Unraveling the complex regulatory pathways that mediate the effects of phosphate on vascular smooth muscle cells (VSMCs) may provide novel targets and therapies to limit the destructive effects of vascular calcification (VC) in patients with chronic kidney disease (CKD). Our previous studies have highlighted several signaling networks associated with VSMC autophagy, but the underlying mechanisms remain poorly understood. Thereafter, the current study was performed to characterize the functional relevance of O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) in high phosphate-induced VC in CKD settings. We generated VC models in 5/6 nephrectomized rats in vivo and VSMC calcification models in vitro. Artificial modulation of OGT (knockdown and overexpression) was performed to explore the role of OGT in VSMC autophagy and VC in thoracic aorta, and in vivo experiments were used to substantiate in vitro findings. Mechanistically, co-immunoprecipitation (Co-IP) assay was performed to examine interaction between OGT and kelch like ECH associated protein 1 (KEAP1), and in vivo ubiquitination assay was performed to examine ubiquitination extent of nuclear factor erythroid 2-related factor 2 (NRF2). OGT was highly expressed in high phosphate-induced 5/6 nephrectomized rats and VSMCs. OGT silencing was shown to suppress high phosphate-induced calcification of VSMCs. OGT enhances KEAP1 glycosylation and thereby results in degradation and ubiquitination of NRF2, concurrently inhibiting VSMC autophagy to promote VSMC calcification in 5/6 nephrectomized rats. OGT inhibits VSMC autophagy through the KEAP1/NRF2 axis and thus accelerates high phosphate-induced VC in CKD.
Background: In hemodialysis (HD) patients, anemia is greatly improved due to regular weekly use of iron and erythropoietin (EPO), but a large number of patients still show persistent anemia. We do a survey to elucidate the influencing factors that contribute to the failure of hemoglobin (Hb) to meet the standard and provide epidemiological data reference for promoting the recognition of renal anemia and improving the treatment effect of renal anemia. Methods: The clinical data of End-Stage Renal Disease (ESRD) HD patients in 22 tertiary hospital HD centers in Liaoning Province from September 2021 to June 2022 were collected by convenient sampling. According to the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) anemia diagnostic criteria. The standard of Hb compliance: Hb ≥110 g/L is considered as Hb compliant, and Hb <110 g/L as Hb noncompliant. The factors influencing Hb up-to-standard in ESRD HD patients and their correlations were analyzed by comparison between the two groups. Results:The results of this study showed that among the 1,652 ESRD patients investigated in Liaoning Province, the prevalence rate of anemia was 89.29% (1,475/1,652), and the Hb compliance rate was 46.25% (764/1,652). The Hb compliance rate in maintenance hemodialysis (MHD) patients with different primary diseases was statistically significant (P<0.05). Compared with the Hb non-standard group, the gender, dialysis access, HD frequency, concurrent infection, primary disease of ESRD patients, red blood cell (RBC) count, hematocrit (HCT), mean RBC Hb concentration, mean RBC Hb content, platelet (PLT), albumin (ALB), total protein (TP), serum creatinine (Cr), serum calcium (Ca), serum potassium (K), ferritin (Fer), serum iron (SI), and transferrin (TRE) saturation were significantly different between both groups (P<0.05).
In December 2019, the 2019 novel coronavirus disease (COVID-19), which has been identified to be caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in China and spread across the world. Higher plasma levels of cytokines, including interleukin (IL)-6, IL-2, IL-7, IL-10, and tumor necrosis factor-α, were found in patients with COVID-19, which implies the occurrence of a cytokine storm and its association with disease severity. Extracorporeal blood purification has been proven to effectively remove the released inflammatory cytokines. In this study, we report on a patient with COVID-19 who benefited from hemoadsorption.
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