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MicroRNAs in Common Human Diseases

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Genomics, Proteomics & Bioinformatics 2012年第5期10卷 246-253页

作者： Yu Li kris v.kowdley Benaroya Research Institute and Center for Liver Disease Digestive Disease InstituteVirginia Mason Medical Center

MicroRNAs （miRNAs） are a class of short non-coding RNA molecules that have attracted tremendous attention from the biological and biomedical research communities over the past decade. With over 1900 miRNAs discovered in humans to date, many of them have already been implicated in common human disorders. Facilitated by high-throughput genomics and bioinformatics in conjunction with traditional molecular biology techniques and animal models, miRNA research is now positioned to make the transition from laboratories to clinics to deliver profound benefits to public health. Herein, we overview the progress of miRNA research related to human diseases, as well as the potential for miRNA to becoming the next generation of diagnostics and therapeutics.

关键词： MicroRNA Human diseases Diagnostics Therapeutics Biomarker

在临床研究中,索磷布韦/维帕他韦用于伴随使用质子泵抑制剂的患者时安全有效

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在临床研究中,索磷布韦/维帕他韦用于伴随使用质子泵抑制剂的患者...

Current perspectives into the evaluation and management of hepatitis B: a review

第十届全国疑难及重症肝病大会

作者： Rafael Esteban Kosh Agarwal Jose Luis Calleja Jean Francois Dufour Steven L.Flamm Stuart C.Gordon Luisa Stamm Liyun Ni Diana Brainard kris v.kowdley Curtis Cooper Juan Antonio Pineda Lluis Castells Maria Buti Sabela Lens UniversityofBarcelona SwedishMedicalCenter GileadSciencesInc. HospitalUniversitarivalld’Hebron GileadSciences Inc. vallD’hebronUniversityHospital NorthwesternUniversityHealthSystem HospitalUniversitarioPuertaDeHierro HospitalUniversitariovirgenDevalme UniversityofBern LiverUnit InternalMedicineDepartmentHospitalUniversitariVallDeHebrón InstituteofLiverStudies King’sCollegeHospitalNHSTrust HenryFordHealthSystem TheOttawaHospital

背景在1期药物相互作用数据可用之前,在有关索磷布韦/维帕他韦(SOF/vEL)的临床试验中禁止伴随使用质子泵抑制剂(PPI)。之后的临床研究允许使用最多20mg的奥美拉唑或等效剂量的药物。本分析评估了接受12周的SOF/vEL治疗并且报告伴随使用...

背景在1期药物相互作用数据可用之前,在有关索磷布韦/维帕他韦(SOF/vEL)的临床试验中禁止伴随使用质子泵抑制剂(PPI)。之后的临床研究允许使用最多20mg的奥美拉唑或等效剂量的药物。本分析评估了接受12周的SOF/vEL治疗并且报告伴随使用PPI的伴有和不伴有代偿期肝硬化的患者的疗效和安全性。

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Hepatobiliary Surgery and Nutrition 2019年第4期8卷 361-369页

作者： vignan Manne Eric Gochanour kris v. kowdley Liver Care Network Swedish Medical Center Seattle WA USA

Hepatitis B is a widespread disease which affects millions of people worldwide. Chronic hepatitis B (CHB) can lead to significant morbidity and mortality due to complications such as cirrhosis and hepatocellular carcinoma. The pathophysiology of hepatitis is critical to diagnosing CHB. Deciding which patients with CHB should be treated is an important decision as treatment can often lead to better outcomes in the appropriate patient population. The nucleos(t)ide analog inhibitors entecavir and tenofovir are currently the mainstay of treatment as they are able to successfully suppress the virus and lead to fewer complications. Novel therapies are currently being developed which may offer a potential cure for this disease in the future.

关键词： Chronic hepatitis B (CHB) hepatocellular carcinoma (HCC) tenofovir entecavir

Characterization of patients with both alcoholic and nonalcoholic fatty liver disease in a large United States cohort

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World Journal of Hepatology 2019年第10期11卷 710-718页

作者： George Khoudari Amandeep Singh Mazen Noureddin Danielle Fritze Rocio Lopez Imad Asaad Eric Lawitz Fred Poordad kris v.kowdley Naim Alkhouri Department of Hospital Medicine Cleveland Clinic FoundationClevelandOH 44195United States Department of Gastroenterology and Hepatology Cleveland ClinicClevelandOH 44195United States Department of Gastroenterology and Hepatology Cedars Sinai Medical CenterLos AngelesCA 90048United States Department of General Surgery Texas Liver Institute and University of Texas HealthSan AntonioTX 78215United States Department of Quantitative Health Sciences Cleveland ClinicClevelandOH 44195United States Department of Gastroenterology Metro Health SystemClevelandOH 44109United States Texas Liver Institute and University of Texas Health San AntonioTX 78215United States Swedish Liver Care Network Swedish Medical CenterSeattleWA 98122United States

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is the hepatic manifestation of the metabolic syndrome(MetS)and is characterized by steatosis in the absence of significant alcohol consumption.However,MetS and significant alcohol intake coexist in certain individuals which may lead to the development of BAFLD.AIM To assess the clinical characteristics of patients with both alcoholic and NAFLD(BAFLD)in a large cohort in the United States.METHODS Adults from the National Health and Nutrition Examination Survey between 2003-2014 were included.NAFLD was diagnosed based on elevated alanine aminotransferase(ALT)and being overweight or obese in the absence of other liver diseases.BAFLD patients met the criteria for NAFLD but also had either MetS or type 2 diabetes and consumed excessive amounts of alcohol.Univariable and multivariable analysis were performed to assess differences between NAFLD and BAFLD and to compare severity based on a validated fibrosis score(FIB4 index).RESULTS The prevalence of NAFLD was at 25.9%(95%CI;25.1-26.8)and that of BAFLD was 0.84%(0.67,1.02)which corresponds to an estimated 1.24 million Americans affected by BAFLD.Compared to NAFLD,patients with BAFLD were more likely to be male,smokers,have higher ALT,aspartate aminotransferase,triglycerides,and lower platelets;Pve advanced fibrosis[adjusted OR(95%CI)based on FIB4 index>2.67 was 3.2(1.4,7.0),P=0.004].CONCLUSION A significant percentage of the American general population is afflicted by BAFLD and these patients tend to have more advanced liver fibrosis.

关键词： Non-alcoholic fatty liver disease Alcoholic liver disease Fatty liver disease

Elafibranor治疗原发性胆汁性胆管炎患者的临床研究

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中国临床药理学杂志 2024年第1期40卷 106-106页

作者： kowdley K v 戴荣源

引自:kowdley K v,et al.Efficacy and safety of elafibranor in primary biliary cholangitis[J/OL].N Engl J Med,2023.2023-11-13[2023-12-05].https://pubmed.***.nlm.***.gov/37962077/.美国西雅图西北肝脏研究所kowdley团队研究了Elafibranor治疗原发性胆汁性胆管炎的疗效和安全性。在这项跨国、3期、双盲、安慰剂对照试验中,研究人员将对熊去氧胆酸反应不足或药物不良反应不可耐受的原发性胆汁性胆管炎患者(按2∶1的比例)进行随机分组,每天接受1次Elafibranor 80 mg或安慰剂。主要终点是第52周的生化缓解(定义为碱性磷酸酶水平<正常范围上限的1.67倍,比基线降低≥15%,总胆红素水平正常)。关键次要终点是第52周碱性磷酸酶水平正常化,以及从基线到第24、52周瘙痒强度的变化[根据最严重瘙痒数值评定量表(the Worst Itch Numeric Rating Scale,WI-NRS)评定]。

关键词：原发性胆汁性胆管炎安慰剂对照疗效和安全性熊去氧胆酸碱性磷酸酶药物不良反应团队研究 DLE

Mitochondrial DNA from hepatocytes as a ligand for TLR9: Drivers of nonalcoholic steatohepatitis?

