Novel Therapies for Nonalcoholic Steatohepatitis (NASH) and Cardiovascular Risk Reduction DOI

Tarun Biswas,

Angelica Lehker,

Debabrata Mukherjee

и другие.

Cardiovascular & Haematological Disorders - Drug Targets, Год журнала: 2024, Номер 24(4), С. 211 - 217

Опубликована: Ноя. 20, 2024

Nonalcoholic steatohepatitis (NASH) is a type of nonalcoholic fatty liver disease (NAFLD) characterized by hepatocyte injury and inflammation, in addition to only the presence steatosis NAFLD. We review existing data on available novel therapies for NASH NAFLD also discuss several development. assessed searching databases PubMed, EMBASE, Web Science (SCI) from their inception dates until September 15, 2024. Search terms used were: disease, steatohepatitis, inflammation injury.Until very recently, therapeutic lifestyle change was primary modality treatment NASH, including modification diet physical activity. The FDA recently approved resmetirom using its expedited approval mechanism NASH. There are pharmacotherapies development which aim at weight loss, insulin sensitization improvement lipid levels, although some drugs may have multiple effects discussed. availability offers patients with an effective adjunctive therapy changes. Several other currently being tested will add our armamentarium.

Язык: Английский

Circadian Control of Hepatic Ischemia/Reperfusion Injury via HSD17B13-Mediated Autophagy in Hepatocytes DOI
Hui Wang,

Meina Guo,

Baoyin Ren

и другие.

Journal of Hepatology, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

1

Rodent model of metabolic dysfunction‐associated fatty liver disease: a systematic review DOI Creative Commons

Xiao‐Shan Cui,

Wanqing Li, Liang Li

и другие.

Journal of Gastroenterology and Hepatology, Год журнала: 2024, Номер unknown

Опубликована: Сен. 25, 2024

Abstract Although significant progress has been made in developing preclinical models for metabolic dysfunction‐associated steatotic liver disease (MASLD), few have encapsulated the essential biological and clinical outcome elements reflective of human condition. We conducted a comprehensive literature review English‐language original research articles published from 1990 to 2023, sourced PubMed, Embase, Web Science, aiming collate studies that provided comparative analysis physiological, metabolic, hepatic histological characteristics between MASLD control groups. The establishment robust rodent model hinges on various factors, including animal species strains, sex, induction agents methodologies, duration induction. Through this review, we aim guide researchers selecting suitable methods constructing aligned with their specific objectives laboratory conditions. Future should strive develop simple, reliable, reproducible models, considering model's sensitivity factors such as light–dark cycles, housing conditions, environmental temperature. Additionally, potential diverse vitro 3D organ technology, warrants further exploration valuable tools unraveling cellular mechanisms underlying fatty disease.

Язык: Английский

Процитировано

3

Liver-specific inactivation of Cideb improves metabolic profiles and ameliorates steatohepatitis and fibrosis in animal models for MASH DOI Creative Commons
Jianhua Zhang, Xujie Liu,

Xian Jin

и другие.

Pharmacological Research, Год журнала: 2025, Номер unknown, С. 107664 - 107664

Опубликована: Фев. 1, 2025

Germline mutations of CIDEB, a lipid droplets (LDs)-associated protein, confer protection against various liver diseases in humans. It remains to be determined whether liver-specific inhibition CIDEB will bring clinical benefits. We aim establish pharmacological proof concept by testing GalNAc-conjugated Cideb surrogate siRNAs respective animal models obesity and MASH develop siRNA drug candidates for investigations. Surrogate targeting mouse were designed evaluated via panel assays. Concurrently, humanized knock-in mice generated as research tool facilitate human therapeutic discovery. In vivo administration the was conducted diet-induced (DIO) model CDAA-HFD MASH. DIO model, knockdown led significant reductions serum total cholesterol (TC) triglyceride (TG) levels, decrease hepatic macro-steatosis notable weight loss. treatment significantly reduced TC TG levels. Furthermore, remarkable steatosis composite NAS score observed with concomitant amelioration fibrosis. Transcriptome analyses revealed that integrin pathways may contribute major activities upon inactivation beyond metabolism. exhibits potential target Liver-targeting are under development hypothesis

Язык: Английский

Процитировано

0

Reversed role of CD36 deficiency in high-fat diet or methionine/choline-deficient diet-induced hepatic steatosis and steatohepatitis DOI Creative Commons

Wenya Zhu,

Jialing Ma, Tingting Zhang

и другие.

