G蛋白与内分泌代谢疾病

由α、β和γ3个亚基组成的G蛋白是G蛋白偶联受体信号的下游转导分子。G蛋白亚基(主要是α亚基)基因突变导致G蛋白功能减退或亢进(G蛋白病),临床上以前者为多见,包括内分泌腺的一些肿瘤、新生儿甲状旁腺功能亢进、假性甲状旁腺功能减退(甲旁减)和假假性甲旁减等。充分认识这些疾病的分子病因与发病机制,有助于提高对这些疾病的认识和防治水平。

免疫球蛋白G4相关性眼眶病的临床研究进展

近年来,免疫球蛋白G4(Ig G4)相关性疾病作为一种新的自身免疫性疾病,受到国内外医学界的的广泛关注。Ig G4相关性疾病以Ig G4+浆细胞浸润和血清Ig G4浓度升高为特征,同时伴有因全身多器官的纤维化而发生肿大、结节性或增生性病变的自身免疫性疾病。当累及眼眶时称为Ig G4相关性眼眶病。目前提出了Ig G4相关性眼眶病的相对完善的诊断标准,然而治疗方面还没有公认有效的手段,目前首选激素治疗。本文就Ig G4相关性眼眶病的临床特征、诊断和治疗的研究进展进行综述。

晚期胃癌XPG及GSTP1基因多态性与奥沙利铂化疗效果的关系

目的探讨人着色性干皮病G组(XPG)及谷胱甘肽巯基转移酶P1(GSTP1)基因多态性与晚期胃癌以奥沙利铂为主的化疗敏感性的关系。方法 80例Ⅳ期胃癌病人化疗前采集外周静脉血,提取DNA,用实时荧光PCR技术检测XPG C46T及GSTP1 A105G基因的单核苷酸多态性(SNP)分型,比较不同基因型与化疗效果的关系。结果 80例病人XPG C46T基因C/C与T/T+C/T及GSTP1 A105G基因A/A与A/G+G/G基因型化疗有效率比较差异均有显著意义(χ2=5.459、5.291,P<0.05)。同时携带XPG C46T C/C和GSTP1 A105G A/G+G/G基因型病人化疗敏感性是同时携带XPG C46T C/T+T/T和GSTP1 A105G A/A基因型病人的4.886倍(OR=4.886,P<0.05)。结论 XPG C46T、GSTP1 A105G基因多态性可能与晚期胃癌病人接受以奥沙利铂为主一线化疗药物化疗后的效果有关。

G-protein beta 3 subunit polymorphisms and essential hypertension： a case-control association study in northern Han Chinese

Objective To explore the association between the three polymorphisms [ C825T, C1429T and G（-350）A] of the gene encoding the G protein beta 3 subunit （GNB3） and hypertension by performing a case-control study in the northern Han Chinese population. Methods We recnaited 731 hypertensive patients and 673 control subjects （the calculated power value was 〉 0.8）. Genotyping was performed to identify C825T, C1429T and G（-350）A polymorphisms using the TaqMan assay. Comparisons of allelic and genotypic frequencies between cases and controls were made by using the chi-square test. Logistic regression analyses were performed to investigate the relationships between the three polymorphisms of GNB3 gene under different genetic models （additive, dominant and recessive models）. Results The genotype dis- tribution and allele frequencies of C825T, C1429T and G（-350）A polymorphisms did not differ significantly between hypertensive patients and control subjects, either when the full sample was assessed, or when the sample was stratified by gender. No significant association was observed between C825T, C 1429T and G（-350）A polymorphisms and the risk of essential hypertension in any genetic model. Linkage dis- equilibrium was only detected between C825T and C 1429T polymorphisms. Haplotype analyses observed that none of the three estimated haplotypes significantly increased the risk of hypertension. Conclusions Our study suggested that the GNB3 gene polymorphisms [C825T, C 1429T and G（-350）A] were not significantly associated with essential hypertension in northern Han Chinese population.

Study of signal transduction factors involved in mycoparasitic response of Trichoderma atroviride

Numerous Trichoderma spp. are mycoparasites and commercially applied as biological control agents against a large number of plant pathogenic fungi. The mycoparasitic interaction is host-specific and several research strategies have been applied to identify the main genes and compounds involved in the antagonist-plant-pathogen three-way interaction. During mycoparasitism, signals from the host fungus are recognised by Trichoderma, stimulating antifungal activities that are accompanied by morphological changes and the secretion of hydrolytic enzymes and antibiotics. Interestingly some morphological changes appeared highly conserved in the strategy of pathogenicity within the fungal world, i.e. the formation of appressoria as well as the secretion of hydrolytic enzymes seem to be general mechanisms of attack both for plant pathogens and mycoparasitic antagonists. This knowledge is being used to identify receptors and key components of signalling pathways involved in fungus-fungus interaction. For this purpose we have cloned the first genes (tmk1, tga1, tga3) from T. atroviride showing a high similarity to MAP kinase and G protein subunits (see abstract by Zeilinger et al.), which have been found to have an important role in pathogenicity by Magnaporthe grisea. To identify the function and involvement of these factors in mycoparasitism by T. atroviride, tmk1, tga1, tga3 disruptant strains were produced. The knock-out mutants were tested by in vivo biocontrol assays for their ability to inhibit soil and foliar plant pathogens such as Rhizoctonia solani, Pythium ultimum and Botrytis cinerea . Disruption of these genes corresponded to a complete loss of biocontrol ability, suggesting a significant role in mycoparasitism. In particular, it has been suggested that tga3 regulates the expression of chitinase-encoding genes, the secretion of the corresponding enzymes and the process of conidiation. Comparative proteome analysis of wild type and disruptants supported this hypothesis, and indicated many changes in the protein profiles of T. atroviride in different interaction conditions with plants and pathogenic hosts.

