REIC/Dkk-3蛋白在肿瘤发生发展中作用

REIC基因在永生化的细胞系和部分肿瘤细胞系中发现并且表达下调,在许多人的肿瘤组织中表达也减少.目前研究认为,REIC/Dkk-3表达下调可能与启动子的甲基化有关.异常REIC/Dkk-3表达所致细胞表型异常在恶性肿瘤发生和演进过程中发挥重要作用.细胞浆型和分泌型REIC与靶蛋白作用后启动细胞信号传导,但是REIC/Dkk-3的生物学功能尚未深入阐述.对REIC/Dkk-3的研究在理论上可以大大推动肿瘤病因学的发展,为肿瘤的诊断和治疗提供一个新的分子靶点,对提高肿瘤患者生存率和生存质量具有很大的促进作用.如果能研发REIC/Dkk-3抗肿瘤重组多肽及增强REIC/Dkk-3作用的化疗药物,也将为肿瘤患者治疗开辟新的途径和思路.本文就REIC/Dkk-3蛋白在肿瘤发生发展中作用进行综述.     

Effects of photoperiod and temperature on reproductive diapause in Ophraella communa (Coleoptera: Chrysomelidae), a potential biocontrol agent against Ambrosia artemisiifolia

Abstract To investigate the seasonal adaptation strategies of Ophraella communa to new habitats, the effects and regulation mechanisms of photoperiod and temperature on the reproductive diapause in a population collected from Changsha, Hunan were examined. Adults showed obvious reproductive diapause, which was regulated by photoperiod and temperature. At 30°C, there was no adult diapause occurring under either long‐day or short‐day conditions; at 25°C the pre‐oviposition period was short and fecundity was high in adult females under L : D 16 : 8 h, whereas under L : D 12 : 12 h, a few females entered reproductive diapause; at 20°C under short‐day conditions, all female adults entered diapause. The pre‐oviposition period was significantly prolonged when the pupae and adults were transferred from long‐days to short‐days, but the day length influence was not obvious when they were transferred only in the adult stage. However, the fecundity dropped greatly no matter whether the photoperiod shifted to short‐days only in the adult stage or whether the shift occurred in both the pupal and adult stage. The fecundity was extremely low when photoperiod shifted from long‐days to short‐days in both pupal and adult stages. This was an indication that the pupal and adult stages were the photoperiod‐sensitive stage for adult reproductive diapause. This was especially true for the photoperiod in the pupal stage, which has a distinctly significant regulative effect on reproductive diapause. Additionally, this article also addresses the reason for different photoperiodic response patterns in reproductive diapause induction between the Changsha strain and the Tsukuba strain (Japan) of O. communa.     

银杏叶提取物对新生SD 乳鼠心肌细胞缺氧损伤的影响

目的:研究银杏叶提取物对缺氧状态下新生SD乳鼠心肌细胞的影响及其可能机制。方法:新生1天SD乳鼠心肌细胞原代培养并利用氮气培养箱模拟低氧构建乳鼠心肌缺氧体外模型。分为3组处理:对照组,缺氧组,缺氧+药物拮抗组。缺氧时间为12 h,通过免疫组化等检测方法,观察各组心肌细胞的损伤情况及心肌Bcl-2、Bax蛋白表达情况。结果:缺氧可以造成新生SD乳鼠心肌细胞凋亡的发生(hypoxia:75.21%±1.21%,control:1.38%±0.45%,P<0.05,n=20),并导致其表达凋亡抑制因子Bcl-2蛋白水平的显著降低(0.125 fold VS control group,P<0.05),促细胞凋亡因子Bax蛋白水平显著升高(3.011fold VS control group,P<0.05);而银杏叶提取物作用后可明显逆转新生SD乳鼠心肌细胞凋亡的发生(EGb761:23.17%±0.43%,hypoxia:73.13%±1.22%,P<0.05,n=20),并明显逆转Bcl-2(5.716 fold VS hypoxia group,P<0.05)、Bax(0.273fold VS hypoxia group,P<0.05)等蛋白的表达水平。结论:凋亡相关因子Bcl-2和Bax等参与缺氧致心肌损伤过程,导致心肌细胞凋亡,银杏叶提取物能降低心肌Bax表达,提高Bcl-2表达,从而保护心肌细胞,抑制凋亡。     

代谢正常肥胖个体发生非酒精性脂肪性肝病的相关性研究

目的:探讨代谢正常肥胖(Metabolically healthy obese,MHO)个体与非酒精性脂肪性肝病(Nonalcoholic fatty liver disease,NAFLD)发生的相关性。方法:选择2006年4月～2010年1月来湖南省人民医院体检中心体检人群共4076例,排除过量饮酒者、乙肝标志物阳性者及相关资料不全者共2830例纳入本研究。其中1367例在1～3年后再次体检。记录受检者身高、体重、血压、血脂、空腹血糖、腹部B超结果。NAFLD采用2010年中华医学会肝病学分会诊断标准中影像学诊断定义,行腹部B超检查进行诊断。结果:1.我院体检人群中MHO合并NAFLD者占51.34%,明显高于正常对照组(P=0.000),MHO组发生NAFLD的OR值为19.967(95%CI,12.646-31.533;P=0.000)。2.随访1～3年后,MHO中NAFLD发病率高于正常对照组(44.44%vs 7.02%,OR=10.600,95%CI,4.873-23.058;P=0.000)。结论:MHO个体合并NAFLD比例较正常对照者升高,MHO个体增加NAFLD患病风险。     

Common molecular etiologies are rare in nonsyndromic Tibetan Chinese patients with hearing impairment

Background

Thirty thousand infants are born every year with congenital hearing impairment in mainland China. Racial and regional factors are important in clinical diagnosis of genetic deafness. However, molecular etiology of hearing impairment in the Tibetan Chinese population living in the Tibetan Plateau has not been investigated. To provide appropriate genetic testing and counseling to Tibetan families, we investigated molecular etiology of nonsyndromic deafness in this population.

