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鸟氨酸脱羧酶抗酶抑制因子1多态性与乙型肝炎肝硬化的关系

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中华肝脏病杂志 2011年第3期19卷 169-173页

作者：彭利军郭津生张哲石虹王剑 scott l.friedman John J.Sninsky 王吉耀上海复旦大学附属中山医院消化科 200032 Division of liver Diseases Mount Sinai School of Medicine New York Celera Corporation Alameda California

目的研究一种高加索人群丙型肝炎肝硬化风险评分模型（cirrhosis risk score，CRS）相关基因的多态性与中国人群乙型肝炎肝硬化的关系，评估该模型在乙型肝炎肝硬化中的应用价值。方法用基质辅助激光解析电离飞行时间质谱法检测相关的1... 详细信息

目的研究一种高加索人群丙型肝炎肝硬化风险评分模型（cirrhosis risk score，CRS）相关基因的多态性与中国人群乙型肝炎肝硬化的关系，评估该模型在乙型肝炎肝硬化中的应用价值。方法用基质辅助激光解析电离飞行时间质谱法检测相关的11个单核苷酸多态性位点，研究人群包括肝硬化组患者和对照组无肝硬化表现者，分析各位点与肝硬化的关系，比较肝硬化组和对照组CRS值的差异。用x^2检验检测哈维平衡验证样本的群体代表性。两组计量资料的比较用f检验或Wilcoxon秩和检验。单个单核苷酸多态性基因型等分类数据与肝硬化发生的关系用Pearson X^2检验，差异有统计学意义的单核苷酸多态性位点进一步用logistic回归分析判断在显性模型、隐性模型和加性模型下基因型与肝硬化发生的关系，计算比值比及95％可信区间，比值比经性别和年龄校正。结果鸟氨酸脱羧酶抗酶抑制因子1基因的rs2679757位点与肝硬化的发生相关（x^2=6．79，P〈0．05），与AA纯合子相比，携带危险等位基因G的GG＋AG基因型显著增加肝硬化的发生风险，比值比为1．63，95％可信区间为1．13～2．35。位于Toll样受体4基因的rs4986791位点和鸟氨酸脱羧酶抗酶抑制因子1基因的rs62522600位点在中国人群中无多态性基因型。其他研究位点与肝硬化的发生无相关性（JD〉0．05）。肝硬化组和对照组的CRS中位数分别为0．57和0．62，两组比较，差异无统计学意义（P〉0．05）。结论鸟氨酸脱羧酶抗酶抑制因子1多态性rs2679757与乙型肝炎肝硬化的发生相关。高加索人群CRS模型相关的两个多态性位点在中国人群中缺乏多态性，该CRS对评估有无乙型肝炎肝硬化的发生无明显价值，其他多态性位点仍需进一步临床验证。

关键词：肝硬化多态性单核苷酸鸟氨酸脱羧酶

A small molecule fibrokinase inhibitor in a model of fibropolycystic hepatorenal disease

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World Journal of Nephrology 2018年第5期7卷 96-107页

作者： Prani Paka Brian Huang Bin Duan Jing-Song li Ping Zhou latha Paka Michael A Yamin scott l friedman Itzhak D Goldberg Prakash Narayan Department of Research and Development Angion Biomedica Corp.UniondaleNY 11553United States Icahn School of Medicine 1 Gustave L.Levy PlaceNew YorkNY 10029United States

AIM To evaluate the novel platelet-derived growth factor receptor and vascular endothelial growth factor receptor dual kinase inhibitor ANG3070 in a polycystic kidney disease-congenital hepatic fibrosis *** At 6 wk of age, PCK rats were randomized to vehicle or ANG3070 for 4 wk. At 10 wk, 24 h urine and left kidneys were collected and rats were continued on treatment for 4 wk. At 14 wk, 24 h urine was collected, rats were sacrificed, and liver and right kidneys were collected for histological evaluation. For Western blot studies, PCK rats were treated with vehicle or ANG3070 for 7 d and sacrificed approximately 30 min after the last *** Compared to the wild-type cohort, the PCK kidney(Vehicle cohort) exhibited a marked increase in kidney and liver mass, hepato-renal cystic volume, hepato-renal fibrosis and hepato-renal injury biomarkers. Intervention with ANG3070 in PCK rats decreased kidney weight, reduced renal cystic volume and reduced total kidney hydroxyproline, indicating significantly reduced rental interstitial fibrosis compared to the PCK-Vehicle cohort. ANG3070 treatment also mitigated several markers of kidney injury, including urinary neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, cystatin C and interleukin-18 levels. In addition, this treatment attenuated key indices of renal dysfunction, including proteinuria, albuminuria and serum blood urea nitrogen and creatinine, and significantly improved renal function compared to the PCK-Vehicle cohort. ANG3070 treatment also significantly decreased liver enlargement, hepatic lesions, and liver fibrosis, and mitigated liver dysfunction compared to the PCK-Vehicle *** These results suggest that ANG3070 has the potential to slow disease, and may serve as a bridge toward hepato-renal transplantation in patients with fibropolycystic disease.

