检索结果-南通市图书馆

Ectopic Tcf1 expression instills a stem-like program in exhausted CD8^(+) T cells to enhance viral and tumor immunity

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Cellular & Molecular Immunology 2021年第5期18卷 1262-1277页

作者： Qiang Shan Sheng’en Hu Xia Chen Derek B.Danahy Vladimir P.Badovinac Chongzhi Zang Hai-Hui Xue Center for Discovery and Innovation Hackensack Meridian HealthNutleyNJ07110USA Department of Microbiology and Immunology Carver College of MedicineUniversity of IowaIowa CityIA52242USA Center for Public health Genomics University of Virginia School of MedicineCharlottesvilleVA22908USA Department of Pathology Carver College of MedicineUniversity of IowaIowa CityIA52242USA Interdisciplinary Immunology Graduate Program Carver College of MedicineUniversity of IowaIowa CityIA52242USA iowa city veterans affairs health care system Iowa CityIA52246USA

Exhausted CD8^(+)T(Tex)cells are dysfunctional due to persistent antigen exposure in chronic viral infection and tumor contexts.A stem cell-like Tex(Tex-stem)subset can self-renew and differentiate into terminally exhausted(Tex-term)***,we show that ectopic Tcf1 expression potently promoted the generation of Tex-stem cells in both a chronic viral infection and preclinical tumor ***1 overexpression diminished coinhibitory receptor expression and enhanced polycytokine-producing capacity while retaining a heightened responses to checkpoint blockade,leading to enhanced viral and tumor ***,ectopically expressed Tcf1 exploited existing and novel chromatin accessible sites as transcriptional enhancers or repressors and modulated the transcriptome by enforcing pre-existing expression patterns in Tex-stem cells,such as enhanced suppression of Blimp1 and Bim and acquisition of new downstream genes,including Mx1,Tox2,and *** findings reveal a pronounced impact of ectopic Tcf1 expression on Tex functional restoration and highlight the therapeutic potential of harnessing Tcf1-enforced transcriptional programs.

关键词： T cell exhaustion Tcf1 Stem cell features

Dextran sodium sulfate colitis murine model: An indispensable tool for advancing our understanding of inflammatory bowel diseases pathogenesis

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 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

Treatment of peripheral diabetic neuropathy in Zucker diabetic fatty (ZDF) rats with cariporide

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Journal of Diabetes Mellitus 2014年第1期4卷 59-66页

作者： Sergey Lupachyk Hanna Shevalye Pierre Watcho Alexander Obrosov Irina G. Obrosova Mark A. Yorek Department of veterans affairs iowa city health care system and Department of Internal Medicine University of Iowa Iowa City USA Pennington Biomedical Research Center Louisiana State University System Baton Rouge USA

To determine the effect of Na+/H+-exchanger-1 on diabetic neuropathy in Type 2 diabetes Zucker diabetic fatty (ZDF) rats and lean controls were treated with cariporide (10 or 20 mg/kg/d), a Na+/H+-exchanger-1 inhibitor, for 4 weeks at 15 weeks of age. Neuropathy endpoints included motor (MNCV) and sensory (SNCV) nerve conduction velocities, thermal nociception, tactile allodynia and intraepidermal nerve fiber density. Advanced glycation endproduct and markers of oxidative stress including nitrated protein levels in sciatic nerve and dorsal root ganglion were also evaluated. Expression of Na+/H+-exchanger-1 in dorsal root ganglion neurons was increased in ZDF rats. At 15 weeks of age ZDF rats displayed hyperglycemia, MNCV and SNCV deficits, thermal hypoalgesia and tactile allodynia. At 20 but not 10 mg/kg/d, cariporide significantly improved MNCV and SNCV deficits, thermal hypoalgesia and tactile allodynia. Cariporide treatment was also associated with reduction of diabetes-induced accumulation of advanced glycation end-product (AGE), oxidative stress and nitrated proteins in sciatic nerve and dorsal root ganglion neurons. In conclusion, these findings support an important role for Na+/H+-exchanger-1 in peripheral diabetic neuropathy, and provide rationale for development of Na+/H+-exchanger-1 inhibitors for treatment of diabetic neural complications.

