Frontiers in pharmacology
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Frontiers in pharmacology · Jan 2020
Suppression of NLRP3 Inflammasome by Erythropoietin via the EPOR/JAK2/STAT3 Pathway Contributes to Attenuation of Acute Lung Injury in Mice.
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common and devastating clinical disorders with high mortality and no specific therapy. An excessive inflammatory response results in the progression of ALI/ARDS, and the NLRP3 inflammasome is a key participant in inflammation. Erythropoietin (EPO), which is clinically used for anemia, reportedly exerts pleiotropic effects in ALI. ⋯ Meanwhile, EPO evidently decreased interleukin-1β (IL-1β) and interleukin-18 (IL-18) secretion, the expression of NLRP3 inflammasome components including pro-IL-1β, NLRP3, and cleaved caspase-1 as well as phosphorylation of nuclear factor-κB (NF-κB) p65, which may be associated with activation of EPO receptor (EPOR), phosphorylation of Janus-tyrosine kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3). However, all the beneficial effects of EPO on ALI and modulation NLRP3 inflammasome were remarkably abrogated by the inhibition of EPOR/JAK2/STAT3 pathway and knockout (KO) of NLRP3 gene. Taken together, this study indicates that EPO can effectively attenuate LPS-induced lung injury in mice by suppressing the NLRP3 inflammasome, which is dependent upon activation of EPOR/JAK2/STAT3 signaling and inhibition of the NF-κB pathway.
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Frontiers in pharmacology · Jan 2020
Ferulic Acid Attenuates Hypoxia/Reoxygenation Injury by Suppressing Mitophagy Through the PINK1/Parkin Signaling Pathway in H9c2 Cells.
Ferulic acid protects against cardiac injury by scavenging free radicals. However, the role of mitophagy in ferulic acid-induced cardioprotection remains obscure. In the present study, H9c2 cells were exposed to hypoxia/reoxygenation and ferulic acid treatment during hypoxia. ⋯ Ferulic acid also antagonistically reduced the activation of mitophagy by rapamycin. These findings suggest that ferulic acid may protect H9c2 cells against ischemia/reperfusion injury by suppressing PINK1/Parkin-dependent mitophagy. Accordingly, our findings may provide a potential target and powerful reference for ferulic acid in clinical prevention and treatment of hypoxia/reoxygenation injury.
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Frontiers in pharmacology · Jan 2020
Efficacy of Chinese Herbal Injections for the Treatment of Primary Nephrotic Syndrome: A Bayesian Network Meta-Analysis of Randomized Controlled Trials.
Considering the adverse reactions and side effects of immunosuppressive and cytotoxic drugs for the treatment of Primary Nephrotic Syndrome (PNS) and the extensive exploration of Chinese herbal injections (CHIs), systematic evaluation of the efficacy of different CHIs in the treatment of PNS is a key imperative. In this study, we performed a network meta-analysis to investigate the efficacy of CHIs in the treatment of PNS. ⋯ CHIs were found to be superior to WM alone in the treatment of PNS and may be beneficial for patients with PNS. WM+YXI and WM+DHI had the potential to be the best CHI with respect to the total clinical effectiveness, 24-h urinary protein excretion and serum albumin. However, more well-designed randomized controlled trials are still warranted.