PTEN和EGFR在胃癌中的表达及相关性研究

目的:检测第10号染色体缺失的磷酸酶和张力蛋白同源物基因PTEN及表皮生长因子受体EGFR在胃癌组织中的表达,探讨两者与胃癌肿瘤行为的关系及意义。方法:采用免疫组织化学染色法(S-P法)检测105例胃癌组织及癌旁正常胃组织中EGFR和PTEN蛋白的表达水平,并将检测结果与临床病理参数进行综合分析。结果:胃癌组织PTEN的表达56.19%明显低于正常组织中的表达的表达92.3%,而胃癌组织EGFR的表达46.67%明显高于正常组织7.62%,(P<0.01)。二者的表达与性别和年龄无相关性(P>0.05),与胃癌的分化程度、浸润深度、淋巴结转移及临床分期有相关性(P<0.05)。结论:PTEN在胃癌组织中呈低表达,EGFR在胃癌组织中存在高表达,与胃癌的发生、发展有一定关系,并与胃癌的分化程度、浸润深度、淋巴结转移及临床分期密切相关,二者呈负相关。     

Exploring the obscure profiles of pharmacological binding sites on voltage-gated sodium channels by BmK neurotoxins

Diverse subtypes of voltage-gated sodium channels (VGSCs) have been found throughout tissues of the brain, muscles and the heart. Neurotoxins extracted from the venom of the Asian scorpion Buthus martensi Karsch (BmK) act as sodium channel-specific modulators and have therefore been widely used to study VGSCs. α-type neurotoxins, named BmK I, BmK αIV and BmK abT, bind to receptor site-3 on VGSCs and can strongly prolong the inactivation phase of VGSCs. In contrast, β-type neurotoxins, named BmK AS, BmK AS-1, BmK IT and BmK IT2, occupy receptor site-4 on VGSCs and can suppress peak currents and hyperpolarize the activation kinetics of sodium channels. Accumulating evidence from binding assays of scorpion neurotoxins on VGSCs, however, indicate that pharmacological sensitivity of VGSC subtypes to different modulators is much more complex than that suggested by the simple α-type and β-type neurotoxin distinction. Exploring the mechanisms of possible dynamic interactions between site 3-/4-specific modulators and region- and/or species-specific subtypes of VGSCs would therefore greatly expand our understanding of the physiological and pharmacological properties of diverse VGSCs. In this review, we discuss the pharmacological and structural diversity of VGSCs as revealed by studies exploring the binding properties and cross-competitive binding of site 3- or site 4-specific modulators in VGSC subtypes in synaptosomes from distinct tissues of diverse species.     

Culture and end of life care: a scoping exercise in seven European countries

Aim

Culture is becoming increasingly important in relation to end of life (EoL) care in a context of globalization, migration and European integration. We explore and compare socio-cultural issues that shape EoL care in seven European countries and critically appraise the existing research evidence on cultural issues in EoL care generated in the different countries.

Methods

We scoped the literature for Germany, Norway, Belgium, the Netherlands, Spain, Italy and Portugal, carrying out electronic searches in 16 international and country-specific databases and handsearches in 17 journals, bibliographies of relevant papers and webpages. We analysed the literature which was unearthed, in its entirety and by type (reviews, original studies, opinion pieces) and conducted quantitative analyses for each country and across countries. Qualitative techniques generated themes and sub-themes.

Results

A total of 868 papers were reviewed. The following themes facilitated cross-country comparison: setting, caregivers, communication, medical EoL decisions, minority ethnic groups, and knowledge, attitudes and values of death and care. The frequencies of themes varied considerably between countries. Sub-themes reflected issues characteristic for specific countries (e.g. culture-specific disclosure in the southern European countries). The work from the seven European countries concentrates on cultural traditions and identities, and there was almost no evidence on ethnic minorities.

Conclusion

This scoping review is the first comparative exploration of the cultural differences in the understanding of EoL care in these countries. The diverse body of evidence that was identified on socio-cultural issues in EoL care, reflects clearly distinguishable national cultures of EoL care, with differences in meaning, priorities, and expertise in each country. The diverse ways that EoL care is understood and practised forms a necessary part of what constitutes best evidence for the improvement of EoL care in the future.     

