Three‐dimensional (3D) cell culture has been reported to increase the therapeutic potentials of mesenchymal stem cells (MSCs). In this study, we aimed to investigate the therapeutic effects of 3D spheroids of human adipose‐derived MSCs for acute kidney injury (AKI). In vitro studies indicated that 3D spheroids of MSCs produced higher levels of extracellular matrix proteins (including collagen I, fibronectin and laminin), and exhibited stronger anti‐apoptotic and anti‐oxidative capacities than two‐dimensional (2D) cultured cells. Furthermore, 3D culture increased the paracrine secretion of cytokines by MSCs, including angiogenic factors (VEGF and basic fibroblast growth factor), anti‐apoptotic factors (epidermal growth factor and hepatocyte growth factor), the anti‐oxidative factor insulin‐like growth factor and the anti‐inflammatory protein tumour necrosis factor‐alpha stimulated gene/protein 6. Consistent with in vitro experiments, 3D spheroids of MSCs showed enhanced survival and paracrine effects in vivo. More importantly, when injected into the kidney of model rats with ischemia‐reperfusion (I/R)‐induced AKI, 3D spheroids were more beneficial in protecting the I/R kidney against apoptosis, reducing tissue damage, promoting vascularization and ameliorating renal function compared with 2D cultured cells. Therefore, the 3D culture strategy improved the therapeutic effects of MSCs, and might be promising for AKI treatment.

ObjectiveMany studies have reported the prognostic predictive value of CD166 as a cancer stem cell marker in cancers of the digestive system; however, its predictive value remains controversial. Here, we investigate the correlation between CD166 positivity in digestive system cancers and clinicopathological features using meta-analysis.MethodsA comprehensive search in PubMed and ISI Web of Science through March of 2013 was performed. Only articles containing CD166 antigen immunohistochemical staining in cancers of the digestive system were included,including pancreatic cancer, esophageal cancer, gastric cancer and colorectal cancer. Data comparing 3- and 5-year overall survival along with other clinicopathological features were collected.ResultsNine studies with 2553 patients who met the inclusion criteria were included for the analysis. The median rate of CD166 immunohistochemical staining expression was 56% (25.4%–76.3%). In colorectal cancer specifically, the results of a fixed-effects model indicated that CD166-positive expression was an independent marker associated with a smaller tumor burden (T category; RR = 0.93, 95%, CI: 0.88–0.98) but worse spread to nearby lymph nodes (N category; RR = 1.17, 95% CI: 1.05–1.30). The 5-year overall survival rate was showed relationship with cytoplasmic positive staining of CD166 (RR = 1.47 95% 1.21–1.79), but no significant association was found in the pool or any other stratified analysis with 3- or 5- year overall survival rate.ConclusionBased on the published studies, different cellular location of CD166 has distinct prognostic value and cytoplasmic positive expression is associated with worse prognosis outcome. Besides, our results also find CD166 expression indicate advanced T category and N-positive status in colorectal cancer specifically.

BackgroundMyeloid ecotropic viral integration site 1 (MEIS1) protein plays a synergistic causative role in acute myeloid leukemia (AML). However, MEIS1 has also shown to be a potential tumor suppressor in some other cancers, such as non-small-cell lung cancer (NSCLC) and prostate cancer. Although multiple roles of MEIS1 in cancer development and progression have been identified, there is an urgent demand to discover more functions of this molecule for further therapeutic design.MethodsMEIS1 was overexpressed via adenovirus vector in clear cell renal cell carcinoma (ccRCC) cells. Western blot and real-time qPCR (quantitative Polymerase Chain Reaction) was performed to examine the protein and mRNA levels of MEIS1. Cell proliferation, survival, in vitro migration and invasion were tested by MTT, colony formation, soft-agar, transwell (in vitro invasion/migration) assays, and tumor in vivo growthwas measured on nude mice model. In addition, flow-cytometry analysis was used to detect cell cycle arrest or non-apoptotic cell death of ccRCC cells induced by MEIS1.ResultsMEIS1 exhibits a decreased expression in ccRCC cell lines than that in non-tumor cell lines. MEIS1 overexpression inhibits ccRCC cells proliferation and induces G1/S arrest concomitant with marked reduction of G1/S transition regulators, Cyclin D1 and Cyclin A. Moreover, MEIS1-1 overexpression also induces non-apoptotic cell death of ccRCC cells via decreasing the levels of pro-survival regulators Survivin and BCL-2. Transwell migration assay (TMA) shows that MEIS1 attenuates in vitro invasion and migration of ccRCC cells with down-regulated epithelial-mesenchymal transition (EMT) process. Further, in nude mice model, MEIS1 inhibits the in vivo growth of Caki-1 cells.ConclusionsBy investigating the role of MEIS1 in ccRCC cells’ survival, proliferation, anchorage-independent growth, cell cycle progress, apoptosis and metastasis, in the present work, we propose that MEIS1 may play an important role in clear cell renal cell carcinoma (ccRCC) development.

