Integrated Network Pharmacology and Experimental Validation Approach to Investigate the Therapeutic Effects of Capsaicin on Lipopolysaccharide-Induced Acute Lung Injury.

An integrated method combining network pharmacology and in vivo experiment was performed to investigate the therapeutic mechanism of capsaicin (Cap) against acute lung injury. The potential key genes and signaling pathways involved in the therapeutic effect of Cap were predicted by the network pharmacology analyses. Additionally, the histological assessment, ELISA, and RT-qPCR were performed to confirm the therapeutic effect and the potential mechanism action involved. Our findings showed that TNF, IL-6, CXCL1, CXCL2, and CXCL10 were part of the top 50 genes. Enrichment analysis revealed that those potential genes were enriched in the TNF signaling pathway and IL-17 signaling pathway. In vivo experiment results showed that Cap alleviated histopathological changes, decreased inflammatory infiltrated cells and inflammatory cytokines, and improved antioxidative enzyme activities in the bronchoalveolar lavage fluid (BALF). Furthermore, Cap treatment effectively downregulated TNF, IL-6, NF-κB, CXCL1, CXCL2, and CXCL10 in lung tissue. Thus, our findings demonstrated that Cap has the therapeutic effect on LPS-induced acute lung injury in neonatal rats via suppression of the TNF signaling pathway and IL-17 signaling pathway.

Changes in humoral immunity, myocardial damage, trace elements, and inflammatory factor levels in children with rotavirus enteritis.

OBJECTIVE: To investigate the changes and significance of humoral immunity, myocardial damage, trace elements and inflammatory factors levels in children with rotavirus enteritis. METHODS: One hundred children with rotavirus enteritis admitted to our hospital from January 2019 to December 2020 were retrospectively selected as the case group, and they were divided into a no dehydration group (33 cases), mild dehydration group (41 cases), and moderate dehydration group (26 cases). Another 100 children with rotavirus-negative enteritis during the same period were selected as the control group. Serum immunoglobulin, cardiac enzyme profile, trace elements, and interleukin-6 (IL-6) levels were compared between the two groups, and among the case groups for different degrees of dehydration. RESULTS: Serum immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin M (IgM), zinc, magnesium, and calcium in the case group were lower than in controls (P<0.05). Serum lactate dehydrogenase (LDH), α-hydroxybutyrate dehydrogenase (α-HBDH), creatine kinase (CK), and creatine kinase isoenzyme (CK-MB) in the case group were higher than in controls (P<0.05). Serum IL-6, interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α) were also higher in cases than controls (P<0.05). Serum IgA, IgG, IgM, zinc, magnesium, and calcium in children with rotavirus enteritis with mild dehydration were lower than those without dehydration, but higher than those with moderate dehydration (P<0.05). Serum LDH, α-HBDH, CK, and CK-MB in children with rotavirus enteritis with mild dehydration were higher than those without dehydration, but lower than those with moderate dehydration (P<0.05). Serum IL-6, IL-8, and TNF-α in children with rotavirus enteritis with mild dehydration were higher than those without dehydration, but lower than those with moderate dehydration (P<0.05). CONCLUSION: Children with rotavirus enteritis with more severe dehydration exhibited lower levels of humoral immunity and trace elements and greater myocardial damage and inflammatory response. Early detection can accurately assess the condition and provide a reference for clinical treatment.

SIRT3 diminishes inflammation and mitigates endotoxin-induced acute lung injury.

Acute lung injury (ALI) is characterized by exuberant proinflammatory responses and mitochondrial dysfunction. However, the link between mitochondrial dysfunction and inflammation in ALI is not well understood. In this report, we demonstrate a critical role for the mitochondrial NAD+-dependent deacetylase, sirtuin-3 (SIRT3), in regulating macrophage mitochondrial bioenergetics, ROS formation, and proinflammatory responses. We found that SIRT3 expression was significantly diminished in lungs of mice subjected to LPS-induced ALI. SIRT3-deficient mice (SIRT3-/-) develop more severe ALI compared with wild-type controls (SIRT3+/+). Macrophages obtained from SIRT3-/- mice show significant alterations in mitochondrial bioenergetic and redox homeostasis, in association with a proinflammatory phenotype characterized by NLRP3 inflammasome activation. The SIRT3 activator viniferin restored macrophage bioenergetic function in LPS-treated macrophages. Viniferin also reduced NLRP3 activation and the production of proinflammatory cytokines, effects that were absent in SIRT3-/- macrophages. In-vivo administration of viniferin reduced production of inflammatory mediators TNF-α, MIP-2, IL-6, IL-1ß, and HMGB1, and diminished neutrophil influx and severity of endotoxin-mediated ALI; this protective effect of vinferin was abolished in SIRT3-/- mice. Taken together, our results show that the induction/activation of SIRT3 may serve as a new therapeutic strategy in ALI by modulating cellular bioenergetics, controlling inflammatory responses, and reducing the severity of lung injury.