Impact of host genetics on gut microbiome: Take-home lessons from human and mouse studies

The intestinal microbiome has emerged as an important component involved in various diseases.Therefore,the interest in understanding the factors shaping its composition is growing.The gut microbiome,often defined as a complex trait,contains diverse components and its properties are determined by a combination of external and internal effects.Although much effort has been invested so far,it is still difficult to evaluate the extent to which human genetics shape the composition of the gut microbiota.However,in mouse studies,where the environmental factors are better controlled,the effect of the genetic background was significant.The purpose of this paper is to provide a current assessment of the role of human host genetics in shaping the gut microbiome composition.Despite the inconsistency of the reported results,it can be estimated that the genetic factor affects a portion of the microbiome.However,this effect is currently lower than the initial estimates,and it is difficult to separate the genetic influence from the environmental effect.Additionally,despite the differences between the microbial composition of humans and mice,results from mouse models can strengthen our knowledge of host genetics underlying the human gut microbial variation.

Genetic Correction and Hepatic Differentiation of Hemophilia B-specific Human Induced Pluripotent Stem Cells

Objective To genetically correct a disease-causing point mutation in human induced pluripotent stem cells （iPSCs） derived from a hemophilia B patient. Methods First, the disease-causing mutation was detected by sequencing the encoding area of human coagulation factor IX （F IX） gene. Genomic DNA was extracted from the iPSCs, and the primers were designed to amplify the eight exons of F IX. Next, the point mutation in those iPSCs was genetically corrected using CRISPR/Cas9 technology in the presence of a 129-nucleotide homologous repair template that contained two synonymous mutations. Then, top 8 potential off-target sites were subsequently analyzed using Sanger sequencing. Finally, the corrected clones were differentiated into hepatocyte-like cells, and the secretion of F IX was validated by immunocytochemistry and ELISA assay.Results The cell line bore a missense mutation in the 6th coding exon （c.676 C〉T） of F IX gene. Correction of the point mutation was achieved via CRISPR/Cas9 technology in situ with a high efficacy at about 22% （10/45） and no off-target effects detected in the corrected iPSC clones. F IX secretion, which was further visualized by immunocytochemistry and quantified by ELISA in vitro, reached about 6 ng/ml on day 21 of differentiation procedure. Conclusions Mutations in human disease-specific iPSCs could be precisely corrected by CRISPR/Cas9 technology, and corrected cells still maintained hepatic differentiation capability. Our findings might throw a light on iPSC-based personalized therapies in the clinical application, especially for hemophilia B.

Detection of CYP2E1,a Genetic Biomarker of Susceptibility to Benzene Metabolism Toxicity in Immortal Human Lymphocytes Derived from the Han Chinese Population

Objective Cytochrome P450 2E1 （CYP2E1） is an important metabolizing enzyme involved in oxidative stress responses to benzene, a chemical associated with bone marrow toxicity and leukemia, We aimed to identify the CYP2E1 genetic biomarkers of susceptibility to benzene toxicity in support of environmental and occupational exposure prevention, and to test whether a model using immortal human lymphocytes might be an efficient tool for detecting genetic biomarkers. Methods Immortalized human lymphocyte cell lines with independent genotypes on four CYP2E1 SNP sites were induced with 0.01% phenol, a metabolite of benzene. CYP2E1 gene function was evaluated by mRNA expression and enzyme activity. DNA damage was measured by Single-Cell Gel Electrophoresis （SCGE）. Results Among the four SNPs, cells with rs2070673TT and rs2030920CC showed higher levels of ~YP2E1 transcription and enzymatic activity than the other genotypes in the same SNP site. Cells with higher gene expression genotypes also showed higher comet rates compared with lower gene expression genotypes. Conclusion These results suggest that CYP2E1 rs2070673 and rs2030920 might be the genetic biomarkers of susceptibility to benzene toxicity and that the immortalized human lymphocytes model might be an efficient tool for the detection of genetic biomarkers of susceptibility to chemicals.