关键词： Congenital hepatic fibrosis Cyst Fibrosis Autosomal recessive polycystic kidney disease Kidney liver Therapy

Polymorphisms of AZIN1 rs2679757 and TRPM5 rs886277 are Associated with Cirrhosis Risk in Chinese Patients with Chronic Hepatitis B

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国际感染病学（电子版） 2012年第2期1卷 103-109页

作者： li-jun Peng Jin-sheng Guo Zhe Zhang li-li liu Yi-rong Cao Hong Shi Jian Wang scott l.friedman John J.Sninsky Ji-yao Wang Division of Digestive Diseases Department of Internal MedicineZhongshan HospitalShanghai Medical CollegeFudan University Division of liver Diseases Mount Sinai School of Medicine Celera Corporation

Objective Genome-wide association studies(GWAS)have linked many single nucleotide polymorphisms(SNPs)to the outcomes of a variety of liver *** aim of the present study was to evaluate the association of several candidate SNPs with the risk and severity of cirrhosis due to chronic hepatitis B in a Chinese *** A total of 714 Chinese participants with persistent HBV infection were *** were divided into cirrhotic(n=429)and non-cirrhotic(n=285)groups based on clinical and pathological *** progression rate and severity of liver cirrhosis were evaluated with an arbitrary t-score *** of six SNPs in five candidate genes were detected with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MAlDI-TOF MS).The genotypic distributions of the SNPs were compared between the age-matched cirrhotic and non-cirrhotic *** association between the risk of SNPs and the severity and progression rate of cirrhosis was further *** Rs2679757 polymorphism of the antizyme inhibitor 1(AZIN1)gene and Rs886277 in the transient receptor potential cation channel subfamily M,member 5 gene(TRPM5)were found to be associated with cirrhosis risk in *** were also correlated with the overall severity and progression rate of *** frequencies of other SNPs were not different between the cirrhosis and non-cirrhosis *** AZIN1 rs2679757 and TRPM5 rs886277 are associated with the risk and the progression rate of HBV-related liver fibrosis in Chinese *** emerging SNPs associated with cirrhosis prognosis warrant further clinical validation in other CHB cohorts or ethnic groups,and merit mechanistic studies to reveal their roles in fibrosis progression.

关键词： Hepatitis B Cirrhosis Single nucleotide polymorphism Antizyme inhibitor 1 Transient receptor potential cation channel subfamily M,member 5

Real-world cure rates for hepatitis C virus treatments that include simeprevir and/or sofosbuvir are comparable to clinical trial results

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World Journal of Virology 2017年第4期6卷 59-72页

作者： Kian Bichoupan Neeta Tandon James F Crismale Joshua Hartman David Del Bello Neal Patel Sweta Chekuri Alyson Harty Michel Ng Keith M Sigel Meena B Bansal Priya Grewal Charissa Y Chang Jennifer leong Gene Y Im lawrence U liu Joseph A Odin Nancy Bach scott l friedman Thomas D Schiano Ponni V Perumalswami Douglas T Dieterich Andrea D Branch Division of liver Diseases Icahn School of Medicine at Mount Sinai Janssen Scientific Affairs LLC Division of General Internal Medicine Icahn School of Medicine at Mount Sinai

AIM To assess the real-world effectiveness and cost of simeprevir(SMV), and/or sofosbuvir(SOF)-based therapy for chronic hepatitis C virus(HCV) *** The real-world performance of patients treated with SMV/SOF ± ribavirin(RBV), SOF/RBV, and SOF/RBV with pegylated-interferon(PEG) were analyzed in a consecutive series of 508 patients with chronic HCV infection treated at a single academic medical center. Patients with genotypes 1 through 4 were included. Rates of sustained virological response-the absence of a detectable serum HCV RNA 12 wk after the end of treatment [sustained virological response(SVR) 12]-were calculated on an intention-to-treat basis. Costs were calculated from the payer's perspective using Medicare/Medicaid fees and Redbook Wholesale Acquisition Costs. Patient-related factors associated with SVR12 were identified using multivariable logistic *** SVR 12 rates were as follows: 86%(95%CI: 80%-91%)among 178 patients on SMV/SOF ± RBV; 62%(95%CI: 55%-68%) among 234 patients on SOF/RBV; and 78%(95%CI: 68%-86%) among 96 patients on SOF/PEG/RBV. Mean costs-per-SVR 12 were $174442(standard deviation: ± $18588) for SMV/SOF ± RBV; $223003(± $77946) for SOF/RBV; and $126496(± $31052) for SOF/PEG/RBV. Among patients on SMV/SOF ± RBV, SVR12 was less likely in patients previously treated with a protease inhibitor [odds ratio(OR): 0.20, 95%CI: 0.06-0.56]. Higher bilirubin(OR: 0.47, 95%CI: 0.30-0.69) reduced the likelihood of SVR12 among patients on SOF/RBV, while FIB-4 score ≥ 3.25 reduced the likelihood of SVR 12(OR: 0.18, 95%CI: 0.05-0.59) among those on SOF/PEG/RBV. CONClUSION SVR 12 rates for SMV and/or SOF-based regimens in a diverse real-world population are comparable to those in clinical trials. Treatment failure accounts for 27% of costs.

