A Multifactorial Risk Score System for the Prediction of Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus.

Purpose: In-depth investigations of risk factors for the identification of diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM) are rare. We aimed to investigate the risk factors for developing DKD from multiple types of clinical data and conduct a comprehensive risk assessment for individuals with diabetes. Methods: We carried out a case-control study, enrolling 958 patients to identify the risk factors for developing DKD in T2DM patients from a database established from inpatient electronic medical records. Multivariable logistic regression was applied to develop a prediction model and the performance of the model was evaluated using the area under the curve (AUC) and calibration curve. A multifactorial risk score system was established according to the Framingham Study risk score. Results: DKD accounted for 34.03% of eligible patients in total. Twelve risk factors were selected in the final prediction model, including age, duration of diabetes, duration of hypertension, fasting blood glucose, fasting C-peptide, insulin use, systolic blood pressure, low-density lipoprotein, γ-glutamyl transpeptidase, platelet, uric acid, and thyroid stimulating hormone; and one protective factor, serum albumin. The prediction model showed an AUC of 0.862 (95% Confidence Interval (CI) 0.834-0.890) with an accuracy of 81.5% in the derivation dataset and an AUC of 0.876 (95% CI 0.825-0.928) in the validation dataset. The calibration curves were excellent and the estimated probability of DKD was more than 80% when the cumulative score for risk factors reached 17 points. Conclusion: Newly recognized risk factors were applied to assess the development of DKD in T2DM patients and the established risk score system was a reliable and feasible tool for assisting clinicians to identify patients at high risk of DKD.

Urinary Exosomal MicroRNAs as New Noninvasive Biomarkers of IgA Nephropathy.

Immunoglobulin A nephropathy (IgAN) is the most common type of primary glomerulonephritis. It is very important to find new noninvasive biomarkers for the diagnosis and treatment of IgAN. The purpose of this study was to explore the clinical value of urinary exosomal miRNAs in IgAN. In this study, urinary exosomes were isolated from 29 IgAN patients and 29 healthy controls. The miRNA was analyzed by high-throughput sequencing. The expression of hsa-miR-451a and hsa-let-7d-3p was examined by real-time quantitative polymerase chain reaction (RT-qPCR). The diagnostic value of miRNAs was evaluated using receiver operating characteristic (ROC) curves. Here, hsa-miR-451a and hsa-let-7d-3p were upregulated in IgAN patients compared with healthy controls. We evaluated the diagnostic value of hsa-miR-451a and hsa-let-7d-3p using ROC curves; hsa-miR-451a (AUC = 0.805, p = 0.001), hsa-mir-7d-3p (AUC = 0.76, p = 0.0049), and the combination of hsa-miR-451a and hsa-let-7d-3p (AUC = 0.8125, p = 0.0007). Hsa-miR-451a has correlations with Lee's grades (r = 0.511, p = 0.021), and 24-h urinary protein excretion (UPE; r = 0.557, p = 0.011). Hsa-let-7d-3p showed correlations with Lee's grades (r = 0.6, p = 0.005), UPE (r = 0.518, p = 0.019), serum creatinine (r = 0.564, p = 0.01), and estimated glomerular filtration rate (r = -0.532, p = 0.016). According to the Oxford classification, for hsa-miR-451a, S0 had lower levels than S1 (p = 0.016); for hsa-mir-7d-3p, M0 had lower levels than M1 (p = 0.05). These findings suggest that hsa-miR-451a and hsa-let-7d-3p may serve as noninvasive biomarkers for the evaluation of IgAN.

Differential Expression of Urinary Exosomal miRNA in Idiopathic Membranous Nephropathy and Evaluation of its Diagnostic Value.

Urinary exosomal miRNA is an ideal non-invasive biomarker of renal disease, but little is known about its ability to diagnose idiopathic membranous nephropathy (IMN). The purpose of this study was to explore the clinical value of urinary exosomal miRNAs in IMN. Urine samples were collected from 36 IMN patients and 36 healthy subjects. Some samples were used to analyze the miRNA profiles of urinary exosomes by high-throughput sequencing. The remaining cases were verified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Additionally, the serum of the patients and healthy people was collected, and the clinical parameters were detected. Through high-throughput sequencing of samples, it was found that 20 miRNAs were markedly down-regulated. MiR-9-5p and miR-30b-5p were selected for verification, and the results were consistent with those of high-throughput sequencing. MiR-9-5p was correlated with the level of triglyceride and estimated glomerular filtration rate. MiR-30b-5p was related to the levels of anti-phospholipase A2 receptor antibody, serum albumin, ß 2-microglobulin and the ratio of global sclerosis/observed glomeruli number. The analysis of Receiver Operating Characteristic curves revealed that miR-30b-5p and miR-9-5p showed a potential diagnostic value for IMN. This study showed that there were significant differences in urinary exosome miRNA profiles between IMN patients and healthy persons. MiR-30b-5p and miR-9-5p may become new non-invasive biomarkers of IMN.

Recombinant water stress protein 1 (Re-WSP1) suppresses colon cancer cell growth through the miR-539/ß-catenin signaling pathway.

BACKGROUND: Nostoc commune Vauch. is a nitrogen-fixing blue-green algae that expresses a large number of active molecules with medicinal properties. Our previous study found that a water stress protein (WSP1) from N. commune and its recombinant counterpart (Re-WSP1) exhibited significant anti-colon cancer activity both in vitro and in vivo. This study is to investigate the effects of Re-WSP1 on proliferation of colon cancer cells and to elucidate the relevant mechanisms. METHODS: Real-time quantitative PCR was used to detect the expression of miR-539 in colon cancer HT-29 and DLD1 cells. Colon cancer cells were transfected with miR-539 mimics and negative controls, and cell proliferation were detected by CCK8 and clonogenic assays. The target gene of miR-539 was predicted, and the dual luciferase reporter gene experiment was used to verify the target gene. After colon cancer cells were transfected with miR-539 mimics or inhibitors, the expression of target gene ß-catenin was detected by Western blot. miR-539 inhibitor confirmed cell proliferation. RESULTS: Re-WSP1 inhibited colon cancer cell growth in a dose-dependent manner. Re-WSP1 inhibited the expression of ß-catenin, which was partly reversed by LiCl treatment. Quantitative PCR analysis showed that the expression of miR-539 was significantly upregulated after Re-WSP1 treatment. Moreover, miR-539 negatively regulated the expression of ß-catenin by directly binding to the 3'UTR of ß-catenin mRNA. The cell growth inhibition and the decrease in ß-catenin expression induced by Re-WSP1 were significantly reversed by miR-539 inhibitor. CONCLUSION: Re-WSP1 suppresses colon cancer cell growth via the miR-539/ß-catenin axis.