肿瘤抗原基因转染的DC疫苗研究进展

树突状细胞是机体内最重要、功能最强的专职抗原递呈细胞,是抗肿瘤免疫的最好佐剂。将不同形式肿瘤抗原负载的DC制成疫苗,可以在体内诱导特异性杀伤性T细胞（CTL）的生成,激发人体有效的特异性抗肿瘤免疫功能。其中肿瘤抗原原因转当的DC疫苗具有很多独特的优点,可望作为一种新型肿瘤疫苗用于肿瘤的防治。本文主要就其作用特点、体内应用的可行性及抗肿瘤作用效果的实验研究进展等方面作一综述。     

基于树突状细胞的抗肿瘤疫苗研究进展

树突状细胞(dendritic cells, DCs)是一类多功能抗原提呈细胞,在固有免疫和适应性免疫应答的启动及调控中发挥着重要作用。目前,大量研究表明机体可通过多种方式调动和调节DC的功能,从而增强其抗肿瘤作用。其中,以肿瘤抗原、肿瘤细胞裂解物或全肿瘤细胞作为刺激物致敏DC得到的DC疫苗,在临床前研究中展示出了可观的抗肿瘤效应,部分DC疫苗已进入临床试验阶段。该文将重点对基于DC的肿瘤疫苗制备方法、临床前及临床研究进展进行综述。     

肿瘤?鄄树突状细胞融合疫苗研究进展

树突状细胞(DC)是功能最强的专职抗原呈递细胞,在抗肿瘤免疫方面发挥着重要的作用．以DC为基础的肿瘤疫苗的研究发展迅速,其中效果最好的是DC/肿瘤融合细胞疫苗——不仅具有DC的抗原呈递功能,也持续产生内源性抗原肽．DC/肿瘤融合细胞疫苗不仅在动物实验中进行了大量的研究,而且已经进入了Ⅰ/Ⅱ期临床试验,结果表明,融合细胞能有效地诱导肿瘤特异性T淋巴细胞反应,病人也能很好地耐受．就DC/肿瘤融合疫苗的研究进展进行综述,并对目前研究中存在的问题作了客观的分析．     

p53转染黑色素瘤细胞修饰的树突状细胞疫苗体外抗肿瘤作用的研究

利用野生型p53质粒转染黑色素瘤B16细胞,反复冻融法提取p53修饰的肿瘤抗原(p53-Ag),将抗原体外冲击同基因小鼠骨髓来源的树突状细胞(dendritic cells,DC)制备特异性DC肿瘤疫苗;观察DC诱导的淋巴细胞增殖反应和细胞毒性T淋巴细胞(cytotoxic T lymphocytes,CTL)对黑色素瘤细胞的细胞毒效应,分析其诱导肿瘤抗原特异性免疫应答的机制。结果显示,p53-肿瘤抗原冲击的DC可显著刺激淋巴细胞增殖,其诱导的CTL效应对肿瘤细胞也有很好的杀伤效果。     

树突状细胞的靶向抗肿瘤治疗进

树突状细胞(dendritic cell,DC)是目前已知体内最强的抗原提呈细胞(ARC),其在肿瘤免疫中具有重要的作用.DC的靶向抗肿瘤治疗成为当今肿瘤免疫治疗的研究热点.本文就DC的抗肿瘤机制、DC基因修饰策略及DC疫苗的临床治疗进展进行综述.     

树突状细胞与抗肿瘤免疫

提高免疫系统对肿瘤的杀伤能力是肿瘤免疫学上目的,随着对免疫肿瘤抗原的了解以及对T细胞免疫反应和肿瘤逃逸机制的进一步认识。方面军一目的已取得了进展,体内含量稀少的抗原递呈细胞-树突状细胞（DC8）是这些机制的关键。体外从外周血祖细胞诱导扩增这些细胞为肿瘤治疗开辟了新纪元。DC8作为肿瘤疫苗,在B细胞淋巴瘤、黑色素瘤、前列腺癌等病人身上已有了一定的疗效。     

