iMeta, Journal Year: 2024, Volume and Issue: 3(6)
Published: Dec. 1, 2024
Gut microbiome is crucial for lipid metabolism in humans and animals. However, how specific gut microbiota their associated metabolites impact fat deposition remains unclear. In this study, we demonstrated that the colonic of lean obese pigs differentially contributes to deposition, as evidenced by transplantation experiments. Notably, higher abundance
Language: Английский
Circulation Research, Journal Year: 2024, Volume and Issue: 135(12), P. 1161 - 1174
Published: Oct. 28, 2024
BACKGROUND: Given the growing acknowledgment of detrimental effects excessive myocardial fibrosis on pathological remodeling after ischemia-reperfusion injury (I/R), targeting modulation may offer protective and therapeutic advantages. However, effective clinical interventions therapies that target remain limited. As a promising chimeric antigen receptor (CAR) cell therapy, whether CAR macrophages (CAR-Ms) can be used to treat I/R remains unclear. METHODS: The expression FAP (fibroblast activation protein) was studied in mouse hearts I/R. CAR-Ms were generated FAP-expressing cardiac fibroblasts phagocytosis activity tested vitro. efficacy safety treating evaluated vivo. RESULTS: significantly upregulated activated as early 3 days Upon demonstrating their ability engulf FAP-overexpressing fibroblasts, we intravenously administered mice at found improved function reduced No toxicities associated with detected heart or other organs 2 weeks Finally, conferred long-term cardioprotection against CONCLUSIONS: Our proof-of-concept study demonstrates potential alleviating potentially opens new avenues for treatment range diseases include fibrotic phenotype.
Language: Английский
Citations
6
Clinical Epigenetics, Journal Year: 2024, Volume and Issue: 16(1)
Published: Nov. 29, 2024
The gut microbiota (GM) plays a critical role in regulating human physiology, with dysbiosis linked to various diseases, including heart failure (HF). HF is complex syndrome significant global health impact, as its incidence doubles each decade of life, and prevalence peaks individuals over 80 years. A bidirectional interaction exists between GM HF, where alterations can worsen the disease's progression. "gut hypothesis HF" suggests that HF-induced changes, such reduced intestinal perfusion altered motility, negatively impact composition, leading increased permeability, release GM-derived metabolites into bloodstream, systemic inflammation. This process creates vicious cycle further deteriorates function. metabolites, trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), secondary bile (BAs), influence gene expression through epigenetic mechanisms, DNA methylation histone modifications. These changes may play crucial mediating effects dysbiotic microbial linking them cardiac contributing progression HF. particularly relevant older individuals, aging itself has been associated both cumulative alterations, intensifying interplay GM, increasing risk elderly. Despite growing body evidence, modifications, remains poorly understood. dynamic nature epigenetics shaped by factors age, diet, lifestyle, presents challenges elucidating precise mechanisms underlying this relationship. Future research should prioritize innovative approaches overcome these limitations. By identifying specific metabolite-induced modifications modulating composition function novel personalized therapeutic strategies for prevention and/or treatment be developed. Moreover, targeted focusing specifically on understanding intricate connections epigenetics, during aging.
