检索结果-南通市图书馆

World Journal of Gastroenterology 2017年第33期23卷 6016-6029页

作者： Derrick D Eichele kusum k kharbanda Department of Internal Medicine Nebraska Medical Center Research Service Veterans Affairs Nebraska-Western Iowa Health Care System Department of Biochemistry and Molecular Biology Nebraska Medical Center

Inflammatory bowel diseases(IBD),including Crohn's disease and ulcerative colitis,are complex diseases that result from the chronic dysregulated immune response in the gastrointestinal tract. The exact etiology is not fully understood,but it is accepted that it occurs when an inappropriate aggressive inflammatory respon-se in a genetically susceptible host due to inciting environmental factors occurs. To investigate the path-ogenesis and etiology of human IBD,various animal models of IBD have been developed that provided indispensable insights into the histopathological and morphological changes as well as factors associated with the pathogenesis of IBD and evaluation of therapeutic options in the last few decades. The most widely used experimental model employs dextran sodium sulfate(DSS) to induce epithelial damage. The DSS colitis model in IBD research has advantages over other various chemically induced experimental models due to its rapidity,simplicity,reproducibility and controllability. In this manuscript,we review the newer publicized advances of research in murine colitis models that focus upon the disruption of the barrier function of the intestine,effects of mucin on the development of colitis,alterations found in microbial balance and resultant changes in the metabolome specifically in the DSS colitis murine model and its relation to the pathogenesis of IBD.

关键词： Dextran sodium sulfate Experimental colitis Inflammatory bowel disease Pathogenesis Intestinal barrier

Treatment options for alcoholic and non-alcoholic fatty liver disease: A review

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

World Journal of Gastroenterology 2017年第36期23卷 6549-6570页

作者： Sukhpreet Singh Natalia A Osna kusum k kharbanda Research Service Veterans Affairs Nebraska-Western Iowa Health Care System Department of Internal Medicine Nebraska Medical Center Department of Biochemistry and Molecular Biology Nebraska Medical Center

Alcoholic liver disease(ALD)and non-alcoholic fatty liver disease(NAFLD)are serious health problems *** two diseases have similar pathological spectra,ranging from simple steatosis to hepatitis to cirrhosis and hepatocellular *** most people with excessive alcohol or calorie intake display abnormal fat accumulation in the liver(simple steatosis),a small percentage develops progressive liver *** extensive research on understanding the pathophysiology of both these diseases there are still no targeted therapies *** treatment for ALD remains as it was 50 years ago:abstinence,nutritional support and corticosteroids(or pentoxifylline as an alternative if steroids are contraindicated).As for NAFLD,the treatment modality is mainly directed toward weight loss and co-morbidity ***,new pathophysiology directed therapies are urgently ***,the involvement of several inter-related pathways in the pathogenesis of these diseases suggests that a single therapeutic agent is unlikely to be an effective treatment ***,a combination therapy towards multiple targets would eventually be *** this review,we delineate the treatment options in ALD and NAFLD,including various new targeted therapies that are currently under *** hope that soon we will be having an effective multi-therapeutic regimen for each disease.

关键词： Alcoholic liver disease Non-alcoholic fatty liver disease Treatment options Glucocorticoids Liver transplantation

Human immunodeficiency virus and hepatotropic viruses comorbidities as the inducers of liver injury progression

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

World Journal of Gastroenterology 2019年第4期25卷 398-410页

作者： Murali Ganesan Larisa Y Poluektova kusum k kharbanda Natalia A Osna Research Service Veterans Affairs Nebraska-Western Iowa Health Care System Department of Internal Medicine University of Nebraska Medical Center Department of Pharmacology and Experimental Neuroscience University of Nebraska Medical Center

Hepatotropic viruses induced hepatitis progresses much faster and causes more liver-related health problems in people co-infected with human immunodeficiency virus(HIV). Although treatment with antiretroviral therapy has extended the life expectancy of people with HIV, liver disease induced by hepatitis B virus(HBV) and hepatitis C virus(HCV) causes significant numbers of non-acquired immune deficiency syndrome(AIDS)-related deaths in coinfected patients. In recent years, new insights into the mechanisms of accelerated fibrosis and liver disease progression in HIV/HCV and HIV/HBV co-infections have been reported. In this paper, we review recent studies examining the natural history and pathogenesis of liver disease in HIV-HCV/HBV co-infection in the era of direct acting antivirals(DAA) and antiretroviral therapy(ART). We also review the novel therapeutics for management of HIV/HCV and HIV/HBV coinfected individuals.

