The relationship between marital adjustment and personality characteristics, medical coping style of infertile patients

目的  探讨不孕不育患者婚姻调适状况与人格特征和医学应对方式的关系，为临床开展心理健康干预提供依据。方法  选取2012年8月—2015年1月某三级甲等医院生殖医学中心治疗的156例已婚不孕不育症患者。采用艾森克人格问卷表（EPQ）、Locke-Wollance婚姻调适测定量表和医学应对问卷（MCMQ），对患者进行调查，分别测评患者婚姻调适状况、人格特征和医学应对方式及其相关性。结果  患者婚姻调适状况与EPQ的P、N及MCMQ屈服呈显著负相关，与EPQ 的E和MCMQ面对则呈显著正相关；EPQ的P、N与MCMQ面对呈负相关，与MCMQ的屈服呈正相关；EPQ的E则与MCMQ面对呈显著正相关。EPQ的P、E、N和MCMQ面对、屈服在婚姻调适状况高中低分组中的比较，差异均有统计学意义（均P＜0.01）。多元逐步回归分析：面对、回避，屈服及精神质（P）等4个因素共解释了不孕不育症患者婚姻调适总变异的26.4%。结论  人格特征、医学应对方式是影响不孕不育症患者婚姻调适的重要因素。Objective: To explore the relationship between marital adjustment and personality characteristics and coping styles of patients with infertility, and to provide evidence for clinical intervention. Methods: A total of 156 patients with infertility were selected from August 2012 to January 2015 in a grade a hospital of reproductive medicine center. This research is a cross - sectional survey. The Eysenck Personality Questionnaire (EPQ), Locke-Wollance marital adjustment test scale and Medical Coping Questionnaire (MCMQ), were investigated, respectively, to evaluate the patient status, marital adjustment and personality characteristics and coping style and their relationship. Results: Patients marital adjustment status and EPQ P, N and MCMQ yield was significantly negative correlated, and EPQ E and MCMQ was significantly positively related; EPQ P, N and MCMQ showed a negative correlation, and MCMQ yield positively correlated; EPQ E, and MCMQ face was significantly positively related, EPQ P, E, N and MCMQ, yield in the marital adjustment the conditions of grouping, the differences were statistically significant (all P < 0.01). Multiple stepwise regression analysis: 4 factors, such as confrontation, avoidance, yield and psychoticism (P), were used to explain the total variation of the adjustment of marriage in infertile patients (26.4%). Conclusion: Personality characteristics, medical coping styles are the important factors influencing the marital adjustment for infertility patients

Effects of common artificial sweeteners at environmentally relevant concentrations on soil springtails and their gut microbiota

Artificial sweeteners (AS) are extensively utilized as sugar substitutes and have been recognized as emerging environmental contaminants. While the effect of AS on aquatic organisms has garnered recent attention, their effects on soil invertebrates and gut microbial communities remain unclear. To address this knowledge gap, we exposed springtails (Folsomia candida) to both single and combined treatments of four typical AS (sucralose [SUC], saccharin [SAC], cyclamate [CYC], and acesulfame [ACE]) at environmentally relevant concentrations of 0.01, 0.1 and 1 mg kg−1 in soil. Following the first-generational exposure, the reproduction of juveniles showed a significant increase under all the AS treatments of 0.1 mg kg−1. The transcriptomic analysis revealed significant enrichment of several Kyoto Encyclopedia of Gene and Genome pathways (e.g., glycolysis/gluconeogenesis, pentose and glucuronate interconversions, amino sugar, and nucleotide sugar metabolism, ribosome, and lysosome) in springtails under all AS treatments. Analysis of gut bacterial microbiota indicated that three AS (SUC, CYC, and ACE) significantly decreased alpha diversity, and all AS treatments increased the abundance of the genus Achromobacter. After the sixth-generational exposure to CYC, weight increased, but reproduction was inhibited. The pathways that changed significantly (e.g., extracellular matrix-receptor interaction, amino sugar and nucleotide sugar metabolism, lysosome) were generally similar to those altered in first-generational exposure, but with opposite regulation directions. Furthermore, the effect on the alpha diversity of gut microbiota was contrary to that after first-generational exposure, and more noticeable disturbances in microbiota composition were observed. These findings underscore the ecological risk of AS in soils and improve our understanding of the toxicity effects of AS on living organisms

