Mirandese language and genetic differentiation in Iberia: a study using X chromosome markers

Background: In the Iberian Peninsula, the Mirandese dialect, spoken in Miranda do Douro (Portugal) close to the north-eastern border with Spain, has attracted much attention.

Aim, subjects and methods: This study focuses on providing further insight into the connections forged between Miranda do Douro and regions in the nearby Province of Zamora. This is in order to better assess the extent to which such relations could have been detained by the current patterns of genetic diversity of the populations, whilst contributing to refining the knowledge on patterns of micro-differentiation within the Peninsula. The genetic characterization of both populations was performed through the analysis of X-chromosomal markers: X-STRs and X-indels.

Results and conclusion: The results showed that Miranda do Douro tended to present slightly lower levels of diversity in comparison to the other studied regions, which can be a discreet sign of isolation of that population over the years that might have led the way to the preservation of a language not spoken anywhere else in the country. The analysis of X-STRs particularly brought to light the presence of a subtle population sub-structure at the micro-geographical area encompassing the north-eastern border, which seems to portray the importance of the political border as a mechanism withholding gene flow between the two countries.     

Negative Association of Domestic Activity and Active Commuting with Metabolic Syndrome in a Chinese Population Aged 35-64 Years

Objective To understand the associations of physical activity domains with metabolic syndrome among a middle-aged Chinese population.
Methods In all, 3326 professional adults aged 35-64 years from Beijing and Zhejiang province were recruited with a cluster random sampling method. The Global Physical Activity Questionnaire was modified, and the recommended Asia-Pacific cut-offs of waist circumstance were introduced into the criteria for metabolic syndrome from the Adult Treatment Panel III. A binary logistic regression model was applied to examine the association of all physical activity domains with the risk of the syndrome.
Results Participants who engaged in domestic activity for 31176 MET-min/week had a 41.6% less chance of having metabolic syndrome [odds ratio (OR), 0.584;95%confidence interval (CI), 0.480-0.710] than those without this activity. In adjusted models, adults who actively commuted for 333 MET-min/week but<528 MET-min/week had a 25%less chance of having the syndrome (OR, 0.750;95%CI, 0.582-0.966) than those who did not. No interaction was detected between the two domains of activity and the syndrome.
Conclusion This study highlighted the independently negative association of traffic and house activity with the prevalence of the syndrome in this sample with a generally low level of moderate activity.     

子痫前期患者血清中 sEng，LXRα的表达及意义

目的：通过研究子痫前期患者血清中可溶性Endoglin（ sEng）、肝X受体α（ LXRα）的表达,探讨这两个因子与子痫前期发生、发展的关系。方法从收住院的子痫前期患者中选出满足研究条件的患者65例,其中轻度子痫前期35例,重度子痫前期30例,同期正常孕妇30例（对照组）。采用酶联免疫吸附双抗体夹心法检测血清中sEng和LXRα的表达水平,并对其进行相关性分析。结果轻度子痫前期组、重度子痫前期组血清中sEng水平分别为（9．49±1．50）μg／L,（20．44±6．44）μg／L,高于对照组sEng水平（2．41±0．46）μg／L,两组比较,P＜0．05;重度子痫前期组sEng水平高于轻度子痫前期组（P＜0．05）;轻度子痫前期组、重度子痫前期组血清中LXRα水平分别为（4．48±0．92）mg／L,（6．05±3．12）mg／L,高于对照组LXRα水平（2．79±0．87）mg／L,两组比较,P＜0．05;重度子痫前期组高于轻度子痫前期组（P＜0．05）;轻度、重度子痫前期患者血清中sEng水平与LXRα水平呈正相关（P＜0．05）。结论子痫前期患者血清中sEng含量、LXRα含量较正常妊娠孕妇增高,sEng,LXRα可能与子痫前期的发生有关;血清中sEng,LXRα可能参与了子痫前期的发展;子痫前期组血清中sEng,LXRα表达水平呈正相关,两者共同作用可能参与了子痫前期的发生、发展过程;血清中sEng,LXRα水平有望成为预测子痫前期和判断子痫前期病情严重程度的指标之一。     

