NSAIDs induce apoptosis in nonproliferating ovarian cancer cells and inhibit tumor growth in vivo

Ovarian cancer (OC) is one of the most lethal gynaecological cancers, which usually has a poor prognosis due to late diagnosis. A large percentage of the OC cell population is in a nonproliferating and quiescent stage, which poses a barrier to success when using most chemotherapeutic agents. Recent studies have shown that several nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in the treatment of OC. Furthermore, we have previously described the molecular mechanisms of NSAIDs' induction of cancer apoptosis. In this report, we evaluated various structurally distinct NSAIDs for their efficacies in inducing apoptosis in nonproliferating OC cells. Although several NSAIDs-induced apoptosis, Flufenamic Acid, Flurbiprofen, Finasteride, Celocoxib, and Ibuprofen were the most potent NSAIDs inducing apoptosis. A combination of these agents resulted in an enhanced effect. Furthermore, we demonstrate that the combination of Flurbiprofen, which targets nonproliferative cells, and Sulindac Sulfide, that affects proliferative cells, strongly reduced tumor growth when compared with a single agent treatment. Our data strongly support the hypothesis that drug treatment regimens that target nonproliferating and proliferating cells may have significant efficacy against OC. These results also provide a rationale for employing compounds or even chemically modified NSAIDs, which selectively and efficiently induce apoptosis in cells during different stages of the cell cycle, to design more potent anticancer drugs.     

Dopamine receptor genetic polymorphisms and body composition in undernourished pastoralists: An exploration of nutrition indices among nomadic and recently settled Ariaal men of northern Kenya

Background  

Minor alleles of the human dopamine receptor polymorphisms, DRD2/TaqI A and DRD4/48 bp, are related to decreased functioning and/or numbers of their respective receptors and have been shown to be correlated with body mass, height and food craving. In addition, the 7R minor allele of the DRD4 gene is at a higher frequency in nomadic compared to sedentary populations. Here we examine polymorphisms in the DRD2 and DRD4 genes with respect to body mass index (BMI) and height among men in two populations of Ariaal pastoralists, one recently settled (n = 87) and the other still nomadic (n = 65). The Ariaal live in northern Kenya, are chronically undernourished and are divided socially among age-sets.     

铅锌镉联合染毒及营养干预对大鼠血液系统的影响研究

目的：了解铅锌镉联合染毒对大鼠血液系统的影响及营养干预对其损伤的修复作用。方法：选择SPF级初断乳Wistar大鼠72只,随机分为对照组、染毒组和干预组,分别采用生理盐水、铅锌镉联合染毒液及染毒后以营养干预液灌胃28天和56天之后,检测其血液系统中五元素和血细胞的指标。结果：染毒组较对照组大鼠血铜、血锌含量高,血钙含量低于对照组,差异均有统计学意义（P〈0．05）;染毒组血铜含量高于干预组,血钙含量低于干预组,差异均有统计学意义（P〈0．05）;干预组红细胞（RBC）计数、血红蛋白（Hb）、血细胞比容（HCT）均高于染毒组,差异均有统计学意义（P〈0．05）;对照组白细胞（WBC）计数高于染毒组、干预组,差异均有统计学意义（P〈0．05）。结论：铅镉对大鼠血铜、血钙、血锌水平有影响;综合营养干预对重金属元素造成的血液系统损伤有明显的拮抗作用,对血液系统有一定的保护及修复作用。     

SELDI-TOF MS of quadruplicate urine and serum samples to evaluate changes related to storage conditions

Proteomic profiling with SELDI-TOF MS has facilitated the discovery of disease-specific protein profiles. However, multicenter studies are often hindered by the logistics required for prompt deep-freezing of samples in liquid nitrogen or dry ice within the clinic setting prior to shipping. We report high concordance between MS profiles within sets of quadruplicate split urine and serum samples deep-frozen at 0, 2, 6, and 24 h after sample collection. Gage R&R results confirm that deep-freezing times are not a statistically significant source of SELDI-TOF MS variability for either blood or urine.     

基于最大熵生态位模型的中华穿山甲潜在适宜生境预测

中华穿山甲（Manis pentadactyla）属于全球极度濒危物种,也是我国一级保护动物。对中华穿山甲的非法捕杀曾导致其种群数量锐减。但是,近年来相关研究报道较少,穿山甲分布状况不明,极大地制约了对该物种的有效保护。搜集了近年来国内中华穿山甲的救护记录和救护新闻,甄别出67个记录分布点,利用最大熵模型软件（MaxEnt）进行因子筛选,结果表明最冷季度降水量、人口密度、年降水量、坡度、坡向、海拔等6个环境变量是与中华穿山甲分布显著相关的影响因子。基于6个主导环境变量构建的MaxEnt模型AUC平均值为0.961±0.014,预测结果达到极好标准。刀切法（Jackknife）表明,其中最冷季度降水量、年降水量、人口密度和海拔是影响中华穿山甲分布的主要因素。中华穿山甲适宜生境（出现概率大于0.498）具有以下特点：最冷季度降水量141.22-439.46 mm,年降水量1471.67-2386.56 mm,人口密度≥390人/km²,海拔<316.98 m。该模型预测中华穿山甲在我国的潜在分布适宜区主要位于我国长江以南地区,总面积约为74.27×10⁴ km²,占国土面积的7.73%,主要集中在江西、广东、湖南和广西省,面积分别占该区域的97.58%,89.65%,76.90%和73.08%;其次是浙江、福建、台湾和安徽省。湖北、江苏、四川、云南、贵州等省份也有中华穿山甲的零星分布。湖北东南部、江苏南部、浙江西南部和福建西北部等与江西接壤的区域也是中华穿山甲的重要潜在分布适宜区。明确中华穿山甲的潜在分布适宜区,可为该物种的种群保护和栖息地管理提供科技支撑。     

Human papillomavirus type 16 E7 oncoprotein associates with the cullin 2 ubiquitin ligase complex, which contributes to degradation of the retinoblastoma tumor suppressor

Human papillomavirus type 16 (HPV16) and other high-risk HPVs are etiologically linked to the development of cervical carcinomas and contribute to a number of other tumors of the anogenital tract, as well as oral cancers. The high-risk HPV E6 and E7 oncoproteins are consistently expressed in cervical cancer cells and are necessary for the induction and maintenance of the transformed phenotype. An important aspect of HPV16 E7's oncogenic activities is destabilization of the retinoblastoma tumor suppressor (pRB) through a ubiquitin/proteasome-dependent mechanism, although the exact molecular mechanism is unknown. Here, we report that HPV16 E7 is associated with an enzymatically active cullin 2 ubiquitin ligase complex and that the HPV16 E7/pRB complex contains cullin 2. Depletion of cullin 2 by RNA interference causes increased steady-state levels and stability of pRB in HPV16 E7-expressing cells, and ectopic expression of HPV16 E7 and the cullin 2 complex leads to pRB ubiquitination in vivo. Hence, we propose that the HPV16 E7-associated cullin 2 ubiquitin ligase complex contributes to aberrant degradation of the pRB tumor suppressor in HPV16 E7-expressing cells.     

On the number of stable equilibria and the simultaneous stability of fixation and polymorphism in two-locus models

It is shown that in simple symmetric two-locus, two-allele constant fitness models the bound of four simultaneously stable equilibria previously accepted for general two-locus, two-allele models is exceeded. Situations with five and six stable equilibria are exhibited. These involve four chromosomal fixations and either one or two polymorphic stable equilibria.