福建漳平奇和洞发现的新石器时代早期人类头骨

2011年在福建漳平奇和洞发现的距今1万年左右的新石器时代早期人类遗骸"奇和洞III号",是迄今在福建地区发现的最早、最完整的古人类头骨,为探讨华南更新世晚期向全新世过渡阶段人类的体质特征及现代人群的形成与分化提供了重要的研究材料。本文对这件头骨进行了研究,奇和洞III号为35岁左右的男性个体,牙齿龋病严重,推测当时人类的经济模式主要以农耕为主。通过与更新世晚期柳江、山顶洞101号及14组新石器时代人类头骨的比较,发现奇和洞III号头骨兼有更新世晚期人类及新石器南、北方居民的混合体质特征:奇和洞III号头骨长而脑量大,似更新世晚期人类;其高而狭窄的面部、宽阔而低矮的鼻部,呈现出不同于南、北方人群的特殊体质特征。主成分分析显示,奇和洞III号与对比的新石器时代各组在头骨的测量数据上没有表现为明显的南、北地区间差异,但在头骨的测量指数或形状上存在时代和地区间的不同。本文研究为新旧石器过渡阶段人类体质特征的变异提供了进一步证据。     

Decreased miR-30b-5p expression by DNMT1 methylation regulation involved in gastric cancer metastasis

miRNAs have emerged as crucial regulators in the regulation of development as well as human diseases, especially tumorigenesis. The aims of this study are to evaluate miR-30b-5p expression pattern and mechanism in gastric carcinogenesis due to which remains to be determined. Expression of miR-30b-5p was analyzed in 51 gastric cancer cases and 4 cell lines by qRT-PCR. The effect of DNA methylation on miR-30b-5p expression was assessed by MSP and BGS. In order to know whether DNMT1 increased miR-30b-5p promoter methylation, DNMT1 was depleted in cell lines AGS and BGC-823. The role of miR-30b-5p on cell migration was evaluated by wound healing assays. Decreased expression of miR-30b-5p was found in gastric cancer samples. In tumor, the expression level of miR-30b-5p was profound correlated with lymph node metastasis (P = 0.019). The level of miR-30b-5p may be restored by DNA demethylation and DNMT1 induced miR-30b-5p promoter methylation. In vitro functional assays implied that enforced miR-30b-5p expression affected cell migration, consistent with tissues analysis. Our findings uncovered that miR-30b-5p is significantly diminished in gastric cancer tissues, providing the first insight into the epigenetic mechanism of miR-30b-5p down-regulation, induced by DNMT1, and the role of miR-30b-5p in gastric cancer carcinogenesis. Overexpression of miR-30b-5p inhibited cell migration. Thus, miR-30b-5p may represent a potential therapeutic target for gastric cancer therapy.     

异色瓢虫过氧化氢酶(Catalase)的基因克隆及序列分析

【目的】克隆异色瓢虫Harmonia axyridis保护酶系中过氧化氢酶(Catalase,CAT)的全长cDNA序列,并分析该基因的基本特性。【方法】采用同源克隆和锚定PCR技术,从异色瓢虫中克隆到HaraxCAT基因的cDNA全序列(GenBank登录号KC991026),并采用生物信息学的相关方法进行了分析。【结果】HaraxCAT的cDNA序列全长1 781 bp,其包含110 bp的3′非编码区域和45 bp的5′非编码区域,可读框长1 626 bp,编码541个氨基酸。预测该基因编码蛋白的分子量为61.55 ku,理论等电点为8.33,包含3个糖基化位点,无信号肽序列和跨膜结构。并且该基因包含了一个长达18个氨基酸的潜在的活性位点序列FDRERIPERVVHAKGAGA和血红素配体信号序列RIFSYGDTH。同源比对不同昆虫的CAT蛋白序列,发现昆虫CAT非常保守,HaraxCAT与其他昆虫的同源性高达65%及以上,与赤拟谷盗Tribolium castaneum同源性最高,达75.25%;系统发育分析表明其与鞘翅目赤拟谷盗和白星金花龟Protaetia brevitarsis亲缘关系最近。【结论】获得异色瓢虫catalase基因的cDNA全长序列,证实昆虫CAT蛋白非常保守。     

Comparative Analysis of the Immunogenicity and Protective Effects of Inactivated EV71 Vaccines in Mice

Background

Enterovirus 71 (EV71) is the major causative agent of hand, foot, and mouth disease (HFMD). Three inactivated EV71 whole-virus vaccines of different strains developed by different manufacturers in mainland China have recently entered clinical trials. Although several studies on these vaccines have been published, a study directly comparing the immunogenicity and protective effects among them has not been carried out, which makes evaluating their relative effectiveness difficult. Thus, properly comparing newly developed vaccines has become a priority, especially in China.

