血管内皮生长因子受体3和神经纤毛蛋白2对胃癌SGC-7901细胞增殖和凋亡的影响

目的探讨分别阻断和联合阻断血管内皮生长因子受体3(Vascular endothelial growth factor receptor 3,VEGFR3)及神经纤毛蛋白2(Neuropilin 2,NRP2)基因的表达对人胃癌SGC-7901细胞株增殖和凋亡的影响。方法将SGC-7901细胞株分为3大组,VEGFR3阻断组、NRP2阻断组和VEGFR3+NRP2阻断组,各大组中又包含空白对照组、脂质体转染组、无义链转染组(NSODN组)和不同浓度反义链转染组(ASODN组)。转染后的各组SGC-7901细胞株经RT-PCR法检测VEGFR3-mRNA及NRP2-mRNA的转录水平。分别采用MTT法和流式细胞术检测细胞的增殖和凋亡情况。结果反义链转染组VEGFR3-mRNA和NRP2-mRNA的转录水平明显低于其各自的空白对照组、脂质体转染组和NSOND组,表明该组成功阻断基因VEGFR3和NRP2的表达。各组细胞的增殖和凋亡情况差异有统计学意义(P<0.05),并呈剂量和时间依赖性。在相同条件下,单独转染VEGFR3-ASODN组对胃癌细胞增殖的抑制及促凋亡作用优于单独转染NRP2-ASODN组,而联合转染组对细胞增殖的抑制及促凋亡作用最明显。结论阻断VEGFR3基因的表达对细胞增殖凋亡的影响大于阻断NRP2基因,联合阻断两个基因的表达,对细胞增殖和凋亡的影响明显大于单独阻断组。     

Secretome Survey of Human Plexiform Neurofibroma Derived Schwann Cells Reveals a Secreted form of the RARRES1 Protein

To bring insights into neurofibroma biochemistry, a comprehensive secretome analysis was performed on cultured human primary Schwann cells isolated from surgically resected plexiform neurofibroma and from normal nerve tissue. Using a combination of SDS-PAGE and high precision LC-MS/MS, 907 proteins were confidently identified in the conditioned media of Schwann cell cultures combined. Label free proteome profiling revealed consistent release of high levels of 22 proteins by the four biological replicates of NF1 Schwann cell cultures relative to the two normal Schwann cell cultures. Inversely, 9 proteins displayed decreased levels in the conditioned media of NF1 relative to normal Schwann cells. The proteins with increased levels included proteins involved in cell growth, angiogenesis and complement pathway while proteins with decreased levels included those involved in cell adhesion, plasminogen pathway and extracellular matrix remodeling. Retinoic acid receptor responder protein-1 (RARRES1), previously described as an integral membrane tumor suppressor, was found exclusively secreted by NF1 Schwann cells but not by normal Schwann cells. All-trans retinoic acid modulated secretion of RARRES1 in a dose dependent manner. This study shows altered secretion of key proteins in NF1 derived Schwann cells. The potential implication of these proteins in neurofibroma biology is discussed.     

Does the Neuroprotective Role of Anandamide Display Diurnal Variations?

The endocannabinoid system is a component of the neuroprotective mechanisms that an organism displays after traumatic brain injury (TBI). A diurnal variation in several components of this system has been reported. This variation may influence the recovery and survival rate after TBI. We have previously reported that the recovery and survival rate of rats is higher if TBI occurs at 1:00 than at 13:00. This could be explained by a diurnal variation of the endocannabinoid system. Here, we describe the effects of anandamide administration in rats prior to the induction of TBI at two different times of the day: 1:00 and 13:00. We found that anandamide reduced the neurological damage at both times. Nevertheless, its effects on bleeding, survival, food intake, and body weight were dependent on the time of TBI. In addition, we analyzed the diurnal variation of the expression of the cannabinoid receptors CB1R and CB2R in the cerebral cortex of both control rats and rats subjected to TBI. We found that CB1R protein was expressed more during the day, whereas its mRNA level was higher during the night. We did not find a diurnal variation for the CB2R. In addition, we also found that TBI increased CB1R and CB2R in the contralateral hemisphere and disrupted the CB1R diurnal cycle.     