关键词： Human immunodeficiency virus Hepatitis C virus Hepatitis B virus Fibrosis Stiffness Treatment

Liver as a target of human immunodeficiency virus infection

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

World Journal of Gastroenterology 2018年第42期24卷 4728-4737页

Liver injury is a characteristic feature of human immunodeficiency virus(HIV) infection, which is the second most common cause of mortality in HIV-infected patients. Now it is recognized that liver plays a key role in HIV infection pathogenesis. Antiretroviral therapy(ART), which suppresses HIV infection in permissive immune cells, is less effective in hepatocytes, thereby making these cells a silent reservoir of HIV infection. In addition to direct hepatotoxic effects of HIV, certain ART treatment modalities provide hepatotoxic effects. The exact mechanisms of HIV-triggered chronic hepatitis progression are not elucidated, but the liver is adversely affected by HIV-infection and liver cells are prominently involved in HIV-elicited injury. These effects are potentiated by second hits like alcohol. Here, we will focus on the incidence of HIV, clinical evidence of HIVrelated liver damage, interactions between HIV and liver cells and the role of alcohol and co-infection with hepatotropic viruses in liver inflammation and fibrosis progression.

关键词： Liver cells Antiretroviral therapy Apoptosis Inflammation Fibrosis Immunodeficiency virus Alcohol

Role of transmethylation reactions in alcoholic liver disease

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

World Journal of Gastroenterology 2007年第37期13卷 4947-4954页

作者： kusum k kharbanda VA Alcohol Research Center Department of Veterans Affairs Medical Center Omaha Nebraska 68105 United States Department of Internal Medicine University of Nebraska Medical Center Omaha Nebraska 68198 United States

Alcoholic liver disease is a major health care problem worldwide. Findings from many laboratories, including ours, have demonstrated that ethanol feeding impairs several of the many steps involved in methionine metabolism. Ethanol consumption predominantly results in a decrease in the hepatocyte level of S-adenosylmethionine and the increases in two toxic metabolites, homocysteine and S-adenosylhomocysteine. These changes, in turn, result in serious functional consequences which include decreases in essential methylation reactions v/a inhibition of various methyltransferases. Of particular interest to our laboratory is the inhibition of three important enzymes, phosphatidylethanolamine methyltransferase, isoprenylcysteine carboxyl methyltransferase and protein L-isoaspartate methyltransferase. Decreased activity of these enzymes results in increased fat deposition, increased apoptosis and increased accumulation of damaged proteins- all of which are hallmark features of alcoholic liver injury. Of all the therapeutic modalities available, betaine has been shown to be the safest, least expensive and most effective in attenuating ethanol-induced liver injury. Betaine, by virtue of aiding in the remethylation of homocysteine, removes both toxic metabolites （homocysteine and S-adenosylhomocysteine）, restores S-adenosylmethionine level, and reverses steatosis, apoptosis and damaged proteins accumulation. In conclusion, betaine appears to be a promising therapeutic agent in relieving the methylation and other defects associated with alcoholic abuse.

关键词： Transmethylation S-adenosylhomocysteine Alcohol Betaine Liver Steatosis Apoptosis Methyltransferases

Role of alcohol in pathogenesis of hepatitis B virus infection

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

World Journal of Gastroenterology 2020年第9期26卷 883-903页

作者： Murali Ganesan Allison Eikenberry Larisa Y Poluektova kusum k kharbanda Natalia A Osna Research Service Veterans Affairs Nebraska-Western Iowa Health Care SystemOmahaNE 68105United States Department of Internal Medicine Division of Gastroenterology and HepatologyUniversity of Nebraska Medical CenterOmahaNE 68105United States

Hepatitis B virus(HBV)and alcohol abuse often contribute to the development of end-stage liver *** abuse not only causes rapid progression of liver disease in HBV infected patients but also allows HBV to persist ***,the mechanism by which alcohol promotes the progression of HBVassociated liver disease are not completely *** mechanisms include a suppressed immune response,oxidative stress,endoplasmic reticulum and Golgi apparatus stresses,and increased HBV ***,more research is necessary to gain a better understanding of these mechanisms such that treatment(s)to prevent rapid liver disease progression in alcohol-abusing HBV patients could be *** this review,we discuss the aforementioned factors for the higher risk of liver diseases in alcohol-induced HBV pathogenies and suggest the areas for future studies in this field.

