Ischemic postconditioning (IPo) attenuates ischemia-reperfusion injuries (IRI) in various organs, of both animals and humans. This study tested the hypothesis that IPo attenuates renal IRI through the upregulation of heat shock protein (HSP)70, HSP27 and heme oxygenase-1 (HO-1, also known as HSP 32) expression. Adult Sprague Dawley rats were subjected to bilateral renal ischemia for 45 min followed by reperfusion for up to 48 h. One group of rats received IPo prior to restoring full perfusion. Another group was administered 100 mg/kg HSP inhibitor quercetin, injected intraperitoneally 1 h prior to ischemia. Control rats received sham operations. Renal IR resulted in severe morphological and pathological changes, with increased serum creatinine and blood urea nitrogen concentrations. IR resulted in increased inflammation by inducing plasma tumor necrosis factor-α and renal nuclear factor kappa-light-chain-enhancer of activated B cells expression. IR also increased lipid peroxidation, as indicated by elevated malondialdehyde content, reduced superoxide dismutase activity and increased renal apoptosis. Renal HSP70, HSP27 and HO-1 mRNA and protein levels were increased by IR and further elevated by IPo. IPo attenuated these changes observed in pathology, lipid peroxidation, apoptosis and inflammation. Quercetin treatment abolished all the protective effects of IPo. In conclusion, this study showed that IPo can attenuate lipid peroxidation, apoptosis and inflammation as well as renal IRI by upregulating the expression of HSP70, HSP27 and HO-1.

Background. There is much evidence that confirms the inextricable link between inflammation and malignancy. Inflammation-related regulators were involved in the progression of kidney renal clear cell carcinoma (KIRC). However, the predictive role of single gene biomarkers is inadequate, and more accurate prognostic models are necessary. We undertook the current research to construct a robust inflammation-related gene signature that could stratify patients with KIRC. Methods. The transcriptome sequencing data along with clinicopathologic information of KIRC were obtained from TCGA. A list of inflammation-related genes was acquired from the Molecular Signatures Database. Using the RNA-seq and survival time data from the TCGA training cohort, an inflammation-related gene signature was built using bioinformatic methods, and its performance in predicting patient prognosis was assessed by Kaplan–Meier and ROC curve analyses. Furthermore, we explored the association of risk score with immune score, stromal score, tumor immune-infiltrating cells (TIICs), immunosuppressive molecules, m6A regulators, and autophagy-related biomarkers. Results. Herein, nine inflammation-related hub genes (ROS1, PLAUR, ACVR2A, KLF6, GABBR1, APLNR, SPHK1, PDPN, and ADORA2B) were determined and used to build a predictive model. All sets, including training set, four testing sets, and the entire TCGA group, were divided into two groups (low and high risk), and Kaplan–Meier curves all showed an adverse prognosis for patients in the high-risk group. ESTIMATE algorithm revealed a higher immune score in the high-risk subgroup. CIBERSORT algorithm illustrated that the high-risk group showed higher-level immune infiltrates. Furthermore, LAG3, TIGIT, and CTLA4 were overexpressed in the high-risk subgroup and positively associated with risk scores. Moreover, except for METTL3 and ALKBH5, the other m6A regulators decreased in the high-risk subgroup. Conclusions. In conclusion, a novel inflammation-related gene signature comprehensively constructed in the current study may help stratify patients with KIRC.

Background: Open heart surgery is performed with the aid of cardiopulmonary bypass (CPB) techniques that may cause neuronal injuries. Objective: This study investigated the potential protective effect of oleocanthal pre-treatment against CPB-induced cerebral injury. Methods: Oleocanthal 30 mg/kg i.p. was administered 3 h before CPB induction in the treated group. Behavioral neurological scores and cerebral injury were assessed to determine the effects of oleocanthal, based on oxidative stress and serum mediators of inflammation by enzyme-linked immunosorbent assay (ELISA). Quantitative Polymerase Chain Reaction (qRT-PCR) was used to estimate the mRNA expression of Toll-like receptor 4 (TLR4) and Interleukin 1 Receptor Associated Kinase 4 (IRAK4) proteins in the cerebral tissue of rats CPB-induced injury. Western blot assay and histopathology were also performed. Results: The findings suggest that pre-treatment with oleocanthal reduced neurological dysfunction and cerebral injury. Parameters of oxidative stress and cytokine levels were reduced in the serum of the oleocanthal treated group compared with the CPB-only group. Pre-treatment with oleocanthal ameliorated the expression of TLR-4, IRAK4, and Zonula occludens-1 (ZO-1) proteins in the cerebral tissue of the CPB-injured rats. Conclusions: The results revealed that treatment with oleocanthal protected against cerebral damage by controlling microglia inflammation through the TLR-4 pathway.