NGFB

Cardiac fibrosis is a significant driver of congestive heart failure, a syndrome that continues to affect a growing patient population globally. Cardiac fibrosis results from a constellation of complex processes at the transcription, receptor, and signaling axes levels. Various mediators and signaling cascades, such as the transformation growth factor-beta pathway, have been implicated in the pathophysiology of cardiac tissue fibrosis. Our understanding of these markers and pathways has improved in recent years as more advanced technologies and assays have been developed, allowing for better delineation of the crosstalk between specific factors. There is mounting evidence suggesting that epigenetic modulation plays a pivotal role in the progression of cardiac fibrosis. Transcriptional regulation of key pro- and anti-fibrotic pathways can accentuate or blunt the rate and extent of fibrosis at the tissue level. Exosomes, micro-RNAs, and long non-coding RNAs all belong to factors that can impact the epigenetic signature in cardiac fibrosis. Herein, we comprehensively review the latest literature about exosomes, their contents, and cardiac fibrosis. In doing so, we highlight the specific transcriptional factors with pro- or anti-fibrotic properties. We also assimilate the data supporting these mediators' potential utility as diagnostic or prognostic biomarkers. Finally, we offer insight into where further work can be done to fill existing gaps to translate pre-clinical findings better and improve clinical outcomes.

The gut microbiota and inflammatory proteins may affect the development of peptic ulcer disease. However, this association remains unclear. We analyzed genome-wide association study data of gut microbiota, inflammatory proteins, and peptic ulcer disease using Mendelian randomization with instrumental variables to assess causal relationships. Various statistical methods, including inverse variance weighting, Mendelian randomization Egger regression, and sensitivity analysis were employed to evaluate the data and calculate mediation ratios. Our findings reveal that the genus Butyriciccus plays a role in mitigating the adverse effects of gastric ulcers by 7.9%, primarily through reducing beta-negative growth factor levels. Additionally, the genus Lachnospiraceae UCG004 can significantly alleviate the negative outcomes of gastric ulcers and reduces hepatocyte growth factor and beta-reserve growth factor levels by 6.39% and 7.45%, respectively. This study highlights the independent and mediating effects of the gut microbiota and inflammatory proteins on peptic ulcers, offering insights on potential pathways and targets for future preventive interventions.

Inflammatory cytokines and migraines have been associated in previous research, but the underlying mechanisms of action are still elusive. The biological functions of metabolites are crucial in the onset of migraine. Our goals were to clarify the cause-and-effect connection between inflammatory cytokines and migraines and explore the potential mediating function of metabolites.

Utilizing summary-level data from genome-wide association studies (GWAS), we conducted two-sample Mendelian randomization (MR) analyses to evaluate the possible causal connection between inflammatory cytokines and migraines. A two-step MR analysis was employed to further investigate the potential mediating pathways of metabolites.

MR analysis identified a total of 9 inflammatory cytokines that were genetically associated with migraines, and we subsequently identified 21 mediated relationships, with 20 metabolites (13 metabolites, 7 ratios) acting as potential mediators between 8 inflammatory cytokines and migraine. The 9 inflammatory cytokines were beta-nerve growth factor levels (β-NGF), T-cell surface glycoprotein CD5 levels (CD5), T-cell surface glycoprotein CD6 isoform levels (CD6), C-X-C motif chemokine 11 levels (CXCL11), interleukin-4 levels (IL-4), oncostatin-M levels (OSM), signalling lymphocytic activation molecule levels (SLAM), C-C motif chemokine 25 levels (CCL25) and monocyte chemoattractant protein-1 levels (MCP-1).

Our research findings provide evidence for both a causal connection between inflammatory cytokines and migraines, as well as a metabolite-mediated pathway. These biomarkers facilitate the detection, diagnosis and treatment of migraines while offering fresh perspectives on their underlying mechanisms.