检索问题
免疫 生长
免疫与生长之间存在着一种普遍存在的“此消彼长”的权衡关系，生物体在面对资源有限或外界压力时，必须在促进生长与维持免疫防御之间做出动态平衡与资源分配。这种机制在植物、昆虫以及人类等动物中都广泛存在，它就像是一个跷跷板：当一边（如免疫防御）需要倾斜时，另一边（如生长或繁殖）就会暂时受到抑制。
为了让你能轻松理解这个看似高深的科学问题，我们不妨把生物体的能量和营养想象成一笔“固定预算的生活费”。如果外界环境很安全，没有病菌来袭，身体就会把大部分钱用来“盖房子”（也就是生长和发育）；但如果病菌大举入侵，身体遇到生存危机，它就必须立刻停工，把钱拿出来“买武器、雇保安”（也就是启动免疫系统对抗敌人）。等把敌人赶跑了，身体才会重新把资源投入到生长中去。
接下来，我们将从植物、昆虫、人类及其他动物等多个角度，详细为你拆解这种奇妙的生物权衡机制。
一、 植物中的“生存与发育”博弈
植物不能像动物那样遇到危险就拔腿跑掉，它们被固定在土壤里，因此必须演化出非常精巧的机制来应对病菌的入侵。当病原体来袭时，植物会主动将体内的资源从生长转移到免疫防御上，这被称为“生长-防御权衡”。
1. 资源的重新定向与“开关”蛋白 以辣椒为例，当一种叫做青枯菌的病菌入侵时，辣椒体内的一种名为CaARF9的蛋白就会发挥双重作用：它既能增强植物对病菌的抵抗力，又会通过抑制其他几个目标基因（如Casmc4、CaLBD37等）的表达来减缓植物自身的生长。在平时没有病菌的安全环境下，CaARF9会和一个叫CaIAA2的蛋白结合在一起，这种结合状态会让CaARF9失去抑制作用，使得植物能够正常生长。但一旦青枯菌入侵，植物体内的防御信号（如水杨酸和茉莉酸）就会被激活，触发一种类似“垃圾处理厂”的机制（泛素-蛋白酶体系统），把CaIAA2蛋白降解掉。失去了CaIAA2的束缚后，CaARF9就开始工作，抑制那些促进生长的基因，从而让植物把能量集中起来对抗感染。
2. 微生物的“外援”与打破权衡 虽然生长和防御常常需要权衡，但植物也有聪明的办法来缓解这种矛盾。植物周围（包括根系和叶片周围）生活着大量的微生物群落，这些微生物就像是植物的“私人医生”和“营养师”。研究表明，植物能够主动管理这些微生物群落，与它们进行双向的沟通。通过利用一些特定的根系共生微生物，植物可以在增强抗病能力的同时，减少因启动免疫反应而带来的生长惩罚，从而实现从“权衡”到“协同”的转变。
3. 激素的指挥与基因的“剪辑” 植物体内的激素也是调节这个跷跷板的关键。例如，油菜素内酯（一种促进植物生长的激素）在感知到病原体存在时，会通过其信号通路中的关键转录因子（如BZR1和HBI1）来抑制免疫反应，确保在安全时优先生长；而当需要防御时，这条通路又会做出相应的调整，以实现成本效益最高的平衡。 此外，植物还能通过基因的“可变剪接”来维持平衡。基因就像是一段剧本，可变剪接就像是把剧本的不同段落重新拼接。在马铃薯中，有一个抗病基因RB，在植物正常生长时，它主要保留一段内含子（剧本中不直接参与演出的部分），形成一个缩短的蛋白版本，不发挥完整的抗病作用；而当致病疫霉感染时，病原体会促使这个基因进行剪接，产生完整的抗病蛋白，从而在不影响平时生长的前提下，迅速启动免疫防御。
4. 木质部发育的让步 植物内部运输水分的管道（木质部）的发育也受此规律制约。木质部细胞的形成需要沉积大量的高碳化合物来构建坚固的“次生细胞壁”。当植物遭遇病原体攻击时，植物会优先启动防御反应，通过水杨酸（一种植物免疫信号分子）的介导，抑制木质部相关基因的表达，延缓木质部的形成，将宝贵的碳资源节省下来用于免疫。
二、 昆虫界的繁殖与免疫抉择
在昆虫的世界里，同样存在着能量分配的难题，主要体现在繁殖和免疫之间的权衡。繁殖后代和对抗感染都是极其消耗能量和生理资源的过程。研究发现，雌性昆虫如果增加繁殖投入，其免疫力就会下降；反过来，如果感染了病原体并激活了免疫系统，它们的繁殖产卵量就会减少。 这种权衡不仅发生在个体内部的生理层面，也体现在群体进化的基因层面。科学家认为，这种竞争主要是为了争夺体内有限的资源。在这个过程中，保幼激素、蜕皮激素以及胰岛素样信号通路扮演了“资源调度员”的角色，它们同时调控着昆虫的卵子发育和免疫系统活性，在繁殖与免疫之间寻找最佳的平衡点。
三、 人类及动物中的免疫与生长互动
在人类和动物中，免疫与生长的互动同样复杂而深刻，贯穿了我们从婴儿到老年的整个生命过程。
1. 生命早期的脆弱与母乳的保护 当我们还是婴儿时，免疫系统是非常不成熟、缺乏经验的，需要随着成长不断学习和建立“免疫记忆”。在这个脆弱的阶段，母乳是保护婴儿健康的完美食物。母乳的成分并非一成不变，而是会随着婴儿的年龄和需求动态变化，其中含有丰富的免疫成分、生长因子、激素和各种营养物质。这些物质不仅能为婴儿提供现成的抗体对抗病原体，还能促进婴儿身体各个系统的健康发育和肠道菌群的平衡，在生长和免疫保护之间提供了最自然的支持。
2. 睡眠：免疫记忆的催化剂 睡眠对免疫系统有着强大的调节作用，尤其是在帮助免疫系统形成“记忆”方面。研究表明，在夜间良好的睡眠（特别是慢波睡眠阶段）中，体内会出现一种有利于免疫的内分泌环境：生长激素和催乳素水平升高，而皮质醇等压力激素水平降低。这种环境能促进T细胞（一种重要的免疫细胞）向淋巴结转移，并增强能促进免疫细胞间交流的细胞因子（如白细胞介素-12）的活性。如果人在接种甲肝疫苗后的当晚能好好睡觉，体内针对该疫苗的特异性T细胞和抗体数量会显著且持久地增加。可以说，优质的睡眠是身体在生长修复与强化免疫之间进行完美协作的体现。
