The Effect of Moringa Isothiocyanate-1 on Renal Damage in Diabetic Nephropathy.

INTRODUCTION: Diabetic nephropathy (DN) is the most common clinical complication of diabetes mellitus. Moringa isothiocyanate-1 (MIC-1) is effective in the treatment of diabetes mellitus, but its mechanism of action in DN remains obscure. This research specifically probed the role of MIC-1 in modulating renal injury in DN. METHODS: Six db/m mice were assigned to control group and twelve db/db mice were randomly allocated to the db/db and db/db + MIC-1 groups. The body and kidney weights of the mice were monitored. Renal function indicators and oxidative stress-related markers were assessed by automatic biochemical analyzer and ELISA method. The pathological changes, apoptosis of renal tissues, extracellular regulated protein kinases (ERK) 1/2/ Nuclear factor erythroid2-related factor 2 (Nrf2) pathway-related markers, and the positive expressions of podocalyxin (Pod) and synaptopodin (Syn) were measured by H&E, PAS, and TUNEL staining, Western blot, and IHC assay. RESULTS: MIC-1 reduced the body and kidney weights, and increased the kidney organ index (calculated as 100*kidney weight/ body weight) in db/db mice. In addition, MIC-1 improved renal function, kidney tissue injury, and apoptosis of db/db mice. MIC1 noticeably repressed the contents of reactive oxygen species (ROS) and malondialdehyde (MDA) and enhanced the contents of (glutathione) GSH, superoxide dismutase (SOD), and catalase (CAT) in db/db mice. At molecular level, db/db mice showed a decrease in p-ERK/ERK, Nrf2, SOD-1, heme oxygenase 1 (HO-1), and CAT and an increase in p- inhibitor kappa B alpha (IKBα) and p-Nuclear factor-kappa B (P65/P65), which were reversed when MIC-1 was administered. Furthermore, MIC-1 facilitated the positive expressions of Pod and Syn of the kidney tissues in db/db mice. CONCLUSION: MIC-1 reduces oxidative stress and renal injury by activating the ERK/Nrf2/HO-1 signaling and repressing the NFκB signaling in db/db mice.  DOI: 10.52547/ijkd.7515.

LncRNA NEAT1 Accelerates the Proliferation, Oxidative Stress, Inflammation, and Fibrosis and Suppresses the Apoptosis Through the miR-423-5p/GLIPR2 Axis in Diabetic Nephropathy.

ABSTRACT: Diabetic nephropathy (DN) is a serious microvascular complication of diabetes. The aim of our study was to investigate the potential mechanism in DN progression. SV40 mesangial cells (MES)13 cells were exposed to high concentration of glucose (HG: 30 mmol/L) for 48 hours to establish a DN cell model in vitro. Bioinformatic software StarBase was adopted to establish the long noncoding RNA (lncRNA)-microRNA-messenger RNA axis. Dual-luciferase reporter assay, RNA immunoprecipitation assay, and RNA pull-down assay were performed to verify intermolecular interaction. LncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) was overexpressed in the serum of patients with DN. HG time-dependently upregulated NEAT1 levels, and HG promotes cell proliferation, oxidative stress, inflammation, and fibrosis and suppressed cell apoptosis in SV40 MES13 cells partly through upregulating NEAT1. NEAT1 functioned as a molecular sponge of miR-423-5p, and NEAT1 silencing-mediated effects were partly overturned by miR-423-5p interference in HG-induced SV40 MES13 cells. Glioma pathogenesis related-2 (GLIPR2) was a target of miR-423-5p. GLIPR2 overexpression in normal concentration of glucose (NG)-induced SV40 MES13 cells partly simulated HG-induced effects. GLIPR2 overexpression partly reversed NEAT1 interference-induced effects in HG-induced SV40 MES13 cells. LncRNA NEAT1 contributed to HG-induced DN progression through the miR-423-5p/GLIPR2 axis in vitro. NEAT1/miR-423-5p/GLIPR2 axis might be a potential target for DN treatment.

Relationship of chronic kidney disease with major air pollutants - A systematic review and meta-analysis of observational studies.

