Roles and Mechanisms of Choline Metabolism in Nonalcoholic Fatty Liver Disease and Cancers DOI Creative Commons
Xin Chen, Wenying Qiu,

Xuqian Ma

et al.

Frontiers in Bioscience-Landmark, Journal Year: 2024, Volume and Issue: 29(5)

Published: May 11, 2024

Choline participates in three major metabolic pathways: oxidation, phosphorylation, and acetylation. Through choline is converted to betaine contributes methyl metabolism epigenetic regulation. phospholipid metabolism, serves as the precursor of phosphocholine, phosphatidylcholine, glycerophosphocholine, other essential compounds, thereby modulating lipid transport. acetylation, transformed into acetylcholine cholinergic neurons, playing a vital role neurotransmission. Moreover, gut microbiota can metabolize trimethylamine-N-oxide, be involved pathogenesis various diseases such nonalcoholic fatty liver disease (NAFLD), cancer, cardiovascular disease, etc. Since implicated development NAFLD diverse cancers, including it may serve therapeutic target for these future. Currently, there are numerous agents targeting treat but most them ineffective some even have adverse effects that lead series complications. Therefore, further research clinical validation required obtain safe efficacious drugs. This review comprehensively summarizes pathway its regulatory mechanisms, elucidates roles mechanisms aforementioned diseases, provides discussion current advances immense potential this field.

Language: Английский

The Role of Short Chain Fatty Acids in Inflammation and Body Health DOI Open Access

Yuhang Du,

Changhao He, Yongcheng An

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 7379 - 7379

Published: July 5, 2024

Short chain fatty acids (SCFAs), mainly including acetate, propionate and butyrate, are produced by intestinal bacteria during the fermentation of partially digested indigestible polysaccharides. SCFAs play an important role in regulating energy metabolism maintaining homeostasis environment also regulatory organs tissues outside gut. In recent years, many studies have shown that can regulate inflammation affect host health, two main signaling mechanisms been identified: activation G-protein coupled receptors (GPCRs) inhibition histone deacetylase (HDAC). addition, a growing body evidence highlights importance every SCFA influencing health maintenance disease development. this review, we summarized advances concerning biological properties their pathways health. Hopefully, it provide systematic theoretical basis for nutritional prevention treatment human diseases.

Language: Английский

Citations

47
Lactobacillus acidophilus suppresses non-alcoholic fatty liver disease-associated hepatocellular carcinoma through producing valeric acid DOI Creative Commons
Harry Cheuk-Hay Lau, Xiang Zhang, Fenfen Ji

et al.

EBioMedicine, Journal Year: 2024, Volume and Issue: 100, P. 104952 - 104952

Published: Jan. 4, 2024

Gut probiotic depletion is associated with non-alcoholic fatty liver disease-associated hepatocellular carcinoma (NAFLD-HCC). Here, we investigated the prophylactic potential of Lactobacillus acidophilus against NAFLD-HCC.

Language: Английский

Citations

46
Molecular mechanisms in MASLD/MASH-related HCC DOI
Xiaobo Wang, Liang Zhang, Bingning Dong

et al.

Hepatology, Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 13, 2024

Liver cancer is the third leading cause of cancer-related deaths and ranks as sixth most prevalent type globally. NAFLD or metabolic dysfunction-associated steatotic liver disease, its more severe manifestation, NASH steatohepatitis (MASH), pose a significant global health concern, affecting approximately 20%-25% population. The increased prevalence disease MASH parallel to increasing rates obesity-associated diseases, including 2 diabetes, insulin resistance, fatty diseases. can progress MASH-related HCC (MASH-HCC) in about 2% cases each year, influenced by various factors such genetic mutations, carcinogen exposure, immune microenvironment, microbiome. MASH-HCC exhibits distinct molecular characteristics compared other causes affects both men women equally. management early intermediate-stage typically involves surgery locoregional therapies, while advanced treated with systemic anti-angiogenic therapies checkpoint inhibitors. In this comprehensive review, we consolidate previous research findings also providing current insights into intricate processes underlying development. We delve MASH-HCC-associated variations somatic progression models, multiomics analysis, immunological microenvironmental impacts, discuss targeted/combined overcome evasion biomarkers recognize treatment responders. By furthering our comprehension mechanisms MASH-HCC, goal catalyze advancement potent strategies, ultimately enhanced patient outcomes.

