Single-cell RNA sequencing advances in revealing the development and progression of MASH: the identifications and interactions of non-parenchymal cells DOI Creative Commons
Ning Meng, Dong-Hui Lu, Liang Dong

et al.

Frontiers in Molecular Biosciences, Journal Year: 2025, Volume and Issue: 12

Published: March 25, 2025

Developing drugs for the treatment of Metabolic Associated Steatohepatitis (MASH) has always been a significant challenge. Researchers have dedicated to exploring and therapeutic strategies alleviate disease progression, but treatments remain limited. This is partly due complexity pathophysiological processes, inadequate knowledge cellular molecular mechanisms in MASH. Especially, liver non-parenchymal cells (NPCs) like Kupffer cells, hepatic stellate sinusoidal endothelial which play critical roles live function, immune responses, fibrosis progression. Deciphering how these function MASH, would help understand processes find potential drug targets. In recent years, new technologies developed single-cell transcriptomic sequencing, making cell-specific transcriptome profiling reality healthy diseased livers. this review, we discussed use sequencing provided us with an in-depth understanding heterogeneous, interactions among tried highlight discoveries MASH by technology. It hoped that summarized features markers various subclusters review could provide technical reference further experiments theoretical basis clinical applications.

Language: Английский

Immunology of human fibrosis DOI
Mallar Bhattacharya, Prakash Ramachandran

Nature Immunology, Journal Year: 2023, Volume and Issue: 24(9), P. 1423 - 1433

Published: July 20, 2023

Language: Английский

Citations

66
Found in translation—Fibrosis in metabolic dysfunction–associated steatohepatitis (MASH) DOI
Shuang Wang, Scott L. Friedman

Science Translational Medicine, Journal Year: 2023, Volume and Issue: 15(716)

Published: Oct. 4, 2023

Metabolic dysfunction–associated steatohepatitis (MASH) is a severe form of liver disease that poses global health threat because its potential to progress advanced fibrosis, leading cirrhosis and cancer. Recent advances in single-cell methodologies, refined models, genetic epigenetic insights have provided nuanced understanding MASH fibrogenesis, with substantial cellular heterogeneity livers providing potentially targetable cell-cell interactions behavior. Unlike mechanisms underlying fibrosis regression are still inadequately understood, although antifibrotic targets been recently identified. A treatment framework could lead noninvasive assessment targeted therapies preserve hepatocellular function restore the liver’s architectural integrity.

Language: Английский

Citations

55
Steatotic Liver Disease: Pathophysiology and Emerging Pharmacotherapies DOI Open Access
Michail Kokkorakis, Emir Muzurović, Špela Volčanšek

et al.

Pharmacological Reviews, Journal Year: 2024, Volume and Issue: 76(3), P. 454 - 499

Published: Jan. 30, 2024

Steatotic liver disease (SLD) displays a dynamic and complex phenotype. Consequently, the metabolic dysfunction-associated steatotic (MASLD)/metabolic steatohepatitis (MASH) therapeutic pipeline is expanding rapidly in multiple directions. In parallel, non-invasive tools for diagnosing monitoring responses to interventions are being studied, clinically feasible findings explored as primary outcomes interventional trials. The realization that distinct subgroups exist under umbrella of SLD should guide more precise personalized treatment recommendations facilitate advancements pharmacotherapeutics. This review summarizes recent updates pathophysiology-based nomenclature outlines both effective pharmacotherapeutics those MASLD/MASH, detailing their mode action current status phase 2 3 clinical Of extensive arsenal MASLD/MASH pipeline, several have been rejected, whereas other, mainly monotherapy options, shown only marginal benefits now tested part combination therapies, yet others still development monotherapies. Although successful drug candidate (or combinations) remains elusive, such approaches will ideally target MASH fibrosis while improving cardiometabolic risk factors. Due urgent need novel strategies potential availability safety tolerability data, repurposing existing approved drugs an appealing option. Finally, it essential highlight and, by extension, MASLD be recognized approached systemic affecting organs, with vigorous implementation interdisciplinary coordinated plans. Significance Statement SLD, including, among others, MASH, considered most prevalent chronic condition than one-fourth global population. aims provide information regarding pathophysiology, diagnosis, management line guidelines Collectively, hoped provided furthers understanding state direct implications stimulates additional research initiatives.

Language: Английский

Citations

31
Opportunities and barriers in omics-based biomarker discovery for steatotic liver diseases DOI Creative Commons
Maja Thiele, Ida Falk Villesen, Lili Niu

et al.

Journal of Hepatology, Journal Year: 2024, Volume and Issue: 81(2), P. 345 - 359

Published: March 28, 2024

The rising prevalence of liver diseases related to obesity and excessive use alcohol is fuelling an increasing demand for accurate biomarkers aimed at community screening, diagnosis steatohepatitis significant fibrosis, monitoring, prognostication prediction treatment efficacy. Breakthroughs in omics methodologies the power bioinformatics have created excellent opportunity apply technological advances clinical needs, instance development precision personalised medicine. Via technologies, biological processes from genes circulating protein, as well microbiome - including bacteria, viruses fungi, can be investigated on axis. However, there are important barriers omics-based biomarker discovery validation, semi-quantitative measurements untargeted platforms, which may exhibit high analytical, inter- intra-individual variance. Standardising methods need validate them across diverse populations presents a challenge, partly due disease complexity dynamic nature expression different stages. Lack validity causes lost opportunities when studies fail provide knowledge needed regulatory approvals, all contributes delayed translation these discoveries into practice. While no matured implementation, extent data generated has enabled hypothesis-free plethora candidate that warrant further validation. To explore many hepatologists detailed commonalities differences between various layers, both advantages approaches.

