Mechanism of miR-365 in regulating BDNF-TrkB signal axis of HFD/STZ induced diabetic nephropathy fibrosis and renal function

Purpose

Diabetic nephropathy (DN) is one of the most serious complications of diabetes that leads to decline of renal function. Although numerous studies have revealed that microRNAs (miRNAs) play essential roles in the progression of DN, whether miR-365 is involved remains elusive.

Methods

The successful construction of DN model was confirmed by ELSIA, hematoxylin–eosin (HE) and Masson staining assay. The expression of miR-365 was detected through RT-qPCR. The levels of BDNF, p-TrkB, α-smooth muscle actin (SMA), collagen IV (Col.IV), transforming growth factor-β1 (TGF-β1), tumor necrosis factor α (TNF-α), and interleukin-6 (IL-6) were evaluated by western blot, IF or ELISA assays. Luciferase reporter assay was used to detect the interaction between miR-365 and BDNF.

Results

The DN mice model was induced by streptozotocin (STZ). Then miR-365 expression was found to upregulate in tissues of DN rat. Furthermore, elevated expression of miR-365 was found in high glucose (HG)-treated HK-2 cells. Silencing of miR-365 suppressed the accumulation of ECM components and secretion of inflammatory cytokines in HK-2 cells. In addition, it was demonstrated that miR-365 could target BDNF. The protein levels of BDNF and p-TrkB were negatively regulated by miR-365 in HK-2 cells. Moreover, inhibition of miR-365 suppressed the levels of SMA, Col.IV, TGF-β1, TNF-α, and IL-6, indicating the renal fibrosis was inhibited by miR-365 knockdown.

Conclusion

MiR-365 could regulate BDNF-TrkB signal axis in STZ induced DN fibrosis and renal function. The results of the current study might provide a promising biomarker for the treatment of DN in the future.

     

The prognostic value of platelet-to-lymphocyte ratio on the long-term renal survival in patients with IgA nephropathy

Purpose

Platelet-to-lymphocyte ratio (PLR) was established showing the poor prognosis in several diseases, such as malignancies and cardiovascular diseases. But limited study has been conducted about the prognostic value of PLR on the long-term renal survival of patients with Immunoglobulin A nephropathy (IgAN).

Methods

We performed an observational cohort study enrolling patients with biopsy-proven IgAN recorded from November 2011 to March 2016. The definition of composite endpoint was eGFR decrease by 50%, eGFR?<?15 mL/min/1.73 m², initiation of dialysis, or renal transplantation. Patients were categorized by the magnitude of PLR tertiles into three groups. The Kaplan–Meier curves and multivariate Cox models were performed to determine the association of PLR with the renal survival of IgAN patients.

Results

330 patients with a median age of 34.0 years were followed for a median of 47.4 months, and 27 patients (8.2%) had reached the composite endpoints. There were no differences among the three groups (PLR?<?106, 106?≤?PLR?≤?137, and PLR?>?137) in demographic characteristics, mean arterial pressure (MAP), proteinuria, and estimated glomerular filtration rate (eGFR) at baseline. The Kaplan–Meier curves showed that the PLR?>?137 group was significantly more likely to poor renal outcomes than the other two groups. Using univariate and multivariate cox regression analyses, we found that PLR?>?137 was an independent prognostic factor for poor renal survival in patients with IgAN. Subgroup analysis revealed that the PLR remained the prognostic value for female patients or patients with eGFR less than 60 mL/min/1.73 m².

Conclusions

Our results underscored that baseline PLR was an independent prognostic factor for poor renal survival in patients with IgAN, especially for female patients or those patients with baseline eGFR less than 60 mL/min/1.73 m².

     

Efficacy of testosterone replacement therapy for treating metabolic disturbances in late-onset hypogonadism: a systematic review and meta-analysis

International Urology and Nephrology - Late onset hypogonadism (LOH) is an age-dependent reduction of testosterone associated with alterations of metabolic profile, including glucose control,...     

Transurethral laser versus open simple prostatectomy for large volume prostates: a systematic review and meta-analysis of randomized controlled trials

The benefit of transurethral laser prostatectomy over open simple prostatectomy (OSP) is controversial in aged symptomatic benign prostatic hyperplasia (BPH) patients with large volume prostates, and the aim of this study is to compare the safety and efficiency of these two methods. Meta-analysis was applied using the Review Manager V5.3 software and the retrieved randomized controlled clinical trials (RCTs) comparing transurethral laser prostatectomy with OSP were analyzed for the treatment of large volume prostates from 2000 to 2019 in PubMed, Web of Science, Cochrane, and EMBASE datasets. Five RCTs assessing transurethral laser prostatectomy versus OSP were considered suitable for this meta-analysis, which included a total of 448 patients, with 232 patients undergoing laser and 216 patients undergoing OSP. Compared with OSP, although transurethral laser prostatectomy required a longer operative time (weighted mean difference (WMD) 27.49 mins; 95% confidence interval (CI) 16.54–38.44; P?<?0.00001) and obtained a less resected prostate weight (WMD ??11.72 g; 95% CI ??21.75 to ??1.70; P?=?0.02), patients undergoing laser prostatectomy benefited from significantly less hemoglobin decline (??0.97 g/dL; 95% CI ??1.31 to ??0.64; P?<?0.00001), shorter time of catheterization (WMD ??3.67 days; 95% CI ??5.60 to ??1.75; P?=?0.0002), shorter length of hospital stay (WMD ??4.75 days; 95% CI ??6.57 to ??2.93; P?<?0.00001), and less blood transfusion (odds ratio 0.10; 95% CI 0.03 to 0.35; P?=?0.0003). During postoperative follow-up, no significant difference was observed between the two groups in IPSS, QoL, Q_max, and PVR. Both transurethral laser prostatectomy and OSP are safe and effective for large prostates that require prostate resection. Taking into account of less blood loss, shorter catheterization time and hospital stay, and less blood transfusion, transurethral laser prostatectomy may be a better treatment for patients with large prostates.

     

Safety and efficacy of thulium laser resection of bladder tumors versus transurethral resection of bladder tumors: a systematic review and meta-analysis

Lasers in Medical Science - The thulium laser resection of bladder tumor (TmLRBT) is widely used in the treatment of non-muscle-invasive bladder cancer (NMIBC), and we conduct this study to compare...     

Application of network pharmacology and molecular docking to elucidate the potential mechanism of Astragalus–Scorpion against prostate cancer

The present study aimed to investigate the molecular mechanism of the Astragalus–Scorpion drug pair in the treatment of prostate cancer (PCa). We employed network pharmacology and molecular docking technology to retrieving the active ingredients and corresponding targets of Astragalus–Scorpion by using TCMSP, BATMAN-TCM, TCMID and Swiss Target Prediction Databases. The targets related to PCa were retrieved through GeneCards. Cytoscape software was used to construct the ‘active ingredient–target disease’ network, and GO and KEGG enrichment analyses were performed on the common targets. Autodock software was used for molecular docking verification. In total, 26 active ingredients, 340 potential targets related to active ingredients and 122 common targets were screened from Astragalus–Scorpion drug pair. The core targets of the protein–protein interaction (PPI) network were JUN, AKT1, IL6, MAPK1 and RELA, whereas the core active ingredients were quercetin, kaempferol, formononetin, 7-o-methylisomucronulatol and calycosin. Nearly 762 GO entries and 154 pathways were obtained by using the pathway enrichment analysis. Molecular docking results revealed that quercetin and kaempferol bind to AKT1 and formononetin binds to RELA, all of which were found to be stable bounds.