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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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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Background: Persistent inflammation, immunosuppression, and catabolism syndrome (PIICS) is associated with high mortality and high health care costs, and there is currently no effective target treatment. Mesenchymal stem cells (MSCs) possess multipotent immunomodulatory properties. LPS-preconditioned type 1 MSCs (MSC1s) are potentially beneficial for PIICS treatment because of their proinflammatory, anti-infective, and healing properties. ⋯ MSC1s also promoted proinflammatory cytokine secretion and reduced the concentration of soluble PD-L1 in vitro. Conclusions: MSC1s can protect mice against critical PIICS, partly by enhancing CD8 + T-cell function. Therefore, MSC1 transplantation is a novel therapeutic candidate for PIICS.
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Traumatic brain injury is one of the main causes of death and disability worldwide, and results in multisystem complications. However, the mechanism of mild traumatic brain injury (MTBI) on lung injury remains unclear. In this study, we used a murine model of MTBI and pneumonia ( Pseudomonas aeruginosa ;) to explore the relationship between these conditions and the underlying mechanism. ⋯ Furthermore, alveolar macrophages from MTBI mice exhibited enhanced bactericidal capacity compared with those from controls ( P < 0.01). Moreover, MTBI + pneumonia mice exhibited less CD86-positive M1 macrophages compared with the pneumonia group ( P < 0.01). Conclusions: MTBI attenuates pneumonia-induced acute lung injury through the modulation of alveolar macrophage bactericidal capacity and M1 polarization in bacterial pneumonia model.
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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.
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Acute pancreatitis (AP) is an inflammation-associated disorder in the digestive system. Ubiquitin-specific peptidase 25 ( USP25 ) can modulate inflammation in diseases. This study expounded on the role of USP25 in pyroptosis of acinar cells in AP. ⋯ We found that USP25 binding to KLF4 inhibited ubiquitination degradation of KLF4 , KLF4 transcriptionally decreased miR-10a-5p expression, and miR-10a-5p targeted GSDMD expression. Finally, rescue experiments proved that KLF4 overexpression or miR-10a-5p suppression enhanced pyroptosis of AP acinar cells. Overall, USP25 stabilized KLF4 expression through deubiquitination, limited miR-10a-5p expression, and increased GSDMD expression, finally promoting pyroptosis of acinar cells in AP.