PubMed

    Azuma, Kanako; Serada, Satoshi; Takamatsu, Shinji; Terao, Naoko; Takeishi, Shunsaku; Kamada, Yoshihiro; Naka, Tetsuji; Miyoshi, Eiji

    2014-11-01

    Sialylation is one of the most important types of glycosylation involved in carcinogenesis and establishment of cancer stemness. We previously showed that increased sialylation is a characteristic glycan change in cancer stem cells (CSCs) from hepatocellular carcinoma. However, the identities of glycoproteins targeted for sialylation remain unknown. In the present study, we identified glycoproteins targeted for sialylation in doxorubicin (DXR)-treated hepatocarcinoma cell line, Huh7, using glycoproteomic analyses. Since CSCs constitute a small subset of cells within carcinoma cell lines, it is difficult to identify sialylated proteins using general glycoproteomic strategies. It is known that treatment with anticancer drug can condense CSCs, we used DXR to concentrate CSCs. In DXR-treated Huh7 cells, isobaric tag for relative and absolute quantitation (iTRAQ) analysis identified 17 sialylated glycoproteins. Most of the identified glycoproteins were cancer-associated proteins. Furthermore, two proteins of approximately 70 kDa were detected using Sambucus sieboldoana agglutinin (SSA) blot analysis and identified as beta-galactosidase and alpha-2-HS-glycoprotein (fetuin-A) by SSA precipitation followed by liquid chromatography-tandem mass spectrometry analyses. Sialylation levels of fetuin-A were increased in DXR-treated Huh7 cell lysates. These changes in sialylation of glycoproteins might be involved in the establishment of cancer stemness.

  11. Treating diet-induced diabetes and obesity with human embryonic stem cell-derived pancreatic progenitor cells and antidiabetic drugs.

    PubMed

    Bruin, Jennifer E; Saber, Nelly; Braun, Natalie; Fox, Jessica K; Mojibian, Majid; Asadi, Ali; Drohan, Campbell; O'Dwyer, Shannon; Rosman-Balzer, Diana S; Swiss, Victoria A; Rezania, Alireza; Kieffer, Timothy J

    2015-04-14

    Human embryonic stem cell (hESC)-derived pancreatic progenitor cells effectively reverse hyperglycemia in rodent models of type 1 diabetes, but their capacity to treat type 2 diabetes has not been reported. An immunodeficient model of type 2 diabetes was generated by high-fat diet (HFD) feeding in SCID-beige mice. Exposure to HFDs did not impact the maturation of macroencapsulated pancreatic progenitor cells into glucose-responsive insulin-secreting cells following transplantation, and the cell therapy improved glucose tolerance in HFD-fed transplant recipients after 24 weeks. However, since diet-induced hyperglycemia and obesity were not fully ameliorated by transplantation alone, a second cohort of HFD-fed mice was treated with pancreatic progenitor cells combined with one of three antidiabetic drugs. All combination therapies rapidly improved body weight and co-treatment with either sitagliptin or metformin improved hyperglycemia after only 12 weeks. Therefore, a stem cell-based therapy may be effective for treating type 2 diabetes, particularly in combination with antidiabetic drugs.

  12. Treating Diet-Induced Diabetes and Obesity with Human Embryonic Stem Cell-Derived Pancreatic Progenitor Cells and Antidiabetic Drugs

    PubMed Central

    Bruin, Jennifer E.; Saber, Nelly; Braun, Natalie; Fox, Jessica K.; Mojibian, Majid; Asadi, Ali; Drohan, Campbell; O’Dwyer, Shannon; Rosman-Balzer, Diana S.; Swiss, Victoria A.; Rezania, Alireza; Kieffer, Timothy J.

    2015-01-01

    Summary Human embryonic stem cell (hESC)-derived pancreatic progenitor cells effectively reverse hyperglycemia in rodent models of type 1 diabetes, but their capacity to treat type 2 diabetes has not been reported. An immunodeficient model of type 2 diabetes was generated by high-fat diet (HFD) feeding in SCID-beige mice. Exposure to HFDs did not impact the maturation of macroencapsulated pancreatic progenitor cells into glucose-responsive insulin-secreting cells following transplantation, and the cell therapy improved glucose tolerance in HFD-fed transplant recipients after 24 weeks. However, since diet-induced hyperglycemia and obesity were not fully ameliorated by transplantation alone, a second cohort of HFD-fed mice was treated with pancreatic progenitor cells combined with one of three antidiabetic drugs. All combination therapies rapidly improved body weight and co-treatment with either sitagliptin or metformin improved hyperglycemia after only 12 weeks. Therefore, a stem cell-based therapy may be effective for treating type 2 diabetes, particularly in combination with antidiabetic drugs. PMID:25801507

  13. Eyes open to stem cells: safety trial may pave the way for cell therapy to treat retinal disease in patients

    PubMed Central

    2011-01-01

    A clinical trial using human embryonic stem cell (hESC) therapy for an inherited retinal degenerative disease is about to commence. The Advanced Cell Technology (ACT) trial will treat patients with Stargardt's macular dystrophy using transplanted retinal pigment epithelium derived from hESCs. Currently, no effective treatment is available for Stargardt's disease so a stem cell-based therapy that can slow progression of this blinding condition could represent a significant breakthrough. While there are some hurdles to clear, the ACT trial is a fine example of translational research that could eventually pave the way for a range of stem cell therapies for the retina and other tissues. PMID:22152341

  14. Polyelectrolyte Multilayer-Treated Electrodes for Real-Time Electronic Sensing of Cell Proliferation.

    PubMed

    Mijares, Geraldine I; Reyes, Darwin R; Geist, Jon; Gaitan, Michael; Polk, Brian J; DeVoe, Don L

    2010-01-01

    We report on the use of polyelectrolyte multilayer (PEM) coatings as a non-biological surface preparation to facilitate uniform cell attachment and growth on patterned thin-film gold (Au) electrodes on glass for impedance-based measurements. Extracellular matrix (ECM) proteins are commonly utilized as cell adhesion promoters for electrodes; however, they exhibit degradation over time, thereby imposing limitations on the duration of conductance-based biosensor experiments. The motivation for the use of PEM coatings arises from their long-term surface stability as promoters for cell attachment, patterning, and culture. In this work, a cell proliferation monitoring device was fabricated. It consisted of thin-film Au electrodes deposited with a titanium-tungsten (TiW) adhesion layer that were patterned on a glass substrate and passivated to create active electrode areas. The electrode surfaces were then treated with a poly(ethyleneimine) (PEI) anchoring layer and subsequent bilayers of sodium poly(styrene sulfonate) (PSS) and poly(allylamine hydrochloride) (PAH). NIH-3T3 mouse embryonic fibroblast cells were cultured on the device, observed by optical microscopy, and showed uniform growth characteristics similar to those observed on a traditional polystyrene cell culture dish. The optical observations were correlated to electrical measurements on the PEM-treated electrodes, which exhibited a rise in impedance with cell proliferation and stabilized to an approximate 15 % increase as the culture approached confluency. In conclusion, cells proliferate uniformly over gold and glass PEM-treated surfaces, making them useful for continuous impedance-based, real-time monitoring of cell proliferation and for the determination of cell growth rate in cellular assays. PMID:27134780

  15. Ipilimumab or Nivolumab in Treating Patients With Relapsed Hematologic Malignancies After Donor Stem Cell Transplant

    ClinicalTrials.gov

    2016-09-21

    Myeloproliferative Neoplasm; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Recurrent Hodgkin Lymphoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Plasma Cell Myeloma

  16. Characterization of ascorbic acid uptake by isolated rat kidney cells

    SciTech Connect

    Bowers-Komro, D.M.; McCormick, D.B. )

    1991-01-01

    Isolated kidney cells accumulated L(1-14C)ascorbic acid in a time-dependent manner and reached a steady state after 15 min at 37 degrees C. Initial velocity for uptake was over 300 pmol/mg protein per min when cells were separated from the bathing solution using a density gradient established during centrifugation. The uptake process was saturable with an apparent concentration at half maximal uptake of 36 mumols/L. Ascorbate uptake was reduced by metabolic inhibitors and was temperature dependent. Although ascorbic acid is an acid anion at pH 7.4, uptake did not appear to be inhibited by other acid anions such as p-aminohippurate and probenecid; however, involvement of the ion gradient established by Na+, H(+)-adenosine triphosphatase could not be confirmed. Replacing the sodium ion with other monovalent ions reduced the accumulation of ascorbate significantly. Isoascorbic and dehydroascorbic acids inhibited ascorbate uptake (34 and 13 mmol/L, respectively), whereas high concentrations of glucose showed some stimulation. These findings indicated that ascorbic acid is reabsorbed by the kidney in a sodium-dependent active transport process that is not common to other acid anions and has some specificity for the ascorbic acid structure.

  17. The effect of ascetic acid on mammalian cells

    SciTech Connect

    Mariana, Oana C; Trujillo, Antoinette; Sanders, Claire K; Burnett, Kassidy S; Freyer, James P; Mourant, Judith R

    2010-01-01

    Effects of the contrast agent, acetic acid, on mammalian cells are studied using light scattering measurements, viability and fluorescence pH assays. Results depend on whether cells are in PBS or are live and metabolizing. Acetic acid is a contrast agent used to aid the detection of cancerous and precancerous lesions of the uterine cervix. Typically 3% or 5% acetic acid is applied to the swface of the cervix and areas of the tissue that turn 'acetowhite' are considered more likely to be precancerous. The mechanism of action of acetic acid has never been understood in detail, although there are several hypotheses. One is that a decrease in pH causes cytokeratins in epithelial cells to polymerize. We will present data demonstrating that this is not the sole mechanism of acetowhitening. Another hypothesis is that a decrease in pH in the nucleus causes deacetylation of the histones which in turn results in a dense chromatin structure. Relevant to this hypothesis we have measured the internal pH of cells. Additional goals of this work are to understand what physical changes result in acetowhitening, to understand why there is variation in how cells respond to acetic acid, and to investigate how acetowhitening affects the light scatter properties measured by a fiber-optic probe we have developed for cervical cancer diagnostics.

  18. Nitric acid treated multi-walled carbon nanotubes optimized by Taguchi method

    NASA Astrophysics Data System (ADS)

    Shamsuddin, Shahidah Arina; Derman, Mohd Nazree; Hashim, Uda; Kashif, Muhammad; Adam, Tijjani; Halim, Nur Hamidah Abdul; Tahir, Muhammad Faheem Mohd

    2016-07-01

    Electron transfer rate (ETR) of CNTs can be enhanced by increasing the amounts of COOH groups to their wall and opened tips. With the aim to achieve the highest production amount of COOH, Taguchi robust design has been used for the first time to optimize the surface modification of MWCNTs by nitric acid oxidation. Three main oxidation parameters which are concentration of acid, treatment temperature and treatment time have been selected as the control factors that will be optimized. The amounts of COOH produced are measured by using FTIR spectroscopy through the absorbance intensity. From the analysis, we found that acid concentration and treatment time had the most important influence on the production of COOH. Meanwhile, the treatment temperature will only give intermediate effect. The optimum amount of COOH can be achieved with the treatment by 8.0 M concentration of nitric acid at 120 °C for 2 hour.

  19. METABOLISM, MICROFLORA EFFECTS, AND GENOTOXICITY IN HALOACETIC ACID-TREATED CULTURES OF RAT CECAL MICROBIOTA

    EPA Science Inventory

    Haloacetic acids are by-products of drinking water disinfection. Several compounds in this class are genotoxic and have been identified as rodent hepatocarcinogens. Enzymes produced by the normal intestinal bacteria can transform some promutagens and procarcinogens to their bio...

