CD38 is the main enzyme for nicotinamide adenine dinucleotide (NAD) degradation in mammalian cells. Decreased NAD levels are closely related to metabolic syndromes and aging-related diseases. Our study showed that CD38 deficiency significantly alleviated angiotensin II (Ang II)-induced vascular remodeling in mice, as shown by decreased blood pressures; reduced vascular media thickness, media-to-lumen ratio, and collagen deposition; and restored elastin expression. However, our bone marrow transplantation assay showed that CD38 deficiency in lymphocytes led to lack of protection against Ang II-induced vascular remodeling, suggesting that the effects of CD38 on Ang II-induced vascular remodeling might rely primarily on vascular smooth muscle cells (VSMCs), not lymphocytes. In addition, we observed that CD38 deficiency or NAD supplementation remarkably mitigated Ang II-induced vascular senescence by suppressing the biogenesis, secretion, and internalization of senescence-associated small extracellular vesicles (SA-sEVs), which facilitated the senescence of neighboring non-damaged VSMCs. Furthermore, we found that the protective effects of CD38 deficiency on VSMC senescence were related to restoration of lysosome dysfunction, particularly with respect to the maintenance of sirtuin-mediated mitochondrial homeostasis and activation of the mitochondria–lysosomal axis in VSMCs. In conclusion, our findings demonstrated that CD38 and its associated intracellular NAD decline are critical for Ang II-induced VSMC senescence and vascular remodeling.

At present, simple, accurate, and efficient prognostic tools for the evaluation of cases with early-stage sepsis in the emergency department (ED) are lacking. An increased blood urea nitrogen to albumin ratio (BAR) has previously been shown to be a valuable biomarker with predictive utility in several diseases. The relationship between BAR and sepsis patient outcomes, however, is not well-understood. This exploration was thus developed for the exploration of the link between BAR values and the short-term prognosis of cases with sepsis. Methods: This was a retrospective cohort research of sepsis cases admitted to the West China Hospital of Sichuan University ED from July 2015 to June 2016. Laboratory data were collected upon ED admission, and 7-day all-cause mortality was the primary study endpoint. Relationships between BAR values and APACE II and SOFA scores were generated assessed with correlation coefficient heatmaps. Independent risk factors were identified through multivariate analyses, with the curves of receiver operating characteristic (ROC) being employed to gauge the value of BAR as a predictor of the risk of mortality in sepsis cases. Results: In sum, 801 patients participated in the present investigation. BAR values were strongly correlated with APACHE II and SOFA scores. In a multivariate logistic regression assessment, BAR was identified as an independent predictor of mortality among patients with sepsis (HR=1.032, 95% CI: 1.010-1.055, P=0.004). BAR exhibited an AUC of 0.741 (95% CI: 0.688-0.793, P<0.001) when used to predict patient mortality risk, with 5.27 being the optimal BAR cut-off. Conclusion:We found that BAR can be used as a reliable biomarker to predict mortality in patients with sepsis.

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emerging evidence suggests that both apoptosis and autophagy contribute to global cerebral ischemia-reperfusion (Gcir)-induced neuronal death, which results from cardiac arrest (ca). However, the mechanism of how Gcir may affect the balance between apoptosis and autophagy resulting from ca remains to be elucidated. additionally, the role of adiponectin (aPn) in reversing the apoptosis and autophagy induced by Gcir following cardiac arrest-cardiopulmonary resuscitation (ca-cPr) is unclear. Thus, the aim of the present study was to investigate how Gcir affect the apoptosis and autophagy in response to ca and to clarify whether aPn may alter the apoptosis and autophagy of neuronal death in Gcir-injured brain post-ca-cPr. using normal controls (Sham group) and two experimental groups [ca-cPr-induced Gcir injury (PcaS) group and exogenous treatment with adiponectin post-ca-cPr (aPn group)], it was demonstrated that both apoptosis and autophagy were observed simultaneously in the brain subjected to Gcir, but apoptosis appeared to be more apparent. exogenous administration of aPn significantly reduced the formation of malondialdehyde, a marker of oxidative stress and increased the expression of superoxide dismutase, an anti-oxidative enzyme, resulting in the stimulation of autophagy, inhibition of apoptosis and reduced brain tissue injury (P<0.05 vs. PcaS). aPn treatment increased the expression of aPn receptor 1 (adipr1) and the phosphorylation of aMP-activated protein kinase (aMPK; Ser182) in brain tissues. in conclusion, Gcir induced apoptosis and inhibited autophagy, contributing to brain injury in ca-cPr. By contrast, aPn reduced the brain injury by reversing the changes of neuronal autophagy and apoptosis induced by Gcir. The possible mechanism might owe to its effects on the activation of aMPK after combining with adipr1 on neurons, which suggests a novel intervention against Gcir injury in ca-cPr conditions.