Paradoxical Impact of Two Folate Receptors,FRα and RFC,in Ovarian Cancer: Effect on Cell Proliferation,Invasion and Clinical Outcome

Despite being an essential vitamin, folate has been implicated to enhance tumor growth, as evidenced by reports on overexpression of folate receptor alpha (FRα) in carcinomas. The role of another folate transporter, reduced folate carrier (RFC), is largely unknown. This study investigated the roles of folate, FRα and RFC in ovarian cancers. We demonstrated FRα mRNA and protein overexpression and reduced RFC expression in association with FRα gene amplification and RFC promoter hypermethylation, respectively. FRα overexpression was associated with tumor progression while RFC expression incurred a favorable clinical outcome. Such reciprocal expression pattern was also observed in ovarian cancer cell lines. Folate was shown to promote cancer cell proliferation, migration and invasion in vitro, and down-regulate E-cadherin expression. This effect was blocked after either stable knockdown of FRα or ectopic overexpression of RFC. This hitherto unreported phenomenon suggests that, RFC can serve as a balancing partner of FRα and confer a protective effect in patients with high FRα-expressing ovarian carcinomas, as evidenced by their prolonged overall and disease-free survivals. In conclusion, we report on the paradoxical impact of FRα (putative oncogenic) and RFC (putative tumor suppressive) in human malignancies. FRα and RFC may potentially be explored as therapeutic target or prognostic marker respectively. We recommend caution and additional research on folate supplements in cancer patients.     

Association between the Melatonin Receptor 1B Gene Polymorphism on the Risk of Type 2 Diabetes,Impaired Glucose Regulation: A Meta-Analysis

Background

Melatonin receptor 1B (MTNR1B) belongs to the seven-transmembrane G protein-coupled receptor superfamily involved in insulin secretion, which has attracted considerable attention as a candidate gene for type 2 diabetes (T2D) since it was first identified as a loci associated with fasting plasma glucose level through genome wide association approach. The relationship between MTNR1B and T2D has been reported in various ethnic groups. The aim of this study was to consolidate and summarize published data on the potential of MTNR1B polymorphisms in T2D risk prediction.

Methods

PubMed, EMBASE, ISI web of science and the CNKI databases were systematically searched to identify relevant studies. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Heterogeneity and publication bias were also tested.

Results

A total of 23 studies involving 172,963 subjects for two common polymorphisms (rs10830963, rs1387153) on MTNR1B were included. An overall random effects per-allele OR of 1.05 (95% CI: 1.02–1.08; P<10⁻⁴) and 1.04 (95% CI: 0.98–1.10; P = 0.20) were found for the two variants respectively. Similar results were also observed using dominant or recessive genetic model. There was strong evidence of heterogeneity, which largely disappeared after stratification by ethnicity. Significant results were found in Caucasians when stratified by ethnicity; while no significant associations were observed in East Asians and South Asians. Besides, we found that the rs10830963 polymorphism is a risk factor associated with increased impaired glucose regulation susceptibility.

Conclusions

This meta-analysis demonstrated that the rs10830963 polymorphism is a risk factor for developing impaired glucose regulation and T2D.     

Change in rainfall drives malaria re-emergence in anhui province, china

Malaria is re-emerging in Anhui Province, China after a decade long’ low level of endemicity. The number of human cases has increased rapidly since 2000 and reached its peak in 2006. That year, the malaria cases accounted for 54.5% of total cases in mainland China. However, the spatial and temporal patterns of human cases and factors underlying the re-emergence remain unclear. We established a database containing 20 years’ (1990–2009) records of monthly reported malaria cases and meteorological parameters. Spearman correlations were used to assess the crude association between malaria incidence and meteorological variables, and a polynomial distributed lag (PDL) time-series regression was performed to examine contribution of meteorological factors to malaria transmission in three geographic regions (northern, mid and southern Anhui Province), respectively. Then, a two-year (2008–2009) prediction was performed to validate the PDL model that was created by using the data collected from 1990 to 2007. We found that malaria incidence decreased in Anhui Province in 1990s. However, the incidence has dramatically increased in the north since 2000, while the transmission has remained at a relatively low level in the mid and south. Spearman correlation analyses showed that the monthly incidences of malaria were significantly associated with temperature, rainfall, relative humidity, and the multivariate El Niño/Southern Oscillation index with lags of 0–2 months in all three regions. The PDL model revealed that only rainfall with a 1–2 month lag was significantly associated with malaria incidence in all three regions. The model validation showed a high accuracy for the prediction of monthly incidence over a 2-year predictive period. Malaria epidemics showed a high spatial heterogeneity in Anhui Province during the 1990–2009 study periods. The change in rainfall drives the reemergence of malaria in the northern Anhui Province.     

Design, synthesis and biological activity of 6-substituted carbamoyl benzimidazoles as new nonpeptidic angiotensin II AT₁ receptor antagonists

A series of 6-substituted carbamoyl benzimidazoles were designed and synthesised as new nonpeptidic angiotensin II AT(1) receptor antagonists. The preliminary pharmacological evaluation revealed a nanomolar AT(1) receptor binding affinity for all compounds in the series, and a potent antagonistic activity in an isolated rabbit aortic strip functional assay for compounds 6f, 6g, 6h and 6k was also demonstrated. Furthermore, evaluation in spontaneous hypertensive rats and a preliminary toxicity evaluation showed that compound 6g is an orally active AT(1) receptor antagonist with low toxicity.     