Ca2+ Influx through TRPC Channels Is Regulated by Homocysteine–Copper Complexes

An elevated level of circulating homocysteine (Hcy) has been regarded as an independent risk factor for cardiovascular disease; however, the clinical benefit of Hcy lowering-therapy is not satisfying. To explore potential unrevealed mechanisms, we investigated the roles of Ca2+ influx through TRPC channels and regulation by Hcy–copper complexes. Using primary cultured human aortic endothelial cells and HEK-293 T-REx cells with inducible TRPC gene expression, we found that Hcy increased the Ca2+ influx in vascular endothelial cells through the activation of TRPC4 and TRPC5. The activity of TRPC4 and TRPC5 was regulated by extracellular divalent copper (Cu2+) and Hcy. Hcy prevented channel activation by divalent copper, but monovalent copper (Cu+) had no effect on the TRPC channels. The glutamic acids (E542/E543) and the cysteine residue (C554) in the extracellular pore region of the TRPC4 channel mediated the effect of Hcy–copper complexes. The interaction of Hcy–copper significantly regulated endothelial proliferation, migration, and angiogenesis. Our results suggest that Hcy–copper complexes function as a new pair of endogenous regulators for TRPC channel activity. This finding gives a new understanding of the pathogenesis of hyperhomocysteinemia and may explain the unsatisfying clinical outcome of Hcy-lowering therapy and the potential benefit of copper-chelating therapy

High glucose enhances store-operated calcium entry by upregulating ORAI/STIM via calcineurin-NFAT signalling

© 2014, Springer-Verlag Berlin Heidelberg. Abstract: ORAI and stromal interaction molecule (STIM) are store-operated channel molecules that play essential roles in human physiology through a coupling mechanism of internal Ca 2+ store to Ca 2+ influx. However, the roles of ORAI and STIM in vascular endothelial cells under diabetic conditions remain unknown. Here, we investigated expression and signalling pathways of ORAI and STIM regulated by high glucose or hyperglycaemia using in vitro cell models, in vivo diabetic mice and tissues from patients. We found that ORAI1-3 and STIM1-2 were ubiquitously expressed in human vasculatures. Their expression was upregulated by chronic treatment with high glucose (HG, 25 mM d-glucose), which was accompanied by enhanced store-operated Ca 2+ influx in vascular endothelial cells. The increased expression was also observed in the aortae from genetically modified Akita diabetic mice (C57BL/6-Ins2 Akita /J) and streptozocin-induced diabetic mice, and aortae from diabetic patients. HG-induced upregulation of ORAI and STIM genes was prevented by the calcineurin inhibitor cyclosporin A and NFATc3 siRNA. Additionally, in vivo treatment with the nuclear factor of activated T cells (NFAT) inhibitor A-285222 prevented the gene upregulation in Akita mice. However, HG had no direct effects on ORAI1-3 currents and the channel activation process through cytosolic STIM1 movement in the cells co-expressing STIM1-EYFP/ORAIs. We concluded that upregulation of STIM/ORAI through Ca 2+ -calcineurin-NFAT pathway is a novel mechanism causing abnormal Ca 2+ homeostasis and endothelial dysfunction under hyperglycaemia. Key message: ORAI1-3 and STIM1-2 are ubiquitously expressed in vasculatures and upregulated by high glucose.Increased expression is confirmed in Akita (Ins2 Akita /J) and STZ diabetic mice and patients.Upregulation mechanism is mediated by Ca 2+ /calcineurin/NFATc3 signalling.High glucose has no direct effects on ORAI1-3 channel activity and channel activation process

Study of RNA Interference Targeting NET-1 Combination with Sorafenib for Hepatocellular Carcinoma Therapy In Vitro

