miR-486通过靶基因Pten/Foxo1调控小鼠肝细胞脂质代谢

该文研究了mi R-486在小鼠肝细胞内是否可通过调控其靶基因Pten(phosphatase and tensin homolog,同源性磷酸酶–张力蛋白)/Foxo1(forkhead box O1,叉头转录因子)进而影响甘油三酯(triglyceride,TG)和极低密度脂蛋白(very low density lipoprotein,VLDL)的合成。采用腺病毒载体感染小鼠肝癌细胞Hepa1-6,并测定靶基因Pten/Foxo1表达及VLDL和TG变化。腺病毒载体感染mi R-486的模拟剂(mimic)和抑制剂(antago)至细胞株Hepa1-6,Ad-mi R-486 mimic组mi R-486水平显著增加(P0.001),PTEN/Fox O1的m RNA和蛋白质水平显著降低,细胞内VLDL含量显著降低(P0.01),TG含量明显增加(P0.05);反之,Ad-mi R-486 antago组mi R-486表达水平受到抑制,PTEN/Fox O1的m RNA和蛋白质水平显著增加(P0.01),且细胞内VLDL含量显著增加(P0.01),TG含量明显降低(P0.05)。该研究结果表明,mi R-486可能通过调节Pten/Foxo1来影响细胞内的VLDL和TG生成。     

P13K／Akt及其靶蛋白FOXO1与非酒精性脂肪性肝病

FOXO转录因子是Forkhead蛋白大家族的一个亚群,在人类的4个同源基因中包括Fox01、Fox02、Fox03a和Fox04。FoxO蛋白质通过丝氨酸或苏氨酸以及赖氨酸残基的磷酸化和乙酰化等后转录修饰后而发挥作用。其中Foxol是含有高度保守DNA结合位点的核转录蛋白,其主要功能是磷脂酰肌醇3。激酶（P13K）／蛋白激酶B（Ala）的底物,在胰岛素信号转导中起负性调节作用,Foxol通过介导胰岛素依赖性微粒体甘油三酯转运蛋白（MTP）的表达,影响肝脏装配和分泌极低密度脂蛋白（VLDL）,维持脂代谢稳定。在胰岛素抵抗和脂肪肝状态下,肝细胞核内Foxol表达明显升高,引起高甘油三酯血症和脂肪肝。有针对性的干预P13姒啵t及Foxol的表达,可能从分子机制上为非酒精性脂肪肝的防治提供广阔前景。     

苏子油对肥胖大鼠肝脏极低密度脂蛋白合成关键基因表达的影响

目的探究富含n-3多不饱和脂肪酸(polyunsaturated fatty acid,PUFA)的苏子油高脂饮食对肥胖大鼠肝脏极低密度脂蛋白(very low density lipoproteins,VLDL)合成关键基因表达的影响。方法造模期:雄性SD大鼠随机分为2组,对照组(normal control group,NC)给予普通日粮,高脂组(high fat group,HF)给予高脂纯合日粮诱发肥胖大鼠模型;干预期:将肥胖大鼠随机分为4组:持续高脂组(consistent high fat group,CHF)和三个苏子油(perilla oil,PO)替代组,根据PO替代CHF中猪油比例的不同将替代组分为20%PO、50%PO、100%PO,4周后测定大鼠血清甘油三酯(tryglyceride,TG)水平;western blotting方法检测肝脏VLDL合成关键蛋白微粒体甘油三脂转运蛋白(microsomal triglyceride transfer protein,MTP)和载脂蛋白B(apolipoprotein B,APOB)蛋白表达;real-time PCR方法检测肝脏Mtp、Apob mRNA表达。结果肥胖大鼠血清TG水平显著高于NC组,并且有严重的脂肪沉积,肝脏MTP和APOB的mRNA、蛋白表达均有不同程度的降低;干预4周后,与CHF组相比,各PO替代组大鼠血清TG水平明显降低,病理切片结果显示肝脏脂肪沉积有明显改善,并且肝脏MTP和APOB的mRNA、蛋白表达均有不同程度的升高。结论不同比例PO替代均能促进肥胖大鼠肝脏VLDL合成与分泌,改善肝脏脂肪沉积,并且PO促进Mtp mRNA、蛋白表达具有剂量依赖性。     

甘油三酯代谢对紫外线照射后HaCaT细胞的影响及机制研究

目的:研究甘油三酯代谢过程对紫外线照射后HaCaT细胞的影响及机制研究。方法:HaCaT细胞分为4组,分别为对照组、紫外线照射组、紫外线照射并予甘油三酯组、紫外线照射并予甘油三酯合成酶抑制剂TOFA组,查看MMP-1、COX-2和IL-1β在mRNA及蛋白水平上的变化,并查看其上游转录因子NF-κB/IκB的表达情况。结果:1)甘油三酯可以抑制紫外线照射后细胞外基质溶解蛋白MMP-1的表达(P0.05)。2)甘油三酯可以抑制紫外线照射后炎症相关蛋白COX-2和IL-1β的表达(P0.05)。3)甘油三酯合成酶抑制剂TOFA可以增强外线照射后细胞外基质溶解蛋白MMP-1以及炎症相关蛋白COX-2和IL-1β的表达(P0.05)。4)其调节过程可能通过NF-κB/IκB信号传导通路实现(P0.05)。结论:甘油三酯对紫外线的照射后的HaCaT细胞有保护作用,若抑制其代谢将减弱其保护作用。     

