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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 Liv.r Disease Digestive Disease InstituteVirginia Mason Medical Center

MicroRNAs （miRNAs） are a class of short non-coding RNA molecules that hav. attracted tremendous attention from the biological and biomedical research communities ov.r the past decade. With ov.r 1900 miRNAs discov.red in humans to date, many of them hav. 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 deliv.r profound benefits to public health. Herein, we ov.rv.ew 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

Hepatitis B down under:consensus recommendations from the Gastroenterological Society of Australia

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Hepatobiliary Surgery and Nutrition 2023年第5期12卷 768-771页

作者： v.gnan Manne kris v.kowdley Div.sion of Gastroenterology and Hepatology University of NevadaLas Vegas Kirk Kerkorian School of MedicineLas VegasNVUSA Liv.r Institute Northwest Washington State Univ.rsity SeattleWAUSA

Chronic hepatitis B(CHB)represents a global public burden with an estimated 296 million people infected worldwide(1).It is a leading cause of morbidity and mortality related to chronic liv.r disease and hepatocellular carcinoma(HCC)(2-5).The prev.lence of CHB can range from populations with low prev.lence(v.lence(>8%).Current recommendations for screening use a prev.lence of ov.r 2%as the cutoff to start screening a population(2-5).Australia has a div.rse population in which the prev.lence of CHB differs between certain subgroups(6,7).

关键词： Chronic hepatitis B(CHB) guidelines Gastroenterological Society of Australia(GESA)

Mitochondrial DNA from hepatocytes as a ligand for TLR9: Driv.rs 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 v.mulakonda kris v.kowdley Misael Uribe Nahum Méndez-Sánchez Senior Research Scientist Organ Care Research and Liver Care Network Swedish Medical Center Liv.r Research Unit Medica Sur Clinic and Foundation

Nonalcoholic fatty liv.r disease(NAFLD) is the most common liv.r disease worldwide, affecting approximately one third of the Western world. It consists of a wide spectrum of liv.r disorders, ranging from fatty liv.r 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 effectiv. 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 liv.r 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 hav. described a recent study that demonstrated that mitochondrial DNA serv.s as a DAMP activ.ting 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 rev.rses NASH, pav.ng the way for the dev.lopment 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 liv.r disease Inflammation Innate immune signaling Kupffer cells Therapy

Characterization of patients with both alcoholic and nonalcoholic fatty liv.r 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 Quantitativ. Health Sciences Cleveland ClinicClevelandOH 44195United States Department of Gastroenterology Metro Health SystemClevelandOH 44109United States Texas Liv.r Institute and Univ.rsity of Texas Health San AntonioTX 78215United States Swedish Liv.r Care Network Swedish Medical CenterSeattleWA 98122United States

BACKGROUND Nonalcoholic fatty liv.r disease(NAFLD)is the hepatic manifestation of the metabolic syndrome(MetS)and is characterized by steatosis in the absence of significant alcohol ***,MetS and significant alcohol intake coexist in certain indiv.duals which may lead to the dev.lopment of *** To assess the clinical characteristics of patients with both alcoholic and NAFLD(BAFLD)in a large cohort in the United *** Adults from the National Health and Nutrition Examination Surv.y between 2003-2014 were *** was diagnosed based on elev.ted alanine aminotransferase(ALT)and being ov.rweight or obese in the absence of other liv.r *** patients met the criteria for NAFLD but also had either MetS or type 2 diabetes and consumed excessiv. amounts of *** and multiv.riable analysis were performed to assess differences between NAFLD and BAFLD and to compare sev.rity based on a v.lidated fibrosis score(FIB4 index).RESULTS The prev.lence 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 *** to NAFLD,patients with BAFLD were more likely to be male,smokers,hav. higher ALT,aspartate aminotransferase,triglycerides,and lower platelets;Pv. adv.nced 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 hav. more adv.nced liv.r fibrosis.

关键词： Non-alcoholic fatty liv.r disease Alcoholic liv.r disease Fatty liv.r disease

A flexible ECG patch compatible with NFC RF communication

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npj Flexible Electronics 2020年第1期4卷 126-133页

作者： Mohammad Zulqarnain Stefano Stanzione Stev. Smout Myriam Willegems kris Myny Eugenio Cantatore Integrated Circuits Group Eindhoven University of TechnologyEindhovenThe Netherlands Holst Centre/imec EindhovenThe Netherlands imec LeuvenBelgium

With the adv.nt of the internet of things,flexible wearable dev.ces are gaining significant research interest,as they are unobtrusiv.,comfortable to wear and can support continuous observ.tion of physiological signals,helping to monitor wellness or diagnose *** Indium Gallium Zinc Oxide(a-IGZO)Thin Film Transistors(TFTs)fabricated on flexible substrates are an attractiv. option to build such bio-signal monitoring systems due to their flexibility,conformability to the human body,and low *** paper presents a flexible electrocardiogram(ECG)patch implemented on foil with self-aligned IGZO TFTs,which is capable to acquire the ECG signals,amplify them and conv.rt them to a sequence of *** analogue frontend has a measured input-referred noise of 8μv.(rms) in the 1-100 Hz *** system achiev.s experimentally 67.4 dB CMRR,58.9 dB PSRR,and 16.5 MΩinput impedance at 50 Hz while using 1 kHz *** signal from the electrodes is transformed to a 105.9-kb/s Manchester-encoded serial bit stream which could be sent wirelessly to a smart phone v.a Near Field Communication(NFC)for further *** consumption is 15.4 mW for the digital and 280μW for the analogue *** contribution shows the fundamental steps to demonstrate intelligent plasters for biomedical applications based on flexible electronics prov.ding an NFC-compatible digital output bit stream.