HBX在肝癌细胞中通过下调miR-199a增强AKT的表达

目的 探讨乙型肝炎病毒X蛋白(hepatitis B virus X protein,HBX)调节miR-199a的表达在HBV相关性肝癌发生中的分子机制.方法 重组HBX腺病毒(Ad-HBX)感染人肝癌HepG2细胞,HBX的siRNA转染稳定表达HBV基因的人肝癌HepG2.2.15细胞,荧光定量PCR方法检测HBV相关性肝癌组织标本和肝癌细胞中HBX、miR-199a、AKT的mRNA表达水平及运用Western blot检测肝癌组织标本和肝癌细胞中HBX、AKT的蛋白表达水平;分别用miR-199a mimics和miR-199a inhibitor的转染肝癌细胞后,荧光定量PCR方法检测肝癌细胞中AKT的mRNA表达水平及运用Westem blot检测肝癌细胞中AKT的蛋白表达水平.结果 miR-199a在HepG2.2.15细胞中表达水平显著低于HepG2细胞,并且证实其表达下调受到了HBX的调控(P＜0.05),HepG2.2.15细胞中AKT表达水平显著高于HepG2细胞(P＜0.05),在HepG2.2.15细胞中过表达miR-199a能明显下调AKT表达水平以及在HepG2细胞中抑制miR-199a能明显上调的AKT表达水平(P＜0.05),此外,miR-199a的表达量在HBV相关性肝癌组织比相应的癌旁组织表达降低.结论 HBX可以通过miR-199a调节AKT导致HBV相关性肝癌发生.     

P2X7受体和肾脏疾病

P2X7受体是三磷酸腺苷(ATP)门控阳离子通道受体,是嘌呤受体P2X家族受体亚型之一。P2X7受体信号通路与IL-1β、IL-6、COX-2等多种炎症因子的生成和释放相关,在多种疾病的发病过程中起到了至关重要的作用。目前以此受体为治疗靶点的P2X7受体拮抗剂已进入临床试验阶段,表现出良好的安全性和疗效。最新研究表明P2X7受体与多种肾脏疾病有关,P2X7受体拮抗剂具有潜在的肾脏疾病治疗作用。本文综述P2X7受体在肾脏疾病中的作用及其可能的作用机制,以期为肾脏疾病治疗的新靶点和新策略提供理论依据。     

肝脏异维甲酸受体α调控脂代谢通路的基因组靶点分析

目的：探讨肝脏异维甲酸受体α（ RXRα）的基因组靶点特征及其下游通路与脂代谢的关系。方法将6只小鼠随机分为观察组和对照组各3只,分别给予维甲酸150 mg／（ kg· d）和等量生理盐水灌胃,共7 d,测定血脂,并用染色体免疫沉淀测序和定量PCR比较RXRα靶基因谱和基因表达差异。结果观察组血清胆固醇和三酰甘油浓度较对照组显著降低（P＜0.05）,肝脏RXRα的基因组靶点和靶基因数均较对照组增加,以转录起始区靶点增幅最大（<58％）。 RXRα的下游通路包括氧化还原、脂肪酸代谢和脂质转运等。观察组脂代谢相关靶基因中<48％（11／23）显著下调,22％（5／23）上调。结论肝脏RXRα及其下游通路是介导维甲酸调控脂代谢通路的重要因子。     

孕烷X受体应答元件萤光素酶报告基因的构建及活性检测

目的建立孕烷X受体(pregnane X receptor,PXR)应答元件萤光素酶报告基因,并检测其活性。方法利用化学合成方法得到五聚体PXR应答元件(everted repeat elelment-6,ER-6元件)5和(direct repeat element-3,DR-3)5序列;将五聚体PXR应答元件序列(ER6或DR3)克隆至p GL3-Promoter载体上;利用萤光素酶报告基因系统检测PXR应答元件报告基因的活性。结果 PXR应答元件萤光素酶报告基因具有明确的活性。PXR激动剂茴香霉素能够剂量依赖地诱导ER6-Luc(R2=0.95;P=0.002 2)和DR3-Luc(R2=0.96;P=0.000 91)报告基因的活性,其EC50值分别为(0.11±0.04)μmol/L和(0.13±0.06)μmol/L;PXR拮抗剂酮康唑能够剂量依赖地降低茴香霉素诱导的ER6-Luc(R2=0.97;P=0.000 85)和DR3-Luc(R2=0.98;P=0.000 11)的活性,IC50值分别为(0.71±0.11)μmol/L和(1.73±0.15)μmol/L。结论成功构建了PXR应答元件报告基因,建立了PXR转录活性的检测方法。     

A meta-analysis of the associations between the Q141K and Q126X ABCG2 gene variants and gout risk