载脂蛋白CⅢ与高甘油三酯血症

载脂蛋白CⅢ(apolipoprotein CⅢ,apoCⅢ)能抑制脂蛋白脂酶的活性及肝脏对富含甘油三酯的脂蛋白(triglyceride-rich lipoproteins,TRLs)残体的摄取,在调节TRLs代谢中具有重要作用。自然发生的APOC3基因突变对人血浆apoCⅢ和甘油三酯浓度均有影响。小鼠过表达人apoCⅢ可产生严重高甘油三酯血症,而APOC3基因敲除小鼠则表现为明显的低甘油三酯血症。除遗传因素外,环境及内分泌因素也会对apoCⅢ的代谢产生影响,这使得以apoCⅢ代谢为靶点来优化脂代谢紊乱和心血管疾病的治疗(尤其在代谢综合征患者中)显得尤为重要。     

新的脂代谢调控基因——货运受体Surf4

Surf4属于Surfeit基因簇成员，在内质网膜中广泛表达和定位，作为货运受体参与多种蛋白质在内质网与高尔基体之间转运。新近发现，Surf4参加载脂蛋白B (Apo B)转运，进而影响极低密度脂蛋白(VLDL)前体的转运，在极低密度脂蛋白分泌中发挥调控作用，敲除肝Surf4能大幅度降低血浆总胆固醇和甘油三酯水平，不会造成肝的脂质堆积和病理改变。这些研究结果表明，Surf4可能是治疗心血管疾病的潜在药物靶标，在心血管疾病的发生发展及其诊疗中具有潜在的临床应用价值。本文就Surf4的主要生理功能，尤其是作为货运受体参与载脂蛋白B在内质网与高尔基体之间转运的货运功能，以及其参与调控脂代谢并与脂代谢相关疾病关系的研究进展进行系统阐述，以期促进对Surf4的认知，并为其深入研究和转化应用提供新思路，为降脂治疗提供新方法，造福于更多高脂血症患者。     

肝脏在高甘油三酯血症中的作用

高甘油三酯血症(HTG)是心脑血管疾病的独立危险因子。肝脏在甘油三酯的合成和分解代谢过程中起着十分重要的作用,肝脏甘油三酯合成过剩或／和甘油三酯分解障碍,均能使血浆甘油三酯升高,形成HTG。肝脏甘油三酯合成过剩的因素包括一些参与甘油三酯合成的酶活性增加;甘油三酯分解代谢延缓的因素包括Angpt13和肝脏X受体(LXR)功能加强,肝脂酶活性受抑制,ApoE2和ApoCⅢ含量升高;既能使甘油三酯合成增加,也能使甘油三酯分解代谢延缓的因素包括餐后,ApoAⅡ与胆固醇酯转移蛋白(CETP)的协同作用等。     

环氧二十碳三烯酸抑制剂通过AKT/FoxO1信号通路抑制棕榈酸诱导的心肌细胞凋亡

目的观察14,15-环氧二十碳三烯酸(14,15-epoxyeicosatrienoic acid,14,15-EET)及其抑制剂14,15-环氧二十碳-5(Z)-烯酸(14,15-epoxyeicosa-5(Z)-enoic acid,14,15-EEZE)对棕榈酸(palmitate acid,PA)诱导心肌细胞凋亡的作用及机制。方法 14,15-EET和14,15-EEZE单独或联合作用于PA诱导后的H9c2细胞,采用噻唑蓝比色法检测细胞增殖,流式细胞术检测细胞凋亡,免疫印迹法测定细胞p-AKT和p-Fox O1蛋白表达水平。结果流式细胞术检测显示,PA诱导下H9c2细胞凋亡率上升,14,15-EET的作用可降低细胞凋亡率,而加用14,15-EEZE使细胞凋亡率上升,14,15-EEZE的单独作用也可提高PA诱导下H9c2细胞的凋亡率。免疫印迹分析显示,PA可降低H9c2细胞p-AKT和p-Fox O1蛋白表达水平,14,15-EET的作用可使p-AKT和p-Fox O1蛋白表达水平明显上升,而加用14,15-EEZE后p-AKT和p-Fox O1的蛋白表达水平明显下降,14,15-EEZE的单独作用可使PA诱导下H9c2细胞的p-AKT和p-Fox O1的表达水平明显下降。结论 14,15-EET可能通过促进AKT/Fox O1信号通路活性抑制棕榈酸诱导的H9c2细胞凋亡,而其抑制剂14,15-EEZE可能通过抑制AKT/Fox O1信号通路活性抑制14,15-EET的抗棕榈酸诱导H9c2心肌细胞凋亡的作用。     

