Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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Background and aims: Genipin, an iridoid derived from geniposide by β-glucosidase hydrolysis, has shown potential benefit in the treatment of heart function insufficiency despite its unclear therapeutic mechanism. This study aimed to investigate the primary cardioprotective mechanism of genipin. We hypothesized that genipin demonstrated the antiapoptosis and anti-inflammation for cardiac protection by inhibiting the cyclooxidase 2 (COX2)-prostaglandin D2 (PGD2) and murine double minute 2 (MDM2)-p53 pathways. ⋯ Genipin also restored the post-MI upregulated expressions of cytochrome c, p53, COX2, and PGD2 and downregulated expression of MDM2 to the approximate baseline. Genipin inhibited apoptotic and inflammatory pathways to prevent post-MI structure-function remodeling. Conclusions: This study showed the cardioprotective mechanism of genipin and implied its potential clinical application for the treatment of ischemic heart failure.
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Introduction: Alda-1, an aldehyde dehydrogenase 2 (ALDH2) activator, has been shown to protect the lung against a variety of diseases including regional ischemia-reperfusion injury, severe hemorrhagic shock, hyperoxia, and so on. The present study was designed to investigate the effectiveness of Alda-1 treatment in alleviating lung injury after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) in swine. Methods: A total of 24 swine were randomized into three groups: sham (n = 6), CA/CPR (n = 10), and CA/CPR + Alda-1 (n = 8). ⋯ Likewise, Alda-1 treatment significantly decreased these pathological damages in lung tissue when compared with the CA/CPR group. Conclusions: Alda-1 treatment was effective to alleviate lung injury after CA/CPR in a swine model, in which the protective role was possibly related to the inhibition of cell apoptosis and ferroptosis. It might provide a novel therapeutic target and a feasible therapeutic drug for lung protection after CA/CPR.
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Intervertebral disc degeneration is a multifactorial pathological disease. miR-199a-5p is exceedingly implicated in regulating degenerative nucleus pulposus cell (DNPC). We explored the roles of miR-199a-5p in DNPCs. Cell morphology and Collagen II-positive expression were observed. ⋯ NF-κB pathway inhibitor promoted DNPC proliferation and inhibited apoptosis. Briefly, miR-199a-5p was upregulated in DNPCs. We discovered for the first time that miR-199a-5p silencing repressed the NF-κB pathway by promoting CDKN1B transcription, thus promoting DNPC proliferation and inhibiting apoptosis.