Prognostic Role of High Stathmin 1 Expression in Patients with Solid Tumors: Evidence from a Meta-Analysis.

BACKGROUND/AIMS: Several recent studies have demonstrated that Stathmin 1expression may be closely associated with prognosis in patients with various types of cancers. In the present study, we conducted a meta-analysis of all available studies in the English literature to assess the prognostic value of Stathmin 1expression in patients with solid cancers. METHODS: The online databases PubMed, Embase, and Web of Science were searched for literature regarding Stathmin 1 and its association with patient outcomes associated with solid cancers. RESULTS: A total of 23 articles including 26 studies that contained 5 335 patients were retrieved and analyzed. Our results indicated that high Stathmin 1 expression yielded a worse overall survival (OS) (hazard ratio [HR] = 2.17, 95% confidence interval [CI]: 1.81-2.60), disease-free survival (DFS) (HR = 2.46, 95% CI: 2.00-3.02), disease-specific survival (DSS) (HR = 1.98, 95% CI: 1.58- 2.47) and progression-free survival (PFS)/recurrence-free survival (RFS) (HR = 2.09, 95% CI: 1.51-2.89). Furthermore, the association of high Stathmin 1 expression with poor survival was significant even for sub-group analyses of different tumor types, ethnicities, methods used to calculate HRs, detected methods, and analysis types. CONCLUSION: In summary, this meta-analysis determined that high Stathmin 1 expression is associated with poor prognosis in patients with solid cancers and expression of this protein could be a clinically useful prognostic biomarker.

Exosomal miR-4639 and miR-210 in Plasma and Urine as Biomarkers in IgA Nephropathy.

BACKGROUND: It has been widely recognized that exosomal miRNAs can participate in the pathogenesis of different renal disorders and serve as disease biomarkers. Although kidney biopsy is still the gold standard for diagnosing and monitoring immunoglobulin A nephropathy (IgAN), it is highly required to identify new and effective noninvasive biomarkers for IgAN, the most frequently detected primary glomerulonephritis worldwide. METHODS: Plasma and urinary exosomes were extracted by PEG precipitation. Size and morphological characteristics of plasma and urinary exosomes were observed by transmission electron microscopy and nanoparticle tracking analysis. The levels of plasma and urinary exosomes were revealed by Western blotting. The expressions of target miRNAs were revealed by in situ hybridization and qRT-PCR. RESULTS: The levels of plasma and urinary exosomes were remarkably enhanced in IgAN patients compared with healthy controls (HCs). The expressions of miR-4639 and miR-210 in IgAN patients were significantly higher in contrast to the individuals with membranous nephropathy, minimal change nephrosis, diabetic nephropathy, or HC. These also played a valuable role in assessing the kidney function and the level of proteinuria. Furthermore, plasma and urinary exosomal miR-4639 expression was associated with more serious and active histological activity (mesangial hypercellularity, crescent, and C3 complement deposition). With an average follow-up of 8 months, miR-4639 and miR-210 expressions in plasma and urinary exosomes were higher in patients with progressive IgAN. Plasma exosomal miR-4639 and miR-210 were better than proteinuria (g/24 h) to estimate renal outcomes. CONCLUSION: Exosomal miR-4639 and miR-210 could be used as valid biomarkers to assist in diagnosis, evaluate severity, and assess disease development of IgAN.

Preconditioning with hyperbaric oxygen induces tolerance against renal ischemia-reperfusion injury via increased expression of heme oxygenase-1.

