Hydrocortisone Sodium Succinate

Stroke remains a major cause of mortality and disability, highlighting the need for new therapeutic targets. This study aimed to systematically identify druggable genes causally associated with stroke risk using genetic and transcriptomic data. A total of 5883 druggable genes were compiled from the Drug–Gene Interaction Database and previous reviews. We integrated data from a large-scale stroke GWAS with blood and brain expression quantitative trait loci (eQTLs) for druggable genes and performed a two-sample Mendelian randomization analysis using eQTLs as genetic instruments for gene expression. Significant findings were validated using colocalization analysis. Expression of prioritized genes was further examined in external bulk (GSE140275) and single-cell (GSE174574) RNA-seq datasets. Finally, protein–protein interaction networks and the Drug Signature Database were employed for downstream functional and therapeutic prediction. The intersection of eQTL data identified 3453 genes in blood and 3150 genes in brain tissues. Mendelian randomization analysis identified ten gene-stroke associations (3 in blood, 7 in brain). Colocalization analysis supported a shared causal variant for 5 of these genes, indicated by high posterior probability of hypothesis 4 values, suggesting potential pathogenic roles. The protein–protein interaction network highlighted 5 core druggable genes ( protein tyrosine kinase 2 , cyclin-dependent kinase 6 , ring finger protein 43 , papilin proteoglycan-like sulfated glycoprotein , and coagulation factor II ) interacting with 20 predicted genes. Myosin light chain kinase inhibitor 7 and staurosporine were the 2 most significant compounds interacting with these genes, followed by simvastatin and cortisol succinate. This study uncovered potential stroke mechanisms and therapeutic targets using integrated multi-omics data, providing a foundation for future clinical applications and drug development strategies. Five druggable genes were identified in stroke ( protein tyrosine kinase 2 , cyclin-dependent kinase 6 , ring finger protein 43 , papilin proteoglycan-like sulfated glycoprotein , and coagulation factor II ). Myosin light chain kinase inhibitor 7, staurosporine, simvastatin, and cortisol succinate were identified as potential drug candidates for stroke. These results could add additional tools to manage stroke.

To assess the effectiveness of cord blood nucleated cell extract (CBNCE) in rheumatoid arthritis (RA) and explore the mechanism preliminarily.

CBNCE injection was prepared by adding HClO₄ and KOH to cord blood. The efficacy of CBNCE was assessed through a lymphocyte proliferation assay. Subsequently, the CIA model was utilized as the RA model, with rats being randomly assigned to a normal group, model group, CBNCE group (1 mL/d), and HSS group (hydrocortisone sodium succinate, 0.2 mL/d). Following a 7-day period of immune system enhancement, continuous medication was administered for the subsequent 21 days. Foot swelling tests, HE staining, flow cytometry, ELISA, WB, and immunofluorescence were conducted.

The average inhibitory rate of CBNCE on lymphocyte proliferation was 83.51%. Compared with the model group, rats in the CBNCE group showed a decrease of inflammatory cell infiltration in ankle tissue. The left hindfoot volume (days 5, 9, 10, and 12-21), Th17 percentage and Th17/Treg ratio in peripheral blood, and the levels of IL-1, IL-6, IL-8, and IL-17 in ankle effusion, as well as the MMP-3 protein expression in synovial tissue were significantly decreased (P < 0.05). There were significant (P < 0.05) increases in the fluorescence intensity of Aggrecan and Collagen type I, as well as in the amounts of IL-4 and IL-10.

CBNCE modulates the Th17/Treg balance by decreasing the Th17 cells, suppressing the secretion of IL-1, IL-6, IL-8, and IL-17, enhancing the secretion of IL-4 and IL-10, and further inhibiting the expression of MMP-3 protein, thereby increasing the level of Aggrecan and Collagen type I. Ultimately, CBNCE alleviates RA. Key Points • Our study was the first to explore the effect and mechanism of cord blood nucleated cell extract in the treatment of rheumatoid arthritis. • This study offers a theoretical foundation and introduces a novel concept for utilizing cord blood in the treatment of rheumatoid arthritis.