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211.
Xiao Zhu Jinfang Zhang Wenguo Fan Yunguo Gong Jianhua Yan Zhidong Yuan Lang Wu Hongjing Cui Haiqing Luo Qingming Kong Li Tang Shuilong Leng Yufeng Liao Weiming Fu Qin Xiao Dongpei Li 《PloS one》2014,9(8)
Chronic infection with Schistosoma japonicum is an important cause of hepatic fibrosis (HF). Human 9q33.3 is one of the most important loci for stress-related diseases. We examined the potential associations of 43 single-nucleotide polymorphisms (SNPs) with S. japonicum infection and HF in epidemic region in China. We identified a SNP (rs10118570 GG in mitogen-activated protein kinase associated protein 1, MAPKAP1) contributes to anti-infection (adjusted OR = 0.35) and anti-fibrogenesis (adjusted RR = 0.44) in the discovery study. Replicative and combined studies showed consistent protective quality for this genotype (replicative: adjusted OR = 0.37 for anti-infection, and adjusted RR = 0.40 for anti-fibrogenesis; Combined: adjusted OR = 0.45 for anti-infection, and adjusted RR = 0.42 for anti-fibrogenesis). Univariate and multivariate analysis in the discovery, replicative and combined studies, suggested that durations (years), splenomegaly, serum ALB and rs10118570 were independent predictors influencing the fibrogenesis. The analysis of gene-gene interaction showed rs10118570 functions independently. We conclude that MAPKAP1 may represent a novel anti-infection and anti-fibrogenesis genomic locus in chronic schistosomiasis japonica. And rs10118570 may be a potential biomarker and target for the treatment of this life-threatening ancient disease. 相似文献
212.
Kue Peng Lim Nicole Ai Leng Chun Siti Mazlipah Ismail Mannil Thomas Abraham Mohd Nury Yusoff Rosnah Binti Zain Wei Cheong Ngeow Sathibalan Ponniah Sok Ching Cheong 《PloS one》2014,9(8)
Regulatory T cells (Tregs), a subset of CD4+ T cells plays a pivotal role in regulating the immune system. An increase in Treg numbers enables cancer progression by dampening the immune system and allowing tumor cells to evade immune detection and destruction. An increase in Treg numbers and expression of inhibitory cytokines including TGF-β and IL-10 are mechanisms by which Tregs exert their immune suppressive function. However, the presence of Tregs and inhibitory cytokines in oral cancer patients is still unclear. In this study, the presence of circulating Tregs in 39 oral cancer patients and 24 healthy donors was examined by studying the presence of the CD4+CD25hiCD127low cell population in their peripheral blood mononuclear cells using flow cytometry. Serum levels of TGF-β and IL-10 were measured by ELISA. T cell subsets of OSCC patients were found to differ significantly from healthy donors where a decrease in CD8+ cytotoxic T cells and an increase in Tregs (CD4+CD25hiCD127low) were observed. Further, the ratio of CD8+ T cells/Tregs was also decreased in patients compared to healthy donors. The presence of Tregs was accompanied by a decrease in IL-10 but not TGF-β secretion in OSCC patients when compared to donors; in addition, the analysis also revealed that an increased presence of Tregs was accompanied by better patient survival. Amongst OSCC patients, smokers had significantly higher levels of TGF-β. It is apparent that the immune system is compromised in OSCC patients and the characterization of the Treg subpopulation could form a basis for improving our understanding of the perturbations in the immune system that occur during OSCC tumorigenesis. 相似文献
213.
Qian Wang Jinmei Peng Yan Sun Jiazeng Chen Tongqing An Chaoliang Leng Lin Li Hongyuan Zhao Xin Guo Xinna Ge Hanchun Yang Zhijun Tian 《PloS one》2014,9(10)
Highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) is a member of the genus Arterivirus within the family Arteriviridae. N and GP3 proteins are the immunodominance regions of the PRRSV viral proteins. To identify the B-cell linear antigenic epitopes within HP-PRRSV N and GP3 proteins, two monoclonal antibodies (mAbs) against N and GP3 proteins were generated and characterized, designated as 3D7 and 1F10 respectively. The mAb 3D7 recognized only HuN4-F112 not the corresponding virulent strain (HuN4-F5). It also recognized two other commercial vaccines (JXA1-R and TJM-F92), but not two other HP-PRRSV strains (HNZJJ-F1 and HLJMZ-F2). The B-cell epitope recognized by the mAb 3D7 was localized to N protein amino acids 7–33. Western blot showed that the only difference amino acid between HuN4-F112-N and HuN4-F5-N did not change the mAb 3D7 recognization to N protein. The epitope targeted by the mAb 1F10 was mapped by truncated proteins. We found a new epitope (68-76aa) can be recognized by the mAb. However, the epitope could not be recognized by the positive sera, suggesting the epitope could not induce antibody in pigs. These results should extend our understanding of the antigenic structure of the N protein and antigen-antibody reactions of the GP3 protein in different species. 相似文献
214.
