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121.
Activation of BRCA1/BRCA2-associated helicase BACH1 is required for timely progression through S phase
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BACH1 (also known as FANCJ and BRIP1) is a DNA helicase that directly interacts with the C-terminal BRCT repeat of the breast cancer susceptibility protein BRCA1. Previous biochemical and functional analyses have suggested a role for the BACH1 homolog in Caenorhabditis elegans during DNA replication. Here, we report the association of BACH1 with a distinct BRCA1/BRCA2-containing complex during the S phase of the cell cycle. Depletion of BACH1 or BRCA1 using small interfering RNAs results in delayed entry into the S phase of the cell cycle. Such timely progression through S phase requires the helicase activity of BACH1. Importantly, cells expressing a dominant negative mutation in BACH1 that results in a defective helicase displayed increased activation of DNA damage checkpoints and genomic instability. BACH1 helicase is silenced during the G(1) phase of the cell cycle and is activated through a dephosphorylation event as cells enter S phase. These results point to a critical role for BACH1 helicase activity not only in the timely progression through the S phase but also in maintaining genomic stability. 相似文献
122.
Oryan Ahmad Alemzadeh Esmat Eskandari Mohammad Hadi 《Probiotics and antimicrobial proteins》2019,11(3):874-886
Probiotics and Antimicrobial Proteins - Kefir is a natural probiotic compound with a long history of health benefits which can improve wound healing. This study investigated the regeneration... 相似文献
123.
Rozita Ziaei Maryam Ayatollahi Ramin Yaghobi Zeinab Sahraeian Nosratollah Zarghami 《Molecular biology reports》2014,41(2):1059-1066
Cell therapy and tissue repair are used in a variety of diseases including tissue and organ transplantation, autoimmune diseases and cancers. Now mesenchymal stem cells (MSCs) are an attractive and promising source for cell-based therapy according to their individual characteristics. Soluble factors which are able to induce MSCs migration have a vital role in cell engraftment and tissue regeneration. Tumor necrosis factor α (TNF-α) is a major cytokine present in damaged tissues. We have investigated the pattern of gene expression of chemokine receptor CXCR4 in nine groups of human bone marrow-derived MSCs stimulated with TNF-α in different dose and time manner. Comparison of TNF-α treated with untreated MSCs revealed the highest expression level of CXCR4 after treatment with 1, and 10 ng/ml of TNF-α in 24 h, and the production of CXCR4 mRNA was regulated up to 216 and 512 fold, respectively. Our results demonstrated the differential gene expression pattern of chemokine receptor CXCR4 in human marrow-derived MSCs stimulated with inflammatory cytokine TNF-α. These findings suggest that in vitro control of both dose and time factors may be important in stem cell migration capacity, and perhaps in future-stem cell transplantation therapies. 相似文献
124.
Alireza Abdanipour Taki Tiraihi Ali Noori-Zadeh Arezo Majdi Ramin Gosaili 《Molecular neurobiology》2014,49(3):1364-1372
Reactive oxygen species and oxidative stress are associated with various cell processes, including cell survival and apoptosis. Oxidative stress has been implicated in the pathogenesis of several neurological disorders including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and multiple sclerosis (MS). In the present study, we evaluated the effects of lovastatin chemoprotection against hydrogen peroxide-induced oxidative stress in bone marrow stromal cell-derived neural stem cells (BMSC-derived NSCs) and whether it has protective effects. BMSC-derived NSCs were pretreated with different doses of lovastatin for 48 h and then exposed to 125 μM H2O2 for 30 min. Using MTT, TUNEL assay, and real-time RT-PCR, we evaluated the effects of lovastatin on cell survival, apoptosis, and PGC-1α and Nrf2 expression rates in pretreated BMSC-derived NSCs compared to control groups. Results showed that apoptosis rate in the lovastatin-pretreated BMSC-derived NSCs was significantly decreased compared to the control group. Our findings suggest that lovastatin protects NSCs against oxidative stress-induced cell death, and therefore, it may be used to promote the survival rate of NSCs and can be a candidate for treatment of oxidative stress-mediated neurological diseases. 相似文献
125.
