Hsa_circ_0008500 inhibits apoptosis of adipose-derived stem cells under high glucose through hsa-miR-1273h-5p/ELK1 axis.

Preliminary researches have confirmed that the number of apoptosis of adipose tissue-derived stem cells (ADSCs) in patients with diabetes is significantly increased, leading to a difficult healing wound. Increasing researches revealed that circular RNAs (circRNAs) can control apoptosis. However, it is still unclear whether and how circRNAs are critical for regulating ADSCs apoptosis. In this study, we utilized in vitro model in which ADSCs were cultivated with normal glucose (NG) (5.5 mM) or high glucose (HG) (25 mM) medium, respectively, and found that more apoptotic ADSCs were observed in HG medium comparing to ADSCs in NG medium. Furthermore, we found that hsa_circ_0008500 attenuated HG-mediated ADSCs apoptosis. In addition, Hsa_circ_0008500 could directly interact with hsa-miR-1273h-5p, acting as a miRNA sponge, which subsequently suppressed Ets-like protein-1(ELK1) expression, the downstream target of hsa-miR-1273h-5p. Thus, these results indicated that targeting the hsa_circ_0008500/hsa-miR-1273h-5p/ELK1 signaling pathway in ADSCs may be a potential target for repairing diabetic wounds.

Diagnostic value of triglyceride and cystatin C ratio in diabetic kidney disease: a retrospective and prospective cohort study based on renal biopsy.

BACKGROUND: Currently, there is a lack of clinical indicators that can accurately distinguish diabetic kidney disease (DKD) from non-diabetic kidney disease (NDKD) in type 2 diabetes. The purpose of this study was to investigate the diagnostic value of triglyceride and cystatin C (TG/ Cys-C) ratio in DKD. Nowadays, there are few studies on the differential diagnosis of TG/ Cys-C ratio between DKD and NDKD. METHODS: The clinical data of patients with type 2 diabetes complicated with proteinuria who underwent renal biopsy from January 2013 to September 2019 in 2 hospitals in Xuzhou were retrospectively collected. According to the pathological classification of kidney, 25 patients in group DKD and 34 patients in non-diabetic kidney disease (NDKD) group were divided into two groups. The admission information and blood biochemical indexes of all patients with renal biopsy were collected, and the TG / Cys-C ratio was calculated. Logistic regression analysis was used to analyze the related factors of DKD in patients with type 2 diabetes and proteinuria. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of TG/Cys-C ratio for DKD in patients with type 2 diabetes and proteinuria. Another 37 patients with type 2 diabetes complicated by proteinuria who were treated in the Department of Nephrology, four hospitals in Xuzhou from October 2019 to October 2021 were selected as the research objects. The TG/Cys-C value cut-off value selected in the retrospective study was selected as the boundary point and divided into two groups according to the values of greater than or equal to the tangent point and less than the tangential point. Serum triglyceride and cystatin C levels were measured and TG / Cys-C ratio was calculated. All patients underwent ultrasound-guided fine-needle renal biopsy. The positive rates of DKD diagnosis in the two groups were compared to verify the predictive value of TG / Cys-C ratio in the diagnosis of DKD. RESULTS: Retrospective study showed that compared with group NDKD, the DKD group had higher systolic blood pressure, higher cystatin C and creatinine, more diabetic retinopathy, longer duration of diabetes, lower hemoglobin concentration, lower glomerular filtration rate, lower cholesterol, lower triglyceride and lower TG/ Cys-C ratio (P < 0.05).Multivariate Logistic regression analysis showed that TG/Cys-C ratio (OR = 0.429, P = 0.009) was a protective factor for DKD in patients with type 2 diabetes and proteinuria. Diabetic retinopathy (OR = 7.054, P = 0.021) and systolic blood pressure (OR = 1.041, P = 0.047) were independent risk factors for DKD in patients with type 2 diabetes complicated with proteinuria. ROC curve showed that the area under the curve predicted by TG/Cys-C ratio for the diagnosis of DKD was 0.816, the sensitivity was 84%, and the specificity was 67.6%. The tangent value of TG / Cys-C ratio is 2.43. Prospective studies showed that in 37 patients with type 2 diabetes and proteinuria, 29 patients had a TG/Cys-C ratio of less than 2.43. The TG/Cys-C ratio of 8 patients was more than 2.43. Ultrasound guided fine needle aspiration biopsy revealed that 22 of the 29 patients had pathological diagnosis of DKD, sensitivity 91.67%, specificity 46.15%, positive predictive value 75.80%, and negative predictive value 75%. CONCLUSION: In type 2 diabetic patients with proteinuria, the ratio of TG/Cys-C has certain predictive value for the diagnosis of DKD.