载脂蛋白CⅢ致动脉粥样硬化的新机制

载脂蛋白CⅢ(apolipoprotein CⅢ,apo CⅢ)在致动脉粥样硬化中有直接作用。首先,apo CⅢ激活血液循环单核细胞,细胞表面黏附分子β1整合素表达上调,促进单核细胞与血管内皮发生黏附;其次,apo CⅢ诱导血管内皮细胞表达血管细胞黏附分子-1(vascular cell adhesion molecule-1,VCAM-1)和细胞间黏附分子-1(intercellular cell adhesion molecule-1,ICAM-1),募集循环中的单核细胞并发生黏附;最后,apo CⅢ诱导血管内皮细胞发生胰岛素抵抗,导致内皮功能紊乱,引发内皮炎症和动脉硬化。     

ANGPTL8调控糖代谢作用机制研究

探讨ANGPTL8在胰岛素作用下对人肝细胞糖代谢影响及可能的作用机制。利用尾静脉水动力转染证实在小鼠肝脏过表达ANGPTL8可提高进食期糖耐受;在Hep G2细胞中利用q PCR检测进食的主要调控因素胰岛素、葡萄糖等对ANGPTL8表达影响,发现单独的葡萄糖或胰岛素对ANGPTL8表达影响不明显,而葡萄糖和胰岛素组合可显著促进ANGPTL8表达;利用Western blotting分析在ANGPTL8敲除(ANGPTL8-/-)和ANGPTL8稳定过表达(ANGPTL8++)的Hep G2细胞中胰岛素介导PI3K/AKT信号通路蛋白及其蛋白磷酸化表达差异,结果显示ANGPTL8可上调胰岛素介导的AKT信号通路中AKT、GSK-3β、Fox O1蛋白磷酸化;PAS染色分析ANGPTL8可促进胰岛素介导的糖原合成。     

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.     

The structure, reproduction and taxonomy of Vidalia and Osmundaria (Rhodophyta, Rhodomelaceae)

Comprises species occurring mostly in subtidal habitats in tropical, subtropical and warm-temperate areas of the world. An analysis of the type species, V. spiralis (Sonder) Lamouroux ex J. Agardh, a species from Australia, establishes basic characters for distinguishing species in the genus. These characters are (1) branching patterns of thalli, (2) flat blades that may be spiralled on their axis, (3) width of the blade, (4) primary or secondary derivation of sterile and fertile branchlets and (5) position of sterile and fertile branchlets on the thalli. Application of the latter two characters provides an important basic method for separation of species into three major groups. Osmundaria , a genus known only in southern Australia, was studied in relation to Vidalia , and its separation from the Vidalia assemblage is not accepted. Species of Vidalia therefore are transferred to the older genus name, Osmundaria. Two new species, Osmundaria papenfussii and Osmundaria oliveae are described from Natal. Confusion in the usage of the epithet, Vidalia fimbriala Brown ex Turner has been clarified, and Vidalia gregaria Falkenberg, described as an epiphyte on Osmundaria pro/ifera Lamouroux, is revealed to be young branches of the host, Osmundaria prolifera.     

New or rare chromosome counts in Artemisia L. (Asteraceae, Anthemideae) and related genera from Kazakhstan

Fifteen chromosome counts of six Artemisia taxa and one species of each of the genera Brachanthemum, Hippolytia, Kaschgaria, Lepidolopsis and Turaniphytum are reported from Kazakhstan. Three of them are new reports, two are not consistent with previous counts and the remainder are confirmations of very scarce (one to four) earlier records. All the populations studied have the same basic chromosome number, x = 9, with ploidy levels ranging from 2x to 6x. Some correlations between ploidy level, morphological characters and distribution are noted.     

肝癌中HBV和HCV基因和抗原的分布及意义

采用原位分子杂交方法检测HCV RNA及HBV X基因;采用免疫组织化学方法研究HCV核心抗原,非结构区C33c抗原及HBxAg在肝细胞肝癌中的定位及分布.结果表明(1)HCV RNA、HBV X基因在肝细胞肝癌组织检出率分别为40%(55/136)和82%(112/136).HCV RNA定位于癌细胞的胞浆内,阳性细胞呈散在、灶状及弥漫分布三种形式;HBV X基因在肝癌细胞中的分布呈胞浆型、核型及核浆型,阳性细胞也呈上述三种分布形式;(2)HCV C33c抗原、核心抗原在肝细胞肝癌中的阳性率为81%(133/164)及86%(141/164).C33c抗原定位于癌细胞及肝细胞的胞浆内;核心抗原既定位于癌细胞核中,又可定位于胞浆中.C33c抗原阳性细胞以灶状分布为主;而核心抗原阳性细     

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.