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Yaghoub Rahimi Amir Mehdizadeh Hojjatollah Nozad Charoudeh Mohammad Nouri Kobra Valaei Shabnam Fayezi Masoud Darabi 《Development, growth & differentiation》2015,57(9):667-674
Stearoyl‐CoA desaturase 1 (SCD1) plays important roles in organ development, glucose tolerance, insulin sensitivity, and cancer. Here, we examined the role of SCD1 for the differentiation of human induced pluripotent stem (hiPS) cells to liver cells by using drug inhibition and biochemical experiments. hiPS cells cultured in a pro‐hepatic medium were exposed to an SCD1 inhibitor at various stages throughout differentiation. Liver‐specific markers, specifically α‐fetoprotein, albumin and urea in conditioned medium, and hepatocyte nuclear factor 4α (HNF4α) and cytochrome P450 7A1 (CYP7A1) gene expressions and triglyceride in cellular extracts were analyzed at various development stages. Measures of hepatocyte‐specific function and triglyceride accumulation in later stages were strongly inhibited a minimum of −29% (P < 0.05) by SCD1 inhibitor in the early stage of hepatic differentiation and effectively reversed (>30%, P < 0.01) by the addition of oleate. The results were also reproducible with human primary mononuclear cells (hPMN). SCD1 inhibitor had no significant effect on liver‐specific markers when it was added in the hepatic maturation stage. However, it strikingly led to higher albumin (1.6‐fold, P = 0.03) and urea (1.9‐fold, P = 0.02) production, and HNF4α (1.9‐fold, P = 0.02) and CYP7A1 (1.3‐fold, P = 0.03) expression upon incubation during the lineage‐commitment stage. Hepatic differentiation from cultured hiPS cells is sensitive to SCD1 inhibition and this sensitivity is affected by the stage of cellular differentiation. Notably, findings also indicate that this notion can be extended to hPMN. The requirement for SCD1 activity in functional differentiation of hepatocytes may have relevance for human liver disease and metabolic dysregulation. 相似文献
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Iman Mehdizadeh Gohari Valeria R. Parreira Victoria J. Nowell Vivian M. Nicholson Kaitlyn Oliphant John F. Prescott 《PloS one》2015,10(4)
A role for type A Clostridium perfringens in acute hemorrhagic and necrotizing gastroenteritis in dogs and in necrotizing enterocolitis of neonatal foals has long been suspected but incompletely characterized. The supernatants of an isolate made from a dog and from a foal that died from these diseases were both found to be highly cytotoxic for an equine ovarian (EO) cell line. Partial genome sequencing of the canine isolate revealed three novel putative toxin genes encoding proteins related to the pore-forming Leukocidin/Hemolysin Superfamily; these were designated netE, netF, and netG. netE and netF were located on one large conjugative plasmid, and netG was located with a cpe enterotoxin gene on a second large conjugative plasmid. Mutation and complementation showed that only netF was associated with the cytotoxicity. Although netE and netG were not associated with cytotoxicity, immunoblotting with specific antisera showed these proteins to be expressed in vitro. There was a highly significant association between the presence of netF with type A strains isolated from cases of canine acute hemorrhagic gastroenteritis and foal necrotizing enterocolitis. netE and netF were found in all cytotoxic isolates, as was cpe, but netG was less consistently present. Pulsed-field gel electrophoresis showed that netF-positive isolates belonged to a clonal population; some canine and equine netF-positive isolates were genetically indistinguishable. Equine antisera to recombinant Net proteins showed that only antiserum to rNetF had high supernatant cytotoxin neutralizing activity. The identifica-tion of this novel necrotizing toxin is an important advance in understanding the virulence of type A C. perfringens in specific enteric disease of animals. 相似文献
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Iman Mehdizadeh Gohari Andrew M. Kropinski Scott J. Weese Valeria R. Parreira Ashley E. Whitehead Patrick Boerlin John F. Prescott 《PloS one》2016,11(2)
The recent discovery of a novel beta-pore-forming toxin, NetF, which is strongly associated with canine and foal necrotizing enteritis should improve our understanding of the role of type A Clostridium perfringens associated disease in these animals. The current study presents the complete genome sequence of two netF-positive strains, JFP55 and JFP838, which were recovered from cases of foal necrotizing enteritis and canine hemorrhagic gastroenteritis, respectively. Genome sequencing was done using Single Molecule, Real-Time (SMRT) technology-PacBio and Illumina Hiseq2000. The JFP55 and JFP838 genomes include a single 3.34 Mb and 3.53 Mb chromosome, respectively, and both genomes include five circular plasmids. Plasmid annotation revealed that three plasmids were shared by