Methods and Findings

This comparative immunogenicity study was carried out on vaccine strains (both live and inactivated), final container products (FCPs) without adjuvant, and corresponding FCPs containing adjuvant (FCP-As) produced by three manufacturers. These vaccines were evaluated by neutralizing antibody (NAb) responses induced by the same or different dosages at one or multiple time points post-immunization. The protective efficacy of the three vaccines was also determined in one-day-old ICR mice born to immunized female mice. Survival rates were observed in these suckling mice after challenge with 20 LD₅₀ of EV71/048M3C2. Three FCP-As, in a dose of 200 U, generated nearly 100% NAb positivity rates and similar geometric mean titers (GMTs), especially at 14–21 days post-inoculation. However, the dynamic NAb responses were different among three vaccine strains or three FCPs. The FCP-As at the lowest dose used in clinical trials (162 U) showed good protective effects in suckling mice against lethal challenge (90–100% survival), while the ED₅₀ of NAb responses and protective effects varied among three FCP-As.

Conclusions

These studies establish a standard method for measuring the immunogenicity of EV71 vaccines in mice. The data generated from our mouse model study indicated a clear dose-response relationship, which is important for vaccine quality control and assessment, especially for predicting protective efficacy in humans when combined with future clinical trial results.     

Renalase's Expression and Distribution in Renal Tissue and Cells

To study renalase''s expression and distribution in renal tissues and cells, renalase coded DNA vaccine was constructed, and anti-renalase monoclonal antibodies were produced using DNA immunization and hybridoma technique, followed by further investigation with immunological testing and western blotting to detect the expression and distribution of renalase among the renal tissue and cells. Anti-renalase monoclonal antibodies were successfully prepared by using DNA immunization technique. Further studies with anti-renalase monoclonal antibody showed that renalase expressed in glomeruli, tubule, mesangial cells, podocytes, renal tubule epithelial cells and its cells supernatant. Renalase is wildly expressed in kidney, including glomeruli, tubule, mesangial cells, podocytes and tubule epithelial cells, and may be secreted by tubule epithelial cells primarily.     

MicroRNA-149 Inhibits Proliferation and Cell Cycle Progression through the Targeting of ZBTB2 in Human Gastric Cancer

An increasing body of evidence indicates that miR-149 can both suppress and promote tumor growth depending on the tumor type. However, the role of miR-149 in the progression of gastric cancer (GC) remains unknown. Here we report that miR-149 is a tumor suppressor in human gastric cancer. miR-149 expression is decreased in GC cell lines and clinical specimens in comparison to normal gastric epithelial cell and tissues, respectively. The expression levels of miR-149 also correlate with the differentiation degree of GC cells and tissues. Moreover, ectopic expression of miR-149 in gastric cancer cells inhibits proliferation and cell cycle progression by down-regulating ZBTB2, a potent repressor of the ARF-HDM2-p53-p21 pathway, with a potential binding site for miR-149 in its mRNA''s 3′UTR. It is also found that ZBTB2 expression increases in GC cells and tissues compared to normal gastric epithelial cell and tissues, respectively. Silencing of ZBTB2 leads to suppression of cell growth and cell cycle arrest in G0/G1 phase, indicating that ZBTB2 may act as an oncogene in GC. Furthermore, transfection of miR-149 mimics into gastric cancer cells induces down-regulation of ZBTB2 and HDM2, and up-regulation of ARF, p53, and p21 compared to the controls. In summary, our data suggest that miR-149 functions as a tumor suppressor in human gastric cancer by, at least partially through, targeting ZBTB2.     

Seroepidemiology of Toxoplasma gondii Infection among Healthy Blood Donors in Taiwan

