A5071850460- Liver Disease Diagnosis and Treatment
- Cancer-related molecular mechanisms research
- Peroxisome Proliferator-Activated Receptors
- Liver physiology and pathology
- RNA modifications and cancer
- Pancreatic function and diabetes
- Drug-Induced Hepatotoxicity and Protection
- Cancer, Hypoxia, and Metabolism
- Lipid metabolism and disorders
- Autophagy in Disease and Therapy
- Endoplasmic Reticulum Stress and Disease
- Drug Transport and Resistance Mechanisms
- Hepatitis C virus research
- Pediatric Hepatobiliary Diseases and Treatments
- Epigenetics and DNA Methylation
- Alcohol Consumption and Health Effects
- Pharmacogenetics and Drug Metabolism
- Biochemical Acid Research Studies
- Rabies epidemiology and control
- Metabolism, Diabetes, and Cancer
- Genetics and Neurodevelopmental Disorders
- Arsenic contamination and mitigation
- FOXO transcription factor regulation
- Acute Myeloid Leukemia Research
- Toxoplasma gondii Research Studies
Cleveland Clinic Lerner College of Medicine
2021-2024
Case Western Reserve University
2022-2024
University of Connecticut
2016-2023
Cleveland Clinic
2022-2023
XinHua Hospital
2023
Yale University
2016-2021
VA Connecticut Healthcare System
2016-2019
Institute for Systems Biology
2016-2018
Wenzhou Medical University
2016
University of Alabama at Birmingham
2002
H19 is an imprinted long noncoding RNA abundantly expressed in embryonic liver and repressed after birth. We show that serves as a lipid sensor by synergizing with the RNA‐binding polypyrimidine tract‐binding protein 1 (PTBP1) to modulate hepatic metabolic homeostasis. interacts PTBP1 facilitate its association sterol regulatory element‐binding 1c mRNA protein, leading increased stability nuclear transcriptional activity. are up‐regulated fatty acids hepatocytes diet‐induced liver, which...
It has been established that nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) members promote survival by upregulating antiapoptotic genes and genetic pharmacological inhibition NF‐κB is required for tumor necrosis (TNF)‐induced hepatocyte apoptosis. In this study, we demonstrate pro‐survival pathway switched to pro‐apoptosis under pyruvate dehydrogenase kinase 4 (PDK4)‐deficient conditions. PDK4‐deficiency triggered hepatic apoptosis concomitantly with increased...
Mixed lineage kinase domain-like pseudokinase (MLKL), a key terminal effector of necroptosis, also plays role in intracellular vesicle trafficking that is critical for regulating liver inflammation and injury alcohol-associated disease (ALD). Although receptor interacting protein 3 (Rip3)-/- mice are completely protected from ethanol-induced injury, Mlkl-/- only partially protected. Therefore, we hypothesized cell-specific functions MLKL may contribute to injury.
Long non-coding RNAs (lncRNAs) are comprised of RNA transcripts exceeding 200 nucleotides in length but lacking identifiable open reading frames (with rare exceptions). Herein, we highlight emerging evidence demonstrating that lncRNAs critical regulators liver metabolic function and diseases. We summarize current knowledges about dysregulated outline the underlying molecular mechanisms by which control hepatic lipid ad glucose metabolism, as well cholestatic disease. lncLSTR, Lnc18q22.2,...
Cholestasis induces the hepatic long non-coding RNA H19, which promotes progression of cholestatic liver fibrosis. However, microRNAs that are dysregulated by H19 during cholestasis remain elusive. Using miRNA-sequencing analysis followed qPCR validation, we identified marked upregulation eight members let-7 family in livers bile duct ligation (BDL) and overexpression. In particular, expression let-7a-1/7d/7f-1 was highly induced H19-BDL but decreased H19KO-BDL livers. Interestingly, nuclear...
Liver regeneration requires intrahepatic and extrahepatic metabolic reprogramming to meet the high hepatic bioenergy demand for liver cell repopulation. This study aims elucidate how pyruvate dehydrogenase kinase 4 (PDK4), a critical regulator of glucose lipid metabolism, coordinates regulation with efficient growth. We found that Pdk4 expression was elevated after two-thirds partial hepatectomy (PHx). In Pdk4-/- PHx mice, liver/body weight ratio more rapidly restored, accompanied by...
Hepatocellular carcinoma (HCC) is a common form of cancer with prevalence worldwide. There are many factors that lead to the development and progression HCC. This study aimed identify potential new tumor suppressors, examine their function as cell cycle modulators, investigate impact on cyclin family proteins cyclin-dependent kinases (CDKs). In this study, pyruvate dehydrogenase kinase (PDK)4 gene was shown have suppressor characteristics. PDK4 expression significantly downregulated in human...