the two newly sequenced genomes, including a NetF/NetE toxins-encoding tcp-conjugative plasmid, a CPE/CPB2 toxins-encoding tcp-conjugative plasmid and a putative bacteriocin-encoding plasmid. The putative beta-pore-forming toxin genes, netF, netE and netG, were located in unique pathogenicity loci on tcp-conjugative plasmids. The C. perfringens JFP55 chromosome carries 2,825 protein-coding genes whereas the chromosome of JFP838 contains 3,014 protein-encoding genes. Comparison of these two chromosomes with three available reference C. perfringens chromosome sequences identified 48 (~247 kb) and 81 (~430 kb) regions unique to JFP55 and JFP838, respectively. Some of these divergent genomic regions in both chromosomes are phage- and plasmid-related segments. Sixteen of these unique chromosomal regions (~69 kb) were shared between the two isolates. Five of these shared regions formed a mosaic of plasmid-integrated segments, suggesting that these elements were acquired early in a clonal lineage of netF-positive C. perfringens strains. These results provide significant insight into the basis of canine and foal necrotizing enteritis and are the first to demonstrate that netF resides on a large and unique plasmid-encoded locus. 相似文献
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OBJECTIVE: To determine the diagnostic accuracy of cytology smears in distinguishing between tube and non-tube structures. METHODS: One hundred cytology smears of fallopian tube and non-tube structures (vessels, round and ovarian ligaments) were prepared from surgically removed uterus and fallopian tube specimens and stained by the Papanicolaou method. The slides were reviewed blindly by pathologists and interpreted as tube or non-tube structures. The results were compared to the histological examination of the same specimens. FINDINGS: Results indicated an overall accuracy of 97% with a specificity of 98% and sensitivity of 96% for cytology smears, taking histology as the gold standard. Positive and negative predictive values were 96.1% and 97.9%, respectively. CONCLUSION: Cytology smears are a convenient and cost effective tool for laboratory confirmation of tubal sterilization. This method can reduce the costs of laboratory examination, especially in developing countries, where tubal sterilizations are done in large cohorts. However, histological slides remain the gold standard in cases of medicolegal problems. 相似文献
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Ghorbanpour Monireh Soltani Behzad Mota Ali Jahanbin Sardroodi Jaber Mehdizadeh Aghdam Elnaz Shayanfar Ali Molavi Ommoleila Mohammad-Rezaei Rahim Ebadi-Nahari Mostafa Ziegler Christopher J. 《Biometals》2022,35(5):1095-1111
BioMetals - A group of bidentate nitrogen and sulfur donor pyrazole derivative ligands abbreviated as Na[RNCS(Pz)], Na[RNCS(PzMe2)], Na[RNCS(PzMe3)], Na[RNCS(PzPhMe)], Na[RNCS(PzPh2)], where... 相似文献
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Davies NA Hodges SJ Pitsillides AA Mookerjee RP Jalan R Mehdizadeh S 《FEBS letters》2006,580(8):2123-2128
The production of nitric oxide (NO) in liver disease and its role in vascular control has been a subject of much interest in recent years. However, the activity of guanylate cyclase (GC), the enzyme activated by NO has received little attention with regard to liver disease. In this study we have utilised a quantitative cytochemical technique to examine the activity of GC on a per cell basis in a rat model of cirrhosis. Our results show a significant reduction in GC activity, indicating that vascular regulation is likely to be substantially affected irrespective of NO generation in this disease model. 相似文献
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Kealley CS Rout MK Dezfouli MR Strounina E Whittaker AK Appelqvist IA Lillford PJ Gilbert EP Gidley MJ 《Biomacromolecules》2008,9(10):2937-2946
We report a multitechnique study of structural organization and molecular mobility for soy glycinin at a low moisture content (<30% w/w) and relate these to its glass-to-rubber transition. Small-angle X-ray scattering (SAXS), differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, and nuclear magnetic resonance (NMR) spectroscopy are used to probe structure and mobility on different length and time scales. NMR (approximately 10(-6) to 10(-3) s) reveals transitions at a higher moisture content (>17%) than DSC or SAXS, which sample for much longer times (approximately 10 to 10(3) s) and where changes are detected at >13% water content at 20 degrees C. The mobility transitions are accompanied by small changes in unit-cell parameters and IR band intensities and are associated with the enhanced motion of the polypeptide backbone. This study shows how characteristic features of the ordered regions of the protein (probed by SAXS and FTIR) and mobile segments (probed by NMR and DSC) can be separately monitored and integrated within a mobility transformation framework. 相似文献