FGF21与代谢性疾病防治及其运动干预

成纤维细胞生长因子21(fibroblast growth factor 21, FGF21)属于成纤维细胞生长因子家族FGF19(fibroblast growth factor 19, FGF19)的亚型,不具有促成纤维细胞生长活性,且不与肝素特异性结合,是一种调节机体代谢的分泌型蛋白。在骨骼肌、肾脏、心脏以及血管和脂肪组织中 fgf21 表达比肝脏中高约7~10倍。FGF21可靶向脑、心脏、骨骼肌以及肾脏和肠等多种组织器官发挥作用。近来证实,FGF21已广泛应用于肝脂、糖脂代谢以及心血管疾病等代谢性疾病的预防与康复,可能成为代谢性疾病预防和康复的有效靶点之一。急性运动后骨骼肌FGF21表达显著升高,耐力运动可改善FGF21对肝脏脂肪调节的抵抗,有氧运动和抗阻运动可显著提高肝脏FGF21表达水平,单次急性运动后小鼠血清FGF21水平呈上升趋势。表明运动可显著提高循环和靶器官FGF21水平。积极开展运动介导的FGF21表达与肝脂、糖脂代谢紊乱及心血管等疾病康复研究,将为代谢性疾病预防与康复及其相关药物筛选提供新思路和新靶点。     

肝细胞FGF21——新发现的机体水平衡调控因子

成纤维细胞生长因子21(fibroblast growth factor21, FGF21)由肝细胞合成并分泌入血,可穿越血脑屏障;该分子属FGF家族,由fgf21基因编码;单次跨膜蛋白β-Klotho是FGF21的辅助受体,FGF21通过β-Klotho与FGF受体(fibroblast growth factor receptors, FGFRs)结合,使β-Klotho与FGF受体发生二聚化及自磷酸化,进而激活其信号传导。     

FGF21的代谢调控及临床应用

成纤维细胞生长因子21(fibroblast growth factor 21,FGF21)是一种新型的参与代谢调控的关键分子,对降低体重和增加机体胰岛素敏感性具有十分显著的作用。大量的临床前和临床研究结果显示,FGF21是治疗肥胖和2型糖尿病潜在的药物靶点,该文从肝脏、脂肪和神经系统等组织入手,对FGF21调控代谢的分子作用机制及临床研究进展作一综述。     

FGF23/α-Klotho信号传导的分子机制

成纤维细胞生长因子23(fibroblast growth factor 23,FGF23)是内分泌型FGFs家族中的重要一员,是一种重要的骨源性调磷激素。FGF23主要通过结合成纤维细胞生长因子受体(fibroblast growth factor receptor,FGFRs)/α-Klotho的复合物来调控肾脏中磷和维生素D的代谢。FGF23信号通路的异常与多种代谢性疾病尤其是慢性肾病(chronic kidney disease,CKD)有非常密切的关系。FGF23水平的不断上升是导致CKD患者疾病进程加快、诱发并发症甚至最终死亡的主要因素。通过对最近发表的FGF23-FGFR1c-α-Klotho三元复合物蛋白结构的分析,更好地阐明FGF23蛋白信号传导的分子机制,为相关疾病的治疗或药物开发提供新的策略。     

β-Klotho在物质能量代谢及肿瘤发展中的作用

β-Klotho(KLB)是Klotho蛋白家族中一员，主要分布在肝、脂肪、胰腺、大脑等器官和组织。KLB是一种单次跨膜蛋白质，也是成纤维细胞生长因子19/21(FGF19/21)靶向激活成纤维细胞生长因子受体(FGFRs)的关键的高亲和力共受体。KLB在FGF21/19-KLB-FGFRs通路中参与机体对血糖、脂质、体重、胆汁酸循环等物质能量的调节，参与多种组织器官中细胞增殖的调节。本文将对KLB的结构特征和分布，以及在FGF19/21-KLB-FGFRs通路中对物质能量的调节作用和肿瘤形成中的作用进行综述。     