树突状细胞和癌症的免疫学治疗

树突状细胞(dendritc cells,DC)是一种抗原提呈细胞,能特异地引发和调控机体免疫。它具有抗原呈现功能而不损害免疫系统,不仅能够激活CD4^ 辅助T细胞和CD8^ 细胞毒性T细胞,还能活化B细胞和自然杀伤细胞。已有的研究让人们看到了癌症疫苗的希望,但还处于早期阶段,有许多尚未确定的因素。因此有关DC疫苗用于对肿瘤的保护性和治疗性免疫还有待于进一步的研究。     

树突状细胞肿瘤疫苗的研究进展

树突状细胞(DC)是目前发现的抗原提呈功能最强的专职抗原提呈细胞。大量实验已证明DC疫苗在抗肿瘤免疫中发挥着重要的作用。随着分子生物学、免疫学、基因工程技术的发展,各种DC疫苗和DC细胞的治疗应运而生,发展迅速。简要综述了DC的生物学特性、DC与肿瘤发生发展的关系、DC抗原的负载方法及其在临床实验中的应用,以为进一步的基础研究和临床实验提供参考。     

树突状细胞在抗感染免疫研究中的最新进展

树突状细胞(Dendritic cell,DC)是体内功能最强的抗原提呈细胞,也是介导机体固有免疫应答和适应性免疫应答的桥梁,其作用也越来越受到科研工作者的关注,而树突状细胞体外培养技术的发展成熟,为设计和发展DC依赖性疫苗提供了科学依据,也为感染性和肿瘤性疾病的预防和治疗展示了很好的应用前景。因此,对树突状细胞抗感染免疫方面研究的最新进展做一综述。     

次级淋巴组织趋化因子在肿瘤疫苗中的应用

次级淋巴组织趋化因子(secondary lymphoid tissue chemokine,SLC)是体内重要的CC亚族趋化成员,能趋化并活化免疫效应细胞,具有抗肿瘤免疫效应.利用SLC的生物学活性用于肿瘤疫苗的研究已取得较大进展,在肿瘤预防和治疗中具有广泛应用前景.该文介绍SLC基因修饰的瘸苗或树突状细胞(dentritic cell,DC),SLC联合协同细胞因子和共刺激分子的疫苗,SLC基因修饰的肿瘤抗原疫苗等的研究进展.     

Role for dopamine in malonate-induced damage in vivo in striatum and in vitro in mesencephalic cultures

Defects in mitochondrial energy metabolism have been implicated in the pathology of several neurodegenerative disorders. In addition, the reactive metabolites generated from the metabolism and oxidation of the neurotransmitter dopamine (DA) are thought to contribute to the damage to neurons of the basal ganglia. We have previously demonstrated that infusions of the metabolic inhibitor malonate into the striata of mice or rats produce degeneration of DA nerve terminals. In the present studies, we demonstrate that an intrastriatal infusion of malonate induces a substantial increase in DA efflux in awake, behaving mice as measured by in vivo microdialysis. Furthermore, pretreatment of mice with tetrabenazine (TBZ) or the TBZ analogue Ro 4-1284 (Ro-4), compounds that reversibly inhibit the vesicular storage of DA, attenuates the malonate-induced DA efflux as well as the damage to DA nerve terminals. Consistent with these findings, the damage to both DA and GABA neurons in mesencephalic cultures by malonate exposure was attenuated by pretreatment with TBZ or Ro-4. Treatment with these compounds did not affect the formation of free radicals or the inhibition of oxidative phosphorylation resulting from malonate exposure alone. Our data suggest that DA plays an important role in the neurotoxicity produced by malonate. These findings provide direct evidence that inhibition of succinate dehydrogenase causes an increase in extracellular DA levels and indicate that bioenergetic defects may contribute to the pathogenesis of chronic neurodegenerative diseases through a mechanism involving DA.     

2018年中国植物科学若干领域重要研究进展

2018年中国植物科学继续呈现快速发展的态势, 我国科学家在国际植物科学主流学术刊物发表论文数量大幅增加, 取得了多项具有重要影响的成果。调控植物生长-代谢平衡实现可持续农业发展入选2018年度中国科学十大进展; 中国被子植物区系进化历史研究入选2018年度中国生命科学十大进展。以水稻为代表的农作物和果蔬等经济作物研究在国际上已呈现出明显的优势, 若干领域已从“追赶”状态跨越到“领跑”地位。该文对2018年中国科学家在植物科学若干领域取得的重要研究成果进行了概括性评述, 旨在全面追踪和报道当前中国植物科学领域的发展前沿和热点, 展示中国科学家所取得的杰出成就。     

