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Calcitriol Suppressed Isoproterenol-induced Proliferation of Cardiac Fibroblasts via Integrinβ3/FAK/Akt Pathway 被引量:2
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作者 Xin-feng WANG Qian LI +3 位作者 Xia SUN Li-ming ZHENG Shao-li CHENG Yan-he ZHU 《Current Medical Science》 SCIE CAS 2023年第1期48-57,共10页
Objective Cardiac fibroblasts(CFs)proliferation and extracellular matrix deposition are important features of cardiac fibrosis.Various studies have indicated that vitamin D displays an anti-fibrotic property in chroni... Objective Cardiac fibroblasts(CFs)proliferation and extracellular matrix deposition are important features of cardiac fibrosis.Various studies have indicated that vitamin D displays an anti-fibrotic property in chronic heart diseases.This study explored the role of vitamin D in the growth of CFs via an integrin signaling pathway.Methods MTT and 5-ethynyl-2′-deoxyuridine assays were performed to determine cell viability.Western blotting was performed to detect the expression of proliferating cell nuclear antigen(PCNA)and integrin signaling pathway.The fibronectin was observed by ELISA.Immunohistochemical staining was employed to evaluate the expression of integrinβ3.Results The PCNA expression in the CFs was enhanced after isoproterenol(ISO)stimulation accompanied by an elevated expression of integrin beta-3(β3).The blockade of the integrinβ3 with a specific integrinβ3 antibody reduced the PCNA expression induced by the ISO.Decreasing the integrinβ3 by siRNA reduced the ISO-triggered phosphorylation of FAK and Akt.Both the FAK inhibitor and Akt inhibitor suppressed the PCNA expression induced by the ISO in the CFs.Calcitriol(CAL),an active form of vitamin D,attenuated the ISO-induced CFs proliferation by downregulating the integrinβ3 expression,and phosphorylation of FAK and Akt.Moreover,CAL reduced the increased levels of fibronectin and hydroxyproline in the CFs culture medium triggered by the ISO.The administration of calcitriol decreased the integrinβ3 expression in the ISO-induced myocardial injury model.Conclusion These findings revealed a novel role for CAL in suppressing the CFs growth by the downregulation of the integrinβ3/FAK/Akt pathway. 展开更多
关键词 vitamin D cardiac fibroblast PROLIFERATION INTEGRIN myocardial fibrosis
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New progress in roles of nitric oxide during hepatic ischemia reperfusion injury 被引量:20
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作者 Ya-Qi Zhang Ning Ding +4 位作者 Yong-Fen Zeng Yuan-Yuan Xiang Mei-Wen Yang Fen-Fang Hong Shu-Long Yang 《World Journal of Gastroenterology》 SCIE CAS 2017年第14期2505-2510,共6页
Hepatic ischemia reperfusion injury (HIRI) is a clinical condition which may lead to cellular injury and organ dysfunction. The role of nitric oxide (NO) in HIRI is complicated and inconclusive. NO produced by endothe... Hepatic ischemia reperfusion injury (HIRI) is a clinical condition which may lead to cellular injury and organ dysfunction. The role of nitric oxide (NO) in HIRI is complicated and inconclusive. NO produced by endothelial nitric oxide synthase (eNOS) activation plays a protective role during early HIRI. But eNOS overexpression and the resulting excessive NO bioavailability can aggravate liver injury. NO induced by inducible nitric oxide synthase (iNOS) may have either a protective or a deleterious effect during the early phase of HIRI, but it may protect the liver during late HIRI. Here, we reviewed the latest findings on the role of NO during HIRI: (1) NO exerts a protective effect against HIRI by increasing NO bioavailability, downregulating p53 gene expression, decreasing inflammatory chemokines, reducing ROS via inhibiting the mitochondrial respiratory chain, activating sGC-GTP-cGMP signal pathway to reduce liver cell apoptosis, and regulating hepatic immune functions; (2) eNOS protects against HIRI by increasing NO levels, several eNOS/NO signal pathways (such as Akt-eNOS/NO, AMPK-eNOS/NO and HIF-1 alpha-eNOS/NO) participating in the anti-HIRI process, and inhibiting over-expression of eNOS also protects against HIRI; and (3) the inhibition of iNOS prevents HIRI. Thus, the adverse effects of NO should be avoided, but its positive effect in the clinical treatment of diseases associated with HIRI should be recognized. 展开更多
