免疫检查点阻断剂促进T细胞应答的影响因素

抑制免疫调节检查点,比如PD-1/PD-L1与CTLA-4,是癌症免疫治疗的前沿科学。然而这样的免疫疗法只对少部分患者的癌症形成有效。本文通过分析肿瘤的成瘤原因、微环境及其自体相关因素后发现这些因素均会导致免疫检查点阻断剂在体内失去T细胞免疫应答。因此,本文描述了免疫系统与宿主肠道微生物群可调控癌症免疫治疗的应答,并且在使用免疫检查点阻断剂的同时或之前调节肠道微生物群可以优化治疗效果。     

肠道微生态与白血病的研究进展

微生物群与人体的健康密切相关,约20%的恶性肿瘤与微生态失调有关。研究显示肠道微生物可以调节造血,其与血液系统疾病的关系逐渐得到研究者的关注,肠道微生物参与白血病的发生发展,影响白血病的治疗效果。较早的暴露于微生物群是儿童白血病的保护性因素,化疗会引起肠道微生物紊乱,肠道微生物可以改变化疗药物的疗效和毒性,其多样性和组成能够预测化疗相关的并发症,通过微生态制剂和粪菌移植可以减少化疗相关的并发症。本文从肠道微生态与白血病及其并发症的关系,以及调节肠道微生态对白血病的影响两个方面的最新进展进行综述。     

肠道微生物群与药物相互作用的研究进展

药物的代谢是机体对药物处置过程的关键步骤,而肠道作为机体中重要的微生态系统,其在药物代谢方面的作用至关重要。肠道微生物群能够对各种药物等外源化合物进行生物转化、积累,并改变这些物质的活性和毒性,从而影响宿主机体对它们的反应。肠道微生物群与药物之间的相互作用相当复杂,亟待更多更加深入、全面的发掘和研究。近年来,随着人们对肠道微生物群代谢及其与药物互作关系,肠道菌-宿主共代谢认知的不断深化,越来越多的研究表明肠道微生物在药代动力学中扮演重要角色。本文通过调研、整理、归纳和总结国内外相关文献资料,对机体肠道微生物的分类、功能,几种常用药物对肠道微生物的影响以及肠道菌群对药物的代谢作用效果与几个主要的机制进行了梳理和综述,并讨论了微生物和药物之间的双向互作。有利于增进对微生物群影响药物疗效及其代谢途径和机制的了解,提高调控肠道微生物改善治疗的可能性,为指导临床合理用药、精准用药、个体化治疗、药物的评价和新药研发等提供科学参考。     

肠道微生物群对肺部免疫微环境稳态影响的研究进展

肠道微生物群是与宿主共生的最大的微生态系统的重要组成部分,它们通过调节宿主的内分泌、代谢、神经和免疫微环境影响人体的多种基本功能。近年来,肠道微生物群对机体局部和远端免疫器官的影响引起了科学家们的广泛关注。肠道微生物和肺之间的相互作用被称为“肠-肺轴”,对肺部免疫微环境稳态的维持至关重要。研究表明,肠道微生物群失调与哮喘、肺炎和囊性纤维化等多种肺部疾病密切相关。本文将对肠道微生物群对肺部免疫微环境稳态的影响及在多种肺部疾病中的作用进行阐述,为临床通过调整肠道微生物群来治疗肺部疾病和维持肺部免疫微环境稳态提供理论依据。     

肠道菌群与肿瘤化疗之间的互作关系

化疗药物的应用是当今治疗恶性肿瘤的主要方法之一。近年来,随着对人体微生物研究的不断深入,肠道菌群在疾病的诊断和治疗中发挥越来越重要的作用。肠道菌群具有调节炎症反应、维持肠道屏障功能稳定和调节免疫反应的作用,其菌株可能作为一种潜在的肿瘤诊断标志物。肠道菌群与化疗药物之间的关系越发紧密,如肠道菌群如何影响化疗药物的作用效果,恶心、呕吐、便秘、骨髓抑制等化疗药物的毒副作用对肠道菌群又有何种影响,应用益生菌后肠道菌群如何变化以及对化疗药物毒副作用有何影响。因此,本文回顾了化疗药物与肠道菌群相互作用研究的进展,希望为国内学者提供肠道菌群和癌症化疗之间关系的理论基础,并为治疗癌症提供新的研究思路。     