关键词： Diabetic Neuropathy Sodium/Hydrogen Exchanges Oxidative Stress

Serelaxin increases the antifibrotic action of rosiglitazone in a model of hepatic fibrosis

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22期23卷 3999-4006页

作者： Robert G Bennett Ronda L Simpson Frederick G Hamel Research Service Nebraska-Western Iowa Health Care System Department of Internal Medicine University of Nebraska Medical Center

To determine the effect of combined serelaxin and rosiglitazone treatment on established hepatic *** fibrosis was induced in mice by carbon tetrachloride administration for 6 wk, or vehicle alone (nonfibrotic mice). For the final 2 wk, mice were treated with rosiglitazone, serelaxin, or both rosiglitazone and serelaxin. Serum liver enzymes and relaxin levels were determined by standard methods. The degree of liver collagen content was determined by histology and immunohistochemistry. Expression of type I collagen was determined by quantitative PCR. Activation of hepatic stellate cells was assessed by alpha-smooth muscle actin (SMA) levels. Liver peroxisome proliferator activated receptor-gamma coactivator 1 alpha (PGC1α) was determined by Western *** of mice with CCl4 resulted in hepatic fibrosis as evidenced by increased liver enzyme levels (ALT and AST), and increased liver collagen and SMA. Monotherapy with either serelaxin or rosiglitazone for 2 wk was generally without effect. In contrast, the combination of serelaxin and rosiglitazone resulted in significantly improved ALT levels (P < 0.05). Total liver collagen content as determined by Sirius red staining revealed that only combination treatment was effective in reducing total liver collagen (P < 0.05). These results were supported by immunohistochemistry for type I collagen, in which only combination treatment reduced fibrillar collagen levels (P < 0.05). The level of hepatic stellate cell activation was modestly, but significantly, reduced by serelaxin treatment alone, but combination treatment resulted in significantly lower SMA levels. Finally, while hepatic fibrosis reduced liver PGC1α levels, the combination of serelaxin and rosiglitazone resulted in restoration of PGC1α protein *** combination of serelaxin and rosiglitazone treatment for 2 wk was effective in significantly reducing established hepatic fibrosis, providing a potential

关键词： Relaxin Peroxisome proliferator-activated receptors Liver cirrhosis Liver diseases Fibrosis

Traumatic brain injury and sight loss in military and veteran populations–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

Military Medical Research 2022年第1期9卷 71-85页

作者： Syeda F.Hussain Zara Raza Andrew T.G.Cash Thomas Zampieri Robert A.Mazzoli Randy H.Kardon Renata S.M.Gomes Research&Innovation Blind Veterans UK12-14 Harcourt StreetLondon W1H 4HDUK. Bravo Victor Research12-14 Harcourt StreetLondon W1H 4HDUK Blinded veterans Association 1101 King StreetSuite 300AlexandriaVirginia 22314USA Department of Ophthalmology Madigan Army Medical Center9040 Jackson AvenueTacomaWashington 98431USA lowa city VA health care system and iowa city VA Center for the Prevention and Treatment of Visual Loss Iowa CityIowa 52246USA department of Ophthalmology and Visual Sciences The University of IowaIowa CityIowa 52242USA Northern Hub for veterans and Military Families Research Department of NursingMidwifery and HealthFaculty of Health and Life SciencesNorthumbria UniversityNewcastle NE77XAUK.

War and combat exposure pose great risks to the vision *** recently,vision related deficiencies and impairments have become common with the increased use of powerful explosive devices and the subsequent rise in incidence of traumatic brain injury(TBI).Studies have looked at the effects of injury severity,aetiology of injury and the stage at which visual problems become *** was little discrepancy found between the frequencies or types of visual dysfunctions across blast and non-blast related groups,however complete sight loss appeared to occur only in those who had a blast-related ***,the more severe the injury,the greater the likelihood of specific visual disturbances occurring,and a study found total sight loss to only occur in cases with greater *** of mild TBI(mTBI)is *** able to identify a potential TBI via visual symptoms may offer a new avenue for diagnosis.

关键词： Traumatic brain injury Visual impairment Military Veteran