关键词 LIVER Hepatic ischemia reperfusion injury Nitric oxide Nitric oxide synthase
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Potential rat model of anxiety-like gastric hypersensitivity induced by sequential stress 被引量:9
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作者 Fu-Chun Jing Jun Zhang +7 位作者 Chen Feng Yuan-Yuan Nian Jin-Hai Wang Hao Hu Bao-De Yang Xiao-Ming Sun Jian-Yun Zheng Xiao-Ran Yin 《World Journal of Gastroenterology》 SCIE CAS 2017年第42期7594-7608,共15页
AIM To establish a rat model of anxiety-like gastric hyper-sensitivity(GHS) of functional dyspepsia(FD) induced by novel sequential stress.METHODS Animal pups were divided into two groups from postnatal day 2: control... AIM To establish a rat model of anxiety-like gastric hyper-sensitivity(GHS) of functional dyspepsia(FD) induced by novel sequential stress.METHODS Animal pups were divided into two groups from postnatal day 2: controls and the sequential-stress-treated. The sequential-stress-treated group received maternal separation and acute gastric irritation early in life and restraint stress in adulthood; controls were reared undisturbed with their mothers. Rats in both groups were followed to adulthood(8 wk) at which point the anxietylike behaviors and visceromotor responses to gastric distention(20-100 mm Hg) and gastric emptying were tested. Meanwhile, alterations in several anxiety-related brain-stomach modulators including 5-hydroxytryptamine(5-HT), γ-aminobutyric acid(GABA), brain-derived neurotrophic factor(BDNF) and nesfatin-1 in the rat hippocampus, plasma and gastric fundus and the 5-HT1 A receptor(5-HT1 AR) in the hippocampal CA1 subfield and the mucosa of the gastric fundus were examined.RESULTS Sequential-stress-treated rats simultaneously demonstrated anxiety-like behaviors and GHS in dose-dependent manner compared with the control group. Although rats in both groups consumed similar amount of solid food, the rate of gastric emptying was lower in the sequentialstress-treated rats than in the control group. Sequential stress significantly decreased the levels of 5-HT(51.91 ± 1.88 vs 104.21 ± 2.88, P < 0.01), GABA(2.38 ± 0.16 vs 5.01 ± 0.13, P < 0.01) and BDNF(304.40 ± 10.16 vs 698.17 ± 27.91, P < 0.01) in the hippocampus but increased the content of nesfatin-1(1961.38 ± 56.89 vs 1007.50 ± 33.05, P < 0.01) in the same site; significantly decreased the levels of 5-HT(47.82 ± 2.29 vs 89.45 ± 2.61, P < 0.01) and BDNF(257.05 ± 12.89 vs 536.71 ± 20.73, P < 0.01) in the plasma but increased the content of nesfatin-1 in it(1391.75 ± 42.77 vs 737.88 ± 33.15, P < 0.01); significantly decreased the levels of 5-HT(41.15 ± 1.81 vs 89.17 ± 2.31, P < 0.01) and BDNF(226.49 ± 12.10 vs 551.36 ± 16.47, P < 0.01) in the gastric fundus but increased the content of nesfatin-1 in the same site(1534.75 ± 38.52 vs 819.63 ± 38.04, P < 0.01). The expressions of 5-HT1 AR in the hippocampal CA1 subfield and the mucosa of the gastric fundus were down-regulated measured by IHC(Optical Density value: Hippocampus 15253.50 ± 760.35 vs 21149.75 ± 834.13; gastric fundus 15865.25 ± 521.24 vs 23865.75 ± 1868.60; P < 0.05, respectively) and WB(0.38 ± 0.01 vs 0.57 ± 0.03, P < 0.01)(n = 8 in each group). CONCLUSION Sequential stress could induce a potential rat model of anxiety-like GHS of FD, which could be used to research the mechanisms of this intractable disease. 展开更多
关键词 Gastric hypersensitivity ANXIETY Functional dyspepsia 5-HYDROXYTRYPTAMINE γ-aminobutyric acid Brain-derived neurotrophic factor NESFATIN-1 Rat model
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Inhibition of human prostate cancer xenograft growth by 125I labeled triple-helin forming oligonucleotide directed against androgen receptor 被引量:6
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作者 ZHANG Yong MA Yi +5 位作者 LU Han-ping GAO Jin-hui LIANG Chang-sheng LIU Chang-zheng ZOU Jun-tao WANG Hua-qiao 《Chinese Medical Journal》 SCIE CAS CSCD 2008年第22期2284-2289,共6页
