Sepsis is the major cause of acute kidney injury (AKI) associated with high mortality rates. Mitochondrial dysfunction contributes to the pathophysiology of septic AKI. Mitophagy is an important mitochondrial quality control mechanism that selectively eliminates damaged mitochondria, but its role and regulation in septic AKI remain largely unknown. Here, we demonstrate the induction of mitophagy in mouse models of septic AKI induced by lipopolysaccharide (LPS) treatment or by cecal ligation and puncture. Mitophagy was also induced in cultured proximal tubular epithelial cells exposed to LPS. Induction of mitophagy under these experimental setting was suppressed by pink1 or park2 knockout, indicating the role of the PINK1/PARK2 pathway of mitophagy in septic AKI. In addition, sepsis induced more severe kidney injury and cell apoptosis in pink1 or park2 knockout mice than in wild-type mice, suggesting a beneficial role of mitophagy in septic AKI. Furthermore, in cultured renal tubular cells treated with LPS, knockdown of pink1 or park2 inhibited mitochondrial accumulation of the autophagy adaptor optineurin (OPTN) and silencing Optn inhibited LPS-induced mitophagy. Taken together, these findings suggest that the PINK1/PARK2 pathway of mitophagy plays an important role in mitochondrial quality control, tubular cell survival, and renal function in septic AKI.

Cisplatin (Cis) can cause chronic kidney disease (CKD) and promote renal fibrosis, but the underlying mechanism is not fully understood. Hypoxia inducible factor-1α (HIF-1α) can promote renal fibrosis in some kidney diseases, but its role in Cis-induced CKD is still unknown. Notch-1 is a recognized molecule that promotes renal fibrosis under pathological circumstances, and evidence shows that HIF-1α and Notch-1 are closely related to each other. In the present study, mice with HIF-1α gene knockout in proximal tubular cells (PTCs) (PT-HIF-1α-KO) were generated and treated with Cis to induce CKD. A human proximal tubular cell line (HK-2) and primary mouse PTCs were used for in vitro studies. The results showed that HIF-1α was increased in the kidneys of Cis-treated wild-type mice, accompanied by elevated Notch-1, Notch-1 intracellular domain (N1ICD), Hes-1 and renal fibrosis. However, these alterations were partially reversed in PT-HIF-1α-KO mice. Similar results were observed in HK-2 cells and primary mouse PTCs. In addition, treating the cells with Cis induced a marked interaction of HIF-1α and N1ICD. Further inhibiting Notch-1 significantly reduced cellular fibrogenesis but did not affect HIF-1α expression. The data suggested that HIF-1α could promote renal fibrosis in Cis-induced CKD by activating Notch-1 both transcriptionally and post-transcriptionally and that HIF-1α may serve as a potential therapeutic target for Cis-induced CKD.

Background: Diet management is a pivotal intervention for chronic kidney disease (CKD) patients. Dietary inflammation index (DII) is developed to evaluate the integral inflammatory potential of a diet pattern. However, research about the association between DII and mortality in CKD is limited.Objective: We conducted a cohort study to investigate the relationship between energy-adjusted DII (E-DII) and the 5-year all-cause and cardiovascular mortality in CKD population.Materials and Methods: CKD participants with complete E-DII data and death status from National Health and Nutrition Examination Survey (1999–2014) were involved in this study. E-DII was calculated based on dietary recall interviews. Smooth curve fitting, Kaplan–Meier survival analysis, and Cox proportional hazards models were used to evaluate the association between E-DII and the 5-year all cause and cardiovascular mortality. Subgroup analysis was also performed.Results: A total of 7,207 participants were included (55.46% elderly and 46.54% male) in this study. The 5-year all-cause and cardiovascular mortality were 16.86 and 4.32%, respectively. Smooth curve fitting showed a “J” shape and near linear relationship between the E-DII score and the 5-year all-cause and cardiovascular mortality, respectively. In multivariate Cox proportional hazards models, the hazard ratios (95% confidence intervals [CI]) for the highest tertile of the E-DII were 1.33 (1.15, 1.54) for all-cause mortality, and 1.54 (1.15, 2.07) for cardiovascular mortality when compared with the lowest tertile of the E-DII. The subgroup analyses revealed relatively stronger associations between the E-DII and the mortality among CKD patients with other death risk factors.Conclusions: Energy-adjusted dietary inflammatory index is independently related with the 5-year all-cause and cardiovascular mortality among CKD patients. Therefore, anti-inflammatory diet patterns should be recommended for CKD patients.