关键词： Cirrhosis Cost Sustained virological response Protease inhibitor Polymerase inhibitor

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肝纤维化：如何阻断进展?

肝脏 2008年第1期13卷 57-57页

作者： scott l. friedman 陆伦根（译） Fishberg Professor and Chief Division of LiverDiseases Mount Sinai School of MedicineNew York NY 10029 USA 不详

阐明肝纤维化或肝脏的疤痕反应一直是现今肝脏病学研究的主要热点，尤其是肝星状细胞（HSC）活化是肝纤维化发生、发展的中心环节，且其活化过程已成为详细了解肝纤维化发生的重要环节。然而，目前对肝纤维化为何会加快肝细胞癌发生了... 详细信息

阐明肝纤维化或肝脏的疤痕反应一直是现今肝脏病学研究的主要热点，尤其是肝星状细胞（HSC）活化是肝纤维化发生、发展的中心环节，且其活化过程已成为详细了解肝纤维化发生的重要环节。然而，目前对肝纤维化为何会加快肝细胞癌发生了解尚不多。

关键词：肝纤维化肝脏病学肝星状细胞疤痕反应癌发生肝细胞活化

Purinergic signaling systems across comparative models of spinal cord injury

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Neural Regeneration Research 2022年第3期17卷 2391-2398页

作者： Eva E.Stefanova Angela l.scott Department of Pathology and Molecular Medicine McMaster UniversityHamiltonONCanada

Within the last several decades,the scientific community has made substantial progress in elucidating the complex pathophysiology underlying spinal cord ***,despite the many advances using conventional mammalian models,both cellular and axonal regeneration following spinal cord injury have remained out of *** this sense,turning to non-mammalian,regenerative species presents a unique opportunity to identify pro-regenerative cues and chara cterize a spinal cord microenvironment permissive to *** the signaling pathways hypothesized to be dysregulated during spinal cord injury is the purinergic signaling *** addition to its well-known role as energy currency in cells,ATP and its metabolites are small molecule neurotransmitte rs that mediate many diverse cellular processes within the central nervous *** our unde rstanding of the roles of the purinergic system following spinal cord injury is limited,this signaling pathway has been implicated in all injury-induced secondary processes,including cellular death,inflammation,reactive gliosis,and neural *** that the purinergic system is also evolutionarily conserved between mammalian and non-mammalian species,comparisons of these roles may provide important insights into conditions responsible for recovery ***,we compare the secondary processes between key model species and the influence of purinergic signaling in each *** our understanding of this signaling system and pro-regenerative conditions continues to evolve,so does the potential for the development of novel therapeutic interventions for spinal cord injury.

关键词： cell death differenriation glia inflammation neurogenesis proliferation purinergic signaling reactive gliosis regeneration spinal cord injury teleost

Perspectives:Gene expression in fisheries management

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Current Zoology 2010年第1期56卷 157-174页

作者： Jennifer l.NIElSEN scott A.PAVEY US Geological Survey Alaska Science Center Department of Biological Sciences Simon Frasier University National Park Service

Functional genes and gene expression have been connected to physiological traits linked to effective production and broodstock selection in aquaculture, selective implications of commercial fish harvest, and adaptive changes reflected in non-commercial fish populations subject to human disturbance and climate change. Gene mapping using single nucleotide polymorphisms （SNPs） to identify functional genes, gene expression （analogue microarrays and real-time PCR）, and digital sequencing technologies looking at RNA transcripts present new concepts and opportunities in support of effective and sustainable fisheries. Genomic tools have been rapidly growing in aquaculture research addressing aspects of fish health, toxicology, and early development. Genomic technologies linking effects in functional genes involved in growth, maturation and life history development have been tied to selection resulting from harvest practices. Incorporating new and ever-increasing knowledge of fish gehomes is opening a different perspective on local adaptation that will prove invaluable in wild fish conservation and management. Conservation of fish stocks is rapidly incorporating research on critical adaptive responses directed at the effects of human dis- turbance and climate change through gene expression studies. Genomic studies of fish populations can be generally grouped into three broad categories： l） evolutionary genomics and biodiversity; 2） adaptive physiological responses to a changing environment; and 3） adaptive behavioral genomics and life history diversity. We review current genomic research in fisheries focusing on those that use microarrays to explore differences in gene expression among phenotypes and within or across populations, information that is critically important to the conservation of fish and their relationship to humans [Current Zoology 56 （1）： 157-174, 2010].

