Immune cell-mediated features of non-alcoholic steatohepatitis

Nature reviews. Immunology, Journal Year: 2021, Volume and Issue: 22(7), P. 429 - 443

Published: Nov. 5, 2021

Non-alcoholic fatty liver disease (NAFLD) includes a range of hepatic manifestations, starting with steatosis and potentially evolving towards non-alcoholic steatohepatitis (NASH), cirrhosis or even hepatocellular carcinoma. NAFLD is major health burden, its incidence increasing worldwide. Although it primarily disturbed metabolism, involves several immune cell-mediated inflammatory processes, particularly when reaching the stage NASH, at which point inflammation becomes integral to progression disease. The cell landscape diverse steady state further evolves during NASH direct consequences for severity. In this Review, we discuss current concepts related role cells in onset NASH. A better understanding mechanisms by contribute pathogenesis should aid design innovative drugs target therapeutic options are limited. (NASH) serious chronic disorder prevalence Metabolic nature, also mobilizes system. Here, Huby Gautier knowledge regarding how subsets affect progression.

Language: Английский

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Oxidative Stress in Liver Pathophysiology and Disease

Antioxidants, Journal Year: 2023, Volume and Issue: 12(9), P. 1653 - 1653

Published: Aug. 22, 2023

The liver is an organ that particularly exposed to reactive oxygen species (ROS), which not only arise during metabolic functions but also the biotransformation of xenobiotics. disruption redox balance causes oxidative stress, affects function, modulates inflammatory pathways and contributes disease. Thus, stress implicated in acute injury pathogenesis prevalent infectious or chronic diseases such as viral hepatitis B C, alcoholic fatty disease, non-alcoholic disease (NAFLD) steatohepatitis (NASH). Moreover, plays a crucial role progression fibrosis, cirrhosis hepatocellular carcinoma (HCC). Herein, we provide overview on effects pathophysiology mechanisms by promotes

Language: Английский

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Oxidative Stress Is a Key Modulator in the Development of Nonalcoholic Fatty Liver Disease

Antioxidants, Journal Year: 2021, Volume and Issue: 11(1), P. 91 - 91

Published: Dec. 30, 2021

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic worldwide, and scientific studies consistently report that NAFLD development can be accelerated by oxidative stress. Oxidative stress induce progression of to NASH stimulating Kupffer cells, hepatic stellate hepatocytes. Therefore, are underway identify role antioxidants in treatment NAFLD. In this review, we have summarized origins reactive oxygen species (ROS) relationship between ROS NAFLD, discussed use as therapeutic agents for

Language: Английский

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Fructose and the Liver

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(13), P. 6969 - 6969

Published: June 28, 2021

Chronic diseases represent a major challenge in world health. Metabolic syndrome is constellation of disturbances affecting several organs, and it has been proposed to be liver-centered condition. Fructose overconsumption may result insulin resistance, oxidative stress, inflammation, elevated uric acid levels, increased blood pressure, triglyceride concentrations both the liver. Non-alcoholic fatty liver disease (NAFLD) term widely used describe excessive infiltration absence alcohol, autoimmune disorders, or viral hepatitis; attributed obesity, high sugar fat consumption, sedentarism. If untreated, NAFLD can progress nonalcoholic steatohepatitis (NASH), characterized by inflammation mild fibrosis addition and, eventually, advanced scar tissue deposition, cirrhosis, finally cancer, which constitutes culmination disease. Notably, fructose recognized as mediator NAFLD, significant correlation between intake degree found preclinical clinical studies. Moreover, risk factor for cancer development. Interestingly, induces number proinflammatory, fibrogenic, oncogenic signaling pathways that explain its deleterious effects body, especially

Language: Английский

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Antioxidant Peptides from Monkfish Swim Bladders: Ameliorating NAFLD In Vitro by Suppressing Lipid Accumulation and Oxidative Stress via Regulating AMPK/Nrf2 Pathway