Toxoplasma gondii is an opportunistic, zoonotic pathogen with a worldwide distribution. There are large variations in the seroprevalence of T. gondii infection in different regions of the world. Although toxoplasmosis became a notifiable communicable disease in Taiwan in 2007, little is known about its epidemiology among the general population. This cross-sectional study aimed to survey the seroprevalence of T. gondii infection and its risk factors among healthy blood donors in Taiwan. Through collaborating with the Taiwan Blood Services Foundation, a total of 1,783 healthy blood donors from all six-branch blood service centers participated in this study. The blood samples were tested for the presence of T. gondii antibodies and DNA using enzyme immunoassays and real-time PCR, respectively. Structured questionnaires were used to gather information on risk factors for T. gondii infection. Of the 1,783 participants, 166 (9.3%) tested positive for anti-Toxoplasma IgG, while 5 (0.28%) tested positive for anti-Toxoplasma IgM. The five IgM positive donors had high avidity antibodies suggestive of past infection. No active parasitemia was detected by real-time PCR assays. Multivariate logistic regression showed that undercooked pork meat consumption (adjusted odds ratio [OR] = 2.9; 95% confidence interval [CI]: 1.3–6.5), raw mussels consumption (adjusted OR = 5.3; 95% CI: 1.5–19.1), having a cat in the household (adjusted OR = 2.0; 95% CI: 1.2–3.2), a lower education level (adjusted OR = 1.6; 95% CI: 1.1–2.3), and donation place in eastern Taiwan (adjusted OR = 2.5; 95% CI: 1.6–3.9) were independent risk factors for Toxoplasma seropositivity. These findings provide information on the seroprevalence and epidemiology of T. gondii infection among healthy blood donors in Taiwan.     

Meta-analysis of the association between common interleukin-1 polymorphisms and dental implant failure

Interleukin-1 (IL) plays a pivotal role in immune–inflammatory response that maintains periodontal homeostasis. A number of epidemiological studies have been conducted to investigate the associations between common polymorphisms of IL-1 (IL-1A, IL-1B) genes and risk of peri-implant disease, but the findings remain inconclusive. Thirteen studies evaluating the association between IL-1 polymorphisms and risk for peri-implant diseases (implant failure/loss, peri-implantitis) were included. Fixed model or random-effects models were applied to calculate overall and ethnicity-specific summary odds ratios (ORs) and corresponding 95 % confidence intervals (CIs) as risk estimates for IL-1 polymorphisms individually or in combination. Heterogeneity and publication bias were evaluated by Q-test, I ² statistic, Begg’s funnel plot and Egger’s test accordingly. The composite genotype of IL-1A (?889) and IL-1B (+3954) was associated with increased risk of implant failure/loss (OR 1.76, 95 % CI 1.21–2.57) and peri-implantitis (OR 2.34, 95 % CI 1.03–5.33). The significance was borderline in European descents (implant failure/loss: OR 1.48, 95 % CI 0.99–2.22; peri-implantitis: OR 1.65, 95 % CI 1.00–2.73). T allele of IL-1B (?511) was associated with increased risk of implant failure/loss (OR 1.28, 95 % CI 1.01–1.62), while the association was not significant in European descents (OR 1.12, 95 % CI 0.85–1.48). These findings support a potential role of IL-1 polymorphisms, particularly the composite genotype of IL-1A (?889) and IL-1B (+3954), in peri-implant disease susceptibility. More studies with large sample size are needed to validate the associations.     

Glycogen Synthase Kinase-3β Is Involved in Electroacupuncture Pretreatment via the Cannabinoid CB1 Receptor in Ischemic Stroke

We have previously shown that electroacupuncture (EA) pretreatment produces neuroprotective effects, which were mediated through an endocannabinoid signal transduction mechanism. Herein, we have studied the possible contribution of the phosphorylated form of glycogen synthase kinase-3β (GSK-3β) in EA pretreatment-induced neuroprotection via the cannabinoid CB1 receptor (CB1R). Focal transient cerebral ischemia was induced by middle cerebral artery occlusion in rats. Phosphorylation of GSK-3β at Ser-9 [p-GSK-3β (Ser-9)] was evaluated in the penumbra tissue following reperfusion. Infarct size and neurological score were assessed in the presence of either PI3K inhibitors or a GSK-3β inhibitor 72 h after reperfusion. Cellular apoptosis was evidenced by TUNEL staining and determination of the Bax/Bcl-2 ratio 24 h after reperfusion. The present study showed that EA pretreatment increased p-GSK-3β(Ser-9) 2 h after reperfusion in the ipsilateral penumbra. Augmented phosphorylation of GSK-3β induced similar neuroprotective effects as did EA pretreatment. By contrast, inhibition of PI3K dampened the levels of p-GSK-3β(Ser-9), and reversed not only the neuroprotective effect but also the anti-apoptotic effect following EA pretreatment. Regulation of GSK-3β by EA pretreatment was abolished following treatment with a CB1R antagonist and CB1R knockdown, whereas two CB1R agonists enhanced the phosphorylation of GSK-3β. Therefore we conclude that EA pretreatment protects against cerebral ischemia/reperfusion injury through CB1R-mediated phosphorylation of GSK-3β.