BackgroundRecently, a variant of ER-α, ER-α36 was identified and cloned. ER-α36 lacks intrinsic transcription activity and mainly mediates non-genomic estrogen signaling. The purpose of this study was to investigate the function and the underlying mechanisms of ER-α36 in growth regulation of endometrial Ishikawa cancer cells.MethodsThe cellular localization of ER-α36 and ER-α66 were determined by immunofluorescence in the Ishikawa cells. Ishikawa endometrial cancer control cells transfected with an empty expression vector, Ishikawa cells with shRNA knockdown of ER-α36 (Ishikawa/RNAiER36) and Ishikawa cells with shRNA knockdown of ER-α66 (Ishikawa/RNAiER66) were treated with E2 and E2-conjugated to bovine serum albumin (E2-BSA, membrane impermeable) in the absence and presence of different kinase inhibitors HBDDE, bisindolylmaleimide, rottlerin, H89 and U0126. The phosphorylation levels of signaling molecules and cyclin D1/cdk4 expression were examined with Western blot analysis and cell growth was monitored with the MTT assay.ResultsImmunofluorescence staining of Ishikawa cells demonstrated that ER-α36 was expressed mainly on the plasma membrane and in the cytoplasm, while ER-α66 was predominantly localized in the cell nucleus. Both E2 and E2-BSA rapidly activated PKCδ not PKCα in Ishikawa cells, which could be abrogated by ER-α36 shRNA expression. E2-and E2-BSA-induced ERK phosphorylation required ER-α36 and PKCδ. However, only E2 was able to induce Camp-dependent protein kinase A (PKA) phosphorylation. Furthermore, E2 enhances cyclin D1/cdk4 expression via ER-α36.ConclusionE2 activates the PKCδ/ERK pathway and enhances cyclin D1/cdk4 expression via the membrane-initiated signaling pathways mediated by ER-α36, suggesting a possible involvement of ER-α36 in E2-dependent growth-promoting effects in endometrial cancer cells.

Archaeological, genetic, and linguistic evidence has supported the idea that northern China is the original center of modern Sino‐Tibetan‐speaking populations. However, the demographic history of subsequent southward migration and genetic admixture of Han Chinese with surrounding indigenous populations remain uncharacterized, and the language shifts and assimilations accompanied by movement of people, or just an adaptation of cultural ideas among populations in central China is still unclear, especially for Tibeto‐Burman‐speaking Tujia and central Han Chinese populations. To resolve this, we genotyped over 60K genome‐wide markers in 505 unrelated individuals from 63 indigenous populations. Our results showed both studied Han and Tujia were at the intermediate position in the modern East Asian North–South genetic cline and there was a correlation between the genetic composition and the latitude. We observed the strong genetic assimilation between Tujia people and central Han Chinese, which suggested massive population movements and genetic admixture under language borrowing. Tujia and central Han Chinese could be modeled as a two‐way admixture deriving primary ancestry from a northern ancestral population closely related to the ancient DevilsCave and present‐day Tibetans and a southern ancestral population closely related to the present‐day Tai‐Kadai and Austronesian‐speaking groups. The ancestral northern population we suspect to be related to the Neolithic millet farming groups in the Yellow River Basin or central China. We showed that the newly genotyped populations in Hubei Province had a higher proportion of DevilsCave or modern Tungusic/Mongolic‐related northern ancestries, while the Hunan populations harbored a higher proportion of Austronesian/Tai‐Kadai‐related southern ancestries.

In the study, the functional recovery and relative comprehensive quality of life of cases of global brachial plexus treated with free functioning muscle transfers were investigated. Patients who received functioning gracilis muscle transfer between August 1999 and October 2014 to reconstruct elbow flexion, wrist and fingers extension were recruited. The mean age of the patients was 26.36 (range, 16–42) years. The mean period of time from gracilis transfer to the last follow-up was 54.5 months (range, 12–185 months). Muscle power, active range of motion of the elbow flexion, wrist extension, and total active fingers extension were recorded. SDS, SAS and DASH questionnaires were given to estimate patients’ quality of life. 35.71% reported good elbow flexion and 50.00% reported excellent elbow flexion. The average ROM of the elbow flexion was 106.5° (range, 0–142°) and was 17.00° (range, 0–72°) for wrist extension. The average DASH score was 51.14 (range, 17.5–90.8). The prevalence of anxiety and depression were 42.86% and 45.24%. Thrombosis and bowstringing were the most common short and long-term complications. Based on these findings, free gracilis transfer using accessory nerve as donor nerve is a satisfactory treatment to reconstruct the elbow flexion and wrist extension in global-brachial-plexus-injured patients.

Our results indicated that LNU is a safe and effective method to treat UTUC. Given the limitations of this study, further multicenter, randomized trials are required to confirm these findings.

