五篇Nature综述:盘点生物学最新前沿
生物通 · 2016/01/23
本期Nature杂志推出了“Frontiers in biology” 特辑,通过五篇前沿综述介绍了近期生物学领域的重要进展,涵盖了癌转移、炎症、信号传导、内质网应激等热点问题。


本期Nature杂志推出了“Frontiers in biology” 特辑,通过五篇前沿综述介绍了近期生物学领域的重要进展,涵盖了癌转移、炎症、信号传导、内质网应激等热点问题。

Metastatic colonization by circulating tumour cells

癌转移是癌症患者死亡的主要原因,也是癌症治疗面临的一大挑战。循环肿瘤细胞转移到远端器官必须克服许多障碍,而我们才开始了解这些过程。这篇文章探讨了循环肿瘤细胞转移到不同器官并建立转移灶的具体机制。文章指出,循环肿瘤细胞需要浸润远端组织、规避免疫防御、适应当地环境、埋下肿瘤的种子、最终爆发并取代宿主组织。正因如此,癌转移的效率并不高。然而一旦癌转移建立起来,现有的癌症疗法往往就搞不定了。深入理解癌转移过程可以帮助人们尽早做出正确诊断,更好的预防和治疗癌转移。

Reparative inflammation takes charge of tissue regeneration

许多慢性和退行性疾病背后都有炎症的身影。不过炎症也能减轻感染、清除受损细胞和起始组织修复。将炎症与损伤修复关联起来的机制,保守存在于低等生物和哺乳动物中,说明这个过程有重要的意义。这篇文章在细胞和分子水平上探讨了组织修复和再生重的保护性炎症。

最近一些研究显示,传统的炎症性细胞因子和Wnt因子能通过特定机制,控制哺乳动物的组织修复和再生。这对于消化系统的再生特别重要,尤其是肠道和肝脏组织。肠道和肝脏组织发生修复异常会引起严重的病理问题。文章指出,炎症的正面效应起到了不可或缺的作用,有助于恢复组织内稳态,避免慢性炎症、纤维化和癌症。

Angiocrine functions of organ-specific endothelial cells

组成血管壁的内皮细胞并不是单纯的“砖块”,它们能释放被称为血管生长因子(angiocrine factor)的旁分泌信号,在器官发育、生长和再生中发挥作用。这篇文章介绍了内皮细胞作为信号中心对器官起到的调节作用。文章指出,组织特异性内皮细胞会通过血管生长因子建立特定的血管环境,积极参与对器官再生的指导,以及内稳态和代谢维持。受伤会使血管生长因子上调,控制局部干/祖细胞的自我更新和分化。理解内皮细胞分配血管生长因子的时空机制,有助于实现无瘢痕的器官修复。

Protein misfolding in the endoplasmic reticulum as a conduit to human disease

在真核细胞中,内质网是负责蛋白折叠和转运的基础细胞器。环境干扰或蛋白合成增加会使内质网出现蛋白质错误折叠,错误蛋白和未折叠蛋白在内质网累积被称为内质网应激。在这种情况下,细胞会激活未折叠蛋白反应以恢复自己的内稳态。如果蛋白错误折叠没有得到解决,细胞就会死亡。这篇文章总结了人们目前对这一过程的认识,探讨了内质网应激与人类疾病的关联。

Antibacterial drug discovery in the resistance era

抗生素抗性是现代医疗卫生领域最紧迫的危机之一。致病菌耐药性的演化以及耐药菌的广泛分布,让原本很容易治疗的疾病变得致命起来。然而,随着耐药菌在世界范围崛起,抗菌药物的研发显得相当失败。这篇文章介绍了抗生素开发和使用的历史,分析了导致耐药菌崛起的因素。文章指出,吸取抗生素研发史上的经验教训,进一步加深对抗生素和微生物的理解,我们将最终获得21世纪的新抗菌药物,在这个耐药时代有效控制细菌感染。