BACKGROUND: Articles concerning the correlation of the risk of chronic kidney disease (CKD) with air contaminant exposure present inconsistent findings and the magnitude of the link is still unclear. Therefore, we planned to systematically and quantitatively investigate the overall strength of proofs in this field. METHODS: Relevant articles on Cochrane, EMBASE, Medline, Web of Science, and CINHAL were searched as per relevant strategies. Only observational studies that disclosed the link of CKD risk with major air pollutants were enrolled, including PM10 and PM2.5, which were particulate matter less than 10 um and less than 2.5 um in erodynamic diameter respectively. Pooled relative risk (RR) and 95 % confidence interval (CI) were determined using random--effects models, regardless of the heterogeneity quantified by I2 statistic. RESULTS: Finally, 7 studies involving 5,812,381 participants were included. The incidence of CKD was increased by long-term exposure to PM10 (including solely estimated exposure to PM10 from studies using PM2.5) (RR 1.08, 95 %CI 1.04-1.11) with considerable heterogeneity (I2 = 79 %), and the risk of CKD was raised by 8% when the long-time exposure to PM10 increased by 10 ug/m3. The pooled RR (95 %CI) with a 10 µg/m3 increase in PM2.5 for risk of CKD was 1.09 (1.03-1.17). Stratified analysis also verified the general negative effects. CONCLUSIONS: Chronic subjection to major air contaminants (PM10 and PM2.5) is more likely to cause CKD. Thus, developing global approaches of air pollution elimination to prevent CKD is urgent.

Comparison between retrograde intrarenal surgery and percutaneous nephrolithotripsy in the management of renal stones: A meta-analysis.

Percutaneous nephrolithotripsy (PCNL) is recommended as the first-line treatment for the management of kidney stones that are ≥2 cm in diameter. Retrograde intrarenal surgery (RIRS) has become increasingly preferred due to its high level of safety and repeatability, particularly in small stones. However, whether PCNL has superior efficacy and lower complication rates when compared with RIRS remains controversial. Therefore, the present meta-analysis was conducted to compare the clinical outcomes of patients treated with PCNL and RIRS as therapy for renal stones. Clinical trials published in PubMed, Web of Science, Excerpta Medica dataBASE (EMBASE), and the Chinese Biomedical Database (CBM) were systematically reviewed to evaluate the efficacy and safety profiles of patients with renal stones who were treated with PCNL or RIRS. Main outcomes measures included stone-free rate, operative time, hospital stay, and complication rate. Results were expressed as risk ratio (RR), or weighted mean difference (WMD) with 95% confidence intervals (CIs). Pooled estimates were calculated using a fixed-effects or random-effects model according to the heterogeneity among the studies. In total, 17 studies [4 randomized controlled trials (RCTs) and 13 cohort studies] involving 1,717 patients met the inclusion criteria, and were included in this meta-analysis. Pooled results showed that PCNL exhibited a significantly higher stone-free rate (RR=0.90, 95% CI: 0.86 to 0.95; P<0.001) but was associated with a longer hospital stay, when compared with RIRS (WMD=-2.72, 95% CI: -3.9 to -1.54; P<0.001). Operative time (WMD=7.86, 95% CI: -0.89 to 16.61; P=0.078) and complication rate (RR=0.71, 95% CI: 0.48 to 1.05; P=0.083) did not significantly differ between the groups. Subgroup analysis revealed that PCNL had a shorter operation time than RIRS in patients with stone sizes ≥2 cm (WMD=12.88, 95% CI: 4.77 to 20.99; P=0.002), and PCNL had a similar stone-free rate as RIRS when the estimates were pooled from RCTs (RR=0.88, 95% CI: 0.76 to 1.01; P=0.078). Compared with PCNL, RIRS had a significantly lower stone-free rate, shorter hospital stay, but a similar operation time and complication rate. Therefore, we propose that RIRS may be an alternative therapy to PCNL, with acceptable efficacy and complication rates for renal stones. Further large-scale, well-conducted RCTs are required to verify our findings.