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Acta Pharmaceutica Sinica B 2020年第1期10卷 123-135页

作者： Xiaoyu Fan xinxin ding Qing-Yu Zhang Department of Pharmacology and Toxicology College of PharmacyUniversity of ArizonaTucsonAZ 85721USA Wadsworth Center New York State Department of HealthSchool of Public HealthUniversity at AlbanyAlbanyNY 12201USA

We examined the impact of gut inflammation on the expression of cytochrome P450(P450)and other biotransformation genes in male mice using a dextran sulfate sodium(DSS)-induced colitis *** P450 isoforms,including CYPIA,CYP2B,CYP2C,and CYP3A,were downregulated,accompanied by decreases in microsomal metabolism of diclofenac and nifedipine,in the liver and small *** impact of the colitis on in vivo clearance of oral drugs varied for four different drugs tested:a small decrease for nifedipine,a relatively large decrease for lovastatin,but no change for pravastatin,and a large decrease in the absorption of cyclosporine *** further assess the scope of influence of gut inflammation on gene expression,we performed genome-wide expression analysis using RNA-seq,which showed down-regulation of many CYPs,non-CYP phase-Ⅰenzymes,phase-Ⅱenzymes and transporters,and up-regulation of many other members of these gene families,in both liver and intestine of adult C57BL/6 mice,by DSS-induced ***,our results indicate that gut inflammation suppresses the expression of many P450s and other biotransformation genes in the intestine and liver,and alters the pharmacokinetics for some but not all drugs,potentially affecting therapeutic efficacy or causing adverse effects in a drug-specific fashion.

关键词： Cytochrome P450 CYP Colitis Intestine Inflammatory bowel disease Drug metabolism Pharmacokinetics Gene expression

An update on the role of intestinal cytochrome P450 enzymes in drug disposition

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Acta Pharmaceutica Sinica B 2016年第5期6卷 374-383页

作者： Fang Xie xinxin ding Qing-Yu Zhang Bioimaging Glaxo Smith KlineKing of Prussia College of Nanoscale Science SUNY Polytechnic Institute Wadsworth Center New York State Department of Health

Oral administration is the most commonly used route for drug *** cytochrome P450(CYP)-mediated metabolism can eliminate a large proportion of some orally administered drugs before they reach systemic circulation,while leaving the passage of other drugs unimpeded.A better understanding of the ability of intestinal P450 enzymes to metabolize various clinical drugs in both humans and preclinical animal species,including the identification of the CYP enzymes expressed,their regulation,and the relative importance of intestinal metabolism compared to hepatic metabolism,is important for improving bioavailability of current drugs and new drugs in ***,we briefly review the expression of drug-metabolizing P450 enzymes in the small intestine of humans and several preclinical animal species,and provide an update of the various factors or events that regulate intestinal P450 expression,including a cross talk between the liver and the *** further compare various clinical and preclinical approaches for assessing the impact of intestinal drug metabolism on bioavailability,and discuss the utility of the intestinal epithelium–specific NADPH-cytochrome P450 reductasenull(IECN) mouse as a useful model for studying in vivo roles of intestinal P450 in the disposition of orally administered drugs.

关键词： Cytochrome P450 Intestine Bioavailability Drug disposition Drug metabolism

The key role of gut-liver axis in pyrrolizidine alkaloid-induced hepatotoxicity and enterotoxicity

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Acta Pharmaceutica Sinica B 2021年第12期11卷 3820-3835页

作者： Yisheng He Jiang Ma Xiaoyu Fan Liang ding xinxin ding Qing-Yu Zhang Ge Lin School of Biomedical Sciences Faculty of Medicinethe Chinese University of Hong KongHong Kong SAR 999077China Department of Pharmacology&Toxicology College of PharmacyUniversity of ArizonaTucsonAZ 85721USA

Pyrrolizidine alkaloids(PAs) are the most common phytotoxins with documented human *** require metabolic activation by cytochromes P450 to generate toxic intermediates which bind to proteins and form protein adducts,thereby causing *** study investigated the role of the gut-liver axis in PA intoxication and the underlying *** exposed mice to retrorsine(RTS),a representative PA,and for the first time found RTS-induced intestinal epithelium damage and disruption to intestinal barrier *** mice with tissue-selective ablation of P450 activity,we found that hepatic P450 s,but not intestinal P450 s,were essential for PA ***,in RTS-exposed,bile duct-cannulated rats,we found the liver-derived reactive PA metabolites were transported by bile into the intestine to exert *** impact of gut-derived pathogenic factors in RTS-induced hepatotoxicity was further studied in mice with dextran sulfate sodium(DSS)-induced chronic *** treatment increased the hepatic endotoxin level and depleted hepatic reduced glutathione,thereby suppressing the PA detoxification *** to RTS-exposed normal mice,the colitic mice displayed more severe RTS-induced hepatic vasculature damage,fibrosis,and ***,our findings provide the first mode-of-action evidence of PA-induced enterotoxicity and highlight the importance of gut barrier function in PA-induced liver injury.

