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HPV18 DNA replication inactivates the early promoter P_(55) activity and prevents viral E6 expression

Virologica Sinica 2016年第5期31卷 437-440页

作者： Xiaohong Wang Haibin Liu Hsu-Kun Wang Craig Meyers louise chow Zhi-Ming Zheng Tumor Virus RNA Biology Section RNA Biology LaboratoryNational Cancer Institute National Institutes of Health Department of Biochemistry and Molecular Genetics University of Alabama at Birmingham Department of Microbiology and Immunology Penn State University College of Medicine

Dear Editor,Human papillomaviruses(HPV)are a large group(>200genotypes)of small double-stranded DNA viruses(https://***/).Although infections by most HPV types are asymptomatic,persistent infections in cervical and an... 详细信息

关键词： HPV18 DNA replication inactivates the early promoter P DNA activity and prevents viral E6 expression

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In Vitro Model Systems to Study the Life cycle of Human Papillomaviruses

In Vitro Model Systems to Study the Life cycle of Human Papi...

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24th International Papillomavirus Conference and Clinical Workshop

作者： louise T.chow Department of Biochemistry and Molecular Genetics University of Alababma at Birmingham AL.USA 35223

＜正＞Productive Phase in Patient Specimens HPVs infect only human squamous epithelia and cannot be propagated in animals. To establish persistent infections,HPV has to gain access to the basal calls of the sqaumous epithelium through a wound. Durthg wound healing,HPV eady genes are actively transcribed, increasing the infected call population,while establishing a steady state viral genome copy number. When wound has been healed,viral DNA and RNA are low in abundance in the lower call strata（basal,parabasal and lower spinous cells）.

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Model systems to study the life cycle of human papillomaviruses and HPV-associated cancers

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Virologica Sinica 2015年第2期30卷 92-100页

作者： louise T.chow Department of Biochemistry and Molecular Genetics University of Alabama at Birmingham Birmingham 35294-0005 USA

The prevalent human papillomaviruses(HPVs) infect either cutaneous or mucosal epithelium. Active Infections lead to epithelial hyperprolifeation and are usually cleared in healthy individuals within a year. Persistent infections in the anogenital tracts by certain high-risk genotypes such as HPV-16, HPV-18 and closely related types, can progress to high grade dysplasias and carcinomas in women and men, including cervical, vulva, penile and anal cancers. A significant fraction of the head and neck cancers are also caused by HPV-16. The viral oncogenes responsible for neoplastic conversion are E6 and E7 that disrupt the pathways controlled by the two major tumor suppressor genes, p53 and members of p RB family. Because HPV cannot be propagated in conventional submerged monolayer cell cultures, organotypic epithelial raft cultures that generate a stratified and differentiated epithelium have been used to study the viral life cycle. This article describes several systems to examine aspects of the viral productive phase, along with the advantages and limitations. Animal model systems of HPV carcinogenesis are also briefly described.

关键词： human papillomaviruses(HPVs) productive program HPV-associated cancers model systems

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A survey of sub-inhibitory concentrations of antibiotics in the environment

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Journal of Environmental Sciences 2021年第1期33卷 21-27页

作者： louise K.M.chow Timothy M.Ghaly Michael R.Gillings Department of Biological Sciences Macquarie UniversityNSW 2109Australia ARC Centre of Excellence in Synthetic Biology Macquarie UniversityNSW 2109Australia

Antibiotics are poorly metabolized,and can enter the environment via human waste streams,agricultural run-off and pharmaceutical *** consequently expect to see a concentration gradient of antibiotic compounds radiating from areas of human *** antibiotics should be thought of as pollutants,as they can accumulate,and have biological *** antibiotic pollutants can increase rates of mutation and lateral transfer events,and continue to exert selection pressure even at sub-inhibitory ***,we conducted a literature survey on environmental concentrations of *** collated 887 data points from 40 peer-reviewed *** then determined whether these concentrations were biologically relevant by comparing them to their minimum selective concentrations,usually defined as between 1/4 and 1/230 of the minimum inhibitory *** concentrations of antibiotics surveyed often fall into this *** general,the antibiotic concentrations recorded in aquatic and sediment samples were *** findings indicate that environmental concentrations of antibiotics are likely to be influencing microbial ecology,and to be driving the selection of antibiotic resistant bacteria.

关键词： Antimicrobial Pollution Evolution Microorganism Environment Antibiotic resistance

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INT-767 improves histopathological features in a dietinduced ob/ob mouse model of biopsy-confirmed nonalcoholic steatohepatitis

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World Journal of Gastroenterology 2018年第2期24卷 195-210页

作者： Jonathan D Roth Michael Feigh Sanne S Veidal louise KD Fensholdt Kristoffer T Rigbolt Henrik H Hansen Li C Chen Mathieu Petitjean Weslyn Friley Niels Vrang Jacob Jelsing Mark Young Intercept Pharmaceuticals Intercept PharmaceuticalsSan DiegoCA 92121United States Gubra Hoersholm DK-2970Denmark PharmaNest Genesis Imaging ServicesPrincetonNJ 08540United States Qualyst Transporter Solutions DurhamNC 27713United States

AIM To characterize the efficacy of the dual FXR/TGR5 receptor agonist INT-767 upon histological endpoints in a rodent model of diet-induced and biopsy-confirmed non-alcoholic steatohepatitis(NASH).METHODS The effects of INT-767 on histological features of NASH were assessed in two studies using Lep^(ob/ob)(ob/ob) NASH mice fed the AMLN diet(high fat with transfat, cholesterol and fructose). In a proof-of-conceptstudy, Lep^(ob/ob)(ob/ob) NASH mice were first dosed with INT-767(3 or 10 mg/kg for 8 wk). A second ob/ob NASH study compared INT-767(3 and 10 mg/kg) to obeticholic acid(OCA)(10 or 30 mg/kg; 16 wk). Primary histological endpoints included qualitative and quantitative assessments of NASH. Other metabolic and plasma endpoints were also assessed. A comparative assessment of INT-767 and OCA effects on drug distribution and hepatic gene expression was performed in C57 Bl/6 mice on standard chow. C57 Bl/6 mice were orally dosed with INT-767 or OCA(1-30 mg/kg) for 2 wk, and expression levels of candidate genes were assessed by RNA sequencing and tissue drug levels were measured by liquid chromatography tandem-mass *** INT-767 dose-dependently(3 and 10 mg/kg, PO, QD, 8 wk) improved qualitative morphometric scores on steatohepatitis severity, inflammatory infiltrates and fibrosis stage. Quantitative morphometric analyses revealed that INT-767 reduced parenchymal collagen area, collagen fiber density, inflammation(assessed by Galectin-3 immunohistochemistry) and hepatocyte lipid droplet area following INT-767 treatment. In a comparative study(16 wk), the FXR agonists OCA(10 and 30 mg/kg) and INT-767(3 and 10 mg/kg) both improved NASH histopathology, with INT-767 exerting greater therapeutic potency and efficacy than OCA. Mechanistic studies suggest that both drugs accumulate similarly within the liver and ileum, however, the effects of INT-767 may be driven by enhanced hepatic, but not ileal, FXR function. CONCLUSION These findings confirm the potenti

关键词： Non-alcoholic steatohepatitis INT-767 Obeticholic acid Liver biopsy FXR TGR5 Mouse model

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