Baligh R. Yehia Ramin S. Herati John A. Fleishman Joel E. Gallant Allison L. Agwu Stephen A. Berry P. Todd Korthuis Richard D. Moore Joshua P. Metlay Kelly A. Gebo for the HIV Research Network 《PloS one》2014,9(7)
Objectives
Guidelines recommend hepatitis C virus (HCV) screening for all people living with HIV (PLWH). Understanding HCV testing practices may improve compliance with guidelines and can help identify areas for future intervention.Methods
We evaluated HCV screening and unnecessary repeat HCV testing in 8,590 PLWH initiating care at 12 U.S. HIV clinics between 2006 and 2010, with follow-up through 2011. Multivariable logistic regression examined the association between patient factors and the outcomes: HCV screening (≥1 HCV antibody tests during the study period) and unnecessary repeat HCV testing (≥1 HCV antibody tests in patients with a prior positive test result).Results
Overall, 82% of patients were screened for HCV, 18% of those screened were HCV antibody-positive, and 40% of HCV antibody-positive patients had unnecessary repeat HCV testing. The likelihood of being screened for HCV increased as the number of outpatient visits rose (adjusted odds ratio 1.02, 95% confidence interval 1.01–1.03). Compared to men who have sex with men (MSM), patients with injection drug use (IDU) were less likely to be screened for HCV (0.63, 0.52–0.78); while individuals with Medicaid were more likely to be screened than those with private insurance (1.30, 1.04–1.62). Patients with heterosexual (1.78, 1.20–2.65) and IDU (1.58, 1.06–2.34) risk compared to MSM, and those with higher numbers of outpatient (1.03, 1.01–1.04) and inpatient (1.09, 1.01–1.19) visits were at greatest risk of unnecessary HCV testing.Conclusions
Additional efforts to improve compliance with HCV testing guidelines are needed. Leveraging health information technology may increase HCV screening and reduce unnecessary testing. 相似文献126.
Access of gene regulatory factors to the eukaryotic genome is modulated by chromatin. The organization of this nucleoprotein complex is highly dynamic and tightly regulated. The control of wide-ranging nuclear processes through the configuration of chromatin is achieved by the concerted actions of ATP-dependent chromatin-remodeling complexes and histone-modifying enzymes, and by the incorporation of specialized histone variants. It is becoming clear that perturbation of these chromatin modifiers can lead to cancer. Recent findings illustrate the mechanisms by which chromatin influences cancer development, and aid understanding of the regulation of chromatin organization, cellular transformation and the connections between tumor suppressor and oncogene function. 相似文献
127.
Vasudevan A Conner SE Gentles RG Faghih R Liu H Dwight W Ireland L Kang CH Esbenshade TA Bennani YL Hancock AA 《Bioorganic & medicinal chemistry letters》2002,12(21):3055-3058
The synthesis and biological evaluation of novel antagonists of the rat H(3) receptor are described. These compounds differ from prototypical H(3) antagonists in that they do not contain an imidazole moiety, but rather a substituted aminopyrrolidine moiety. A systematic modification of the substituents on the aminopyrrolidine ring was performed using pre-formatted precursor sets, where applicable, to afford several compounds with high affinity and selectivity for the H(3) receptor. 相似文献
128.