2017年中国植物科学若干领域重要研究进展

2017年中国植物科学继续保持高速发展态势, 重大成果频出, 具体表现在中国植物学家在国际顶级学术期刊发表的文章数量平稳上升。中国植物科学领域的研究工作者成果精彩纷呈, 如新型广谱抗病机制的发现、水稻广谱抗病遗传基础及机制和疫霉菌诱发病害成灾机制研究等。2017年中国生命科学领域十大进展评选中, 有两项植物科学领域的研究成果入选。水稻生物学、进化与基因组学和激素生物学等领域学科发展突出。另外, 值得一提的是, 长期从事高等植物与代谢途径调控分子网络研究和水稻品种设计育种的李家洋院士的研究成果“水稻高产优质性状形成的分子机理及品种设计”荣获2017年国家自然科学一等奖。这一具有重大国际影响的开创性贡献标志着中国植物科学在该领域的国际科学前沿居于引领和卓越地位。该文对2017年中国本土科学家在植物科学若干领域取得的重要研究成果进行了系统梳理, 旨在全面追踪和报道当前中国植物科学领域发展的最新前沿动态, 与广大读者共同分享我国科学家所取得的辉煌成就。     

我国葫芦科植物离体培养研究进展

葫芦科植物包括多种瓜类蔬菜,对其进行离体培养研究具有重要的理论和实践意义。综述了国内在葫芦科植物器官培养、体细胞胚胎发生、花药培养、原生质体培养和体细胞杂交及离体遗传转化等方面取得的研究进展,并对葫芦科植物离体培养、遗传转化与育种的前景作了展望。     

SSTR5 ablation in islet results in alterations in glucose homeostasis in mice

Somatostatin (SST) peptide is a potent inhibitor of insulin secretion and its effect is mediated via somatostatin receptor 5 (SSTR5) in the endocrine pancreas. To investigate the consequences of gene ablation of SSTR5 in the mouse pancreas, we have generated a mouse model in which the SSTR5 gene was specifically knocked down in the pancreatic beta cells (betaSSTR5Kd) using the Cre-lox system. Immunohistochemistry analysis showed that SSTR5 gene expression was absent in beta cells at three months of age. At the time of gene ablation, betaSSTR5Kd mice demonstrated glucose intolerance with lack of insulin response and significantly reduced serum insulin levels. Insulin tolerance test demonstrated a significant increase of insulin clearance in vivo at the same age. In vitro studies demonstrated an absence of response to SST-28 stimulation in the betaSSTR5Kd mouse islet, which was associated with a significantly reduced SST expression level in betaSSTR5Kd mice pancreata. In addition, betaSSTR5Kd mice had significantly reduced serum glucose levels and increased serum insulin levels at 12 months of age. Glucose tolerance test at an older age also indicated a persistently higher insulin level in betaSSTR5Kd mice. Further studies of betaSSTR5Kd mice had revealed elevated serum C-peptide levels at both 3 and 12 months of age, suggesting that these mice are capable of producing and releasing insulin to the periphery. These results support the hypothesis that SSTR5 plays a pivotal role in the regulation of insulin secretion in the mouse pancreas.     

2018年中国植物科学若干领域重要研究进展

2018年中国植物科学继续呈现快速发展的态势, 我国科学家在国际植物科学主流学术刊物发表论文数量大幅增加, 取得了多项具有重要影响的成果。调控植物生长-代谢平衡实现可持续农业发展入选2018年度中国科学十大进展; 中国被子植物区系进化历史研究入选2018年度中国生命科学十大进展。以水稻为代表的农作物和果蔬等经济作物研究在国际上已呈现出明显的优势, 若干领域已从“追赶”状态跨越到“领跑”地位。该文对2018年中国科学家在植物科学若干领域取得的重要研究成果进行了概括性评述, 旨在全面追踪和报道当前中国植物科学领域的发展前沿和热点, 展示中国科学家所取得的杰出成就。     

我国葫芦科植物离体培养研究进展

葫芦科植物包括多种瓜类蔬菜,对其进行离体培养研究具有重要的理论和实践意义.综述了国内在葫芦科植物器官培养、体细胞胚胎发生、花药培养、原生质体培养和体细胞杂交及离体遗传转化等方面取得的研究进展,并对葫芦科植物离体培养、遗传转化与育种的前景作了展望.     

