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Gα_s Relays Sphingosine-1-Phosphate Receptor 1 Signaling to Stabilize Vascular Endothelial-Cadherin at Endothelial Junctions to Control Mouse Embryonic Vascular Integrity

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Journal of Genetics and Genomics 2015年第11期42卷 613-624页

作者： Ximing Shao Ke Liu Yi Fan Zhihao Ding Min Chen Minyan Zhu Lee S.Weinstein Hongchang Li Huashun Li West China Developmental and Stem Cell Institute West China Second HospitalSichuan University State Key Laboratory of Biotherapy and Cancer Center West China HospitalSichuan Universityand Collaborative Innovation Center for Biotherapy Shenzhen Key Laboratory for Molecular Biology of Neural Development Laboratory of Developmental and Regenerative BiologyInstitute of Biomedicine and BiotechnologyShenzhen Institutes of Advanced TechnologyChinese Academy of Sciences National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health SARITEX Center for Stem Cell Engineering Translational Medicine Shanghai East HospitalTongji University School of Medicine Nerdbio inc. SIP Biobay

Sphingosine-1-phosphate receptor 1 （S1PR1）, a G protein-coupled recep （GPCR）. controls vasct stability by stabilizing vascular endothelial （VE）-cadherin junctional localization and inhibiting vascular endothelial growth factor receptor 2（VEGFR2） signaling. However, the molecular mechanisms that link S1PR1 signaling to intracellular effectors remain *** this study,we demonstrate that the heterotrimeric G protein subfamily member Gαs, encoded by GNAS,acts as a relay mediator of S1PR1 signaling to control vascular integrity by stabilizing VE-cadherin at endothelial junctions. The endothelial cell -spectific deletion of Gαs in mice causes early embryonic lethality with massive hemorrhage and a disorganized *** immunostaining results revealed that Gαs deletion remarkably reduces the junctional localization of VE-cadherin, whereas the mull cell coverage of the vessels is not *** addition, we found-that Gαs depletion blocks the S1PR1-activation induced VE-cadherin stabilization at junctons,supporting that Gαs acts downstream of S1PR1 signaling ThuS, our results demonstrate that Gαs is an essential mediator to relay S1PR1 signaling and maintain vascular integrity.

关键词： Gαs VE-eadherin S1PR1 signaling adherens junctions vascular integrity

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Clinical correlations between chronic hepatitis C infection and decreasing bone mass density after treatment with interferon-alpha

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Asian Pacific Journal of Tropical Biomedicine 2017年第2期7卷 161-165页

作者： Vahid Babaei Masoud Ghorbani Nastaran Mohseni Hojjat Afraid Yassaman Saghaei Shahram Teimourian Department of Medical Genetics Iran University of Medical SciencesTehranIran Department of Research and Development Research and Production ComplexPasteur Institute of IranKarajIran biotechnology Research Center Biotechnology DepartmentVenom&Biotherapeutics Molecules LaboratoryPasteur Institute of IranTehranIran Iranian Blood Transfusion Organization TehranIran

Objective: To compare the bone mass density in chronic hepatitis patients before and after interferon-a ***: A total of 70 patients with chronic hepatitis C were treated with interferon-a and were evaluated. The treatment dosage was three million IU three times a week for one year. All the patients underwent bone mass density detection at lumbar spine and femoral neck before and after the interferon-a treatment. All the necessary information such as age,sex, and laboratory test, history of occurrence of fractures, lifestyle, and menopause status was collected by interviewers face-to-face from participants at the research visit. Smoking was categorized by whether participants were nonsmokers or smokers. Menopause was designated if there had been complete cessation of menses for more than 12 months. All statistical analyses were performed by SPSS version 14(SPSS, inc., Chicago, IL, USA).Results: Among 70 patients, 52% were male, 48% were female and the mean age was(57.0 ± 9.6) years(range: 24–79). Twenty-nine percent of the patients had a history of smoking. The mean body mass index was(24.4 ± 3.6) kg/m^2(range: 18.4–35.3). Of the70 cases, 21 had high fibrosis-4. The prevalence of overall fracture history was 2.9%(two patients).Conclusions: Chronic hepatitis C virus infection did inc.ease the risk of development of metabolic bone disease in this cohort. Indeed, greater reduction of bone mass density occurs in advanced liver fibrosis. The bone loss in earlier stages of chronic hepatitis C infection is likely to result from inc.eased bone reduction rather than decreased bone formation. Overall, these observations suggest an important role for chronic hepatitis C virus infection in inc.eased bone turnover in osteodystrophy pathogenesis.

