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Introduction This study aims to explore the effect and related molecular mechanism of miR-153-3p on high glucose-stimulated human glomerular mesangial cells. Materials and methods The quantitative real-time polymerase chain reaction (qPCR) assay was employed to check miR-153-3p and PAQR3 expression levels in diabetic nephropathy patients. (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT assay was applied to investigate the effects of miR-153-3p transfection or PAQR3 administration on mesangial cell (MC) activity. ELISA assays were used to check the expression levels of extracellular matrix (ECM) related proteins. The bioinformatics method and dual-luciferase reporter assay were employed together to anticipate and check the targeting relationship between miR-153-3p and PAQR3. Western blot assays were applied to check the PAQR3, PI3K and AKT expression after miR-153-3p transfection or PAQR3 administration. Results The expression level of miR-153-3p was lower in diabetic nephropathy patients, while the expression of PAQR3 was concomitantly higher. Upregulation of miR-153-3p can reduce MC proliferation and ECM accumulation. Further research indicated that miR-153-3p directly regulated PAQR3 expression via coupling with the 3’-UTR of PAQR3. Finally, the fact that miR-153-3p regulates the PI3K/AKT pathway by PAQR3 was confirmed. Conclusion MiR-153-3p regulates the PI3K/AKT pathway through PAQR3, thereby playing a role in regulating cell proliferation and ECM accumulation in high glucose-stimulated MCs.

Lianglan Shen,* Hongli Yang,* Xingxing Fang, Huaxing Huang, Wubin Yao, Dongmei Chen, Yan Shen Department of Nephrology, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu, 226001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan Shen Tel/Fax +86-0513-85061346Email ntmcsy@126.comPurpose: To investigate the association of Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors and acute kidney injury in comparison to other classes of drugs.Patients and Methods: A total of 4966 diabetes mellitus patients were investigated for developing Acute Kidney Injury (AKI) who were under prescription with the following class of drugs viz. SGLT2 Inhibitors, Dipeptidyl peptidase-4 (DDP4) inhibitors, Nonsteroidal anti-inflammatory drugs (NSAIDs), first-line drugs and anti-biotics. The primary outcome was based on the hospital encounter and Kidney Disease Improving Global Outcome (KDIGO) threshold values were used to assess the serum creatinine concentration. The secondary outcome was assessed based on the concentration level of serum creatinine after 90 days of hospital admission and evaluation of the KDIGO threshold values.Results: The study observed that the risk of causing AKI for SGLT2 inhibitors was 5.59% which was comparatively low compared to other class of the investigated drugs (DPP4 inhibitors = 6.47%, antibiotics = 6.30%, first-line drugs = 6.82% and NSAIDs = 10.65%). The multivariate analysis observed that ibuprofen, celecoxib, indomethacin, insulin, cephalexin, and alogliptin were mostly associated with an increased rate of AKI. SGLT2 inhibitors have the lowest risk for developing AKI compared to other drugs and control.Conclusion: AKI incidence is relatively low after initiation of SLGT2 inhibitors and concludes that regulatory warnings from certain health agencies about its risk for AKI on prescription are unwarranted.Keywords: SGLT2 inhibitor, DPP4, acute kidney injury, NSAID, type-2 diabetes

Additional file 1. The CNV plot of NIPT and prenatal diagnosis of sub-chromosomal CNVs hemolyzed sample 1.

Additional file 2. The CNV plot of NIPT and prenatal diagnosis of sub-chromosomal CNVs hemolyzed sample 2.

To investigate the effect of adiponectin (APN) on the oxidative stress-apoptotic pathway of podocytes under high glucose conditions, podocytes were categorized into a control group (5.5 mmol/L, normal glucose, NG), high glucose group (30 mmol/L, high glucose, HG), and an APN intervention group (HG+APN). The expression of podocyte cytoskeleton proteins (nephrin/podocin/synaptopodin), p-AMPK activity, and the NADPH oxidase family (NOX1/NOX4) and apoptosis-related proteins p53 and PUMA (p53 up-regulated apoptotic regulator) were detected by RT-PCR and Western blotting. The total RNA extracted by nano-magnetic beads was retrieved into DNA by the MagBeads Total RNA Extraction Kit, and cDNA was synthesized through reverse transcription. Podocyte apoptosis was detected by flow cytometry. In comparison with the control group, the high glucose group exhibited the reduced expression of podocyte cytoskeleton proteins, decreased p-AMPK activity, increased expression of NOX1, NOX4, P53, and PUMA, and increased podocyte apoptosis (28.15%±1.38%). APN intervention could significantly restore the expression of cytoskeleton proteins, increase the activity of p-AMPK, reduce the expression of NOX1, NOX4, P53, and PUMA, and reduce the apoptosis of podocytes (9.15%±1.98%). The protective effect of APN disappeared when AMPK was inhibited. APN may inhibit oxidative stress-apoptosis of podocytes under high glucose conditions through the activation of AMPK.

We aimed to evaluate the effects of valsartan in combination with febuxostat on serum uric acid, highsensitivity C-reactive protein and cardiac function of patients with chronic kidney disease plus hyperuricemia (HUA). A total of 144 patients with chronic kidney disease and hyperuricemia treated from June 2014 to June 2018 were retrospectively analyzed. They were divided into group A and group B according to treatment regimen. Both groups were given high-quality low-protein diet, and comprehensive treatments such as decrease of blood pressure, correction of anemia, supplementation of α-ketoacid, and correction of water, electrolyte and acid-base balances. Group A was administered 80 mg/d valsartan, based on which group B was given 40 mg/d febuxostat. Serum uric acid and high-sensitivity C-reactive protein levels were measured on the 2nd day after enrollment and after 2 mo of treatment, respectively. Echocardiographic examination was conducted. Before treatment, the two groups had similar serum levels of uric acid and high-sensitivity C-reactive protein (p>0.05). After treatment, such levels significantly decreased (p 0.05). After treatment left atrial diameter, left ventricular end diastolic diameter, left ventricular enddiastolic volume and left ventricular end-systolic volume significantly reduced, and ejection fraction and fraction shortening significantly increased (p

Background Diabetic nephropathy (DN) is one of the common chronic microvascular complications of diabetes, and podocyte injury and dysfunction are strictly related to the pathogenesis of DN. Studies have shown that ligustilide (LIG) has anti-inflammatory, antioxidant, and anti-apoptotic activities. This study was designed to investigate the therapeutic effect of LIG in DN rats and their mechanisms. Methods DN rat models (n=10) were induced by streptozotocin (STZ) combined with a high-fat diet. Rats in the LIG group were intragastrically administered with LIG daily for eight weeks, and animals in the positive control group were treated with Losartan potassium. The body weight and blood glucose were checked weekly during the treatment. The pathological changes of kidney tissue were observed with hematoxylin and eosin (HE) staining. Blood lipid profiles and renal function-related markers, including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), blood urea nitrogen (BUN), and serum creatinine (Scr) were monitored using a biochemical analyzer. The protein expression of nephrin was determined by immunohistochemistry and Western blotting. Finally, Western blot was used to determine the protein expression of Sirtuin 1 (SIRT1) and nuclear factor-kappa B (NF-κB). Results Compared with the healthy control group, rats in the DN group have slower weight gain, increased blood sugar level, renal lesions, and impaired renal function, along with decreased nephrin expression, abnormally activated NF-κB, and inhibited SIRT1 protein expression. All the above conditions were improved after intervention with either losartan potassium or LIG. Conclusions LIG attenuates podocyte injury by regulating the SIRT1/NF-κB signaling pathway and thereby exerts its protective effect on renal function in DN rats.