Dynamic changes of gut microbiota in mouse models of metabolic dysfunction‐associated steatohepatitis and its transition to hepatocellular carcinoma DOI

Yu‐Li Wang,

Chang Liu, Yongyu Yang

и другие.

The FASEB Journal, Год журнала: 2024, Номер 38(13)

Опубликована: Июль 5, 2024

Abstract Dysbiosis of gut microbiota may account for pathobiology in simple fatty liver (SFL), metabolic dysfunction‐associated steatohepatitis (MASH), fibrotic progression, and transformation to MASH‐associated hepatocellular carcinoma (MASH‐HCC). The aim the present study is investigate dysbiosis this progression. Fecal microbial rRNA‐16S sequencing, absolute quantification, histopathologic, biochemical tests were performed mice fed high fat/calorie diet plus fructose glucose drinking water (HFCD‐HF/G) or control (CD) 2, 16 weeks, 14 months. Histopathologic examination verified an early stage SFL, MASH, fibrotic, MASH‐HCC progression with disturbance lipid metabolism, injury, impaired mucosal barrier as indicated by loss occludin ileum mucosa. Gut occurred 2 weeks reduced α diversity, expansion Kineothrix , Lactococcus Akkermansia ; shrinkage Bifidobacterium Lactobacillus etc., at a genus level. was found MAHS initiation, much more profound through MASH‐fibrotic oncogenic Moreover, specific species, such johnsonii alysoides confirmed optimized method quantification. Dynamic alterations characterized three stages its HCC transformation. findings suggest that extent accompanied MASH HCC, shrinking emerging species least part pathologic, metabolic, immunologic fibrogenic malignant transition liver.

Язык: Английский

MASLD: a systemic metabolic disorder with cardiovascular and malignant complications DOI Open Access
Giovanni Targher, Christopher D. Byrne, Herbert Tilg

и другие.

Gut, Год журнала: 2024, Номер unknown, С. gutjnl - 330595

Опубликована: Янв. 16, 2024

Non-alcoholic fatty liver disease (NAFLD) has rapidly become the most common chronic globally and is currently estimated to affect up 38% of global adult population. NAFLD a multisystem where systemic insulin resistance related metabolic dysfunction play pathogenic role in development its relevant liver-related morbidities (cirrhosis, failure hepatocellular carcinoma) extrahepatic complications, such as cardiovascular (CVD), type 2 diabetes mellitus, kidney disease, certain types cancers. In 2023, three large multinational associations proposed that dysfunction-associated steatotic (MASLD) should replace term NAFLD; name chosen non-alcoholic steatohepatitis was (MASH). Emerging epidemiological evidence suggests an excellent concordance rate between MASLD definitions—that is, ~99% individuals with meet criteria. this narrative review, we provide overview literature on (a) recent data risk developing CVD malignant (b) underlying mechanisms by which (and factors strongly linked MASLD) may increase these complications (c) diagnosis assessment potential treatments reduce people or MASH.

Язык: Английский

Процитировано

242
Aetiology of liver disease and response to immune checkpoint inhibitors: An updated meta-analysis confirms benefit in those with non-viral liver disease DOI
Tim Meyer,

Sevasti Galani,

Andre Lopes

и другие.

Journal of Hepatology, Год журнала: 2023, Номер 79(2), С. e73 - e76

Опубликована: Апрель 21, 2023

Язык: Английский

Процитировано

46
Gut microbiota modulate CD8 + T cell immunity in gastric cancer through Butyrate/GPR109A/HOPX DOI Creative Commons
Xiang Yu,

Jinzhou Ou,

Lingzhi Wang

и другие.

Gut Microbes, Год журнала: 2024, Номер 16(1)

Опубликована: Фев. 6, 2024

The gut microbiota and Short-chain fatty acids (SCFAs) can influence the progression of diseases, yet role these factors on gastric cancer (GC) remains uncertain. In this work, analysis composition SCFA content in blood feces both healthy individuals GC patients indicated that significant reductions abundance intestinal bacteria involved production were observed compared with controls. ABX mice transplanted fecal from developed more tumors during induction had lower levels butyric acid. Supplementation butyrate along H. pylori N-methyl-N-nitrosourea (MNU) WT GPR109A−/−mice resulted fewer IFN-γ+ CD8+ T cells, but effect was significantly weakened after knockout GPR109A. Furthermore, vitro cells co-cultured or CAR-Claudin 18.2+ as well vivo tumor-bearing studies, have enhanced killing function against through G protein-coupled receptor 109A (GPR109A) homologous domain protein box (HOPX). Together, data highlighted restoration microbial cell cytotoxicity via GPR109A/HOPX, thus inhibiting carcinogenesis, which suggests a novel theoretical foundation for management GC.

Язык: Английский

Процитировано

28
Pharmacological therapy of metabolic dysfunction-associated steatotic liver disease-driven hepatocellular carcinoma DOI Creative Commons
Yumin Wang, Joshua S. Fleishman,

Tongda Li

и другие.

Frontiers in Pharmacology, Год журнала: 2024, Номер 14

Опубликована: Янв. 19, 2024

In light of a global rise in the number patients with type 2 diabetes mellitus (T2DM) and obesity, non-alcoholic fatty liver disease (NAFLD), now known as metabolic dysfunction-associated (MAFLD) or steatotic (MASLD), has become leading cause hepatocellular carcinoma (HCC), annual occurrence MASLD-driven HCC expected to increase by 45%–130% 2030. Although MASLD serious major public health threat globally, exact molecular mechanisms mediating remain an open problem, necessitating future investigation. Meanwhile, emerging studies are focusing on utility bioactive compounds halt progression HCC. this review, we first briefly review recent progress possible pathogenesis for We then discuss application mitigate through different modulatory encompassing anti-inflammatory, lipid metabolic, gut microbial pathways, providing valuable information treatment prevention Nonetheless, clinical research exploring effectiveness herbal medicines is still warranted.