Cholestasis causes ductular reaction in the liver where reactive cholangiocytes not only proliferate but also gain a neuroendocrine-like phenotype, leading to inflammatory cell infiltration and extracellular matrix deposition contributing development progression of cholestatic fibrosis. This study aims elucidate role miR-200c cholestasis-induced biliary fibrosis cholangiocyte activation. We found that was extremely abundant reduced by cholestasis bile duct ligation (BDL) mouse model;...
Acetaminophen (APAP)-induced liver injury is one of the most frequent causes acute failure worldwide. Significant increases in levels miRNA-21 both tissues and plasma have been observed APAP-overdosed animals humans. However, mechanistic effect on remains unknown. In this study, we generated a new hepatocyte-specific knockout (miR-21-HKO) mouse line. miR-21-HKO background-matched sibling wild-type (WT) mice were treated with toxic dose APAP. Compared WT mice, miR-21 HKO showed an increased...
Hepatoblastoma (HB) is the most common liver tumor in children. Despite recent improvements treatment strategies, survival of children with hepatoblastoma remains poor. In this study, we identified a novel role microRNA-26a-5p (miR-26a-5p), lin-28 homolog B (LIN28B), Ras-related nuclear protein (RAN), and aurora kinase A (AURKA) HB. The expression LIN28B, RAN, AURKA was significantly up-regulated human HB livers cell lines. Knockdown LIN28B RAN by small interfering RNAs inhibited...
Background and Aims: Interferon (IFN) signaling is critical to the pathogenesis of alcohol-associated hepatitis (AH), yet mechanisms for activation this system are elusive. We hypothesize that host-derived 5S rRNA pseudogene (RNA5SP) transcripts regulate IFN production modify immunity in AH. Approach Results: Mining transcriptomic datasets revealed patients with severe (sAH), hepatic expression genes regulated by IFNs was perturbed gene sets involved were enriched. RNA5SP also increased...
Acetaminophen (APAP) is a commonly used pain and fever reliever but also the most frequent cause of drug-induced liver injury. The mechanism pertaining acetaminophen toxicity has been well documented, whereas mechanisms hepatotoxicity are not established. Serine (or cysteine) peptidase inhibitor, clade A, member 3N (SerpinA3N), serine protease synthesized in role SerpinA3N relation to APAP-induced injury known. Wild-type hepatocyte-specific knockout (HKO) mice were injected intraperitoneally...
Aberrant hepatic lipid metabolism is the major cause of non-alcoholic fatty liver disease (NAFLD) and associated with insulin resistance type 2 diabetes. Serine (or cysteine) peptidase inhibitor, clade A, member 3N (SerpinA3N) highly expressed in liver; however, its functional role regulating NAFLD metabolic disorders are not known. Male wildtype hepatocyte Serpina3N knockout (HKO) mice were fed a control diet, methionine- choline-deficient diet or high-fat high-sucrose to induce markers...
Pyruvate dehydrogenase kinase 4 (PDK4) is a metabolism switch that regulates glucose oxidation and the tricarboxylic acid cycle (TCA cycle) in mitochondria. Liver detoxifies xenobiotics constantly challenged by various injuries. This study aims at understanding how loss of regulator PDK4 contributes to liver Wild-type (WT) Pdk4 knockout (Pdk4-/-) mice different ages were examined for spontaneous hepatic apoptosis. Juvenile or adult two genotypes insulted diethylnitrosamine (DEN), arsenic,...
Background: Dichloroacetate (DCA), a pan-pyruvate dehydrogenase kinase inhibitor, ameliorates multiple pathological conditions and tissue injury shows strong potential for clinical applications. Here, we investigated the preventive effects of DCA in murine model alcohol-associated liver disease. Methods: C57BL/6J mice were subjected to acute-on-chronic disease treated with DCA. Livers assessed histology, biochemistry, gene expression. Mass spectrometry was used compare protein expression...
Objective Pyruvate dehydrogenase kinase 4 (PDK4) is a mitochondrial protein and key metabolic regulator of glucose oxidation. However, the role PDK4 in development hepatocellular carcinoma (HCC) remains unknown, which focus this study. Methods In vivo model: Male 15‐day‐old wild‐type (WT) or Pdk4 knockout (Pdk4 −/− ) mice given i.p. injections single dose diethylnitrosamine( DEN) (25 mg/kg body weight). vitro knockdown Huh7 Hep3B cells using shRNAs. Cell viability was evaluated by MTS colony...
To propose a modified approach to measuring femoro-epiphyseal acetabular roof (FEAR) index while still abiding by its definition and biomechanical basis, compare the reliabilities of two methods. classification for medial sourcil edges. We retrospectively reviewed consecutive series patients treated with periacetabular osteotomy and/or hip arthroscopy. A FEAR was defined. Lateral center-edge angle, Sharp's Tonnis angle on all hips, as well original approaches were measured. Intra-...
The Publisher regrets that this article is an accidental duplication of has already been published, http://dx.doi.org/10.1016/j.livres.2017.09.001. duplicate therefore withdrawn. full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal