International immunopharmacology
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Int. Immunopharmacol. · Mar 2020
Muscone relieves inflammatory pain by inhibiting microglial activation-mediated inflammatory response via abrogation of the NOX4/JAK2-STAT3 pathway and NLRP3 inflammasome.
Previous studies have shown that muscone, a pharmacologically active ingredient isolated from musk, has excellent effects on anti-inflammation. However, its effect on microglia activation-induced inflammatory pain is not known yet. In the present study, a mouse BV2 microglia cell activation-mediated inflammatory model was developed with LPS induction, and a mouse inflammatory pain model was established with CFA injection. ⋯ Furthermore, muscone inhibited the CFA-induced NOX4, p-JAK2/p-STAT3, and NLRP3 inflammasome expression in spinal cord of mice. In conclusion, this study uncovered that muscone relieved inflammatory pain by inhibiting microglial activation-mediated inflammatory response via abrogation of the NOX4/JAK2-STAT3 pathway and NLRP3 inflammasome. This finding of muscone is promising for treating inflammatory pain.
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Int. Immunopharmacol. · Mar 2020
Saikosaponin-d attenuated lipopolysaccharide-induced depressive-like behaviors via inhibiting microglia activation and neuroinflammation.
Saikosaponin-d (SSd), a triterpenoid saponins compound extracted from Radix Bupleuri, has been demonstrated to effectively alleviate chronic mild stress-induced depressive behaviors in rats, but the underlying molecular mechanisms are still uncertain. Increasing evidence indicated that microglia activation and inflammatory responses were involved in the pathogenesis of depression. Thus, we desired to induce inflammation-related depressive-like behaviors in mice by injecting lipopolysaccharide (LPS) to investigate whether the antidepressant effect of SSd is related to inhibiting inflammation. ⋯ Enzyme-linked immunosorbent assay (ELISA) results showed that SSd pretreatment suppressed LPS-induced overexpression of inflammatory factors such as interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α both in vivo and in vitro. Immunostaining and western blot analysis results demonstrated that SSd pretreatment also inhibited LPS-induced HMGB1 translocation from nuclear to extracellular and decreased the protein levels of TLR4, p-IκB-α, NF-κBp65. These results suggested that SSd effectively improved LPS-induced inflammation-related depressive-like behaviors by inhibiting LPS-induced microglia activation and neuroinflammation, and the possible mechanism might associate with the regulation of the HMGB1/TLR4/NF-κB signaling pathway.
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Int. Immunopharmacol. · Mar 2020
Observational StudyPrognostic value of an inflammatory biomarker-based clinical algorithm in septic patients in the emergency department: An observational study.
To develop an inflammatory biomarker-based, simple-to-use nomogram for the early identification of septic patients at high risk of mortality in the emergency department (ED). ⋯ This proposed simple-to-use nomogram based on age, NLR, PLR, LMR and RDW provides a relatively accurate mortality prediction for septic patients in the ED.
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Int. Immunopharmacol. · Mar 2020
Meta AnalysisPredictive effect of PD-L1 expression for immune checkpoint inhibitor (PD-1/PD-L1 inhibitors) treatment for non-small cell lung cancer: A meta-analysis.
Programmed death-ligand-1 (PD-L1) is a well-known predictive biomarker in non-small cell lung cancer (NSCLC) patients, however, its accuracy remains controversial. Here, we investigated the correlation between PD-L1 expression level and efficacy of its inhibitors, and hence assessed the predictive effect of PD-L1 expression. ⋯ PD-L1 can be a predictive biomarker for ORR. Nevertheless, PD-L1 expression is not a good predictive tool for OS and PFS.
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Int. Immunopharmacol. · Mar 2020
ReviewThe role of JAK/STAT signaling pathway and its inhibitors in diseases.
The JAK/STAT signaling pathway is an universally expressed intracellular signal transduction pathway and involved in many crucial biological processes, including cell proliferation, differentiation, apoptosis, and immune regulation. It provides a direct mechanism for extracellular factors-regulated gene expression. Current researches on this pathway have been focusing on the inflammatory and neoplastic diseases and related drug. ⋯ In addition, there is increasing evidence indicates that the persistent activation of JAK/STAT signaling pathway is closely related to many immune and inflammatory diseases, yet the specific mechanism remains unclear. Therefore, it is necessary to study the detailed mechanisms of JAK/STAT signaling in disease formation to provide critical reference for clinical treatments of the diseases. In this review, we focus on the structure of JAKs and STATs, the JAK/STAT signaling pathway and its negative regulators, the associated diseases, and the JAK inhibitors for the clinical therapy.