OBJECTIVE: Renal ischemia/reperfusion (I/R) injury occurs in both native and transplanted kidneys. Hyperbaric oxygen (HBO) has been shown to prevent I/R injury in different tissues. The aim of this study was to evaluate the effect of HBO on renal I/R injury in rats. MATERIALS AND METHODS: Male Sprague-Dawley rats were randomly assigned to three groups. The sham group (n = 8) received right nephrectomy. The I/R (n = 8) and HBO + I/R groups (n = 8) received 45 min left renal ischemia followed by 24 h of reperfusion after right nephrectomy. The HBO + I/R group (n = 8) received 100% oxygen at 2.5 atmosphere absolute (ATA), for 1 h at every 12 h interval for 2 d. Reperfusion was performed 24 h later after the last HBO exposure. RESULTS: In HBO + I/R group, blood urea nitrogen (BUN) and creatinine levels decreased significantly compared with the sham and I/R groups (P < 0.01). Activities of superoxide dismutase (SOD) were increased in renal tissue in the HBO + I/R groups. The content of malondialdehyde (MDA) were decreased in the HBO + I/R groups. Kidney samples from HBO + I/R group rats revealed markedly reduced histological damage under histopathological examination. The animals treated with HBO showed significantly elevated heme oxygenase-1 (HO-1) protein and mRNA levels expression compared with I/R group (P < 0.05). CONCLUSIONS: Hyperbaric oxygen preconditioning (HBO-PC) can protect renal I/R injury against oxidative stress, and the up-regulation of HO-1 expression plays an essential role in HBO induced preconditioning effect.

MiRNA-124 regulates the sensitivity of renal cancer cells to cisplatin-induced necroptosis by targeting the CAPN4-CNOT3 axis.

BACKGROUND: Currently, drug-resistance is a major challenge in the treatment of renal cancer. Although microRNAs (miRNAs) have been reported to contribute to the incidence of drug resistance in renal cancer, the bio-functional roles and underlying regulatory mechanisms of novel miRNAs in cisplatin resistance remain largely unclear. METHODS: In this study, miRNA microarray analysis was applied to evaluate miRNA changes induced by cisplatin on RCC (renal cell carcinoma) cell lines. Then, Caki-1 and 786-0 cells were transfected with miR (miRNA)-124 mimics to observe cisplatin resistance in RCC cell lines after up-regulation of miR-124. TargetScan was used to identify putative protein-coding gene targets of miR-124. Further, the interaction between calpain small subunit 1 (Capn4) and CCR4-NOT transcription complex subunit 3 (CNOT3) was detected by quantitative real-time PCR (qPCR) and western blotting, and confirmed by co-immunoprecipitation. The effect of Capn4 and/or CNOT3 on cell viability and half maximal inhibitory concentration (IC50) value of miR-124 overexpressed Caki-1 and 786-O cells to cisplatin was evaluated using the Cell Counting Kit-8 (CCK-8) assay. And the effect of Capn4 and/or CNOT3 on the level of necroptosis in miR-124 overexpressed Caki-1 and 786-O cells to cisplatin was evaluated by flow cytometric analysis. Then, four groups of 786-0 cells (miR-124, miR-124+ Capn4, miR-124+ CNOT3, miR-124+ Capn4+ CNOT3) were inoculated into nude mice to observe the effect of cisplatin on tumor formation. RESULTS: miR-124 was found to be markedly elevated in renal cancer cells by cisplatin. Functionally, the overexpression of miR-124 reduced the sensitivity of renal cancer cells to cisplatin and CAPN4 was found to be a direct target of miR-124, which can negatively regulated CAPN4 expression. Moreover, ectopic expression of CAPN4 reversed the impairment of miR-124 on cisplatin-sensitivity and cisplatin-induced necroptosis. Mechanically, the present study revealed that CAPN4 could directly interact with CNOT3 and promote its degradation, and that the cisplatin-resistant phenotype was reversed by up-regulation of CNOT3. CONCLUSIONS: Therefore, miR-124 is an important inhibitor in cisplatin-induced necroptosis, and the miR-124-CAPN4-CNOT3 signaling axis plays a critical role in the emergence of cisplatin-resistance.

Structural Characterization and Antioxidant Activity of Exopolysaccharide from Soybean Whey Fermented by Lacticaseibacillus plantarum 70810.

