Alpha-kinase1 promotes tubular injury and interstitial inflammation in diabetic nephropathy by canonical pyroptosis pathway

BACKGROUND: Alpha-kinase 1 (ALPK1) is a master regulator in inflammation and has been proved to promote renal fibrosis by promoting the production of IL-1ß in diabetic nephropathy (DN) mice. Pyroptosis is involved in high glucose (HG)-induced tubular cells injury, characterized by activation of Gasdermin D (GSDMD) and the release of IL-1ß and IL-18, resulting in inflammatory injury in DN. It is reasonable to assume that ALPK1 is involved in pyroptosis-related tubular injury in DN. However, the mechanism remains poorly defined. METHODS: Immunohistochemistry (IHC) staining was performed to detect the expression of pyroptosis- and fibrosis-related proteins in renal sections of DN patients and DN mice. DN models were induced through injection of streptozotocin combined with a high-fat diet. Protein levels of ALPK1, NF-κB, Caspase-1, GSDMD, IL-1ß, IL-18 and α-SMA were detected by Western blot. HK-2 cells treated with high-glucose (HG) served as an in vitro model. ALPK1 small interfering RNA (siRNA) was transfected into HK-2 cells to down-regulate ALPK1. The pyroptosis rates were determined by flow cytometry. The concentrations of IL-1ß and IL-18 were evaluated by ELISA kits. Immunofluorescence staining was used to observe translocation of NF-κB and GSDMD. RESULTS: The heat map of differentially expressed genes showed that ALPK1, Caspase-1 and GSDMD were upregulated in the DN group. The expression levels of ALPK1, Caspase-1, GSDMD and CD68 were increased in renal biopsy tissues of DN patients by IHC. ALPK1expression and CD68+ macrophages were positively correlated with tubular injury in DN patients. Western blot analysis showed increased expressions of ALPK1, phospho-NF-κB P65, GSDMD-NT, and IL-1ß in renal tissues of DN mice and HK-2 cells, accompanied with increased renal fibrosis-related proteins (FN, α-SMA) and macrophages infiltration in interstitial areas. Inhibition of ALPK1 attenuated HG-induced upregulation expressions of NF-κB, pyroptosis-related proteins Caspase-1, GSDMD-NT, IL-1ß, IL-18, α-SMA, and pyroptosis level in HK-2 cells. Also, the intensity and nuclear translocation of NF-κB and membranous translocation of GSDMD were ameliorated in HG-treated HK-2 cells after treatment with ALPK1 siRNA. CONCLUSIONS: Our data suggest that ALPK1/NF-κB pathway initiated canonical caspase-1-GSDMD pyroptosis pathway, resulting in tubular injury and interstitial inflammation of DN.

Effects of parental involvement on children s eye use behavior / 中国学校卫生

Objective@#To analyze the correlation between parental involvement and the formation of good eye use behavior in children,and to provide theoretical basis for more accurate prevention and control of myopia.@*Methods@#A total of 2 726 children and their parents from 3 primary schools were selected from April to May 2021 by clustering sampling method. Children s ocular parameters, eye use behavior, general characteristics of parents, and parental involvement were collected through ocular measurements and questionnaires, respectively.@*Results@#Parental involvement was associated with family economic, parental education level, and parental myopic status( P <0.05). Children s myopia risk was associated with parental involvement: lower myopia risk was associated with frequent parental involvement in behavioral management of child sleep and child outdoor activities( P <0.01). Parents who always/frequently participate in the management of children s eye behavior have an average daily screen time of <2 h ( OR= 1.95 , 95%CI =1.31-2.90), and daily outdoor activity time>2 h ( OR=0.78, 95%CI =0.65-0.93), daily sleep time >8 h ( OR= 0.52 , 95%CI =0.40-0.68), daily continuous reading and writing time <1 h ( OR=1.33, 95%CI =1.30-1.56), reading and writing The distance from the desktop > 30 cm ( OR=0.57, 95%CI =0.34-0.95) had a statistically significant effect ( P <0.05).@*Conclusion@#High parental involvement may help school age children develop good eye habits and reduce the risk of childhood myopia. Parental involvement is higher among those who had myopia themselves, and parental involvement is positively associated with total household income and parental literacy.

Advances in antitumor functions and mechanisms of apolipoprotein A-Ⅰ / 中国肿瘤临床

Apolipoprotein A-Ⅰ (ApoA-Ⅰ), the predominant protein in plasma HDL, regulates cholesterol metabolism and exhibits anti-in-flammatory and antioxidant functions. Multiple clinical studies suggest that serum ApoA-Ⅰ levels are associated with the occurrence, development, and prognosis of malignant tumors. Laboratory research also shows that ApoA-Ⅰ and ApoA-Ⅰ mimetics exert antitumor ef-fects through antioxidation, immunoregulation, cholesterol metabolism, lysophosphatidic acid binding, and anti-angiogenesis. This pa-per reviews the role of ApoA-Ⅰ and ApoA-Ⅰ peptides in tumorigenesis and their potential value in diagnosis, treatment, and prognosis.

Cardiovascular effects of sexual activity.

Sexuality is a major way of intimacy in human being and it is very important in gender relationship, contributing to over all health. However, since association between sexual activity and sudden death determined by forensic autopsies related to cardiac or cerebral causes has been reported, some people with heart disease often abstain from sexual activity that could affect the quality of life. It is therefore important to learn the physical demand of sexual activity and the risk it may trigger. For decades, the cardiologists have conducted observational studies and clinical trials on healthy volunteers or patients. The most common indices responding to cardiovascular risks of sexuality were variances of blood pressure (BP) and heart rate (HR), monitored by ambulatory blood pressure and dynamic electrocardiogram recording. BP and HR increase during the coitus just briefly and quickly recover to baseline level. Peak coital BP occurred at onset of plateau phase and quickly decreased, instead of emerged at orgasm as most people supposed. The metabolic equivalent of energy expenditure during the orgasm was relatively modest when compared with other physical exertion such as cycling. Epidemiological studies have suggested that sexual activity has favorable effect on health in the long term. This review summarizes and discusses the advances in the researches dealing with cardiovascular effects of sexual activity to better inform the cardiac patients.