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References from Repurposed metformin–apigenin combination therapy for metabolic dysfunction-associated steatohepatitis: from integrative multi-omics discovery to in vivo validation. Local targets link to admitted publications; unresolved targets remain external evidence.
Exogenous PP2A inhibitor exacerbates the progression of nonalcoholic fatty liver disease via NOX2-dependent activation of miR21
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Low metformin causes a more oxidized mitochondrial NADH/NAD redox state in hepatocytes and inhibits gluconeogenesis by a redox-independent mechanism
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Phospholipid metabolism in the liver - implications for phosphatidylserine in non-alcoholic fatty liver disease
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Semaglutide therapy for metabolic dysfunction-associated steatohepatitis: november 2025 updates to AASLD practice guidance
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MNDA, a PYHIN factor involved in transcriptional regulation and apoptosis control in leukocytes
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Mendelian randomization with invalid instruments: effect estimation and bias detection through egger regression
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The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD)
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Muetabolic dysfunction-associated steatotic liver disease: a condition of heterogeneous metabolic risk factors, mechanisms and comorbidities requiring holistic treatment
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Nicotinamide adenine dinucleotide phosphate oxidases and metabolic dysfunction-associated steatotic liver disease
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A european survey to identify challenges in the management of metabolic dysfunction-associated steatotic liver disease
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Profiling tumor infiltrating immune cells with CIBERSORT
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Resmetirom therapy for metabolic dysfunction-associated steatotic liver disease: october 2024 updates to AASLD practice guidance
10.1097/hep.0000000000001112 · 2025 · External reference
Clec12a controls colitis by tempering inflammation and restricting expansion of specific commensals
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Diet-induced mouse model of fatty liver disease and nonalcoholic steatohepatitis reflecting clinical disease progression and methods of assessment
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Sparstolonin B attenuates early liver inflammation in experimental NASH by modulating TLR4 trafficking in lipid rafts via NADPH oxidase activation
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Steatohepatitis: a tale of two hits
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NOX2-generated oxidative stress is associated with severity of ultrasound liver steatosis in patients with non-alcoholic fatty liver disease
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Therapeutic landscape of metabolic dysfunction-associated steatohepatitis (MASH)
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EASL-EASD-EASO clinical practice guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD)
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A nomogram to predict mortality in patients with severe fever with thrombocytopenia syndrome
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Sparse kernel learning with LASSO and bayesian inference algorithm
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NADPH oxidase is implicated in the pathogenesis of oxidative phosphorylation dysfunction in mice fed a high-fat diet
10.1038/srep23664 · 2016 · External reference
Electronic health record-based genome-wide meta-analysis provides insights on the genetic architecture of non-alcoholic fatty liver disease
10.1016/j.xcrm.2021.100437 · 2021 · External reference
Exposure to plasma From Non-alcoholic fatty liver disease patients affects hepatocyte viability, generates mitochondrial dysfunction, and modulates pathways involved in fat accumulation and inflammation
10.3389/fmed.2021.693997 · 2021 · External reference
A phase 3, randomized, controlled trial of resmetirom in NASH with liver fibrosis
10.1056/nejmoa2309000 · 2024 · External reference
Metformin action: concentrations matter
10.1016/j.cmet.2015.01.003 · 2015 · External reference
Hydrophilic metformin and hydrophobic biguanides inhibit mitochondrial complex I by distinct mechanisms
10.1038/s41594-025-01710-6 · 2026 · External reference
The MR-Base platform supports systematic causal inference across the human phenome
10.7554/elife.34408 · 2018 · External reference
Obesity accelerates epigenetic aging of human liver
10.1073/pnas.1412759111 · 2014 · External reference
Rac1 signaling mediates the protection of apigenin against hepatic lipid accumulation and insulin resistance
10.1016/j.biopha.2025.118265 · 2025 · External reference
TAK1-mediated autophagy and fatty acid oxidation prevent hepatosteatosis and tumorigenesis
10.1172/jci74068 · 2014 · External reference
The crucial regulatory role of type I interferon in inflammatory diseases
10.1186/s13578-023-01188-z · 2023 · External reference
Nonphagocytic activation of NOX2 Is implicated in progressive nonalcoholic steatohepatitis During aging
10.1002/hep.31118 · 2020 · External reference
KEGG: kyoto encyclopedia of genes and genomes
10.1093/nar/28.1.27 · 2000 · External reference