Genetics of inflammatory bowel disease: The role of the HLA complex

The human leucocyte antigen （HLA） complex on chromosome 6p21.3 is the most extensively studied genetic region in Inflammatory bowel disease （IBD）. Consistent evidence of linkage to IBD3 （6p21.1-23）, an area which encompasses the HLA complex, has been demonstrated for both Crohn＇s disease and ulcerative colitis, and a number of replicated associations with disease susceptibility and phenotype have recently emerged. However, despite these efforts the HLA susceptibility gene （s） for IBD remain elusive, a consequence of strong linkage disequilibrium, extensive polymorphism and high gene density across this region. This article reviews current knowledge of the role of HLA complex genes in IBD susceptibility and phenotype, and discusses the factors currently limiting the translation of this knowledge to clinical practice.

Genetic diversity for grain Zn concentration in finger millet genotypes:Potential for improving human Zn nutrition

Nearly half of the world population suffers from micronutrient malnutrition,particularly Zn deficiency.It is important to understand genetic variation for uptake and translocation behaviors of Zn in relevant crop species to increase Zn concentration in edible parts.In the present study,genetic variation in grain Zn concentration of 319 finger millet genotypes was assessed.Large genetic variation was found among the genotypes,with concentrations ranging from 10 to 86 μg g^(-1)grain.Uptake and translocation studies with Zn/^(65) Zn application in 12 selected low-Zn genotypes showed wide variation in root uptake and shoot translocation,with genotypes GEC331 and GEC164 showing greater uptake and translocation.Genotypes GEC164 and GEC543 showed increased grain Zn concentration.Genotypes GEC331 and GEC164 also showed improved yield under Zn treatment.Appreciable variation in grain Zn concentration among finger millet genotypes found in this study offers opportunities to improve Zn nutrition through breeding.

Optimization of Biodynamic Seated Human Models Using Genetic Algorithms

Many biodynamic models have been derived using trial and error curve-fitting technique, such that the error between the computed and measured biodynamic response functions is minimum. This study developed a biomechanical model of the human body in a sitting posture without backrest for evaluating the vibration transmissibility and dynamic response to vertical vibration direction. In describing the human body motion, a three biomechanical models are discussed (two models are 4-DOF and one model 7-DOF). Optimization software based on stochastic techniques search methods, Genetic Algorithms (GAs), is employed to determine the human model parameters imposing some limit constraints on the model parameters. In addition, an objective function is formulated comprising the sum of errors between the computed and actual values (experimental data). The studied functions are the driving-point mechanical impedance, apparent mass and seat- to-head transmissibility functions. The optimization process increased the average goodness of fit and the results of studied functions became much closer to the target values (Experimental data). From the optimized model, the resonant frequencies of the driver parts computed on the basis of biodynamic response functions are found to be within close bounds to that expected for the human body.

Genetically modified human umbilical cord blood cells as a promising strategy for treatment of spinal cord injury

Spinal cord injury （SCI） continues to be a pressing health and social problem. The injury leads to neuronal and glial cell death accompanied by degeneration of nerve fibers. There are currently no particularly effective treatments. SCI causes profound disabil- ity of people affected and has attracted increased attention in the international field of neuroregeneration. For the past two decades, much hope has been placed in cell therapies for the restoration of both structure and function of the injured spinal cord. Embryonic and neural stem cells, olfactory ensheathing cells, microglia-like cells, Schwann cells, mesenchymal stem cells.

Advances in homology directed genetic engineering of human pluripotent and adult stem cells

The ability to introduce precise genomic modifications in human cells has profound implications for both basic and applied research in stem cells, ranging from identification of genes regulating stem cell self-renewal and multilineage differentiation to therapeutic gene correction and creation of in vitro models of human diseases. However, the overall efficiency of this process is challenged by several factors including inefficient gene delivery into stem cells and low rates of homology directed site-specific targeting. Recent studies report the development of novel techniques to improve gene targeting efficiencies in human stem cells; these methods include molecular engineering of viral vectors to efficiently deliver episomal genetic sequences that can participate in homology directed targeting, as well as the design of synthetic proteins that can introduce double-stranded breaks in DNA to initiate such recombination events. This review focuses on the potential of these new technologies to precisely alter the human stem cell genome and also highlights the possibilities offered by the combination of these complementary strategies.

