A5067281481- Liver Disease Diagnosis and Treatment
- Alcohol Consumption and Health Effects
- Phosphodiesterase function and regulation
- Liver Disease and Transplantation
- Diet, Metabolism, and Disease
- Liver physiology and pathology
- Drug-Induced Hepatotoxicity and Protection
- Blood properties and coagulation
- Adenosine and Purinergic Signaling
- Diet and metabolism studies
- Gut microbiota and health
- Epigenetics and DNA Methylation
- Neuroinflammation and Neurodegeneration Mechanisms
- Erythrocyte Function and Pathophysiology
- RNA modifications and cancer
- Hepatitis C virus research
- Cancer-related gene regulation
- Histone Deacetylase Inhibitors Research
- Immune Cell Function and Interaction
- Genomics, phytochemicals, and oxidative stress
- Inflammatory mediators and NSAID effects
- Cancer-related molecular mechanisms research
- Gastrointestinal motility and disorders
- Mast cells and histamine
- Folate and B Vitamins Research
University of Louisville
2015-2024
University of Louisville Hospital
2011-2020
University of Nebraska Medical Center
2013
University Medical Centre Mannheim
2013
Heidelberg University
2013
University Hospital Heidelberg
2013
Louisville VA Medical Center
2011-2013
Louisville Metabolic and Atherosclerosis Research Center
2012
University of Glasgow
2011
Enteric dysbiosis plays an essential role in the pathogenesis of alcoholic liver disease (ALD). Detailed characterization alterations gut microbiome is needed for understanding their pathogenic ALD and developing effective therapeutic approaches using probiotic supplementation. Mice were fed liquid Lieber-DeCarli diet without or with alcohol (5% v/v) 6 weeks. A subset mice administered Lactobacillus rhamnosus GG (LGG) from to 8 Indicators intestinal permeability, hepatic steatosis,...
Obesity and the metabolic syndrome are closely correlated with hepatic steatosis. Simple steatosis in nonalcoholic fatty liver disease can progress to steatohepatitis (NASH), which be a precursor more serious diseases, such as cirrhosis hepatocellular carcinoma. The pathogenic mechanisms underlying progression of NASH remain unclear; however, inflammation, proinflammatory cytokines, oxidative stress have been postulated play key roles. We previously reported that patients elevated serum...
Emerging research evidence has established the critical role of gut-liver axis in development alcohol-associated liver disease (ALD). The present study employed 16S rRNA gene and whole genome shotgun (WGS) metagenomic analysis combination with a revised microbial dataset to comprehensively detail butyrate-producing communities associated butyrate metabolic pathways affected by chronic ethanol feeding. Specifically, data demonstrated that decrease several bacterial genera belonging distinct...
Increased plasma and hepatic TNF-alpha activity has been implicated in the pathogenesis of alcoholic liver disease (ALD). We previously reported that monocytes from patients show enhanced constitutive as well LPS-inducible NF-kappaB activation production. Studies have shown cAMP plays an important role regulating expression, elevation cellular suppresses The effects chronic ethanol exposure on levels TNF expression were examined vitro rat primary Kupffer cells obtained a clinically relevant...
Background Binge, as well chronic, alcohol consumption affects global histone acetylation leading to changes in gene expression. It is becoming increasingly evident that these histone‐associated epigenetic modifications play an important role the development of alcohol‐mediated hepatic injury. Methods C 57 BL /6 mice were gavaged 3 times (12‐hour intervals) with ethanol ( EtOH ; 4.5 g/kg). Hepatic deacetylase Hdac ) m RNA s assessed by q RT ‐ PCR . Total HDAC activity was estimated a...
Dysregulation of microRNA (miRNA) expression is associated with hallmarks aggressive tumor phenotypes, e.g., enhanced cell growth, proliferation, invasion, and anchorage independent growth in prostate cancer (PCa). Serum-based miRNA profiling involved 15 men diagnosed non-metastatic (stage I, III) metastatic IV) PCa five age-matched disease-free using arrays select targets confirmed by quantitative real-time PCR (qRT-PCR). The effect miR-186-5p inhibition or ectopic on cellular behavior...
Alcoholic liver disease (ALD) is a major cause of liver-related mortality. There still no US Food and Drug Administration-approved therapy for ALD, therefore, identifying therapeutic targets needed. Our previous work demonstrated that ethanol exposure leads to up-regulation cAMP-degrading phosphodiesterase 4 (PDE4) expression, which compromises normal cAMP signaling in monocytes/macrophages hepatocytes. This effect on contributes dysregulated inflammatory response altered lipid metabolism....
