视黄醇结合蛋白4与2型糖尿病微血管病变的研究进展

视黄醇结合蛋白4（Retinolbindingprotein4,RBP4）是一种分泌型视黄醇结合蛋白,主要由肝脏合成,在协助视黄醇发挥生理功能中起着重要的作用。近年研究发现,RBP4是一种新的循环性脂肪因子,亦能由脂肪组织特异性分泌,它不仅能够抑制肌肉组织中的胰岛素信号通路,而且能够促进糖异生,增加肝糖输出,从而导致胰岛素抵抗的发生,增加糖尿病的发病风险。目前RBP4与2型糖尿病（Type2diabetes mellitus,T2DM）关系逐渐受到人们的重视,本文就RBP4的生理功能、RBP4与T2DM微血管病变的研究进展作一综述。     

锌转运蛋白8与1型和2型糖尿病的研究进展

ZnT8(zinc transporter,member8)是锌离子转运蛋白,主要定位于胰岛β细胞,能将胞浆锌离子转运至胰岛素储存/分泌性囊泡内,其转运功能降低会影响胰岛素合成、储存和分泌,能增加2型糖尿病(T2DM)的发病风险。ZnT8蛋白也可作为抗原引起β细胞自身免疫损伤,诱发1型糖尿病(T1DM)。ZnT8基因多态性是引起其锌离子转运功能和免疫原性变化的重要因素,与糖尿病的发生、发展密切相关。该文综述了ZnT8与T1DM和T2DM的研究进展,提示ZnT8可作为糖尿病防治的新药物靶点。     

干扰视黄醇结合蛋白4对猪脂肪细胞PI3K/Akt信号通路的影响

视黄醇结合蛋白4(Retinol binding protein 4,RBP4)是一种脂肪细胞分泌因子,其表达水平的升高与胰岛素抵抗及Ⅱ型糖尿病等疾病密切相关,但具体作用机制尚不清楚。为明确此机制,通过包装RBP4干扰慢病毒并侵染猪前体脂肪细胞。运用胰岛素激活及诱导胰岛素抵抗模型,利用QRT-PCR及Western blotting方法检测RBP4的干扰效率及处理组PI3K/Akt信号通路相关基因的表达。结果显示RBP4的基因及蛋白的干扰效率达到60%(P<0.01)以上。进一步研究发现在胰岛素诱导及胰岛素抵抗的情况下,LH1-shRBP4干扰后可显著提高胰岛素信号通路AKT2、PI3K、GLUT4和IRS1基因mRNA的表达;明显促进AKT2、PI3K和IRS1蛋白的磷酸化;提高AKT2、PI3K和GLUT4基因的总蛋白水平。总之,RBP4干扰通过上调PI3K/Akt胰岛素信号通路相关因子的表达及其磷酸化水平,提高了胰岛素敏感性。此研究将为胰岛素抵抗相关疾病的治疗提供新思路。     

视黄醇结合蛋白4在病理妊娠中的研究进展

视黄醇结合蛋白4(Retinol binding protein 4,RBP4)是近年来新发现的一种脂肪细胞因子,在动物与人类的研究中均发现其与胰岛素抵抗的发生及糖、脂代谢的调节密切相关,随着机体胰岛素抵抗及糖脂代谢异常程度的增加,RBP4水平上升。在妊娠期,母体脂肪量增加并伴有不同程度的胰岛素抵抗。在正常妊娠时,RBP4随着妊娠的进展而升高,且与胰岛素抵抗程度增加相一致。与正常妊娠相比,妊娠期糖尿病(gestational diabetes mellitus,GDM)患者的RBP4升高更明显,且RBP4的升高水平与GDM预后相关。研究发现早期RBP4的升高可以预测GDM的发生,此外控制RBP4水平可能干预GDM发展。RBP4在妊娠期高血压疾病中升高;RBP4在脐血中的水平与胎儿生长密切相关,在小于胎龄儿中水平下降,在大于胎龄儿中升高;RBP4与早产的关系并不明确。进一步研究RBP4在病理妊娠的作用机制,可为病理妊娠的发生发展和防治提供新方向。     