Cancer has been a major public health issue all over the world and cancer patients diagnosed at early stages have a comparatively favorable prognosis. The association between specific dysregulated expressed microRNA-155 (miRNA-155, miR-155) and tumorigenesis has been identified by numerous studies. However, perplexity and inconsistence arise from a wide range of studies due to heterogeneity. Therefore, this meta-analysis was carried out to validate the association between miR-155 and tumorigenesis together with the clinical applicability of miR-155.Relevant studies were searched, identified, and selected from PubMed, Embase, Cochrane, Sinomed, and Wanfang database until July 5, 2015. Then, the sensitivity, specificity, and area under the summary receiver operator characteristic curve (AUC) were calculated to assess the overall performance miR-155 for cancer detection.A total of 25 studies were included in the meta-analysis with a total number of 1896 cancer patients and 1226 healthy controls. The overall sensitivity and specificity was 76.8% (95%CI: 71.1–81.7%) and 82.9% (95% CI: 77.5–87.3%), respectively. In addition, the pooled AUC and partial AUC was 0.867 and 0.718, respectively. Results from subgroup analyses suggested that the diagnostic accuracy of miR-155 in the Caucasian group was significantly higher than that in the Asian group. Similarly, serum sample type may provide better diagnostic value of miR-155 than plasma. Apart from that, miR-155 in breast cancer achieved the highest accuracy compared with miR-155 in other types of cancer.Results from meta-analysis suggested that miR-155 had great potential as a novel noninvasive biomarker for human cancer detection, particularly when breast cancer or Caucasian is involved. However, well-designed cohort or case control studies with large sample size should be implemented to confirm the diagnostic value of miR-155.

Bladder cancer is one of the causes of cancer‑related death and has a high mortality rate. Daidzein, a natural isoflavone compound predominantly extracted from soybeans, has been reported to exhibit several bioactivities, including anti-tumor. However, the effects of daidzein on bladder cancer remains unrevealed. Here we investigated the effects and molecular mechanisms of daidzein on bladder cancer using multiple in vitro cell lines and in vivo xenograft mice studies. Our results showed that daidzein reduced cell viability in a time- and concentration‑dependent manner. Daidzein significantly impaired colony formation, caused G1/S cell cycle arrest and induced apoptosis of the bladder cancer cells. We also verified that daidzein efficiently suppressed RT112 cell xenograft tumor growth in nude mice. Mechanism studies indicated that significant down-regulation of the FGFR3 signaling pathway was responsible for the efficacy of daidzein. The phosphorylation levels of FGFR3, Akt and Erk proteins were suppressed in association with the decreasing of some apoptosis-suppressing molecules under the daidzein treatment. Knockdown of endogenous FGFR3 impaired the activity of daidzein against bladder cancer, which suggested that the effect of daidzein was mainly mediated by FGFR3 pathway. In addition, the function model of daidzein was similar with FGFR3 antagonist PD173074 in RT112 cells. Taken together, the results this study demonstrate that daidzein is capable of inhibiting bladder cancer growth and might be a novel effective chemotherapeutic agent for the application to combat bladder carcinoma.

Asiatic acid (AA) has been demonstrated to exhibit anti-diabetic activity. However, the mechanisms and underlying signaling pathways remain to be elucidated. The present study was performed to confirm the protective effect of AA and demonstrate its ability to regulate the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase-3β (GSK-3β) signaling pathway in db/db mice. Db/db mice fed on a high-fat diet were used to model diabetes mellitus. Modeled mice were divided randomly into the model control, pioglitazone hydrochloride tablet (PH) and AA groups. Age-matched C57 BL/6J mice served as normal controls. Lipid and glucose levels, and glycogen synthesis rates were assessed following treatment. Pathological changes were detected using hematoxylin and eosin staining. Expression of the PI3K/AKT/GSK-3β signaling pathway at the mRNA level was measured using quantitative polymerase chain reaction analysis. The model control group revealed typical characteristics of obesity and diabetes, including high glucose and lipid levels, and decreased glycogen synthesis. Four weeks of treatment with AA or PH ameliorated these abnormalities. AA and PH treatments mitigated the upregulation of PI3K, AKT, insulin receptor, and insulin receptor substrate-1 mRNA expression in modeled mice. Furthermore, AA and PH treatments decreased GSK-3β and glucose-6-phosphatase mRNA expression compared with the normal control group. The results of the present study confirmed that AA possesses anti-diabetic activity in db/db mice. The PI3K/AKT/GSK-3β signaling pathway may mediate this protective effect.

MicroRNA (MiR)-506 serves a vital role in several types of cancer. However, the role of miR-506 in bladder cancer (BCa) progression remains to be investigated. The present study demonstrated that miR-506 expression was downregulated in BCa tissues and cell lines. Meanwhile, overexpression of miR-506 inhibited cell proliferation, migration and invasion. Additionally, upregulated miR-506 increased E-cadherin, and reduced N-cadherin and Vimentin expression levels, as markers of epithelial-to-mesenchymal transition. RWD domain containing 4 (RWDD4) was revealed to be a miR506 target in BCa cells, and the downregulation of RWDD4 was found to suppress BCa cell proliferation, migration and invasion. In summary, miR-506 may suppress the aggressive properties of human BCa cells by targeting RWDD4, and thus may be a novel therapeutic target in human BCa.