Genetic diversity of Mansonia altissima A. Chev. under different regimes of human impact in the Akure Forest Reserve,Nigeria

Mansonia altissima is an important West African timber tree species. For the purpose of examining the effect of human impact on its genetic diversity, genetic diversity and spatial genetic structure of the species under different regimes of human impact were investigated in the Akure Forest Reserve, Nigeria, using 504 amplified fragment length polymorphism （AFLP） markers. The results indicate a very low genetic diversity in M. altissima within the forest reserve （He = 0.045; PPL = 16.75%; Br = 1.162）. The highest genetic diversity was observed in the primary forest （H e= 0.062; PPL - 21.00%; Br = 1.204）, with the lowest genetic diversity in the isolated forest patch （He = 0.032; PPL = 9.00%; B r= 1.089）. A significant and pronounced spatial genetic structure was found in the logged forest and in the isolated forest patch. In contrast, the primary forest exhibited very weak spatial genetic structuring. As expected, no spatial genetic structure was found in the planted stands of M. altissima. From a conservation point of view, our results suggest that genetic diversity ofM. altissima is at risk in the forest reserve. The scale of human impact in the study area could pose a serious threat to the maintenance of genetic diversity of the species. These results would offer practical applications in the conservation of other tropical tree species.

Benefits of Genetic Engineering to the Environment and Human Health

The purpose of this essay is to argue that the genetic engineering may bring about benefits to human health and the environment.By means of research of secondary source collection,relevant evidence is selected,evaluated and organized into three main parts:improving agricultural environment,providing effective medical therapy and supplying safe and nutrition food to human body.In order to explain the benefits that created by genetic engineering technologies,examples based on opinions of experts and results of experts' experiments are used.The research results strongly suggest that the genetic engineering has positive effects on environment and mankind.Base on those finds,the argument is justified that genetic engineering is certainly beneficial to the environment and human health.In the future,more attention and researches should be focus on the genetic engineering with the purpose of benefiting human beings and the natural worlds.

Human a Type Genetic Engineering Interference Essence Injection

The highest-level interference essence against virus and turnour genetic engineering medicine is a new type created in the 1980s. Compared with chemical medicines, the interference essence has a special effect in the treatment of viruses and tumours. The human a, type genetic engineering interference essense is prepared by the Institute of Viruses of the Chinese Academy of Preventive Medical Sciences, the Shanghai Vaccine

Embryonic, genetic and clinical outcomes of fresh versus vitrified oocyte: A retrospective cohort study

Objective:To compare embryonic development,ploidy status and clinical outcomes between fresh and frozen-thawed oocytes.Methods:This retrospective cohort study evaluated 83 fertilization cycles including both fresh and frozen oocytes from 79 patients at the HP Fertility Center of Hai Phong International Hospital of Obstetrics and Pediatrics in Vietnam.The patient underwent several ovarian stimulation cycles to accumulate a certain number of oocytes that would be vitrified.In the last oocyte retrieval,all patient’s oocytes including both frozen and fresh would be fertilized.The outcomes included the rates of oocyte survival,cleavage embryo,blastocyst,ploidy status,pregnancy,biochemical pregnancy and clinical pregnancy.Results:The oocyte survival rate after thawing was 96.5%.No statistically significant difference was found when comparing fresh and frozen oocytes regarding fertilization rate(78.1%vs.75.5%,P=0.461),usable cleavage embryo rate(86.9%vs.87.2%,P=0.916)but usable blastocyst rate was found higher statistically in the frozen oocyte group(44.4%vs.54.0%,P=0.049).The percentages of euploid,aneuploid and mosaic embryos between the fresh group and the vitrified group had no significant differences(33.8%vs.31.6%,P=0.682;51.0%vs.54.2%,P=0.569;15.2%vs.12.4%,P=0.787;respectively).The rates of pregnancy,biochemical pregnancy and clinical pregnancy had no statistical difference(68.8%vs.64.8%,P=0.764;12.5%vs.3.6%,P=0.258;37.5%vs.46.4%,P=0.565).17 Mature oocytes are the minimum to have at least one euploid embryo.Conclusions:Oocyte vitrification does not affect embryonic,genetic and clinical results.The number of mature oocytes should be considered for fertilization in some cases.

