Diabetic nephropathy (DN) remains one of the severe complications associated with diabetes mellitus. It is worthwhile to uncover the underlying mechanisms of clinical benefits of human urine‐derived ...stem cells (hUSCs) in the treatment of DN. At present, the clinical benefits associated with hUSCs in the treatment of DN remains unclear. Hence, our study aims to investigate protective effect of hUSC exosome along with microRNA‐16‐5p (miR‐16‐5p) on podocytes in DN via vascular endothelial growth factor A (VEGFA). Initially, miR‐16‐5p was predicated to target VEGFA based on data retrieved from several bioinformatics databases. Notably, dual‐luciferase report gene assay provided further verification confirming the prediction. Moreover, our results demonstrated that high glucose (HG) stimulation could inhibit miR‐16‐5p and promote VEGFA in human podocytes (HPDCs). miR‐16‐5p in hUSCs was transferred through the exosome pathway to HG‐treated HPDCs. The viability and apoptosis rate of podocytes after HG treatment together with expression of the related factors were subsequently determined. The results indicated that miR‐16‐5p secreted by hUSCs could improve podocyte injury induced by HG. In addition, VEGA silencing could also ameliorate HG‐induced podocyte injury. Finally, hUSC exosomes containing overexpressed miR‐16‐5p were injected into diabetic rats via tail vein, followed by qualification of miR‐16‐5p and observation on the changes of podocytes, which revealed that overexpressed miR‐16‐5p in hUSCs conferred protective effects on HPDCs in diabetic rats. Taken together, the present study revealed that overexpressed miR‐16‐5p in hUSC exosomes could protect HPDCs induced by HG and suppress VEGFA expression and podocytic apoptosis, providing fresh insights for novel treatment of DN.
Long non‐coding RNA (lncRNA) lnc‐ISG20 has been found aberrantly up‐regulated in the glomerular in the patients with diabetic nephropathy (DN). We aimed to elucidate the function and regulatory ...mechanism of lncRNA lnc‐ISG20 on DN‐induced renal fibrosis. Expression patterns of lnc‐ISG20 in kidney tissues of DN patients were determined by RT‐qPCR. Mouse models of DN were constructed, while MCs were cultured under normal glucose (NG)/high glucose (HG) conditions. The expression patterns of fibrosis marker proteins collagen IV, fibronectin and TGF‐β1 were measured with Western blot assay. In addition, the relationship among lnc‐ISG20, miR‐486‐5p, NFAT5 and AKT were analysed using dual‐luciferase reporter assay and RNA immunoprecipitation. The effect of lnc‐ISG20 and miR‐486/NFAT5/p‐AKT axis on DN‐associated renal fibrosis was also verified by means of rescue experiments. The expression levels of lnc‐ISG20 were increased in DN patients, DN mouse kidney tissues and HG‐treated MCs. Lnc‐ISG20 silencing alleviated HG‐induced fibrosis in MCs and delayed renal fibrosis in DN mice. Mechanistically, miR‐486‐5p was found to be a downstream miRNA of lnc‐ISG20, while miR‐486‐5p inhibited the expression of NFAT5 by binding to its 3'UTR. NFAT5 overexpression aggravated HG‐induced fibrosis by stimulating AKT phosphorylation. However, NFAT5 silencing reversed the promotion of in vitro and in vivo fibrosis caused by lnc‐ISG20 overexpression. Our collective findings indicate that lnc‐ISG20 promotes the renal fibrosis process in DN by activating AKT through the miR‐486‐5p/NFAT5 axis. High‐expression levels of lnc‐ISG20 may be a useful indicator for DN.
Protein disulfide isomerases A6 (PDIA6) belongs to the PDI family. Recently, PDIA6 was found to have a close association with various cancers. However, there has been little investigation into the ...biological functions of PDIA6 in bladder cancer (BC). In this study, we explored the expression
pattern and functional significance of PDIA6 in BC. We found that PDIA6 was overexpressed in BC tissues and cell lines. The in vitro study showed that PDIA6 downregulation significantly inhibited BC proliferation and invasion. In addition, the in vivo experiment demonstrated that PDIA6 downregulation
decreased the volume, weight, and metastasis of tumors. Furthermore, PDIA6 downregulation reduced the protein expression of β-catenin, cyclin D1, and c-Myc and thus suppressed the Wnt/β-catenin signaling pathway. In conclusion, we suggest that PDIA6 could be targeted for the treatment
of BC.
