Article in Hepatology communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
2 · The registry
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
5 · Who and what money
Authors and funding
13 authors.
Jianguo WuDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.ORCID 0000-0001-9801-5267
Emily HuangDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.ORCID 0000-0002-7393-1282
Megan R McMullenDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Vaibhav SinghDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.ORCID 0000-0001-5075-8045
Marko MrdjenDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Annette BellarDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Li WangIndependent Researcher, Tucson, Arizona, USA.
Nicole WelchDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.ORCID 0000-0002-4655-5146
Jaividhya DasarathyDepartment of Family Medicine, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio, USA.
Srinivasan DasarathyDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.ORCID 0000-0003-1774-0104
David StreemDepartment of Psychiatry and Psychology, Cleveland Clinic Lutheran Hospital, Cleveland, Ohio, USA.
J Mark BrownDepartment of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA.ORCID 0000-0003-2708-7487
Laura E NagyDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.ORCID 0000-0002-0580-2809
Funding
Project Two - Exercise Training Decreases Alcohol Drinking by an FGF21-Dependent MechanismP50AA024333 · NIAAA · CLEVELAND CLINIC LERNER COM-CWRU · PI Jonathan Mark Brown · 2016 to 2026
$19.6M
The Cleveland Digestive Diseases Research Core Center (DDRCC)P30DK097948 · NIDDK · CASE WESTERN RESERVE UNIVERSITY · PI Theresa Torres Pizarro · 2015 to 2026
$15.6M
Non Alcoholic Steatohepatitis Clinical Research NetworkU01DK061732 · NIDDK · CLEVELAND CLINIC LERNER COM-CWRU · PI Srinivasan Dasarathy · 2002 to 2026
$12.2M
Transcriptional and non-transcriptional functions of IRF3 in ALDR01AA027456 · NIAAA · CLEVELAND CLINIC LERNER COM-CWRU · PI LAURA E. NAGY · 2019 to 2026
$3.5M
Integrated Therapies for Alcohol use in Alcohol-associated Liver Disease (ITAALD)- Cleveland Clinic Clinical CenterU01AA026976 · NIAAA · CLEVELAND CLINIC LERNER COM-CWRU · PI Srinivasan Dasarathy, David Streem · 2018 to 2026
$3.2M
Metaorganismal Endocrinology in Cardiometabolic DiseaseR01DK130227 · NIDDK · CLEVELAND CLINIC LERNER COM-CWRU · PI Jonathan Mark Brown · 2021 to 2026
$2.8M
Novel mechanism based treatment to improve tissue injury in alcoholic hepatitisR01AA028190 · NIAAA · CLEVELAND CLINIC LERNER COM-CWRU · PI DASARATHY, SRINIVASAN, NAGY, LAURA E. · 2020 to 2024
$2.8M
Dark GPCR signaling underlying the Microbiome-Gut-Brain Axis for Alzheimer's Disease and Related DementiaRF1NS133812 · NINDS · CLEVELAND CLINIC LERNER COM-CWRU · PI BROWN, JONATHAN MARK, CHENG, FEIXIONG · 2023 to 2023
$2.3M
Sarcopenia in cirrhosis is mediated by a hyperammonemic stress responseR01DK113196 · NIDDK · CLEVELAND CLINIC LERNER COM-CWRU · PI DASARATHY, SRINIVASAN, HATZOGLOU, MARIA · 2018 to 2021
$2.3M
Novel therapeutics for alcoholic hepatitis - Cleveland Translational ComponentU01AA021890 · NIAAA · CLEVELAND CLINIC LERNER COM-CWRU · PI NAGY, LAURA E. · 2012 to 2017
$1.6M
Microbial metabolites and Innate Immunity in AH: Biomarkers of injury and repairU01AA026938 · NIAAA · CLEVELAND CLINIC LERNER COM-CWRU · PI NAGY, LAURA E. · 2018 to 2023
$1.4M
Mechanisms of Malnutrition in Cirrhosis with Portosystemic ShuntingR01GM119174 · NIGMS · CLEVELAND CLINIC LERNER COM-CWRU · PI DASARATHY, SRINIVASAN · 2017 to 2020
backgroundDichloroacetate (DCA), a pan-pyruvate dehydrogenase kinase inhibitor, ameliorates multiple pathological conditions and tissue injury and shows strong potential for clinical applications. Here, we investigated the preventive effects of DCA in a murine model of alcohol-associated liver disease.
methodsC57BL/6J mice were subjected to the acute-on-chronic model of alcohol-associated liver disease and treated with DCA. Livers were assessed in liver histology, biochemistry, and gene expression. Mass spectrometry was used to compare protein expression and metabolite levels.
resultsDCA inhibited hepatic expression of inflammatory genes but did not prevent steatosis and hepatocellular injury in ethanol-fed mice. Consistently, DCA repressed the expression of mRNAs for inflammatory genes in LPS-stimulated murine bone-marrow-derived macrophages and human monocytic THP-1 cells and inhibited both gene expression and protein release of interleukin-1 beta. DCA prevented hepatic accumulation of isovaleric acid in ethanol-fed mice, a short-chain fatty acid primarily produced by gut microbiota. In vitro, isovaleric acid potentiated LPS's effects, while DCA prevented this proinflammatory action. Ethanol feeding increased the expression of proteins involved in diverse metabolic pathways, including branched-chain amino acid (BCAA) degradation. In ethanol-fed mice, hepatic Fischer's ratio (the molar ratio of BCAAs to aromatic amino acids Phe and Tyr) and BTR (the molar ratio of BCAAs to Tyr) showed a decrease compared to pair-fed mice; however, this decrease was not observed in DCA-treated ethanol-fed mice. DCA blunted the ethanol-induced increase of BCKDHA, the rate-limiting enzyme in BCAA catabolism, and cytochrome P450 2E1.
conclusionsEthanol-induced hepatic inflammatory responses and metabolic disturbances were prevented by DCA in mice, indicating the potential to develop pyruvate dehydrogenase kinase inhibitors as an effective therapy to treat alcohol-associated liver disease.
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.
The pyruvate dehydrogenase kinase inhibitor dichloroacetate mitigates alcohol-induced hepatic inflammation and metabolic disturbances in mice. · full record | Socratic