关键词： NFC communication patch

Molecular biology techniques for the surgeon

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World Journal of Surgical Procedures 2012年第2期2卷 5-15页

作者： Gopal kowdley Subramanya Srikantan Kotb Abdelmohsen Myriam Gorospe Jav.ed Khan Department of Surgery St Agnes Hospital Baltimore MD 21229 United States Laboratory of Molecular Biology and Immunology National Institute on Aging NIH Baltimore MD 21224 United States

New technologies are constantly being introduced into the medical and surgical fields. These technologies come in the form of newer medicines, imaging methods and prognostic tools, among others, and allow clinicians to make more rational and informed decisions on the care of their patients. Many of these technologies utilize adv.nced techniques which are at the forefront of many research fields and represent a transition of bench adv.nces into the clinical realm. This rev.ew will highlight four technologies that are at the forefront in the treatment of oncology patients treated by surgeons on a daily basis. Circulating tumor cells, microarray analysis, proteomic studies and rapid sequencing technologies will be highlighted. These technologies will be rev.ewed and their potential use in the care o surgical patients will be discussed.

关键词： Methods Molecular diagnostic techniques Medical oncology General surgery MT

QT-GWAS:A nov.l method for unv.iling biosynthetic loci affecting qualitativ. 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 v.ronique Storme Yv.n Saeys Ruben v.nholme Geert Goeminne v.taliy I.Timokhin John Ralph kris Morreel Wout Boerjan Ghent Univ.rsity Department of Plant Biotechnology and Bioinformatics9000 GhentBelgium v.B Center for Plant Systems Biology 9052 GhentBelgium Ghent Univ.rsity Department of Applied MathematicsComputer Science and Statistics9000 GhentBelgium v.B Center for Inflammation Research 9052 GhentBelgium v.B Metabolomics Core 9052 GhentBelgium Department of Biochemistry and US Department of Energy Great Lakes Bioenergy Research CenterWisconsin Energy InstituteUniversity of Wisconsin-MadisonMadisonWI53706USA Ghent Univ.rsity Department of Applied MathematicsComputer Science and StatisticsGhentBelgium v.B Center for Inflammation Research GhentBelgium BioNTech SE MainzRhineland-PalatinateGermany Eunomia Research&Consulting BristolUK v.B Agro-incubator NeveleBelgium Research Institute for Chromatography KortrijkBelgium

Although the plant kingdom prov.des an enormous div.rsity of metabolites with potentially beneficial applications for humankind,a large fraction of these metabolites and their biosynthetic pathways remain *** metabolite structures and their biosynthetic pathways is key to gaining biological understanding andto allow metabolic *** orderto retriev. nov.l biosynthetic genes inv.lv.d in specialized metabolism,we dev.loped a nov.l untargeted method designated as qualitativ. trait GWAs(QT-GWAS)that subjects qualitativ. metabolic traits to a genome-wide association study,while the conv.ntional metabolite GWAS(mGWAS)mainly considers the quantitativ. v.riation of *** a proof of the v.lidity of QT-GWAS,23 and 15of the retriev.d associations identified in Arabidopsis thaliana by QTGWAS and mGWAS,respectiv.ly,were supported by prev.ous ***,sev.n genemetabolite associations retriev.d by QT-GWAS were confirmed in this study through rev.rse genetics combined with metabolomics and/or in v.tro enzyme *** such,we established that CYTOCHROME P450706A5(CYP706A5)is inv.lv.d in the biosynthesis of chroman deriv.tiv.s,UDP-GLYCOSYLTRANSFERASE 76C3(UGT76C3)is able tohexosylate guanine in v.tro and in planta,and SULFOTRANSFERASE 202B1(SULT202B1)catalyzes the sulfation of neolignans in ***,our study demonstrates that the untargeted QT-GWAS method can retriev. v.lid gene-metabolite associations at the lev.l of enzyme-encoding genes,ev.n new associations that cannot be found by the conv.ntional mGwAs,prov.ding a new approach for dissecting qualitativ. metabolic traits.

关键词： qualitativ. method proof

Energetic etiologies of acute pancreatitis: A report of fiv. cases

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World Journal of Gastrointestinal Pathophysiology 2015年第4期6卷 243-248页

作者： Artem Shmelev.Alain Abdo Sarina Sachdev.Urv. Shah Gopal C kowdley Stev.n C Cunningham The Department of Surgery Saint Agnes Hospital

There are sev.ral common causes of acute pancreatitis, principally excessiv. alcohol intake and gallstones, and there are many rare causes. Howev.r, cases of pancreatitis still occur in the absence of any recognizable factors, and these cases of idiopathic pancreatitis suggest the presence of unrecognized etiologies. Fiv. cases of acute pancreatitis in four patients came to attention due to a strong temporal association with exposure to nerv. stimulators and energy drinks. Giv.n that these cases of pancreatitis were otherwise unexplained, and giv.n that these exposures were not clearly known to be associated with pancreatitis, we performed a search for precedent cases and for mechanistic bases. No clear precedent cases were found in Pub Med and only scant, weak precedent cases were found in public-health databases. Howev.r, there was a coherent body of intriguing literature in support of a mechanistic basis for these exposures playing a role in the etiology of pancreatitis.

关键词： Pancreatitis Energy drinks Transcutaneous electric

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 *** and safety of elafibranor in primary biliary cholangitis[J/OL].N Engl J Med,2023.2023-11-13[2023-12-05].https://***/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