  20. The removal torque of titanium screw inserted in rabbit tibia treated by dual acid etching.

    PubMed

    Cho, Sung-Am; Park, Kyung-Tae

    2003-09-01

    Chemical acid etching alone of the titanium implant surface have the potential to greatly enhance osseointegration without adding particulate matter (e.g. TPS or hydroxyapatite) or embedding surface contaminants (e.g. grit particles). The aims of the present study were to evaluate any differences between the machined and dual acid etching implants with the removal torque as well as topographic analysis. A total of 40 custom-made, screw-shaped, commercially pure titanium implants with length of 5 mm and an outer diameter of 3.75 mm were divided into 4 groups, 10 screws in each, and chemical modification of the titanium implant surfaces were achieved using HF and HCl/H(2)SO(4) dual acid etching. The first exposure was to hydrofluoric acid and the second was to a combination of hydrochloric acid and sulfuric acid. The tibia metaphysics was exposed by incisions through the skin, fascia, and periosteum. One implant of each group was inserted in every rabbit, 2 in each proximal tibia metaphysics. Every rabbit received 3 implants with acid etched surfaces and 1 implant with a machined surface. Twelve weeks post-surgically, 7 rabbits were sacrificed, Subsequently, the leg was stabilized and the implant was removed under reverse torque rotation with a digital torque gauge (Mark-10 Corporation, USA) (Fig. 1). Twelve weeks after implant placement, the removal torque mean values were the dual acid etched implants (24%HF+HCl/H(2)SO(4), group C) required a higher average force (34.7 Ncm), than the machined surface implants (group A) (p=0.045) (Mann-Whiteney test). Scanning electron micrographs of acid etching of the titanium surface created an even distribution of very small (1-2 microm) peaks and valleys, while machining of the titanium surface created typical microscopically grooved surface characteristics. Nonetheless, there was no difference in surface topography between each acid etched implant groups. Therefore, chemically acid etching implant surfaces have higher

  1. High cell density propionic acid fermentation with an acid tolerant strain of Propionibacterium acidipropionici.

    PubMed

    Wang, Zhongqiang; Jin, Ying; Yang, Shang-Tian

    2015-03-01

    Propionic acid is an important chemical with wide applications and its production via fermentation is of great interest. However, economic production of bio-based propionic acid requires high product titer, yield, and productivity in the fermentation. A highly efficient and stable high cell density (HCD) fermentation process with cell recycle by centrifugation was developed for propionic acid production from glucose using an acid-tolerant strain of Propionibacterium acidipropionici, which had a higher specific growth rate, productivity, and acid tolerance compared to the wild type ATCC 4875. The sequential batch HCD fermentation at pH 6.5 produced propionic acid at a high titer of ∼40 g/L and productivity of 2.98 g/L h, with a yield of ∼0.44 g/g. The product yield increased to 0.53-0.62 g/g at a lower pH of 5.0-5.5, which, however, decreased the productivity to 1.28 g/L h. A higher final propionic acid titer of >55 g/L with a productivity of 2.23 g/L h was obtained in fed-batch HCD fermentation at pH 6.5. A 3-stage simulated fed-batch process in serum bottles produced 49.2 g/L propionic acid with a yield of 0.53 g/g and productivity of 0.66 g/L h. These productivities, yields and propionic acid titers were among the highest ever obtained in free-cell propionic acid fermentation.

  2. Neural stem cell transplantation as a therapeutic approach for treating lysosomal storage diseases.

    PubMed

    Shihabuddin, Lamya S; Cheng, Seng H

    2011-10-01

    Treating the central nervous system manifestations of subjects with neuropathic lysosomal storage diseases remains a major technical challenge. This is because of the low efficiency by which lysosomal enzymes in systemic circulation are able to traverse the blood brain barrier into the central nervous system. Intracranial transplantation of neural stems cells genetically modified to overexpress the respective deficient enzymes represents a potential approach to addressing this group of diseases. The unique properties of neural stem cells and progenitor cells, such as their ability to migrate to distal sites, differentiate into various cell types and integrate within the host brain without disrupting normal function, making them particularly attractive therapeutic agents. In addition, neural stem cells are amenable to ex vivo propagation and modification by gene transfer vectors. In this regard, transplanted cells can serve not only as a source of lysosomal enzymes but also as a means to potentially repair the injured brain by replenishing the organ with healthy cells and effecting the release of neuroprotective factors. This review discusses some of the well-characterized neural stem cell types and their possible use in treating neuropathic lysosomal storage diseases such as the Niemann Pick A disease.

  3. Proteomic Retrieval from Nucleic Acid Depleted Space-Flown Human Cells

    NASA Technical Reports Server (NTRS)

    Hammond, D. K.; Elliott, T. F.; Holubec, K.; Baker, T. L.; Allen, P. L.; Hammond, T. G.; Love, J. E.

    2006-01-01

    Compared to experiments utilizing humans in microgravity, cell-based approaches to questions about subsystems of the human system afford multiple advantages, such as crew safety and the ability to achieve statistical significance. To maximize the science return from flight samples, an optimized method was developed to recover protein from samples depleted of nucleic acid. This technique allows multiple analyses on a single cellular sample and when applied to future cellular investigations could accelerate solutions to significant biomedical barriers to human space exploration. Cell cultures grown in American Fluoroseal bags were treated with an RNA stabilizing agent (RNAlater - Ambion), which enabled both RNA and immunoreactive protein analyses. RNA was purified using an RNAqueous(registered TradeMark) kit (Ambion) and the remaining RNA free supernatant was precipitated with 5% trichloroacetic acid. The precipitate was dissolved in SDS running buffer and tested for protein content using a bicinchoninic acid assay (1) (Sigma). Equal loads of protein were placed on SDS-PAGE gels and either stained with CyproOrange (Amersham) or transferred using Western Blotting techniques (2,3,4). Protein recovered from RNAlater-treated cells and stained with protein stain, was measured using Imagequant volume measurements for rectangles of equal size. BSA treated in this way gave quantitative data over the protein range used (Fig 1). Human renal cortical epithelial (HRCE) cells (5,6,7) grown onboard the International Space Station (ISS) during Increment 3 and in ground control cultures exhibited similar immunoreactivity profiles for antibodies to the Vitamin D receptor (VDR) (Fig 2), the beta isoform of protein kinase C (PKC ) (Fig 3), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (Fig 4). Parallel immunohistochemical studies on formalin-fixed flight and ground control cultures also showed positive immunostaining for VDR and other biomarkers (Fig 5). These results are

  4. Noxious sensory perceptions in patients with mild to moderate rosacea treated with azelaic acid 15% gel.

    PubMed

    Draelos, Zoe Diana

    2004-10-01

    Patients with rosacea form a unique subset of the sensitive skin population because of the barrier defects inherent in this condition and the increased propensity for burning/stinging from topical products. This propensity for burning/ stinging when medications, skin care products, or cosmetics are applied to the facial skin has been frequently documented but never quantified. The objective of this 2-week study was to determine the prevalence of heightened neurosensory perceptions of burning/stinging in a random population of 40 women with mild to moderate rosacea defined as 15 or fewer inflammatory papules or pustules. Also evaluated was the effect of azelaic acid 15% gel on barrier function and facial stinging utilizing transepidermal water loss (TEWL), corneometry, and lactic acid facial sting tests as noninvasive measurement criteria. At baseline, the incidence of lactic acid stinging among these rosacea subjects was 62.5%, which is substantially higher than observed in the general population. Two weeks after application of azelaic acid 15% gel, no evidence of barrier damage was noted on TEWL or corneometry tests. Moreover, there was no statistical relationship between lactic acid stinging and a stinging response that is occasionally reported with exposure to azelaic acid 15% gel. PMID:15551720

  5. Decay resistance of wood treated with boric acid and tall oil derivates.

    PubMed

    Temiz, Ali; Alfredsen, Gry; Eikenes, Morten; Terziev, Nasko

    2008-05-01

    In this study, the effect of two boric acid concentrations (1% and 2%) and four derivates of tall oil with varying chemical composition were tested separately and in combination. The tall oil derivates were chosen in a way that they consist of different amounts of free fatty, resin acids and neutral compounds. Decay tests using two brown rot fungi (Postia placenta and Coniophora puteana) were performed on both unleached and leached test samples. Boric acid showed a low weight loss in test samples when exposed to fungal decay before leaching, but no effect after leaching. The tall oil derivates gave better efficacy against decay fungi compared to control, but are not within the range of the efficacy needed for a wood preservative. Double impregnation with boric acid and tall oil derivates gave synergistic effects for several of the double treatments both in unleached and leached samples. In the unleached samples the double treatment gave a better efficacy against decay fungi than tall oil alone. In leached samples a better efficacy against brown rot fungi were achieved than in samples with boron alone and a nearly similar or better efficacy than for tall oil alone. Boric acid at 2% concentration combined with the tall oil derivate consisting of 90% free resin acids (TO-III) showed the best performance against the two decay fungi with a weight loss less than 3% after a modified pure culture test.

  6. Effect of citric acid irrigation on the fracture resistance of endodontically treated roots

    PubMed Central

    Arslan, Hakan; Barutcigil, Cagatay; Karatas, Ertugrul; Topcuoglu, Huseyin Sinan; Yeter, Kubra Yesildal; Ersoy, Ibrahim; Ayrancı, Leyla Benan

    2014-01-01

    Objective: The aim of this study was to evaluate the effect of citric acid irrigation on root fracture in different concentrations and at various time exposures on root fracture. Materials and Methods: Forty-eight human mandibular incisors with similar dimensions were selected. The specimens were decoronated, then divided into 6 groups as follows: A group without instrumentation and filling (G1) and the 5 other groups with canal preparation and irrigation of distilled water (G2), 10% citric acid for 1 min (G3), 50% citric acid for 1 min (G4), 10% citric acid for 10 min (G5), and 50% citric acid for 10 min (G6). In the experimental groups, the canals were obturated and subjected to the strength test. Statistical analysis was performed using Kruskal-Wallis test (P = 0.05). Results: G6 showed the highest fracture resistance (629.97 N), and G3 showed the lowest fracture resistance (507.76 N). However, there was no statistically significant difference among the groups. Conclusions: The results of this study suggest that use of citric acid is safe in terms of fracture resistance. PMID:24966750

  7. Stem cell therapy emerging as the key player in treating type 1 diabetes mellitus.

    PubMed

    Vanikar, Aruna V; Trivedi, Hargovind L; Thakkar, Umang G

    2016-09-01

    Type 1 diabetes mellitus (T1DM) is an autoimmune disease causing progressive destruction of pancreatic β cells, ultimately resulting in loss of insulin secretion producing hyperglycemia usually affecting children. Replacement of damaged β cells by cell therapy can treat it. Currently available strategies are insulin replacement and islet/pancreas transplantation. Unfortunately these offer rescue for variable duration due to development of autoantibodies. For pancreas/islet transplantation a deceased donor is required and various shortfalls of treatment include quantum, cumbersome technique, immune rejection and limited availability of donors. Stem cell therapy with assistance of cellular reprogramming and β-cell regeneration can open up new therapeutic modalities. The present review describes the history and current knowledge of T1DM, evolution of cell therapies and different cellular therapies to cure this condition. PMID:27424148

  8. Stem cell therapy emerging as the key player in treating type 1 diabetes mellitus.

    PubMed

    Vanikar, Aruna V; Trivedi, Hargovind L; Thakkar, Umang G

    2016-09-01

    Type 1 diabetes mellitus (T1DM) is an autoimmune disease causing progressive destruction of pancreatic β cells, ultimately resulting in loss of insulin secretion producing hyperglycemia usually affecting children. Replacement of damaged β cells by cell therapy can treat it. Currently available strategies are insulin replacement and islet/pancreas transplantation. Unfortunately these offer rescue for variable duration due to development of autoantibodies. For pancreas/islet transplantation a deceased donor is required and various shortfalls of treatment include quantum, cumbersome technique, immune rejection and limited availability of donors. Stem cell therapy with assistance of cellular reprogramming and β-cell regeneration can open up new therapeutic modalities. The present review describes the history and current knowledge of T1DM, evolution of cell therapies and different cellular therapies to cure this condition.

  9. Concise Review: Prospects of Bone Marrow Mononuclear Cells and Mesenchymal Stem Cells for Treating Status Epilepticus and Chronic Epilepsy.

