siRNA干扰HIF-1α表达对高糖高胰岛素诱导的肥大心肌细胞的影响

目的 研究胰岛素受体底物1(insulin receptor substrate 1,IRS1)和缺氧诱导因子1a(hypoxia inducible factor 1a,HIF-1a)在高糖高胰岛素诱导的肥大心肌细胞中的表达及其之间的关系;观察siRNA沉默HIF-1a基因对高糖高胰岛素诱导的心肌细胞肥大的影响.方法 新生大鼠心肌细胞培养48h后,换用无血清DMEM培养液并分别加入高糖高胰岛素、高糖高胰岛素+HIF-1a-siRNA培养48h,未加入任何药物的心肌细胞在无血清DMEM培养液中继续培养48h作为对照.通过心肌细胞表面积、总蛋白含量指标检测心肌细胞肥大,并利用Real time PCR检测转染前后HIF-1a mRNA表达变化及免疫细胞化学方法检测HIF-1a及IRS1蛋白水平的表达.结果 高糖高胰岛素可增加心肌细胞表面积、总蛋白含量、HIF-1a mRNA以及HIF-1a表达,并降低IRS1表达.转染siRNA后使HIF-1a基因的表达下降,能部分抑制心肌细胞的肥大,降低心肌细胞表面积和总蛋白含量,但对IRS1表达的影响不明显.在对正常对照组和高糖高胰岛素组中IRS1表达量与HIF-1a表达量进行相关分析表明,两者的表达量成负相关.结论 通过siRNA技术对HIF-1a的有效沉默可明显地抑制高糖高胰岛素诱导大鼠乳鼠心肌细胞肥大,并且这种作用可能是通过作用于IRS1/PI3K/ Akt/MTOR途径来实现的.     

Shifts of bacteriochlorophyll and carotenoid absorption bands linked to cytochrome c-555 photooxidation in Chromatium

Shifts in the absorption bands of bacteriochlorophyll and carotenoids in Chromatium vinosum chromatophores were measured after short actinic flashes, under various conditions. The amplitude of the bacteriochlorophyll band shift correlated well with the amount of cytochrome c-555 that was oxidized by P₈₇₀⁺ after a flash. No bacteriochlorophyll band shift appeared to accompany the photooxidation of P₈₇₀ itself, nor the oxidation of cytochrome c-552 by P₈₇₀⁺. The carotenoid band shift also correlated with cytochrome c-555 photooxidation, although a comparatively small carotenoid shift did occur at high redox potentials that permitted only P₈₇₀ oxidation.

The results explain earlier observations on infrared absorbance changes that had suggested the existence of two different photochemical systems in Chromatium. A single photochemical system accounts for all of the absorbance changes.

Previous work has shown that the photooxidations of P₈₇₀ and cytochrome c-555 cause similar changes in the electrical charge on the chromatophore membrane. The specific association of the band shifts with cytochrome c-555 photooxidation therefore argues against interpretations of the band shifts based on a light-induced membrane potential.     

Peptide models of four possible insulin folding intermediates with two disulfides

The single-chain insulin (PIP) can spontaneously fold into native structure through preferred kinetic intermediates. During refolding, pairing of the first disulfide A20-B19 is highly specific, whereas pairing of the second disulfide is likely random because two two-disulfide intermediates have been trapped. To get more details of pairing property of the second disulfide, four model peptides of possible folding intermediates with two disulfides were prepared by protein engineering, and their properties were analyzed. The four model peptides were named [A20-B19, A7-B7]PIP, [A20-B19, A6-B7]PIP, [A20-B19, A6-A11]PIP, and [A20-B19, A7-A11]PIP according to their remaining disulfides. The four model peptides all adopt partially folded structure with moderate conformational differences. In redox buffer, the disulfides of the model peptides are more easily reduced than those of the wild-type PIP. During in vitro refolding, the reduced model peptides share similar relative folding rates but different folding yields: The refolding efficiency of the reduced [A20-B19, A7-A11]PIP is about threefold lower than that of the other three peptides. The present results indicate that the folding intermediates corresponding to the present model peptides all adopt partially folded conformation, and can be formed during PIP refolding, but the chance of forming the intermediate with disulfide [A20-B19, A7-A11] is much lower than that of forming the other three intermediates.     

