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01:16 EST 24th February 2020 | BioPortfolio

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Showing PubMed Articles 1–25 of 940 from Hepatology (Baltimore, Md.)

Elevated fructose and uric acid via aldose reductase contribute to experimental and human alcoholic liver disease.

Alcohol-associated liver disease (ALD) is a common chronic liver disease worldwide with high morbidity and mortality, and no FDA-approved therapies. Fructose (dietary or endogenous), its metabolite uric acid, and aldose reductase (AR, the only endogenous enzyme that produces fructose) are strongly associated with the development of non-alcoholic fatty liver disease (NAFLD). However, the role of AR or its metabolites in ALD remains understudied and was examined using human specimens, cultured cells and mouse...

Inflammation-induced LINC00665 increases the malignancy through activating PKR/NF-κB pathway in hepatocellular carcinoma.

NF-κB signaling pathway is important for linking inflammation and tumorigenesis. Here, we characterized a NF-κB-signaling-activation induced long intergenic non-coding RNA in hepatocellular carcinoma (HCC), LINC00665 that contributes to the enhanced cell proliferation of HCC cells both in vitro and in vivo. LINC00665 physically interacts with the double-stranded RNA (dsRNA)-activated protein kinase (PKR) and enhances its activation, and maintains PKR protein stability by blocking ubiquitin/proteasome-depe...

Hepatic ChREBP activation limits NAFLD development in a mouse model for Glycogen Storage Disease type Ia.

Glycogen storage disease type Ia (GSD Ia) is an inborn error of metabolism caused by defective glucose-6-phosphatase (G6PC) activity. GSD Ia patients exhibit severe hepatomegaly due to glycogen and triglyceride (TG) accumulation in the liver. We have previously shown that the activity of Carbohydrate Response Element Binding Protein (ChREBP), a key regulator of glycolysis and de novo lipogenesis, is increased in GSD Ia. In the current study we assessed the contribution of ChREBP to non-alcoholic fatty liver...

Model for End-stage Liver Disease-Lactate and Prediction of Inpatient Mortality in Patients with Chronic Liver Disease.

As compared to other chronic diseases, patients with chronic liver disease (CLD) have significantly higher inpatient mortality; accurate models to predict inpatient mortality are lacking. Serum lactate (LA) may be elevated in patients with CLD due to both tissue hypoperfusion as well as decreased lactate clearance. We hypothesized that a parsimonious model consisting of Model for End-stage Liver Disease (MELD) and LA at admission may predict inpatient mortality in patients with CLD.

Acetaminophen Hepatotoxicity: Strong offense and weakened defense.

Oxidative stress refers to the consequences of exposure to reactive oxygen species. In many disease conditions, interruption along the mitochondrial electron transport chain (ETC) leads to build up of electrons which are transferred to O2. Reactive oxygen species (ROS) then can oxidize any chemical constituent of cells. This causes thiol-disulfide redox stress or imbalance which activates or inhibits many enzymes and signal transduction pathways. Countering oxidative/redox stress is antioxidant defense whic...

Safety First: Favoring Prophylactic/Preemptive over Delayed Treatment in D+/R- Transplants.

The report from Kapila and colleagues on their use of HCV-viremic donors as a "transplant center" protocol that accessed direct-acting antivirals (DAAs) via the recipient's insurance is important, giving us a glimpse into "real world" and contrasting with much of the published data thus far. Similar to other reports, high rates of SVR were achieved, though a small percentage failed initial treatment, even when conventional durations of DAAs were used, and serious complications, specifically fibrosing chole...

Estrogen acts via estrogen receptor 2b to regulate hepatobiliary fate during vertebrate development.

During liver development bipotent progenitor cells differentiate into hepatocytes and biliary epithelial cells (BECs) to ensure a functional liver required to maintain organismal homeostasis. The developmental cues controlling the differentiation of committed progenitors into these cell types, however, are incompletely understood. Here, we discover an essential role for estrogenic regulation in vertebrate liver development to affect hepatobiliary fate decisions. Exposure of zebrafish embryos to 17β-estradi...

Susceptibility of rat steatotic liver to ischemia-reperfusion is treatable with liver-selective matrix metalloproteinase inhibition.

This study examined whether enhanced susceptibility of steatotic liver to I/R injury is due to impaired recruitment of bone marrow (BM) progenitors of LSECs (also called sprocs) with diminished repair of injured LSECs and whether restoring signaling to recruit BM sprocs reduces I/R injury.

Hepatitis C vaccine: 10 good reasons for continuing.

The introduction of direct-acting antivirals (DAAs) has revolutionized hepatitis C treatment. Short courses of treatment with these drugs are highly beneficial to patients, eliminating the hepatitis C virus (HCV) without adverse effects. However, this outstanding success is tempered by the continuing difficulty eradicating the virus worldwide. These new treatments are slowing the epidemic in some parts of the world, but the screening of subjects for treatment remains a difficult task. In other parts of the ...

Novel endothelial LECT2/Tie1 signaling in liver fibrosis.

