A5089241342- Liver Disease Diagnosis and Treatment
- HIV Research and Treatment
- Hepatitis C virus research
- Extracellular vesicles in disease
- Phagocytosis and Immune Regulation
- Alcohol Consumption and Health Effects
- Cytomegalovirus and herpesvirus research
- Cancer-related molecular mechanisms research
- Osteoarthritis Treatment and Mechanisms
- MicroRNA in disease regulation
- Inflammasome and immune disorders
- HIV-related health complications and treatments
- Liver physiology and pathology
- Hepatitis B Virus Studies
- Virus-based gene therapy research
- Autophagy in Disease and Therapy
- Effects of Radiation Exposure
- Endoplasmic Reticulum Stress and Disease
- Curcumin's Biomedical Applications
- Pharmacological Effects of Medicinal Plants
- Drug-Induced Hepatotoxicity and Protection
- Pancreatic function and diabetes
- Protein Kinase Regulation and GTPase Signaling
- Lipid metabolism and disorders
- Immune Cell Function and Interaction
University of Nebraska Medical Center
2017-2023
VA Nebraska Western Iowa Health Care System
2019-2022
Nebraska Medical Center
2018
King George's Medical University
2015-2016
Institute of Nuclear Medicine & Allied Sciences
2014
HIV-1 infection in the era of combined antiretroviral therapy has been associated with premature aging. Among various features neurocognitive disorders, astrocyte senescence surmised as a potential cause contributing to HIV-1-induced brain aging and impairments. Recently, lncRNAs have also implicated play essential roles onset cellular senescence. Herein, using human primary astrocytes (HPAs), we investigated role lncRNA TUG1 Tat-mediated We found that HPAs exposed Tat resulted significant...
ABSTRACT Despite the efficacy of combination antiretroviral therapy (ART) in controlling human immunodeficiency virus (HIV‐1) replication, cytotoxic viral proteins such as HIV‐1 transactivator transcription (Tat) persist tissues brain. Although does not infect neuronal cells, it is susceptible to Tat protein‐mediated toxicity, leading neuroinflammation that underlies HIV‐associated neurocognitive disorders (HAND). Given role extracellular vesicles (EVs) both cellular homoeostasis and under...
This review covers some important new aspects of the alcohol-induced communications between liver parenchymal and non-parenchymal cells leading to injury development. The information exchange various cell types may promote end-stage disease progression involves multiple mechanisms, such as direct cell-to-cell interactions, extracellular vesicles (EVs) or chemokines, cytokines, growth factors contained in fluids/cell culture supernatants. Here, we highlighted role EVs derived from...
In an era of improved survival due to modern antiretroviral therapy, liver disease has become a major cause morbidity and mortality, resulting in death 15–17% human immunodeficiency virus (HIV)-infected patients. Alcohol enhances HIV-mediated damage promotes the progression advanced fibrosis cirrhosis. However, mechanisms behind these events are uncertain. Here, we hypothesize that ethanol metabolism potentiates accumulation HIV hepatocytes, causing oxidative stress intensive apoptotic cell...
Alcohol-induced progression of hepatitis C virus (HCV) infection is related to dysfunction innate immunity in hepatocytes. Endogenously produced interferon (IFN)α induces activation interferon-stimulated genes (ISGs) via triggering the Janus kinase-signal transducer and activator transcription 1 (STAT1) pathway. This requires protein methyltransferase 1-regulated arginine methylation STAT1. Here, we aimed study whether STAT1 also depended on levels demethylase jumonji domain-containing 6...
Although the causes of hepatotoxicity among alcohol-abusing HIV patients are multifactorial, alcohol remains least explored “second hit” for HIV-related hepatotoxicity. Here, we investigated whether metabolically derived acetaldehyde impairs lysosomes to enhance HIV-induced We exposed Cytochrome P450 2E1 (CYP2E1)-expressing Huh 7.5 (also known as RLW) cells an acetaldehyde-generating system (AGS) 24 h. then infected (or not) with HIV-1ADA them again AGS another 48 Lysosome damage was...