关键词： Hepatitis C Interferon alpha Bone mass density Liver fibrosis Bone mass loss

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CD147-spike protein is a novel route for SARS-CoV-2 infection to host cells

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Signal Transduction and Targeted Therapy 2021年第1期6卷 95-104页

作者： Ke Wang Wei Chen Zheng Zhang Yongqiang Deng Jian-Qi Lian Peng Du Ding Wei Yang Zhang Xiu-Xuan Sun Li Gong Xu Yang Lei He Lei Zhang Zhiwei Yang Jie-Jie Geng Ruo Chen Hai Zhang Bin Wang Yu-Meng Zhu Gang Nan Jian-Li Jiang Ling Li Jiao Wu Peng Lin Wan Huang Liangzhi Xie Zhao-Hui Zheng Kui Zhang Jin-Lin Miao Hong-Yong Cui Min Huang Jun Zhang Ling Fu Xiang-Min Yang Zhongpeng Zhao Shihui Sun Hongjing Gu Zhe Wang Chun-Fu Wang Yacheng Lu Ying-Ying Liu Qing-Yi Wang Huijie Bian Ping ZhuZhi-Nan Chen National Translational Science Center for Molecular Medicine&Department of Cell Biology Fourth Military Medical UniversityXi’an 710032China Beijing Institute of biotechnology Beijing 100071China State Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and EpidemiologyBeijing 100071China Tangdu Hospital Fourth Military Medical UniversityXi’an 710038China MOE Key Laboratory for Nonequilibrium Synthesis and Modulation of Condensed Matter Xi’an Jiaotong UniversityXi’an 710049China Sino Biological inc. Beijing 100176China Department of Clinical Immunology Xijing HospitalFourth Military Medical UniversityXi’an 710032China School of Basic Medicine Fourth Military Medical UniversityXi’an 710032China

In face of the everlasting battle toward COVID-19 and the rapid evolution of SARS-CoV-2,no specific and effective drugs for treating this disease have been reported until ***-converting enzyme 2(ACE2),a receptor of SARS-CoV-2,mediates the virus infection by binding to spike *** ACE2 is expressed in the lung,kidney,and intestine,its expressing levels are rather low,especially in the *** the great infectivity of COVID-19,we speculate that SARS-CoV-2 may depend on other routes to facilitate its ***,we first discover an interaction between host cell receptor CD147 and SARS-CoV-2 spike *** loss of CD147 or blocking CD147 in Vero E6 and BEAS-2B cell lines by anti-CD147 antibody,Meplazumab,inhibits SARSCoV-2 *** of human CD147 allows virus entry into non-susceptible BHK-21 cells,which can be neutralized by CD147 extracellular *** loads are detectable in the lungs of human CD147(hCD147)mice infected with SARS-CoV-2,but not in those of virus-infected wild type ***,virions are observed in lymphocytes of lung tissue from a COVID-19 *** T cells with a property of ACE2 natural deficiency can be infected with SARS-CoV-2 pseudovirus in a dosedependent manner,which is specifically inhibited by ***,CD147 mediates virus entering host cells by ***,our study reveals a novel virus entry route,CD147-spike protein,which provides an important target for developing specific and effective drug against COVID-19.

关键词： ACE2 CD147 intestine

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生物植体表面活化改性(英文)

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稀有金属材料与工程 2010年第S2期39卷 1-9页

作者：黄毓虹郑海兴 Audrey Lin Ichiro Nishimura Zhejiang California International Nanosystems Institute ZCNI-Chemat Joint R&D Center for Sol-Gel Technology Chemat Technology inc. Biochemat DivisionNorthridge UCLA School of Dentistry The Weintraub Center for Reconstructive Biotechnology and Division of Advanced ProsthodonticsBiomaterials and Hospital Dentistry

研究目标是建立通用的纳米级表面涂层技术, 修改粗糙的钛表面化学牙种植体,同时保持微米级水平的表面形貌。以表面形貌调控表面化学,可能会引起生物活性、加速植入种植体表面的整合、缩短移植后的愈合时间。羟基磷灰石(HA)具有生物相容... 详细信息