Angiogenesis and capillarization are completely distinct pathophysiological processes mediated by different subtypes of endothelial cells (ECs) in the liver. Both processes have been linked to liver fibrogenesis, but previous studies have not addressed this distinction explicitly. Leukocyte cell-derived chemotaxin 2 (LECT2) is a secreted protein mainly produced by hepatocytes with expression in ECs as well, whose role in the liver has been poorly understood.

New drugs for non-alcoholic steatohepatitis and HIV infection: great expectations with a great absent?

In recent years, there has been an increasing number of clinical trials for the treatment of non-alcoholic steatohepatitis (NASH). People living with HIV (PLWH) are commonly excluded from these studies, usually due to concerns over drug-drug interactions (DDI) associated with antiretroviral therapy (ART). The Steatohepatitis in HIV Emerging Research (SHIVER) Network, a group of international experts in hepatology and infectious diseases, discusses our current understanding on the interaction between HIV and...

Biomarkers for hepatobiliary cancers.

The clinical management of primary liver cancer such as hepatocellular carcinoma and cholangiocarcinoma has significantly changed in the last 3 years. The introduction of new systemic therapies, including immune-based therapies and biomarker driven therapies, has significantly improved survival, particularly in patients at advanced stages. Survival is still poor, and projections from the World Health Organization underscore the need to improve outcomes in these patients. Biomarkers have emerged as powerful ...

Re: "Somatic Mutations Increase Hepatic Clonal Fitness and Regeneration in Chronic Liver Disease".

Studies of somatic mutations have historically focused on those occurring during carcinogenesis, but recent research suggests functional mutations can accumulate in the absence of cancer. Zhu and colleagues recently published an extensive analysis of exome sequencing from 82 livers, describing a complex mutational landscape and identifying mutations that promote cellular fitness without inducing carcinogenesis (1). Advancing fibrosis stage was associated with increasing number and size of mutant clones whic...

The Histone Methyltransferase G9a Promotes Cholangiocarcinogenesis through Regulation of the Hippo Pathway Kinase LATS2 and YAP Signaling Pathway.

Cholangiocarcinoma (CCA) is a highly malignant epithelial tumor of the biliary tree with poor prognosis. In the current study, we present novel evidence that the histone-lysine methyltransferase G9a is upregulated in human CCA and that G9a enhances CCA cell growth and invasiveness through regulation of the Hippo pathway kinase LATS2 and YAP signaling pathway. Kaplan-Meier survival analysis revealed that high G9a expression is associated with poor prognosis of CCA patients. In experimental systems, depletion...

Transcriptomic traces of adult human liver progenitor cells.

Advances in single-cell sequencing technology have facilitated the precise study of gene expression patterns in the mouse liver, revealing a previously unknown degree of heterogeneity within hepatocyte, cholangiocyte, endothelial, and immune cell compartments. Yet, translating lessons learned from the mouse liver to the human liver remains difficult, a situation underscored by the increasing incidence of liver disease in the United States and exacerbated by our limited understanding of the cellular composit...

Serial transient elastography examinations to monitor patients with type 2 diabetes: A prospective cohort study.

Type 2 diabetes is an important risk factor for nonalcoholic fatty liver disease (NAFLD) and advanced fibrosis. Current international guidelines recommend the use of non-invasive tests as initial assessments for NAFLD, but the role of non-invasive tests as monitoring tools has not been established. We aimed to study the role of transient elastography as a monitoring tool in patients with type 2 diabetes. We recruited patients with type 2 diabetes without viral hepatitis or excessive alcohol intake from a co...

Acute Liver Failure (ALF) in Pregnancy: How Much Is Pregnancy-Related?

Acute liver failure (ALF), characterized by sudden onset of coagulopathy (INR ≥ 1.5) and encephalopathy may occur during pregnancy, either as a pregnancy-associated etiology or as an unrelated and co-incidental liver injury. The U.S. Acute Liver Failure Study Group comprised of 33 tertiary care liver centers has enrolled consecutive patients with ALF or acute liver injury (ALI: INR≥ 2.0 with no encephalopathy), over two decades.

Assessing the time-dependent impact of performance status on outcomes after liver transplantation.

Identifying how the prognostic impact of performance status (PS) differs according to the indication, era and time-period ('epoch') after liver transplantation (LT) could have implications for the selection and treatment of patients on the waitlist. We used national data from the UK and Ireland to assess the impact of PS on mortality separately for HCC and non-HCC recipients. We assessed pre-LT PS using the 5-point modified Eastern Cooperative Oncology Group (ECOG) scale and used Cox-regression methods to e...

Bespoken nanoceria: A new effective treatment in experimental hepatocellular carcinoma.

Despite the availability of new generation drugs, hepatocellular carcinoma (HCC) is still the third most frequent cause of cancer-related deaths worldwide. Cerium oxide nanoparticles (CeO NPs) have emerged as a novel antioxidant agent in experimental liver disease because of their antioxidant, anti-inflammatory and antisteatotic properties. In the present study, we aimed to elucidate the potential of CeO NPs as therapeutic agent in HCC.


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