Non genetic risk factors of long-QT syndrome

The purpose of the present study is to provide guidelines regarding risk factors that may worsen the Long-QT Syndrome (LQTS), based on available literature. This review evaluates the current knowledge on these risk factors of acquired LQTS, with an emphasis on non genetic risk factors, including environmental factors. PubMed was searched for literature in English from 1999 to 2011 on the molecular and clinical studies of Long-QT syndrome. We agree, with recent investigations described in the literature, that variety of factors, inherited or environmental, can influence expression of ion channel proteins with impact on repolarization.

2010-2020年江苏省牛乳中SCC变化模式对奶牛场隐性乳房炎发病规律的影响

奶牛隐性乳房炎(subclinical mastitis,SCM)是一种无症状表现的乳房炎,通常表现为体细胞数(somatic cell count,SCC)升高、乳脂率下降等。为探究SCC变化模式影响下江苏地区奶牛场SCM发病规律的因素,本研究收集了江苏地区14个牧场2010-2020年荷斯坦牛群体改良(dairy herd improvement,DHI)记录853936条,在划分4种SCC变化模式(持续健康、新感染、治愈和持续感染)基础上,利用卡方检验探究不同牧场规模、胎次、产犊季节、产犊间隔和305 d产奶量对荷斯坦牛4种SCC变化模式的影响。结果表明:所有DHI记录中4种SCC变化模式百分比分别为83.52%(持续健康)、6.02%(新感染)、5.89%(持续感染)和4.57%(治愈),牧场规模、胎次、产犊季节、产犊间隔和305 d产奶量对荷斯坦牛SCC变化模式分布均有极显著影响(P<0.01)。其中,中小型牧场、较高胎次、春季产犊、产犊间隔大于441 d和305 d产奶量为13001~15000 kg的奶牛下一泌乳月SCC升高的概率较大,增加了奶牛患SCM风险;规模在5000头以上的牧场、1胎牛、秋季产犊和305 d产奶量为9001~11000 kg的奶牛持续健康的比例均最高。综上所述,牧场规模、胎次、产犊季节、产犊间隔和305 d产奶量对SCC变化模式的分布均有极显著影响,该结果为江苏地区规模化牧场SCM防控提供了参考。

Improved genetic algorithm freely searching for dangerous slip surface of slope

Based on the slice method of the non-circular slip surface for the calculation of integral stability of slope, an improved genetic algorithm was proposed, which can freely search for the most dangerous slip surface of slope and the corresponding minimum safety factor without supposing the geometric shape of the most dangerous slip surface. This improved genetic algorithm can simulate the genetic evolution process of organisms and avoid the local minimum value compared with the classical methods. The results of engineering cases show that it is a global optimal algorithm and has many advantages, such as higher efficiency and shorter time than the simple genetic algorithm.

Reduction of tumorigenicity of SMMC-7721 hepatoma cells by vascular endothelial growth factor antisense gene therapy