研究目标是建立通用的纳米级表面涂层技术, 修改粗糙的钛表面化学牙种植体,同时保持微米级水平的表面形貌。以表面形貌调控表面化学,可能会引起生物活性、加速植入种植体表面的整合、缩短移植后的愈合时间。羟基磷灰石(HA)具有生物相容性和骨传导材料特点,HA 涂层具有促进骨骼生长的优点,但涂层易脱落,有混合晶相弊端。本文介绍了凯美特(Chemat)公司的一项新技术(BioFun),即设计一种新型室温自组装,在粗糙度为微米级水平的植体表面来制备纳米级促进骨生长表面。表面经过发射扫描电镜,X 射线光电子能谱,EDS 和 SMM 分析得到表征。生物相容性和生物植入物的表面活性研究在动物体外和体内进行。在动物体外,大鼠骨髓基质干细胞培养试验表明新型植体表面技术是生物相容的,也是无毒的。纳米羟基磷灰石植入已通过官能 10993 生物相容性面板测试。实验植入物或无 HA 纳米粒子的手术放置在植入大鼠股骨和推入式测试后 2 个星期愈合。这些数据表明,HA 纳米粒子沉积加速早期骨整合的过程,可能增加其剪切粘结强度。总之,BioFun 技术可创建一个纳米尺度的成骨表面,HA 纳米颗粒沉积并没有改变钛基板的预期微观形貌,而创造了新的纳米级形貌,这明显有利于加速骨植入的融合。

关键词：骨传导骨整合表面功能化种植种植牙

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MicroRNA-21, 204 and 125b Play Potential Roles in Tumorigenesis of Melanoma

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Advances in Bioscience and biotechnology 2015年第12期6卷 677-692页

作者： Chengtan Li Xiayu Wang Ya’ni Chen Xiaohua Tan Wen Li Sheng Yan Weibin Cai Xianrong Xu Liangwen Xu Lei Yang Yutao Yan School of Medicine Hangzhou Normal University Hangzhou China IHRC inc. Atlanta GA USA

Aim: The high mortality rate of melanoma is due to partially the lack of good diagnostic markers and treatment strategies. Over the past several years, several microRNA (miRNA) profiling studies have been performed on melanoma tissues, but with extremely inc.nsistency, the diagnostic value of miRNA candidates in melanoma remains under debate. Thus, this study aims to systematically evaluate the consistency of miRNAs tissue in multiple independent studies in melanoma. Method: Eligible studies were screened and selected from the PubMed, EMBASE, and Web of Science. A systematic analysis of published miRNA expression studies that compared the miRNA expression profiles between melanoma tissues and normal skin tissue was conducted. A vote-counting strategy was followed with the collection of information. Real time PCRs were employed to validate miRNA candidates with high consistency. Targets of consistent miRNAs were predicted by online programs (like miRTarBase, *** and TargetScanHuman 6.2). Enrichment analyses for gene ontology (GO) terms and Kyoto encyclopedia of genes and genomes (KEGG) pathways were carried out with Database for Annotation, Visualization, and Integrated Discovery (DAVID). Results: A total of 303 differentially expressed miRNAs were reported in the 10 miRNA-profiling studies during comparison of melanoma tissues with normal tissues;132 were up-regulated in melanoma, and 171 were down-regulated. However, in the group of consistently reported miRNAs (cutoff > 3 times), only moderate numbers of consistent and differentially expressed miRNAs were selected. miRNA-21 was found inc.eased in 5 different studies, miRNA-146b, miRNA-17 and miRNA-18a were reported up-regulated in 4 profiling studies. Meanwhile, miRNA-204 and miRNA-125b were found down-regulated in 5 studies, miRNA-141, miRNA-149, miRNA-224, miRNA-200b, miRNA-200c were consistently decreased in just 4 out of 10 profiling studies in total. The directions of differential expression of these

关键词： Melanoma miRNA Systematic Analysis Programmed Cell Death Transcription

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Inhibition of African swine fever virus in liquid and feed by medium-chain fatty acids and glycerol monolaurate

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Journal of Animal Science and biotechnology 2021年第2期12卷 569-578页

作者： Joshua A.Jackman Astghik Hakobyan Hovakim Zakaryan Charles C.Elrod School of Chemical Engineering Sungkyunkwan UniversitySuwon 16419Republic of Korea Group of Antiviral Defense Mechanisms Institute of Molecular Biology of NASYerevanArmenia Natural Biologics inc. NewfieldNY 14867USA. Department of Animal Science Cornell UniversityIthacaNY 14853USA