    PubMed

    Agadi, Satish; Shetty, Ashok K

    2015-07-01

    Mononuclear cells (MNCs) and mesenchymal stem cells (MSCs) derived from the bone marrow and other sources have received significant attention as donor cells for treating various neurological disorders due to their robust neuroprotective and anti-inflammatory effects. Moreover, it is relatively easy to procure these cells from both autogenic and allogenic sources. Currently, there is considerable interest in examining the usefulness of these cells for conditions such as status epilepticus (SE) and chronic epilepsy. A prolonged seizure activity in SE triggers neurodegeneration in the limbic brain areas, which elicits epileptogenesis and evolves into a chronic epileptic state. Because of their potential for providing neuroprotection, diminishing inflammation and curbing epileptogenesis, early intervention with MNCs or MSCs appears attractive for treating SE as such effects may restrain the development of chronic epilepsy typified by spontaneous seizures and learning and memory impairments. Delayed administration of these cells after SE may also be useful for easing spontaneous seizures and cognitive dysfunction in chronic epilepsy. This concise review evaluates the current knowledge and outlook pertaining to MNC and MSC therapies for SE and chronic epilepsy. In the first section, the behavior of these cells in animal models of SE and their efficacy to restrain neurodegeneration, inflammation, and epileptogenesis are discussed. The competence of these cells for suppressing seizures and improving cognitive function in chronic epilepsy are conferred in the next section. The final segment ponders issues that need to be addressed to pave the way for clinical application of these cells for SE and chronic epilepsy.

  10. Effect of hyperthermic CO2-treated dendritic cell-derived exosomes on the human gastric cancer AGS cell line

    PubMed Central

    WANG, JINLIN; WANG, ZHIYONG; MO, YANXIA; ZENG, ZHAOHUI; WEI, PEI; LI, TAO

    2015-01-01

    The aim of the present study was to determine the antitumor effects of hyperthermic CO2 (HT-CO2)-treated dendritic cell (DC)-derived exosomes (Dex) on human gastric cancer AGS cells. Mouse-derived DCs were incubated in HT-CO2 at 43°C for 4 h. The exosomes in the cell culture supernatant were then isolated. Cell proliferation was analyzed using the cell counting kit-8 (CCK-8) assay. Cell apoptosis was observed using flow cytometry, Hoechst 33258 staining and the analysis of caspase-3 activity. In addition, the proliferation of tumor cells was evaluated in xenotransplant nude mice. HT-CO2 markedly inhibited cell proliferation, as assessed by the CCK-8 assay, and also induced apoptosis in a time-dependent manner, as demonstrated by Annexin V/propidium iodide flow cytometry, caspase-3 activity and morphological analysis using Hoechst fluorescent dye. It was also revealed that HT-CO2-treated Dex decreased the expression of heat shock protein 70 and inhibited tumor growth in nude mice. In conclusion, HT-CO2 exerted an efficacious immune-enhancing effect on DCs. These findings may provide a novel strategy for the elimination of free cancer cells during laparoscopic resection. However, the potential cellular mechanisms underlying this process require further investigation. PMID:26170979

  11. Concise Review: Prospects of Bone Marrow Mononuclear Cells and Mesenchymal Stem Cells for Treating Status Epilepticus and Chronic Epilepsy.

    PubMed

    Agadi, Satish; Shetty, Ashok K

    2015-07-01

    Mononuclear cells (MNCs) and mesenchymal stem cells (MSCs) derived from the bone marrow and other sources have received significant attention as donor cells for treating various neurological disorders due to their robust neuroprotective and anti-inflammatory effects. Moreover, it is relatively easy to procure these cells from both autogenic and allogenic sources. Currently, there is considerable interest in examining the usefulness of these cells for conditions such as status epilepticus (SE) and chronic epilepsy. A prolonged seizure activity in SE triggers neurodegeneration in the limbic brain areas, which elicits epileptogenesis and evolves into a chronic epileptic state. Because of their potential for providing neuroprotection, diminishing inflammation and curbing epileptogenesis, early intervention with MNCs or MSCs appears attractive for treating SE as such effects may restrain the development of chronic epilepsy typified by spontaneous seizures and learning and memory impairments. Delayed administration of these cells after SE may also be useful for easing spontaneous seizures and cognitive dysfunction in chronic epilepsy. This concise review evaluates the current knowledge and outlook pertaining to MNC and MSC therapies for SE and chronic epilepsy. In the first section, the behavior of these cells in animal models of SE and their efficacy to restrain neurodegeneration, inflammation, and epileptogenesis are discussed. The competence of these cells for suppressing seizures and improving cognitive function in chronic epilepsy are conferred in the next section. The final segment ponders issues that need to be addressed to pave the way for clinical application of these cells for SE and chronic epilepsy. PMID:25851047

  12. Wnt5a-treated midbrain neural stem cells improve dopamine cell replacement therapy in parkinsonian mice.

    PubMed

    Parish, Clare L; Castelo-Branco, Gonçalo; Rawal, Nina; Tonnesen, Jan; Sorensen, Andreas Toft; Salto, Carmen; Kokaia, Merab; Lindvall, Olle; Arenas, Ernest

    2008-01-01

    Dopamine (DA) cell replacement therapy in Parkinson disease (PD) can be achieved using human fetal mesencephalic tissue; however, limited tissue availability has hindered further developments. Embryonic stem cells provide a promising alternative, but poor survival and risk of teratoma formation have prevented their clinical application. We present here a method for generating large numbers of DA neurons based on expanding and differentiating ventral midbrain (VM) neural stem cells/progenitors in the presence of key signals necessary for VM DA neuron development. Mouse VM neurospheres (VMNs) expanded with FGF2, differentiated with sonic hedgehog and FGF8, and transfected with Wnt5a (VMN-Wnt5a) generated 10-fold more DA neurons than did conventional FGF2-treated VMNs. VMN-Wnt5a cells exhibited the transcriptional and biochemical profiles and intrinsic electrophysiological properties of midbrain DA cells. Transplantation of these cells into parkinsonian mice resulted in significant cellular and functional recovery. Importantly, no tumors were detected and only a few transplanted grafts contained sporadic nestin-expressing progenitors. Our findings show that Wnt5a improves the differentiation and functional integration of stem cell-derived DA neurons in vivo and define Wnt5a-treated neural stem cells as an efficient and safe source of DA neurons for cell replacement therapy in PD.

  13. Electricity generation from synthetic acid-mine drainage (AMD) water using fuel cell technologies

    SciTech Connect

    Shaoan Cheng; Brian A. Dempsey; Bruce E. Logan

    2007-12-15

    Acid-mine drainage (AMD) is difficult and costly to treat. We investigated a new approach to AMD treatment using fuel cell technologies to generate electricity while removing iron from the water. Utilizing a recently developed microbial fuel cell architecture, we developed an acid-mine drainage fuel cell (AMD-FC) capable of abiotic electricity generation. The AMD-FC operated in fed-batch mode generated a maximum power density of 290 mW/m{sup 2} at a Coulombic efficiency greater than 97%. Ferrous iron was completely removed through oxidation to insoluble Fe(III), forming a precipitate in the bottom of the anode chamber and on the anode electrode. Several factors were examined to determine their effect on operation, including pH, ferrous iron concentration, and solution chemistry. Optimum conditions were a pH of 6.3 and a ferrous iron concentration above about 0.0036 M. These results suggest that fuel cell technologies can be used not only for treating AMD through removal of metals from solution, but also for producing useful products such as electricity and recoverable metals. Advances being made in wastewater fuel cells will enable more efficient power generation and systems suitable for scale-up. 35 refs., 8 figs.

  14. In vitro photodynamic therapy of MG-63 osteosarcoma cells mediated by aminolevulinic acid

    NASA Astrophysics Data System (ADS)

    Rossi, Vincent M.; White, Bradley M.; Newton, Mariko J.; Jacques, Steven L.; Baugher, Paige J.

    2011-02-01

    This is an in vitro study of photodynamic therapy (PDT) in the MG-63 line of human osteosarcoma cells, as mediated by aminolevulinic acid (ALA). The primary goal of this work is to determine the feasibility and effectiveness of treating osteosarcoma through PDT. In addition, this work is aimed at determining whether the resulting cell death occurs through apoptosis or cellular necrosis. The MG-63 cells are treated with increasing concentrations of ALA from 0.1-10 mM ALA, leading to the accumulation of the photosensitizer protoporphyrin IX (PpIX) within the cells. After incubation periods of 4 and 24 hours in ALA, the cells are illuminated by 0-10 J/cm2 of 636 nm light in order to activate the PpIX and induce oxidative damage to the cells. Light is administered by an 8x12 array of LED's, which are controlled by an Arduino Duemilanove microcontroller board in order to assure ease of use along with accurate levels of exposure. Controls for this experiment include 0 J/cm2 of light exposure for all experimental concentrations of ALA, as well as illuminating cells that have not been incubated in ALA at all experimental levels of illumination. MG-63 cells are analyzed through fluorimetry and MTT assays in order to determine the effectiveness of ALA mediated PDT of osteosarcoma.

  15. Mechanical Aspects of Microtubule Bundling in Taxane-Treated Circulating Tumor Cells

    PubMed Central

    Kim, MunJu; Rejniak, Katarzyna A.

    2014-01-01

    Microtubules play an important role in many cellular processes, including mitotic spindle formation and cell division. Taxane-based anticancer treatments lead to the stabilization of microtubules, thus preventing the uncontrolled proliferation of tumor cells. One of the striking physical features of taxane-treated cells is the localization of their microtubules, which can be observed via fluorescent microscopy as an intense fluorescent band and are referred to as a microtubule bundle. With the recent advances in capturing and analyzing tumor cells circulating in a patient’s blood system, there is increasing interest in using these cells to examine a patient’s response to treatment. This includes taxanes that are used routinely in clinics to treat prostate, breast, lung, and other cancers. Here, we have used a computational model of microtubule mechanics to investigate self-arrangement patterns of stabilized microtubules, which allowed for the identification of specific combinations of three physical parameters: microtubule stiffness, intracellular viscosity, and cell shape, that can prevent the formation of microtubule bundles in cells with stabilized microtubules, such as taxane-treated cells. We also developed a method to quantify bundling in the whole microtubule aster structure and a way to compare the simulated results to fluorescent images from experimental data. Moreover, we investigated microtubule rearrangement in both suspended and attached cells and showed that the observed final microtubule patterns depend on the experimental protocol. The results from our computational studies can explain the heterogeneous bundling phenomena observed via fluorescent immunostaining from a mechanical point of view without relying on heterogeneous cellular responses to the microtubule-stabilizing drug. PMID:25185559

  16. Taurolithocholic acid promotes intrahepatic cholangiocarcinoma cell growth via muscarinic acetylcholine receptor and EGFR/ERK1/2 signaling pathway.

    PubMed

    Amonyingcharoen, Sumet; Suriyo, Tawit; Thiantanawat, Apinya; Watcharasit, Piyajit; Satayavivad, Jutamaad

    2015-01-01

    Cholangiocarcinoma (CCA) is a malignant cancer of the biliary tract and its occurrence is associated with chronic cholestasis which causes an elevation of bile acids in the liver and bile duct. The present study aimed to investigate the role and mechanistic effect of bile acids on the CCA cell growth. Intrahepatic CCA cell lines, RMCCA-1 and HuCCA-1, were treated with bile acids and their metabolites to determine the growth promoting effect. Cell viability, cell cycle analysis, EdU incorporation assays were conducted. Intracellular signaling proteins were detected by western immunoblotting. Among eleven forms of bile acids and their metabolites, only taurolithocholic acid (TLCA) concentration dependently (1-40 µM) increased the cell viability of RMCCA-1, but not HuCCA-1 cells. The cell cycle analysis showed induction of cells in the S phase and the EdU incorporation assay revealed induction of DNA synthesis in the TLCA-treated RMCCA-1 cells. Moreover, TLCA increased the phosphorylation of EGFR, ERK 1/2 and also increased the expression of cyclin D1 in RMCCA-1 cells. Furthermore, TLCA-induced RMCCA-1 cell growth could be inhibited by atropine, a non-selective muscarinic acetylcholine receptor (mAChR) antagonist, AG 1478, a specific EGFR inhibitor, or U 0126, a specific MEK 1/2 inhibitor. These results suggest that TLCA induces CCA cell growth via mAChR and EGFR/EKR1/2 signaling pathway. Moreover, the functional presence of cholinergic system plays a certain role in TLCA-induced CCA cell growth.