AIM To test the hypothesis to block VEGFexpression of SMMC-7721 hepatoma cells mayinhibit tumor growth using the rat hepatomamodel.METHODS Amplifiy the 200 VEGF cDNAfragment and insert it into human U6 genecassette in the reverse orientation transcribingsmall antisense RNA which could specificallyinteract with VEGF165, and VEGF121 mRNA.Construct the retroviral vector containing thisantisense VEGF U6 cassette and package thereplication-deficient recombinant retrovirus.SMMC-7721 cells were transduced with thesevirus and positive clones were selected withG418. PCR and Southern blot analysis wereperformed to determine if U6 cassette integratedinto the genomic DNA of positive clone.Transfected tumor cells were evaluated for RNAexpression by ribonuclease protection assays.The VEGF protein in the supernatant of parentaltumor cells and genetically modified tumor cellswas determined with ELISA. In vitro and in vivogrowth properties of antisense VEGF cell clonein nude mice were analyzed.RESULTS Restriction enzyme digestion andPCR sequencing verified that the antisense VEGFRNA retroviral vector was successfullyconstructed. After G418 selection, resistantSMMC-7721 cell clone was picked up. PCR andSouthern blot analysis suggested that U6cassette was integrated into the cell genomicDNA. Stable SMMC-7721 cell clone transducedwith U6 antisense RNA cassette could express200bp small antisense VEGF RNA and secretereduced levels of VEGF in culture condition.Production of VEGF by antisense transgeneexpressing cells was 65 ± 10 ng / L per 106 cells,420 ± 45 ng/L per 106 cells in sense group and 485± 30 ng/L per 106 cells in the negative control group, (P＜0.05). The antisense-VEGF cell clone appeared phenotypically indistinguishable from SMMC-7721 cells and SMMC-7721 cells transfected sense VEGF. The growth rate of the antisense-VEGF cell clone was the same as the control cells. When S. C. was implanted into nude mice, growth of antisense-VEGF cell lines was greatly inhibited compared with control cells.CONCLUSION Expression of antisense VEGFRNA in SMMC-7721 cells could decrease thetumorigenicity, and antisense-VEGF genetherapy may be an adjuvant treatment forhepatoma.

GSTM1,GSTT1,GSTP1 and CYP1A1 genetic polymorphisms and susceptibility to esophageal cancer in a French population:Different pattern of squamous cell carcinoma and adenocarcinoma

AIM: To evaluate the association between CYPIA1 and GSTs genetic polymorphisms and susceptibility to esophageal squamous cell carcinoma (SCC) and esophageal adenocarcinorna (ADC) in a high risk area of northwest of France.METHODS: A case-control study was conducted to investigate the genetic polymorphisms of these enzymes (CYPIAI*2C and GSTP1 exon 7 Val alleles, GSTM1 *2/*2 and GSl-l-l*2/*2 null genotypes). A total of 79 esophagealcancer cases and 130 controls were recruited. RESULTS: GSTM2*2/*2 and CYP1A1*1A/*2C genotype frequencies were higher among squamous cell cardnomas at a level close to statistical significance (OR = 1.83, 95% CI0.88-3.83, P= 0.11; OR = 3.03, 95% CI 0.93-9.90, P= 0.07,respectively). For GSTP1 polymorphism, no difference wasfound between controls and cases, whatever their histological status. Lower frequency of GST/-1 deletion was observed in ADC group compared to controls with a statistically significant difference (OR=13.31, 95% CI 1.66-106.92, P<0.01).CONCLUSION: In SCC, our results are consistent with the strong association of this kind of turnout with tobacco exposure. In ADC, our results suggest 3 distinct hypotheses:(1) activation of exogenous procarcinogens, such as small halogenated compounds by GSTTI', (2) contribution of GSTT1 to the inflammatory response of esophageal mucosa, which is known to be a strong risk factor for ADC,possibly through leukotriene synthesis; (3) higher sensitivity to the inflammatory process associated with intracellular depletion of glutathione.

GSTT1,GSTM1 and CYP2E1 genetic polymorphisms in gastric cancer and chronic gastritis in a Brazilian population

MIM:To test the hypothesis that,in the Southeastern Brazilian population,the GSTT1,GSTM1 and CYP2E1 polymorphisms and putative risk factors are associated with an increased risk for gastric cancer.METHODS:We conducted a study on 100 cases of gastric cancer(GC),100 cases of chronic gastritis(CG),and 150 controls(C).Deletion of the GSTT1 and GSTM1 genes was assessed by multiplex PCR.CYP2E1/PsА genotyping was performed using a PCR-RFLP assay.RESULTS:No relationship between GSTT1/GSTM1 deletion and the c1/c2 genotype of CYP2E1 was observed among the three groups.However,a significant difference between CG and C was observde,due to a greater number of GSTT1/GSTM1 positive genotypes in the CG group.The GSTT1 null genotype occurred more frequently in Negroid subjicts,and the GSTM1 null genotype was observed mainly in individuals with chronic gastritis infected with H pylori.CONCLUSION:Our findings indecate that there is no obvious relationship between the GSTT1,GSTM1 and CYP2E1 polymorphisms and gastric cancer.