Язык: Английский

Процитировано

11
Advances and challenges in molecular understanding, early detection, and targeted treatment of liver cancer DOI

Ji Shi,

Xu Zhu, Jun‐Bo Yang

и другие.

World Journal of Hepatology, Год журнала: 2025, Номер 17(1)

Опубликована: Янв. 6, 2025

In this review, we explore the application of next-generation sequencing in liver cancer research, highlighting its potential modern oncology. Liver cancer, particularly hepatocellular carcinoma, is driven by a complex interplay genetic, epigenetic, and environmental factors. Key genetic alterations, such as mutations TERT, TP53, CTNNB1, alongside epigenetic modifications DNA methylation histone remodeling, disrupt regulatory pathways promote tumorigenesis. Environmental factors, including viral infections, alcohol consumption, metabolic disorders nonalcoholic fatty disease, enhance hepatocarcinogenesis. The tumor microenvironment plays pivotal role progression therapy resistance, with immune cell infiltration, fibrosis, angiogenesis supporting survival. Advances checkpoint inhibitors chimeric antigen receptor T-cell therapies have shown potential, but unique immunosuppressive milieu presents challenges. Dysregulation Wnt/β-catenin underscores need for targeted therapeutic strategies. Next-generation accelerating identification enabling more precise diagnosis personalized treatment plans. A deeper understanding these molecular mechanisms essential advancing early detection developing effective against cancer.

Язык: Английский

Процитировано

1
Single-cell transcriptome analysis of liver immune microenvironment changes induced by microplastics in mice with non-alcoholic fatty liver DOI Creative Commons
Wangrui Liu, Meng Li, Huaqi Guo

и другие.

The Science of The Total Environment, Год журнала: 2023, Номер 912, С. 168308 - 168308

Опубликована: Ноя. 15, 2023

Recent studies have discovered that tiny particles of microplastics (MPs) at the nano-scale level can enter body organisms from environment, potentially causing metabolic ailments. However, further investigation is required to understand alterations in immune microenvironment associated with non-alcoholic fatty liver disease (NAFLD) occurrence following exposure MPs. Experiments were performed using mice, which given a normal chow or high-fat diet (NCD HFD, respectively) plus free drinking sterile water without MPs, respectively. Employing an impartial technique known as unbiased single-cell RNA-sequencing (scRNA-seq), cellular (single-cell) pathology landscape NAFLD and related changes identified cell populations induced MPs HFD treatment assessed. The results showed mice groups had remarkably greater activity scores than those NCD groups. Moreover, administration worsened histopathological mice's liver, leading hepatic steatosis, inflammatory infiltrations ballooning degeneration. Following construction sing-cell resolution transcriptomic atlas 43,480 cells livers indicated groups, clear heterogeneity potential cell-to-cell cross-talk could be observed. Specifically, we observed exacerbated pro-inflammatory response influenced stemness hepatocytes during feeding. Importantly, significantly increase infiltration infiltrating liver-protecting Vsig4

Язык: Английский

Процитировано

21
Macrophage metabolism in nonalcoholic fatty liver disease DOI Creative Commons
Wenhui Zhang, Ren Lang

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Окт. 4, 2023

Nonalcoholic fatty liver disease (NAFLD) and its inflammatory often progressive subtype nonalcoholic steatohepatitis (NASH), have emerged as significant contributors to hepatic morbidity worldwide. The pathophysiology of NAFLD/NASH is multifaceted, variable, remains incompletely understood. pivotal role liver-resident recruited macrophages in the pathogenesis NAFLD NASH widely acknowledged a crucial factor innate immunity. remarkable plasticity enables them assume diverse activation polarization states, dictated by their immunometabolism microenvironment functional requirements. Recent studies field elucidated that alterations metabolic profile can profoundly influence state functionality, thereby influencing various pathological processes. This review primarily focuses on elucidating states macrophages, highlighting correlation between characteristics transition from pro-inflammatory anti-inflammatory phenotypes. Additionally, we explore potential targeting macrophage metabolism promising therapeutic approach for management NAFLD/NASH.

Язык: Английский

Процитировано

16
The multiple mechanisms and therapeutic significance of rutin in metabolic dysfunction-associated fatty liver disease (MAFLD) DOI

Qianzhuo Wang,

Yingjuan Zhang,

Ruiling Lu

и другие.

Fitoterapia, Год журнала: 2024, Номер 178, С. 106178 - 106178

Опубликована: Авг. 15, 2024

Язык: Английский

Процитировано

6
Drp1: Focus on Diseases Triggered by the Mitochondrial Pathway DOI

Fulin Sun,

Min Fang, Huhu Zhang

и другие.

Cell Biochemistry and Biophysics, Год журнала: 2024, Номер 82(2), С. 435 - 455

Опубликована: Март 4, 2024

Язык: Английский

Процитировано

5
Prognostic significance of hemoglobin, albumin, lymphocyte, and platelet (HALP) score in breast cancer: a propensity score-matching study DOI Creative Commons
Tongchao Jiang, Haishuang Sun, Shuyu Xue

и другие.

Cancer Cell International, Год журнала: 2024, Номер 24(1)

Опубликована: Июль 2, 2024

The hemoglobin-albumin-lymphocyte-platelet (HALP) score functions as a comprehensive index that assesses the systemic inflammatory response, nutritional, and immune status. This study aimed to explore relationship between preoperative HALP prognosis of BC patients develop predictive nomograms.

Язык: Английский

Процитировано

5