视黄醇结合蛋白4对肾脏疾病早期诊断的评估

视黄醇结合蛋白4(RBP4)是一类合成于肝脏且广泛分布于人体血液、尿液等其它体液中的维生素A运载蛋白,它在协助维生素A发挥生理功能中起着决定性的作用。近年来的研究表明:当近端肾小管受损时,人体血液或尿液中视黄醇结合蛋白4的含量会出现不同程度的升高。同时它与糖尿病肾病、营养性疾病的发展等其它疾病都在临床上存在着一定的相关性。临床上已将RBP4的含量测定作为判定肾功能有效且成熟的指标之一。目前临床上对视黄醇结合蛋白4的检测主要是传统的酶联免疫法、免疫比浊法等,近年来随着研究水平的不断提高,对RBP4的检测方法已有逐渐转向新型的快速检测方法的趋势。本文在对视黄醇结合蛋白4的理化性质、在肾脏等各类疾病方面的应用以及新型临床检测方法等方面作一综述,随着研究的不断完善,视黄醇结合蛋白4的更多临床意义将逐渐显现。     

2型糖尿病患者尿视黄醇结合蛋白与视网膜病变的相关性

目的 探讨2型糖尿病患者尿视黄醇结合（RBP）与视网膜病变相关性。方法 采用酶联免疫法检测158例2型糖尿病患者24h尿视黄醇结合蛋白排泄（24hURBP）及24h尿白蛋白排泄（24hUAE）,并同时用眼底镜仔细检查其眼氏。结果 糖尿病视网膜病变（DR）发生率随着24hURBP、24hUAE增加而显著增高,24hURBP、24hUAE也随DR的程度加重而显著增加。结论 2型糖尿病患者DR与尿RBP、尿白蛋白呈正相关。     

前蛋白转化酶1(PC1)与胰岛素原转化的研究进展

前蛋白转化酶1(Proprotein convertase 1,PC1)是胰岛素原转换为胰岛素的一个重要关键酶,PC1缺陷导致胰岛素原转化障碍、高胰岛素原血症.2型糖尿病(T2DM)患者存在高胰岛素原血症,是原发的β细胞功能受损的表现,是胰岛素原向胰岛素转化过程出现障碍所致.胰岛素原与胰岛素(insulin,INS)的比例失调是T2DM(type 2 diabetes mellitus)的一个重要特点,甚至是T2DM发病的一个独立预测指标.因此,研究PC1与胰岛素原转化、胰岛素原增高的确切机制和意义对2型糖尿病的防治是有肯定意义的.     

视黄醇结合蛋白RBP4可与多种核受体相互作用

视黄醇结合蛋白 (retinolbindingprotein ,RBP4 )是体内一种重要的转运蛋白 ,主要负责结合、转运全反式视黄醇 (维生素A ,VitA ) .VitA及其衍生物如11 cis 视黄醛、all trans 视黄酸等 ,均是体内非常重要的疏水分子 ,与视觉循环、胚胎发育等多种过程有关 .RBP4的功能障碍会导致     

糖尿病不同发展阶段胰岛功能的变化趋势*

目的:研究糖尿病不同发展阶段胰岛素敏感性及胰岛素分泌功能的改变,指导2型糖尿病的早期诊断。方法:57例行OGTT体检者,分为NGT、IGT、IFG+IGT、新诊断T2DM四组,并行IVGTT,采用HOMA-IR评估胰岛素敏感性,采用葡萄糖处置指数[DI1=HOMA-β/HOMA-IR,DI2=ΔI30/ΔG30/HOMA-IR,DI3=MBCI×IAI,DI4=AIR0-10/HOMA-IR]及AUCINS/HOMA-IR评估胰岛素分泌功能。结果:IGT、IFG+IGT、新诊断T2DM组HOMA-IR无统计学差异(P>0.05),均显著高于NGT组(P<0.05)。IGT、IFG+IGT、新诊断T2DM组DI1逐步降低(P<0.05);NGT、IGT组DI1无统计学差异(P>0.05)。NGT、IGT、IFG+IGT、新诊断T2DM组DI2、DI3、DI4逐步降低(P<0.05)。IFG+IGT、新诊断T2DM组OGTTAUCINS/HOMA-IR逐步降低(P<0.05),且显著低于NGT组(P<0.05);NGT、IGT组OGTTAUCINS/HOMA-IR无统计学差异(P>0.05)。结论:(1)IGT阶段胰岛素抵抗及胰岛素1相、早期相分泌功能的下降同时存在。IFG+IGT阶段胰岛素1相、早期相分泌进一步下降,并出现基础相、2相分泌的减少,胰岛素抵抗加重不明显。新诊断T2DM阶段胰岛素各相分泌进一步减少,胰岛素抵抗加重不明显。(2)在T2DM发生过程中,胰岛素分泌功能下降较胰岛素敏感性下降更为明显。(3)胰岛素抵抗及胰岛素1相、早期相分泌功能的下降是T2DM的预测因子。(4)IFG+IGT阶段应积极干预。     