Background The failure of hormone treatment for advanced prostate cancer might be related to aberrant activation of the androgen receptor. We have shown that 125I labeled triple-helix forming oligonucleotide (TFO) a... Background The failure of hormone treatment for advanced prostate cancer might be related to aberrant activation of the androgen receptor. We have shown that 125I labeled triple-helix forming oligonucleotide (TFO) against the androgen receptor gene inhibits androgen receptor expression and cell proliferation of LNCaP prostate cancer cells in vitro. This study aimed at exploring the effects of the 125I-TFO on prostate tumor growth in vivo using a nude mouse xenograft model. Methods TFO was labeled with 125I by the iodogen method. Thirty-two nude mice bearing LNCaP xenograft tumors were randomized into 4 groups and were intratumorally injected with 125I-TFO, unlabeled TFO, Na125I and normal saline. Tumor size was measured weekly. The tumor growth inhibition rate (RI) was calculated by measurement of tumor weight. The expression of the androgen receptor gene was performed by RT-PCR and immunohistochemical study. The prostate specific antigen (PSA) serum levels were measured by enzyme linked immunosorbent assay. The tumor cell apoptosis index (AI) was detected by TUNEL assay. Results Tumor measurements showed that tumor development was significantly inhibited by either 125I-TFO or TFO, with tumor RIs of 50.79% and 32.80% respectively. 125I-TFO caused greater inhibition of androgen receptor expression and higher AIs in tumor tissue than TFO. Both the tumor weight and the PSA serum levels in 125I-TFO treated mice ((0.93±0.15) g and (17.43±1.85) ng/ml, respectively) were significantly lower than those ((1.27±0.21) g and (28.25±3.41) ng/ml, respectively) in TFO treated mice (all P〈0.05). Na 125I did not significantly affect tumor growth and androgen receptor expression in tumor tissue. Conclusions The 125I-TFO can effectively inhibit androgen receptor expression and tumor growth of human prostate cancer xenografts in vivo. The inhibitory efficacy of 125I-TFO is more potent than that of TFO, providing a reference for future studies of antigen radiotherapy. 展开更多
关键词 prostate cancer androgen receptor OLIGONUCLEOTIDES iodine radioisotopes gene therapy
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High-throughput 16S rDNA sequencing of the pulmonary microbiome of rats with allergic asthma 被引量:4
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作者 Yang Xiong Sen Hu +4 位作者 Hongyao Zhou Hui Zeng Xuan He Dongni Huang Xiaoyu Li 《Genes & Diseases》 SCIE 2020年第2期272-282,共11页
A decrease in microbial infection in adolescents is implicated with an increase in the incidence of asthma and allergic diseases in adulthood,indicating that the microbiome plays a critical role in asthma.However,the ... A decrease in microbial infection in adolescents is implicated with an increase in the incidence of asthma and allergic diseases in adulthood,indicating that the microbiome plays a critical role in asthma.However,the microbial composition of the lower respiratory tract remains unclear,hindering the further exploration of the pathogenesis of asthma.This study aims to explore the microbial distribution and composition in the lungs of normal rats and rats with allergic asthma via 16S rDNA sequencing.The DNA of the pulmonary microbiome was extracted from the left lungs collected from normal control group(NC),saline control group(SC),and allergic asthma group(AA)under aseptic conditions.After the 16s rDNA V4eV5 region was amplified,the products were sequenced using Illumina high-throughput technology and subjected to operational taxonomic unit(OTU)cluster and taxonomy analysis.The OTU values of AA increased significantly compared with those of NC and SC.Microbiome structure analysis showed that the dominant phylum of the pulmonary microbiome changed from Proteobacteria in NC to Firmicutes in AA.Linear discriminant analysis indicated that the key microbiomes involved in the three groups varied. 展开更多
关键词 16S rDNA Allergic asthma Illumina sequencing Pulmonary microbiome RATS
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Effects of chitooligosaccharide-zinc on the ovarian function of mice with premature ovarian failure via the SESN2/NRF2 signaling pathway 被引量:1
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作者 LI Jia CHEN Yu-Hang +5 位作者 XU Jia-Yu LIU Jiang-Ying FU Jia-Cheng CAO Xiu-Ping HUANG Jian ZHENG Yue-Hui 《Chinese Journal of Natural Medicines》 SCIE CAS CSCD 2021年第10期721-731,共11页