  17. Delivery of nucleic acid therapeutics by genetically engineered hematopoietic stem cells

    PubMed Central

    Doering, Christopher B.; Archer, David; Spencer, H. Trent

    2010-01-01

    Several populations of adult human stem cells have been identified, but only a few of these are in routine clinical use. The hematopoietic stem cell (HSC) is arguably the most well characterized and the most routinely transplanted adult stem cell. Although details regarding several aspects of this cell’s phenotype are not well understood, transplant of HSCs has advanced to become the standard of care for the treatment of a range of monogenic diseases and several types of cancer. It has also proven to be an excellent target for genetic manipulation, and clinical trials have already demonstrated the usefulness of targeting this cell as a means of delivering nucleic acid therapeutics for the treatment of several previously incurable diseases. It is anticipated that additional clinical trials will soon follow, such as genetically engineering HSCs with vectors to treat monogenic diseases such as hemophilia A. In addition to the direct targeting of HSCs, induced pluripotent stem (iPS) cells have the potential to replace virtually any engineered stem cell therapeutic, including HSCs. We now know that for the broad use of genetically-modified HSCs for the treatment of non-lethal diseases, e.g. hemophilia A, we must be able to regulate the introduction of nucleic acid sequences into these target cells. We can begin to refine transduction protocols to provide safer approaches to genetically manipulate HSCs and strategies are being developed to improve the overall safety of gene transfer. This review focuses on recent advances in the systemic delivery of nucleic acid therapeutics using genetically-modified stem cells, specifically focusing on i) the use of retroviral vectors to genetically modify HSCs, ii) the expression of fVIII from hematopoietic stem cells for the treatment of hemophilia A, and iii) the use of genetically engineered hematopoietic cells generated from iPS cells as treatment for disorders of hematopoiesis. PMID:20869414

  18. Ultraviolet-ozone-treated PEDOT:PSS as anode buffer layer for organic solar cells.

    PubMed

    Su, Zisheng; Wang, Lidan; Li, Yantao; Zhao, Haifeng; Chu, Bei; Li, Wenlian

    2012-08-17

    Ultraviolet-ozone-treated poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS)was used as the anode buffer layer in copper phthalocyanine (CuPc)/fullerene-based solar cells. The power conversion efficiency of the cells with appropriated UV-ozone treatment was found to increase about 20% compared to the reference cell. The improved performance is attributed to the increased work function of the PEDOT:PSS layer, which improves the contact condition between PEDOT:PSS and CuPc, hence increasing the extraction efficiency of the photogenerated holes and decreasing the recombination probability of holes and electrons in the active organic layers.

  19. Lactic Acid Bacteria Convert Human Fibroblasts to Multipotent Cells

    PubMed Central

    Ohta, Kunimasa; Kawano, Rie; Ito, Naofumi

    2012-01-01

    The human gastrointestinal tract is colonized by a vast community of symbionts and commensals. Lactic acid bacteria (LAB) form a group of related, low-GC-content, gram-positive bacteria that are considered to offer a number of probiotic benefits to general health. While the role of LAB in gastrointestinal microecology has been the subject of extensive study, little is known about how commensal prokaryotic organisms directly influence eukaryotic cells. Here, we demonstrate the generation of multipotential cells from adult human dermal fibroblast cells by incorporating LAB. LAB-incorporated cell clusters are similar to embryoid bodies derived from embryonic stem cells and can differentiate into endodermal, mesodermal, and ectodermal cells in vivo and in vitro. LAB-incorporated cell clusters express a set of genes associated with multipotency, and microarray analysis indicates a remarkable increase of NANOG, a multipotency marker, and a notable decrease in HOX gene expression in LAB-incorporated cells. During the cell culture, the LAB-incorporated cell clusters stop cell division and start to express early senescence markers without cell death. Thus, LAB-incorporated cell clusters have potentially wide-ranging implications for cell generation, reprogramming, and cell-based therapy. PMID:23300571

  20. Materials characterization of phosphoric acid fuel cell system

    NASA Technical Reports Server (NTRS)

    Venkatesh, Srinivasan

    1986-01-01

    The component materials used in the fabrication of phosphoric acid fuel cells (PAFC) must have mechanical, chemical, and electrochemical stability to withstand the moderately high temperature (200 C) and pressure (500 kPa) and highly oxidizing nature of phosphoric acid. This study discusses the chemical and structural stability, performance and corrosion data on certain catalysts, catalyst supports, and electrode support materials used in PAFC applications.

  1. Glucocorticoid regulation of amino acid transport in anucleate rat hepatoma (HTC) cells

    PubMed Central

    1981-01-01

    The transport of alpha-aminoisobutyric acid (AIB) by rat hepatoma tissue culture (HTC) cells is rapidly and reversibly inhibited by dexamethasone and other glucocorticoids. To investigate the role of the nucleus in the regulation of transport and to determine whether steroid hormones or steroid-receptor complexes may have direct effects on cytoplasmic or membrane functions, we have examined the regulation of transport by dexamethasone in anucleate HTC cells. Cytoplasts prepared from suspension cultures of HTC cells fully retain active transport of AIB with the same kinetic properties as intact cells. However, the uptake of AIB is not inhibited by dexamethasone or other corticosteroids. Neither is the inhibited rate of transport, manifested by cytoplasts prepared from dexamethasone-treated cells, restored to normal upon removal of the hormone. Anucleate cells exhibit specific, saturable binding of [3H]dexamethasone; however, the binding is reduced compared with that of intact cells. The nucleus is thus required for the glucocorticoid regulation of amino acid transport in HTC cells. PMID:7217203

  2. Cinnamic acid induces apoptotic cell death and cytoskeleton disruption in human melanoma cells.

    PubMed

    Niero, Evandro Luís de Oliveira; Machado-Santelli, Gláucia Maria

    2013-05-23

    Anticancer activities of cinnamic acid derivatives include induction of apoptosis by irreversible DNA damage leading to cell death. The present work aimed to compare the cytotoxic and genotoxic potential of cinnamic acid in human melanoma cell line (HT-144) and human melanocyte cell line derived from blue nevus (NGM). Viability assay showed that the IC50 for HT-144 cells was 2.4 mM, while NGM cells were more resistant to the treatment. The growth inhibition was probably associated with DNA damage leading to DNA synthesis inhibition, as shown by BrdU incorporation assay, induction of nuclear aberrations and then apoptosis. The frequency of cell death caused by cinnamic acid was higher in HT-144 cells. Activated-caspase 3 staining showed apoptosis after 24 hours of treatment with cinnamic acid 3.2 mM in HT-144 cells, but not in NGM. We observed microtubules disorganization after cinnamic acid exposure, but this event and cell death seem to be independent according to M30 and tubulin labeling. The frequency of micronucleated HT-144 cells was higher after treatment with cinnamic acid (0.4 and 3.2 mM) when compared to the controls. Cinnamic acid 3.2 mM also increased the frequency of micronucleated NGM cells indicating genotoxic activity of the compound, but the effects were milder. Binucleation and multinucleation counting showed similar results. We conclude that cinnamic acid has effective antiproliferative activity against melanoma cells. However, the increased frequency of micronucleation in NGM cells warrants the possibility of genotoxicity and needs further investigation.

  3. Cinnamic acid induces apoptotic cell death and cytoskeleton disruption in human melanoma cells

    PubMed Central

    2013-01-01

    Anticancer activities of cinnamic acid derivatives include induction of apoptosis by irreversible DNA damage leading to cell death. The present work aimed to compare the cytotoxic and genotoxic potential of cinnamic acid in human melanoma cell line (HT-144) and human melanocyte cell line derived from blue nevus (NGM). Viability assay showed that the IC50 for HT-144 cells was 2.4 mM, while NGM cells were more resistant to the treatment. The growth inhibition was probably associated with DNA damage leading to DNA synthesis inhibition, as shown by BrdU incorporation assay, induction of nuclear aberrations and then apoptosis. The frequency of cell death caused by cinnamic acid was higher in HT-144 cells. Activated-caspase 3 staining showed apoptosis after 24 hours of treatment with cinnamic acid 3.2 mM in HT-144 cells, but not in NGM. We observed microtubules disorganization after cinnamic acid exposure, but this event and cell death seem to be independent according to M30 and tubulin labeling. The frequency of micronucleated HT-144 cells was higher after treatment with cinnamic acid (0.4 and 3.2 mM) when compared to the controls. Cinnamic acid 3.2 mM also increased the frequency of micronucleated NGM cells indicating genotoxic activity of the compound, but the effects were milder. Binucleation and multinucleation counting showed similar results. We conclude that cinnamic acid has effective antiproliferative activity against melanoma cells. However, the increased frequency of micronucleation in NGM cells warrants the possibility of genotoxicity and needs further investigation. PMID:23701745

  4. Ursodeoxycholic acid inhibits overexpression of P-glycoprotein induced by doxorubicin in HepG2 cells.

    PubMed

    Komori, Yuki; Arisawa, Sakiko; Takai, Miho; Yokoyama, Kunihiro; Honda, Minako; Hayashi, Kazuhiko; Ishigami, Masatoshi; Katano, Yoshiaki; Goto, Hidemi; Ueyama, Jun; Ishikawa, Tetsuya; Wakusawa, Shinya

    2014-02-01

    The hepatoprotective action of ursodeoxycholic acid (UDCA) was previously suggested to be partially dependent on its antioxidative effect. Doxorubicin (DOX) and reactive oxygen species have also been implicated in the overexpression of P-glycoprotein (P-gp), which is encoded by the MDR1 gene and causes antitumor multidrug resistance. In the present study, we assessed the effects of UDCA on the expression of MDR1 mRNA, P-gp, and intracellular reactive oxygen species levels in DOX-treated HepG2 cells and compared them to those of other bile acids. DOX-induced increases in reactive oxygen species levels and the expression of MDR1 mRNA were inhibited by N-acetylcysteine, an antioxidant, and the DOX-induced increase in reactive oxygen species levels and DOX-induced overexpression of MDR1 mRNA and P-gp were inhibited by UDCA. Cells treated with UDCA showed improved rhodamine 123 uptake, which was decreased in cells treated with DOX alone. Moreover, cells exposed to DOX for 24h combined with UDCA accumulated more DOX than that of cells treated with DOX alone. Thus, UDCA may have inhibited the overexpression of P-gp by suppressing DOX-induced reactive oxygen species production. Chenodeoxycholic acid (CDCA) also exhibited these effects, whereas deoxycholic acid and litocholic acid were ineffective. In conclusion, UDCA and CDCA had an inhibitory effect on the induction of P-gp expression and reactive oxygen species by DOX in HepG2 cells. The administration of UDCA may be beneficial due to its ability to prevent the overexpression of reactive oxygen species and acquisition of multidrug resistance in hepatocellular carcinoma cells.

  5. Therapeutic Vaccination against Adjuvant Arthritis Using Autoimmune T Cells Treated with Hydrostatic Pressure

    NASA Astrophysics Data System (ADS)

    Lider, Ofer; Karin, Nathan; Shinitzky, Meir; Cohen, Irun R.

