Another tool in the genome-wide association study arsenal: population-based detection of somatic gene conversion

The hunt for the genetic contributors to complex disease has used a number of strategies, resulting in the identification of variants associated with many of the common diseases affecting society. However most of the genetic variants detected to date are single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) and fall far short of explaining the full genetic component of any given disease. An as yet untapped genomic mechanism is somatic gene conversion and deletion, which could be complicit in disease risk but has been challenging to detect in genome-wide datasets. In a recent publication in BMC Medicine by Kenneth Ross, the author uses existing datasets to look at somatic gene conversion and deletion in human disease. Here, we describe how Ross's recent efforts to detect such occurrences could impact the field going forward.     

人胎盘间充质干细胞的生物学特性及超微结构

目的 研究胎盘间充质干细胞生物学特性和超微结构,并探讨其在骨组织工程学中修复重建的应用前景.方法 胎盘间充质干细胞,测定其细胞周期及凋亡率情况,原子力显微镜观察细胞的表面结构,及向成骨细胞诱导分化.结果 人胎盘间充质干细胞为成纤维细胞样,增殖能力强,9.7％的细胞处于G2/M期或者S期.超微结构分析显示其细胞代谢活跃,黏附能力强,能被诱导分化为成骨细胞.结论 人胎盘间充质干细胞具备适合应用于骨组织工程学的良好生物学特性,并避免了免疫排斥和伦理问题,可望成为骨组织修复重建中的一个新的治疗途径.     

Schizophrenia in Malaysian families: A study on factors associated with quality of life of primary family caregivers

Background

Schizophrenia is a chronic illness which brings detrimental effects in the caregivers' health. This study was aimed at highlighting the socio-demographic, clinical and psychosocial factors associated with the subjective Quality of Life (QOL) of Malaysian of primary family caregivers of subjects with schizophrenia attending an urban tertiary care outpatient clinic in Malaysia.

Methods

A cross-sectional study was performed to study patient, caregiver and illness factors associated with the QOL among 117 individuals involved with caregiving for schizophrenia patients. The study used WHOQOL-BREF to assess caregivers' QOL and Brief Psychiatric Rating Scale (BPRS) to assess the severity of patients' symptoms. Social Readjustment Rating Scale (SRRS) assessed the stress level due to life events.

Results

The mean scores of WHOQOL-BREF in physical, psychological, social and environmental domains were 66.62 (14.36), 61.32 (15.52), 62.77 (17.33), 64.02 (14.86) consecutively. From multiple regression analysis, factors found to be significantly associated with higher QOL were higher educational level among caregivers in social and environmental domains; caregivers not having medical problem/s in physical and psychological domains; later onset and longer illness duration of illness in social domains; patients not attending day care program in environmental domain; lower BPRS score in physical and environmental domains. SRRS score of caregivers was also found to have a significant negative correlation with QOL in environmental and psychological domains. Other factors were not significantly associated with QOL.

Conclusion

Caregivers with more social advantages such as higher educational level and physically healthier and dealing with less severe illness had significantly higher QOL in various aspects. Supporting the caregivers in some of these modifiable factors in clinical practice is important to achieve their higher level QOL.     

窦房结细胞裂解液对大鼠骨髓间充质干细胞的诱导分化作用

目的:观察不同浓度的窦房结细胞裂解液对骨髓间充质干细胞(MSCs)的诱导分化作用.方法:体外分离乳鼠窦房结细胞并制备窦房结细胞裂解液.密度梯度离心法分离成年SD大鼠骨髓MSCs,分别加入含1、2、4和8倍浓度的窦房结细胞裂解液培养基诱导培养,普通培养基培养作对照,观察细胞形态变化,并通过免疫荧光染色法检测MSCs心肌特...     

远端缺血预处理在婴幼儿心脏外科手术中的心肺保护作用

目的 观察远端缺血预处理对婴幼儿心肺功能的保护作用.方法 将48例先天性心脏病患儿随机分为远端缺血预处理组(RIPC组)和对照组.分别在麻醉诱导后,超滤结束时,ICU1、3、6、12、24 h采集血标本,测定肌钙蛋白I(cTnI)浓度,记录动脉血氧分压、气道阻力、氧和指数、肺顺应性.结果 术后RIPC组血清cTnI升高水平低于对照组,但差异无统计学意义(P＞0.05),RIPC组ICU 3 h血清cTnI水平显著低于对照组(10.8±8.5比16.3±15.9,P＜0.01).ICU时间RIPC组高于对照组[(4±2)d比(3±1)d,P＜0.05).结论 远端缺血预处理对心肌的缺血再灌注损伤有保护作用,对肺功能未产生有利影响.