The involvement of p38 MAPK in transforming growth factor β1-induced apoptosis in murine hepatocytes

We reported in this manuscript that TGF-β1 induces apoptosis in AML12 murine hepatocytes, which is associated with the activation of p38 MAPK signaling pathway. SB202190, a specific inhibitor of p38 MAPK, strongly inhibited the TGF-β1-induced apoptosis and PAI-1 promoter activity. Treatment of cells with TGF-β1 activates p38. Furthermore, over-expression of dominant negative mutant p38 also reduced the TGF-β1-induced apoptosis. The data indicate that the activation of p38 is involved in TGF-β1-mediated gene expression and apoptosis.

Glutathione S-transferases M1,T1 genotypes and the risk of gastric cancer:A case-control study

AIM Glutathione S-transferases (GSTs are involved in the detoxification of many potential carcinogens and appear to play a critical role in the protection from the effects of carcinogens. The contribution of glutathione Stransferases M1 and T1 genotypes to susceptibility to the risk of gastric cancer and their interaction with cigarette smoking are still unclear. The aim of this study was to determine whether there was any relationship between genetic polymorphisms of GSTM1 and GSTT1 and gastric cancer.METHODS A population based case - control study was carried out in a high-risk area, Changle County, Fujian Province, China. The epidemiological data were collected by a standard questionnaire and blood samples were obtained from 95 incidence gastric cancer cases and 94 healthy controls. A polymerase chain reaction method was used to detect the presence or absence of the GSTM1 and GSTT1 genes in genomic DNA. Logistic regression model was employed in the data analysis.RESULTS An increase in risk for gastric cancer was found among carriers of GSTM1 null genotype. The adjusted odds ratio (OR) was 2.63 [95% Confidence Interval (95% CI) 1.17-5.88], after controlling for age,gender, cigarette smoking, alcohol drinking, and fish sauce intake. The frequency of GSTT1 null genotype in cancer cases (43.16%) was not significantly different from that in controls (50.00%). However, the risk for gastric cancer in those with GSTM1 null and GSTT1 nonnull genotype was significantly higher than in those with both GSTM1 and GSTT1 non-null genotype (OR = 2.77,95% Cl 1.15- 6.77). Compared with those subjects who never smoked and had normal GSTM1 genotype, Ors were 1.60 (95% CI: 0.62- 4.19) for never smokers with GSTM1 null type, 2.33 (95% CI 0.88- 6.28) for smokers with normal GSTM1, and 8.06 (95% CI 2.83- 23.67) for smokers with GSTM1 null type.CONCLUSIONS GSTM1 gene polymorphisms may be associated with genetic susceptibility of stomach cancer and may modulate tobacco-related carcinogenesis of gastric cancer.

Adenovirus-mediated expression of pig α(1,3) galactosyltransferase reconstructs Gal α(1,3) Gal epitope on the surface of human tumor cells

Gal α(1, 3) Gal (gal epitope) is a carbohydrate epitope and synthesized in large amount by α(1, 3) galactosyltransferase [α(1, 3) GT] enzyme on the cells of lower mammalian animals such as pigs and mice. Human has no gal epitope due to the inactivation of α(1, 3) GT gene but produces a large amount of antibodies (anti-Gal) which recognize Gal α(1, 3) Gal structures specifically. In this study, a replication deficient recombinant adenoviral vector Ad5sGT containing pig α(1, 3) GT cDNA was constructed and characterized. Adenoviral vector-mediated transfer of pig α(1, 3) GT gene into human tumor cells such as malignant melanoma A375, stomach cancer SGC-7901, and lung cancer SPC-A-1 was reported for the first time. Results showed that Gal epitope did not increase the sensitivity of human tumor cells to human complement-mediated lysis, although human complement activation and the binding of human IgG and IgM natural antibodies to human tumor cells were enhanced significantly after Ad5sGT transduction. Appearance of gal epitope on the human tumor cells changed the expression of cell surface carbohydrates reacting with Ulex europaeus I (UEA I) lectins, Vicia villosa agglutinin (VVA), Arachis hypogaea agglutinin (PNA), and Glycine max agglutinin (SBA) to different degrees. In addition, no effect of gal epitope on the growth in vitro of human tumor cells was observed in MTT assay.