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Март 5, 2025

Cluster of differentiation 36 (CD36) is highly expressed in the liver patients with metabolic dysfunction-associated fatty disease (MAFLD) or steatohepatitis (MASH). However, precise role CD36 MAFLD/MASH controversial. In current study, we aimed to uncover early stage induced by high-fat diet (HFD) and methionine/choline-deficient (MCD) diet. CD36-/- mice littermate control were fed a normal food (NCD); HFD MCD for 6 weeks. We determined that deficiency attenuated HFD-induced hepatic steatosis while exacerbating diet-induced steatohepatitis. Mechanistically, reduced expression acid synthase (FASN), sterol regulatory element binding protein 1c (SREBP1c), acetyl-CoA carboxylase alpha (ACC1), thereby inhibiting de novo synthesis. The superoxide dismutase genes involving oxidation was inhibited oxidation, had no effect on these mice. Meanwhile, diet-reduced further deficiency. Thus, MCD-induced ROS inflammation enhanced By lipidomic analysis, found levels triglyceride (TG), diacylglycerols (DG), acylcarnitine (AcCA), ceramide (Cer) LPC increased, phosphatidylcholine/phosphatidylethanolamine (PC/PE) decreased diet-treated compared wild type Indeed, serine palmitoyltransferase 2 (SPTLC2), key rate-limiting enzyme synthesis, higher improves MAFLD accelerating MASH via promoting Cer, LPC, TG DG accumulation accelerate inflammation. complex needs more investigation discover effective strategy when targeting CD36.

Язык: Английский

Процитировано

0

Gelsolin's Protective Role in MASH through F‐Actin Regulation and P53 Degradation DOI Creative Commons
Yiwei Lu, Tong Ji, Zhichao Ye

и другие.

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Май 20, 2025

Abstract Hepatic steatosis, inflammation, and fibrosis are the hallmarks of metabolic‐associated steatohepatitis (MASH), a serious health risk. This study emphasizes how important gelsolin (GSN) is to pathophysiology MASH. The results show that GSN significantly overexpressed in both MASH patients animal models. Under models, Gsn knockout (KO) ( −/− ) mice demonstrate exacerbated hepatic fibrosis, underscoring GSN's protective function. Remarkably, adeno‐associated virus (AAV)‐mediated restoration substantially alleviates these pathological features, indicating its therapeutic potential. Mechanistically, absence leads increased F‐actin polymerization heightened activation Yes‐associated protein (YAP), thereby intensifying inflammatory response. Subsequently, experimental data identify co‐expression relationship between MDM2, found facilitate ubiquitination subsequent degradation P53 via crucial process for liver protection. These findings imply essential controlling molecular pathways by encouraging P53's MDM2‐mediated degradation, which lessens severity steatosis. research offers new understandings mechanisms suggests as viable target reduce damage preserve homeostasis.

Язык: Английский

Процитировано

0

Hepatocyte nuclear factor 4-Alpha: a key regulator in liver carcinogenesis DOI Creative Commons

Hayam Hamdy,

Chang Shen,

Jiashun Xu

и другие.

Cellular Oncology, Год журнала: 2025, Номер unknown

Опубликована: Май 20, 2025

Язык: Английский

Процитировано

0

Polygenic Risk Score for Metabolic Dysfunction-Associated Steatotic Liver Disease and Steatohepatitis: A Narrative Review DOI Open Access
Tatsuo Kanda, Reina Sasaki, Hiroyuki Abé

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(11), С. 5164 - 5164

Опубликована: Май 28, 2025

Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic steatohepatitis (MASH) are spreading worldwide as the most critical causes of cirrhosis hepatocellular carcinoma (HCC). Thus, improving screening managing strategies for patients with MASLD or MASH is necessary. A traditional non-systemic review provided this narrative. Genetic variations associated development MASH, such PNPLA3, TM6SF2, GCKR, MBOAT7, MERTK, HSD17B13, were initially reviewed. PNPLA3 genetic variants appeared to be strongly increased pathogenesis MASLD, cirrhosis, HCC. We also reviewed useful polygenic risk score (PRS) their related occurrence PRSs better predictors HCC in than any single-nucleotide polymorphisms. RNA interference antisense nucleotides against HSD17B13 being developed. Multidisciplinary collaboration cooperation involving hepatologists, geneticists, pharmacologists, pathologists should resolve complicated problems MASH. This narrative highlights importance susceptibility PRS predictive markers personalized medicine future.