Apoptosis in experimental myocardial infarction in situ and in the perfused heart in vitro

We report the appearance of apoptotic cells in experimental myocardial infarction (rabbit heart) in in situ and in vitro preparations. Apoptosis was recognized by intravital staining with Hoechst 33342 (Ho342), by nick-end labeling (TUNEL) and by DNA laddering. A steady rise in the relative number of apoptotic cardiomyocytes (apoptotic index) was noted in in situ preparations. Apoptosis was first noted 6 h after the onset of ischemia with its highest value occurring after 72 h. Apoptotic nuclei were absent in remote areas of the left and right ventricles. Apoptotic nuclei within the infarcted area showed diminished intensity of Ho342 fluorescence. Three days after ischemia, a border zone adjacent to the infarcted area consisting of apoptotic macrophages was recognized. A novel finding was the appearance of apoptotic cardiomyocytes in the isolated perfused ischemic heart. Occurring as early as 50 min after the onset of ischemia, a high apoptotic index was present adjacent to the ligature placed around the coronary artery. This observation provides the opportunity to selectively examine factors leading to apoptosis in the ischemic heart under controlled experimental conditions.     

Changes in aquatic vegetation in Rhine floodplain streams in Alsace in relation to disturbance

Abstract. Changes are described in aquatic vegetation in oligotrophic, groundwater-fed Rhine floodplain streams in Alsace (eastern France), resulting from disturbance. Disturbance factors include changes in nutrients, either permanent ones - effluent from a waste water treatment plant or trout hatcheries - or periodic ones: flooding. Regular inputs of high levels of phosphate and ammonia modified the macrophyte vegetation in these streams. The floristic composition, which was characteristic of oligotrophic waters upstream of the eutrophicated sector, changed to that of a eutrophic situation as originally found downstream. Periodic disturbance by floods which normally occur once a year, irregularly eutrophicates the small streams, causing the development of a mixture of eutrophic and oligotrophic species. Six macrophyte communities are distinguished, indicating different trophic levels. The aquatic vegetation is adapted to the variations of phosphate and ammonia levels. Hence, aquatic macrophytes can be used as bio-indicators of fluctuations in water nutrient levels in relation to the type of disturbance.     

Morphine-potentiated platelet aggregation in in vitro and platelet plug formation in in vivo experiments

The detailed mechanisms underlying morphine-signaling pathways in platelets remain obscure. Therefore, we systematically examined the influence of morphine on washed human platelets. In this study, washed human platelet suspensions were used for in vitro studies. Furthermore, platelet thrombus formation induced by irradiation of mesenteric venules with filtered light in mice pretreated with fluorescein sodium was used for an in vivo thrombotic study. Morphine concentration dependently (0.6, 1, and 5 microM) potentiated platelet aggregation and the ATP release reaction stimulated by agonists (i.e., collagen and U46619) in washed human platelets. Yohimbine (0.1 microM), a specific alpha(2)-adrenoceptor antagonist, markedly abolished the potentiation of morphine in platelet aggregation stimulated by agonists. Morphine also potentiated phosphoinositide breakdown and intracellular Ca(2+) mobilization in human platelets stimulated by collagen (1 microg/ml). Moreover, morphine (0.6-5 microM) markedly inhibited prostaglandin E(1) (10 microM)-induced cyclic AMP formation in human platelets, while yohimbine (0.1 microM) significantly reversed the inhibition of cyclic AMP by morphine (0.6 and 1 microM) in this study. The thrombin-evoked increase in pH(i) was markedly potentiated in the presence of morphine (1 and 5 microM). Morphine (2 and 5 mg/g) significantly shortened the time require to induce platelet plug formation in mesenteric venules. We concluded that morphine may exert its potentiation in platelet aggregation by binding to alpha(2)-adrenoceptors in human platelets, with a resulting inhibition of adenylate cyclase, thereby reducing intracellular cyclic AMP formation followed by increased activation of phospholipase C and the Na(+)/H(+) exchanger. This leads to increased intracellular Ca(2+) mobilization, and finally potentiation of platelet aggregation and of the ATP release reaction.