关键词： Pyrrolizidine alkaloid Cytochrome P450 Inflammatory bowel disease Intestinal injury Liver injury Gut-liver axis

A Polysaccharide-based Hydrogel and PLGA Microspheres for Sustained P24 Peptide Delivery: An In vitro and In vivo Study Based on Osteogenic Capability

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Chemical Research in Chinese Universities 2019年第5期35卷 908-915页

作者： CAI Qing QIAO Chunyan NING Jun ding xinxin WANG Haoyang ZHOU Yanmin Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling School of StomotologyJilin UniversityChangchun 130021P.R.China The First Hospital of Jilin University Changchun 130021P.R.China

A bone morphogenetic protein-2(BMP-2) derived synthetic oligopeptide, S [PO4]KIPKASSVPTELSAISTLYLDDD(P24), has shown great potential for facilitating bone regeneration. However, P24 cannot be directly used onto bone defects, while a continuous sustained delivery of P24 may lead to a better formation of bone tissue. Based on this issue, we have developed a sustained delivery system incorporating P24-loaded poly(lactide-co-glycolide)(PLGA) microspheres and nano-hydroxyapatite(n-HA) into the composite hydrogel. The P24-contained compound material was characterized with NMR, FTIR and SEM to demonstrate the fomiation of compound structure containing P24, PLGA and n-HA. A continuous drug release of P24 was observed for over 60 d that evidently enhanced the efficiency in promoting the proliferation of MC3T3-E1 cells and the secrete of alkaline phosphatase(ALP) in vitro. Moreover, the osteoinduction eflect of the hydrogel system with P24 peptide niicrospheres was demonstrated in vivo and manifested by the result of immunohistochemistry. This novel injectable composite hydrogel is expected to be applied to improving the bone defect treatment in bone tissue engineering.

关键词： BMP-2 derived peptide Hydrogel PLGA microsphere Osteogenesis Tissue engineering

Preferential expression of cytochrome CYP CYP2R1 but not CYP1B1 in human cord blood hematopoietic stem and progenitor cells

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Acta Pharmaceutica Sinica B 2014年第6期4卷 464-469页

作者： Shuoqi Xu Zhihua Ren Yanan Wang xinxin ding Yongping Jiang Biopharmaceutical R&D Center Chinese Academy of Medical Sciences&Peking Union Medical CollegeSuzhou 215126China Biopharmagen Corp. Suzhou 215126China Department of Clinical Laboratory Suzhou Municipal Affiliated Hospital of Nanjing Medical UniversitySuzhou 215002China

Cytochrome P450(CYP)enzymes metabolize numerous endogenous substrates,such as retinoids,androgens,estrogens and vitamin D,that can modulate important cellular processes,including proliferation,differentiation and *** aim of this study is to characterize the expression of CYP genes in CD34+human cord blood hematopoietic stem and early progenitor cells(CBHSPCs)as a first step toward assessment of the potential biological functions of CYP enzymes in regulating the expansion or differentiation of these ***34+CBHSPCs were purified from umbilical cord blood via antibody affinity *** of CD34+CBHSPCs was assessed using fluorescence-activated cell *** was isolated from purified CD34+CBHSPCs and total mononuclear cells(MNCs)for RNA-PCR analysis of CYP *** human CYPs were detected in the initial screening with qualitative RT-PCR in CD34+*** quantitative RNA-PCR analysis of the detected CYP transcripts yielded evidence for preferential expression of CYP2R1 in CD34+CBHSPCs relative to MNCs;and for greater expression of CYP1B1 in MNCs relative to CD34+*** findings provide the basis for further studies on possible functions of CYP2R1 and CYP1B1 in CBHSPCs'proliferation and/or differentiation and their potential utility as targets for drugs designed to modulate CD34+CBHSPC expansion or differentiation.

关键词： Cytochrome P450 CYP2R1 CYP1B1 CD34+ Hematopoietic stem cells Gene expression

A message from the Co-Editor-in-Chief

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Acta Pharmaceutica Sinica B 2021年第6期11卷 1364-1364页

作者： xinxin ding Co-Editor-in-Chief of APSB.

