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Inflammatory storms and endothelial barrier dysfunction are the central pathophysiological features of acute respiratory distress syndrome (ARDS). Intermedin (IMD), a member of the calcitonin gene-related peptide (CGRP) family, has been reported to alleviate inflammation and protect endothelial cell (EC) integrity. However, the effects of IMD on ARDS have not been clearly elucidated. In the present study, clinical ARDS data were used to explore the relationship between serum IMD levels and disease severity and prognosis, and we then established a model to predict the possibility of hospital survival. Mouse models of ARDS and LPS-challenged endothelial cells were used to analyze the protective effect and underlying mechanism of IMD. We found that in patients with ARDS, increased serum IMD levels were associated with reduced disease severity and increased rates of hospital survival. IMD alleviated the LPS-induced inflammatory response by decreasing proinflammatory cytokines, NF-κB p65 expression and NF-κB p65 nuclear translocation. In addition, IMD stabilized the endothelial barrier by repairing adherens junctions (AJs), cytoskeleton and capillary leakage. IMD exerted protective effects against ARDS on pulmonary endothelial cells, at least partly, through PI3K/Akt/eNOS signaling, while IMD's anti-inflammation effect was mediated through an eNOS-independent mechanism. Our study may provide new therapeutic insight for ARDS treatment.Dihydroartemisinin (DHA), a sesquiterpene lactone derived from artemisinin, has been reported to possess anti-inflammation and anti-cancer activities. But its underlying protective mechanisms on dextran sodium sulphate (DSS)-induced colitis remain rarely reported. Procyanidin C1 in vitro We applied a network pharmacology approach to predict the collective targets of DHA and acute colitis. GO and KEGG analyses were performed to investigate the enriched biological functions and signaling pathways of the collective targets. Furthermore, a DSS-induced colitis model was established to observe the protective effects of DHA. 83 common targets of DHA and acute colitis were identified and predominantly involved in several inflammation-related signaling pathways in colitis such as NOD-like receptor and MAPK signaling pathways. Additionally, DHA in vivo improved the clinical symptoms, reduced the production of pro-inflammatory factors IL-1β, IL-6 and TNF-α, and suppressed the formation of NLRP3 inflammasome. Moreover, DHA inhibited the phosphorylation of NF-κB p65 and p38 MAPK, but upregulated PPARγ and Ki-67 levels compared to the DSS group. Additionally, we found that DHA suppressed p38 activator-induced pro-inflammatory response, and p38 inhibitor attenuated the clinical symptoms and reduced the expression levels of pro-inflammatory mediators and NLRP3 while up-regulated the expression levels of PPARγ and Ki-67. Molecular docking analysis further verified the binding mode towards the DHA and p38 MAPK. In conclusion, DHA could protect DSS-induced colitis via suppressing the activation of NLRP3 inflammasome and p38 MAPK signaling.

There is still an unmet need for a simple and reliable biomarker for diagnosis and disease activity of spondyloarthritis. Recent studies indicated that calprotectin could act as a biomarker for spondyloarthritis. Therefore, this systematic review and meta-analysis aims to evaluate the levels of serum and fecal calprotectin in spondyloarthritis and the associations with disease activity.

PubMed, Web of Science and Cochrane Library were comprehensively searched from inception to July 1st, 2019. The pooled standard mean differences (SMDs) were used to estimate the differences of the levels of serum and fecal calprotectin between spondyloarthritis patients and controls. Spearman correlation coefficients were used for evaluating the associations between the levels of serum and fecal calprotectin and disease activity of spondyloarthritis patients. The use of fixed-effect or random-effects model depended on heterogeneity.

Among 257 searched studies, 20 studies were finally included for analysis. Serum and fecal calprotectin were both significantly increased in spondyloarthritis patients compared to matched controls (SMD=1.49, 95% CI=0.91 to 2.08; SMD=2.29, 95% CI=0.25 to 4.33). The pooled correlation coefficients between serum or fecal calprotectin and CRP, ESR, BASDAI and BASFI were 0.353, 0.228, 0.225, 0.131 and 0.185, 0.163, 0.280, 0.196 respectively.

Our study indicated that serum and fecal calprotectin were significantly increased in spondyloarthritis patients, and associated with disease activity. Serum and fecal calprotectin were potential biomarkers for the diagnosis and disease activity of spondyloarthritis.

Our study indicated that serum and fecal calprotectin were significantly increased in spondyloarthritis patients, and associated with disease activity. Serum and fecal calprotectin were potential biomarkers for the diagnosis and disease activity of spondyloarthritis.LQFM219 is a molecule designed from celecoxibe (COX-2 inhibitor) and darbufelone (inhibitor of COX-2 and 5-LOX) lead compounds through a molecular hybridisation strategy. Therefore, this work aimed to investigate the antinociceptive and anti-inflammatory activities of this new hybrid compound. The acute oral systemic toxicity of LQFM219 was evaluated via the neutral red uptake assay. Acetic acid-induced abdominal writhing and CFA-induced mechanical hyperalgesia were performed to evaluate the antinociceptive activity, and the anti-oedematogenic activity was studied by CFA-induced paw oedema and croton oil-induced ear oedema. Moreover, the acute anti-inflammatory activity was determined by carrageenan-induced pleurisy. In addition, cell migration, myeloperoxidase enzyme activity, and TNF-α and IL-1β levels were determined in pleural exudate. Moreover, a redox assay was conducted using electroanalytical and DPPH methods. The results demonstrated that LQFM219 was classified as GHS category 4, and it showed better free radical scavenger activity compared to BHT. Besides, LQFM219 decreased the number of writhings induced by acetic acid and the response to the mechanical stimulus in the CFA-induced mechanical hyperalgesia test. Furthermore, LQFM219 reduced oedema formation, cell migration, and IL-1β and TNF-α levels in the pleural cavity and inhibited myeloperoxidase enzyme activity. Thus, our study provides that the new pyrazole derivative, LQFM219, demonstrated low toxicity, antinociceptive and anti-inflammatory potential in vitro and in vivo.