苯并芘处理对人支气管上皮细胞热休克蛋白70和着色性干皮病G蛋白表达的影响

目的探讨苯并芘(Benzo[a]pyrene,BaP)作用下的人支气管上皮细胞(16HBE)热休克蛋白70(Heatshock protein 70,Hsp70)和着色性干皮病G蛋白(Xeroderma pigmentosum group G,XPG)表达的时间效应特征,并分析二者之间可能存在的关联性。方法用8μmol/L BaP处理16HBE细胞0、1、2、4、8、12、24和48 h,以彗星实验检测细胞DNA损伤并以Olive尾矩值(Olive Tail Moments,OTM)评价DNA损伤程度,以Western-blot检测Hsp70和XPG的表达水平,并以激光共聚焦法检测二者的共定位。结果染毒1～2h时OTM值变化率最大,与正常细胞相比,除染毒1h组外其余各组OTM值均显著性增高(P﹤0.01);Hsp70和XPG的表达随染毒时间逐渐增高,12 h时达到峰值,激光共聚焦结果显示BaP染毒细胞后Hsp70和XPG的结合在细胞核内增强。结论在该试验条件下,XPG在执行核苷酸切除修复作用时可能有Hsp70的参与,其具体机制还有待其他实验进一步加以证实。

Update on autoimmune hepatitis

Autoimmune hepatitis (AIH) is a necroinflammatory liver disease of unknown etiology that occurs in children and adults of all ages. Characteristics are its autoimmune features,hyperglobulinemia (IgG),and the presence of circulating autoantibodies,as well as a response to immunosuppressant drugs. Current treatment consists of prednisone and azathioprine and in most patients this disease has become very treatable. Over the past 2 years,a couple of new insights into the genetic aspects,clinical course and treatment of AIH have been reported,which will be the focus of this review. In particular,we concentrate on genome-wide microsatellite analysis,a novel mouse model of AIH,the evaluation of a large AIH cohort for overlap syndromes,suggested novel criteria for the diagnosis of AIH,and the latest studies on treatment of AIH with budenoside and mycophenolate mofetil.

Mc-Cune-Albright综合征1例报道

Mc—Cune—Albright综合征是一种罕见G蛋白病，主要病因为体细胞在胚胎形成过程中GNAS基因发生哭变，致cAMP在细胞内堆积，激活G蛋白-cAMP依赖性受体，促进靶激素分泌，引起内分泌腺体功能亢进。因属合子期突变，故为非遗传性疾病。Mc—Cune—Albright综合征以多发性骨纤维异常增生、皮肤色素沉着、性早熟为特征性临床表现，发病率在1／100000到1／1000000之间，女性发病率明显高于男性，国内外报道的男女发病率之比约为1：8，男性患者尤其罕见。本院于2012年12月收治了1例以“左肱骨病理性骨折”入院的男性患者，临床诊断为Mc—Cune—Albright综合征。

In vivo gene expression profiling of the entomopathogenic fungus Beauveria bassiana elucidates its infection stratagems in Anopheles mosquito

The use of entomopathogenic fungi to control mosquitoes is a promising tool for reducing vector-borne disease transmission. To better understand infection stratagems of insect pathogenic fungi, we analyzed the global gene expression profiling of Beauveria bassiana at 36, 60, 84 and 108 h after topical infection of Anopheles stephensi adult mosquitoes using RNA sequencing （RNA-Seq）. A total of 5,354 differentially expressed genes （DEGs） are identified over the course of fungal infection. When the fungus grows on the mosquito cuticle, up-regulated DEGs include adhesion-related genes involved in cuticle attachment, Pthl l-like GPCRs hypothesized to be involved in host recognition, and extracellular enzymes involved in the degradation and penetration of the mosquito cuticle. Once in the mosquito hemocoel, the fungus evades mosquito immune system probably through up-regulating expression of 13-1,3-glucan degrading enzymes and chitin synthesis enzymes for remodeling of cell walls. Moreover, six previous unknown SSCP （small secreted cysteine-rich proteins） are significantly up-regulated, which may serve as ＂effectors＂ to suppress host defense responses. B. bassiana also induces large amounts of antioxidant genes to mitigate host-generated exogenous oxidative stress. At late stage of infection, B. bassiana activates a broad spectrum of genes including nutrient degrading enzymes, some transporters and metabolism pathway components, to exploit mosquito tissues and hemolymph as a nutrient source for hyphal growth. These findings establish an important framework of knowledge for further comprehensive elucidation of fungal pathogenesis and molecular mechanism of Beauveria-mosquito interactions.