3. 运动与压力的双刃剑 运动是调节免疫系统的有效方式，但过度运动却会带来截然不同的效果。适度的运动有助于健康，但严重的剧烈运动会被身体视为一种“压力”，导致短暂的免疫抑制状态。在这种压力下，体内的神经内分泌系统会释放大量激素，引发肌肉损伤和炎症反应，进而影响免疫功能。有趣的是，不仅是身体上的压力，心理压力同样会削弱免疫力。而“大笑”作为一种积极的情绪体验，被证明能有效对抗压力。大笑可以降低血液中皮质醇、肾上腺素等压力激素的水平，从而逆转压力反应，并对免疫系统产生积极影响。
4. 生长激素的多面性 提到生长，就不能不提生长激素（GH）。生长激素及其介导物质胰岛素样生长因子1（IGF-1）不仅能促进骨骼变长，还在调节代谢和维持心血管、肌肉、骨骼功能中起重要作用。如果儿童时期缺乏生长激素，不仅会导致身材矮小，成年后还可能出现心脏、肌肉、代谢等多方面的异常。 在鱼类的研究中，科学家发现生长激素对免疫系统也有显著的调节作用，它能增强鱼类的非特异性防御和特异性抗体产生。然而，生长和免疫之间也存在微妙的博弈。在探讨心血管疾病的治疗时，有学者提出，驱动生殖轴的激素（如雄激素）在促进某些生长特征的同时，可能会抑制免疫系统并增加心血管疾病风险。这再次印证了生长、生殖与免疫之间存在深层的能量与机制博弈。
5. 衰老中的免疫衰退与铁元素陷阱 随着年龄增长，免疫系统会逐渐走向衰退，这也是为什么老年人更容易感染疾病和患癌的原因。最新研究揭示了一个关于老年脾脏的有趣机制：在衰老的过程中，脾脏这个重要的免疫器官会积累有毒的铁和血红素，形成一个充满压力的微环境。在这种恶劣环境中，为了活下去，T细胞（免疫主力军）会主动降低体内的游离铁含量，以抵抗一种叫做“铁死亡”的细胞毁灭途径。然而，这种保命的策略却带来了巨大的代价：T细胞因为缺乏足够的铁，无法被有效激活来执行杀伤病原体或癌细胞的任务。这生动地展示了在老化过程中，免疫细胞为了生存而牺牲了功能，是一种典型的生存与功能的权衡。
6. 外界威胁对生命进程的干扰 有时候，外界的感染不仅会引起短暂的免疫波动，还会对生长或疾病潜伏期产生长远影响。例如，孕妇如果在怀孕期间暴露在空气污染（尤其是细颗粒物PM）中，这些污染物不仅会引发母体全身的炎症反应，还会通过胎盘影响胎儿的呼吸系统、免疫状态、大脑发育和心血管代谢健康，对后代的生长轨迹造成长期负面影响。 对于儿童癌症幸存者来说，疾病本身和治疗（如某些靶向药物）常常会导致严重的生长发育障碍，这需要医生密切关注并通过激素治疗等手段进行干预。 更令人震惊的是，呼吸道病毒感染（如流感或新冠病毒）甚至能“唤醒”体内潜伏的癌细胞。在小鼠实验和人类临床数据中，这些病毒感染引发的全身炎症会导致肺部处于休眠状态的乳腺癌细胞重新开始增殖，增加癌症转移的风险。这表明，免疫系统的剧烈活动有时可能会成为打破其他生理平衡的推手。
总结
无论是在扎根泥土的植物、四处飞舞的昆虫，还是复杂精密的人类身体中，“免疫”与“生长”都是一场永恒的生命双步舞。生物体必须精打细算地分配有限的能量，在“茁壮成长”与“抵御外敌”之间寻找最优解。从植物降解抑制蛋白、剪辑基因剧本，到昆虫调度激素、人类依靠睡眠和母乳，再到老化的T细胞在缺铁中挣扎求生，生命演化出了千变万化的策略。理解这种权衡关系，不仅能让我们更敬畏生命的智慧，也为未来提高农作物抗病产量、研发新疫苗以及治疗人类衰老相关疾病提供了宝贵的科学启示。
References
1CaIAA2-CaARF9 module mediates the trade-off between pepper growth and immunity.PubMed
Weiwei Cai, Yilin Tao, Xingge Cheng, et al.
To challenge the invasion of various pathogens, plants re-direct their resources from plant growth to an innate immune defence system. However, the underlying mechanism that coordinates the induction of the host immune response and the suppression of plant growth remains unclear. Here we demonstrate that an auxin response factor, CaARF9, has dual roles in enhancing the immune resistance to Ralstonia solanacearum infection and in retarding plant growth by repressing the expression of its target genes as exemplified by Casmc4, CaLBD37, CaAPK1b and CaRROP1. The expression of these target genes not only stimulates plant growth but also negatively impacts pepper resistance to R. solanacearum. Under normal conditions, the expression of Casmc4, CaLBD37, CaAPK1b and CaRROP1 is active when promoter-bound CaARF9 is complexed with CaIAA2. Under R. solanacearum infection, however, degradation