Pathophysiology, development, and mortality of major non-communicable diseases in metabolic dysfunction-associated steatotic liver disease: a comprehensive review
10.7150/ijbs.117211 · 2025 · External reference
PDB-2-PBv3.0: an updated protein block database
10.1142/s0219720020500092 · 2020 · External reference
Immune cell infiltration landscapes in pediatric acute myocarditis analyzed by CIBERSORT
10.1016/j.jjcc.2020.08.004 · 2021 · External reference
Resmetirom: first approval
10.1007/s40265-024-02045-0 · 2024 · External reference
Pro-inflammatory hepatic macrophages generate ROS through NADPH oxidase 2 via endocytosis of monomeric TLR4-MD2 complex
10.1038/s41467-017-02325-2 · 2017 · External reference
PubChem in 2021: new data content and improved web interfaces
10.1093/nar/gkaa971 · 2021 · External reference
Intermittent fasting attenuates metabolic-dysfunction-associated steatohepatitis by enhancing the hepatic autophagy-lysosome pathway
10.3390/nu15214574 · 2023 · External reference
Integrative transcriptomic and genomic analyses unveil the IFI16 variants and expression as MASLD progression markers
10.1097/hep.0000000000000805 · 2025 · External reference
Metformin, phenformin, and galegine inhibit complex IV activity and reduce glycerol-derived gluconeogenesis
10.1073/pnas.2122287119 · 2022 · External reference
WGCNA: an R package for weighted correlation network analysis
10.1186/1471-2105-9-559 · 2008 · External reference
NFATc1 signaling drives chronic ER stress responses to promote NAFLD progression
10.1136/gutjnl-2021-325013 · 2022 · External reference
The ratio of phosphatidylcholine to phosphatidylethanolamine influences membrane integrity and steatohepatitis
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10.1093/bioinformatics/btn025 · 2008 · External reference
Metformin in non-alcoholic fatty liver disease: a systematic review and meta-analysis
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The uric acid crystal receptor Clec12A potentiates type I interferon responses
10.1073/pnas.1821351116 · 2019 · External reference
Metformin alleviates inflammatory response in non-alcoholic steatohepatitis by restraining signal transducer and activator of transcription 3-mediated autophagy inhibition in vitro and in vivo
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High dietary fructose drives metabolic dysfunction-associated steatotic liver disease via activating ubiquitin-specific peptidase 2/11beta-hydroxysteroid dehydrogenase type 1 pathway in mice
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Clinical and pathological characteristics of metabolic dysfunction-associated steatotic liver disease and the key role of epigenetic regulation: implications for molecular mechanism and treatment
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Simultaneous dual-channel tracking lipid droplets dynamic behaviors and revealing the protective role in nonalcoholic fatty liver in mice
10.1021/acs.analchem.5c03758 · 2025 · External reference
Effects of dark chocolate on endothelial function in patients with non-alcoholic steatohepatitis
10.1016/j.numecd.2017.10.027 · 2017 · External reference
Does Nox2 overactivate in children with nonalcoholic fatty liver disease?
10.1089/ars.2018.7596 · 2019 · External reference
Moderated estimation of fold change and dispersion for RNA-Seq data with DESeq2
10.1186/s13059-014-0550-8 · 2014 · External reference
Apigenin reduces the excessive accumulation of lipids induced by palmitic acid via the AMPK signaling pathway in HepG2 cells
10.3892/etm.2019.7905 · 2019 · External reference
Metformin's therapeutic efficacy in the treatment of diabetes does not involve inhibition of mitochondrial glycerol phosphate dehydrogenase
10.2337/db20-1143 · 2021 · External reference
Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase
10.1038/nature13270 · 2014 · External reference
Weight loss and weight regain in usual clinical practice: results from the TARGET-NASH observational cohort
10.1016/j.cgh.2021.01.023 · 2022 · External reference
Innate immune sensing of cell death in disease and therapeutics
10.1038/s41556-024-01491-y · 2024 · External reference
Apigenin alleviated high-fat-diet-induced hepatic pyroptosis by Mitophagy-ROS-CTSB-NLRP3 pathway in mice and AML12 cells
10.1021/acs.jafc.2c07581 · 2023 · External reference
Divergent effect of diabetes on fibrosis response to semaglutide and resmetirom in noncirrhotic MASH: a meta-analysis of randomized trials
10.1016/j.medj.2025.100959 · 2026 · External reference
TIFAB regulates the TIFA-TRAF6 signaling pathway involved in innate immunity by forming a heterodimer complex with TIFA
10.1073/pnas.2318794121 · 2024 · External reference
Clec12a is an inhibitory receptor for uric acid crystals that regulates inflammation in response to cell death
10.1016/j.immuni.2013.12.015 · 2014 · External reference
Therapeutic horizons in metabolic dysfunction-associated steatohepatitis
10.1172/jci186425 · 2025 · External reference
TIFAB regulates USP15-Mediated p53 signaling during stressed and malignant hematopoiesis
10.1016/j.celrep.2020.01.093 · 2020 · External reference
Comprehensive study of the murine MASH models' applicability by comparing human liver transcriptomes
10.1016/j.lfs.2025.123723 · 2025 · External reference
Metabolomic/lipidomic-based analysis of plasma to diagnose hepatocellular ballooning in patients with non-alcoholic fatty liver disease: a multicenter study
10.1111/hepr.13528 · 2020 · External reference
Metformin-induced TTP mediates communication between kupffer cells and hepatocytes to alleviate hepatic steatosis by regulating lipophagy and necroptosis