关键词： Fish genome Fisheries management Conservation Gene expression

Technology advancing the study of animalcognition： using virtual reality to presentvirtually simulated environments to investigatenonhuman primate spatial cognition

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Current Zoology 2017年第1期63卷 97-108页

作者： Francine l. DOlINS Kenneth SCHWEllER scott MIlNE Department of Behavioral Sciences University of Michigan-Dearborn Dearborn MI 48128 USA Ape Cognition and Conservation Initiative Des Moines IA USA Impact Madagascar Nanisana Antananarivo 101Madagascar Africa

Virtual simulated environments provide multiple ways of testing cognitive function and evaluatingproblem solving with humans （e.g., Woollett et al. 2009）. The use of such interactive technologyhas increasingly become an essential part of modern life （e.g., autonomously driving vehicles, glo-bal positioning systems （GPS）, and touchscreen computers; Chinn and Fairlie 2007; Brown 2011）.While many nonhuman animals have their own forms of technology, such as chimpanzees whocreate and use tools, in captive animal environments the opportunity to actively participate withinteractive technology is not often made available. Exceptions can be found in some state-of-the-art zoos and laboratory facilities （e.g., Mallavarapu and Kuhar 2005）. When interactive technologyis available, captive animals often selectively choose to engage with it. This enhances the animal＇ssense of control over their immediate surroundings （e.g., Clay et al. 2011; Ackerman 2012）. Suchself-efficacy may help to fulfill basic requirements in a species＇ daily activities using problem solv-ing that can involve foraging and other goal-oriented behaviors. It also assists in fulfilling thestrong underlying motivation for contrafreeloading and exploration expressed behaviorally bymany species in captivity （Young 1999）. Moreover, being able to present nonhuman primates vir-tual reality environments under experimental conditions provides the opportunity to gain insightinto their navigational abilities and spatial cognition. It allows for insight into the generation andapplication of internal mental representations of landmarks and environments under multiple con-ditions （e.g., small- and large-scale space） and subsequent spatial behavior. This paper reviewsmethods using virtual reality developed to investigate the spatial cognitive abilities of nonhumanprimates, and great apes in particular, in comparison with that of humans of multiple age *** make recommendations about training, best practices, and also pi

关键词： animal cognition, apes, bonobos, chimpanzees, nonhuman primates, spatial cognition, virtual reality.

Modelling sulphate-enhanced cadmium uptake by Zea mays from nutrient solution under conditions of constant free Cd^(2+) ion activity

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Journal of Environmental Sciences 2010年第7期22卷 1080-1085页

作者： Ulrico J.lópez-Chuken scott D.Young Division of Environmental Sciences School of ChemistryUniversidad Autónoma de Nuevo León Division of Agricultural & Environmental Sciences School of Biosciencesthe University of Nottingham

A controlled hydroponic experiment was undertaken to investigate Cd uptake in relation to the activity of Cd species in solution other than the free ion （Cd^2＋） by maintaining a constant Cd^2＋ activity under variable SO4^2- and Cl^- concentrations exposed to maize （Zea mays vat. Cameron） plants. The objectives of these experiments were：（1） to distinguish and quantify the different uptake rates of free and inorganic-complexed Cd from nutrient solution, and （2） to model the uptake of Cd by maize with a Biotic ligand Model （BlM） in a system which facilitates the close examination of root characteristics. Results of the current experiments suggest that, in addition to the free ion, CdSO4^0 complexes are important factors in determining Cd uptake in nutrient solution by maize plants. Higher nominal SO4^2- concentrations in solution generally resulted in a greater Cd accumulation by maize plants than predicted by the Cd^2＋ activity. A better integration of the complete dataset for the 3 harvest times （6, 9 and 11 days after treatment） was achieved by including consideration of both the duration of Cd exposure and especially the root surface area to express Cd uptake. Similarly, the fit of the BlM was also improved when taking into account exposure time and expressing uptake in terms of root morphological parameters.

关键词： free ion activity model biotic ligand model root surface area Cd complexation metal exposure time hydroponics plant uptake