The dynamical transmission of intermediate-energy protons through a polycarbonate (PC) conical capillary with taper angle from 0.48° to 2° are simulated. The results show that for small taper angle ...of 0.48°, the transmission of 100 keV protons is dominated by the deposited-charge-assisted specular reflection. This reflection effect decreases with the increase of the taper angle. When the taper angle is increased to 2°, the transmission of the protons is mainly influenced by small angle scattering, which is consistent with the experimental data. The asymptotic transmission rate decreases with the increase of the capillary taper angle. These results suggest that the deposited-charge-assisted specular reflection is significant in focusing several-hundred-keV protons.
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•Expression of ETS2 is up-regulated in RCC tissues and cell lines.•Down-regulation of ETS2 inhibits RCC cell invasion and metastasis.•Down-regulation of ETS2 inhibits the EMT process ...in RCC cells.•The PI3K/Akt pathway underlies the promoting effect of ETS2 on RCC cells.
V-ets erythroblastosis virus E26 oncogene homolog 2 (ETS2), belonging to the ETS family of transcription factors, is implicated in a broad range of cellular functions. Recently, ETS2 has been found playing an important role in the progression of some types of cancers. However, it remains unclear whether ETS2 has any effects on renal cell carcinoma (RCC). In this study, we investigated the biological functions of ETS2 in RCC. The results showed that ETS2 was highly expressed in RCC tissues and cell lines and its expression had an association with clinicopathological characteristics of RCC patients. In addition, down-regulation of ETS2 significantly inhibited RCC cell invasion in vitro and metastasis in vivo as well as suppressed the epithelial-mesenchymal transition (EMT) process. We also found that ETS2 down-regulation significantly reduced the levels of PI3K and Akt phosphorylation in RCC cells. Taken together, we suggest that ETS2 is of potential value as a molecular target for RCC treatment.
In practical operations, the carbon monoxide (CO) distribution in an opposite-wall-firing furnace (OWFF) is characterized by a high concentration near the side walls and a low concentration in the ...center, accompanied by a series of combustion-related issues. To find the reasons for the CO distribution, a numerical study was conducted on a 660 MWe OWFF. The CO concentration profiles, distribution coefficients of coal and air, mixing coefficients, and the aerodynamic characteristics were extracted for analysis. The CO distribution within the furnace greatly depends on the mixing of coal and air. A mismatch between the aerodynamic behaviors of coal and air causes the non-uniform distribution of CO. Taking into consideration that distinctive flow patterns exist within the different regions, the formation mechanisms of the CO distribution can be divided into two components: (1) In the burner region, the collision of opposite flows leads to the migration of gas and particles toward the side wall which, together with the vortexes formed at furnace corners, is responsible for unburned particles concentrated and oxygenized from the furnace center to the side wall. Thus, high CO concentrations appear in these areas. (2) As the over-fire air (OFA) jet is injected into the furnace, it occupies the central region of furnace and pushes the gas from the burner region outward to the side wall, which is disadvantageous for the mixing effect in the side wall region. As a consequence, a U-shaped distribution of CO concentration is formed. Our results contribute to a theoretical basis for facilitating the control of variation in CO concentration within the furnace.
Benign prostatic hyperplasia (BPH) is highly prevalent among older men, impacting on their quality of life, sexual function, and genitourinary health, and has become an important global burden of ...disease. Transurethral plasmakinetic resection of prostate (TUPKP) is one of the foremost surgical procedures for the treatment of BPH. It has become well established in clinical practice with good efficacy and safety. In 2018, we issued the guideline "2018 Standard Edition". However much new direct evidence has now emerged and this may change some of previous recommendations. The time is ripe to develop new evidence-based guidelines, so we formed a working group of clinical experts and methodologists. The steering group members posed 31 questions relevant to the management of TUPKP for BPH covering the following areas: questions relevant to the perioperative period (preoperative, intraoperative, and postoperative) of TUPKP in the treatment of BPH, postoperative complications and the level of surgeons' surgical skill. We searched the literature for direct evidence on the management of TUPKP for BPH, and assessed its certainty generated recommendations using the grade criteria by the European Association of Urology. Recommendations were either strong or weak, or in the form of an ungraded consensus-based statement. Finally, we issued 36 statements. Among them, 23 carried strong recommendations, and 13 carried weak recommendations for the stated procedure. They covered questions relevant to the aforementioned three areas. The preoperative period for TUPKP in the treatment of BPH included indications and contraindications for TUPKP, precautions for preoperative preparation in patients with renal impairment and urinary tract infection due to urinary retention, and preoperative prophylactic use of antibiotics. Questions relevant to the intraoperative period incorporated surgical operation techniques and prevention and management of bladder explosion. The application to different populations incorporating the efficacy and safety of TUPKP in the treatment of normal volume (< 80 ml) and large-volume (≥ 80 ml) BPH compared with transurethral urethral resection prostate, transurethral plasmakinetic enucleation of prostate and open prostatectomy; the efficacy and safety of TUPKP in high-risk populations and among people taking anticoagulant (antithrombotic) drugs. Questions relevant to the postoperative period incorporated the time and speed of flushing, the time indwelling catheters are needed, principles of postoperative therapeutic use of antibiotics, follow-up time and follow-up content. Questions related to complications incorporated types of complications and their incidence, postoperative leukocyturia, the treatment measures for the perforation and extravasation of the capsule, transurethral resection syndrome, postoperative bleeding, urinary catheter blockage, bladder spasm, overactive bladder, urinary incontinence, urethral stricture, rectal injury during surgery, postoperative erectile dysfunction and retrograde ejaculation. Final questions were related to surgeons' skills when performing TUPKP for the treatment of BPH. We hope these recommendations can help support healthcare workers caring for patients having TUPKP for the treatment of BPH.