10.1016/j.metabol.2023.155516 · 2023 · External reference
Metformin and the liver: unlocking the full therapeutic potential
10.3390/metabo14040186 · 2024 · External reference
Efficient design for Mendelian randomization studies: subsample and 2-sample instrumental variable estimators
10.1093/aje/kwt084 · 2013 · External reference
Mechanisms behind NAFLD: a system genetics perspective
10.1007/s11883-023-01158-3 · 2023 · External reference
A multisociety Delphi consensus statement on new fatty liver disease nomenclature
10.1016/j.jhep.2023.06.003 · 2023 · External reference
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10.1186/1471-2105-12-77 · 2011 · External reference
Phase 3 trial of semaglutide in metabolic dysfunction-associated steatohepatitis
10.1056/nejmoa2413258 · 2025 · External reference
Ligand docking and binding site analysis with PyMOL and autodock/vina
10.1007/s10822-010-9352-6 · 2010 · External reference
Cytoscape: a software environment for integrated models of biomolecular interaction networks
10.1101/gr.1239303 · 2003 · External reference
Effect of apigenin on protein expressions of PPARs in liver tissues of rats with nonalcoholic steatohepatitis
10.3760/cma.j.issn.1007-3418.2015.02.010 · 2015 · External reference
Curcumin prevents proteins expression changes of oxidative phosphorylation, cellular stress response, and lipid metabolism proteins in liver of mice fed a high-fructose diet
10.1016/j.jprot.2022.104595 · 2022 · External reference
Metformin alleviates hepatosteatosis by restoring SIRT1-mediated autophagy induction via an AMP-activated protein kinase-independent pathway
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Metformin restores parkin-mediated mitophagy, suppressed by cytosolic p53
10.3390/ijms17010122 · 2016 · External reference
MASH: the nexus of metabolism, inflammation, and fibrosis
10.1172/jci186420 · 2025 · External reference
Multiple hits, including oxidative stress, as pathogenesis and treatment target in non-alcoholic steatohepatitis (NASH)
10.3390/ijms141020704 · 2013 · External reference
Metformin targets mitochondrial glycerophosphate dehydrogenase to control rate of oxidative phosphorylation and growth of thyroid cancer in vitro and in vivo
10.1158/1078-0432.ccr-17-3167 · 2018 · External reference
Metabolic dysfunction-associated steatotic liver disease in adults: a review
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CETSA and thermal proteome profiling strategies for target identification and drug discovery of natural products
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Loss of tifab, a del(5q) MDS gene, alters hematopoiesis through derepression of toll-like receptor-TRAF6 signaling
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Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases
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Large-scale cis- and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression
10.1038/s41588-021-00913-z · 2021 · External reference
DGIdb 2.0: mining clinically relevant drug-gene interactions
10.1093/nar/gkv1165 · 2016 · External reference
TAZ-Induced cybb contributes to liver tumor formation in non-alcoholic steatohepatitis
10.1016/j.jhep.2021.11.031 · 2022 · External reference
Apigenin as an emerging hepatoprotective agent: current status and future perspectives
10.3389/fphar.2024.1508060 · 2024 · External reference
Chemical imaging unveils mitochondria as the major site of medicinal biguanide accumulation within cells
10.1016/j.heliyon.2024.e34595 · 2024 · External reference
Associations of the intake of individual and multiple flavonoids with metabolic dysfunction associated steatotic liver disease in the United States
10.3390/nu17020205 · 2025 · External reference
TIFAB modulates metabolic pathways in KMT2A::MLLT3-induced AML through HNF4A
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Roburic acid inhibits glucocorticoid-induced osteonecrosis of the femoral head associated osteoclast activity via targeting PTP1B
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Accumulation of metformin by tissues of the normal and diabetic mouse
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Blockade of chronic type I interferon signaling to control persistent LCMV infection
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Advances in the acting mechanism and treatment of gut microbiota in metabolic dysfunction-associated steatotic liver disease
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Apigenin prevents metabolic syndrome in high-fructose diet-fed mice by Keap1-Nrf2 pathway
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Structure of glycerol-3-phosphate dehydrogenase, an essential monotopic membrane enzyme involved in respiration and metabolism
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10.1155/2020/5273914 · 2020 · External reference
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Global consensus recommendations for metabolic dysfunction-associated steatotic liver disease and steatohepatitis
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TIFAB accelerates MLL-AF9-Induced acute myeloid leukemia through upregulation of HOXA9
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Deficiency of mitochondrial glycerol 3-Phosphate dehydrogenase contributes to hepatic steatosis
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Effects of eicosapentaenoic acid on the glycerophosphate shuttle-regulated inflammatory and thermogenic responses
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