Daytime napping, a habit widely adopted globally, has an unclear association with obesity. In this study, we executed a meta-analysis to explore the relationship between daytime napping and obesity. We conducted a comprehensive search of the PubMed, Embase, Cochrane Library, Scopus, PsycINFO, and Web of Science databases for pertinent articles published up to April 2023. Random-effects models were utilized to calculate odds ratios (ORs) with 95% confidence intervals (CIs), and we assessed the heterogeneity of the included studies using the I² statistic. To explore potential sources of heterogeneity, subgroup analyses were performed. The methodological quality of the studies was evaluated using the Newcastle–Ottawa Scale (NOS), and funnel plots were employed to detect any publication bias. Sensitivity analyses were conducted by sequentially omitting each study. We conducted a meta-analysis of twelve studies that included one each from the UK and Spain, five from the USA, and five from China, totalling 170,134 participants, to probe the association between napping and obesity. The pooled analysis suggested a higher risk of obesity in individuals who nap (OR: 1.22 [1.10–1.35], p < 0.001, I² = 87%) compared to non-nappers. The meta-analysis results revealed variations in the summary ORs for studies conducted in China, Spain, the USA, and the UK. The ORs for China, Spain, the USA, and the UK were 1.05 (95% CI 0.90–1.23), 9.36 (95% CI 4.74–18.45), 1.27 (95% CI 1.10–1.47), and 1.39 (95% CI 1.32–1.47), respectively. A subgroup analysis based on age within the American population disclosed that napping in both adults and children heightened obesity incidence. A subgroup analysis based on nap duration found a significant rise in obesity occurrence when nap duration exceeded one hour, but no clear relationship emerged when nap duration was less than 1 h. In a subgroup analysis based on the definition of obesity, napping did not demonstrate a significant relationship with obesity when diagnostic criteria set obesity at a BMI of 25 or above. However, when the criteria were set at a BMI of 28 or 30 or more, napping significantly increased obesity risk. Our meta-analysis indicates a positive association between daytime napping and the risk of obesity. However, given the limited number of included studies, potential confounding factors might not have been fully addressed. Future well-designed prospective studies are required to further investigate this relationship. Large-scale studies are necessary to confirm our findings and elucidate the underlying mechanisms that drive these associations and causation.

Endoplasmic reticulum (ER) degradation via autophagy is a process that maintains ER homeostasis when cells are in a state of stress and is associated with many diseases; however, the role of hypoxia inducible factor-1α (HIF-1α)-mediated ER degradation and the related regulatory pathway in acute kidney injury (AKI) still needs to be further established. In the present study, an in vivo AKI model was induced in mice via the ischemia‒reperfusion (IR) method. The results revealed that HIF-1α and BNIP3 were increased, and autophagy and ER degradation were activated in the kidneys of AKI mice, whereas HIF-1α knockout significantly inhibited BNIP3, autophagy and ER degradation, accompanied by aggravated kidney injury. Overexpression of HIF-1α in vitro significantly increased BNIP3, autophagy and ER degradation, whereas inhibition of BNIP3 significantly reversed the effects of HIF-1α. In addition, the in vitro inhibition of autophagy with chloroquine significantly reversed the effects of HIF-1α on cell apoptosis. Moreover, selectively overexpressing BNIP3 on the ER membrane significantly increased ER degradation via autophagy and decreased cell apoptosis in vitro. These data indicate that HIF-1α/BNIP3-mediated ER degradation via autophagy in tubular cells protects against IR-induced AKI.