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Renal fibrosis (RF) is an important pathogenesis for renal function deterioration in chronic kidney disease. Secreted frizzled-related protein 5 (SFRP5) is an anti-fibrotic adipokine but its direct role on RF remains unknown. It was aimed to study the protective effect of SFRP5 against RF and interference with Wnt/β‐catenin signaling pathway for the first time. First, the therapeutic efficacy of SFRP5 was evaluated by adenovirus overexpression in rats with unilateral ureteral obstruction (UUO) in vivo. Thirty-six rats were randomly divided into the sham, UUO, and SFRP5 (UUO + Ad-SFRP5) groups. Half rats in each group were selected at random for euthanasia at 7 days and the others until 14 days. Then, the transforming growth factor (TGF)-β1-induced epithelial–mesenchymal transition (EMT) was established in HK-2 cells in vitro. The cells were divided into four groups: the control group, the TGF-β1 group, the TGF-β1 + SFRP5 group, and the TGF-β1 + SFRP5 + anti-SFRP5 group. The makers of EMT and Wnt/β‐catenin pathway proteins were investigated. In the UUO model, expression of SFRP5 showed compensatory upregulation, and adenoviral-mediated SFRP5 over-expression remarkably attenuated RF, as demonstrated by maintenance of E-cadherin and suppression of α-smooth muscle actin (SMA). In vitro, SFRP5 was shown to inhibit TGF-β1-mediated positive regulation of α-SMA, fibronectin, collagen I but negative regulation of E-cadherin. Furthermore, SFRP5 abrogated activation of Wnt/β-catenin, which was the essential pathway in EMT and RF pathogenesis. The changes after a neutralizing antibody to SFRP5 confirmed the specificity of SFRP5 for inhibition. These findings suggest that SFRP5 can directly ameliorate EMT and protect against RF by inhibiting Wnt/β-catenin pathway.

Objective To explore the protective effect of polypeptide Apelin on podocyte mitochondria in diabetic nephropathy and underling mechanisms. Methods Human renal podocytes were divided into four experimental groups: control group, high glucose(HG) group(glucose 25 mmol/L, 48 h), Apelin intervention HG group (Apelin-13 1 μmol/L, 48 h) and Apelin group (Apelin-13 1 μmol/L, 48 h). The podocyte apoptosis was observed by TUNEL staining, the expression of mitochondrial membrane protein FUNDC1 was detected by Western blot, and the binding of mitochondrial fission protein DRP1 to FUNDC1 was examined by immunoprecipitation. The 8-week-old male mice were divided into three experimental groups: control group, diabetes group (intraperitoneal injection of streptozotocin 150 mg/kg, only one time) and Apelin intervention DM group (intraperitoneal injection of Apelin-13 0.3 μmol/kg, daily). The morphology of renal was observed by PAS staining and transmission electron microscopy. Plasma creatinine (Cr), urea nitrogen, urinary albumin and creatinine were detected by ELISA kit. The level of creatinine clearance rate (Ccr) and urinary albumin/creatinine (ACR) was calculated. Results Compared with the control group, the podocyte apoptosis and expression of FUNDC1 in the HG group increased significantly (P＜0.05), and the combination of mitochondrial fission division protein DRP1 to FUNDC1 raised. Meanwhile, compared with the HG group, the number of apoptosis, the expression of FUNDC1 (P＜0.05), and the combination of DRP1 to FUNDC1 all reduced in Apelin intervention HG group. Animal experiments showed that the kidney structure of the control group was intact. In the DM group, the number of podocytes decreased significantly, the foot processes were fused and dropped off. In the Apelin intervention DM group, podocyte lesions were less severe than those in the DM group. Compared with the control group, the level of plasma Cr, BUN and urine ACR in the DM group increased, while the level of Ccr decreased significantly (P＜0.05). However, compared with the DM group, the level of above biomarkers in the Apelin intervention DM group was improved(P＜0.05).Conclusions Apelin keeps mitochondrial homeostasis and reduces podocyte apoptosis by inhibiting the expression of mitochondrial membrane protein FUNDC1, which may contribute to alleviation of diabetic nephropathy.

Recent studies have shown that microRNA-16-5p (miR-16-5p) plays a crucial role in the pathological mechanism of vascular calcification. Nevertheless, the expression profile of miR-16-5p in maintenance hemodialysis (MHD) patients who are predisposed to vascular calcification remains unknown. This study aims to investigate the potential associations between calcification risk and serum miR-16-5p expression among MHD patients. This cross-sectional study involved 132 MHD patients from the Dialysis Center of Beijing Friendship Hospital between 1 January 2019 and 31 December 2020. The degree of calcification in MHD patients was assessed using the Abdominal aortic calcification (AAC) score, and miR-16-5p expression was quantified using quantitative real-time polymerase chain reaction (qRT-PCR) with the 2–ΔΔCT method. Statistical analyses, including spearman correlation, linear regression and logistic regression analysis were used to explore the associations between laboratory parameters and AAC score. Calcifications were observed in 79(59.80%) patients. The linear regression showed a one-quartile decrease in miR-16-5p expression led to a significant increase in the AAC score by 5.336 (95% CI: 2.670–10.662, p = 0.000). Multivariate logistic regression analyses revealed that decreased miR-16-5p expression, reduced serum urea nitrogen, elevated white blood cell count, and longer dialysis vintage were significantly associated with an increased incidence of vascular calcification. The Area Under the Curve (AUC) of the Receiver Operating Characteristic (ROC) of the miR-16-5p-based logistic regression model was 0.842 (95% CI: 0.771–0.913, p = 0.000). There was an independent association between miR-16-5p expression and calcification degree. Lower miR-16-5p expression levels seem to be a potential risk factor of vascular calcification in MHD patients. [ABSTRACT FROM AUTHOR]

