Green Tea Polyphenol (-)-Epicatechin Pretreatment Mitigates Hepatic Steatosis in an In Vitro MASLD Model.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is becoming more prominent globally due to an increase in the prevalence of obesity, dyslipidemia, and type 2 diabetes. A great deal of studies have proposed potential treatments for MASLD, with few of them demonstrating promising results. The aim of this study was to investigate the potential effects of (-)-epicatechin (EPI) on the development of MASLD in an in vitro model using the HepG2 cell line by determining the metabolic viability of the cells and the levels of PPARα, PPARγ, and GSH.

Pretreatment of Garlic Oil Extracts Hampers Epithelial Damage in Cell Culture Model of Peptic Ulcer Disease.

Peptic ulcer disease is a chronic disease affecting up to 10% of the world's population. Proton pump inhibitors, such as lansoprazole are the gold standard in the treatment of ulcer disease. However, various studies have shown the effectiveness of garlic oil extracts in the treatment of ulcer disease.

Targeted delivery of mitochondria to the liver in rats.

Background And Aim: Mitochondrial damage is commonly involved in liver injury. We have previously shown that normal mitochondria can be coated with a carrier protein to form complexes that are specifically taken up by liver cells in culture. The aim of the current study was to determine whether mitochondrial complexes could be specifically delivered to the livers of living rats by intravenous injection.

An Improved Method for Preparation of Uniform and Functional Mitochondria from Fresh Liver.

As the major energy source for mammalian cells, mitochondria have been the subject of numerous studies. However, the isolation and purification of healthy mitochondria, especially from fresh tissue, remains challenging. The most popular methods and kits involve various centrifugation steps which require substantial time and equipment but do not consistently provide pure preparations of functional mitochondria.

Targeted transplantation of mitochondria to hepatocytes.

Background: Mitochondrial defects in hepatocytes can result in liver dysfunction and death. Hepatocytes have cell-surface asialoglycoprotein receptors (AsGRs) which internalize AsGs within endosomes. The aim of this study was to determine whether mitochondria could be targeted to hepatocytes by AsGR-mediated endocytosis.

The Molecular and Structural Basis of HBV-resistance to Nucleos(t)ide Analogs.

Infection with hepatitis B virus (HBV) is a worldwide health problem. Chronic hepatitis B can lead to fibrosis, liver cirrhosis, and hepatocellular carcinoma (HCC). Management of the latter two conditions often requires liver transplantation.

Secondary Structural Elements of the HCV X-region Involved in Viral Replication.

Background And Aims: The noncoding regions in the 3'-untranslated region (UTR) of the hepatitis C virus (HCV) genome contain secondary structures that are important for replication. The aim of this study was to identify detailed conformational elements of the X-region involved in HCV replication.

Methods: Ribonucleic acid (RNA) structural analogs X94, X12, and X12c were constructed to have identical conformation but 94%, 12%, and 0% sequence identity, respectively, to the X region of HCV genotype 2a.

Effects of short RNA structural analogues against hepatitis C virus genotypes 2, 3 and 4 in replicon cells.

Objective: To determine whether computer-predicted short RNA structural analogues could inhibit hepatitis C virus (HCV) genotype 2a, 3a and 4a replication in cultured cells.

Methods: Short RNA sequences, X12, X12a and X12b, designed to be identical in secondary structure to the X region in the 3'-untranslated region (3'-UTR) of the HCV 1b genome, as well as shorter stem-loop components of X region, were inserted into a plasmid and transfected into separate Huh7.5 human hepatoma cells stably transfected with subgenomic replicons for genotypes 2a, 3a and 4a.

Update on the Development of Anti-Viral Agents Against Hepatitis C.

Hepatitis C virus (HCV) infects nearly 170 million people worldwide and causes chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The search for a drug regimen that maximizes efficacy and minimizes side effects is quickly evolving. This review will discuss a wide range of drug targets currently in all phases of development for the treatment of HCV.

Pharmacogenetic selection of transplanted human hepatocytes in immunocompetent rats.

Objective: To introduce a genetic survival advantage for transplanted human hepatocytes over host cells in rats.

Methods: Green fluorescent protein (GFP) was introduced into Huh-7 human hepatoma cells to create fluorescent GFP-Huh-7 cells. mRNA of CYP2E1, the enzyme that converts acetaminophen (APA) into hepatotoxic intermediates, was quantified by real-time polymerase chain reaction (PCR).

Animal models for the study of hepatitis C virus infection and replication.

Hepatitis C virus (HCV) hepatitis, initially termed non-A, non-B hepatitis, has become one of the leading causes of cirrhosis and hepatocellular carcinoma worldwide. With the help of animal models, our understanding of the virus has grown substantially from the time of initial discovery. There is a paucity of available animal models for the study of HCV, mainly because of the selective susceptibility limited to humans and primates.

Granulomatous liver diseases: a review.

Granulomas that consist of focal accumulations of macrophages are commonly found in the liver due to stimulation of the immune system by a number of agents. Manifestations are variable depending on whether the underlying cause is a systemic disease or a primary hepatic granulomatous reaction. This article describes the common causes, presentation, histopathology, and manifestations of granulomatous diseases as well as various diagnostic and management strategies.

Effects of PEG-interferon-alpha-2A on Schistosoma mansoni infection in mice.