Mitogenomic phylogeny of the Percichthyidae and Centrarchiformes (Percomorphaceae): comparison with recent nuclear gene-based studies and simultaneous analysis

Delineation of the fish family Percichthyidae (Percomorphaceae) has a long and convoluted history, with recent morphological-based studies restricting species members to South American and Australian freshwater and catadromous temperate perches. Four recent nuclear gene-based phylogenetic studies, however, found that the Percichthyidae was not monophyletic and was nested within a newly discovered inter-familial clade of Percomorphaceae, the Centrarchiformes, which comprises the Centrarchidae and 12 other families. Here, we reexamined the systematics of the Percichthyidae and Centrarchiformes based on new mitogenomic information. Our mitogenomic results are globally congruent with the recent nuclear gene-based studies although the overall amount of phylogenetic signal of the mitogenome is lower. They do not support the monophyly of the Percichthyidae, because the catadromous genus Percalates is not exclusively related to the freshwater percichthyids. The Percichthyidae (minus Percalates) and Percalates belong to a larger clade, equivalent to the Centrarchiformes, but their respective sister groups are unresolved. Because all recent analyses recover a monophyletic Centrarchiformes but with substantially different intra-relationships, we performed a simultaneous analysis for a character set combining the mitogenome and 19 nuclear genes previously published, for 22 centrarchiform taxa. This analysis furthermore indicates that the Centrarchiformes are divided into three lineages and the superfamily Cirrhitoidea is monophyletic as well as the temperate and freshwater centrarchiform perch-like fishes. It also clarifies some of the relationships within the freshwater Percichthyidae.     

乏氧和辐射诱导的miR-1290 促进宫颈癌细胞EMT发生

目的:研究mi R-1290在宫颈癌Hela细胞上皮间质转化中的作用。方法:模拟肿瘤放射治疗的分割疗法,单次2 Gyγ射线连续照射宫颈癌Hela、Siha细胞诱导辐射抗性细胞株;采用micro RNA芯片技术比较辐射抗性细胞与亲本细胞中mi RNA的表达谱差异;经不同条件乏氧和辐射处理宫颈癌Hela细胞后检测mi R-1290的表达水平;借助mi R-1290及mi R-1290-inhibition慢病毒表达载体,调变mi R-1290在Hela细胞的表达;调变mi R-1290后,划痕实验及Transwell侵袭实验比较Hela细胞的侵袭和转移能力;蛋白质印迹法检测细胞中E钙黏素(E-cadherin)和N钙黏素(N-cadherin)的表达。结果:在宫颈癌辐射抗性细胞中mi R-1290表达水平显著升高(P0.05);乏氧和辐射可诱导mi R-1290在宫颈癌Hela细胞中表达(P0.05);上调表达mi R-1290,Hela细胞出现了明显的间质细胞的形态改变,细胞的侵袭和转移能力明显增强(P0.05)。在Hela细胞中上调表达mi R-1290,降低了细胞中E-cadherin的表达,同时升高了N-cadherin的表达(P0.05)。结论:乏氧和辐射可诱导mi R-1290在宫颈癌Hela细胞中表达,mi R-1290通过调控E-cadherin和N-cadherin的表达促进宫颈癌Hela细胞发生EMT。     

Acute psychiatric care: approaches to increasing the range of services and improving access and quality of care

Acute services for mental health crises are very important to service users and their supporters, and consume a substantial share of mental health resources in many countries. However, acute care is often unpopular and sometimes coercive, and the evidence on which models are best for patient experience and outcomes remains surprisingly limited, in part reflecting challenges in conducting studies with people in crisis. Evidence on best ap­proaches to initial assessment and immediate management is particularly lacking, but some innovative models involving extended assessment, brief interventions, and diversifying settings and strategies for providing support are potentially helpful. Acute wards continue to be central in the intensive treatment phase following a crisis, but new approaches need to be developed, evaluated and implemented to reducing coercion, addressing trauma, diversifying treatments and the inpatient workforce, and making decision‐making and care collaborative. Intensive home treatment services, acute day units, and community crisis services have supporting evidence in diverting some service users from hospital admission: a greater understanding of how best to implement them in a wide range of contexts and what works best for which service users would be valuable. Approaches to crisis management in the voluntary sector are more flexible and informal: such services have potential to complement and provide valuable learning for statutory sector services, especially for groups who tend to be underserved or disengaged. Such approaches often involve staff with personal experience of mental health crises, who have important potential roles in improving quality of acute care across sectors. Large gaps exist in many low‐ and middle‐income countries, fuelled by poor access to quality mental health care. Responses need to build on a foundation of existing community responses and contextually relevant evidence. The necessity of moving outside formal systems in low‐resource settings may lead to wider learning from locally embedded strategies.     

Microbial Metabolite Signaling Is Required for Systemic Iron Homeostasis

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