The Role of Thyroid Hormone Signaling in the Prevention of Digestive System Cancers

Thyroid hormones play a critical role in the growth and development of the alimentary tract in vertebrates. Their effects are mediated by nuclear receptors as well as the cell surface receptor integrin α_Vβ₃. Systemic thyroid hormone levels are controlled via activation and deactivation by iodothyronine deiodinases in the liver and other tissues. Given that thyroid hormone signaling has been characterized as a major effector of digestive system growth and homeostasis, numerous investigations have examined its role in the occurrence and progression of cancers in various tissues of this organ system. The present review summarizes current findings regarding the effects of thyroid hormone signaling on cancers of the esophagus, stomach, liver, pancreas, and colon. Particular attention is given to the roles of different thyroid hormone receptor isoforms, the novel integrin α_Vβ₃ receptor, and thyroid hormone-related nutrients as possible protective agents and therapeutic targets. Future investigations geared towards a better understanding of thyroid hormone signaling in digestive system cancers may provide preventive or therapeutic strategies to diminish risk, improve outcome and avert recurrence in afflicted individuals.     

Association of ER-Alpha Gene Polymorphism with Metabolic Phenotypes in Chinese Hans

Recently, two polymorphisms (rs1884052 and rs3778099) of estrogen receptor α (ER-alpha) gene were identified as being associated with primary quantitative bone mineral density (BMD) in a genome-wide association (GWA) study in Framingham cohorts. In this study we aimed at investigating the association of rs1884052 and rs3778099, and another polymorphism (rs2234693) located at intron 1 of the ER-alpha gene with BMD, body mass index (BMI), glucose, triglyceride, and total cholesterol (CHO) levels in Chinese Hans. We recruited 425 consecutive adult volunteers who had a physical examination in the Jinan Maternity and Child Care Hospital. We did not observe significant association of rs1884052 and rs3778099 with BMD, BMI, glucose, triglyceride, and total cholesterol (CHO) levels. For rs2234693, increased levels of BMD for hip, spine or whole-body regions were consistently observed in TT/TC genotype carriers than in CC genotype carriers, although the board line significance diminished after adjusting for age and gender. However, significant association of rs2234693 with glucose and CHO levels were observed in our sample. Subjects with TC/CC genotypes were associated with an increased level of glucose (p = 0.013) and CHO (p = 0.032) levels than subjects with TT genotypes. In conclusion, we did not confirm the association of rs1884052 and rs3778099 with BMD originally discovered in a GWA study; however, we made novel discoveries that rs2234693 was associated with glucose and CHO levels in Chinese Hans. Y. Chen and X. Jiang have contributed equally.     

新城疫病毒自然宿主细胞膜受体的鉴定

目的鉴定鸡源副黏病毒F48E9株的自然宿主细胞膜受体。方法采用蛋白膜提取试剂盒提取鸡胚成纤维细胞膜蛋白,用改进的间接ELISA方法检测鸡源副黏病毒分离株F48E9与细胞膜的结合活性,利用病毒铺覆蛋白印迹技术(VOPBA)鉴定新城疫病毒(NDV)的自然宿主细胞膜受体。结果NDV与鸡胚成纤维细胞膜有很强的结合力,在转印鸡胚成纤维细胞膜蛋白的PVDF膜上有几条明显的疑似受体条带,相对分子质量介于35000～60000之间。结论初步鉴定了NDV自然宿主细胞膜的受体,其疑似受体蛋白的性质及在新城疫病毒致病中的作用尚有待进一步研究。     

益生性乳酸菌黏附性研究进展

综述了益生性乳酸菌的功能作用,及乳酸菌在人体肠道中的黏附、定居、抑菌等与人体肠道黏膜组成的主要化学成分的相关性。详述了近些年来有关乳酸菌之所以能在人体内定居的黏附性的研究,如黏附素、黏附受体、影响黏附素的影响因子等,以期有助于高黏附益生性乳酸菌株的选育及其益生菌制剂制备。     

Impaired timing precision produced by striatal D2 receptor overexpression is mediated by cognitive and motivational deficits.

Increased striatal dopamine D2 receptor activity is thought to contribute to the pathophysiology of schizophrenia. To model this condition in mice, Kellendonk et al. (2006) generated transgenic mice that selectively overexpress the D2 receptor in striatum (D2OE). Drew et al. (2007) reported that D2OE mice display deficits in interval timing and motivation. The present study further explored the impaired timing in D2OE mice. Experiment 1 assessed the role of motivation in producing timing deficits in the peak procedure and found that performance in D2OE mice was improved by increasing motivation. In addition, performance was impaired in control mice when motivation was decreased. In Experiment 2, we found that D2OE mice have no timing impairment when tested using the bisection task, a procedure in which the measure of timing performance is less influenced by motivation to respond. In Experiment 3, we also used the bisection task and found selective impairment in timing of long durations in D2OE mice. These results suggest that striatal D2 overexpression impairs timing by decreasing motivation and through its impact on working memory and/or sustained attention. (PsycINFO Database Record (c) 2010 APA, all rights reserved)