In some regions of the world, co-existence of schistosomiasis and hepatitis C (HCV) infection is common. Because the morbidity in human schistosomiasis is primarily due to host cell-mediated immune response, it was of interest to determine the effects on Schistosoma mansoni infection of an immune stimulator used in the standard treatment of HCV infection. Schistosoma mansoni -infected mice were treated with PEG-interferon-alpha-2a (PEG-IFN-alpha) by subcutaneous injection.

Inhibition of hepatitis C virus replication by single-stranded RNA structural mimics.

Aim: To examine the effect of hepatitis C virus (HCV) structural mimics of regulatory regions of the genome on HCV replication.

Methods: HCV RNA structural mimics were constructed and tested in a HCV genotype 1b aBB7 replicon, and a Japanese fulminant hepatitis-1 (JFH-1) HCV genotype 2a infection model. All sequences were computer-predicted to adopt stem-loop structures identical to the corresponding elements in full-length viral RNA.

Host susceptibility to schistosomes: effect of host sera on cell proliferation of Schistosoma mansoni schistosomula.

To determine effects of the sera on cell proliferation, schistosomula of Schistosoma mansoni (20-days-old) were incubated in medium containing fetal calf serum plus hamster (highly susceptible host) portal or peripheral venous serum, or rat (poorly susceptible host) portal or peripheral venous serum in the presence of bromodeoxyuridine (BrdU). Compared with schistosomula cultured in presence of control medium containing fetal calf serum alone, BrdU labeling indices (BLIs) were increased by 39% in the presence of portal, but not in peripheral, serum of hamsters. In contrast, no significant differences were observed in the BLIs in rat portal, or peripheral, sera or in control media.

Human uridine-cytidine kinase phosphorylation of ribavirin: a convenient method for activation of ribavirin for conjugation to proteins.

Ribavirin is a synthetic nucleoside analog that is used for the treatment of hepatitis C virus (HCV) infection. Its primary toxicity is hemolytic anemia, which sometimes necessitates dose reduction or discontinuation of therapy. Selective delivery of ribavirin into liver cells would be desirable to enhance its antiviral activity and avoid systemic side effects.

A novel G418 conjugate results in targeted selection of genetically protected hepatocytes without bystander toxicity.

G418, an aminoglycoside neomycin analogue, is an antimicrobial agent that interferes with protein synthesis and has been used extensively for selection of mammalian cell lines that possess neomycin resistance (NR). It is potent and nonspecific in its effects that occur through tight binding to ribosomal elements. Because of the potent intracellular effect, we wondered whether G418 could be used to select a specific cell type based on receptor-mediated endocytosis.

Potential role of RNAi in the treatment of HCV infection.

Chronic HCV infection is a leading cause of chronic hepatitis and its sequelae, liver cirrhosis and hepatocellular carcinoma. Current therapeutic options are limited, associated with significant adverse effects and costly. Accordingly, there is strong impetus to develop novel therapeutic strategies that act through alternate mechanisms.

siRNA-resistance in treated HCV replicon cells is correlated with the development of specific HCV mutations.

RNA interference (RNAi) has been extremely effective against hepatitis C viral (HCV) gene expression in short-term cell culture. Our aim was to determine whether long-term RNAi might result in HCV-resistant mutants. Huh7 HCV subgenomic replicon cells were transfected with short interfering RNAs (siRNAs).

Potential applications of siRNA in hepatitis C virus therapy.

Small interfering RNAs (siRNAs) are short RNA duplexes approximately 21 nucleotides long. When introduced into mammalian cells, siRNA can silence specific gene expression. Hepatitis C virus (HCV) replicates in the cytoplasm of liver cells without integration into the host genome.

Novel delivery methods for treatment of viral hepatitis: an update.

Viral hepatitis represents the most common cause of chronic liver disease worldwide. Currently approved therapies for chronic hepatitis B include IFN, an immune modulator, and nucleoside analogues lamivudine and adefovir. For chronic hepatitis C, a combination of pegylated IFN-alpha and ribavirin represents the standard treatment.

A novel immunocompetent rat model of HCV infection and hepatitis.

Background & Aims: Hepatitis C virus (HCV) infects millions of people worldwide. Therapy is limited, and treatment does not produce a sustained response in the majority of patients. Development of new agents has been hampered by the lack of a convenient animal model.

Inhibition of HBV replication by siRNA in a stable HBV-producing cell line.

Potent inhibition of endogenous gene expression by RNA interference has been achieved by using sequence-specific posttranscriptional gene silencing through the action of small interfering RNA molecules (siRNA). In these reports, the natural function of genes could be deduced through the ensuing loss of function. Based on the extraordinary effectiveness in silencing endogenous genes, we wondered whether siRNA could be applied against viral replication in a hepatitis B virus (HBV) model using HBV-specific siRNA.

Hepatitis B virus infection of transplanted human hepatocytes causes a biochemical and histological hepatitis in immunocopetentent rats.

Aim: To characterize the host response to hepatitis B virus (HBV) infection in human hepatocytes transplanted into immunocompetent rodent rats tolerized by, and transplanted with primary human hepatocytes.

Methods: One week after the transplantation, rats were inoculated with HBV, and viral gene expression, replication, and host response was monitored.

Results: HBV DNA was detectable in serum for at least 60 days.