Fibroblast growth factor 21 reverses high‐fat diet‐induced impairment of vascular function via the anti‐oxidative pathway in ApoE knockout mice

Circulating endothelial progenitor cells (EPCs), which function in vascular repair, are the markers of endothelial dysfunction and vascular health. Fibroblast growth factor 21 (FGF21), a liver‐secreted protein, plays a crucial role in glucose homeostasis and lipid metabolism. FGF21 has been reported to attenuate the progression of atherosclerosis, but its impact on EPCs under high oxidative stress conditions remains unclear. In vitro studies showed that the β‐klotho protein was expressed in cultured EPCs and that its expression was upregulated by FGF21 treatment. Hydrogen peroxide (H₂O₂)‐induced oxidative stress impaired EPC function, including cell viability, migration and tube formation. Pretreatment with FGF21 restored the functions of EPCs after the exposure to H₂O₂. Administration of N(ω)‐nitro‐L‐arginine methyl ester (L‐NAME), an inhibitor of nitric oxide synthase, inhibited the effects of FGF21 in alleviating oxidative injury by suppressing endothelial nitric oxide synthase (eNOS). In an in vivo study, the administration of FGF21 significantly reduced total cholesterol (TC) and blood glucose levels in apolipoprotein E (ApoE)‐deficient mice that were fed a high‐fat diet (HFD). Endothelial function, as reflected by acetylcholine‐stimulated aortic relaxation, was improved after FGF21 treatment in ApoE‐deficient mice. Analysis of mRNA levels in the aorta indicated that FGF21 increased the mRNA expression of eNOS and upregulated the expression of the antioxidant genes superoxide dismutase (SOD)1 and SOD2 in ApoE‐deficient mice. These data suggest that FGF21 improves EPC functions via the Akt/eNOS/nitric oxide (NO) pathway and reverses endothelial dysfunction under oxidative stress. Therefore, administration of FGF21 may ameliorate a HFD‐induced vascular injury in ApoE‐deficient mice.     

Indirect measurement of the lag time distribution of single cells of Listeria innocua in food

The distribution of log counts at a given time during the exponential growth phase of Listeria innocua measured in food samples inoculated with one cell each was applied to estimate the distribution of the single-cell lag times. Three replicate experiments in broth showed that the distribution of the log counts is a linear mapping of the distribution of the detection times measured by optical density. The detection time distribution reflects the lag time distribution but is shifted in time. The log count distribution was applied to estimate the distributions of the lag times in a liquid dairy product and in liver paté after different heat treatments. Two batches of ca. 100 samples of the dairy product were inoculated and heated at 55 degrees C for 45 min or at 62 degrees C for 2 min, and an unheated batch was incubated at 4 degrees C. The final concentration of surviving bacteria was ca. 1 cell per sample. The unheated cells showed the shortest lag times with the smallest variance. The mean and the variance of the lag times of the surviving cells at 62 degrees C were greater than those of the cells treated at 55 degrees C. Three batches of paté samples were heated at 55 degrees C for 25 min, 62 degrees C for 81 s, or 65 degrees C for 20 s. A control batch was inoculated but not heated. All paté samples were incubated at 15 degrees C. The distribution of the lag times of the cells heated at 55 degrees C was not significantly different from that of the unheated cells. However, at the higher temperatures, 62 degrees C and 65 degrees C, the lag duration was longer and its variance greater.     

All politics is local: the case of Macrocephalon maleo conservation on Sulawesi, Indonesia

The rich biodiversity of the Indonesian island of Sulawesi is subject to a high rate of deforestation and other pressures. Its plight is symbolized by the deteriorating conservation status of the maleo, an iconic galliform bird that is both striking in appearance and intimately bound up with local traditions. After a series of international-led projects during the 1980s and early 1990s conservation efforts petered out until recently when there has been an upsurge in local-led concern and action. To capitalize on this a workshop was held in 2010 to share local perceptions, lessons and concerns about the species and these conservation efforts. The workshop was dominated by members of local communities and their elected or traditional representatives, although there was also a wide variety of other stakeholders present, including from national species conservation and local government agencies. Whilst there is a need for more information to underpin the actions necessary to ensure the survival of this species, the overwhelming perception of participants was that continued decentralization of policy making and budgetary responsibility would enhance the conservation efforts for this species (and other elements of biodiversity) considerably. This would allow the upsurge in locally-led conservation activities to be continued and expanded.     

C 族GPCRs 的半胱氨酸富集区的研究进展及药学意义

C族GPCRs是体内重要的受体,参与众多重要的生理和病理进程,并具有复杂的结构和激活机制。在体内该族受体形成组成性的二聚体并具有七螺旋跨膜结构(heptahelical transmembrane domain,HD)、捕蝇草模块(venus flytrap domain,VFT)和半胱氨酸富集区(cysteine-rich domain,CRD)。本文系统介绍了近年来CRD单体的序列和结构解析,以及参与受体激活过程的机制研究的历程和进展。同时也展望了这些基础研究成果对于开发新的更具有成药性的以C族GPCRs为靶点的变构剂的指导意义。