Language: Английский
Citations
6
Advanced Science, Journal Year: 2025, Volume and Issue: unknown
Published: March 16, 2025
Abstract Myocardial ischemia/reperfusion (I/R) injury is a major contributor to myocardial damage, leading adverse cardiac remodeling and dysfunction. Recent studies have highlighted the potential of gut microbiota‐derived metabolites in modulating outcomes. Here, cardioprotective effects commensal bacterium Flavonifractor plautii ( F. ) its metabolite desaminotyrosine (DAT) against I/R are investigated. We showed that prophylactic gavage attenuates as evidenced by improved function reduced injury. also found DAT recapitulates these Transcriptomic analysis has revealed preserves tissue immune responses Mechanistically, promotes cardiomyocyte survival through modulation nicotinamide adenine dinucleotide phosphate (NADP + /NADPH) ratio. Further, suppressed macrophage proinflammatory activities inflammation via reduction interleukin‐6 (IL‐6) production. Taken together, our findings indicate exert pleiotropic injury, suggesting them therapeutic options for alleviating
Language: Английский
Citations
0
Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)
Published: March 27, 2025
Heart injury has been characterized by the irreversible loss of cardiomyocytes comprising contractile tissues heart and thus strategies enabling adult cardiomyocyte proliferation are highly desired for treating various diseases. Here, we test ability human induced pluripotent stem cell-derived primitive macrophages (hiPMs) their conditioned medium (hiPM-cm) to promote enhance cardiac regeneration in mice. We find that hiPMs proliferation, which is recapitulated hiPM-cm through activation multiple pro-proliferative pathways, a secreted proteome analysis identifies five proteins participating this activation. Subsequent vivo experiments show promotes Lastly, enhances improves function injured mouse hearts. Together, our study demonstrates efficacy using promoting serve as an innovative treatment disease. Reactivating key post-injury. authors from iPSC-derived induces regeneration.
Language: Английский
Citations
0
World Journal of Cardiology, Journal Year: 2025, Volume and Issue: 17(4)
Published: April 21, 2025
Heart failure (HF) has emerged as one of the foremost global health threats due to its intricate pathophysiological mechanisms and multifactorial etiology. Adenosine triphosphate (ATP)-induced cell death represents a novel form regulated deaths, marked by cellular energy depletion metabolic dysregulation stemming from excessive ATP accumulation, identifying uniqueness compared other processes modalities such programmed necrosis. Growing evidence suggests that ATP-induced (AICD) is predominantly governed various biological pathways, including metabolism, redox homeostasis intracellular calcium equilibrium. Recent research shown AICD crucial in HF induced pathological conditions like myocardial infarction, ischemia-reperfusion injury, chemotherapy. Thus, it essential investigate function pathogenesis HF, this may provide foundation for development targeted therapies treatment strategies. This review synthesizes current advancements understanding link between while further elucidating involvement cardiac remodeling progression.
Language: Английский
Citations
0
Nutrients, Journal Year: 2024, Volume and Issue: 16(21), P. 3706 - 3706
Published: Oct. 30, 2024
: This review investigates the impact of bioactive molecules produced by probiotics on child health, focusing their roles in modulating gut microbiota, enhancing immune function, and supporting overall development. Key metabolites, including short-chain fatty acids (SCFAs), bacteriocins, exopolysaccharides (EPSs), vitamins, gamma-aminobutyric acid (GABA), are highlighted for ability to maintain regulate inflammation, support neurodevelopment.
Language: Английский
Citations
3
Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)
Published: Aug. 27, 2024
The kidney is vulnerable to ischemia and reperfusion (I/R) injury that can be fatal after major surgery. Currently, there are no effective treatments for I/R-induced injury. Trimethylamine N-oxide (TMAO) a gut-derived metabolite linked many diseases, but its role in remains unclear. Here, our clinical data reveals an association between preoperative systemic TMAO levels postoperative patients post-cardiopulmonary bypass By genetic deletion of TMAO-producing enzyme flavin-containing monooxygenase 3 (FMO3) dietary supplementation choline modulate levels, we found aggravated acute through the triggering endoplasmic reticulum (ER) stress worsened subsequent renal fibrosis TGFβ/Smad signaling activation. Together, study underscores negative highlights therapeutic potential modulation by targeting FMO3, thereby mitigating preventing fibrosis. This elucidates FMO3 as approach
Language: Английский
Citations
1
iMeta, Journal Year: 2024, Volume and Issue: 3(6)
Published: Dec. 1, 2024
Gut microbiome is crucial for lipid metabolism in humans and animals. However, how specific gut microbiota their associated metabolites impact fat deposition remains unclear. In this study, we demonstrated that the colonic of lean obese pigs differentially contributes to deposition, as evidenced by transplantation experiments. Notably, higher abundance
Language: Английский
Citations
1