Abstract：

Objective To investigate the protective effect of remote ischemic preconditioning (RIPC) on infants subject to cardiac surgery. Methods Forty-eighty infants were randomized into two groups: RIPC group ( n = 24) and control group ( n = 24). Blood samples were taken after the induction of anesthesia, at the end of ultrafiltration, and at 1,3, 6, 12 and 24 h after ICU arrival for determination of plasma cardiac troponin I (cTnI) concentrations. The pulmonary functional data including artery blood oxygen pressure (PaO2), airway resistance, oxygenation index (OI) and pulmonary compliance were recorded. Results Levels of plasma cTnI were lower in RIPC group than in control group, but there was no significant difference ( P ＞ 0. 05). Levels of plasma cTnI at 3 h after ICU arrival in RIPC group were markedly lower than in control group ( 10. 8 ± 8.5 vs. 16. 3 ± 15.9,P ＜ 0. 01 ). The ICU time in RIPC group was significantly longer than in control group[(4 ± 2) days vs. (3 ± 1 ) days,P ＜ 0. 05 )]. Conclusion RIPC appears to protect the heart against ischemia-reperfusion injury, but can not improve the pulmonary function or the postoperative clinical course in the settings of cardiac surgery of infants.     

攻毒扶正法对非酒精性脂肪性肝炎大鼠瘦素、胰岛素的影响

目的：观察攻毒扶正法对非酒精性脂肪性肝炎（NASH）大鼠瘦素（LEP）、胰岛素（INS）的影响。方法：用高脂饲料与四氯化碳（CCl4）制备NASH大鼠模型,分别用乙肝系列中成药（乙肝清热解毒颗粒、乙肝益气解郁颗粒、乙肝养阴活血颗粒）、辛伐他丁溶液进行灌胃。分为正常组,模型组,辛伐他丁组,清热解毒组,益气解郁组,养阴活血组,清热解毒合益气解郁组（简称清解合益气组）,清热解毒合养阴活血组（简称清解合养阴组）共8组,每组12只。用药4周后显微镜下观察NASH大鼠肝脏HE染色切片,并对肝组织病变程度评分。检测肝功能、血脂、LEP、INS情况。结果：模型组肝组织病变程度评分明显高于正常组（P〈0.01）,丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）升高,总胆固醇（TCh）升高明显（P〈0.01）,LEP、INS水平均升高（P〈0.05）。治疗组均可降低LEP水平,肝组织病变评分降低。中药组的ALT、AST、TC、LEP、INS含量有下降趋势（P〈0.05或〈0.01）;辛伐他丁组能降低ALT、INS含量,差异无显著性意义。结论：NASH大鼠体内有明显LEP、INS水平升高趋势。各治疗组均能降低大鼠体内LEP、INS水平。通过各类指标的检测,中药组改善作用更为明显。证明攻毒扶正法治疗NASH大鼠有切实的作用。     

Structural studies of B-type Aurora kinase inhibitors using computational methods

Aim:

To characterize the structural features of quinazoline-based Aurora B inhibitors that influence its inhibitor activity.

Methods:

Two geometrical methods, Method 1 and Method 2, were used to develop the 3D-QSAR models. The most active ligand was used as the template for the alignment of all the ligands in Method 1, and a conformer of the cocrystal ligand was used as the template for the alignment of all the ligands in Method 2.

Results:

The models suggest that highly active ligands can be designed by varying the R1 substituent at position 7 of the quinazoline ring with positively charged, bulky, hydrophobic groups, while bulky and hydrophobic groups around the thiazole ring are desirable for higher activity.

Conclusion:

This study emphasizes that the bioactive conformer is rather different from the minima. The steric, electrostatic, and hydrophobic field effects contribute to its inhibitory activity.     

Antidepressant-like effects of cannabidiol in mice: possible involvement of 5-HT1A receptors

Background and purpose:

Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa that induces anxiolytic- and antipsychotic-like effects in animal models. Effects of CBD may be mediated by the activation of 5-HT_1A receptors. As 5-HT_1A receptor activation may induce antidepressant-like effects, the aim of this work was to test the hypothesis that CBD would have antidepressant-like activity in mice as assessed by the forced swimming test. We also investigated if these responses depended on the activation of 5-HT_1A receptors and on hippocampal expression of brain-derived neurotrophic factor (BDNF).

Experimental approach:

Male Swiss mice were given (i.p.) CBD (3, 10, 30, 100 mg·kg⁻¹), imipramine (30 mg·kg⁻¹) or vehicle and were submitted to the forced swimming test or to an open field arena, 30 min later. An additional group received WAY100635 (0.1 mg·kg⁻¹, i.p.), a 5-HT_1A receptor antagonist, before CBD (30 mg·kg⁻¹) and assessment by the forced swimming test. BDNF protein levels were measured in the hippocampus of another group of mice treated with CBD (30 mg·kg⁻¹) and submitted to the forced swimming test.

Key results:

CBD (30 mg·kg⁻¹) treatment reduced immobility time in the forced swimming test, as did the prototype antidepressant imipramine, without changing exploratory behaviour in the open field arena. WAY100635 pretreatment blocked CBD-induced effect in the forced swimming test. CBD (30 mg·kg⁻¹) treatment did not change hippocampal BDNF levels.

Conclusion and implications:

CBD induces antidepressant-like effects comparable to those of imipramine. These effects of CBD were probably mediated by activation of 5-HT_1A receptors.