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Bladder cancer (BCa) threatens human health due to the high occurrence and mortality. Nowadays, more and more researchers focussed on the molecular mechanisms and biological functions of miRNAs in human cancers. The present study aims to study the biological role of miR-454-3p and miR-374b-5p in BCa. The expression levels of miR-454-3p and miR-374b-5p were detected in BCa tissues and cell lines by qRT-PCR analysis. Kaplan–Meier analysis revealed that the expression levels of miR-454-3p and miR-374b-5p were positively correlated with the overall survival (OS) rate of BCa patients. Gain-of-function assays were conducted to demonstrate the inhibitory effects of miR-454-3p and miR-374b-5p on the invasion, migration, and epithelial–mesenchymal transition (EMT) of BCa cells. Mechanically, ZEB2 was found to be a target of both miR-454-3p and miR-374b-5p. Rescue assays revealed that ZEB2 reversed the inhibitory effects of miR-454-3p and miR-374b-5p on the invasion and migration of BCa cell lines. In summary, miR-454-3p and miR-374b-5p negatively regulated invasion and migration of BCa cell lines via targetting ZEB2.

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The immune response contributes to ongoing secondary tissue destruction following spinal cord injury (SCI). Although infiltrating neutrophils and monocytes have been well studied in this process, T-cells have received less attention. The objective of this study was to assess locomotor recovery and tissue morphology after SCI in athymic (nude) rats, in which T-cell numbers are reduced. Results in athymic rats were compared with heterozygote littermates with normal T-cell profiles and with Sprague-Dawley rats from previous studies in our lab. Following transection of rat spinal cords at T10, we assessed the animals' locomotor recovery on a weekly basis for up to 11 weeks, using the Basso-Beattie-Bresnahan locomotor rating scale. Nude rats showed better locomotor recovery than did heterozygote or Sprague-Dawley rats, achieving scores of 5.6 +/- 0.8 versus 1.0 +/- 0.0, respectively (p = 0.002), at 4 weeks postinjury. The improved recovery of nude rats persisted for the 11-week postinjury assessment period, and was consistent with improved spinal reflexes rather than with recovery of descending motor pathways. Anatomical evaluation at 11 weeks indicated no difference in nude versus heterozygote rats in the size or distribution of cavities caudal to the transection site, but secondary damage was more severe rostral to the transection site in heterozygote rats. In neither group did cavities extend beyond 4 mm caudal to the transection site, and were therefore not directly responsible for the functional differences between the two groups. Cellular expression of the microglia/macrophage antigen ectodysplasin A (ED1) was reduced in nude rats as compared to heterozygotes, but no difference was observed in expression levels of 5-hydroxytryptamine, the 200-kDa neurofilament, or glial fibrillary acidic protein. The findings of the study show that a reduction in T-cell numbers significantly improves locomotor recovery after spinal cord transection, indicating a deleterious role for these immune cells in neural repair after trauma.

Nobiletin is a polymethoxy flavonoid isolated from Citrus depressa and Citrus reticulata. It has been reported that nobiletin can suppress tumors. We primarily explored the antitumor effects of nobiletin and the associated potential mechanisms in ACHN and Caki-2 renal carcinoma cells. A CCK-8 assay and cloning experiments were used to assess cell viability, and a transwell assay and scratch test were used to assess metastatic ability. The cell cycle was analyzed by flow cytometry, whereas apoptosis was analyzed using flow cytometry and a terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay. Protein expression was examined by Western blot and immunofluorescence. Renal cancer cells were subcutaneously transplanted into nude mice for in vivo studies. The data showed that nobiletin administration significantly dose-and time-dependently suppressed renal cancer cell proliferation; moreover, nobiletin treatment induced cell cycle arrest in the G0/G1 phase and promoted apoptosis. Immunofluorescence analysis indicated that nobiletin decreased the nuclear localization of signal transducer and activator of transcription 3 (STAT3) and YY1-associated protein 1 (YY1AP1). Western blot showed that the levels of phosphorylated SRC, phosphorylated AKT serine/threonine kinase (AKT), and phosphorylated STAT3 were decreased, whereas that of phosphorylated YY1AP1 was increased. The results further showed that application of insulin-like growth factor 1 (IGF1) was able to reverse the nobiletin-induced changes in the levels of phosphorylated AKT, phosphorylated STAT3, and phosphorylated YY1AP1, and could also reverse the antitumor effects of nobiletin. The results of in vivo experiments showed that, compared to the control, tumor volume and weight were both reduced following nobiletin treatment. In conclusion, our study demonstrated that nobiletin can inhibit renal carcinoma cell viability and provides a novel therapeutic approach for the treatment of kidney cancer.