关键词： Hepatitis B virus Alcohol Immunity Oxidative stress Liver disease

Cellular fi bronectin stimulates hepatocytes to produce factors that promote alcohol-induced liver injury

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

World Journal of Hepatology 2011年第2期3卷 45-55页

作者： Razia S Aziz-Seible Benita L McVicker kusum k kharbanda Carol A Casey Department of Biochemistry and Molecular Biology University of Nebraska Medical Center985870Nebraska Medical CenterOmahaNE68198-5870United States Liver Study Unit Omaha Veterans Affairs Medical Center4101 Woolworth AvenueOmahaNE68105United States

AIM:To examine the consequences of cellular f ibronectin(cFn)accumulation during alcohol-induced injury,and inv estigate whether increased cFn could have an effect on hepatocytes(HCs)by producing factors that could cont ribute to alcohol-induced liver ***:HCs were isolated from rats fed a control or ethanol liquid diet for four to six *** c Fn(up to 7.5 μg/mL)was added to cells cultured for 20 h,and viability(lactate dehydrogenase),apoptosis(caspase activity)and se cretion of proinflammat-ory cytokines(tumor ne c rosis fac tor alpha,TNF-α and interleukin 6,IL-6),mat rix metalloproteinases(MMPs)and their inhibitors(tissue inhibitors of metall-oproteinases,TIMPs)was det *** ation of iodinated cFn was det ermined over a 3 h time period in the ***:cFn degradation is impaired in HCs isolated from ethanol-fed animals,leading to its accumulation in the *** of exogenous cFn did not affect viability of HCs from control or ethanolfed animals,and apoptosis was affected only at the higher *** retion of MMPs,TIMPs,TNF-α and IL-6,however,was increased by exogenously added cFn,with HCs from ethanolfed animals showing increased susceptibility compared to the ***:These results suggest that the elevated amounts of cFn observed in alcoholic liver injury can stimulate hepatocytes to produce factors which promote further tissue damage.

关键词： Alcoholic liver diseases Hepatocytes Fibronectin Asialoglycoprotein receptor Inflammation Fibrosis

Lack of hepcidin expression attenuates steatosis and causesfibrosis in the liver

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

World Journal of Hepatology 2016年第4期8卷 211-225页

作者： Sizhao Lu Robert G Bennett kusum k kharbanda Duygu Dee Harrison-Findik Department of Biochemistry University of Nebraska Medical CenterOmahaNE 68198-5870United States Division of Endocrinology Department of Internal MedicineUniversity of Nebraska Medical CenterOmahaNE 68198-4130United States Nebraska-Western Iowa VA Health Care System OmahaNE 68105United States Division of Gastroenterology and Hepatology Department of Internal MedicineUniversity of Nebraska Medical CenterOmahaNE 68198-2000United States

AIM: To investigate the role of key iron-regulatory protein, hepcidin in non-alcoholic fatty liver disease(NAFLD). METHODS: Hepcidin(Hamp1) knockout and floxed control mice were administered a high fat and high sucrose(HFS) or a regular control diet for 3 or 7 mo. Steatosis, triglycerides, fibrosis, protein and gene expression in mice livers were determined by histological and biochemical techniques, western blotting and realtime polymerase chain reaction. RESULTS: knockout mice exhibited hepatic iron accumulation. Despite similar weight gains, HFS feeding induced hepatomegaly in floxed, but not knockout, mice. The livers of floxed mice exhibited higher levels of steatosis, triglycerides and c-Jun N-terminal kinase(JNk) phosphorylation than knockout mice. In contrast, a significant increase in fibrosis was observed in knockout mice livers within 3 mo of HFS administration. The hepatic gene expression levels of sterol regulatoryelement-binding protein-1c and fat-specific protein-27, but not peroxisome proliferator-activated receptoralpha or microsomal triglyceride transfer protein, were attenuated in HFS-fed knockout mice. knockout mice fed with regular diet displayed increased carnitine palmitoyltransferase-1a and phosphoenolpyruvate carboxykinase-1 but decreased glucose-6-phosphatase expression in the liver. In summary, attenuated steatosis correlated with decreased expression of lipogenic and lipid storage genes, and JNk phosphorylation. Deletion of Hamp1 alleles per se modulated hepatic expression of beta-oxidation and gluconeogenic genes. CONCLUSION: Lack of hepcidin expression inhibits hepatic lipid accumulation and induces early development of fibrosis following high fat intake. Hepcidin and iron may play a role in the regulation of metabolic pathways in the liver, which has implications for NAFLD pathogenesis.