Guoyang Huang Jiajun Xu Li Xu Shifeng Wang Runping Li Kan Liu Juan Zheng Zhiyu Cai Kun Zhang Yuandeng Luo Weigang Xu 《PloS one》2014,9(1)
Objective
Hyperbaric oxygen (HBO) preconditioning (HBO-PC) has been testified to have protective effects on spinal cord injury (SCI). However, the mechanisms remain enigmatic. The present study aimed to explore the effects of HBO-PC on primary rat spinal neurons against oxidative injury and oxygen-glucose deprivation (OGD) and the relationship with heat shock proteins (HSPs).Methods
Primary rat spinal neurons after 7 days of culture were used in this study. HSPs were detected in rat spinal neurons following a single exposure to HBO at different time points by Western blot. Using lactate dehydrogenase release assay and cell counting kit-8 assay, the injuries induced by hydrogen peroxide (H2O2) insult or OGD were determined and compared among neurons treated with HBO-PC with or without HSP inhibitors.Results
The results of Western blot showed that HSP27, HSP70 and HSP90 have a slight but not significant increase in primary neurons following HBO exposure. However, HSP32 expression significantly increased and reached highest at 12 h following HBO exposure. HBO-PC significantly increased the cell viability and decreased the medium lactate dehydrogenase content in cultures treated with H2O2 or OGD. Pretreatment with zinc protoporphyrin IX, a specific inhibitor of HSP32, significantly blocked the protective effects of HBO-PC.Conclusions
These results suggest that HBO-PC could protect rat spinal neurons in vitro against oxidative injury and OGD mostly by up-regulating of HSP32 expression. 相似文献215.
Fang Yuan Min Chen Jianchao Yang Bingying Leng Baoshan Wang 《In vitro cellular & developmental biology. Plant》2014,50(5):610-617
Limonium bicolor, a typical recretohalophyte, has a specialized salt-secreting structure in the epidermis called the salt gland and plays a significant role in improving saline land. Understanding the molecular mechanisms of salt secretion and salt gland development requires an efficient L. bicolor transformation system, which is described in this report. Leaf explants were incubated with Agrobacterium tumefaciens strain EHA105 harboring the plasmid pTCK303 containing the β-glucuronidase gene (GUS) as the transgene reporter and the hygromycin B resistance gene as a selectable marker. Up to 96.9% of leaves were induced to regenerate shoots on an Murashige and Skoog (MS) medium supplemented with 4.4 μM 6-benzyladenine and 1.1 μM α-naphthaleneacetic acid; roots were induced on the MS medium containing 2.5 μM indole-3-butyric acid. This tissue culture system was suitable for Agrobacterium-mediated transformation of L. bicolor. Pre-cultivated explants (2 d old) were incubated with Agrobacterium (0.6–0.7 at OD600) in a shaking culture for 20 min; the explants and bacterium were co-cultivated for 4 d in the dark before the explants were transferred to a selection medium containing 8 mg/L hygromycin B and 600 mg/L piperacillin sodium (added to prevent continued Agrobacterium growth). Histochemical assays and PCR to detect the GUS gene showed that transformation frequency was 4.43%. Quantitative PCR and Northern blotting further verified the integration and presence of the GUS gene in L. bicolor. This is the first report of an Agrobacterium-based transformation system for L. bicolor. The system will facilitate a research on the identity and function of genes involved in salt gland development and salt secretion. 相似文献
216.
217.
细胞色素P450酶系循环催化的新途径 总被引:1,自引:0,他引:1
细胞色素P45 0酶系的循环催化反应需要电子供体NADPH或NADH等辅助因子系统 ,因此它在实际应用中受到制约。用电极电解或锌粉作电子供体取代NADPH辅助因子可以获得与NADPH相似的底物转换率。此外 ,还讨论了P45 0的“定向进化”产生的突变体在无NADPH等辅助因子存在下 ,通过“过氧化物途径”使底物羟基化。 相似文献
218.
