Amelioration of Renal Injury by Resveratrol in a Rat Renal Transplantation Model via Activation of the SIRT1/NF-κB Signaling Pathway.

Purpose: The improvement of the long-term survival of patients receiving kidney transplantation remains challenging. Ischemia reperfusion injury (IRI) reduces long-term renal graft survival in the early posttransplantation phase. However, few studies have investigated the effects of IRI on the pathogenesis of chronic renal graft failure. Silent information regulator 1 (SIRT1) regulates antioxidative stress and inflammatory response and protects against IRI. This study is aimed at investigating the role of resveratrol (RSV), an SIRT1 activator, in preventing renal injury in a rat renal transplantation model. Methods: A classical F334-to-LEW orthotopic renal transplantation rat model was established. The experiment group was treated with RSV from three days prior to kidney transplantation and the treatment lasted until the day of harvest. Uninephrectomized F344 and Lewis rats were used as controls. After 12 weeks, the effects of RSV were evaluated according to renal function, histopathology, immunohistochemistry, and western blotting. The activities of oxidative stress-related markers and proinflammatory cytokines were also assessed. Results: RSV treatment significantly ameliorated renal function and histopathological lesions in kidney-transplanted rats and increased the levels of GSH, SOD, and CAT and decreased the levels of MDA and iNOS. Furthermore, RSV also inhibited the expression of proinflammatory cytokines/chemokines such as TNF-α, CD68, and IL-6 in kidney-transplanted rats. In addition, the transplant group displayed significantly lower level of SIRT1 and higher level of Ac-NF-κBp65. RSV increased the expression of SIRT1 and decreased the expression of Ac-NF-κBp65. Conclusion: SIRT1 plays an important role in the pathogenesis of chronic renal allograft dysfunction. It is a potential therapeutic agent for ameliorating inflammation and oxidative stress-induced renal injury following kidney transplantation by activating the SIRT1/NF-κB signaling pathway.

Potential role of anti-inflammatory HDL subclasses in metabolic unhealth/obesity.

High-density lipoprotein (HDL) particles comprising heterogeneous subclasses of different functions exert anti-inflammatory effects by interacting with immune-response cells. However, the relationship of HDL subclasses with immune-response cells in metabolic unhealth/obesity has not been defined clearly. The purpose of this study was to delineate the relational changes of HDL subclasses with immune cells and inflammatory markers in metabolic unhealth/obesity to understand the role of anti-inflammatory HDL subclasses. A total of 316 participants were classified by metabolic health. HDL subclasses were detected by microfluidic chip electrophoresis. White blood cell (WBC) counts and lymphocytes were assessed using automatic haematology analyser. Levels of high-sensitivity C-reactive protein (hs-CRP) and interleukin 6 (IL-6) were measured. In our study, not only the distribution of HDL subclasses, but also HDL-related structural proteins changed with the deterioration of metabolic disease. Moreover, lymphocytes and inflammation factors significantly gradually increased. The level of HDL2b was negatively associated with WBC, lymphocytes and hs-CRP in multivariable linear regression analysis. In multinomial logistic regression analysis, high levels of HDL3 and low levels of HDL2b increased the probability of having an unfavourable metabolic unhealth/obesity status. We supposed that HDL2b particles may play anti-inflammation by negatively regulating lymphocytes activation. HDL2b may be a therapeutic target for future metabolic disease due to the anti-inflammatory effects.

Comparison of Novel Metabolic Indices in Estimation of Chronic Kidney Diseases in a Southern Chinese Population.

BACKGROUND: To determine the optimal cut-off values and evaluate the associations of product of triacylglycerol and glucose (TyG), lipid accumulation product (LAPI), visceral adiposity index (VAI) with chronic kidney diseases (CKD) stratified by sex. METHODS: From January to April 2018, our team had conducted a large-scale cross-sectional survey that contained 2720 individuals on the southern coast of China. Logistic regression analysis and receiver operating characteristic (ROC) analyses were used to evaluate the optimal cut-off and value of TyG, LAPI, VAI for predicting CKD. RESULTS: A multivariate logistic regression analysis found that the TyG had the better value of prediction for the presence of CKD for the highest quartile vs the lowest quartile in both males (OR: 3.65; 95% CI, 2.04-6.52; p<0.001) and females (OR: 3.50; 95% CI, 2.20-5.56; p<0.001), followed by LAPI and VAI, when further adjusted for cofounder factors, LAPI and VAI both lost their independence, and only TyG remains its significant association with CKD in both males (OR: 2.81; 95% CI, 1.25-6.30; p<0.001) and females (OR: 3.22; 95% CI, 1.56-6.61; p<0.001). ROC curve showed that TyG had the highest AUC for predicting CKD in males (AUC: 0.618). TyG (AUC: 0.670) and LAPI (AUC: 0.670) both had the highest AUC in females. United predicted models which contain TyG were conducted for predicting CKD in males (AUC: 758) and females (AUC: 0.773) and results indicated that multivariate analysis of TyG and other traditional factors can impressively improve the accuracy of predictive probability for CKD. CONCLUSION: TyG is a priority to the other two novel indices and may become valuable makers and have strong predictive power for predicting CKD, especially in females.

The Product of Red Blood Cells and Hematocrit Can Be Used as a Novel Indicator of Impaired Fasting Blood Glucose Status.