FGF21代谢调节机制的研究进展

代谢综合征在全世界广泛流行，我国代谢综合征的发病率已达24.2%。代谢综合征是糖尿病和心血管疾病发病的危险因素。成纤维细胞生长因子21(fibroblast growth factor 21,FGF21)是一种代谢信号调节蛋白，外源性FGF21类似物具有降低血糖、血脂和体重等多种药理作用，但FGF21调节代谢的机制目前仍不明确，可能涉及脂联素依赖途径、非脂联素依赖途径和大脑中枢调节途径等。临床研究发现，高水平的FGF21与代谢综合征的发生、发展和不良预后密切相关，存在“FGF21抵抗”。本文旨在概述FGF21代谢调节机制的最新研究进展，以期为代谢性疾病的临床诊疗和研究提供新思路。     

成纤维细胞生长因子21的研究进展*

成纤维细胞生长因子21（fibroblast growth factor 21,FGF21）是一种主要的脂肪代谢调节因子,主要在肝脏中表达;FGF21有助于肝脏的脂肪代谢以及生酮反应,可以促进脂肪细胞摄取葡萄糖,促进胰岛素分泌,延缓肿瘤的发展等功能。近年来研究过程中发现,FGF21可以用于糖尿病和降血脂等其他代谢疾病治疗。主要对FGF21的特点,作用机理及其分子机制进行了概括,并对FGF21在糖尿病治疗和降血脂方面的研究进行了综述。     

FGF21对能量代谢的调控

成纤维细胞生长因子21（fibroblast growth factor 21,FGF21）作为一种不依赖胰岛素的血糖调节因子,目前已被看做是治疗2型糖尿病的一个潜在的新型治疗因素.大量鼠类及灵长类动物模型的实验结果显示：FGF21可通过作用于脂肪组织及胰腺来降低血糖和甘油三酯含量,从而预防饮食诱导的肥胖及胰岛素抵抗.此外,FGF21也被证明可作为一种主要的内源性调控子,在禁食和酮症时起着关键的调控作用.然而,一些临床观察实验的结果表明,临床观察实验与动物模型实验之间虽然具有一定的相似性,但也存在很多不同,因而目前FGF21在人体中的生理学作用仍不明确.     

FGFs/FGFRs系统对骨调节的研究进展

成纤维细胞生长因子家族(fibroblast growth factors,FGFs)及其受体FGFRs系统影响骨骼发育和形成过程,FGF与细胞表面FGFR结合,激活信号通路调控多种细胞生长、分化和凋亡。骨是FGF的重要靶器官,研究表明FGFs/FGFRs系统对骨组织成骨细胞、破骨细胞、软骨细胞的增殖和分化起重要调控作用,本文就FGFs/FGFRs系统对骨组织调节研究进展进行综述。     

成纤维细胞生长因子9在抑郁症及其运动干预调节中的作用

成纤维细胞生长因子9（fibroblast growth factor 9, FGF9）是成纤维细胞生长因子（fibroblast growth factor,FGF）家族成员之一,属于一种自分泌或旁分泌生长因子。在脑组织中,FGF9主要表达于海马和皮质区,具有促进细胞增殖和维持细胞存活的功能。研究发现,FGF家族在抑郁症患者的多个脑区出现表达紊乱,FGF9在抑郁行为中扮演着负调控角色,但其介导抑郁行为的分子机制尚不清楚。本文综述了FGF9及其家族成员在抑郁中的作用; 围绕其受体（FGFR）信号在中枢神经系统中的功能特点,深入分析FGF9调节抑郁行为中的作用机制;结合运动抗抑郁的神经营养假说,提出经由FGFR/GSK3β/β-catenin通路的FGF信号,可能介导抑郁症的运动干预机制的假设。这些将为FGF9介导抑郁行为和运动抗抑郁的有关研究提供理论的基础和探索的思路。     

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.