This special APSB issue marks the beginning of a series of celebratory events for the 10-year anniversary of the *** was June 2011, when the first issue of the journal was *** has been an exciting decade for the growth of the journal, which began publishing bimonthly and was changed to monthly in 2020to meet the ever-increasing demand for journal space. The inaugural issue had 10 articles, including two reviews and eight research articles. From the beginning, the editors set high standards and expectations. The annual editorial report for the first year showed a rejection rate of 85%;today, the rejection rate is over 93%. The initial goal of reaching an impact factor of 3 was quickly reached;now the impact factor is above 7. The journal has established itself as a leading international journal in pharmaceutical sciences in a relatively short time, an accomplishment well worth celebrating!

关键词： journal accomplishment publishing

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Editor Profile

Acta Pharmaceutica Sinica B 2012年第2期2卷 91-91页

作者： ding, xinxin New York State Dept Hlth Empire State PlazaBox 509 Albany NY 12201 USA

*** ding received a Bachelor’s degree in 1982,in Biology,from the Nanjing University,Nanjing,China,and a *** in 1988,in Biological Chemistry,from the University of Michigan,Ann Arbor,Michigan,*** is currently a Professor of Molecular Genetics,Neuroscience,and Toxicology,and the Director of Toxicology Track,of the School of Public Health,State University of New York at Albany,and the Chief of the Laboratory of Molecular Toxicology,at the Wadsworth Center for Laboratories and Research,New York State Department of *** also has concurrent faculty appointments at the Peking Union Medical College&Chinese Academy of Medical Sciences and at the Nanjing University.

关键词： Director Nanjing Michigan

Impact of Online Comments on Purchase Intention of College Student Consumers under Online Shopping

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Asian Agricultural Research 2016年第12期8卷 29-34页

作者： Mojing CHEN Guifang CHAO xinxin ding College of Economics and Management Huazhong Agricultural University Hubei Rural Development Research Center

With the rapid development of network technology,online shopping has been constantly growing,and how to make better use of the dissemination effect of online comment has become an imperative and practical issue. Based on review of the existing literature,this paper established the theoretical research model and used the literature research and empirical research combined method to analyze the impact of online comment on purchase intention of college student consumers under online shopping. The research results indicate that the quantity,quality,valence and timeliness of online comments exert a significant impact on the purchase intention of college student consumers.

关键词： Online comment College student consumers Purchase intention

Empirical Research on Influence Factors of "Leading Enterprise + Farmer" Channel Stability-Taking Personal Relation as the Regulated Variable

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Asian Agricultural Research 2017年第1期9卷 41-46页

作者： xinxin ding Daosheng LI Mojing CHEN College of Economics and Management Huazhong Agricultural University

In the cooperation model of leading enterprise + farmer,channel stability is always a prominent problem. Based on previous researches,taking farmers in Hainan region as investigation object,the influence factors of channel stability of leading enterprise + farmer are studied by combining the background of formal contract and using the combination method of theory and demonstration. Contract item design,trading cost,product specificity,power structure,information asymmetry and social relationship are contained in analytic framework to establish theoretic model. Research results show that in formal channel management,when contract clause design is more explicit,product specificity is stronger,power structure is more balanced,information share degree is higher,and trading cost is lower,channel is more stable,and farmer's willing to renew contract is stronger. Meanwhile,social relationship plays stronger regulation role.

关键词： Formal control Channel stability Relationship Influence factor

Empirical Research on Farmer's Breaching Behavior in Order Contract

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Asian Agricultural Research 2016年第12期8卷 43-47页

作者： Guifang CHAO Mojing CHEN xinxin ding College of Economics and Management Huazhong Agricultural University Hubei Rural Development Research Center

In " leading enterprise + farmer" cooperation model,farmer's behavior of breaching contract exists generally. In this paper,from the angle of incomplete contract,the influencial factors of farmer breaking contract are analyzed. It is found that farmer sex,age,culture degree and farming period have obvious effects on the behavior of breaching contract. Under regulating effect of relationship quality,farmer assest specificity,exogenous uncertainty and endogenous uncertainty affect farmer's breaking behavior. That is,the higher the farmer assest specificity,the lower the farmer breaching tendency; higher exogenous uncertainty causes that farmer is easy to generate breaching behavior; higher endogenous uncertainty causes that farmer is also easy to take breaching behavior.

关键词： Farmer breaching Relationship quality Assest specificity Uncertainty