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关键词： Accelerated skin aging   Compound K   Epidermis   Inflammaging   IL-17A   UVB  

摘要： We evaluated the anti-accelerated epidermal skin aging effects of compound K (CK) on keratinocytes using IL-17A and ultraviolet B. CK restored epidermal functions and reduced the induction of pro-inflammatory cytokines by inhibiting NF-kappa B and p38 MAPK activation. CK plays a significant role in controlling accelerated epidermal skin aging.

关键词： acute-on-chronic liver failure (ACLF)   acute kidney injury (AKI)   serum   cystatin C   metallothionein  

摘要： Background/Aims: Acute-on-chronic liver failure (ACLF) is a complication of cirrhosis associated with systemic inflammation and organ dysfunction. In ACLF, the development of acute kidney injury (AKI) is associated with poor outcomes. FABP1, NGAL, Cys C and IL-18 have been shown to correlate with ACLF severity and mortality. Hence, our study aimed to evaluate the association of these biomarkers with organ dysfunctions, particularly AKI, in an Indian ACLF patient cohort. Methods: 151 study participants including ACLF (n = 91;with AKI n = 63, no-AKI n = 28), non-liver AKI (n = 30) and healthy controls (n = 30) were recruited. Serum ELISA was performed for biomarker estimation. Data interpolation and graphical representation were performed using GraphPad Prism and statistical analyses performed using STATA 14.0. Results: FABP1 and Cys C levels were higher in ACLF-AKI patients compared to ACLF no-AKI (P-value <= 0.0005). Serum Cys C levels were significantly increased in non-liver AKI compared to ACLF-AKI (P-value <= 0.001). AUROC analysis showed better performance of Cys C (AUC 0.79;95% CI (0.68-0.89)) compared to serum creatinine (AUC 0.71;95% CI (0.61-0.82)) in discriminating AKI and noAKI. Correlation analysis revealed positive correlations of FABP1 with creatinine and urea, Cys C with creatinine, urea and OF-Kidney, NGAL, and IL-18 with general markers of organ dysfunction. Plasma MTs) measured in a subset of ACLF patients were elevated in progression-to-AKI. Conclusion: Our study showed that in an Indian population of ACLF patients with a high short-term mortality, serum Cys C and FABP1 were elevated in ACLF-AKI, however did not have predictive potential for ACLF-AKI. Cys C levels were significantly higher in non-liver AKI patients vs. ACLF-AKI and correlated with markers of kidney dysfunction whereas NGAL and IL-18 represented higher inflammation and total organ dysfunction. Hence, we conclude that these biomarkers were elevated in ACLF-AKI but did not have predi

关键词： CRSwNP   EGPA   eosinophilic asthma   hyper-eosinophilic syndrome hyper-eosinophilia   IL-5   mepolizumab   NUCALA  

摘要： The Interleukin-5 (IL-5)-mediated pathogenic role of eosinophils in airway disorders including severe eosinophilic asthma (SEA), chronic rhinosinusitis with nasal polyps (CRSwNP), eosinophilic granulomatosis with polyangiitis (EGPA), and rare hyper-eosinophilic syndrome (HES) is well established. Mepolizumab, an IL-5-targeting humanised antibody, is approved as an add-on maintenance therapy for SEA, EGPA, CRSwNP, and HES. Here, we review the safety and efficacy findings of mepolizumab in clinical trials and real-world evidence studies in patients with SEA, CRSwNP, EGPA, and HES. We specifically explore the data on mepolizumab that support early initiation of IL-5-targeted therapy to maximise its corticosteroid-sparing effect. This review consolidates the clinical data on mepolizumab, highlights other promising IL-5-targeting agents, and supports the IL-5 pathway as the key therapeutic target across eosinophilic indications.

摘要： We read with great interest the article by Leung et al. who investigated the predictive performance of alanine aminotransferase (ALT) to quantitative hepatitis B surface antigen (qHBsAg) ratio for HBsAg seroclearance after entecavir cessation in p...

关键词： Bone inflammation   Lipopolysaccharide   TLR4   IFN gamma   IL-10   M-CSF   RANKL  

摘要： The inflammatory response in bone tissue often triggered by LPS is a complex process. Since LPS through TLR4 and in presence of IFN gamma activates osteoclast differentiation and bone resorption, therefore, suppression of osteoclastogenesis through inhibition of TLR4 vs IFN gamma mediated inflammation could be a reasonable strategy for the treatment of inflammatory bone loss. Administration of anti-TLR4 (30 mg/kg) and anti-IFN gamma antibodies (6.6 mg/kg) were utilized before LPS (5 mg/kg) challenge and subsequently mice were treated with mouse IL-10 (0.02 mg/kg). Then RBMCs were isolated from different groups of mice and stimulated (in vitro) with M-CSF (10 ng/ml) and RANKL (10 ng/ml) to induce bone marrow cell differentiation in presence of LPS (100 ng/ml). The involvement of RANKL and M-CSF in the regulation of bone inflammation underlines the intricate signaling pathways. Furthermore, the study sheds light on the potential therapeutic effects of exogenous IL-10 possibly through STAT3 signaling in the RBMCs. The use of antibodies against TLR4 and IFN gamma, in conjugation with IL-10in LPS bone damage model, appears to downregulate the activation of NF-kappa B, and reduction of many proinflammatory cytokines regulating the inflammatory cascade in RBMC. This suggests a promising avenue for the development of treatments aimed at mitigating bone inflammation associated with bacterial infections. Therefore, inhibition of TLR4 and IFN gamma could be explored as potential therapeutic agents against LPS induced bone loss.