Vascular calcification (VC) is highly prevalent in patients undergoing hemodialysis, and is a significant contributor to the mortality rate. Therefore, biomarkers that can accurately predict the onset of VC are urgently required. Our study aimed to investigate serum miR-15a levels in relation to VC and to develop a predictive model for VC in patients undergoing hemodialysis at the Beijing Friendship Hospital hemodialysis center between 1 January 2019 and 31 December 2020. The patients were categorized into two groups: VC and non-VC. Logistic regression (LR) models were used to examine the risk factors associated with VC. Additionally, we developed an miR-15a-based nomogram based on the results of the multivariate LR analysis. A total of 138 patients under hemodialysis were investigated (age: 58.41 ± 13.22 years; 54 males). VC occurred in 79 (57.2%) patients. Multivariate LR analysis indicated that serum miR-15a, age, and WBC count were independent risk factors for VC. A miR-15a-based nomogram was developed by incorporating the following five predictors: age, dialysis vintage, predialysis nitrogen, WBC count, and miR-15a. The receiver operating characteristic (ROC) curve had an area under the curve of 0.921, diagnostic threshold of 0.396, sensitivity of 0.722, and specificity of 0.932, indicating that this model had good discrimination. This study concluded that serum miR-15a levels, age, and white blood cell (WBC) count are independent risk factors for VC. A nomogram constructed by integrating these risk factors can be used to predict the risk of VC in patients undergoing hemodialysis. [ABSTRACT FROM AUTHOR]

Background: Neurovascular coupling (NVC) reflects the close connection between neural activity and cerebral blood flow (CBF) responses, providing new insights to explore the neuropathological mechanisms of various diseases. Non‐dialysis patients with chronic kidney disease (CKD) exhibit cognitive decline, but the underlying pathological mechanisms are unclear. Methods: The prospective study involved 53 patients with stage 1–3a CKD (CKD1–3a), 78 patients with stage 3b–5 CKD (CKD3b–5), and 52 healthy controls (HC). Our investigation involved voxel‐based assessments of both global and regional BOLD signal characteristics. Additionally, we explored the correlations between neuroimaging indices, Montreal Cognitive Assessment (MoCA) scores, and clinical laboratory findings. Results: Compared to HC, the CKD3b–5 and CKD1–3a groups exhibited lower ALLF and ReHo in the default mode network (DMN), higher CBF in bilateral hippocampus (HIP), higher susceptibility values in bilateral caudate nucleus (CAU) and putamen (PUT), and lower susceptibility values in bilateral HIP. At the global level, the coupling coefficients were lower in CKD1–3a and CKD3b–5 groups than in HC. At the ROI level, the CBF‐ALFF and CBF‐ReHo coupling in HIP and basal ganglia regions were lower in CKD3b–5 groups than in the CKD1–3a group. Most importantly, susceptibility‐ALFF in ANG.R may mediate the effects of phosphorus on cognitive decompensation in patients with CKD1‐3a. Conclusions: Non‐dialysis patients with CKD exhibit abnormal NCV, which is associated with the cognitive decline. Specifically, the susceptibility‐ALFF may serve as a valuable biomarker for early assessment of cognitive decline in CKD, offering insights into the pathogenesis of cognitive decline in CKD. [ABSTRACT FROM AUTHOR]