关键词： Hamp Iron Non-alcoholic steatohepatitis Metabolic genes Steatosis non-alcoholic fatty liverdisease Steatohepatitis

Lysosome and proteasome dysfunction in alcohol-induced liver injury

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Liver Research 2019年第3期3卷 191-205页

作者： Terrence M.Donohue.Jr Natalia A.Osna kusum k.kharbanda Paul G.Thomes Research Service Department of Veterans AffairsNebraska-Western Iowa Health Care SystemOmahaNEUSA Department of Internal Medicine Section of Gastroenterology and HepatologyUniversity of Nebraska Medical CenterOmahaNEUSA Department of Biochemistry and Molecular Biology University of Nebraska Medical CenterOmahaNEUSA Department of Pharmacology and Experimental Neuroscience University of Nebraska Medical CenterOmahaNEUSA College of Public Health University of Nebraska Medical CenterOmahaNEUSA

The review describes research findings on the influence of alcohol consumption on two crucial catabolic systems in hepatocytes:the lysosome and the ubiquitin-proteasome system(UPS).The lysosome is a membrane-bound organelle that degrades all aging and/or damaged organelles and hydrolyzes all forms of *** UPS is mostly *** carries out the majority of its functions in the soluble portion of the cytoplasm(cytosol)and degrades nearly all intracellular proteins,particularly those with short half-lives,so that their levels are tightly *** review will briefly discuss the epidemiology of alcohol abuse and the spectrum of alcohol-induced liver disease(AILD).We will explain why ethanol(EtOH)metabolism,but not EtOH alone,is ***,we will summarize how heavy drinking alters hepatic catabolic systems,resulting in liver enlargement that develops from hepatocyte swelling due,in part,to aberrant accumulation of undegraded lipid droplets(steatosis)and undegraded proteins(proteopathy).Our detailed description of each catabolic system will highlight its discoverer(s)and emphasize each system’s *** important,we will review the evidence that chronic EtOH consumption disrupts hepatic lysosome biogenesis and inhibits the UPS by impeding hepatic proteasome *** will become evident that each of these EtOH-induced defects has far-reaching functional ***,we will describe current and potential therapeutic interventions for alleviating EtOH-induced liver *** most effective intervention is the cessation of EtOH ***,there are other potential approaches using natural or synthetic compounds that activate autophagy or the proteasome to enhance the degradation of accumulated lipid droplets or proteins,respectively,which could alleviate *** approaches,now in their early stages of investigation,will also be discussed in this review.

关键词： Alcohol Lysosome Proteasome Ethanol Liver Proteostasis Lipostasis Alcohol-induced liver disease(AILD)

Prolonged feeding with guanidinoacetate, a methyl group consumer, exacerbates ethanol-induced liver injury

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

World Journal of Gastroenterology 2016年第38期22卷 8497-8508页

作者： Natalia A Osna Dan Feng Murali Ganesan Priya F Maillacheruvu David J Orlicky Samuel W French Dean J Tuma kusum k kharbanda Research Service Veterans Affairs Nebraska-Western Iowa Health Care System Department of Internal Medicine 982000 Nebraska Medical Center Department of Pathology University of Colorado Denver Department of Anatomic Pathology Harbor UCLA Medical Center Department of Biochemistry and Molecular Biology 985870 Nebraska Medical Center

AIM To investigate the hypothesis that exposure to guanidinoacetate(GAA, a potent methyl-group consumer) either alone or combined with ethanol intake for a prolonged period of time would cause more advanced liver pathology thus identifying methylation defects as the initiator and stimulator for progressive liver *** Adult male Wistar rats were fed the control or ethanolLieber De Carli diet in the absence or presence of GAA supplementation. At the end of 6 wk of the feeding regimen, various biochemical and histological analyses were conducted. RESULTS Contrary to our expectations, we observed that GAA treatment alone resulted in a histologically normal liver without evidence of hepatosteatosis despite persistence of some abnormal biochemical parameters. This protection could result from the generation of creatine from the ingested GAA. Ethanol treatment for 6 wk exhibited changes in liver methionine metabolism and persistence of histological and biochemical defects as reported before. Further, when the rats were fed the GAA-supplemented ethanol diet, similar histological and biochemical changes as observed after 2 wk of combined treatment, including inflammation, macroand micro-vesicular steatosis and a marked decrease in the methylation index were noted. In addition, rats on the combined treatment exhibited increased liver toxicity and even early fibrotic changes in a subset of animals in this group. The worsening liver pathology could be related to the profound reduction in the hepatic methylation index, an increased accumulation of GAA and the inability of creatine generated to exert its hepato-protective effects in the setting of *** To conclude, prolonged exposure to a methyl consumer superimposed on chronic ethanol consumption causes persistent and pronounced liver damage.

关键词： Methyl balance S-adenosylmethionine S-adenosylhomocysteine Guanidinoacetate Alcohol