Quick K Zhao J Eijkelkamp N Linley JE Rugiero F Cox JJ Raouf R Gringhuis M Sexton JE Abramowitz J Taylor R Forge A Ashmore J Kirkwood N Kros CJ Richardson GP Freichel M Flockerzi V Birnbaumer L Wood JN 《Open biology》2012,2(5):120068
Transient receptor potential (TRP) channels TRPC3 and TRPC6 are expressed in both sensory neurons and cochlear hair cells. Deletion of TRPC3 or TRPC6 in mice caused no behavioural phenotype, although loss of TRPC3 caused a shift of rapidly adapting (RA) mechanosensitive currents to intermediate-adapting currents in dorsal root ganglion sensory neurons. Deletion of both TRPC3 and TRPC6 caused deficits in light touch and silenced half of small-diameter sensory neurons expressing mechanically activated RA currents. Double TRPC3/TRPC6 knock-out mice also showed hearing impairment, vestibular deficits and defective auditory brain stem responses to high-frequency sounds. Basal, but not apical, cochlear outer hair cells lost more than 75 per cent of their responses to mechanical stimulation. FM1-43-sensitive mechanically gated currents were induced when TRPC3 and TRPC6 were co-expressed in sensory neuron cell lines. TRPC3 and TRPC6 are thus required for the normal function of cells involved in touch and hearing, and are potential components of mechanotransducing complexes. 相似文献
129.
Background
Ventilator-associated pneumonia (VAP) carries significant mortality and morbidity. Predicting which patients will become infected could lead to measures to reduce the incidence of VAP.Methodology/Principal Findings
The goal was to begin constructing a model for VAP prediction in critically-injured trauma patients, and to identify differentially expressed genes in patients who go on to develop VAP compared to similar patients who do not. Gene expression profiles of lipopolysaccharide stimulated blood cells in critically injured trauma patients that went on to develop ventilator-associated pneumonia (n = 10) was compared to those that never developed the infection (n = 10). Eight hundred and ten genes were differentially expressed between the two groups (ANOVA, P<0.05) and further analyzed by hierarchical clustering and principal component analysis. Functional analysis using Gene Ontology and KEGG classifications revealed enrichment in multiple categories including regulation of protein translation, regulation of protease activity, and response to bacterial infection. A logistic regression model was developed that accurately predicted critically-injured trauma patients that went on to develop VAP (VAP+) and those that did not (VAP−). Five genes (PIK3R3, ATP2A1, PI3, ADAM8, and HCN4) were common to all top 20 significant genes that were identified from all independent training sets in the cross validation. Hierarchical clustering using these five genes accurately categorized 95% of patients and PCA visualization demonstrated two discernable groups (VAP+ and VAP−).Conclusions/Significance
A logistic regression model using cross-validation accurately predicted patients that developed ventilator-associated pneumonia and should now be tested on a larger cohort of trauma patients. 相似文献130.
CD28, cytotoxic T-lymphocyte associated antigen 4 (CTLA4), inducible costimulator (ICOS) and programmed cell death 1 are closely-linked genes located on chromosome 2q and encode co-stimulatory molecules, which are T-cell activity regulators. The principal assignment of T-cell mediated immune response in allograft rejection is an interesting topic of multiple studies. Although the variation in these genes may influence the graft survival and the amount of immunosuppression needed, the studies so far have been restricted solely to the CTLA4 gene. In 145 patients who underwent liver allograft transplantation, 10 single nucleotide polymorphisms of CD28, CTLA4, ICOS, and PD.1 genes were defined. To distinguish the polymorphisms of all 10 SNPs, PCR-RFLP method was used and according to the standard criteria, acute rejection episodes were determined. CTLA4-1661, AA genotype was significantly more frequent in the patients with acute rejection and AG genotype was significantly more frequent in the patients without rejection. Frequencies of CTLA4+49 AG A allele and CTLA4-1661AG A allele were significantly higher than those of CTLA4+49 AG and CTLA4-1661AG, G allele in the patients with acute rejection. ICOS+693, GG genotype and G allele were significantly less frequent in the patients with acute rejection and CD28 CT genotype was significantly more in patients with acute rejection. The present results demonstrate that potentially functional genetic variation in T-cell co-stimulatory molecules including ICOS, CTLA4 and CD28 can influence liver transplant outcome. 相似文献