Acute ischemic stroke (AIS) is one of the leading causes of death and disabilities, and as such, it is of utmost importance to identify novel treatment options. Current acute treatments for AIS are limited to either thrombectomy or thrombolysis, both of which must be initiated within 4.5-6 hours of symptom onset. Remote ischemic conditioning (RIC) is a promising non-invasive treatment that is thought to activate the body’s own protective mechanisms against damaging ischemia through circulating microRNAs (miRNAs). Here, we investigate the transcriptional changes in human brain microvascular endothelial cells (HBMECs) transfected with four selected RIC-upregulated miRNAs (RIC-miRNAs), miR-16-5p, miR-144-3p, miR-182-5p, and miR-451a, under oxygen and glucose deprivation (OGD) - mimicking the initial stages of AIS. Pronounced transcriptional changes were present after RIC-miRNA transfection, with 149 unique downregulated and 212 upregulated differentially expressed genes in HBMECs after OGD and RIC-miRNA transfection compared to all other conditions. These genes were involved in cell cycle regulation, DNA replication and pathways of energy metabolism. However, we saw no direct effect on cell viability after RIC-miRNA transfection and OGD. In conclusion, our study suggests that the selected RIC-miRNAs regulate pathways that may facilitate endothelial cell recovery and remodeling events from ischemic damage, offering new therapeutic avenues for AIS.

Objective:Polycystic ovary syndrome (PCOS) is characterized by reproductive dysfunctions and metabolic disorders. This study aims to compare the therapeutic effectiveness of glucagon-like peptide-1 receptor agonist (GLP-1RA) + Metformin (Met) versus co-cyprindiol (cyproterone acetate/ethinylestradiol, CPA/EE) + Met in overweight PCOS women and identify potential biomarkers. Methods: In this prospective, open-label randomized controlled trial, we recruited 60 overweight PCOS women into two groups at a 1:1 ratio to receive CPA/EE (2 mg/day) + Met (1,500 mg/day) or GLP-1RA (liraglutide, 0.6-1.2 mg/day) + Met (1,500 mg/day) for 12 weeks. The clinical effectiveness and adverse effects were evaluated, followed by plasma proteomic analysis and verification of critical biomarkers by ELISA. Results: Both interventions improved menstrual cycle, polycystic ovaries, LH levels, and LH/FSH ratio; meanwhile reduced the body weight, BMI, HbA1c, FBG, OGTT-30 min insulin, IL-6 and TNF-α. Whereas, GLP-1RA + Met showed a more robust improvement on HbA1c, HOMA-IR, lipid profiles, inflammatory parameters, and ovulation. CPA/EE + Met was more effective in reducing hyperandrogenemia. Plasma proteomic analysis revealed that the interventions altered proteins involved in reactive oxygen species detoxification (PRDX6, GSTO1, GSTP1, GSTM2), platelet degranulation (FN1), and the immune response (SERPINB9). Conclusions: CPA/EE+Met or GLP-1RA + Met treatment improved reproductive functions and alleviated metabolic disorders in overweight PCOS women. GLP-1RA + Met had a superior improvement in metabolism and inflammation. The novel plasma biomarkers PRDX6, FN1, and SERPINB9, might be indicators and targets for PCOS treatment.