Background:The ongoing African swine fever virus(ASFv)epidemic has had a major impact on pig production globally and biosecurity efforts to curb ASFv infectivity and transmission are a high *** has been recently identified that feed and feed ingredients,along with drinking water,can serve as transmission vehicles and might facilitate transboundary spread of ***,it is important to test the antiviral activity of regulatory compatible,antiviral feed additives that might inhibit ASFv infectivity in *** promising group of feed additive candidates inc.udes medium-chain fatty acids(MCFA)and monoglyceride derivatives,which are known to disrupt the lipid membrane surrounding certain enveloped viruses and ***:The antiviral activities of selected MCFA,namely caprylic,capric,and lauric acids,and a related monoglyceride,glycerol monolaurate(GML),to inhibit ASFv in liquid and feed conditions were investigated and suitable compounds and inc.usion rates were identified that might be useful for mitigating ASFv in feed *** assays showed that all tested MCFA and GML inhibit *** was more potent than MCFA because it worked at a lower concentration and inhibited ASFv due to direct virucidal activity along with one or more other antiviral ***-dependent feed experiments further showed that sufficiently high GML doses can significantly reduce ASFv infectivity in feed in a linear manner in periods as short as 30 min,as determined by infectious viral titer ***-linked immunosorbent assay(ELISA)experiments revealed that GML treatment also hinders antibody recognition of the membrane-associated ASFv p72 structural protein,which likely relates to protein conformational changes arising from viral membrane ***:Together,the findings in this study indicate that MCFA and GML inhibit ASFv in liquid conditions and that GML is also able to reduce ASFv infectivity in feed,which may help to curb disease tr

关键词： African swine fever virus Antiviral Feed pathogen mitigation MCFA Medium-chain fatty acids Monoglycerides

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Evaluation of Various Factors Affecting Bioconversion of L-Tyrosine to L-DOPA by Yeast Yarrowia lipolytica-NCIM 3450 Using Response Surface Methodology

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Natural Products and Bioprospecting 2014年第3期4卷 141-147页

作者： Swati T.Gurme Shripad N.Surwase Sushama A.Patil Jyoti P.Jadhav Department of biotechnology Shivaji UniversityVidyanagarKolhapur 416004India Department of Microbiology Shivaji UniversityKolhapur 416004India

3,4-Dihydroxy L-phenylalanine(L-DOPA)is considered a potent drug for the treatment of Parkinson *** and nutritional parameters where optimized by using Yarrowia lipolytica-NCIM 3450 to accomplished the highest production of *** of critical components were completed by using a Plackett–Burman design,while further optimization was carried out using the Box–Behnken *** optimized factor levels predicted by the model were pH 6.1,1.659 g L^(-1)yeast extract,1.491 g L^(-1)L-tyrosine and 0.0290 g L^(-1)*** predicted yield of L-DOPA with these levels was 1.319 g L^(-1),while actual yield obtained was 1.273 g L^(-1).The statistical analysis revealed that model is significant with F value 19.55 and R2 value *** process resulted in a 3.594-fold inc.ease in the yield of LDOPA.L-DOPA was confirmed by HPTLC and HPLC ***,Yarrowia lipolytica-NCIM 3450 has potential to be a new source for the production of L-DOPA.

关键词： L-DOPA L-tyrosine RSM Yarrowia lipolytica

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Pharmacokinetics of sifuvirtide, a novel anti-HIV-1 peptide, in monkeys and its inhibitory concentration in vitro1

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Acta Pharmacologica Sinica 2005年第10期26卷 1274-1280页

作者： Shu-jia DAI~2, Gui-fang DOU~3, Xiao-hong QIAN~(4,5), Hai-feng SONG~4, Zhong-ming TANG~2, De-sheng LIU~2, Xiu-wen LIU~2, Liu-meng YANG~6, Yong-tang ZHENG~6, Qing LIANG~7 ~2 Laboratory of Metabolism of biotechnology Derived Drugs, Beijing Institute of Radiation Medicine, Beijing 100850 ~3 Laboratory of Drug Metabolism and Pharmacokinetics, Beijing Institute of Transfusion Medicine, Beijing 100850 ~5 Laboratories of Genomics and Proteomics, Beijing Institute of Radiation Medicine, Beijing 100850 ~6 Laboratory of Molecular hnmunopharmacology, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223 ~7 FusoGen Pharmaceuticals inc. Tianjin 300051, China Laboratory of Metabolism of biotechnology Derived Drugs Beijing Institute of Radiation Medicine Beijing China Laboratory of Drug Metabolism and Pharmacokinetics Beijing Institute of Transfusion Medicine Beijing China Laboratories of Genomics and Proteomics Beijing Institute of Radiation Medicine Beijing China Laboratory of Molecular Immunopharmacology Kunming Institute of Zoology Chinese Academy of Sciences Kunming China FusoGen Pharmaceuticals inc Tianjin China