Язык: Английский

Процитировано

0

Role of PNPLA3 in Hepatic Stellate Cells and Hepatic Cellular Crosstalk DOI Creative Commons
Maria Castanho Martins,

Emmanuel Dauda Dixon,

Giulia Lupo

и другие.

Liver International, Год журнала: 2024, Номер unknown

Опубликована: Окт. 12, 2024

ABSTRACT Aims Since its discovery, the patatin‐like phospholipase domain containing 3 (PNPLA3) (rs738409 C>G p.I148M) variant has been studied extensively to unravel molecular function. Although several studies proved a causal relationship between PNPLA3 I148M and MASLD development particularly fibrosis, pathological mechanisms promoting this phenotype have not yet fully clarified. Methods We summarise latest data regarding in hepatic stellate cells (HSCs) activation macrophage biology or path inflammation‐induced fibrosis. Results Elegant but contradictory ascribed hydrolase an acyltransferase The results lipid accumulation, which predisposes hepatocyte lipotoxicity lipo‐apoptosis, producing DAMPs, cytokines chemokines leading recruitment of macrophages HSCs, propagating Recent showed that alters HSCs via attenuation PPARγ, AP‐1, LXRα TGFβ activity signalling. Conclusions advent refined techniques isolating made PNPLA3's direct role for liver fibrosis more apparent. However, many other still need detailed investigations.

Язык: Английский

Процитировано

2

Pharmacotherapy of Liver Fibrosis and Hepatitis: Recent Advances DOI Creative Commons

Liangtao Zhao,

Haolan Tang,

Zhangjun Cheng

и другие.

Pharmaceuticals, Год журнала: 2024, Номер 17(12), С. 1724 - 1724

Опубликована: Дек. 20, 2024

Liver fibrosis is a progressive scarring process primarily caused by chronic inflammation and injury, often closely associated with viral hepatitis, alcoholic liver disease, metabolic dysfunction-associated steatotic disease (MASLD), drug-induced autoimmune (AILD). Currently, there are very few clinical antifibrotic drugs available, effective targeted therapy lacking. Recently, emerging immunomodulators have shown promising results in animal studies, some entered research phases. This review aims to systematically the molecular mechanisms underlying fibrosis, focusing on advancements drug treatments for hepatic fibrosis. Furthermore, since progression or endpoint of many diseases, it crucial address etiological treatment secondary prevention We will also pharmacological available common hepatitis leading

Язык: Английский

Процитировано

2

Novel Therapies for Nonalcoholic Steatohepatitis (NASH) and Cardiovascular Risk Reduction DOI

Tarun Biswas,

Angelica Lehker,

Debabrata Mukherjee

и другие.

Cardiovascular & Haematological Disorders - Drug Targets, Год журнала: 2024, Номер 24(4), С. 211 - 217

Опубликована: Ноя. 20, 2024

Nonalcoholic steatohepatitis (NASH) is a type of nonalcoholic fatty liver disease (NAFLD) characterized by hepatocyte injury and inflammation, in addition to only the presence steatosis NAFLD. We review existing data on available novel therapies for NASH NAFLD also discuss several development. assessed searching databases PubMed, EMBASE, Web Science (SCI) from their inception dates until September 15, 2024. Search terms used were: disease, steatohepatitis, inflammation injury.Until very recently, therapeutic lifestyle change was primary modality treatment NASH, including modification diet physical activity. The FDA recently approved resmetirom using its expedited approval mechanism NASH. There are pharmacotherapies development which aim at weight loss, insulin sensitization improvement lipid levels, although some drugs may have multiple effects discussed. availability offers patients with an effective adjunctive therapy changes. Several other currently being tested will add our armamentarium.

Язык: Английский

Процитировано

0