死亡受体信号通路耐受机制及肿瘤治疗CSCD

死亡受体介导的凋亡通路是治疗肿瘤的理想方案。凋亡通路中具有复杂的调控机制,控制细胞的生死存亡。其中有多类抗凋亡因子,致使肿瘤细胞对凋亡信号耐受,使得凋亡在肿瘤治疗领域的应用受限。临床前体外细胞及裸鼠研究发现,单独靶向这些死亡受体或抗凋亡因子的药物或与传统化疗联合可以有效引起肿瘤细胞凋亡,但临床II期实验没有明显治疗效果。本综述总结分析多种抗凋亡因子产生的耐受机制以及靶向药物的研究现状,提出同时靶向死亡受体、c-FLIP及IAP是治疗肿瘤的理想方案。     

死亡受体信号通路耐受机制及肿瘤治疗

死亡受体介导的凋亡通路是治疗肿瘤的理想方案。凋亡通路中具有复杂的调控机制,控制细胞的生死存亡。其中有多类抗凋亡因子,致使肿瘤细胞对凋亡信号耐受,使得凋亡在肿瘤治疗领域的应用受限。临床前体外细胞及裸鼠研究发现,单独靶向这些死亡受体或抗凋亡因子的药物或与传统化疗联合可以有效引起肿瘤细胞凋亡,但临床II期实验没有明显治疗效果。本综述总结分析多种抗凋亡因子产生的耐受机制以及靶向药物的研究现状,提出同时靶向死亡受体、c-FLIP及IAP是治疗肿瘤的理想方案。     

肠道菌群与孤独症发病关系的研究进展

肠道菌群与人体的健康或疾病状态息息相关,在营养摄取、免疫与内分泌调节、药物代谢中都起着重要的作用,并能通过微生物群-肠-脑轴影响中枢神经系统的发育与功能。流行病学数据显示,肠道菌群的组成变化与多种中枢系统疾病相关。其中,孤独症是一类以社交障碍、刻板行为、兴趣狭隘为主要临床特征的神经发育障碍性疾病。由于孤独症与胃肠道疾病之间联系紧密且其发病率正逐年上升,人们愈发关注肠道菌群在孤独症发病过程中的作用。研究发现,肠道菌群能够影响孤独症患者的中枢神经系统发育,导致异常的行为表现并诱发胃肠症状等。本文总结了影响肠道菌群组成的因素,并从微生物群-肠-脑轴的角度讨论了肠道菌群影响孤独症的方式,同时介绍了孤独症患者肠道菌群疗法的有效性与临床前景。     

microRNA对肺癌化疗耐药性影响的研究进展

化疗耐药性是肺癌治疗的主要挑战之一,导致许多患者的化疗方案无效,并延误了接受合适治疗的时机。因此,研究肺癌化疗耐药性的机制是至关重要的。microRNA (miRNA)作为小分子片段RNA,参与了许多生命过程的调节,并在细胞耐药性产生过程中发挥重要的作用。研究表明,在化疗过程中,miRNAs可以通过降低多种药物耐药性相关基因的表达或促进细胞逃逸凋亡,参与耐药性的调节。然而,对于miRNAs介导的化疗耐药性产生机制的研究还不完善。现有研究表明,特定miRNAs的改变可能与多种癌症的获得性耐药相关,并调节肺癌细胞对化疗药物的敏感性。对miRNAs在肺癌耐药性中的作用及研究进展进行系统阐述。     

放射性药物在肿瘤靶向治疗中的应用

放射性药物指供临床诊断或治疗用的放射性核素制剂或其标记化合物。放射性核素靶向治疗是利用对肿瘤细胞具有特异高亲和力的分子载体将核素定向导入特定的肿瘤组织,对肿瘤进行治疗。与传统的放疗和化疗相比,其具有选择性杀伤肿瘤细胞的特点。随着核医学的发展,SPECT/CT、PET/CT的普及,新靶点的发现和新型放射性药物的研发,利用放射性药物进行靶向治疗在肿瘤临床治疗中占据的地位越来越重要。本文简述了放射性药物的分类、组成及特点;综述了针对肿瘤相关抗原的放射免疫药物在非霍奇金淋巴瘤、结直肠癌和前列腺癌中的应用;受体介导的放射性核素药物在治疗神经内分泌肿瘤、前列腺癌和乳腺癌中的临床应用以及基于基因修饰的放射性药物在肿瘤靶向治疗中的实验研究进展。最后总结了放射性药物在肿瘤靶向治疗中的应用前景与面临的挑战,以期为靶向治疗肿瘤的放射性药物的开发和临床应用提供一些参考。     

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.