OBJECTIVE: To explore whether the red blood cell count multiplied by hematocrit index (RBCHct) in blood routine parameters can indicate the risk of impaired fasting blood glucose (IFG), and whether it is related to insulin resistance and inflammation. METHODS: In this cross-sectional study, previous history of diabetes was excluded, and people with normal and impaired IFG were included. We use Spearman analysis to evaluate the correlation between RBCHct index and fasting plasma glucose, insulin resistance homeostasis model assessment (HOMA-IR), and hypersensitive C-reactive protein (hs-CRP). Binary logistic regression analysis was used to evaluate the RBCHct index for assessing the potential risk of IFG, and the receiver operating characteristic (ROC) curve was used to evaluate the RBCHct index for diagnosing insulin resistance and chronic low-grade inflammatory efficacy among those with IFG. RESULTS: Correlation analysis showed that the RBCHct index and fasting plasma glucose (r=0.088, P=0.003); HOMA-IR (r=0.199, P<0.001); and hs-CRP (r=0.097, P=0.001) were positively correlated. After adjusting for confounding factors, the risk of IFG in the third and fourth quartiles of the RBCHct index increased to 1.889 and 3.048 times. The area under the ROC curve of the RBCHct index for diagnosis of insulin resistance state (HOMA-IR) was 0.695 (p<0.001), and the area under the ROC curve of the RBCHct index for the diagnosis of chronic low-inflammatory state (hs-CRP) was 0.641 (P=0.010). CONCLUSION: The RBCHct index may be a potential indicator for assessing the risk of prediabetes and is closely related to whether the body is in a state of insulin resistance and inflammation under IFG.

Alpha1-Antitrypsin in Urinary Extracellular Vesicles: A Potential Biomarker of Diabetic Kidney Disease Prior to Microalbuminuria.

PURPOSE: Diabetic kidney disease (DKD), which is related to inflammation and immune response, is the primary vascular complication of diabetes mellitus and also the leading etiology of end-stage renal disease. Urinary extracellular vesicles (UEVs) are an attractive source for biomarker detection as they involve molecular constituents derived from their parental sections of the nephron. In this study, we aimed to search for a potential biomarker in UEVs for the early diagnosis and prediction of DKD, especially before the emergence of microalbuminuria. PATIENTS AND METHODS: UEVs were isolated from the urine of healthy subjects, pre-diabetic, and diabetic patients with varying degrees of kidney damage by ultracentrifugation, and the extracted UEVs were used to measure alpha1-antitrypsin (α1-AT) by Western blot. To explore the function of α1-AT in the inflammatory process leading to DKD, we silenced the expression of α1-AT in renal tubular epithelial cells using cell transfection techniques to assess the differential expression of the inflammatory factors such as MCP-1 and TNF-α using qRT-PCR. RESULTS: There was no expression of α1-AT in the UEVs of either healthy or pre-diabetic subjects. Its expression was significantly increased in the UEVs of diabetic patients with normoalbuminuria (prior to microalbuminuria), which was more sensitive and more stable than other renal indexes to predict DKD. Additionally, the expression of α1-AT in UEVs was gradually upregulated with the aggravation of DKD and the decline of renal function. In vitro, the mRNA expression of MCP-1 and TNF-α was significantly decreased when the generation of α1-AT in tubular epithelial cells was inhibited under high glucose stimulation. CONCLUSION: Our results suggest that α1-AT derived from UEVs, especially in diabetic patients with normoalbuminuria, might serve as a potential noninvasive biomarker for diagnosis of DKD early in the development of the disease and may predict the future decline of renal function.

Comparison of the Value of Neutrophil to High-Density Lipoprotein Cholesterol Ratio and Lymphocyte to High-Density Lipoprotein Cholesterol Ratio for Predicting Metabolic Syndrome Among a Population in the Southern Coast of China.

BACKGROUND: This study aimed to determine the optimal cutoff values and evaluate the associations of neutrophil to high-density lipoprotein cholesterol ratio (NHR) and lymphocyte to high-density lipoprotein cholesterol ratio (LHR) with metabolic syndrome (MetS), stratified by sex. METHODS: A large-scale cross-sectional survey was conducted among 1401 adults from January to April 2018 in six communities in Wanzhai Town, Zhuhai City, on the southern coast of China. Receiver operating characteristics (ROC) analyses and logistic regression analysis were conducted to assess the optimal cutoff and value of NHR and LHR for predicting MetS. RESULTS: Hematological parameters showed the correlation with the occurrence of MetS (red blood cells, hemoglobin, and white blood cells and subtypes). Binomial logistic regression analysis found that LHR (OR: 3.671; 95% CI: 2.385-5.651; p<0.001) and NHR (OR: 1.728; 95% CI: 1.353-2.207; p<0.001) can predict MetS in females, independent of confounding factors. Although LHR (OR: 1.571; 95% CI: 1.001-2.468; p=0.05) and NHR (OR: 1.163; 95% CI: 0.909-1.48; p<0.01) were independent risk factors for MetS in males after adjustment for age, current smoking, current alcohol use, physical activity,  educational attainment, waist circumference, systolic pressure, diastolic pressure and hypersensitive C-reactive protein (hs-CRP), when further adjusted for fasting plasma glucose level, LHR and NHR, both lost their independence. ROC curves showed that LHR had the highest AUC for predicting MetS in females and NHR had the highest AUC in males. The cutoff points of LHR and NHR were 1.36 and 2.31 in females, and 1.96 and 3.38 in males. CONCLUSION: LHR and NHR may become valuable makers and have strong predictive power for predicting MetS, especially in females.