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World Journal of Gastroenterology 2016年第31期22卷 6965-6971页

作者： Priya Handa Akhila vemulakonda kris v.kowdley Misael Uribe Nahum Méndez-Sánchez Senior Research Scientist Organ Care Research and Liver Care Network Swedish Medical Center Liver Research Unit Medica Sur Clinic and Foundation

Nonalcoholic fatty liver disease(NAFLD) is the most common liver disease worldwide, affecting approximately one third of the Western world. It consists of a wide spectrum of liver disorders, ranging from fatty liver to nonalcoholic steatohepatitis(NASH), which consists of steatosis, ballooning injury and inflammation. Despite an alarming growth in the statistics surrounding NAFLD, there are as yet no effective therapies for its treatment. Innate immune signaling has been thought to play a significant role in initiating and augmenting hepatic inflammation, contributing to the transition from nonalcoholic fatty liver to NASH. An immune response is triggered by countless signals called damage-associated molecular patterns(DAMPs) elicited by lipid-laden and damaged hepatocytes, which are recognized by pattern recognition receptors(PRRs) on hepatic immune cells to initiate inflammatory signaling. In this editorial, in addition to summarizing innate immune signaling in NAFLD and discussing potential therapies that target innate immune pathways, we have described a recent study that demonstrated that mitochondrial DNA serves as a DAMP activating a hepatic PRR, TLR9, in mice and in the plasma of NASH patients. In addition to identifying a new ligand for TLR9 during NASH progression, the study shows that blocking TLR9 reverses NASH, paving the way for the development of future NASH therapy.

关键词： TLR9 Damage-associated molecular patterns Products of microbial metabolism produced by pathogens Mitochondrial DNA Hepatocytes Nonalcoholic steatohepatitis Nonalcoholic fatty liver disease Inflammation Innate immune signaling Kupffer cells Therapy

Philippine retinoblastoma initiative multi-eye center study 2010-2020

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International Journal of Ophthalmology(English edition) 2024年第1期17卷 144-156页

作者： Roland Joseph D.Tan Gary John v.Mercado Patricia E.Cabrera Paulita Pamela P.Astudillo Rolando Enrique D.Domingo Josept Mari S.Poblete Charmaine Grace M.Cabebe Adriel vincent R.Te Melissa Anne S.Gonzales Jocelyn G.Sy Beltran Alexis A.Aclan Jayson T.So Fatima G.Regala Kimberley Amanda K.Comia Josemaria M.Castro Mara Augustine S.Galang Aldous Dominic C.Cabanlas Benedicto Juan E.Aguilar Gabrielle S.Evangelista Jo Michael Maniwan Andrei P.Martin Calvin Y.Martinez John Alfred H.Lim Rena Ivy Bascuna Rachel M.Ng Kevin B.Agsaoay kris Zanna A.Acluba-Arao Ellaine Rose v.Apostol Beatriz M.Prieto Department of Ophthalmology and visual Sciences Philippine General HospitalManila 1000Philippines Department of Ophthalmology Baguio General Hospital and Medical CenterBaguio City 2600Philippines Department of Ophthalmology Manila Doctors HospitalManila 1000Philippines Department of Ophthalmology Rizal Medical CenterPasig City 1600Philippines Department of Ophthalmology Jose B.Lingad Memorial Regional HospitalPampanga 2000Philippines Department of Ophthalmology Southern Philippines Medical CenterDavao City 8000Philippines Department of Ophthalmology East Avenue Medical CenterQuezon City 1100Philippines Department of Ophthalmology Northern Mindanao Medical CenterCagayan de Oro City 9000Philippines Department of Ophthalmology Cebu Velez General HospitalCebu City 6000Philippines Legazpi Eye Center Legazpi City 4500Philippines Department of Ophthalmology Cagayan Valley Medical CenterTuguegarao City 3500Philippines

AIM:To provide a comprehensive and more representative national data on the disease,especially on treatment options and outcomes,and to determine access of retinoblastoma patients from Luzon,visayas and Mindanao to eye care,and determine if access is associated with delay in consultation,staging and outcomes.METHODS:Cohort study of retinoblastoma patients seen in eleven institutions located in the three major areas of the Philippines namely Luzon,vizayas and Mindanao from 2010-2020.RESULTS:Totally 636 patients,involving 821 eyes,were included.Majority(57%)were from Luzon and were seen in institutions in Luzon(72%).Annually,58±10 new cases were seen with 71%having unilateral disease.Median delay of consultation remained long at 9(3,17)mo,longest in patients with unilateral disease(Pvisayas(Pved by 484 patients while intravenous chemotherapy was received by 469.There were 250(39%)patients alive,195(31%)dead,85(13%)abandoned,17(3%)refused and 89(14%)with no data.CONCLUSION:This study presents the largest cohort of retinoblastoma patients in the Philippines in terms of patients’and participating institutions’number and geographical location and type of institution(private and public).It also presents more comprehensive data on the treatments used and outcomes(survival,globe salvage,and vision retention rates).Delay in consultation was still long among patients leading to advanced disease stage and lower survival rate.Despite increasing capacity to diagnose and manage retinoblastoma in the country,the delay of consultation remains long primarily due to accessibility issues to eye care institutions especially in the visayas and financial concerns.The delay was still significant that overall survival rate remain low.