HIV-1 infection impairs liver function, and diseases have become a leading cause of morbidity in infected patients. The immunopathology damage caused by remains unclear. We used chimeric mice dually reconstituted with human immune system hepatocytes to address the relevance model pathobiology questions related survival presence systemic infection. TK-NOG males were transplanted mismatched hematopoietic stem/progenitor cells hepatocytes; albumin concentration blood monitored for...
Alcohol abuse is common in people living with HIV-1 and dramaticallyenhances the severity of HIV-induced liver damage by inducing oxidative stress lysosomaldysfunction cells. We hypothesize that increased release extracellular vesicles(EVs) hepatocytes humanized mouse model linked to lysosome dysfunction. The study was performed on primary human hepatoma RLWXP-GFP (Huh7.5 cells stably transfected CYP2E1 XPack-GFP) validated ethanol-fed liverhumanizedfumarylacetoacetate hydrolase (Fah)-/-,...
Recently, we found that both HIV and acetaldehyde, an alcohol metabolite, induce hepatocyte apoptosis, resulting in the release of large extracellular vesicles called apoptotic bodies (ABs). The engulfment these ABs by hepatic stellate cells (HSC) leads to their profibrotic activation. This study aims establish mechanisms HSC activation after from acetaldehyde HIV-exposed hepatocytes (ABAGS+HIV). In vitro experiments were performed on Huh7.5-CYP (RLW) generate LX2 used as HSC. To ABs, RLW...
Antiretroviral drug (ARV) metabolism is linked largely to hepatic cytochrome P450 activity. One ARV class known be metabolized by intestinal and CYP3A are the protease inhibitors (PIs). Plasma concentrations boosted such as cobisistat ritonavir (RTV). Studies of drug-drug interactions limited since enzyme pathways human specific. While immune-deficient mice reconstituted with cells an excellent model study ARVs during immunodeficiency virus type 1 (HIV-1) infection, they cannot reflect...
The use of immunodeficient mice transplanted with human hematopoietic stem cells is an accepted approach to study human-specific infectious diseases such as HIV-1 and investigate multiple aspects immune system development. However, mouse are different in sialylation patterns proteins due evolutionary mutations the CMP-N-acetylneuraminic acid hydroxylase (CMAH) gene that prevent formation N-glycolylneuraminic from N-acetylneuraminic acid. How changes glycoproteins’ chemistry affect phenotype...
Despite the increased life expectancy of patients infected with human immunodeficiency virus-1 (HIV-1), liver disease has emerged as a common cause their morbidity. The immunopathology caused by HIV-1 remains elusive. Small xenograft animal models hepatocytes and immune system can recapitulate biology disease's pathogenesis. Herein, protocol is described to establish dual humanized mouse model through CD34+ hematopoietic stem/progenitor cells (HSPCs) transplantation, study observed in...
Primary fibroblasts are not suitable for in vitro macrocolony assay due to their inability form distinct colonies. Here we present a modification of agarose overlay that yielded extensive improvement colony formation and assessment radiosensitivity.Macrocolony was assessed primary human VH10 HDFn with or without using 0.5% growth medium at 24 h post-seeding. Malignant cell lines (A549, U87) transformed non-malignant (AA8 hamster, MRC5 human) were used comparison.Agarose caused significant...
Approximately 3.5% of the global population is chronically infected with Hepatitis B Virus (HBV), which puts them at high risk end-stage liver disease, persistent infection potentiated by alcohol consumption. However, mechanisms underlying effects on HBV persistence remain unclear. Here, we aimed to establish in vivo/ex vivo evidence that suppresses peptides-major histocompatibility complex (MHC) class I antigen display primary human hepatocytes (PHH), diminishes recognition and clearance...
The morbidity and mortality of human immunodeficiency virus (HIV)-infection is often associated with liver disease, which progresses slowly into severe dysfunction. There are multiple insults exacerbate HIV-related injury, including HIV-associated dysregulation lipid metabolism fat turnover, co-infections hepatotropic viruses alcohol abuse. As we reported before, exposure hepatocytes to HIV metabolites causes high oxidative stress, impairs proteasomal lysosomal functions leading accumulation...