The metabolite 2-Methylbutyrylcarnitine does not Promote Atherosclerosis in Apolipoprotein E-Deficient Mice DOI Creative Commons

Jielu Wen,

Zhengde Zhao,

Zhipeng Cen

et al.

BIO Integration, Journal Year: 2024, Volume and Issue: 5(1)

Published: Jan. 1, 2024

Abstract Background: Although 2-methylbutyrylcarnitine (2MBC) has been associated with metabolic disorders and promotes thrombosis, its effect on atherosclerosis remains elusive. This study was aimed at investigating the role of 2MBC in development. Methods Results: Apolipoprotein E-deficient (ApoE −/− ) mice were fed a Western diet for 18 weeks to induce atherosclerosis, then administered once-daily gavage or vehicle weeks. Parameters systemic lipid metabolism detected. did not upregulate plasma total cholesterol (TC), low-density lipoprotein (LDL-C), high-density (HDL-C) levels, triglycerides (TG) levels further upregulated Western-diet-induced treated 2MBC, thus suggesting that this compound may contribute hypertriglyceridemia. In addition, had no development, as evidenced by alterations plaque area, exacerbation local inflammation, effects stability. RAW264.7 macrophages used investigate oxidized lipoprotein-induced foam cell formation vitro. Treatment affect uptake cells. The addition relative mRNA inflammation-associated genes when lipopolysaccharide. destructive vascular endothelium, we stimulated human umbilical vein endothelial cells (HUVECs) (ox-LDL). Ox-LDL alter expression monocyte chemotactic protein-1 adhesion molecule-1. Furthermore, combined ox-LDL stimulation SR-A1 ABCA1 HUVECs. Conclusions: Our provides first evidence does promote increase intravascular exacerbate degree stability ApoE mice.

Language: Английский

Gut Microbiota at the Crossroad of Hepatic Oxidative Stress and MASLD DOI Creative Commons
Fabrizio Termite,

S. Archilei,

Francesca D’Ambrosio

et al.

Antioxidants, Journal Year: 2025, Volume and Issue: 14(1), P. 56 - 56

Published: Jan. 6, 2025

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic condition marked by excessive lipid accumulation in hepatic tissue. This disorder can lead to range of pathological outcomes, including metabolic steatohepatitis (MASH) and cirrhosis. Despite extensive research, the molecular mechanisms driving MASLD initiation progression remain incompletely understood. Oxidative stress peroxidation are pivotal "multiple parallel hit model", contributing cell death tissue damage. Gut microbiota plays substantial role modulating oxidative through multiple pathways: impairing intestinal barrier, which results bacterial translocation inflammation; modifying bile acid structure, impacts signaling cascades involved lipidic metabolism; influencing hepatocytes' ferroptosis, form programmed death; regulating trimethylamine N-oxide (TMAO) activating platelet function, both recently identified as pathogenetic factors MASH progression. Moreover, various exogenous impact gut its involvement MASLD-related stress, such air pollution, physical activity, cigarette smoke, alcohol, dietary patterns. manuscript aims provide state-of-the-art overview focused on intricate interplay between microbiota, peroxidation, pathogenesis, offering insights into potential strategies prevent associated complications.

Language: Английский

Citations

1
Targeted codelivery of nitric oxide and hydrogen sulfide for enhanced antithrombosis efficacy DOI
Weiliang Deng,

Zhixin Xu,

Hua Tong

et al.

Bioactive Materials, Journal Year: 2025, Volume and Issue: 48, P. 29 - 42

Published: Feb. 13, 2025

Language: Английский

Citations

1
The gut microbiota in thrombosis DOI
My Phung Khuu, Nadja Paeslack,

Olga Dremova

et al.

Nature Reviews Cardiology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 17, 2024

Language: Английский

Citations

7
Gut Microbiota and Their Metabolites as Modulators of Vascular Complications in Diabetes DOI Creative Commons

Meng Yun Duan,

Jielu Wen,

Anning Chen

et al.

Published: Jan. 7, 2025

Review Gut Microbiota and Their Metabolites as Modulators of Vascular Complications in Diabetes Meng Duan 1,2,3,†, Jielu Wen 1,2,†, Anning Chen 1,2,† Sifan 1,2,* 1 Guangdong Provincial Key Laboratory Malignant Tumor Epigenetics Gene Regulation, Guangdong-Hong Kong Joint for RNA Medicine, Medical Research Center, Sun Yat-Sen Memorial Hospital, University, Guangzhou 510000, China 2 Nanhai Translational Innovation Center Precision Immunology, Foshan 528200, 3 Zhongshan School Yat-sen * Correspondence: [email protected] † These authors contributed equally to this work. Received: 8 November 2024; Revised: 29 Accepted: 24 December Published: 7 January 2025 Abstract: With the global rise population aging, along with increasing burden overweight obesity, prevalence diabetes is expected surge dramatically. Microvascular macrovascular complications are leading causes death among patients type diabetes. Recent advancements have provided evidence suggesting that gut microbiota directly or indirectly regulate vascular function. This review focuses on complex interactions between its metabolites In particular, we highlight novel therapeutic effects interventions such probiotics, dietary modifications, fecal transplantation improving composition reducing risk findings not only provide new insights into pathological mechanisms diabetic but also reveal ideas guiding formulation future treatment strategies.

