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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Sepsis is a life-threatening disease due to a dysregulated host response to infection, with an unknown regulatory mechanism for prognostic necroptosis-related genes (NRGs). Using GEO datasets GSE65682 and GSE134347, we identified six NRG biomarkers ( ATRX , TSC1 , CD40 , BACH2 , BCL2 , and LEF1 ) with survival and diagnostic significance through Kaplan-Meier (KM) and receiver operating characteristic (ROC) analyses. Afterward, the ingenuity pathway analysis (IPA) highlighted enrichment in hepatic fibrosis pathways and BEX2 protein. ⋯ Additionally, DrugBank analysis identified paclitaxel, docetaxel, and rasagiline as potential BCL2-targeting sepsis treatments. Finally, real-time quantitative PCR confirmed ATRX, TSC1, and LEF1 downregulation in sepsis samples, contrasting CD40's increased expression in CTL samples. In conclusion, ATRX , TSC1 , CD40 , BACH2 , BCL2 , and LEF1 may be critical regulatory targets of necroptosis in sepsis, providing a basis for further necroptosis-related studies in sepsis.
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Background: One of the mechanisms responsible for the high mortality rate of acute myocardial infarction is myocardial ischemia-reperfusion injury (MI-RI). The present study focused on the role and regulatory mechanisms of specificity protein 1 (SP1) and ubiquitin-specific protease 46 (USP46) in oxygen-glucose deprivation/reperfusion (OGD/R)-induced cardiomyocyte injury. Methods: OGD/R was used to treat cardiomyocytes AC16 to mimic ischemia-reperfusion in vitro. ⋯ SP1 could enhance the transcription of USP46, and USP46 overexpression reversed SP1 silencing-mediated effects on OGD/R-induced cardiomyocytes. SP1 mediated the AMPK signaling via USP46. Conclusion: SP1 mediated OGD/R-induced cardiomyocyte inflammation, OxS injury, apoptosis, and ferroptosis by inactivating the AMPK signaling via enhancing the transcription of USP46.
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Background: Sepsis-induced acute kidney injury (SI-AKI) is a kind of kidney dysfunction, which brings a lot of suffering. This study aimed to figure out the role of the miR-218-5p/PGC-1α axis in SI-AKI. Methods: AKI mouse model was established through cecal ligation and puncture. ⋯ Inhibition of PGC-1α annulled the role of miR-218-5p silencing in cells. In vivo , miR-218-5p overexpression partly reversed the protective role of ZLN005 in SI-AKI mice. Conclusion: miR-218-5p targeted PGC-1α to disrupt mitochondrial biogenesis, thereby exacerbating SI-AKI.
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Sepsis causes dysfunction in different organs, but the pathophysiological mechanisms behind it are similar and mainly involve complex hemodynamic and cellular dysfunction. The importance of microcirculatory dysfunction in sepsis is becoming increasingly evident, in which endothelial dysfunction and glycocalyx degradation play a major role. This study aimed to investigate the effects of hydrogen-rich saline (HRS) on renal microcirculation in septic renal failure, and whether Sirt1 was involved in the renoprotective effects of HRS. ⋯ Compared with the CLP group, HRS reduced renal apoptosis and upregulated Sirt1 expression, and inhibited the NF-κB/MMP9 signaling pathway. In addition, HRS did not damage immune function in septic rats as well. Generally speaking, our results suggest that HRS can alleviate the inflammatory response, inhibit glycocalyx shedding, improve septic kidney injury, and enhance survival rate.
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Backgrounds: This study aimed to investigate the relationship between Cx43 expression and autophagy mediated by the AMPK-mTOR-Ulk1 signaling pathway in jaundice heart. Methods: In this study, a jaundice model was established in common bile duct ligation (CBDL) rats. Cardiac injury was assessed using various methods including myocardial injury indicators, echocardiography, transmission electron microscopy, hematoxylin and eosin staining, Masson staining, immunohistochemical analyses, and immunofluorescence staining. ⋯ In addition, we observed that increased autophagy led to decreased Cx43 expression, which negatively affected cardiac function. Conclusions: CBDL induces myocardial injury in rats and activates autophagy through the AMPK-mTOR-ULK pathway, resulting in decreased Cx43 protein levels. A moderate increase in early autophagy in CBDL can improve cardiac injury, while late inhibition of autophagy can reduce myocardial injury.