After a stroke, it is essential that recovery of function of the upper limb is maximized in order to enable activities of daily living. The hand plays an important role in the function of the upper limb. This study examined the effectiveness of contralaterally controlled functional electrical stimulation (CCFES) on recovery of active dorsiflexion of the wrist and upper limb functioning in patients in the early-phase after stroke (<15 days post-stroke). CCFES significantly shortened the time for regaining wrist dorsiflexion, and improved the upper extremity function and general health of patients with early-phase stroke, compared with conventional neuro muscular electrical stimulation. CCFES therefore has potential as a clinical intervention. Objectives: To investigate the effectiveness of contra laterally controlled functional electrical stimulation (CCFES) on the recovery of active wrist dorsiflexion and upper limb function in patients with early-phase stroke (<15 days poststroke). Methods: Patients in the CCFES group were treated with routine rehabilitation combined with CCFES, while those in the conventional neuromuscular electrical stimulation (NMES) group were treated with routine rehabilitation combined with NMES. Time intervals from stroke onset to appearance of wrist dorsiflexion, and from onset of treatment to appearance of wrist dorsiflexion were recorded (in days). Functional assessments were also performed at baseline and endpoint. Results: Nineteen out of 21 patients in the CCFES group and 12 out of 20 patients in the NMES group regained active wrist dorsiflexion during the treatment and follow-up period (90.5% vs 60%, p = 0.025). The mean time interval from onset of treatment to appearance of active wrist dorsiflexion was signifcantly shorter in the CCFES group than in the NMES group (p < 0.001). The CCFES group had signifcantly higher scores for upper extremity function (p = 0.001), strength of extensor carpi (p = 0.002), active ROM for wrist dorsiflexion (p = 0.003), activities of daily living score (p = 0.023) and ICF score (p < 0.001) than the NMES group at the endpoint. Conclusion: CCFES signifcantly shortened the time for regaining wrist dorsiflexion, and improved the upper extremity function and general health of patients with early-phase stroke. CCFES therefore has potential as a clinical intervention.

BackgroundEvidence about the association between Bisphenol A (BPA) and the risk of recurrent miscarriage (RM) in human being is still limited.ObjectiveWe evaluated the association of urinary BPA concentrations with RM in human being.MethodsA hospital-based 1:2 matched case-control study on RM was carried out in Suzhou and Kunshan in Jiangsu Province in China between August 2008 and November 2011. Total urinary BPA concentrations in 264 eligible urine samples (102 RM patients and 162 controls) were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The Wilcoxon test and conditional logistic regression were used to estimate the differences between the groups and odds ratios (OR) with 95% confidence intervals (CI), respectively.ResultsThe median ± IQR (interquartile range) (P 75-P 25) values of non-creatinine-adjusted total urinary BPA levels in the RM patients and the controls were 1.66±3.69ng/ml and 0.58±1.07ng/ml, respectively (0.98±2.67μg/g Cr (creatinine) and 0.40±0.77μg/g Cr. The adjusted BPA level was significantly higher in the RM patients than in the controls (Wilcoxon test, Z = 4.476, P<0.001). Higher level of urinary BPA was significantly associated with an increased risk of RM (P-trend <0.001). Compared to the groups with urinary BPA levels less than 0.16μg/g Cr, the women with levels of 0.40–0.93μg/g Cr and 0.93μg/g Cr or above had a significantly higher risk of RM (OR = 3.91, 95%CI: 1.23–12.45 and OR = 9.34, 95%CI: 3.06–28.44) that persisted after adjusting for confounding factors. The time from recently RM date to recruitment does not significantly influence the urinary BPA level (P = 0.090).ConclusionExposure to BPA may be associated with RM risk.