番茄COBRA基因克隆、表达模式及生物信息学分析

COBRA作为一种重要的胞外糖基磷脂酰肌醇(GP-I)锚定蛋白,影响植物细胞壁中纤维素含量及细胞的定向伸长。目前已有多个拟南芥、玉米及水稻的COBRA基因的突变体被研究。而有关番茄COBRA基因克隆的研究尚未见报道。本研究利用RT-PCR技术克隆了一个假定编码番茄COBRA蛋白的SlCOBRA基因,并在GenBank注册(JN398667)。序列测定和分析表明,该序列由6个外显子组成,编码444个氨基酸残基;氨基酸序列中存在COBRA蛋白的CCVS保守基序,N端的跨膜信号肽及C-末端的疏水性尾部和GPI锚定ω-位点。系统进化分析表明番茄SlCOBRA与拟南芥AtCOB具有80%氨基酸序列同源性,聚在一个分支上。Real-time PCR分析番茄各个组织中COBRA基因的表达结果表明番茄COBRA为组成型表达,在营养器官(根、茎、叶)中的表达量高于花和果实,尤其在成熟的果实中(从转色期到红熟期)表达量明显减少。     

苜蓿叶象啮小蜂寿命及产卵量的研究

在室内通过对苜蓿叶象啮小蜂Tetrastichus incertus（Ratzeburg）寿命、产卵量的研究发现,苜蓿叶象啮小蜂有较高的产卵量和寄生能力;在不喂食的条件下,苜蓿叶象啮小蜂产卵量最高,单头雌蜂的产卵范围为45粒-209粒,平均117粒,最高日产卵量为31粒;其寿命可达18d,最多可寄生37头寄主;苜蓿叶象啮小蜂与寄主在1：5的情况下寄生率达56.00%,并随着寄主密度的增大,苜蓿叶象啮小蜂的产卵量也有逐渐升高的趋势。     

Effects of silkworm larvae powder containing manganese superoxide dismutase on immune activity of mice

To study the function of silkworm larvae powder containing superoxide dismutase and potential practical development, we investigated the safety assessment and effects on immune activity of mice such as the growth of immunity-related organs, delayed-type hypersensitivity (DTH) and charcoal particle clearance ability. The mean body weights in treated mice were significantly heavier than that of control, meanwhile, the ratio of splenocytes/body weight and the thoracic gland/body weight in treated mice was significantly enhanced after 30 days treated with silkworm larvae powder containing manganese superoxide dismutase. The treated mice resulted in a profound activation of the DTH and charcoal particle clearance, and indicated the treated mice have stronger phagocytic activity to exogenous materials. Our data also indicated the feeding treatment was safe with 360 folds of recommended human dosage in acute toxic test. In long-term test, there were no effects of silkworm larvae powder containing SOD on treated mice’s growth and inside organs as long as 90 days. Further the electronic microscope investigation showed the intestine, liver, splenocyte and stomach in mice were no obvious changes both in organs and sub-organs such as nucleus, endoplasmic reticulum, mitochondrion, Golgi and peroxisomes after treated for as long as 90 days.     

RNA 沉默的病毒抑制子

RNA 沉默是一种在真核生物体内普遍保守的、通过核酸序列特异性的相互作用来抑制基因表达的调控机制 . RNA 沉默的一种重要生物学效应是防御病毒的侵染,而针对寄主的这种防御机制,许多植物病毒已演化通过编码 RNA 沉默的抑制子来克服这种防御反应 . 目前,已从植物、动物和人类病毒中鉴定了 20 多种 RNA 沉默的抑制子,围绕抑制子的鉴定和作用机理研究已成为病毒学研究的一个热点 . 对 RNA 沉默抑制子的发现、鉴定方法、作用机理及与病毒病症状形成的关系、动物病毒的沉默抑制子等方面的最新进展做了综述,并对沉默抑制子的应用和存在的问题进行了讨论 .     

细叶百合的生物量和营养分配

 以栽培的2年生细叶百合（Lilium pumilum）为材料,于2000年的生长季从蕾期至种子成熟期进行6次取样,对其各器官生物量和氮、磷元素的配置进行了动态研究。结果表明,细叶百合虽然以种子繁殖为主,但在整个生长季用于生殖器官的生物量投资的比例并不很大,大量干物质分配到地下器官鳞茎中（平均为60.17%）;茎、叶的生物量分配比例仅次于鳞茎;雄蕊生物量分配比例明显高于雌蕊。在叶萌动及展叶初期植株全氮百分含量最高;从春季萌动至秋季果实成熟,叶中的氮呈逐渐递减的趋势;茎和生殖器官的全氮含量在蕾期最大;生殖器官与叶、鳞茎的全氮含量相关显著。磷在生殖器官的含量较高,这与磷在植物有性生殖过程中的重要作用相一致;生殖器官与茎的全磷含量相关显著。地下器官全氮、全磷随季节变化有增多的趋势;地上各器官全氮、全磷相关显著,随季节变化有明显减少的趋势。