Nature杂志每年都会推出一次“Frontiers in biology”特辑。去年一月份的特辑介绍了将复杂神经连接与行为学功能联系起来的杏仁核神经回路,先天免疫系统的新组分——先天淋巴细胞,哺乳动物感知营养的不同途径,程序性坏死(necroptosis)的调控、起始和执行,以及DNA甲基化的功能和调控。

去年五月,Science杂志以封面形式重点介绍了生物学最新前沿——浮游生物学。说到对地球生命至关重要的生态系统,大多数人首先会想到热带雨林,其实浮游生物也同样重要。Tara Ocean联盟的研究团队经过三年半的考察,首次正式发布了自己的研究成果,通过五篇论文揭示了一个鲜为人知的浮游世界。

谈到生物学前沿,我们不能不提环状RNA。生物学家们几十年前就知道存在一种不寻常的分子,环状RNA(circRNA)。与线性RNA相比,circRNA受到的关注比较少,也比较难于研究。在生物信息学、生化分析和深度测序的帮助下,研究者们现在对这些神秘分子有了空前的认识。最近的一些研究,为人们揭示了circRNA在神经系统中的惊人丰度和潜在功能。

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  • Metastatic colonization by circulating tumour cells

    Metastasis is the main cause of death in people with cancer. To colonize distant organs, circulating tumour cells must overcome many obstacles through mechanisms that we are only now starting to understand. These include infiltrating distant tissue, evading immune defences, adapting to supportive niches, surviving as latent tumour-initiating seeds and eventually breaking out to replace the host tissue. They make metastasis a highly inefficient process. However, once metastases have been established, current treatments frequently fail to provide durable responses. An improved understanding of the mechanistic determinants of such colonization is needed to better prevent and treat metastatic cancer.

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  • Reparative inflammation takes charge of tissue regeneration

    Inflammation underlies many chronic and degenerative diseases, but it also mitigates infections, clears damaged cells and initiates tissue repair. Many of the mechanisms that link inflammation to damage repair and regeneration in mammals are conserved in lower organisms, indicating that it is an evolutionarily important process. Recent insights have shed light on the cellular and molecular processes through which conventional inflammatory cytokines and Wnt factors control mammalian tissue repair and regeneration. This is particularly important for regeneration in the gastrointestinal system, especially for intestine and liver tissues in which aberrant and deregulated repair results in severe pathologies.

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  • Angiocrine functions of organ-specific endothelial cells

    Endothelial cells that line capillaries are not just passive conduits for delivering blood. Tissue-specific endothelium establishes specialized vascular niches that deploy sets of growth factors, known as angiocrine factors. These cues participate actively in the induction, specification, patterning and guidance of organ regeneration, as well as in the maintainance of homeostasis and metabolism. When upregulated following injury, they orchestrate self-renewal and differentiation of tissue-specific resident stem and progenitor cells into functional organs. Uncovering the mechanisms by which organotypic endothelium distributes physiological levels of angiocrine factors both spatially and temporally will lay the foundation for clinical trials that promote organ repair without scarring.

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  • Protein misfolding in the endoplasmic reticulum as a conduit to human disease

    In eukaryotic cells, the endoplasmic reticulum is essential for the folding and trafficking of proteins that enter the secretory pathway. Environmental insults or increased protein synthesis often lead to protein misfolding in the organelle, the accumulation of misfolded or unfolded proteins — known as endoplasmic reticulum stress — and the activation of the adaptive unfolded protein response to restore homeostasis. If protein misfolding is not resolved, cells die. Endoplasmic reticulum stress and activation of the unfolded protein response help to determine cell fate and function. Furthermore, endoplasmic reticulum stress contributes to the aetiology of many human diseases.

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  • Antibacterial drug discovery in the resistance era

    The looming antibiotic-resistance crisis has penetrated the consciousness of clinicians, researchers, policymakers, politicians and the public at large. The evolution and widespread distribution of antibiotic-resistance elements in bacterial pathogens has made diseases that were once easily treatable deadly again. Unfortunately, accompanying the rise in global resistance is a failure in antibacterial drug discovery. Lessons from the history of antibiotic discovery and fresh understanding of antibiotic action and the cell biology of microorganisms have the potential to deliver twenty-first century medicines that are able to control infection in the resistance era.

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