The aim of this study is to explore the inhibitory effects of RNA interference (RNAi) targeting NET-1 or combined with sorafenib on HCC in vitro and in vivo and the possible underlying mechanisms. The expressions of NET-1 mRNA and protein were detected by RT-QPCR and western blot. The ability of proliferation was determined by CCK-8 assay. Apoptosis was examined by flow cytometry (FCM). Abilities of migration and invasion were measured by scratch-wound assay and transwell assay. MHCC97H cells with stable transfection of NET-1shRNA were injected subcutaneously to prepare nude mice model of HCC and Caspase-3, Caspase-8, and Caspase-9 mRNAs of tumor tissues in different groups were examined. NET-1 mRNA and protein were reduced sharply in MHCC97H cells transfected with NET-1shRNA. The abilities of proliferation and migration were inhibited and apoptosis was promoted in either NET-1shRNA or sorafenib as compared with untreated cells in vitro and in vivo (P<0.05). The mRNA levels of caspase-3, caspase-8, and caspase-9 of tumor tissues were reduced in different treatment groups compared with untreated group, particularly in combination group. (P<0.05). The combination NET-1shRNA with sorafenib dramatically enhanced the effects of sorafenib antitumor ,which may involve in blocking ras signaling pathway and stimulating apoptotic pathways simultaneously

T-type Ca 2+ channel blocker mibefradil blocks ORAI channels via acting on extracellular surface

Background and purposeMibefradil (Mib), a T‐type Ca2+ channel blocker, has been investigated for treating solid tumours. However, its underlying mechanisms are still unclear. Here we aimed to investigate the pharmacological aspect of Mib on ORAI store‐operated Ca2+ channels.Experimental approachHuman ORAI1‐3 in tetracycline‐regulated pcDNA4/TO vectors was transfected into HEK293 T‐REx cells with STIM1 stable expression. The ORAI currents were recorded by whole‐cell and excised‐membrane patch clamp. Ca2+ influx or release was measured by Fura‐PE3/AM. Cell growth and death were monitored by WST‐1, LDH assays and flow cytometry.Key resultsMib inhibited ORAI1, ORAI2 and ORAI3 currents in a dose‐dependent manner. The IC50 for ORAI1, ORAI2 and ORAI3 was 52.6 μM, 14.1 μM and 3.8 μM, respectively. Outside‐out patch demonstrated that perfusion of 10 μM Mib to the extracellular surface completely blocked ORAI3 currents and single channel activity evoked by 2‐APB. Intracellular application of Mib did not alter ORAI3 channel activity. Mib at higher concentrations (>50 μM) inhibited Ca2+ release, but had no effect on cytosolic STIM1 translocation evoked by thapsigargin. The inhibition of Mib on ORAI channels is structure‐related, since other T‐type Ca2+ channel blockers with different structures, such as ethosuximide and ML218, had no or very small effect on ORAI channels. Moreover, Mib inhibited cell proliferation, induced apoptosis and arrested cell cycle progression.Conclusions and implicationsOur results suggest that Mib is a potent extracellular ORAI channel blocker, which provides a new pharmacological profile for the compound in regulating cell growth and death as an anti‐cancer drug

Structure of the Mouse TRPC4 Ion Channel

Members of the transient receptor potential (TRP) ion channels conduct cations into cells. They mediate functions ranging from neuronally mediated hot and cold sensation to intracellular organellar and primary ciliary signaling. Here we report a cryo-electron microscopy (cryo-EM) structure of TRPC4 in its unliganded (apo) state to an overall resolution of 3.3 Å. The structure reveals a unique architecture with a long pore loop stabilized by a disulfide bond. Beyond the shared tetrameric six-transmembrane fold, the TRPC4 structure deviates from other TRP channels with a unique cytosolic domain. This unique cytosolic N-terminal domain forms extensive aromatic contacts with the TRP and the C-terminal domains. The comparison of our structure with other known TRP structures provides molecular insights into TRPC4 ion selectivity and extends our knowledge of the diversity and evolution of the TRP channels