    1987-07-01

    An ideal treatment for autoimmune diseases would be a nontoxic means of specifically neutralizing the autoreactive lymphocytes responsible for the disease. This goal has been realized in experimental autoimmunity models by immunizing rats or mice against their own autoimmune cells such that the animals generate an immune response specifically repressive to the disease-producing lymphocytes. This maneuver, termed lymphocyte vaccination, was demonstrated to be effective using some, but not all, autoimmune helper T-lymphocyte lines. We now report that T lymphocytes, otherwise incapable of triggering an immune response, can be transformed into effective immunogens by treating the cells in vitro with hydrostatic pressure. Clone A2b, as effector clone that recognized cartilage proteoglycan and caused adjuvant arthritis in Lewis rats, is such a cell. Untreated A2b could not trigger an immune response, but inoculating rats with pressure-treated A2b induced early remission of established adjuvant arthritis as well as resistance to subsequent disease. Specific resistance to arthritis was associated with anti-idiotypic T-cell reactivity to clone A2b and could be transferred from vaccinated rats to naive recipients using donor lymphoid cells. Aggregation of T-lymphocyte membrane components appeared to be important for an immune response because the effects of hydrostatic pressure could be reproduced by treatment of A2b with chemical cross-linkers or with agents disrupting the cytoskeleton. Populations of lymph node cells from antigen-primed rats, when treated with hydrostatic pressure, could also induce suppression of disease. Thus, effective vaccines can be developed without having to isolate the autoimmune T lymphocytes as lines or clones. These results demonstrate that effector T lymphocytes suitably treated may serve as agents for specifically controlling the immune system.

  6. CONJUGATED LINOLEIC ACIDS (CLA) DECREASE THE BREAST CANCER RISK IN DMBA-TREATED RATS.

    PubMed

    Białek, Agnieszka; Tokarz, Andrzej; Zagrodzki, Paweł

    2016-01-01

    The aim of this study was to investigate how supplementation of diet of female Sprague-Dawley rats with different doses of conjugated linoleic acids and for a varied period of time influences breast cancer risk, fatty acids profile and lipids peroxidation in chemically induced mammary tumors. Animals were divided into nine groups with different modifications of diet (vegetable oil, 1.0 or 2.0% of CLA) and period of supplementation, which lasted after (A), before (B) and before and after (BA) carcinogenic agent--7,12-dimethylbenz[a]anthracene administration at 50th day of life. Mammary adenocarcinomas occurred in all groups, but CLA supplementation decreased the cancer morbidity. Two percent CLA seems to be excessive because of the coexisting cachexia. Two CLA isomers (9-cis, 11-trans and 10-trans, 12-cis) were detected in tumors but content of rumenic acid was higher. Dietary supplementation significantly influenced some unsaturated fatty acids content (C18:2 n-6 trans, C20:1, C20:5 n-3, C22:2), but the anti- or prooxidant properties of CLA were not confirmed. CLA can inhibit chemically induced mammary tumors development in female rats, but their cytotoxic action seems not to be connected with lipids peroxidation. CLA isomers differ with their incorporation into cancerous tissues and they influence the content of some other fatty acids. PMID:27180424

  7. Alteration in the fatty acid composition of liver, kidney and plasma from diethylhexyl phthalate-treated rats

    SciTech Connect

    Okita, J.R.; Okita, R.T. )

    1990-02-26

    Cytochromes P-450 are induced in rat liver microsomes by a number of compounds which cause peroxisome proliferation. One such compound, diethylhexyl phthalate (DEHP), induces P-450 IVA1 which catalyzes {omega}- and ({omega}-1)-hydroxylation of fatty acids. In liver of rats fed DEHP, there is a 10-fold induction of {omega}-hydroxylation of laurate and ({omega}-1)-hydroxylation of palmitate, as compared to control rat liver. There is a 3-fold induction of other hydroxylations, such as W-hydroxylation of palmitate and {omega}- ({omega}-1)-hydroxylation of syristate. Despite these increases in hydroxylase activity, the authors have not been able to demonstrate increases in hydroxy fatty acids or dicarboxylic acids in liver or plasma of rats fed DEHP. However, alterations in the fatty acid composition of lipids in liver, kidney cortex and plasma were observed. They consistently observed increases in oleate (expressed as mol% of total fatty acid) in liver (11% in control increased to 24% in DEHP-treated), kidney cortex (12% to 16%) and plasma (13% to 24%). This increase in oleate was quite striking when expressed as ug/gm tissue or ug/al plasma. DEHP treatment resulted in increased oleate in mitochondrial, microsomal and cytosolic fractions of liver.

  8. Citric acid and ethylene diamine tetra-acetic acid as effective washing agents to treat sewage sludge for agricultural reuse.

    PubMed

    Ren, Xianghao; Yan, Rui; Wang, Hong-Cheng; Kou, Ying-Ying; Chae, Kyu-Jung; Kim, In S; Park, Yong-Jin; Wang, Ai-Jie

    2015-12-01

    This paper presents the effects of different concentrations of citric acid (CA) and ethylene diamine tetra-acetic acid (EDTA) when used as additive reagents for the treatment of sewage sludge for agricultural use. Herein, both the retention of nutrients and removal of metals from the sewage sludge are examined. The average removal rate for the metals after treatment by CA decreased in the order Cu>Pb>Cd>Cr>Zn, while the rates after treatment by EDTA decreased in the order of Pb>Cu>Cr>Cd>Zn. After treatment with CA and EDTA, total nitrogen and total phosphorus concentrations in the sludge decreased, while the content of available nitrogen and Olsen-P increased. In addition, a multi-criteria analysis model-fuzzy analytic network process method (with 3 main factors and 12 assessment sub-factors) was adopted to evaluate the effectiveness of different treatment methods. The results showed that the optimal CA and EDTA concentrations for sewage sludge treatment were 0.60 and 0.125 mol/L, respectively.

  9. Citric acid and ethylene diamine tetra-acetic acid as effective washing agents to treat sewage sludge for agricultural reuse.

    PubMed

    Ren, Xianghao; Yan, Rui; Wang, Hong-Cheng; Kou, Ying-Ying; Chae, Kyu-Jung; Kim, In S; Park, Yong-Jin; Wang, Ai-Jie

    2015-12-01

    This paper presents the effects of different concentrations of citric acid (CA) and ethylene diamine tetra-acetic acid (EDTA) when used as additive reagents for the treatment of sewage sludge for agricultural use. Herein, both the retention of nutrients and removal of metals from the sewage sludge are examined. The average removal rate for the metals after treatment by CA decreased in the order Cu>Pb>Cd>Cr>Zn, while the rates after treatment by EDTA decreased in the order of Pb>Cu>Cr>Cd>Zn. After treatment with CA and EDTA, total nitrogen and total phosphorus concentrations in the sludge decreased, while the content of available nitrogen and Olsen-P increased. In addition, a multi-criteria analysis model-fuzzy analytic network process method (with 3 main factors and 12 assessment sub-factors) was adopted to evaluate the effectiveness of different treatment methods. The results showed that the optimal CA and EDTA concentrations for sewage sludge treatment were 0.60 and 0.125 mol/L, respectively. PMID:26235448

  10. New anti-GD2 monoclonal antibodies produced from gamma-interferon-treated neuroblastoma cells.

    PubMed

    Gross, N; Beck, D; Portoukalian, J; Favre, S; Carrel, S

    1989-04-15

    Three monoclonal antibodies (IgG2) have been produced from hybridomas obtained by fusion of murine myeloma cells and spleen cells of mice hyperimmunized with gamma-interferon-treated neuroblastoma cells. The 3 MAbs, 7A4, 2A6 and IG8, detected an antigen present on neuroblastoma tumors and cell lines, but also on some neuro-ectoderm-derived tissues and cells. All 3 clones were shown to react with an epitope of the di-sialo-ganglioside GD2 molecules highly expressed by some neuro-ectoderm-derived tumors, mainly neuroblastoma. Whereas MAb IG8 specificity was restricted to GD2 and its o-acylated form, MAb 2A6 and 7A4 were also able to detect GD3 at high concentration of antibody as shown by TLC analysis and immunodetection. The 3 MAbs were able to lyse 100% neuroblastoma cells in the presence of rabbit or human complement. Direct binding assays with 125I-labelled MAbs showed that MAb 7A4 might be a good candidate for in vivo immunolocalization experiments. The high proportion of anti-GD2 MAbs obtained by our fusion and the increased binding of anti-GD2 MAbs on gamma-IFN-treated neuroblastoma cells suggests a modulation of the exposure and an increase in the immunogenicity of GD2 induced by gamma-IFN.

  11. Induction of Apoptosis in TNF-Treated L929 Cells in the Presence of Necrostatin-1

    PubMed Central

    Sawai, Hirofumi

    2016-01-01

    It has been shown that necroptosis—caspase-independent programmed necrotic cell death—can be induced by treatment with tumor necrosis factor (TNF) in the L929 murine fibrosarcoma cell line, even in the absence of a caspase inhibitor. Although it was reported that necrostatin-1—a specific inhibitor of necroptosis—inhibited TNF-induced necroptosis in L929 cells, it has not been elucidated whether the cells eventually die by apoptosis in the presence of necrostatin-1. In this paper, induction of apoptosis was demonstrated in TNF-treated L929 cells in the presence of necrostatin-1. Co-treatment with cycloheximide expedited apoptosis induction in necrostatin-1/TNF-treated L929 cells: typical apoptotic morphological changes, including membrane blebbing and nuclear fragmentation, induction of caspase-3 activity, proteolytic activation of caspases-3, -8, and -9, and cleavage of poly(ADP-ribose) polymerase (PARP) (a well-known substrate of caspase-3) were observed. Moreover, co-treatment with Z-VAD-fmk (a pan-caspase inhibitor) inhibited apoptosis by completely inhibiting caspases, resulting in a shift from apoptosis to necroptosis. In contrast, co-treatment with Z-Asp-CH2-DCB (a caspase inhibitor preferential to caspase-3) inhibited apoptosis without expediting necroptosis. These results indicate that apoptosis can be induced in TNF-treated L929 cells when the cells are protected from necroptosis, and support the notion that partial activation of caspase-8 in the presence of a caspase inhibitor preferential to caspase-3 suppresses both apoptosis and necroptosis. PMID:27739412

  12. Effects of valproic acid and pioglitazone on cell cycle progression and proliferation of T-cell acute lymphoblastic leukemia Jurkat cells

    PubMed Central

    Jazi, Marie Saghaeian; Mohammadi, Saeed; Yazdani, Yaghoub; Sedighi, Sima; Memarian, Ali; Aghaei, Mehrdad

    2016-01-01

    Objective(s): T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignant tumor. Administration of chemical compounds influencing apoptosis and T cell development has been discussed as promising novel therapeutic strategies. Valproic acid (VPA) as a recently emerged anti-neoplastic histone deacetylase (HDAC) inhibitor and pioglitazone (PGZ) as a high-affinity peroxisome proliferator-activated receptor-gamma (PPARγ) agonist have been shown to induce apoptosis and cell cycle arrest in different studies. Here, we aimed to investigate the underlying molecular mechanisms involved in anti-proliferative effects of these compounds on human Jurkat cells. Materials and Methods: Treated cells were evaluated for cell cycle progression and apoptosis using flowcytometry and MTT viability assay. Real-time RT-PCR was carried out to measure the alterations in key genes associated with cell death and cell cycle arrest. Results: Our findings illustrated that both VPA and PGZ can inhibit Jurkat E6.1 cells in vitro after 24 hr; however, PGZ 400 μM presents the most anti-proliferative effect. Interestingly, treated cells have been arrested in G2/M with deregulated cell division cycle 25A (Cdc25A) phosphatase and cyclin-dependent kinase inhibitor 1B (CDKN1B or p27) expression. Expression of cyclin D1 gene was inhibited when DNA synthesis entry was declined. Cell cycle deregulation in PGZ and VPA-exposed cells generated an increase in the proportion of aneuploid cell population, which has not reported before. Conclusion: These findings define that anti-proliferative effects of PGZ and VPA on Jurkat cell line are mediated by cell cycle deregulation. Thus, we suggest PGZ and VPA may relieve potential therapeutic application against apoptosis-resistant malignancies.

