作者机构：
[Yang, Xiudeng; Tang, Yamei; Tang, Aiguo] Cent S Univ, Xiangya Hosp 2, Dept Lab Med, Changsha 410011, Hunan, Peoples R China.;[Wei, Qinling] Sun Yat Sen Univ, Affiliated Hosp 3, Dept Psychiat, Guangzhou 510631, Guangdong, Peoples R China.;[Lang, Bing; Zhang, Xianghui; Liu, Yong] Cent S Univ, Xiangya Hosp 2, Dept Psychiat, Changsha 410011, Hunan, Peoples R China.;[Lang, Bing; Zhang, Xianghui; Liu, Yong] Cent S Univ, Mental Hlth Inst, Changsha, Hunan, Peoples R China.;[Lang, Bing; Zhang, Xianghui; Liu, Yong] Hunan Key Lab Psychiat & Mental Hlth, Changsha, Hunan, Peoples R China.
通讯机构：
[Liu, Yong] C;[Liu, Yong] H;Cent S Univ, Xiangya Hosp 2, Dept Psychiat, Changsha 410011, Hunan, Peoples R China.;Cent S Univ, Mental Hlth Inst, Changsha, Hunan, Peoples R China.;Hunan Key Lab Psychiat & Mental Hlth, Changsha, Hunan, Peoples R China.
关键词：
AVP/AVPR1a;CD38;FES;OXT/OXTR;mRNA
摘要：
Schizophrenia (SZ) is a severe neuropsychiatric disorder with significant social cognition impairment. Increasing evidence has suggested that neuropeptides oxytocin (OXT) and arginine vasopressin (AVP) are important mediators of complex social cognition and behavior associates with SZ. In the present study, forty-three first-episode schizophrenia (FES) patients and forty-seven healthy controls (HC) were included. The peripheral mRNA expression of OXT, OXT receptor (OXTR), AVP, AVP 1a receptor (AVPR1a) and CD38 was determined by real-time quantitative polymerase chain reaction (RT-qPCR). The FES patients have a relatively higher mRNA level of OXT and OXTR genes and lower expression of AVP and CD38 genes than HC. No difference was found for AVPR1a between FES patients and HC. As for the sex difference, the mRNA expression of OXT and OXTR showed no difference in both male and female FES patients compared to HC group. The AVP and CD38 genes in female FES patients showed decreased mRNA expression than female HC. Our findings support disrupted OXT and AVP systems in the FES patients.
摘要：
Advanced osteosarcoma (OS) is usually treated by preoperative and postoperative chemotherapy, but there are a very limited number of active agents. Celecoxib (Cel) is a COX-2-selective nonsteroidal anti-inflammatory drug and its antitumoral effect has been shown widely in a variety of cancers including OS cells in vitro. However, the potential combinational effect of Cel with other biological therapy has not been reported in OS cells. In this study, the effects of Cel, miR-34a mimics, and their combination on cell proliferation (MTT assay), migration (in-vitro scratch assay), invasion (transwell assay), mRNA (real-time PCR), and protein (Western blot) expression of associated signal transductions were investigated in cultured MG63 cells. The results showed that miR-34a mimics transfection and Cel treatment significantly decreased cell viability, migration, and invasion in MG63 cells, with their combination being more effective. In contrast, miR-34a inhibitors transfection exerted an effect opposite to miR-34a mimics on cell viability, migration, and invasion. The antitumoral effects of miR-34a, Cel, and their combination were observed in significant up-regulated expression of PTEN and GSK-3β, down-regulated expression of ROCK1, Notch1, and MMP9 as well as Akt Ser473 phosphorylation. Our data suggested that miR-34a exerts a combinational effect with Cel on the cell proliferation, migration, and invasion in OS cells through regulating Notch1/ROCK1–PTEN–Akt–GSK-3β signaling and MMP9 gene expression.
摘要：
Peptide toxins often have divergent pharmacological functions and are powerful tools for a deep review on the current understanding of the structure-function relationships of voltage-gated sodium channels (VGSCs). However, knowing about the interaction of site 3 toxins from tarantula venoms with VGSCs is not sufficient. In the present study, using whole-cell patch clamp technique, we determined the effects of Jingzhaotoxin-I (JZTX-I) on five VGSC subtypes expressed in HEK293 cells. The results showed that JZTX-I could inhibit the inactivation of rNav1.2, rNav1.3, rNav1.4, hNav1.5 and hNav1.7 channels with the IC50 of 870 +/- 8 nM, 845 +/- 4 nM, 339 +/- 5 nM, 335 +/- 9 nM, and 348 +/- 6 nM, respectively. The affinity of the toxin interaction with subtypes (rNav1.4, hNav1.5, and hNav1.7) was only 2-fold higher than that for subtypes (rNav1.2 and rNav1.3). The toxin delayed the inactivation of VGSCs without affecting the activation and steady-state inactivation kinetics in the physiological range of voltages. Site-directed mutagenesis indicated that the toxin interacted with site 3 located at the extracellular S3 S4 linker of domain IV, and the acidic residue Asp at the position1609 in hNav1.5 was crucial for JZTX-I activity. Our results provide new insights in single key residue that allows toxins to recognize distinct ion channels with similar potency and enhance our understanding of the structure-function relationships of toxin-channel interactions. (C) 2015 Elsevier Ltd. All rights reserved.