关键词： retinoblastoma Philippines clinical profile

QT-GWAS:A novel method for unveiling biosynthetic loci affecting qualitative metabolic traits

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Molecular Plant 2023年第7期16卷 1212-1227页

作者： Marlies Brouckaert Meng Peng RenéHofer lias El Houari Chiarina Darrah veronique Storme Yvan Saeys Ruben vanholme Geert Goeminne vitaliy I.Timokhin John Ralph kris Morreel Wout Boerjan Ghent University Department of Plant Biotechnology and Bioinformatics9000 GhentBelgium vIB Center for Plant Systems Biology 9052 GhentBelgium Ghent University Department of Applied MathematicsComputer Science and Statistics9000 GhentBelgium vIB Center for Inflammation Research 9052 GhentBelgium vIB Metabolomics Core 9052 GhentBelgium Department of Biochemistry and US Department of Energy Great Lakes Bioenergy Research CenterWisconsin Energy InstituteUniversity of Wisconsin-MadisonMadisonWI53706USA Ghent University Department of Applied MathematicsComputer Science and StatisticsGhentBelgium viB Center for Inflammation Research GhentBelgium BioNTech SE MainzRhineland-PalatinateGermany Eunomia Research&Consulting BristolUK vIB Agro-incubator NeveleBelgium Research Institute for Chromatography KortrijkBelgium

Although the plant kingdom provides an enormous diversity of metabolites with potentially beneficial applications for humankind,a large fraction of these metabolites and their biosynthetic pathways remain unknown.Resolving metabolite structures and their biosynthetic pathways is key to gaining biological understanding andto allow metabolic engineering.In orderto retrieve novel biosynthetic genes involved in specialized metabolism,we developed a novel untargeted method designated as qualitative trait GWAs(QT-GWAS)that subjects qualitative metabolic traits to a genome-wide association study,while the conventional metabolite GWAS(mGWAS)mainly considers the quantitative variation of metabolites.As a proof of the validity of QT-GWAS,23 and 15of the retrieved associations identified in Arabidopsis thaliana by QTGWAS and mGWAS,respectively,were supported by previous research.Furthermore,seven genemetabolite associations retrieved by QT-GWAS were confirmed in this study through reverse genetics combined with metabolomics and/or in vitro enzyme assays.As such,we established that CYTOCHROME P450706A5(CYP706A5)is involved in the biosynthesis of chroman derivatives,UDP-GLYCOSYLTRANSFERASE 76C3(UGT76C3)is able tohexosylate guanine in vitro and in planta,and SULFOTRANSFERASE 202B1(SULT202B1)catalyzes the sulfation of neolignans in vitro.Collectively,our study demonstrates that the untargeted QT-GWAS method can retrieve valid gene-metabolite associations at the level of enzyme-encoding genes,even new associations that cannot be found by the conventional mGwAs,providing a new approach for dissecting qualitative metabolic traits.

关键词： qualitative method proof

Circulating tumor cells in head and neck cancer:A review

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2016年第2期2卷 -页

作者： Kyle P. McMullen Jeffrey J. Chalmers Jas C. Lang Pawan Kumar kris R. Jatana Department of 0tolaryngology-Head and Neck Surgery Wexner Medical Center at 0hio State University Columbus 0H USA William G. Lowrie Department of Chemical and Biomolecular Engineering 0hio State University Columbus 0H USA

Carcinoma of the head and neck represents 3.5% of all cancers, and the vast majority of these tumors are squamous cell carcinoma (HNSCC). With a stable overall survival rate of 50% among all stages, there is continued interested in developing measures for early detection and disease aggressiveness. Circulating tumor cells (CTCs) have been identified as a potential marker for early metastatic disease, response to treatment, and surveillance in head and neck squamous cell carcinoma. In this article, techniques of CTC detection, applications of CTC technology, and outcomes of HNSCC patients will be discussed.

关键词： Circulating tumor cell Head and neck cancer Metastasis Squamous cell