我国地方人类遗传资源监管对策研究

人类遗传资源是国家自然科技资源不可或缺的组成部分,也是维护国家安全、公众健康和社会公共利益的重要战略资源。为推动人类遗传资源的有效保护和合理利用,健全和优化地方人类遗传资源管理体系,通过梳理国家人类遗传资源管理政策和法规,总结2004—2021年国家人类遗传资源行政审批监管现状;并且从人类遗传资源发展规划和方案、行政许可和处罚、管理专家委员会建设三个方面了解了地方人类遗传资源管理现状及其进展,探讨分析出地方人类遗传资源管理工作存在监管不明晰、监督检查难度较大、服务能力有限等主要问题,从而结合问题成因和地方管理工作实际,有针对性地从人类遗传资源明确监管政策与程序、完善监督检查机制、提升管理服务能力的视角出发提出具体的对策建议。

基因权的证成和体系

基因科技对人的主体性造成冲击,需要通过立法对于人的基因利益予以保障。基因具有人格性,同时也负载着经济利益。现有的权利体系无法全面涵盖基因上的利益关系,基因权成为一项新型权利。基因权的证成建立在基因具有道德意义的基础上,又因为其关涉人的物种尊严、人格尊严和身体尊严,并具有巨大的经济利益,而使得基因权表现为立体化多面向的权利束。基因权利体系包括基因隐私权、基因平等权、基因知情权和基因利益分享权。在我国现行权利框架下,适宜以单行法的方式完善基因权利制度。

人类遗传资源安全的刑法全面性保护

为贯彻落实总体国家安全观,并回应人类遗传资源安全管理的规范发展要求,《刑法修正案(十一)》专门增设第三百三十四条之一,但却仍不足以全面保障人类遗传资源安全。究其原因,一是未规定单位犯罪,二是未全面规制非法提供和买卖人类遗传资源的行为,三是未同等保护人类遗传资源材料和人类遗传资源信息。在总体国家安全观的背景下,涉及人类遗传资源的前置法规制体系日趋完善。刑法全面保护人类遗传资源安全的关键,在于填补非法采集人类遗传资源、走私人类遗传资源材料罪的规范漏洞,合理解释关联罪名则是当下最优解。具体而言,把人类遗传资源信息解释为公民个人信息中的生物识别信息,并将侵犯人类遗传资源安全的行为解释为出售、提供或以其他方法非法获取公民个人信息,从而借助侵犯公民个人信息罪,全面评价自然人或者单位实施的非法采集、非法提供、买卖人类遗传资源材料、人类遗传资源信息的行为。

论非法植入基因编辑、克隆胚胎罪保护法益

随着世界范围内基因编辑技术的发展,人类有了攻克遗传疾病的希望。但是“基因编辑婴儿”案的出现,使我们必须思考如何通过法律来防范基因编辑技术对人类生活的冲击。在刑法规制层面,准确把握非法植入基因编辑、克隆胚胎罪的保护法益是进一步思考的前提。既往的研究将该罪法益限定为人性尊严、医疗秩序或人类遗传安全,但这并非真正的适格法益,无助于法益机能的发挥。合理界定该罪法益的方向应当是综合分析规范目的、法益性质、价值判断以及行为对象。基于以上方法,将非法植入基因编辑、克隆胚胎罪的保护法益确定为人类遗传基因具有合理性。该法益界定一方面明确了“情节严重”的类型,另一方面可以作为出罪事由的判定标准,划定了犯罪行为与科研行为的界限。