Marine Drugs, Journal Year: 2023, Volume and Issue: 21(6), P. 360 - 360

Published: June 16, 2023

In this study, we investigate the ameliorating functions of QDYD (MSP2), ARW (MSP8), DDGGK (MSP10), YPAGP (MSP13) and DPAGP (MSP18) from monkfish swim bladders on an FFA-induced NAFLD model HepG2 cells. The lipid-lowering mechanisms revealed that these five oligopeptides can up-regulate expression phospho-AMP-activated protein kinase (p-AMPK) proteins to inhibit sterol regulatory element binding protein-1c (SREBP-1c) increasing lipid synthesis up-regulating PPAP-α CPT-1 promoting β-oxidation fatty acids. Moreover, significantly reactive oxygen species' (ROS) production, promote activities intracellular antioxidases (superoxide dismutase, SOD; glutathione peroxidase, GSH-PX; catalase, CAT) bring down content malondialdehyde (MDA) derived peroxidation. Further investigations regulation oxidative stress was achieved through activating nuclear factor erythroid 2-related 2 (Nrf2) pathway raise levels heme oxygenase 1 (HO-1) downstream antioxidant proteases. Therefore, could serve as candidate ingredients develop functional products for treating NAFLD.

Language: Английский

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Nuclear Receptors Linking Metabolism, Inflammation, and Fibrosis in Nonalcoholic Fatty Liver Disease

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(5), P. 2668 - 2668

Published: Feb. 28, 2022

Nonalcoholic fatty liver disease (NAFLD) and its progressive form nonalcoholic steatohepatitis (NASH) comprise a spectrum of chronic diseases in the global population that can lead to end-stage hepatocellular carcinoma (HCC). NAFLD is closely linked metabolic syndrome, comorbidities such as type 2 diabetes, obesity insulin resistance aggravate disease, while promotes cardiovascular risk affected patients. The pathomechanisms are multifaceted, combining hepatic factors including lipotoxicity, mechanisms cell death inflammation with extrahepatic disturbance dysbiosis. Nuclear receptors (NRs) family ligand-controlled transcription regulate glucose, fat cholesterol homeostasis modulate innate immune functions, macrophages. In parallel derangement NAFLD, altered NR signaling frequently observed might be involved pathogenesis. Therapeutically, clinical data indicate single drug targets thus far have been insufficient for reaching patient-relevant endpoints. Therefore, combinatorial treatment strategies multiple or drugs actions could possibly bring advantages, by providing more holistic therapeutic approach. this context, peroxisome proliferator-activated (PPARs) other NRs great interest they wide-ranging multi-organ activities associated NASH progression regression. review, we summarize recent advances understanding pathogenesis focusing on death, immunometabolism role NRs. We outline novel discuss remaining challenges.

Language: Английский

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Role of silymarin as antioxidant in clinical management of chronic liver diseases: a narrative review

Annals of Medicine, Journal Year: 2022, Volume and Issue: 54(1), P. 1548 - 1560

Published: May 28, 2022

Chronic liver disease (CLD), manifested as hepatic injury, is a major cause of global morbidity and mortality. CLD progresses to fibrosis, cirrhosis, and—ultimately—hepatocellular carcinoma (HCC) if left untreated. The different phenotypes based on their respective clinical features causative agents include alcoholic (ALD), non-alcoholic fatty (NAFLD), metabolic-associated (MAFLD), drug-induced injury (DILI). preferred treatment modality for includes lifestyle modification diet, along with limited pharmacological symptomatic treatment. Moreover, oxidative stress (OS) an important pathological mechanism underlying all phenotypes; hence, the use antioxidants manage justified. Based available evidence, silymarin can be utilized hepatoprotective agent, given its potent antioxidant, antifibrotic, anti-inflammatory properties. role in suppressing OS has been well established, therefore recommended ALD NAFLD guidelines approved by Russian Medical Scientific Society Therapists Gastroenterology Russia. However, discuss positioning original protocols agent managing concomitantly other therapies, expert panel international medical professionals was convened 11 November 2020. reviewed approaches prevention OS, existing patient management CLD, evidence effectiveness reducing inflammation presented form narrative review.Key messagesAn ALD, NAFLD, MAFLD, DILI establish consensus recommendations that common pathophysiological these conditions.The also discussed therapies.The 140 mg three times day chronic diseases such DILI.