Language: Английский

Citations

0
Inhibition of platelet activation process upon tris (2-chloroethyl) phosphate exposure: Role of PFKP-mediated glycolysis and the pentose phosphate pathway DOI
Ziyuan Li, Pu Chen, Yongfeng Lin

et al.

Environmental Pollution, Journal Year: 2025, Volume and Issue: unknown, P. 125714 - 125714

Published: Jan. 1, 2025

Language: Английский

Citations

0
VCP downstream metabolite glycerol-3-phosphate (G3P) inhibits CD8+T cells function in the HCC microenvironment DOI Creative Commons
Cheng Cheng,

Qingrui Zha,

Linmao Sun

et al.

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

Published: Jan. 23, 2025

Abstract CD8 + T cells within the tumor microenvironment (TME) are often functionally impaired, which limits their ability to mount effective anti-tumor responses. However, molecular mechanisms behind this dysfunction remain incompletely understood. Here, we identified valosin-containing protein (VCP) as a key regulator of suppression in hepatocellular carcinoma (HCC). Our findings reveal that VCP suppresses activation, expansion, and cytotoxic capacity both vitro vivo, significantly contributing immunosuppressive nature TME. Mechanistically, stabilizes expression glycerol-3-phosphate dehydrogenase 1-like (GPD1L), leading accumulation (G3P), downstream metabolite GPD1L. The accumulated G3P diffuses into TME directly interacts with SRC-family tyrosine kinase LCK, critical component T-cell receptor (TCR) signaling pathway cells. This interaction heightens phosphorylation Tyr505, inhibitory residue, ultimately reducing LCK activity impairing TCR signaling. Consequently, lose functional capacity, diminishing fight against HCC. Importantly, demonstrated targeting combination anti-PD1 therapy HCC growth restores function cells, suggesting synergistic therapeutic potential. These highlight previously unrecognized mechanism involving suppressing T-cell-mediated immunity TME, positioning promising upstream target for enhancing immunotherapy

Language: Английский

Citations

0
From gut to blood: How microbiome metabolites orchestrate platelet function DOI

Rahul Garg

Journal of Hematology and Allied Sciences, Journal Year: 2025, Volume and Issue: 0, P. 1 - 5

Published: Jan. 30, 2025

The gut microbiome’s role in human health has gained significant attention, particularly regarding its metabolites’ influence on platelet function and cardiovascular health. This comprehensive review examines the complex relationship between microbial metabolites activity, focusing key compounds such as trimethylamine N-oxide, 2-methylbutyrylcarnitine, phenylacetylglutamine. These affect through both direct mechanisms, involving specific receptor interactions calcium signaling pathways, indirect effects systemic inflammation. Recent research revealed that elevated levels of these correlate with increased risk altered response to antiplatelet therapy. Understanding opens new avenues for therapeutic intervention, including targeted metabolic pathway inhibition personalized medicine approaches. While progress been made, continued is needed fully elucidate network microbiome-platelet develop effective strategies.

Language: Английский

Citations

0
Comprehensive review of the expanding roles of the carnitine pool in metabolic physiology: beyond fatty acid oxidation DOI Creative Commons

Feng Xiang,

Zhimin Zhang, Jingchen Xie

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 14, 2025

Traditionally, the carnitine pool is closely related to fatty acid metabolism. However, with increasing research, pleiotropic effects of have gradually emerged. The purpose this review comprehensively investigate emerging understanding role pool, carnitine/acylcarnitines are not only auxiliaries or metabolites oxidation, but also play more complex and diverse roles, including energy metabolism, mitochondrial homeostasis, epigenetic regulation, regulation inflammation immune system, tumor biology, signal transduction, neuroprotection. This provides an overview network synthesis, transport, shuttle, potential be used as communication molecules, biomarkers therapeutic targets for multiple diseases, profound on intercellular communication, metabolic interactions between organs overall health. summarize multidimensional biological beyond its traditional in oxidation systemic mediated by carnitine/acylcarnitine provide new perspectives pharmacological research treatment innovation strategies prevention a variety diseases.

Language: Английский

Citations

0
Elevated Levels of Foreign Microparticles in the Blood of Patients with Digestive System Diseases DOI
Jie Song, Yunqing Wang,

Yunxia Ji

et al.

Environmental Science & Technology Letters, Journal Year: 2025, Volume and Issue: unknown

Published: April 14, 2025

Language: Английский

Citations

0
Microbial metabolites associated in stool and left ventricle of heart failure patients revealed by meta-analysis DOI Creative Commons
Emily Wissel,

Hsin-Yuan Chien,

Ke-Hsuan Wei

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 25, 2025

Language: Английский

Citations

0