Language: Английский

Citations

16
FBP1 controls liver cancer evolution from senescent MASH hepatocytes DOI
Li Gu, Yahui Zhu, Shuvro P. Nandi

et al.

Nature, Journal Year: 2025, Volume and Issue: 637(8045), P. 461 - 469

Published: Jan. 1, 2025

Language: Английский

Citations

4
Development of a novel non-invasive biomarker panel for hepatic fibrosis in MASLD DOI Creative Commons
Lars Verschuren, Anne Linde Mak, Arianne van Koppen

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 29, 2024

Accurate non-invasive biomarkers to diagnose metabolic dysfunction-associated steatotic liver disease (MASLD)-related fibrosis are urgently needed. This study applies a translational approach develop blood-based biomarker panel for detection in MASLD. A molecular gene expression signature identified from diet-induced MASLD mouse model (LDLr-/-.Leiden) is translated into human based on biopsy transcriptomic profiles and protein levels patient serum samples. The resulting consists of IGFBP7, SSc5D Sema4D. LightGBM modeling using this demonstrates high accuracy predicting stage (F0/F1: AUC = 0.82; F2: 0.89; F3/F4: 0.87), which replicated an independent validation cohort. overall the outperforms predictions by existing markers Fib-4, APRI FibroScan. In conclusion, here we show mechanism-related with three able identify patients mild or advanced hepatic accuracy.

Language: Английский

Citations

15
The Proteomics of MASLD Progression: Insights From Functional Analysis to Drive the Development of New Therapeutic Solutions DOI Creative Commons
Carlos J. Pirola, Tomas Fernández Gianotti, Silvia Sookoian

et al.

Alimentary Pharmacology & Therapeutics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading chronic worldwide, with alarming prevalence reaching epidemic proportions.

Language: Английский

Citations

1
Unraveling Metabolic Dysfunction-Associated Steatotic Liver Disease Through the Use of Omics Technologies DOI Open Access
Maria V. Bourganou, Maria Chondrogianni, Ioannis Kyrou

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1589 - 1589

Published: Feb. 13, 2025

Non-alcoholic fatty liver disease (NAFLD), now referred to as metabolic dysfunction-associated steatotic (MASLD), is the most prevalent disorder globally, linked obesity, type 2 diabetes, and cardiovascular risk. Understanding its potential progression from simple steatosis cirrhosis hepatocellular carcinoma (HCC) crucial for patient management treatment strategies. The disease's complexity requires innovative approaches early detection personalized care. Omics technologies-such genomics, transcriptomics, proteomics, metabolomics, exposomics-are revolutionizing study of MASLD. These high-throughput techniques allow a deeper exploration molecular mechanisms driving progression. Genomics can identify genetic predispositions, whilst transcriptomics proteomics reveal changes in gene expression protein profiles during evolution. Metabolomics offers insights into alterations associated with MASLD, while exposomics links environmental exposures MASLD pathology. By integrating data various omics platforms, researchers map out intricate biochemical pathways involved This review discusses roles technologies enhancing understanding highlights diagnostic therapeutic targets within spectrum, emphasizing need non-invasive tools staging development.

Language: Английский

Citations

1
Systems Biology Approach Uncovers Candidates for Liver-Heart Interorgan Crosstalk in HFpEF DOI

Stefano Strocchi,

Luo Liu, Rongling Wang

et al.

Circulation Research, Journal Year: 2024, Volume and Issue: 135(8), P. 873 - 876

Published: Aug. 29, 2024

Language: Английский

Citations

5
Exploring Biomarkers in Nonalcoholic Fatty Liver Disease Among Individuals With Type 2 Diabetes Mellitus DOI
Fariba Ahmadizar, Zobair M. Younossi

Journal of Clinical Gastroenterology, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Integrating biomarkers into a comprehensive strategy is crucial for precise patient management, especially considering the significant healthcare costs associated with diseases. Current studies emphasize urgent need paradigm shift in conceptualizing nonalcoholic fatty liver disease (NAFLD), now renamed metabolic dysfunction–associated steatotic (MASLD). Biomarkers are emerging as indispensable tools accurate diagnosis, risk stratification, and monitoring progression. This review classifies conventional novel categories, such lipids, insulin resistance, hepatic function, cutting-edge imaging/omics, evaluates their potential to transform approach MASLD among individuals type 2 diabetes mellitus (T2D). It focuses on critical role of early detection, enhancing predictive accuracy, discerning responses interventions (pharmacological or lifestyle modifications). Amid this discussion, complexities relationship between T2D explored, factors like age, gender, genetics, ethnicity, socioeconomic background. enhance effectiveness support global initiatives reduce burden MASLD, thereby improving public health outcomes. recognizes promising diagnostic precision while candidly addressing challenges implementing these advancements clinical practice. The transformative emerges central theme, reshape our understanding trajectories, prognosis, customization personalized therapeutic strategies improved From future perspective, identifying early-stage biomarkers, environmental impact through exposomes, applying multiomics may reveal additional insight development.

Language: Английский

Citations

5