Increased plasma and hepatic TNF-α expression is well documented in patients with alcoholic hepatitis implicated the pathogenesis of liver disease. We have previously shown that monocytes from show increased constitutive LPS-induced NF-κB activation production. Our recent studies showed chronic ethanol exposure significantly decreased cellular cAMP levels both LPS-stimulated unstimulated Kupffer cells, leading to an increase LPS-inducible production by affecting induction TNF mRNA...
Abstract Alcohol‐induced hepatic steatosis is a significant risk factor for progressive liver disease. Cyclic adenosine monophosphate ( cAMP ) signalling has been shown to significantly regulate lipid metabolism; however, the role of altered homeostasis in alcohol‐mediated never studied. Our previous work demonstrated that increased expression phosphodiesterase 4 (Pde4), which specifically hydrolyses and decreases levels, plays pathogenic development inflammation/injury. The aim this study...
Ethanol-mediated down-regulation of carnitine palmitoyltransferase-1 (CPT-1A) gene expression plays a major role in the development hepatic steatosis; however, underlying mechanisms are not completely elucidated. Tributyrin, butyrate prodrug that can inhibit histone deacetylase (HDAC) activity, attenuates steatosis and injury. The present study examined beneficial effect tributyrin/butyrate attenuating ethanol-induced pathogenic epigenetic affecting CPT-1A promoter–histone modifications...
Background and Aims Alcohol‐associated liver disease (ALD) is a common chronic worldwide with high morbidity mortality, no Food Drug Administration–approved therapies. Fructose (dietary or endogenous), its metabolite uric acid, aldose reductase (AR, the only endogenous enzyme that produces fructose) are strongly associated development of nonalcoholic fatty disease. However, role AR metabolites in ALD remains understudied was examined using human specimens, cultured cells, mouse model...
<i>S</i>-Adenosylmethionine (SAM) treatment has anti-inflammatory, cytoprotective effects against endotoxin-induced organ injury. An important component of the anti-inflammatory action SAM involves down-regulation lipopolysaccharide (LPS)-induced transcriptional induction tumor necrosis factor-α (TNF) expression by monocytes/macrophages. We examined effect on and activity LPS-induced up-regulation phosphodiesterase 4 (PDE4), which regulates cellular cAMP levels TNF expression. LPS RAW 264.7,...
Anti-inflammatory and antifibrotic effects of the broad spectrum phosphodiesterase (PDE) inhibitor pentoxifylline have suggested an important role for cyclic nucleotides in pathogenesis hepatic fibrosis; however, studies examining specific PDEs are lacking. Endotoxemia Toll-like receptor 4 (TLR4)-mediated inflammatory profibrotic signaling play a major development fibrosis. Because cAMP-specific PDE4 critically regulates lipopolysaccharide (LPS)-TLR4–induced cytokine expression, its...
Abstract Activation and transdifferentiation of hepatic stellate cells (HSC) into migratory myofibroblasts is a key process in liver fibrogenesis. Cell migration requires an active remodeling the cytoskeleton, which tightly regulated coordinated by Rho‐specific guanine nucleotide exchange factors (GEFs) Rho family small GTPases. Rho‐associated kinase (ROCK) promotes assembly focal adhesions actin stress fibers regulating cytoskeleton organization. GEF protein directly activated cAMP 1...
Alterations in the gut-microbiome-brain axis are increasingly being recognized to be involved Alzheimer's disease (AD) pathogenesis. However, functional consequences of enteric dysbiosis linking gut microbiota and brain pathology AD progression remain largely undetermined. The present work investigated causal role age-associated temporal decline butyrate-producing bacteria butyrate etiopathogenesis AD. Longitudinal metagenomics, neuropathological, memory analyses were performed 3×Tg-AD mouse...
Recently, we have demonstrated that acute alcohol exposure due to binge drinking leads hepatic steatosis with the deregulation of histone deacetylase (HDAC) expression. Various class I, II, and IV HDACs were down-regulated, whereas expression HDAC3 was solely up-regulated. Hence, in present work, specifically examined mechanistic role development occurring response administration.C57BL/6 mice gavaged 3 times ethanol (EtOH) at a dose 4.5 g/kg. HDAC inhibitor, Trichostatin A (TSA)...