Killing effect of TNF-related apoptosis inducing ligand regulated by tetracycline on gastric cancer cell line NCI-N87

AIM To clone the cDNA fragment of human TRAIL (TNFrelated apoptosis inducing ligand) into a tetracyclineregulated gene expression system, the RevTet-On system, transduce expression vectors into a gastric carcinoma cell line-NCl-N87 and examine the effects of controlled expression of TRAIL in vitro on the gastric carcinoma cells.METHODS The full-length cDNA of TRAIL was inserted into a vector under the control of the tetracyclineresponsive element (TRE) to obtain the plasmid pRevTRETRAIL, which was transfected into a packaging cell line PT67. In addition, vector pRev-Tet- On and pRevTRE were also transfected into PT67 separately. After hygromycin and G418 selection, the viral titer was determined. The medium containing retroviral vectors was collected and used to transduce a gastric carcinoma cell line NCI-N87.The resulting cell line NCI-N87-Tet-On-TRE-TRAIL and a control cell line, NCI-N87-Tet-On-TRE, were established.TRAIL expression in the cell line was induced by incubating cells with doxycycline (Dox), which is a tetracycline analogue. The killing effect on gastric carcinoma cells was analyzed after induction.RESULTS The recombinant plasmid pRev-TRE-TRAIL was constructed. After hygromycin or G418 selection, the producer cell lines PT67-TRE, PT67-TRE-TRAIL and PT67TetOn were obtained, with titers of about 108CFU@ L-1 By transducing NCI-N87 cells with retroviral vectors from these cell lines, stable cell lines NCI-N87-Tet-On-TRETRAIL (NN3T) and control cell line NCI-N87-Tet-On-TRE (NN2T) were established. The growth curves of the selected cell lines were the same with the wild type NCIN87. When Dox was added, cell death was obvious in the test groups (29% -77%), whereas no difference was observed in control and wild type cell lines. With the addition of a medium from the test group, human leukemia cell line Jurkat was activated till death (83%), indicating the secretion of active TRAIL proteins from the test cells to the medium.CONCLUSION With the use of the RevTet-On system, a regulated expression system for TRAIL was constructed.Using this system, the selected killing effect of TRAIL on gastric carcinoma cell line NCI-N87 could be observed.

The expression and antigenicity identification of recombinant rat TGF-β1 in bacteria

In order to study structure-function details of TGF-β1, the recombinant mature form of rat TGF-β1 was expressed in bacteria. Synthesis of the 112 amino-acid carboxyl-terminal part of TGF-β1 (amino acid 279-390) was controlled by an inducible gene expression system based on bacteriophage T7 RNA polymerase. This system allowed an active and selective synthesis of recombinant TGF-β1. The molecular weight of expressed TGF-β1 monomer determined on SDS-polyacrylamide gel under reducing conditions was about 13 kD. Serial detergent washes combined with a single gel-filtration purification step were sufficient to purify the expression product to homogeneity. Amino-terminal sequencing revealed that the N-terminal of the recombinant protein was identical to the published data. In Western blot analysis the recombinant polypeptide showed excellent antigenicity against polyclonal TGF-β1 antibody. The mature recombinant rat TGF-β1 expressed in this study provides a useful tool for future detailed structural and functional studies.