Soybean whey is a high-yield but low-utilization agricultural by-product in China. In this study, soybean whey was used as a substrate of fermentation by Lacticaseibacillus plantarum 70810 strains. An exopolysaccharide (LPEPS-1) was isolated from soybean whey fermentation by L. plantarum 70810 and purified by ion-exchange chromatography. Its preliminary structural characteristics and antioxidant activity were investigated. Results show that LPEPS-1 was composed of mannose, glucose, and galactose with molar ratios of 1.49:1.67:1.00. The chemical structure of LPEPS-1 consisted of →4)-α-D-Glcp-(1→, →3)-α-D-Galp-(1→ and →2)-α-D-Manp-(1→. Scanning electron microscopy (SEM) revealed that LPEPS-1 had a relatively rough surface. In addition, LPPES-1 exhibited strong scavenging activity against DPPH and superoxide radicals and chelating ability on ferrous ion. This study demonstrated that soybean whey was a feasible fermentation substrate for the production of polysaccharide from L. plantarum 70810 and that the polysaccharide could be used as a promising ingredient for health-beneficial functional foods.

miR-106b promotes proliferation and invasion by targeting Capicua through MAPK signaling in renal carcinoma cancer.

Background: miR-106b has been reported to play a vital role in pathogenesis of some types of cancer, whilst the role of miR-106b in renal carcinoma cancer (RCC) remains unknown. Purpose: The objective of this study was to identify the mechanism of miR-106b regulating the progression of renal carcinoma. Method: The expression of miR-106b was analyzed in RCC cell lines, RCC and adjacent normal renal tissues through qRT-PCR assays. Target mRNA of miR-106b was predicted with databases and verified by luciferase reporter assays. And the effects of miR-106b or targeted mRNA on cell proliferation, invasion, the process of epithelial-mesenchymal transitions (EMTs) were assessed in vitrothrough CCK-8, transwell cell invasion assays, qRT-PCR and Western blotting assays respectively. In addition, the effects of miR-106b on the growth of xenografts mice were analyzedin vivo. Results: The results demonstrated that miR-106b was significantly increased both in RCC tissues and cell lines. Luciferase reporter assays revealed that miR-106b inhibited Capicua expression by targeting its 3'-UTR sequence. And miR-106b promoted cell proliferation, invasion, EMT progression in RCC cellin vitro, as well as promoted the tumor growth of 786-O cells derived xenografts mice. Additionally, loss of Capicua promoted the activation of MAPK signaling pathway. Conclusion: The study suggested that miR-106b regulated RCC progression through MAPK signaling pathway partly by targeting Capicua, which might provide valuable evidence for therapeutic target development of RCC.

Transperitoneal versus extraperitoneal approach in laparoscopic radical prostatectomy: A meta-analysis.

BACKGROUND: To compare the transperitoneal approach with extraperitoneal approach in laparoscopic radical prostatectomy (LRP) (including pure and robotic-assisted LRP) using meta-analytic techniques. METHODS: Medline (PubMed), Embase, Ovid, CMB, and Cochrane databases were searched for studies that compared the transperitoneal and extraperitoneal approaches in LRP from January 2000 to January 2017. Outcomes included were operative time, operative bloods joss (milliliters), rate of transfusion, rate of open conversion, rate of intraoperative complications, rate of postoperative complications, and time of postoperative catheterization. RESULTS: Thirteen studies including 1674 patients were selected for the meta-analysis. 850 (50.8%) cases had undergone transperitoneal LRP (TLRP) and 824 (49.2%) cases had undergone the extraperitoneal LRP (ELRP). Comparison of operative time between the TLRP group and the ELRP group showed no significant differences (weighted mean difference [WMD] = 21.21,95%CI = -1.16-43.57, P = .06). No significant differences were observed in blood loss (WMD = -6.04, 95%CI = -43.38-31.29, P = .75) and the rate of transfusion (odds ratio [OR] = 1.03, 95%CI = 0.55-1.96, P = .92) between the 2 groups. No significant differences were observed for the rate of intraoperative complications (OR = 1.25, 95%CI = 0.57-2.21, P = .75) and the rate of open conversion (OR = 1.12, 95%CI = 0.32-4.97, P = .75). Significant differences were observed in the TLRP group compared with the ELRP group (OR = 1.69, 95%CI: 1.23-2.32, P = .001) regarding the rate of postoperative complications. CONCLUSIONS: Our meta-analysis findings revealed that the TLRP group showed no significant differences in most important indicators compared with ELRP. Moreover, TLRP showed higher rate of postoperative complications compared with ELRP.