Chitooligosaccharide-zinc(COS·Zn)is a powerful anti-oxidant and anti-aging scavenger,whose anti-oxidative ability immensely exceeds vitamin C.Therefore,this study was aimed to investigate the protective effects o... Chitooligosaccharide-zinc(COS·Zn)is a powerful anti-oxidant and anti-aging scavenger,whose anti-oxidative ability immensely exceeds vitamin C.Therefore,this study was aimed to investigate the protective effects of COS·Zn against premature ovarian failure(POF)and potential mechanisms.Female KM adult mice were divided into the following groups:a treatment group(150 mg·kg^(−1)·d^(−1) COS·Zn),a treatment group(300 mg·kg^(−1)·d^(−1) COS·Zn),a prevention group,two control groups and two CY/BUS groups.COS·Zn(150,300 mg·kg^(−1)·d^(−1))and COS·Zn(300 mg·kg^(−1)·d^(−1))were therapeutically and preventatively administered to POF mice in the treatment and prevention studies,respectively.All the groups were administered for 21 days.Fewer primary and secondary follicles were observed in the COS·Zn-treated groups(including the treatment and prevention groups)than those of the control groups.Meanwhile,the ovarian index and the levels of FSH and LH notably increased in the treatment and prevention groups compared with those in the CY/BUS group.The levels of MVH,OCT4 and PCNA in the treatment group(300·kg^(−1)·d^(−1) COS·Zn)and MVH in the prevention group remarkably increased compared with those in the CY/BUS groups.Meanwhile,the levels of P53 and P16 protein were down-regulated in the treatment and prevention groups compared with those in the CY/BUS groups.Additionally,the amounts of Sestrin2(SESN2)and SOD2 protein were obviously higher in the treatment group(150 mg·kg^(−1)·d^(−1) COS·Zn)than those in the CY/BUS groups.Similarly,the amounts of NRF2 and SESN2 protein were up-regulated in the prevention group.Besides,an increased GSH level was observed in the two treatment groups,compared with that in the CY/BUS groups,and the same trend was also present in the prevention group.Taken together,COS·Zn improves the ovarian and follicular development through regulating the SESN2/NRF2 signaling pathway.These results suggest the role of COS·Zn as a novel agent for the treatment and prevention of POF. 展开更多
关键词 Premature ovarian failure Chitooligosaccharide-zinc Sestrin2-nrf2 Ovarian function AGING
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Morphological and physiological comparison of taxa comprising the Sporothrix schenckii complex
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作者 Ming-dan ZHAO Xun ZHOU +1 位作者 Ting-ting LIU Zhi-bang YANG 《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 SCIE CAS CSCD 2015年第11期940-947,共8页
Based on recent molecular data, it has been suggested that Sporothrix globosa is the main causal agent of sporotrichosis in China. The objective of this study was to compare the morphology, growth characteristics, pat... Based on recent molecular data, it has been suggested that Sporothrix globosa is the main causal agent of sporotrichosis in China. The objective of this study was to compare the morphology, growth characteristics, patterns of carbon source usage, and susceptibility to antifungal agents among Sporothrix strains. A total of 15 clinical strains confirmed to be S. globosa, from three different regions of China, and 11 ex-type strains from the CBS-KNAW biodiversity center were obtained. The elongated conidia of S. pal/ida, S. variecibatus, S. schenckii, and S. schenckii luriei were clearly different from the subglobose and globose conidia of S. globosa strains. S. schenckii is able to assimilate sucrose, raffinose, and ribitol. Susceptibility profiles of these Sporothrix species were evaluated by measuring minimum inhibitory concentrations (MICs). Fluconazole, itraconazole, terbinafine, and amphotericin B showed good activity against most S. globosa clinical isolates from China. Potassium iodide also showed a low MIC against S. pal/ida, while fluconazole showed a high MIC for S. mexicana, S. humicola, S. g/obosa, S. schenckii, and S. inflata; these strains might be considered tolerant. The species showed differences in susceptibility to antifungal drugs and should therefore be properly identified during diagnosis prior to designing therapeutic strategies. 展开更多
关键词 Sporothrix globosa Phenotypic characters Antifungal susceptibility
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