Aim: To study the pharmacokinetics of sifuvirtide, a novel anti-human immunodeficiency virus （HIV） peptide, in monkeys and to compare the inhibitory concentrations of sifuvirtide and enfuvirtide on HIV-1-infected-cell fusion. Methods: Monkeys received 1.2 mg/kg iv or sc of sifuvirtide. An on-line solid-phase extraction procedure combined with liquid chromatography tandem mass spectrometry （SPELC/MS/MS） was established and applied to determine the concentration of sifuvirtide in monkey plasma. A four-127I iodinated peptide was used as an internal standard. Fifty percent inhibitory concentration (IC50) of sifuvirtide on cell fusion was determined by co-cultivation assay. Results: The assay was validated with good precision and accuracy. The calibration curve for sifuvirtide in plasma was linear over a range of 4.88-5000μg/L, with correlation coefficients above 0.9923. After iv or sc administration, the observed peak concentrations of sifuvirtide were 10 626±2 886μg/L and 528±191μg/L, and the terminal imination half-lives (T1/2) were 6.3±0.9 h and 5.5±1.0 h, respectively. After sc, Tmaxwas 0.25-2h, and the absolute bioavailability was 49%±13%. Sifuvirtide inhibited the syncytium formation between HIV-1 chronically infected cells and uninfected cells with an IC50of 0.33μg/L. Conclusion: An on-line SPE-LC/MS/MS approach was established for peptide pharmacokinetic studies. Sifuvirtide was rapidly absorbed subcutaneously into the blood circulation. The T1/2of sifuvirtide was remarkably longer than that of its analog, enfuvirtide, reported in healthy monkeys and it conferred a long-term plasma concentration level which was higher than its IC50in vitro.

关键词： sifuvirtide pharmacokinetics HIV HIV fusion inhibitors enfuvirtide on-line solid-phase extraction macaque

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Biotransformation of endosulfan by the tiger worm, <i>Eisenia fetida</i>

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Journal of Agricultural Chemistry and Environment 2012年第1期1卷 20-27页

作者： Byeoung-Soo Park Jae-Hong Yoo Jeong-Han Kim Jang-Eok Kim Sung-Eun Lee Agricultural Microbiology Division National Academy of Agricultural Science RDA Suwon South Korea Division of Applied Biology and Chemistry Kyungpook National University Daegu South Korea Resarch Station Nanotoxtech Inc. Ansan South Korea School of Agricultural biotechnology Seoul National University Seoul South Korea

This study assesses the role of the earthworm, Eisenia fetida, in the breakdown of endosulfan in a soil environment. Two strains of E. fetida were used in this study to assess the effect of salinity on toxicity and metabolism of endosulfan in these earthworms. One strain of E. fetida (R) was reared in high salinity soil (over 2.0 dS/m of electric conductivity) from Shiwha lake, Korea. A control strain (W) was reared in pig manure compost. Acute toxicity of endosulfan was lower in the R strain when endosulfan was injected. In vitro metabolic studies of endosulfan based on microsomal preparations showed that both strains produced two major metabolites, endosulfan sulfate and endosulfan diol. The production rate of endodulfan sulfate was not significantly different between the strains, while endosulfan diol production was significantly different. In vivo metabolism studies showed only one primary metabolite, endosulfan sulfate, was produced by both strains. HPLC-MS/MS analysis showed annetocin was the indicative protein newly expressed in the R strain in relation to salinity exposure. These findings suggest salinity may induce hydrolyzing enzymes to produce endosulfan diol from endosulfan.

关键词： Endosulfan Endosulfan Diol Endosulfan Sulfate Eisenia Fetida Salinity LC-MS/MS Annetocin

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The role of T-cell immunoglobulin mucin-3 and its ligand galectin-9 in antitumor immunity and cancer immunotherapy

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Science China(Life Sciences) 2017年第10期60卷 1058-1064页

作者： Riyao Yang Mien-Chie Hung Department of Molecular and Cellular Oncology The University of Texas MD Anderson Cancer Center Center for Molecular Medicine and Graduate Institute of Biomedical Sciences China Medical University Department of biotechnology Asia University

Cancer treatment in the past few years has been transformed by a new kind of therapy that targets the immune system instead of the cancer itself to reinvigorate antitumor immunity with astonishing results. However, primary and acquired resistance to this type of treatment, namely immune checkpoint blockade(ICB), continue to counter treatment efficacy. In many cases, resistance has been attributed to defective or chronically enhanced interferon signaling and/or upregulation of alternative immune checkpoints,inc.uding T-cell immunoglobulin mucin-3(Tim-3) and its ligand galactin-9(Gal-9). In this article, we briefly describe the current knowledge of common checkpoint resistance mechanisms, focusing on the Tim-3/Gal-9 pathway as an alternative checkpoint that holds great promise as another target for ICB.

关键词： cancer Tim-3 galectin-9 immune checkpoints immunotherapy

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