Background End-stage renal disease (ESRD) patients on maintenance haemodialysis (HD) often have damage to brain white matter (WM) and cognitive impairment. However, whether this damage is caused by maintenance HD or renal dysfunction is unclear. Herein we investigate the natural progression of WM damage in patients with ESRD and the effects of HD on WM using tract-based spatial statistics (TBSS) and fixel-based analysis (FBA). Methods Eighty-one ESRD patients, including 41 with no dialysis (ND) and 40 on HD, and 46 healthy controls (HCs) were enrolled in this study. The differences in WM among the three groups [ESRD patients with HD (ESRD-HD), ESRD patients without HD (ESRD-ND) and HCs] were analysed using TBSS and FBA. Pairwise comparison was then used to compare the differences in WM between two groups. The relationships between WM and neurocognitive assessments/clinical data were analysed in ESRD patients with and without HD. Results The damage to WM in ESRD-ND and ESRD-HD appeared around the lateral ventricles in TBSS, while FBA reflected that the changes had extended to adjacent WM in the anterior hemisphere, with a larger region in ESRD-HD compared with ESRD-ND and the brainstem was also widely affected in ESRD-HD. The Montreal Cognitive Assessment (MoCA) scores were lower in the ESRD-HD group. RD in the body of the corpus callosum were negatively correlated with MoCA scores in both groups. Fiber density and cross-section (FDC) in the left thalamo-prefrontal projection (T_PREFL) and left and right cingulum (CGL and CGR) were positively correlated with MoCA scores in both groups. Creatinine (Cr) was positively correlated with FDC in some frontal projection fibres in the striatum and thalamus, CG and fronto-pontine tract and was positively correlated with FD mainly in premotor projection fibres in the striatum and thalamus in the ESRD-HD group. Cr was negatively correlated with mean and radial diffusivity in regions of the corona radiata in the ESRD-ND group. Conclusions FBA is more sensitive in detecting differences between ESRD patients and HCs. When ESRD patients receive maintenance HD, the degree of WM damage may not be aggravated, but the range of damaged WM may be expanded, especially in the anterior hemisphere and brainstem. Some of these changes in the anterior hemisphere may contribute to cognitive decline. [ABSTRACT FROM AUTHOR]

Wheat ground to different degrees was fermented in high-temperature Daqu (HT-Daqu) to evaluate the effects of grinding on fermentation and the maturity ratio. After fermentation, the microbial community structures and functional characteristics of three categories (black, yellow, and white) of HT-Daqu were analyzed via metagenomic sequencing. The temperature of the low-grinding-degree group reached 60 °C in the shortest time, with time gaps observed in three temperature rises with no prolonged overheating. Yellow Daqu accounted for 82.37% of the mature Daqu in this group, which was the highest ratio among the three groups with different grinding degrees. The total relative abundance of major bacteria in black and yellow Daqu of the high-grinding-degree group was more than 28.95%, which was higher than that in the other two groups. Aspergillus, Rasamsonia, Paecilomyces, and Talaromyces dominated the microbial community in the medium- and low-grinding-degree groups, accounting for more than 73.95% of the total, significantly higher than the high-grinding-degree group. The genes of glycoside hydrolases in black and yellow Daqu were mainly contributed by Eurotiales including Rasamsonia, Aspergillus, and Paecilomyces (46.78%~62.33%), while those in white Daqu were found to be mainly derived from Saccharopolyspora. These results demonstrate the importance of the grinding degree of wheat on the quality of Daqu and identifies the microbial sources of genes encoding different carbohydrate-active enzymes. The findings have a practical significance for understanding the fermentation of HT-Daqu comprehensively and guiding the production of HT-Daqu scientifically. [ABSTRACT FROM AUTHOR]

The aim of this article is to review the application progress of proteomics technology in brain injury research in recent years, point out the current problems that need to be overcome, and explore the application prospects of proteomics analysis in brain injury. This study also aims to retrieve all literature on brain injury and proteomics and summarize it. Through searching and screening, the widespread application of proteomics technology in the treatment of traumatic brain injury (TBI) and the use of a large number of TBI biomarkers were discovered. The pathways mediated by some biomarkers and the physiological and pathological mechanisms of occurrence were elucidated. The current classification of brain injury is mainly based on subjective evaluation of clinical symptoms, combined with objective imaging. However, its practical value is often limited when applied to prognosis evaluation in brain injury. Proteomics technology can make up for this deficiency and provide a reference for the prevention and treatment of brain injury. [ABSTRACT FROM AUTHOR]

Background The effectiveness of multitarget combination therapy with a corticosteroid, cyclosporine and mycophenolate mofetil for idiopathic membranous nephropathy (IMN) is unclear. In the present study, we aimed to compare the efficacy and safety of multitarget therapy with a cyclical corticosteroid–cyclophosphamide regimen in patients with IMN. Methods This was a single-centre, prospective, randomized, controlled trial. We randomly assigned patients with IMN to receive multitarget therapy (a combination of prednisone, cyclosporine and mycophenolate mofetil) or 6-month cyclical treatment with a corticosteroid and cyclophosphamide. The study patients were followed up for 12 months. The primary outcome was a composite of complete or partial remissions at 12 months. Adverse events were also assessed. Results The study cohort comprised 78 patients, 39 of whom received multitarget therapy and the other 39 cyclical alternating treatment with a corticosteroid and cyclophosphamide. At 12 months, 31 of 39 patients (79%) in the multitarget therapy group and 34 of 39 (87%) in the corticosteroid–cyclophosphamide group had achieved complete or partial remissions (relative risk 0.93; 95% confidence interval 0.72–1.21; P  = .85; log-rank test). The prevalence of adverse events was significantly lower in the multitarget therapy group than in the corticosteroid–cyclophosphamide group [46% (18 of 39) vs 74% (29 of 39); P  < .05]. Conclusions Multitarget therapy for IMN patients is noninferior to cyclical alternating treatment with corticosteroid and cyclophosphamide in inducing proteinuria remission and has a better safety profile than the corticosteroid–cyclophosphamide combination. [ABSTRACT FROM AUTHOR]