  13. Effects of valproic acid and pioglitazone on cell cycle progression and proliferation of T-cell acute lymphoblastic leukemia Jurkat cells

    PubMed Central

    Jazi, Marie Saghaeian; Mohammadi, Saeed; Yazdani, Yaghoub; Sedighi, Sima; Memarian, Ali; Aghaei, Mehrdad

    2016-01-01

    Objective(s): T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignant tumor. Administration of chemical compounds influencing apoptosis and T cell development has been discussed as promising novel therapeutic strategies. Valproic acid (VPA) as a recently emerged anti-neoplastic histone deacetylase (HDAC) inhibitor and pioglitazone (PGZ) as a high-affinity peroxisome proliferator-activated receptor-gamma (PPARγ) agonist have been shown to induce apoptosis and cell cycle arrest in different studies. Here, we aimed to investigate the underlying molecular mechanisms involved in anti-proliferative effects of these compounds on human Jurkat cells. Materials and Methods: Treated cells were evaluated for cell cycle progression and apoptosis using flowcytometry and MTT viability assay. Real-time RT-PCR was carried out to measure the alterations in key genes associated with cell death and cell cycle arrest. Results: Our findings illustrated that both VPA and PGZ can inhibit Jurkat E6.1 cells in vitro after 24 hr; however, PGZ 400 μM presents the most anti-proliferative effect. Interestingly, treated cells have been arrested in G2/M with deregulated cell division cycle 25A (Cdc25A) phosphatase and cyclin-dependent kinase inhibitor 1B (CDKN1B or p27) expression. Expression of cyclin D1 gene was inhibited when DNA synthesis entry was declined. Cell cycle deregulation in PGZ and VPA-exposed cells generated an increase in the proportion of aneuploid cell population, which has not reported before. Conclusion: These findings define that anti-proliferative effects of PGZ and VPA on Jurkat cell line are mediated by cell cycle deregulation. Thus, we suggest PGZ and VPA may relieve potential therapeutic application against apoptosis-resistant malignancies. PMID:27635203

  14. Beta Cell Mass Restoration in Alloxan-Diabetic Mice Treated with EGF and Gastrin.

    PubMed

    Song, Imane; Patel, Oelfah; Himpe, Eddy; Muller, Christo J F; Bouwens, Luc

    2015-01-01

    One week of treatment with EGF and gastrin (EGF/G) was shown to restore normoglycemia and to induce islet regeneration in mice treated with the diabetogenic agent alloxan. The mechanisms underlying this regeneration are not fully understood. We performed genetic lineage tracing experiments to evaluate the contribution of beta cell neogenesis in this model. One day after alloxan administration, mice received EGF/G treatment for one week. The treatment could not prevent the initial alloxan-induced beta cell mass destruction, however it did reverse glycemia to control levels within one day, suggesting improved peripheral glucose uptake. In vitro experiments with C2C12 cell line showed that EGF could stimulate glucose uptake with an efficacy comparable to that of insulin. Subsequently, EGF/G treatment stimulated a 3-fold increase in beta cell mass, which was partially driven by neogenesis and beta cell proliferation as assessed by beta cell lineage tracing and BrdU-labeling experiments, respectively. Acinar cell lineage tracing failed to show an important contribution of acinar cells to the newly formed beta cells. No appearance of transitional cells co-expressing insulin and glucagon, a hallmark for alpha-to-beta cell conversion, was found, suggesting that alpha cells did not significantly contribute to the regeneration. An important fraction of the beta cells significantly lost insulin positivity after alloxan administration, which was restored to normal after one week of EGF/G treatment. Alloxan-only mice showed more pronounced beta cell neogenesis and proliferation, even though beta cell mass remained significantly depleted, suggesting ongoing beta cell death in that group. After one week, macrophage infiltration was significantly reduced in EGF/G-treated group compared to the alloxan-only group. Our results suggest that EGF/G-induced beta cell regeneration in alloxan-diabetic mice is driven by beta cell neogenesis, proliferation and recovery of insulin. The

  15. Lovastatin increases arachidonic acid levels and stimulates thromboxane synthesis in human liver and monocytic cell lines.

    PubMed Central

    Hrboticky, N; Tang, L; Zimmer, B; Lux, I; Weber, P C

    1994-01-01

    The effect of lovastatin (LOV), the inhibitor of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase, on linoleic acid (LA, 18:2n-6) metabolism was examined in human monocytic Mono Mac 6 (MM6) and hepatoma Hep G2 cells. The desaturation of LA was examined after LOV (72 h, 10 microM) or dimethylsulfoxide (LOV carrier, < 0.1%) and [14C]LA (last 18 h, 0.3 microCi, 5 microM). In both cell lines, LOV reduced the percentage of 14C label associated with LA and increased the percentage of label in the 20:4n-6 and the 22:5n-6 fractions. In Hep G2 but not MM6 cells, this effect was fully reversible by means of coincubation with mevalonic acid (500 microM), but not with cholesterol or lipoproteins. In both cell lines, the LOV-mediated increase in LA desaturation resulted in dose-dependent reductions of LA and elevations of AA in cellular phospholipids. The lipids secreted by LOV-treated Hep G2 cells were also enriched in arachidonic acid (AA). In the MM6 cells, LOV increased release of thromboxane upon stimulation with the calcium ionophore A23187. In summary, our findings of higher LA desaturation and AA enrichment of lipids secreted by the Hep G2 cells suggest that LOV treatment may increase the delivery of AA from the liver to extrahepatic tissues. The changes in membrane fatty acid composition can influence a variety of cellular functions, such as eicosanoid synthesis in monocytic cells. The mechanism appears to be related to the reduced availability of intermediates of cholesterogenesis. PMID:8282787

  16. Genetic Code Expansion of Mammalian Cells with Unnatural Amino Acids.

    PubMed

    Brown, Kalyn A; Deiters, Alexander

    2015-09-01

    The expansion of the genetic code of mammalian cells enables the incorporation of unnatural amino acids into proteins. This is achieved by adding components to the protein biosynthetic machinery, specifically an engineered aminoacyl-tRNA synthetase/tRNA pair. The unnatural amino acids are chemically synthesized and supplemented to the growth medium. Using this methodology, fundamental new chemistries can be added to the functional repertoire of the genetic code of mammalian cells. This protocol outlines the steps necessary to incorporate a photocaged lysine into proteins and showcases its application in the optical triggering of protein translocation to the nucleus.

  17. Acid treatment of melanoma cells selects for invasive phenotypes.

    PubMed

    Moellering, Raymond E; Black, Kvar C; Krishnamurty, Chetan; Baggett, Brenda K; Stafford, Phillip; Rain, Matthew; Gatenby, Robert A; Gillies, Robert J

    2008-01-01

    Solid tumors become acidic due to hypoxia and upregulated glycolysis. We have hypothesized that this acidosis leads to more aggressive invasive behavior during carcinogenesis (Nature Reviews Cancer 4:891-899, 2004). Previous work on this subject has shown mixed results. While some have observed an induction of metastasis and invasion with acid treatments, others have not. To investigate this, human melanoma cells were acclimated to low pH growth conditions. Significant cell mortality occurred during acclimation, suggesting that acidosis selected for resistant phenotypes. Cells maintained under acidic conditions exhibited a greater range of motility, a reduced capacity to form flank tumors in SCID mice and did not invade more rapidly in vitro, compared to non-selected control cells. However, re-acclimation of these selected cells to physiological pH gave rise to stable populations with significantly higher in vitro invasion. These re-acclimated cells maintained higher invasion and higher motility for multiple generations. Transcriptomic analyses of these three phenotypes revealed significant differences, including upregulation of relevant pathways important for tissue remodeling, cell cycle control and proliferation. These results reinforce the hypothesis that acidosis promotes selection of stable, more invasive phenotypes, rather than inductive changes, which would be reversible.

  18. Enhanced cell growth on nanotextured GaN surface treated by UV illumination and fibronectin adsorption.

    PubMed

    Li, Jingying; Han, Qiusen; Wang, Xinhuan; Yang, Rong; Wang, Chen

    2014-11-01

    Semiconductors are important materials used for the development of high-performance biomedical devices. Gallium nitride (GaN) is a well-known III-nitride semiconductor with excellent optoelectronic properties as well as high chemical stability and biocompatibility. The formation of tight interfaces between GaN substrates and cells would be crucial for GaN-based devices used for probing and manipulating biological processes of cells. Here we report a strategy to greatly enhance cell adhesion and survival on nanotextured GaN surface which was treated by UV illumination and fibronectin (FN) adsorption. Cell studies showed that the UV/FN treatment greatly enhanced cell adhesion and growth on nanotextured GaN surfaces. These observations suggest new opportunities for novel nanotextured GaN-based biomedical devices.

  19. Folic Acid Supplementation Stimulates Notch Signaling and Cell Proliferation in Embryonic Neural Stem Cells

    PubMed Central

    Liu, Huan; Huang, Guo-wei; Zhang, Xu-mei; Ren, Da-lin; X. Wilson, John

    2010-01-01

    The present study investigated the effect of folic acid supplementation on the Notch signaling pathway and cell proliferation in rat embryonic neural stem cells (NSCs). The NSCs were isolated from E14–16 rat brain and grown as neurospheres in serum-free suspension culture. Individual cultures were assigned to one of 3 treatment groups that differed according to the concentration of folic acid in the medium: Control (baseline folic acid concentration of 4 mg/l), low folic acid supplementation (4 mg/l above baseline, Folate-L) and high folic acid supplementation (40 mg/l above baseline, Folate-H). NSCs were identified by their expression of immunoreactive nestin and proliferating cells by incorporation of 5'bromo-2'deoxyuridine. Cell proliferation was also assessed by methyl thiazolyl tetrazolium assay. Notch signaling was analyzed by real-time PCR and western blot analyses of the expression of Notch1 and hairy and enhancer of split 5 (Hes5). Supplementation of NSCs with folic acid increased the mRNA and protein expression levels of Notch1 and Hes5. Folic acid supplementation also stimulated NSC proliferation dose-dependently. Embryonic NSCs respond to folic acid supplementation with increased Notch signaling and cell proliferation. This mechanism may mediate the effects of folic acid supplementation on neurogenesis in the embryonic nervous system. PMID:20838574

  20. Treating cutaneous squamous cell carcinoma using ALA PLGA nanoparticle-mediated photodynamic therapy in a mouse model

    NASA Astrophysics Data System (ADS)

    Wang, Xiaojie; Shi, Lei; Tu, Qingfeng; Wang, Hongwei; Zhang, Haiyan; Wang, Peiru; Zhang, Linglin; Huang, Zheng; Wang, Xiuli; Zhao, Feng; Luan, Hansen

    2015-03-01

    Background: Squamous cell carcinoma (SCC) is a common skin cancer and its treatment is still difficult. The aim of this study was to evaluate the effectiveness of nanoparticle (NP)-assisted ALA delivery for topical photodynamic therapy (PDT) of cutaneous SCC. Methods: UV-induced cutaneous SCCs were established in hairless mice. ALA loaded polylactic-co-glycolic acid (PLGA) NPs were prepared and characterized. The kinetics of ALA PLGA NPs-induced protoporphyrin IX (PpIX) fluorescence in SCCs, therapeutic efficacy of ALA NP-mediated PDT, and immune responses were examined. Results: PLGA NPs could enhance PpIX production in SCC. ALA PLGA NP mediated topical PDT was more effective than free ALA of the same concentration in treating cutaneous SCC. Conclusion: PLGA NPs provide a promising strategy for delivering ALA in topical PDT of cutaneous SCC.

  1. COMPARISON OF GENE EXPRESSION IN KIDNEY AND URINARY BLADDER FROM RATS TREATED WITH DIMETHYLARSINIC ACID

    EPA Science Inventory

    Arsenic is widespread in the environment and a human carcinogen. A major metabolite of inorganic arsenic (iAs) in most species, including humans, is dimethylarsinic acid (DMA), which is also used as a pesticide. Unlike iAs, DMA induces urinary bladder tumors in rats. DMA is belie...

  2. LIME TREATMENT LAGOONS TECHNOLOGY FOR TREATING ACID MINE DRAINAGE FROM TWO MINING SITES

    EPA Science Inventory

    Runoff and drainage from active and inactive mines are someof the most environmentally damaging land uses i the US. Acid Mine drainage (AMD) from mining sites across the country requires treatment because of high metal concentrations that exceed regulatory standards for safe disc...