Language: Английский

Citations

43
Bifidobacterium breve-derived indole-3-lactic acid ameliorates colitis-associated tumorigenesis by directing the differentiation of immature colonic macrophages DOI Creative Commons
Yuke Li, Qingxiang Li,

Ruoshui Yuan

et al.

Theranostics, Journal Year: 2024, Volume and Issue: 14(7), P. 2719 - 2735

Published: Jan. 1, 2024

Aim: To elucidate dynamics and functions in colonic macrophage subsets, their regulation by Bifidobacterium breve (B.breve) its associated metabolites the initiation of colitis-associated colorectal cancer (CAC).Methods: Azoxymethane (AOM) dextran sodium sulfate (DSS) were used to create a CAC model.The tumor-suppressive effect B. variations subsets evaluated.Intestinal macrophages ablated determine role protective effects breve.Efficacious molecules produced identified non-targeted targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis.The molecular mechanism was further verified murine bone marrow-derived (BMDMs), derived from human peripheral blood mononuclear cells (hPBMCs), demonstrated mice.Results: alleviated colitis symptoms, delayed tumorigenesis, promoted phenotypic differentiation immature inflammatory into mature homeostatic macrophages.On contrary, ablation intestinal largely annulled breve.Microbial analysis contents revealed enrichment probiotics depletion potential pathogens following supplementation.Moreover, indole-3-lactic acid (ILA) positively correlated with mice highly enriched culture supernatant breve.Also, addition ILA directly AKT phosphorylation restricted pro-inflammatory response BMDMs hPBMCs vitro.The abolished aryl hydrocarbon receptor (AhR) antagonist CH-223191 or inhibitor MK-2206.Furthermore, could protect against tumorigenesis regulating mice; AhR abrogated relieving tumorigenesis.Conclusion: breve-mediated tryptophan metabolism ameliorates precancerous milieu inhibit directing macrophages.

Language: Английский

Citations

22
Interplay between gut microbiome, host genetic and epigenetic modifications in MASLD and MASLD-related hepatocellular carcinoma DOI

Suki Ha,

Vincent Wai‐Sun Wong, Xiang Zhang

et al.

Gut, Journal Year: 2024, Volume and Issue: 74(1), P. 141 - 152

Published: June 29, 2024

Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a wide spectrum of injuries, ranging from hepatic steatosis, metabolic steatohepatitis (MASH), fibrosis, cirrhosis to MASLD-associated hepatocellular carcinoma (MASLD-HCC). Recent studies have highlighted the bidirectional impacts between host genetics/epigenetics and gut microbial community. Host genetics influence composition microbiome, while microbiota their derived metabolites can induce epigenetic modifications affect development MASLD. The exploration intricate relationship microbiome genetic/epigenetic makeup is anticipated yield promising avenues for therapeutic interventions targeting MASLD its associated conditions. In this review, we summarise effects alterations in MASLD-HCC. We further discuss research findings demonstrating genetics/epigenetics, emphasising significance interconnection prevention treatment.

Language: Английский

Citations

21
Role of Probiotics against Human Cancers, Inflammatory Diseases, and Other Complex Malignancies DOI Open Access
Hammad Naeem,

Hammad Ul Hassan,

Muhammad Shahbaz

et al.

Journal of Food Biochemistry, Journal Year: 2024, Volume and Issue: 2024, P. 1 - 23

Published: Feb. 7, 2024

Probiotics have growing medical importance as a result of their potential in the prevention and therapeutic support several complex diseases, including different types cancers. The anticarcinogenic properties probiotics are attributed to various mechanisms, alterations composition intestinal microbiota, suppression cell proliferation, stimulation apoptosis, inhibition NF-kB, reduction levels H2AX, 8-hydroxy-deoxyguanosine, RIG-I, downregulation IL-17, TNF signaling pathway. Furthermore, demonstrated significant advantages management other diabetes, obesity, cardiovascular diseases. had considerable effect reducing inflammatory infiltration occurrence precancerous lesions. Additionally, administration led decrease appearance level genes related proinflammatory pathways, NF-κB, pathways. However, further research studies required comprehend processes via which exert effects authenticate alternative interventions.