Background: Gout is an inflammatory disease in which genetic factors play a role. ABCG2 is a urate transporter, and the Q141K and Q126X variants of ABCG2 have been associated with a risk of developing gout, though previous studies of these associations have been inconsistent. Therefore, we conducted a meta-analysis to explore the relationship between these genetic variants and gout. Methods: We examined 8 electronic literature databases. In total, 9 eligible articles on the associations between the Q141K (rs2231142) and Q126X (rs72552713) variants and gout risk, including 11 case-control studies were selected. We used odds ratios (OR) and 95% confidence intervals (CI) to assess the strength of these relationships in dominant, recessive, and co-dominant models. Results: This study included 6652 participants (2499 gout patients and 4153 controls). The Q141K variant was found to significantly increase the risk of gout in Asians (dominant model: OR=2.64, 95% CI=2.04-3.43, P=0.02 for heterogeneity; recessive model: OR=3.19, 95% CI=2.56-3.97, P=0.28 for heterogeneity; co-dominant model: OR=1.37, 95% CI=1.18-1.59, P=0.09 for heterogeneity) and other populations (dominant model: OR=1.85, 95% CI=1.20-2.85, P<0.0001 for heterogeneity; recessive model: OR=3.78, 95% CI=2.28-6.27, P=0.19 for heterogeneity; co-dominant model: OR=1.48, 95% CI=1.26-1.74, P=0.19 for heterogeneity). The Q126X variant also significantly increased the risk of gout in Asians (dominant model: OR=3.87, 95% CI=2.07-7.24, P=0.06 for heterogeneity). Conclusions: These results suggest associations between the rs2231142 and rs72552713 ABCG2 gene polymorphisms and gout risk, which led to unfavorable outcomes. However, studies with larger sample sizes and homogeneous populations should be performed to confirm these results.     

硫化氢保护被ATP损伤的PC12细胞

目的:观察硫化氢的供体硫氢化钠(Na HS)对三磷酸腺苷(ATP)诱导的PC12细胞活力、胞内Ca2+浓度([Ca2+]i)及膜通透性的变化,探讨硫化氢神经保护作用的嘌呤信号机制。方法:将对数生长期高分化的PC12细胞,随机分为4组,分别为(1)正常对照组:常规培养,不进行ATP处理;(2)ATP组:接种细胞24 h后ATP处理;(3)Na HS+ATP组:Na HS预先孵育30 min后再用ATP处理,并且Na HS始终存在于反应体系中;(4)KN-62(P2X7受体阻断剂)+ATP组:KN-62预先孵育30 min,其余同Na HS+ATP组。MTT检测各组细胞活力,Fura-2/AM荧光染料检测各组[Ca2+]i,检测荧光染料YO-PRO-1的相对荧光单位以反映膜的通透性。结果:(1)0.3mmol/L ATP对细胞活力无影响,但1、3、5、10 mmol/L ATP则呈浓度依赖式明显降低细胞活力,200μmol/L Na HS干预可明显逆转ATP引起的细胞活力下降(P0.05),而800μmol/L Na HS预处理则加剧ATP对PC12细胞的损伤(P0.05)。(2)ATP处理PC12细胞会引起[Ca2+]i迅速升高并且呈浓度依赖性,Na HS预处理能对抗ATP引起的[Ca2+]i升高(P0.05)。(3)随着ATP浓度的增加及作用时间的延长,PC12细胞内YO-PRO-1的荧光强度显著增加,Na HS预处理可明显减少细胞对YO-PRO-1的摄取(P0.05)。结论:硫化氢可保护ATP损伤的PC12细胞,可能与其抑制[Ca2+]i升高和YO-PRO-1荧光增强有关。     

Different definition of microvascular angina

We sometimes encounter patients with microvascular angina (MVA), a disease characterized by anginal pain without abnormal coronary arteriographic findings or coronary spasm. More than 40 years have passed since MVA was first confirmed. The terms ‘syndrome X’, ‘cardiac syndrome X’ and ‘microvascular dysfunction’ have also been used to describe conditions similar to MVA, but all with slightly different definitions. The cause of MVA seems almost certain to be organic and functional abnormalities of the small arteries of the heart. Patients with MVA are likely to suffer from endothelial dysfunction and other microvascular abnormalities of both the coronary and peripheral arteries. The major treatment of MVA has been medication, most often calcium channel blockers. The prognosis of MVA is generally excellent, although symptoms remain in many studies. Some MVA patients with accompanying hypertensive heart disease have gone on to develop progressive left ventricular dysfunction, with poor prognosis. The different definitions applied to the terms used to describe this condition, what we refer to here as MVA, can confound issues involved in diagnosis, prognosis and proper treatment. Therefore, it is extremely important to distinguish primary MVA without underlying heart disease from secondary MVA to explore the disease mechanism and examine the clinical characteristics. It is more than 40 years since Likoff first confirmed this disease; therefore, all researchers know that strict diagnostic criteria for MVA should be immediately established.