Changing trends of cardiovascular risk factors among Indians:a review of emerging risks

The global burden of disease due to cardiovascular diseases(CVDs) is escalating,and the changing trends of CVD risk factors are identified among Indians experiencing rapid health transition.Contributory causes include:growing population with demographic shifts and altered age profile,socio-economic factors,lifestyle changes due to urbanization.Indians are also having genetic predisposition to cardiovascular diseases and adult are susceptible to vascular disease linking possible gene-environment interactions influencing ethnic diversity.Altered diets with more of junk foods along with diminished physical activity are additive factors contributing to the acceleration of CVD epidemics,along with all form of tobacco use.The pace of health transition,however,varies across geographical regions from urban to rural population with consequent variations in the relative burdens of the dominant CVDs.A comprehensive public health response must be looked to plan over all strategies to integrate policies and programs that effectively impact on the multiple determinants of CVDs to provide protection over the life span through primordial,primary and secondary prevention.Populations as well as individuals at risk must be protected through initiatives,enable nutritionbased preventive strategies to protect and promote cardiovascular health.

High IFN-α expression is associated with the induction of experimental autoimmune uveitis (EAU) in Fischer 344 rat

Th1-response plays a crucial role in determining pathogenesis of organ-specific autoimmune diseases. It is believed that both IL-12 and INF-a are initiators to regulate Th1-response. In our experimental autoimmune uveitis (EAU) model, both Lewis and Fischer 344 rats share the same MHC class II molecules, while Lewis rat is EAU susceptible and Fischer 344 rat is EAU resistant. However, under the same condition of immunization, if pertussis toxin (PTX) was injected intraperitoneally as an additional adjuvant, Fischer 344 rat can develop EAU. In this study we investigate which mechanisms are involved in the induction of EAU in CFA + R16 + PTX treated (CRP- treated) Fischer 344 rats. In vivo and in vitro data demonstrated that Th1-cytokine, IFN- mRNA expression was significantly increased in disease target tissue-eyes and in draining lymph node cells of CRP-treated Fischer 344 rat. When IL-12 and IFN-a mRNA expression were compared in the experimental groups, only IFN-a mRNA expression was associated with EAU development. To distinguish the sources of IFN-a producing cells, it was observed that IFN-a expression was mainly produced by macrophages. It was further confirmed that normal macrophage from Fischer 344 rat was able to produce significant IFN-a in the presence of PTX. The data strongly suggested that IFN-a might be involved in initiating Th1-cell differentiation and in turn contribute to the induction of EAU. High IFN-a expression induced by PTX may represent a novel pathway to initiate Th1 response in Fischer 344 rat.

非酒精性脂肪性肝病发病机制的研究进展

非酒精性脂肪性肝病(NAFLD)是一种与胰岛素抵抗密切相关的代谢应激性肝损伤,是目前世界上最常见的慢性肝病,可导致肝硬化、肝细胞癌和终末期肝病。针对NAFLD,临床上暂时无特异性的治疗措施。本文就近几年来国内外关于NAFLD的发病机制及危险因素的最新进展进行综述,如代谢相关因素、肠道微生态紊乱、氧化应激、遗传、自主神经系统等,旨在为临床治疗NAFLD提供新的思路。

非遗传因素对杜泊羊和湖羊初生重的影响

【目的】为探究非遗传因素对羔羊初生重的影响,对肉用的杜泊羊和湖羊的初生重进行测定,分析了两个品种间初生重的差异。【方法】利用SAS9.2软件进行最小二乘方差分析。【结果】杜泊羊的初生重极显著高于湖羊(P<0.01),且出生年份、性别和出生类型对于杜泊羊和湖羊的初生重均有极显著性影响(P<0.01);出生月份对于湖羊和杜泊羔羊的初生重均有显著性影响(P<0.05)。【结论】出生年份、月份、性别、出生类型等非遗传因素对不同绵羊品种初生重影响不同,在估算种羊初生重的遗传参数时,应考虑到非遗传因素的影响,从而对育种值进行准确的估算。