ACTH independent macronodular adrenal hyperplasia (AIMAH) is a rare disorder characterized by bilateral macronodular hyperplasia of the adrenal glands and increased cortisol production with subclinical or overt Cushing's syndrome. Although the family clustering of AIMAH is infrequent, we have tried our best to find such a familial affected pedigree with complete clinical information and successfully collect adrenalectomy tissue samples from two members of this family. Using whole exome sequencing and several variant prioritization strategies based on disease network analysis, we identified Endothelin receptor type A (EDNRA) Ser420Thr mutation as a causative mutation of AIMAH. EDNRA is a member of G protein coupled receptor family and is involved in cardiovascular or polycystic kidney disease. Our findings indicate that the mutation of EDNRA at S420T site should be regard as a potential AIMAH causative variation in familial and sporadic affected patients.

Abstract. The aim of the present study was to investigate the pathogenesis of metastatic prostate carcinoma, to find the metabolic pathways changed in the disease and to screen out the potential therapeutic drugs. GSE38241 was downloaded from Gene Expression Omnibus; the Geoquery package was applied to preprocessed expression profiling, and the differentially-expressed genes (DEGs) were selected with limma (linear regression model packages). Next, WikiPathways cluster analysis was performed for DEGs on a Gene Set Analysis Toolkit V2 platform, and DEGs with hypergeometric algorithms were calculated through gene set enrichment analysis. A total of 1,126 DEGs were identified between the normal prostate and metastatic prostate carcinoma. In addition, KPNA4, SYT1, PLCB1, SPRED1, MBNL2, RNF165, MEF2C, MBNL1, ZFP36L1 and CELF2, were found to be likely to play significant roles in the process of metastatic prostate carcinoma. The small molecules STOCK1N-35874 and 5182598 could simulate the state of normal cells well, while the small molecules MS-275 and quinostatin could simulate the state of metastatic prostate carcinoma cells. In conclusions, the small molecules STOCK1N-35874 and 5182598 were identified to be good potential therapeutic drugs for the treatment of metastatic prostate carcinoma, while the two small molecules MS-275 and quinostatin could cause metastatic prostate carcinoma.

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To report our experience of pure laparoscopic and robot-assisted laparoscopic reconstructive surgery in congenital megaureter, seven patients (one bilateral) with symptomatic congenital megaureter underwent pure laparoscopic or robot-assisted laparoscopic surgery. The megaureter was exposed at the level of the blood vessel and was isolated to the bladder narrow area. Extreme ureter trim and submucosal tunnel encapsulation or papillary implantations and anti-reflux ureter bladder anastomosis were performed intraperitoneally by pure laparoscopic or robot-assisted laparoscopic surgery. The clinical data of seven patients after operation were analyzed, including the operation time, intraoperative complications, intraoperative bleeding volumes, postoperative complications, postoperative hospitalization time and pathological results. All of the patients were followed. The operation was successfully performed in seven patients. The mean operation times for pure laparoscopic surgery and robotic-assistant laparoscopic surgery were 175 (range: 150–220) and 187 (range: 170–205) min, respectively, and the mean operative blood loss volumes were 20 (range: 10–30) and 28.75 (range: 15–20) ml, respectively. There were no intraoperative complications. The postoperative drainage time was 5 (range: 4–6) and 5.75 (range: 5–6) d, respectively, and the indwelling catheter time was 6.33 (range: 4–8) d and 7 (range: 7–7) d, respectively. The postoperative hospitalization time was 7.67 (range: 7–8) d and 8 (range: 7–10) d, respectively. There was no obvious pain, no secondary bleeding and no urine leakage after the operation. Postoperative pathology reports revealed chronic urothelial mucosa inflammation. The follow-up results confirmed that all patients were relieved of their symptoms. Both pure laparoscopic and robot-assisted laparoscopic surgery using different anti-reflux ureter bladder anastomoses are safe and effective approaches in the minimally invasive treatment of congenital megaureter.

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