  3. Adsorption and release of ofloxacin from acid- and heat-treated halloysite.

    PubMed

    Wang, Qin; Zhang, Junping; Zheng, Yue; Wang, Aiqin

    2014-01-01

    Halloysite nanotube is an ideal vehicle of the controlled release of drugs. In this study, we systematically investigated the effects of acid- and heat-treatments on the physicochemical properties, structure and morphology of halloysite by XRD, FTIR, SEM and TEM. Afterwards, the adsorption and in vitro release properties of halloysite for cationic ofloxacin (OFL) were evaluated. The results indicate that HCl treatment has no influence on the crystal structure of halloysite, whereas it becomes amorphous after calcined at temperature higher than 500 °C. Both acid- and heat-treatments have no evident influence on the tubular structure of halloysite. OFL was adsorbed onto halloysite via electrostatic interaction between protonated OFL and negative halloysite surface, cation exchange as well as electrostatic interaction between the OFL-Al(3+) complexes and the negative halloysite surface. Acid-treatment facilitates the release of the adsorbed OFL compared with the natural halloysite in spite of a slight decrease of adsorption capacity. However, heat-treatment results in a sharp decrease of adsorption capacity for OFL owning to the OFL-promoted dissolution of aluminum and the disappearance of the porous structure. Although heat-treatment also facilitates release of the adsorbed OFL, the amount of OFL released is in fact less than the natural halloysite owing to the very low adsorption capacity. Thus, acid-activation is an effective protocol to improve the adsorption and release of halloysite for cationic drug molecules.

  4. Use of branched chain amino acids for treating hepatic encephalopathy: clinical experiences.

    PubMed Central

    Rossi Fanelli, F; Cangiano, C; Capocaccia, L; Cascino, A; Ceci, F; Muscaritoli, M; Giunchi, G

    1986-01-01

    The efficacy of branched chain amino acids in two consecutive clinical studies in patients with severe hepatic encephalopathy was tested. In the preliminary uncontrolled study 19 patients with grade 3-4 hepatic encephalopathy were given an intravenous solution containing leucine 11 g/l, isoleucine 9 g/l, and valine 8.4 g/l in 20% dextrose. A complete recovery of mental state was obtained in all patients in a mean time of 20.5 hours. In a subsequent controlled study 40 patients with grade 3-4 hepatic encephalopathy were randomly assigned to receive intravenous branched chain amino acid in 20% dextrose (group A) or oral lactulose (group B). Twelve patients (70.6%) in group A and eight (47%) in group B regained consciousness in a mean time of 27.6 and 31.5 hours, respectively. The difference in the recovery rate between the two groups, although evident, was not significant. Intravenous branched chain amino acids are thus at least as effective as lactulose in reversing hepatic coma. These data argue strongly in favour of a therapeutic effect of branched chain amino acids in the treatment of hepatic encephalopathy in patients with chronic liver failure. PMID:3539709

  5. LABORATORY EVALUATION OF ZERO-VALENT IRON TO TREAT WATER IMPACTED BY ACID MINE DRAINAGE

    EPA Science Inventory

    This study examines the applicability and limitations of granular zero-valent iron for the treatment of water impacted by mine wastes. Rates of acid neutralization and of metal (Cu, Cd, Ni, Zn, Hg, Al, and Mn) and metalloid (As) uptake were determined in batch systems using simu...

  6. Gold Nanoparticles Enhance the Anticancer Activity of Gallic Acid against Cholangiocarcinoma Cell Lines.

    PubMed

    Rattanata, Narintorn; Daduang, Sakda; Wongwattanakul, Molin; Leelayuwat, Chanvit; Limpaiboon, Temduang; Lekphrom, Ratsami; Sandee, Alisa; Boonsiri, Patcharee; Chio-Srichan, Sirinart; Daduang, Jureerut

    2015-01-01

    Gold nanoparticles (GNPs) were conjugated with gallic acid (GA) at various concentrations between 30 and 150 μM and characterized using transmission electron microscopy (TEM) and UV-Vis spectroscopy (UV-VIS). The anticancer activities of the gallic acid-stabilized gold nanoparticles against well-differentiated (M213) and moderately differentiated (M214) adenocarcinomas were then determined using a neutral red assay. The GA mechanism of action was evaluated using Fourier transform infrared (FTIR) microspectroscopy. Distinctive features of the FTIR spectra between the control and GA-treated cells were confirmed by principal component analysis (PCA). The surface plasmon resonance spectra of the GNPs had a maximum absorption at 520 nm, whereas GNPs-GA shifted the maximum absorption values. In an in vitro study, the complexed GNPs-GA had an increased ability to inhibit the proliferation of cancer cells that was statistically significant (P<0.0001) in both M213 and M214 cells compared to GA alone, indicating that the anticancer activity of GA can be improved by conjugation with GNPs. Moreover, PCA revealed that exposure of the tested cells to GA resulted in significant changes in their cell membrane lipids and fatty acids, which may enhance the efficacy of this anticancer activity regarding apoptosis pathways.

  7. Contact Lenses: A Delivery Device for Stem Cells to Treat Corneal Blindness.

    PubMed

    Bobba, Samantha; Di Girolamo, Nick

    2016-04-01

    : Worldwide, 45 million people are blind. Corneal blindness is a major cause of visual loss, estimated to affect 10 million. For the most difficult to treat patients, including those with a disease called limbal stem cell deficiency, a donor corneal graft is not a viable option; thus, patients are treated with specialized stem cell grafts, which fail in a significant proportion (30 to 50%) of subjects. This unacceptable failure rate means there is a pressing need to develop minimally invasive, long-lasting, cost-effective therapies to improve patient quality of life and lessen the economic burden. Restoring vision in patients with severe corneal disease is the main focus of our research program; however, to achieve our goals and deliver the best quality stem cell therapy, we must first understand the basic biology of these cells, including their residence, the factors that support their long-term existence, markers to identify and isolate them, and carriers that facilitate expansion, delivery, and protection during engraftment. We recently achieved some of these goals through the discovery of stem cell markers and the development of a novel and innovative contact lens-based cell transfer technique that has been successfully trialed on patients with corneal blindness. Although several popular methodologies are currently available to nurture and transfer stem cells to the patients' ocular surface, contact lenses provide many advantages that will be discussed in this review article. The job for clinician-researchers will be to map precisely how these cells contribute to restoring ocular health and whether improvements in the quality of cells and the cell delivery system can be developed to reduce disease burden.

  8. DNA damage kinetics and apoptosis in ivermectin-treated Chinese hamster ovary cells.

    PubMed

    Molinari, Gabriela; Kujawski, Maciej; Scuto, Anna; Soloneski, Sonia; Larramendy, Marcelo L

    2013-11-01

    A comet assay was used to analyze DNA damage kinetics in Chinese hamster ovary (CHO-K1) cells induced by antiparasitic ivermectin (IVM) and the IVM-containing technical formulation Ivomec® (IVO; 1% IVM). Cells were treated with 50 µg ml(-1) IVM and IVO for 80 min, washed and re-incubated in antiparasiticide-free medium for 0-24 h until assayed using the single-cell gel electrophoresis assay (SCGE). Cell viability remained unchanged up to 3 h of incubation. After 6 h of treatment, cell survival decreased up to 75% and 79% in IVM- and IVO-treated cultures, respectively, remaining unchanged within 12-24 h after treatment. For both anthelmintics, biphasic behavior in DNA damage occurred during the incubation time. A time-dependent increase of IVM- and IVO-induced DNA damage was observed within 0 to 3 h after pulse treatment, revealed by a progressive decrease of undamaged cells and an increase in slightly damaged and damaged cells. Finally, a time-dependent decrease in IVM- and IVO-induced DNA damage was revealed by a progressive decrease of slightly damaged cells and the absence of damaged cells simultaneously with an increase in the frequency of undamaged cells during the final 18 h of incubation. Flow cytometry analysis revealed that both compounds are able to induce a marked increase in early and late apoptosis. Based on our observations, we could conclude that the decrease in DNA lesions is mostly related to IVM-induced cytotoxicity rather than attributable to a repair process.

  9. Radiofrequency field-induced thermal cytotoxicity in cancer cells treated with fluorescent nanoparticles

    PubMed Central

    Glazer, Evan S.; Curley, Steven A.

    2010-01-01

    Background Non-ionizing radiation, such as radiofrequency (RF) field and near infrared laser, induces thermal cytotoxicity in cancer cells treated with gold nanoparticles (AuNP). Quantum dots (QD) are fluorescent semiconducting nanoparticles that we hypothesize will induce similar injury following RF field irradiation. Methods AuNP and two types of QD (cadmium-selenide and indium-gallium-phosphide) conjugated to cetuximab (C225), a monoclonal antibody against human epidermal growth factor receptor (EGFR-1), demonstrated concentration-dependent heating in a RF field. We investigated the effect of RF field exposure after targeted nanoparticle treatment in a co-culture of two human cancer cell lines that have differential EGFR-1 expression (a high expressing pancreatic carcinoma, Panc-1, and a low expressing breast carcinoma, Cama-1). Results RF exposed Panc-1 or Cama-1 cells not containing AuNP or QD had a viability greater than 92%. The viability of Panc-1 cells exposed to the RF field after treatment with 50 nM Au-C225 was 39.4% ± 8.3% without injury to bystander Cama-1 cells (viability was 93.7% ± 1.0%, p ~ 0.0006). Panc-1 cells treated with targeted Cd-Se QD were only 47.5% viable after RF field exposure (p < 0.0001 compared to RF only Panc-1 control cells). Targeted InGaP QD decreased Panc-1 viability to 58.2% ± 3.4% after RF field exposure (p ~ 0.0004 compared to Cama-1 and Panc-1 controls). Conclusion We selectively induced RF field cytotoxicity in Panc-1 cells without injury to bystander Cama-1 cells utilizing EGFR-1 targeted nanoparticles, and demonstrated an interesting bifunctionality of fluorescent nanoparticles as agents for both cancer cell imaging and treatment. PMID:20564640

  10. Resynthesis of sphingomyelin from plasma-membrane phosphatidylcholine in BHK cells treated with Staphylococcus aureus sphingomyelinase.

    PubMed Central

    Allan, D; Quinn, P

    1988-01-01

    About 60-65% of the total sphingomyelin in intact BHK cells is in a readily accessible pool which is rapidly degraded by Staphylococcus aureus sphingomyelinase. No more sphingomyelin is broken down in cells which have been fixed with glutaraldehyde or lysed with streptolysin O, suggesting that all the sphingomyelin which is available to the enzyme is on the cell surface. The inaccessible pool of sphingomyelin does not equilibrate with the plasma-membrane pool, even after prolonged incubation. Experiments using [3H]-choline show that much more phosphocholine is released from the intact cells treated with sphingomyelinase than can be accounted for by breakdown of the original cell-surface pool of sphingomyelin; the excess appears to be a consequence of the breakdown of sphingomyelin newly resynthesized at the expense of a pool of phosphatidylcholine which represents about 8% of total cell phosphatidylcholine and may reside in the plasma membrane. This would be consistent with resynthesis of cell-surface sphingomyelin by the phosphatidylcholine: ceramide phosphocholinetransferase pathway, which has previously been shown to be localized in the plasma membrane. However, in [3H]palmitate-labelled cells there appeared to be no accumulation of the diacylglycerol expected to be produced by this reaction, and no enhanced synthesis of phosphatidate or phosphatidylinositol; instead there was an increased synthesis of triacylglycerol. A similar increase in labelling of triacylglycerol was seen in enzyme-treated cells where the sphingomyelinase was subsequently removed, allowing resynthesis of sphingomyelin which occurred at a rate of about 25% of total sphingomyelin/h. Treatment of BHK cells with sphingomyelinase caused no change in the rates of fluid-phase endocytosis or exocytosis as measured with [3H]inulin. PMID:2848498