Tazeen Hasan Jafar Ngiap Chuan Tan Rupesh Madhukar Shirore John Carson Allen Eric Andrew Finkelstein Siew Wai Hwang Agnes Ying Leng Koong Peter Kirm Seng Moey Gary Chun-Yun Kang Chris Wan Teng Goh Reena Chandhini Subramanian Anandan Gerard Thiagarajah Chandrika Ramakrishnan Ching Wee Lim Jianying Liu for SingHypertension Study Group 《PLoS medicine》2022,19(6)
BackgroundDespite availability of clinical practice guidelines for hypertension management, blood pressure (BP) control remains sub-optimal (<30%) even in high-income countries. This study aims to assess the effectiveness of a potentially scalable multicomponent intervention integrated into primary care system compared to usual care on BP control.Methods and findingsA cluster-randomized controlled trial was conducted in 8 government clinics in Singapore. The trial enrolled 916 patients aged ≥40 years with uncontrolled hypertension (systolic BP (SBP) ≥140 mmHg or diastolic BP (DBP) ≥90 mmHg).Multicomponent intervention consisted of physician training in risk-based treatment of hypertension, subsidized losartan-HCTZ single-pill combination (SPC) medications, nurse training in motivational conversations (MCs), and telephone follow-ups. Usual care (controls) comprised of routine care in the clinics, no MC or telephone follow-ups, and no subsidy on SPCs. The primary outcome was mean SBP at 24 months’ post-baseline. Four clinics (447 patients) were randomized to intervention and 4 (469) to usual care. Patient enrolment commenced in January 2017, and follow-up was during December 2018 to September 2020. Analysis used intention-to-treat principles. The primary outcome was SBP at 24 months. BP at baseline, 12 and 24 months was modeled at the patient level in a likelihood-based, linear mixed model repeated measures analysis with treatment group, follow-up, treatment group × follow-up interaction as fixed effects, and random cluster (clinic) effects.A total of 766 (83.6%) patients completed 2-year follow-up. A total of 63 (14.1%) and 87 (18.6%) patients in intervention and in usual care, respectively, were lost to follow-up. At 24 months, the adjusted mean SBP was significantly lower in the intervention group compared to usual care (−3.3 mmHg; 95% CI: −6.34, −0.32; p = 0.03). The intervention led to higher BP control (odds ratio 1.51; 95% CI: 1.10, 2.09; p = 0.01), lower odds of high (>20%) 10-year cardiovascular risk score (OR 0.67; 95% CI: 0.47, 0.97; p = 0.03), and lower mean log albuminuria (−0.22; 95% CI: −0.41, −0.02; p = 0.03). Mean DBP, mortality rates, and serious adverse events including hospitalizations were not different between groups. The main limitation was no masking in the trial.ConclusionsA multicomponent intervention consisting of physicians trained in risk-based treatment, subsidized SPC medications, nurse-delivered motivational conversation, and telephone follow-ups improved BP control and lowered cardiovascular risk. Wide-scale implementation of a multicomponent intervention such as the one in our trial is likely to reduce hypertension-related morbidity and mortality globally.Trial registrationTrial Registration: Clinicaltrials.gov .Tazeen H Jafar and colleagues present findings from a cluster-randomized controlled trial conducted to evaluate the effectiveness of an intervention designed to manage hypertension. NCT02972619相似文献
219.
Hong-Guang Zhang Bin Wang Yong Yang Xuan Liu Junjie Wang Ning Xin Shifeng Li Ying Miao Qiuyu Wu Tingting Guo Yukang Yuan Yibo Zuo Xiangjie Chen Tengfei Ren Chunsheng Dong Jun Wang Hang Ruan Miao Sun Xingshun Xu Hui Zheng 《Cell research》2022,32(10):897
Depression is a serious public-health issue. Recent reports have suggested higher susceptibility to viral infections in depressive patients. However, how depression affects antiviral innate immune signaling remains unknown. Here, we revealed a reduction in expression of Abelson helper integration site 1 (AHI1) in the peripheral blood mononuclear cells (PBMCs) and macrophages from the patients with major depressive disorder (MDD), which leads to attenuated antiviral immune response. We found that depression-related arginine vasopressin (AVP) induces reduction of AHI1 in macrophages. Further studies demonstrated that AHI1 is a critical stabilizer of basal type-I-interferon (IFN-I) signaling. Mechanistically, AHI1 recruits OTUD1 to deubiquitinate and stabilize Tyk2, while AHI1 reduction downregulates Tyk2 and IFN-I signaling activity in macrophages from both MDD patients and depression model mice. Interestingly, we identified a clinical analgesic meptazinol that effectively stimulates AHI1 expression, thus enhancing IFN-I antiviral defense in depression model mice. Our study promotes the understanding of the signaling mechanisms of depression-mediated antiviral immune dysfunction, and reveals meptazinol as an enhancer of antiviral innate immunity in depressive patients.Subject terms: Innate immunity, Ubiquitylation, Cell signalling 相似文献
220.
Expression of baculovirus anti-apoptotic genes p35 and op-iap in cotton (Gossypium hirsutum L.) enhances tolerance to verticillium wilt 总被引:1,自引:0,他引:1