Establishment and Validation of a Nomogram Model for Prediction of Diabetic Nephropathy in Type 2 Diabetic Patients with Proteinuria.

Purpose: To establish and validate the nomogram model for predicting diabetic nephropathy (DN) in type 2 diabetes mellitus (T2DM) patients with proteinuria. Methods: A total of 102 patients with T2DM and proteinuria who underwent renal biopsy were included in this study. According to pathological classification of the kidney, the patients were divided into two groups, namely, a DN group (52 cases) and a non-diabetic renal disease (NDRD) group (50 cases). The clinical data were collected, and the factors associated with diabetic nephropathy (DN) were analyzed with multivariate logistic regression. A nomogram model for predicting DN risk was constructed by using R4.1 software. Receiver operator characteristic (ROC) curves were generated, and the K-fold cross-validation method was used for validation. A consistency test was performed by generating the correction curve. Results: Systolic blood pressure (SBP), diabetic retinopathy (DR), hemoglobin (Hb), fasting plasma glucose (FPG) and triglyceride/cystatin C (TG/Cys-C) ratio were independent factors for DN in T2DM patients with proteinuria (P<0.05). The nomogram model had good prediction efficiency. If the total score of the nomogram exceeds 200, the probability of DN is as high as 95%. The area under the ROC curve was 0.9412 (95% confidence interval (CI) = 0.8981-0.9842). The 10-fold cross-validation showed that the prediction accuracy of the model was 0.8427. The Hosmer-Lemeshow (H-L) test showed that there was no significant difference between the predicted value and the actual observed value (X 2 = 6.725, P = 0.567). The calibration curve showed that the fitting degree of the DN nomogram prediction model was good. Conclusion: The nomogram model constructed in the present study improves the diagnostic efficiency of DN in T2DM patients with proteinuria, and it has a high clinical value.

Effect of Riluzole on the Expression of HCN2 in Dorsal Root Ganglion Neurons of Diabetic Neuropathic Pain Rats.

Neuropathic pain since early diabetes swamps patients' lives, and diabetes mellitus has become an increasingly worldwide epidemic. No agent, so far, can terminate the ongoing diabetes. Therefore, strategies that delay the process and the further complications are preferred, such as diabetic neuropathic pain (DNP). Dysfunction of ion channels is generally accepted as the central mechanism of diabetic associated neuropathy, of which hyperpolarization-activated cyclic nucleotide-gated 2 (HCN2) ion channel has been verified the involvement of neuropathic pain in dorsal root ganglion (DRG) neurons. Riluzole is a benzothiazole compound with neuroprotective properties on intervention to various ion channels, including hyperpolarization-activated voltage-dependent channels. To investigate the effect of riluzole within lumbar (L3-5) DRG neurons from DNP models, streptozocin (STZ, 70 mg/kg) injection was recruited subcutaneously followed by paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL), which both show significant reduction, whilst relieved by riluzole (4 mg/kg/d) administration, which was performed once daily for 7 consecutive days for 14 days. HCN2 expression was also decreased in line with alleviated behavioral tests. Our results indicate riluzole as the alleviator to STZ-induced DNP with involvement of downregulated HCN2 in lumbar DRG by continual systemic administration in rats.

CircARHGAP12 Triggers Mesenchymal Stromal Cell Autophagy to Facilitate its Effect on Repairing Diabetic Wounds by Sponging miR-301b-3p/ATG16L1 and miR-301b-3p/ULK2.

Circular RNAs have been confirmed to play vital roles in the development of human diseases. Nevertheless, their effects on modulating mesenchymal stromal cells (MSCs) to heal diabetic wounds are still elusive. In this study, our data revealed that MSCs treated with high glucose displayed an evident reduction in circARHGAP12 expression, whereas autophagy mediated by circARHGAP12 suppressed high glucose-triggered apoptosis of MSCs. Mechanistically, circARHGAP12 was capable of directly interacting with miR-301b-3p and subsequently sponged microRNA to modulate the expression of the miR-301b-3p target genes ATG16L1 and ULK2 and the downstream signaling pathway. Moreover, circARHGAP12 promoted the survival of MSCs in diabetic wounds in vivo and accelerated wound healing. Collectively, these results suggest that circARHGAP12/miR-301b-3p/ATG16L1 and circARHGAP12/miR-301b-3p/ULK2 regulatory networks might be an underlying therapeutic target for MSCs in diabetic wound healing.