糖尿病治疗药物应用及研究进展

糖尿病(DM)是以糖代谢失常的一种常见疾病,以高血糖为主要标志,其中I型糖尿病多发生于青少年,因胰岛素分泌缺乏,必须依赖胰岛素治疗。2型糖尿病多见于中老年人,主要由对胰岛素不敏感(即胰岛素抵抗)所致。自1992年第一个治疗DM的特效药物胰岛素问世以来,抗糖尿病药物的研发已取得长足进展,一些基于新的作用靶点的抗糖尿病药物已进入临床前或临床研究阶段。     

A Unique Protease Cleavage Site Predicted in the Spike Protein of the Novel Pneumonia Coronavirus (2019-nCoV) Potentially Related to Viral Transmissibility

正Dear Editor,In December 2019, a novel human coronavirus caused an epidemic of severe pneumonia(Coronavirus Disease 2019,COVID-19) in Wuhan, Hubei, China(Wu et al. 2020; Zhu et al. 2020). So far, this virus has spread to all areas of China and even to other countries. The epidemic has caused 67,102 confirmed infections with 1526 fatal cases     

Curcuminoids as inhibitors of thioredoxin reductase: A receptor based pharmacophore study with distance mapping of the active site

Curcumin is the yellow pigment of turmeric that interacts irreversibly forming an adduct with thioredoxin reductase (TrxR), an enzyme responsible for redox control of cell and defence against oxidative stress. Docking at both the active sites of TrxR was performed to compare the potency of three naturally occurring curcuminoids, namely curcumin, demethoxy curcumin and bis-demethoxy curcumin. Results show that active sites of TrxR occur at the junction of E and F chains. Volume and area of both cavities is predicted. It has been concluded by distance mapping of the most active conformations that Se atom of catalytic residue SeCYS498, is at a distance of 3.56 from C13 of demethoxy curcumin at the E chain active site, whereas C13 carbon atom forms adduct with Se atom of SeCys 498. We report that at least one methoxy group in curcuminoids is necessary for interation with catalytic residues of thioredoxin. Pharmacophore of both active sites of the TrxR receptor for curcumin and demethoxy curcumin molecules has been drawn and proposed for design and synthesis of most probable potent antiproliferative synthetic drugs.     

Comparative morphology of the carpel in the Liliaceae: Hewardieae, Petrosavieae, and Tricyrteae

The young pistils in the melanthioid tribes, Hewardieae, Petrosavieae and Tricyrteae, are uniformly tricarpellate and syncarpous. They lack raphide idioblasts. All are multiovulate, with bitegmic ovules. The Petrosavieae are marked by the presence of septal glands and incomplete syncarpy. Tepals and stamens adhere to the ovary in the Hewardieae and the Petrosavieae but not in the Tricyrteae. Two vascular bundles occur in the stamens of the Hewartlieae and Tricyrtis latifolia. Ventral bundles in the upper part of the ovary of the Hewardieae are continuous with compound septal bundles and placental bundles in the lower part. Putative ventral bundles occur in the alternate position in the Tricyrteae and putative placental bundles in the opposite. position in the Petrosavieae. The dichtomously branched stigma in each carpel of the Tricyrteae is supplied by a bifurcated dorsal bundle.     

