The regulation of NLRP3 inflammasome expression during the development of cardiac contractile dysfunction in chronic kidney disease The regulation of NLRP3 inflammasome expression during the development of cardiac contractile dysfunction in chronic kidney disease

Diosmin, a natural flavone glycoside acquired through dehydrogenation of the analogous flavanone glycoside hesperidin, is plentiful in many citrus fruits. Glioblastoma multiforme (GBM) is the most malignant primary brain tumor; the average survival time of GBM patients is less than 18 months after standard treatment. The present study demonstrated that diosmin, which is able to cross the blood–brain barrier, inhibited GBM cell growth in vitro and in vivo. Diosmin also impeded migration and invasion by GBM8401and LN229 GBM cells by suppressing epithelial-mesenchymal transition, as indicated by increased expression of E-cadherin and decreased expression of Snail and Twist. Diosmin also suppressed autophagic flux, as indicated by increased expression of LC3-II and p62, and induced cell cycle arrest at G1 phase. Importantly, diosmin did not exert serious cytotoxic effects toward control SVG-p12 astrocytes, though it did reduce astrocyte viability at high concentrations. These findings provide potentially helpful support to the development of new therapies for the treatment of GBM.

Dipeptidyl peptidase-4 inhibitor (DPP4i) is a widely used antidiabetic agent. Emerging cases of DPP4i-associated bullous pemphigoid (DBP), whose pathogenesis remains unclear, have been reported. Thus, a retrospective study was conducted from January 2016 to June 2021 to determine the clinical, laboratory, and histopathological features of DBP and idiopathic bullous pemphigoid (IBP). We set up in vitro experiments using vildagliptin-treated HaCaT keratinocytes to validate what we found by analyzing published RNA sequencing data about the genes related to the dermal–epidermal junction. We also observed IL-6 expression by HaCaT cells treated with vildagliptin. We enrolled 20 patients with DBP and 40 patients with IBP. The total Bullous Pemphigoid Disease Area Index (BPDAI) score was similar in both groups. However, the BPDAI score of erosions and blisters in DBP was significantly higher than that in IBP (24.6 vs. 16.68, p = 0.0189), and the score for urticaria and erythema was lower in DBP (12 vs. 19.05, p = 0.0183). The pathological features showed that the mean infiltrating eosinophil number per high-power field was significantly lower in DBP than in IBP (16.7 vs. 27.08, p = 0.023). The expression of LAMA3, LAMB3, LAMC2, DST, and COL17A1 decreased significantly in vildagliptin-treated human keratinocytes. On the other hand, IL-6, the hallmark cytokine of bullous pemphigoid (BP) severity, was found to be upregulated in HaCaT cells by vildagliptin. These experimental findings imply less of a requirement for eosinophil infiltration to drive the inflammatory cascades in DBP blistering. Both immunologic and non-immunologic pathways could be employed for the development of DBP. Our findings may help explain the higher incidence of non-inflammatory BP that was observed in DBP.

Psoriatic disease, encompassing psoriasis and -psoriatic arthritis, is a chronic inflammatory condition with bidirectional associations with type 2 diabetes mellitus. Current evidence regarding dipeptidyl peptidase-4 inhibitors’ effects on psoriatic disease presents conflicting findings, with the impact on psoriatic arthritis remaining unexplored. This study aimed to investigate the association between dipeptidyl peptidase-4 inhibitors use and psoriatic disease risk in diabetic patients. A nationwide population-based cohort study was conducted using Taiwan’s National Health Insurance Research Database (2009–2021), including 78,865 patients with type 2 diabetes mellitus: 15,773 dipeptidyl peptidase-4 inhibitors users and 63,092 matched controls. Primary outcomes were incident psoriasis and psoriatic arthritis. During a median follow-up of 7.08 years, 393 cases developed psoriatic disease: 51 cases in the dipeptidyl peptidase-4 inhibitors cohort vs 342 cases in controls. Dipeptidyl peptidase-4 inhibitors therapy was associated with significantly lower psoriatic disease risk (adjusted hazard ratio 0.583, 95% confidence interval 0.430–0.696). Individual dipeptidyl peptidase-4 inhibitors demonstrated varying protective effects, with alogliptin showing the strongest protection. In vitro experiments confirmed that dipeptidyl peptidase-4 inhibitors significantly attenuated inflammatory responses in human skin cells. This large-scale nationwide study demonstrates that dipeptidyl peptidase-4 inhibitors use is associated with a 41.7% lower risk in psoriatic disease in diabetic patients.