Methods

A total of 114 unrelated deaf Tibetan children from the Tibet Autonomous Region were enrolled. Five prominent deafness-related genes, GJB2, SLC26A4, GJB6, POU3F4, and mtDNA 12S rRNA, were analyzed. Inner ear development was evaluated by temporal CT. A total of 106 Tibetan hearing normal individuals were included as genetic controls. For radiological comparison, 120 patients, mainly of Han ethnicity, with sensorineural hearing loss were analyzed by temporal CT.

Results

None of the Tibetan patients carried diallelic GJB2 or SLC26A4 mutations. Two patients with a history of aminoglycoside usage carried homogeneous mtDNA 12S rRNA A1555G mutation. Two controls were homozygous for 12S rRNA A1555G. There were no mutations in GJB6 or POU3F4. A diagnosis of inner ear malformation was made in 20.18% of the Tibetan patients and 21.67% of the Han deaf group. Enlarged vestibular aqueduct, the most common inner ear deformity, was not found in theTibetan patients, but was seen in 18.33% of the Han patients. Common molecular etiologies, GJB2 and SLC26A4 mutations, were rare in the Tibetan Chinese deaf population.

Conclusion

The mutation spectrum of hearing loss differs significantly between Chinese Tibetan patients and Han patients. The incidence of inner ear malformation in Tibetans is almost as high as that in Han deaf patients, but the types of malformation vary greatly. Hypoxia and special environment in plateau may be one cause of developmental inner ear deformity in this population.     

Genome shuffling improves thermotolerance and glutamic acid production of <Emphasis Type="Italic">Corynebacteria glutamicum</Emphasis>

Genome shuffling was used to improve the thermotolerance of l-glutamic acid-producing strain Corynebacteria glutamicum. Five strains with subtle improvements in high temperature tolerance and productivity were selected by ultraviolet irradiation and diethyl sulfate mutagenesis. An improved strain (F343) was obtained by three rounds of genome shuffling of the five strains as mentioned above. The cell density of F343 was four times higher than that of ancestor strains after 24 h of cultivation at 44°C, and importantly, the yield of l-glutamic acid was increased by 1.8-times comparing with that of the ancestor strain at 38°C in a 5-L fermentor. With glucose supplement and two-stage pH control, the l-glutamate acid concentration of F343 reached 119 g/L after fermentation for 30 h. The genetic diversity between F343 and its ancestors was also evaluated by amplified fragment length polymorphism analysis. Results suggest that the phenotypes for both thermotolerance and l-glutamic acid production in F343 were evolved.     

Identification and evaluation of apoptotic compounds from Garcinia oligantha

Four new compounds, oliganthins A-D (1-4), and one known caged xanthone gaudichaudione H (5) were isolated from the stems of Garcinia oligantha. The structures of the new compounds were elucidated by spectroscopic evidences. All of the five compounds were evaluated for their apoptosis-inducing effects using HeLa-C3 cells which have been genetically engineered to produce a fluorescent biosensor capable of detecting caspase-3 activation. All of them induced cell apoptosis at 10 μM or lower concentrations. The apoptotic activity of oliganthins A, B and gaudichaudione H were further confirmed by detecting the cleavage of PARP, which is the substrate of activated caspase-3, in these compounds-treated cells using the method of Western blot. Moreover, the values of IC(50) were measured for all five compounds on HeLa cells using the MTT assay. Among them, gaudichaudione H had the lowest IC(50) value of 0.90 μM, while the other four new compounds had IC(50) values of 1.58, 1.52, 4.15, and 7.82 μM, respectively. These results show that gaudichaudione H has the strongest apoptosis-inducing effect and cell growth inhibition effect among these xanthones and it may have the potential to be developed into a new anticancer agent.     

Mouse-adapted H9N2 influenza A virus PB2 protein M147L and E627K mutations are critical for high virulence

H9N2 influenza viruses have been circulating worldwide in multiple avian species and have repeatedly infected humans to cause typical disease. The continued avian-to-human interspecies transmission of H9N2 viruses raises concerns about the possibility of viral adaption with increased virulence for humans. To investigate the genetic basis of H9N2 influenza virus host range and pathogenicity in mammals, we generated a mouse-adapted H9N2 virus (SD16-MA) that possessed significantly higher virulence than wide-type virus (SD16). Increased virulence was detectable after 8 sequential lung passages in mice. Five amino acid substitutions were found in the genome of SD16-MA compared with SD16 virus: PB2 (M147L, V250G and E627K), HA (L226Q) and M1 (R210K). Assessments of replication in mice showed that all of the SD16-MA PB2, HA and M1 genome segments increased virus replication; however, only the mouse-adapted PB2 significantly increased virulence. Although the PB2 E627K amino acid substitution enhanced viral polymerase activity and replication, none of the single mutations of mouse adapted PB2 could confer increased virulence on the SD16 backbone. The combination of M147L and E627K significantly enhanced viral replication ability and virulence in mice. Thus, our results show that the combination of PB2 amino acids at position 147 and 627 is critical for the increased pathogenicity of H9N2 influenza virus in mammalian host.