👤 Andżelika Borkowska

Exercise-induced inflammation has been shown to influence iron metabolism. Conversely, ischemic preconditioning (IPC) has been proposed as a strategy to modulate post-exercise response, especially inflammation and neurotrophic factor secretion. In this study we analyzed the effects of a 14-days IPC intervention on the post-exercises changes of the selected Iron metabolism, inflammation and neurotrophic markers in the population of non-training healthy young man. Forty healthy, untrained young men voluntarily participated in this study and were randomly assigned to two groups: an IPC group (n = 20), which underwent a 14-day IPC intervention, and a placebo (SHAM) group (n = 20). Five participants from the IPC group and seven from the SHAM group did not complete the protocol and were excluded from the analyzes. Venous blood samples were collected at rest, immediately after and 2 h after the Wingate test. Selected inflammatory and neurotrophic markers were analyzed, including IL-6, IL-10, IL-15, LIF, BDNF, IGF-1, NGF, sAPPα, FSTL-1, and GDF-15. Additionally, serum levels of iron (Fe), hepcidin (Hpc), ferritin (Fer), erythroferrone (ERFE), and erythropoietin (EPO) were assessed. IPC increased resting ferritin (~ + 9%, p < 0.05), hepcidin (~ + 12%, p < 0.05), and erythroferrone (~ + 10%, p < 0.05) concentrations. The intervention also enhanced post-exercise IGF-1 (+ 8%, p = 0.03) and sAPPα (+ 10%, p = 0.04) release and reshaped cytokine profiles, with greater early elevations of GDF-15 and IL-15 (p < 0.05) and faster normalization of FSTL-1 within 2 h (p < 0.05). IPC further affected neurotrophic signaling, showing lower 2-h post-exercise BDNF levels (p < 0.05) and distinct IGF-1 kinetics (p < 0.01). Anaerobic performance remained unchanged (p > 0.05). Ischemic preconditioning induces coordinated alterations in iron metabolism and modulates inflammatory and neurotrophic responses to anaerobic exercise, without affecting physical performance in untrained individuals. Show less

Neurological disorders cause over 11 million deaths annually worldwide, highlighting the urgent need for new therapeutic strategies to improve current treatment outcomes. Nerve growth factor (NGF) is a key regulator of neuronal survival, and modifying mesenchymal stem cells (MSC) to enhance their neurotrophic activity is a promising therapeutic strategy. However, the broader molecular consequences of NGF overexpression in MSC remain unclear. This study examined how NGF overexpression affects neurotrophin secretion and apoptosis-related protein expression in Wharton's jelly MSC (WJ-MSC). WJ-MSC were lentivirally transduced to overexpress NGF and differentiated for 12 days. NGF, BDNF, TrkA, TrkB, IL-13, and TNF-α were quantified using ELISA (n = 3 biological replicates; assays in duplicate). Thirty-five apoptosis-related proteins were assessed using the Proteome Profiler Human Apoptosis Array (assays in duplicate). Data were analyzed using one-way ANOVA or multiple t-test. NGF overexpression increased extracellular NGF (↑∼220 %, p < 0.0001) and reduced BDNF secretion (↓∼35 %, p < 0.05). Soluble phosphorylated TrkA/TrkB increased significantly in supernatants (↑30-60 %, p < 0.05). IL-13 rose modestly without statistical significance, and TNF-α remained undetectable. Early proteome changes showed upregulation of pro-apoptotic proteins (p21 ↑97 %, phospho-p53 ↑30 %) with concurrent reductions in anti-apoptotic markers (BCL2 ↓66 %, HSP60 ↓58 %). After 12 days, the apoptotic profile remained predominantly pro-apoptotic, despite selective increases in BCLXL (↑92 %), clusterin (↑102 %), and survivin (↑38 %) indicating only partial compensatory responses. NGF overexpression enhances neurotrophin-related signaling but produces a sustained pro-apoptotic shift in WJ-MSC, suggesting limited benefit for cell survival. These findings require confirmation using functional apoptosis assays and in vivo models. Show less

Glucagon-like peptide-1 (GLP-1) is a hormone known for its critical functions in managing blood sugar and offering cardiovascular benefits. Our study focuses on Glucagon Like Peptide 1 Receptor (GLP1R) agonists that act beyond glycemic control in cardiovascular and metabolic health. A comprehensive bioinformatic analysis was conducted, incorporating GLP1R, Gastric Inhibitory Polypeptide Receptor (GIPR), Gastric Inhibitory Polypeptide (GIP) and glucagon receptor (GCGR) to assess the effects of GLP1R agonists on gene and metabolite interactions. Interaction network analysis revealed 130 common genes among GLP1R, GLP1R/GIPR, GLP1R/GIP, and GLP1R/GIPR/GCGR associated with diabetes-related processes, including obesity and hyperglycemia. Enriched terms related to cardiovascular diseases, such as hypertension, calcium regulation in cardiac cells, and amino acid accumulation-induced mTOR activation. We also observed enrichment in gene sets linked to longevity and less recognized terms like fatty liver disease. In GLP1R/GIP, behavior-related terms and gastric acid secretion were identified; GLP1R/GIPR/GCGR linked to fibrosarcoma, thought/speech disturbances, and adipogenesis. The metabolite-gene layer revealed enrichment in galactose metabolism, platelet homeostasis, and nitric-oxide pathways. We found that GLP1R agonists network-level associations are stronger with heart diseases than sodium-glucose co-transporter 2 inhibitors, suggesting greater therapeutic benefits. Integrating networks with metabolites highlighted key interactors and clarified GLP1R agonists' mechanisms and therapeutic potential. Show less

Natural compounds, such as resveratrol (Res), are currently used as adjuvants for anticancer therapies. To evaluate the effectiveness of Res for the treatment of ovarian cancer (OC), we screened the response of various OC cell lines to the combined treatment with cisplatin (CisPt) and Res. We identified A2780 cells as the most synergistically responding, thus optimal for further analysis. Because hypoxia is the hallmark of the solid tumor microenvironment, we compared the effects of Res alone and in combination with CisPt in hypoxia (pO Show less