  11. Use of stem cell transplantation to treat epilepsy: A Web of Science-based literature analysis

    PubMed Central

    Yin, Zhongmin; Dong, Yushu; Zhang, Jiyang; Wang, Li

    2012-01-01

    OBJECTIVE: To identify global research trends in the use of stem cell transplantation to treat epilepsy. DATA RETRIEVAL: We performed a bibliometric analysis of studies on the use of stem cell transplantation to treat epilepsy during 2002–2011, retrieved from Web of Science, using the key words epilepsy or epileptic or epilepticus or seizure and “stem cell”. SELECTION CRITERIA: Inclusion criteria: (a) peer-reviewed published articles on the use of stem cell transplantation to treat epilepsy indexed in Web of Science; (b) original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material, and news items. MAIN OUTCOME MEASURES: (a) Annual publication output; (b) type of publication; (c) publication by research field; (d) publication by journal; (e) publication by author; (f) publication by country and institution; (g) publications by institution in China; (h) most-cited papers; and (i) papers published by Chinese authors or institutions. RESULTS: A total of 460 publications on the use of stem cell transplantation to treat epilepsy were retrieved from Web of Science, 2002–2011. The number of publications gradually increased over the 10-year study period. Articles and reviews constituted the major types of publications. More than half of the studies were in the field of neuroscience/neurology. The most prolific journals for this topic were Epilepsia, Bone Marrow Transplantation, and Journal of Neuroscience. Of the 460 publications, almost half came from American authors and institutions; relatively few papers were published by Chinese authors or institutions. CONCLUSION: Literature on stem cell transplantation for epilepsy includes many reports of basic research, but few of clinical trials or treatments. Exact effects are not yet evaluated. Epilepsy rehabilitation is a long-term, complex, and comprehensive system engineering. With advances in medical development, some effective medical, social and educational measures

  12. Nutritional interventions to prevent and treat osteoarthritis. Part I: focus on fatty acids and macronutrients.

    PubMed

    Lopez, Hector L

    2012-05-01

    Osteoarthritis (OA) is the most common cause of musculoskeletal disability in elderly individuals, and it places an enormous economic burden on society. Management of OA is primarily focused on palliative relief by using agents such as nonsteroidal anti-inflammatory drugs and analgesics. However, such an approach is limited by a narrow therapeutic focus that fails to address the progressive and multimodal nature of OA. Given the favorable safety profile of most nutritional interventions, identifying disease-modifying nutritional agents capable of improving symptoms and also preventing, slowing, or even reversing the degenerative process in OA should remain an important paradigm in translational and clinical research. Applying advances in nutritional science to musculoskeletal medicine remains challenging, given the fluid and dynamic nature of the field, along with a rapidly developing regulatory climate over manufacturing and commerce requirements. The aim of this article is to review the available literature on effectiveness and potential mechanism of macronutrients for OA, with a focus on the following: long-chain ω-3 essential fatty acids eicosapentaenoic acid and docosahexaenoic acid, functional ω-6 fatty acid γ-linolenic acid, and macronutrient composition of background diet. There also is a discussion about the concept of rational polysupplementation via the strategic integration of multiple nutraceuticals with potential complementary mechanisms for improving outcomes in OA. As applied nutritional science evolves, it will be important to stay on the forefront of proteomics, metabolomics, epigenetics, and nutrigenomics, because they hold enormous potential for developing novel therapeutic and prognostic breakthroughs in many areas of medicine, including OA.

  13. Requirements of glycerol and fatty acid for triglyceride synthesis and ketogenesis by hepatocytes from normal and triiodothyronine-treated rats

    SciTech Connect

    Olubadewo, J.O.; Heimberg, M.

    1985-11-15

    Hepatocytes from T3-treated rats synthesized less triglyceride and more ketone bodies from (1-/sup 14/C)oleate at all concentrations from 0-2 mM, than did hepatocytes from euthyroid animals; addition of 1.0 mM glycerol increased triglyceride synthesis and reduced ketogenesis in hepatocytes from T3-treated rats to the rates observed in euthyroid hepatocytes in the absence of added glycerol. Glycerol did not alter triglyceride synthesis, but reduced ketogenesis genesis by euthyroid hepatocytes. It is probable from these and other data that, in the hyperthyroid rat, glycero-3-P, and not fatty acid, is rate limiting for synthesis of triglyceride, and, secondarily for reducing rates of ketogenesis in the hepatocyte.

  14. Citric acid induces cell-cycle arrest and apoptosis of human immortalized keratinocyte cell line (HaCaT) via caspase- and mitochondrial-dependent signaling pathways.

    PubMed

    Ying, Tsung-Ho; Chen, Chia-Wei; Hsiao, Yu-Ping; Hung, Sung-Jen; Chung, Jing-Gung; Yang, Jen-Hung

    2013-10-01

    Citric acid is an alpha-hydroxyacid (AHA) widely used in cosmetic dermatology and skincare products. However, there is concern regarding its safety for the skin. In this study, we investigated the cytotoxic effects of citric acid on the human keratinocyte cell line HaCaT. HaCaT cells were treated with citric acid at 2.5-12.5 mM for different time periods. Cell-cycle arrest and apoptosis were investigated by 4,6-diamidino-2-phenylindole dihydrochloride (DAPI) staining, flow cytometry, western blot and confocal microscopy. Citric acid not only inhibited proliferation of HaCaT cells in a dose-dependent manner, but also induced apoptosis and cell cycle-arrest at the G2/M phase (before 24 h) and S phase (after 24 h). Citric acid increased the level of Bcl-2-associated X protein (BAX) and reduced the levels of B-cell lymphoma-2 (BCL-2), B-cell lymphoma-extra large (BCL-XL) and activated caspase-9 and caspase-3, which subsequently induced apoptosis via caspase-dependent and caspase-independent pathways. Citric acid also activated death receptors and increased the levels of caspase-8, activated BH3 interacting-domain death agonist (BID) protein, Apoptosis-inducing factor (AIF), and Endonuclease G (EndoG). Therefore, citric acid induces apoptosis through the mitochondrial pathway in the human keratinocyte cell line HaCaT. The study results suggest that citric acid is cytotoxic to HaCaT cells via induction of apoptosis and cell-cycle arrest in vitro.

  15. Cell Adhesion and in Vivo Osseointegration of Sandblasted/Acid Etched/Anodized Dental Implants

    PubMed Central

    Kim, Mu-Hyon; Park, Kyeongsoon; Choi, Kyung-Hee; Kim, Soo-Hong; Kim, Se Eun; Jeong, Chang-Mo; Huh, Jung-Bo

    2015-01-01

    The authors describe a new type of titanium (Ti) implant as a Modi-anodized (ANO) Ti implant, the surface of which was treated by sandblasting, acid etching (SLA), and anodized techniques. The aim of the present study was to evaluate the adhesion of MG-63 cells to Modi-ANO surface treated Ti in vitro and to investigate its osseointegration characteristics in vivo. Four different types of Ti implants were examined, that is, machined Ti (control), SLA, anodized, and Modi-ANO Ti. In the cell adhesion study, Modi-ANO Ti showed higher initial MG-63 cell adhesion and induced greater filopodia growth than other groups. In vivo study in a beagle model revealed the bone-to-implant contact (BIC) of Modi-ANO Ti (74.20% ± 10.89%) was much greater than those of machined (33.58% ± 8.63%), SLA (58.47% ± 12.89), or ANO Ti (59.62% ± 18.30%). In conclusion, this study demonstrates that Modi-ANO Ti implants produced by sandblasting, acid etching, and anodizing improve cell adhesion and bone ongrowth as compared with machined, SLA, or ANO Ti implants. These findings suggest that the application of Modi-ANO surface treatment could improve the osseointegration of dental implant. PMID:25955650

  16. Stem cell transplantation with S-59 photochemically treated T-cell add-backs to establish allochimerism in murine thalassemia.

    PubMed

    Kuypers, Frans A; Watson, Gordon; Sage, Ezra; Walters, Mark C; Hamrick, James; Hearst, John E

    2005-01-01

    Hematopoietic cell transplantation (HCT) from HLA-identical sibling donors has curative potential for beta-thalassemia. The probability of surviving free of thalassemia under these conditions is approximately 85%. The application of this therapy is limited because many patients lack an HLA-identical sibling donor. HLA-mismatched stem cell transplantation for thalassemia is severely restricted by graft rejection and the risks for graft-versus-host disease (GVHD). Thus, the development of a novel method that facilitates immunological tolerance and improves the safety of HLA-mismatched HCT would greatly expand the opportunity of HCT for thalassemia patients. We hypothesized that removal of T cells from the donor hematopoietic stem cell preparation and subsequent add-back after photochemical treatment with S-59, a psoralen, would promote and stabilize the engraftment and significantly reduce the risk of GVHD. This was tested in a MHC-mismatched HCT model of murine thalassemia. S-59-treated T cells were infused simultaneously with bone marrow-derived stem cells into mice with a heterozygous deletion of one beta-globin alleles that had been conditioned with a sublethal dose of total body irradiation. Mice that received treated T cells showed increased engraftment compared to those that did not receive T cells. T-cell treatment improved survival without GVHD compared to recipients that received untreated T cells. We conclude that photochemical treatment of T cells facilitates engraftment and minimizes GVHD in allo-HCT for murine thalassemia, and sets the stage for further development of such protocols for the treatment of patients with thalassemia.

  17. Tolfenamic acid inhibits neuroblastoma cell proliferation and induces apoptosis: a novel therapeutic agent for neuroblastoma.

    PubMed

    Eslin, Don; Sankpal, Umesh T; Lee, Chris; Sutphin, Robert M; Maliakal, Pius; Currier, Erika; Sholler, Giselle; Khan, Moeez; Basha, Riyaz

    2013-05-01

    Current therapeutic options for recurrent neuroblastoma have poor outcomes that warrant the development of novel therapeutic strategies. Specificity protein (Sp) transcription factors regulate several genes involved in cell proliferation, survival, and angiogenesis. Sp1 regulates genes believed to be important determinants of the biological behavior of neuroblastoma. Tolfenamic acid (TA), a non-steroidal anti-inflammatory drug, is known to induce the degradation of Sp proteins and may serve as a novel anti-cancer agent. The objective of this investigation was to examine the anti-cancer activity of TA using established human neuroblastoma cell lines. We tested the anti-proliferative effect of TA using SH-SY5Y, CHLA90, LA1 55n, SHEP, Be2c, CMP 13Y, and SMS KCNR cell lines. Cells were treated with TA (0/25/50/100 µM) and cell viability was measured at 24, 48, and 72 h post-treatment. Selected neuroblastoma cell lines were treated with 50 µM TA for 24 and 48 h and tested for cell apoptosis using Annexin-V staining. Caspase activity was measured with caspase 3/7 Glo kit. Cell lysates were prepared and the expression of Sp1, survivin, and c-PARP were evaluated through Western blot analysis. TA significantly inhibited the growth of neuroblastoma cells in a dose/time-dependent manner and significantly decreased Sp1 and survivin expression. Apart from cell cycle (G0/G1) arrest, TA caused significant increase in the apoptotic cell population, caspase 3/7 activity, and c-PARP expression. These results show that TA effectively inhibits neuroblastoma cell growth potentially through suppressing mitosis, Sp1, and survivin expression, and inducing apoptosis. These results show TA as a novel therapeutic agent for neuroblastoma.

  18. Integral edge seals for phosphoric acid fuel cells

    DOEpatents

    Granata, Jr., Samuel J.; Woodle, Boyd M.; Dunyak, Thomas J.

    1992-01-01

    A phosphoric acid fuel cell having integral edge seals formed by an elastomer permeating an outer peripheral band contiguous with the outer peripheral edges of the cathode and anode assemblies and the matrix to form an integral edge seal which is reliable, easy to manufacture and has creep characteristics similar to the anode, cathode and matrix assemblies inboard of the seals to assure good electrical contact throughout the life of the fuel cell.

  19. Donor Umbilical Cord Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies

    ClinicalTrials.gov

    2015-12-18

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Erythroleukemia (M6a); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Adult Pure Erythroid Leukemia (M6b); B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; Blastic Phase Chronic Myelogenous Leukemia; Burkitt Lymphoma; Childhood Acute Erythroleukemia (M6); Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Juvenile Myelomonocytic Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Previously Treated Myelodysplastic Syndromes; Prolymphocytic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult

  20. Ursolic acid and oleanolic acid from Eriobotrya fragrans inhibited the via