Language: Английский

Citations

17
Hepatocellular carcinoma: signaling pathways and therapeutic advances DOI Creative Commons

Jiaojiao Zheng,

Siying Wang, Lei Xia

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Feb. 6, 2025

Abstract Liver cancer represents a major global health concern, with projections indicating that the number of new cases could surpass 1 million annually by 2025. Hepatocellular carcinoma (HCC) constitutes around 90% liver and is primarily linked to factors incluidng aflatoxin, hepatitis B (HBV) C (HCV), metabolic disorders. There are no obvious symptoms in early stage HCC, which often leads delays diagnosis. Therefore, HCC patients usually present tumors advanced incurable stages. Several signaling pathways dis-regulated cause uncontrolled cell propagation, metastasis, recurrence HCC. Beyond frequently altered therapeutically targeted receptor tyrosine kinase (RTK) involved differentiation, telomere regulation, epigenetic modification stress response also provide therapeutic potential. Investigating key their inhibitors pivotal for achieving advancements management At present, primary approaches (TKI), immune checkpoint (ICI), combination regimens. New trials investigating therapies involving ICIs TKIs or anti-VEGF (endothelial growth factor) therapies, as well combinations two immunotherapy The outcomes these expected revolutionize across all Here, we here comprehensive review cellular pathways, potential, evidence derived from late-stage clinical discuss concepts underlying earlier trials, biomarker identification, development more effective therapeutics

Language: Английский

Citations

6
Liver diseases: epidemiology, causes, trends and predictions DOI Creative Commons

Can Gan,

Yuan Yuan, Haiyuan Shen

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Feb. 4, 2025

Abstract As a highly complex organ with digestive, endocrine, and immune-regulatory functions, the liver is pivotal in maintaining physiological homeostasis through its roles metabolism, detoxification, immune response. Various factors including viruses, alcohol, metabolites, toxins, other pathogenic agents can compromise function, leading to acute or chronic injury that may progress end-stage diseases. While sharing common features, diseases exhibit distinct pathophysiological, clinical, therapeutic profiles. Currently, contribute approximately 2 million deaths globally each year, imposing significant economic social burdens worldwide. However, there no cure for many kinds of diseases, partly due lack thorough understanding development these Therefore, this review provides comprehensive examination epidemiology characteristics covering spectrum from conditions manifestations. We also highlight multifaceted mechanisms underlying initiation progression spanning molecular cellular levels networks. Additionally, offers updates on innovative diagnostic techniques, current treatments, potential targets presently under clinical evaluation. Recent advances pathogenesis hold critical implications translational value novel strategies.

Language: Английский

Citations

3
Current Therapeutic Landscape for Metabolic Dysfunction-Associated Steatohepatitis DOI Open Access

Arun George Devasia,

Adaikalavan Ramasamy, Chen Huei Leo

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1778 - 1778

Published: Feb. 19, 2025

In recent years, “metabolic dysfunction-associated steatotic liver disease” (MASLD) has been proposed to better connect disease metabolic dysfunction, which is the most common chronic worldwide. MASLD affects more than 30% of individuals globally, and it diagnosed by combination hepatic steatosis obesity, type 2 diabetes, or two risk factors. begins with buildup extra fat, often greater 5%, within liver, causing hepatocytes become stressed. This can proceed a severe form, steatohepatitis (MASH), in 20–30% people, where inflammation causes tissue fibrosis, limits blood flow over time. As fibrosis worsens, MASH may lead cirrhosis, failure, even cancer. While pathophysiology not fully known, current “multiple-hits” concept proposes that dietary lifestyle factors, genetic epigenetic factors contribute elevated oxidative stress inflammation, fibrosis. review article provides an overview pathogenesis evaluates existing therapies as well pharmacological drugs are currently being studied clinical trials for MASH.

Language: Английский

Citations

2
Gut–X axis DOI Creative Commons
Lin Xu, Yu Zhang, Xueyan Li

et al.

iMeta, Journal Year: 2025, Volume and Issue: 4(1)

Published: Feb. 1, 2025

Abstract Recent advances in understanding the modulatory functions of gut and microbiota on human diseases facilitated our focused attention contribution to pathophysiological alterations many extraintestinal organs, including liver, heart, brain, lungs, kidneys, bone, skin, reproductive, endocrine systems. In this review, we applied “gut–X axis” concept describe linkages between other organs discussed latest findings related axis,” underlying mechanisms potential clinical intervention strategies.

Language: Английский

Citations

2