Selection with two alleles and complete dominance

For a plant selection model with frequency-independent viabilities, fertilities and selfing rates, it is shown that apart from global fixation, for certain parameter combinations a protected polymorphism and facultative fixation (either allele may become fixed according to initial frequencies) may both occur. Facultative fixation requires different selling rates for the dominant and recessive type. Protection of the polymorphism requires resource allocation for male and female function. In this connection the problem of purely genetically caused population extinction is discussed.
For general frequency dependence and regular segregation, the chances for establishment of a completely recessive gene are compared to those of a completely dominant gene. It is proven that the process of establishment of the recessive gene, despite a fitness advantage, may be considerably endangered by drift effects if random mating prevails. The recessive gene may reach the same effectivity in establishment as a dominant gene, only if the recessive homozygote mates exclusively with its own type during the period of establishment.     

Composition and diversity of bird communities in Swedish farmland–forest mosaic landscapes

CapsuleThe amount of forest (at local and landscape scales) and occurrence of residual habitats at the local scale are shown to be the major factors influencing bird community composition in farmland–forest landscapes in central Sweden.

Aims To investigate the importance of local habitat and landscape structure for breeding birds in farmland–forest landscapes in central Sweden.

Methods Breeding birds were censused at 292 points. A detailed habitat mapping was made within 300 m of the points. Within a 300–600 m radius only two major habitats (forests and arable fields) were identified.

Results Cluster analyses of bird communities identified three site types that also differed in habitat composition: (i) partially forested sites in forested landscapes; (ii) heterogeneous sites with residual habitats in mosaic landscapes; and (iii) field-dominated farmland sites in open landscapes. A total of 19 of 25 farmland bird species (restricted to farmland or using both farmland and forest) had the highest abundance in farmland sites with mosaics of forest and farmland, while only six farmland species had the highest abundance in field-dominated sites. The bird community changed from being dominated by farmland species to being dominated by forest species (common in forest landscapes without farmland) at small proportions (10–20%) of forest at the local scale. A major difference in habitat composition between heterogeneous and field-dominated sites was the occurrence of different residual habitats (e.g. shrubby areas and seminatural grasslands). These habitats seemed to influence bird community composition more than land-use, despite covering <10% of the area. Seminatural grasslands were important for bird community composition and species-richness, but grazing seemed to be less important. Among different land-use types, cereal crops were the least preferred fields. Set-asides with tall vegetation and short rotation coppices were positively associated with species-richness of farmland birds.

Conclusion In general, the composition of the landscape was important for bird community composition, although amount and distribution of forests, occurrence of residual habitats and land-use of fields at the local scale had the strongest influence on bird community composition. The possible implications of these patterns for managing farmland–forest landscapes are discussed.     

Chemical constituents from the fruits of Rhus typhina L. and their chemotaxonomic significance

This work describes the isolation and characterization of twenty-nine compounds from the fruits of Rhus typhina L., including eleven flavonoids (1–11), eleven phenols (12–22), two pentacyclic triterpenes (23–24), two organic acids (25–26), one lumichrome (27), one courmarin (28) and one pyrimidine (29) on the basis of their spectroscopic data. Compounds apigenin (1), daidzein (4), orobol (5), 3′, 5, 5′, 7-tetrahydroxyflavanone (6), naringenin (7), butein (8), (-)-catechin (9), quercetin-3-O-α-L-(3″-O-galloyl)-rhamnoside (11), 2-hydroxybenzoic acid (13), 4-hydroxybenzaldehyde (14), vanillin (15), methyl 3,4-dihydroxybenzoate (16), 3,5-dihydroxybenzamide (18), tyrosol (19), caffeic acid (20), 3-(2,4,6-trihydroxyphenyl)-1-(4-hydroxyphenyl)-propan-1-one (21), phlorizin (22), friedelin (23), oleanolic acid (24), 4,4-dimethyl-heptanedioic acid (25), anthranilic acid (26), lumichrome (27), scoparone (28) and uracil (29) have not been recorded before in this plant. This is the first report on the occurrence of compounds 4–7, 9, 11, 13–14, 16, 18–21, 25–29 from the genus Rhus. Moreover, the chemotaxonomic significance of these isolated compounds was also summarized.