Language: Английский

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Exosomes derived from human umbilical cord mesenchymal stem cells ameliorate experimental non-alcoholic steatohepatitis via Nrf2/NQO-1 pathway

Free Radical Biology and Medicine, Journal Year: 2022, Volume and Issue: 192, P. 25 - 36

Published: Sept. 10, 2022

Language: Английский

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Computational modeling of imines based anti-oxidant and anti-esterases compounds: Synthesis, single crystal and In-vitro assessment

Computational Biology and Chemistry, Journal Year: 2023, Volume and Issue: 104, P. 107880 - 107880

Published: May 8, 2023

Language: Английский

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Oxidative Stress–Induced Liver Damage and Remodeling of the Liver Vasculature

American Journal Of Pathology, Journal Year: 2023, Volume and Issue: 193(10), P. 1400 - 1414

Published: June 23, 2023

As an organ critically important for targeting and clearing viruses, bacteria, other foreign material, the liver operates via immune-tolerant, anti-inflammatory mechanisms indispensable to immune response. Stress stress-induced factors disrupt homeostatic balance in liver, inflicting tissue damage, injury, remodeling. These include oxidative stress (OS) induced by viral infections, environmental toxins, drugs, alcohol, diet. A recurrent theme seen among stressors common multiple diseases is induction of mitochondrial dysfunction, increased reactive oxygen species expression, depletion ATP. Inflammatory signaling additionally exacerbates condition, generating a proinflammatory, immunosuppressive microenvironment activation apoptotic necrotic that integrity morphology. pathways initiate significantly contribute development steatosis, inflammation, fibrosis, cirrhosis, cancers. In addition, hypoxia OS directly enhance angiogenesis lymphangiogenesis chronic diseases. Late-stage consequences these conditions often narrow outcomes transplantation or result death. This review provides detailed perspective on various specific focus role different with special emphasis molecular mechanisms. It also highlights how resultant changes vasculature correlate pathogenesis. Stress-induced health issues are one major challenges modern society. Stress, which defined "conditions where demand exceeds natural regulatory capacity organism, particular situations unpredictability uncontrollability,"1Koolhaas J.M. Bartolomucci A. Buwalda B. de Boer S.F. Flugge G. Korte S.M. Meerlo P. Murison R. Olivier Palanza Richter-Levin Sgoifo Steimer T. Stiedl O. van Dijk Wohr M. Fuchs E. revisited: critical evaluation concept.Neurosci Biobehav Rev. 2011; 35: 1291-1301Crossref PubMed Scopus (982) Google Scholar can alter normal homeostasis human physiological psychological status.2Vere C.C. Streba C.T. L.M. Ionescu A.G. Sima F. 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Poghosyan Verheem Padera T.P. Rinkes I. Kranenburg Hagendoorn drainage patterns follow segmental anatomy model.Sci 1021808Crossref Lymphatic capillaries, thin-walled single layered (LECs), collect lymph, rich cellular proteins, lipoproteins, lymphocytes, drain collecting Collecting unlike covered muscle pump nodes.21Burchill Scholar,24Tanaka Iwakiri system: structure, function, markers, lymphangiogenesis.Cell Gastroenterol Hepatol. 2: 733-749Abstract About 70% 80% parenchymal hepatocytes. Hepatocytes crucial metabolism, innate regulation, protein synthesis, secretion circulation.25Schulze R.J. Schott M.B. Casey Tuma McNiven biology hepatocyte: membrane trafficking machine.J Cell Biol. 218: 2096-2112Crossref (80) Scholar,26Zhou Z. Xu M.J. 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