非综合征型唇腭裂病因学研究进展:遗传与环境及遗传-环境交互作用

非综合征型唇腭裂(non-syndromic oral cleft,NSOC)是一种常见的口腔颌面部出生缺陷,其发病机制复杂,受遗传和环境因素共同作用的影响。该文全面综述了NSOC的病因学研究现状,并展望了未来的研究方向。在遗传学方面探究了候选基因和通路研究的发现,揭示了基因组关联研究的最新发现以及全外显子测序和全基因组测序的突破。在环境危险因素方面回顾了营养不足、母体药物暴露、辐射、环境污染和孕期感染等对NSOC的影响,强调了这些因素与颌面部发育的紧密联系。更进一步,该文详细论述了遗传与环境的交互作用,并展望了NSOC病因学未来研究的可能方向,这些展望将提供更全面、精准的NSOC治疗和预防策略。

非遗传因素对湖羊羔羊初生重的影响

为探究非遗传因素对湖羊早期生长发育的影响,以南疆某羊场2022年8月—2023年4月1172只湖羊母羊所产的2679只羔羊为研究对象,采用非遗传因素各水平间的多重比较分析羔羊的出生年月、胎次、同胞数和性别等对其初生重的影响。结果表明,出生年月、出生胎次对羔羊初生重的影响不显著(P>0.05);同胞数和性别对羔羊初生重的影响极显著(P<0.01)。因此,在对湖羊进行早期生长性状的选育时,模型中固定效应应包括出生同胞数。在条件允许的情况下,可以使用性控精液控制羔羊出生性别,这有利于提高繁殖效率,增加养殖收益。

乙肝疫苗接种无弱应答与遗传因素关系的研究

为了研究乙肝疫苗接种无弱应答的发生机制，本次研究首先对经过严格筛选的无弱应答和强应答（对照）者一级亲属（分别有８０和７９人）自然状况下的ＨＢＶ感染率进行比较。结果显示，无弱应答组ＨＢＶ的感染率为３３．８％，明显高于强应答组的１５．２％（Ｐ＝０．０１１）。在此基础上，进一步观察了无弱应答和强应答组一组亲属中乙肝三项指标全阴性和单项抗－ＨＢｓ低水平者５６人（分别为２７和２９人）接种乙肝疫苗后Ｔ７时抗－ＨＢｓ的分布情况，两组分别随访到２４人和２８人，结果无弱应答组的ＧＭＴ显著低于强应答组的ＧＭＴ。表明无弱应答具有一定的遗传易患性。

影响氯吡格雷反应个体差异的非遗传与遗传因素研究进展

氯吡格雷在急性冠脉综合征患者中应用广泛,然而超过30%的患者出现氯吡格雷抵抗,影响其临床应用。本文拟综述合并疾病、药物相互作用等非遗传因素和ABCB1、对氧磷酶-1(PON-1)与CYP2C19基因多态性等遗传因素对氯吡格雷反应个体差异影响的最新研究进展,以期使临床上能合理有效使用氯吡格雷。

影响中国美利奴羊(新疆型)羔羊初生重的非遗传因素分析

【目的】为了探讨主要非遗传因素对中国美利奴羊(新疆型)羔羊初生重的影响,收集2×104条中国美利奴羊(新疆型)羔羊鉴定记录。【方法】利用SAS8.1软件的GLM程序,分析出生类型、性别、群别、出生年以及月份对中国美利奴羊(新疆型)羔羊初生重的影响。【结果】公母羔的平均初生重分别为3.609和3.501 kg;性别对羔羊初生重有极显著影响(P<0.01);产羔数对羔羊初生重也有极显著影响(P<0.01),单羔的初生重高于双羔。群别和出生年对羔羊初生重也存在着极显著影响(P<0.01);出生月份对羔羊初生重无显著影响(P>0.05)。【结论】分析大量的记录资料讨论了出生类型等5个非遗传因素对中国美利奴羊羔羊(新疆型)初生重的影响,以期为今后估计美利奴羊遗传参数和育种值时固定效应的划分和选育提供一定的依据。