甘肃省人民医院药物临床试验人类遗传资源管理情况与思考

人类遗传资源是推动新药研发、助力人类健康研究的重要资源,也是维护国家安全的重要内容。近年来,我国发布多项法律法规以规范人类遗传资源的合理使用,明确人类遗传资源采集、利用和出境等具体流程和措施。药物临床试验机构作为新药研发的参与者,应遵守法律法规,不断完善人类遗传资源管理体系,对人类遗传资源进行有效保护。本研究通过回顾2020—2022年甘肃省人民医院药物临床试验机构涉及人类遗传资源项目审批类型、数量和原因,分析《人类遗传资源管理条例实施细则》实施后对涉及人类遗传资源项目审批可能产生的变化,结合药物临床试验全流程人类遗传资源管理实践,对建立人类遗传资源管理制度、组织培训、优化管理流程等提出建议,以进一步提高人类遗传资源管理水平。

人类遗传资源管理体系中存在的问题与建议

描述了近年来我国人类遗传资源管理法律法规的发展过程,并对人类遗传资源管理法律法规的现状进行分析。基于人类遗传资源管理现状,分析实际人类遗传资源管理工作中所存在的缺乏入境和入境后管理相关规定、人类遗传资源销毁相关规定需进一步明确、相关配套法律法规亟需完善等问题。最后,根据以上问题提出具有针对性的完善建议,提出人类遗传资源入境和入境后管理措施,建议科学研究人类遗传资源销毁标准,并提出完善人类遗传资源管理法律体系,加强各法律之间的联系,从而加强对人类遗传资源的管理与保护。

VDR基因多态性与宫颈病变及HPV感染转归的相关性

目的 分析维生素D受体(vitamin D receptor, VDR)基因多态性与宫颈病变的关系,并探讨其对高危型人乳头瘤病毒(high risk-human papillomavirus, HR-HPV)感染转归的影响。方法 选取2020年9月至2021年10月于山西医科大学第二医院行阴道镜检查的患者376例,将病理结果示慢性宫颈炎和宫颈上皮内瘤变Ⅰ级者设为对照组(188例),宫颈上皮内瘤变Ⅱ级及以上者(CINⅡ+)为病例组(188例)。收集患者外周静脉血行VDR基因多态性检测,包括FOKI、BsmL、Apal和Taql的单核苷酸多态性(single nucleotide polymorphisms, SNPs)位点,分析VDR基因多态性与宫颈病变的关系。对选择行宫颈锥形切除术进行治疗的142例CINⅡ-Ⅲ级患者的HPV转归情况进行6个月的随访,根据随访结果分为HPV转阴者和同一型别HPV持续感染者,即转阴组和持续感染组,分析VDR基因多态性是否影响HPV感染的转归。结果 随访结果显示,104例患者的HPV感染呈转阴状态,33例患者持续感染同一型别的HPV,而另外5例患者则感染了其他型别的HPV。VDR基因多态性检测结果表明,FOKI SNPs ff基因型及f等位基因与CINⅡ+发生显著相关(P<0.05),并且与HR-HPV持续感染相关(P<0.05);TaqI SNPs tt及Tt基因型均增加CINⅡ+发生的风险(P<0.05),t等位基因与CINⅡ+发生风险增加有关(P<0.05),但与HPV持续感染未见相关性(P>0.05)。结论 VDR基因多态性与宫颈病变及HR-HPV感染转归相关,其中FOKI SNPs ff基因型及f等位基因和TaqI SNPs tt、Tt基因型及t等位基因与宫颈病变的发生存在关联,并且FOKI SNPs ff基因型及f等位基因可能影响HR-HPV感染的转归结果。

国内外异种器官移植的现状及进展

器官短缺已成为阻碍器官移植发展的主要难题,异种移植是解决全球器官匮乏最有价值的方法之一。近年来,基因工程技术的发展和新型免疫抑制药的研发为异种移植提供了新的理论基础。国外陆续开展基因修饰猪-非人灵长类动物或脑死亡受者的相关异种移植研究,并取得一些实质性的进展,但大部分的研究仍处于临床前阶段,距离投入临床跨越巨大。因此,本文结合目前国内外最新的临床前实验研究进展,对异种移植的历史、基因修饰技术发展、异种移植排斥反应及免疫抑制方案等问题进行综述,以期为异种移植的进一步研究提供参考,促进异种移植临床应用,造福更多终末期疾病患者。