To increase the success rate of surgical treatment in patients with hypospadias.
220 cases of hypospadias underwent one-stage urethra plasty. After the penis was straightened, urethra plasty was ...performed with pediculated preputial entoplastron (Duckett's method) in 195 cases; with combination of scrotal septum and pediculated preputial entoplastron in 20 cases; with free bladder mucosa transplantation in 2 cases. The self-made dual silastic tubes with lateral mini-holes were applied to support new urethra in all the cases.
The patients were followed up for 1 - 8 years. 208 cases achieved successful results. There were 2 cases of urethral fistula, 6 cases of urethral stenosis at anastomosis site, 4 cases of stenosis at urethral orifice.
The success rate (94.5%) suggests great advantages of the self-made dual tube with lateral mini-holes to support new urethra. It can facilitate drainage and irrigation and reduce the complications such as infection, fistula and stenosis.
To determine the protective effect of ONO-1078, a leukotriene receptor antagonist, on focal cerebral ischemia induced by endothelin-1 in rats.
Slow microinjection of endothelin-1 (120 pmol in 6 ...microL, for > 6 min) into the region near the middle cerebral artery was used to induce focal cerebral ischemia. ONO-1078 (0.1 mg.kg-1) was i.p. injected 1 h before endothelin-1 injection. Neurological symptoms, brain edema, brain infarction size, and the survival neurons in cortex and striatum were observed 24 h after ischemia.
Intracerebral microinjection of endothelin-1 induced remarkable neurological symptoms, brain infarction, brain edema, and decrease of survival neurons in the cortex and striatum. In rats pretreated with ONO-1078, endothelin-1-induced brain edema and brain infarction size were decreased. The numbers of survival neurons in striatum and cortex were increased significantly. The neurological symptoms were improved but not significantly.
ONO-1078 possesses neuroprotective effect against cerebral isch
Numerous previous studies explored the influence of matrix metalloproteinase 2 (MMP-2) expressions on renal cell carcinoma (RCC), yet inconsistent results were reported.
This study aims to derive a ...more precise estimation of the associations between MMP-2 and RCC.
A total of 115 patients with RCC were selected; meanwhile, 45 patients with traumatic rupture of renal cysts or renal calculi were recruited and normal kidney tissues were collected as control group. The expression level of MMP-2 protein was detected by using immunohistochemistry. A meta-analysis was performed by using Comprehensive Meta-analysis 2.0 (CMA 2.0).
The positive expression rate of MMP-2 protein in the RCC tissues was evidently higher than that in the normal renal tissues (P < 0.001). The positive expression rate of MMP-2 protein in patients with tumor size > 5 cm, with lymph node metastasis (LNM), with well-differentiated RCC, and stage III-IV RCC was significantly higher, compared with the patients with tumor size ≤ 5 cm, without LNM, with moderate/low-differentiated RCC, and with stage I-II RCC, respectively (all P < 0.05). There was statistical significance in the 5-year survival rate between the patients with positive MMP-2 protein expression and those with negative MMP-2 protein expression (P = 0.037). These results were further confirmed by the meta-analysis.
MMP-2 protein expression is significantly associated with historical grade, TNM stage, tumor size and LNM in RCC, suggesting that MMP-2 may serve as a biological marker for the prognosis in RCC.
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