of CaIAA2 is triggered by SA and JA-mediated signalling defence by the ubiquitin-proteasome system, which enables CaARF9 in the absence of CaIAA2 to repress the expression of Casmc4, CaLBD37, CaAPK1b and CaRROP1 and, in turn, impeding plant growth while facilitating plant defence to R. solanacearum infection. Our findings uncover an exquisite mechanism underlying the trade-off between plant growth and immunity mediated by the transcriptional repressor CaARF9 and its deactivation when complexed with CaIAA2.
2Bioactive Components of Human Milk and Their Impact on Child's Health and Development, Literature Review.PubMed
Hubert Szyller, Katarzyna Antosz, Joanna Batko, et al.
The composition of human breast milk is an ideal combination of substances necessary for the healthy development of an infant's body while protecting from pathogens and the balanced development of the microbiota. Its composition is dynamic and changes with the age of the child, meeting their current needs. The study provides a thorough overview of human milk components, such as immunological components, growth factors, hormones, carbohydrates, lipids, minerals, and vitamins. Authors focus on capturing the most important aspects of the effects of these substances on a newborn's body, while also looking for specific connections and describing the effects on given systems. Supplementation and the use of ingredients are also discussed. The purpose of this paper is to present the current state of knowledge about the bioactive components of human milk and their impact on the growth, development, and health of the young child.
3Sleep and immune function.PubMed
Luciana Besedovsky, Tanja Lange, Jan Born
Sleep and the circadian system exert a strong regulatory influence on immune functions. Investigations of the normal sleep-wake cycle showed that immune parameters like numbers of undifferentiated naïve T cells and the production of pro-inflammatory cytokines exhibit peaks during early nocturnal sleep whereas circulating numbers of immune cells with immediate effector functions, like cytotoxic natural killer cells, as well as anti-inflammatory cytokine activity peak during daytime wakefulness. Although it is difficult to entirely dissect the influence of sleep from that of the circadian rhythm, comparisons of the effects of nocturnal sleep with those of 24-h periods of wakefulness suggest that sleep facilitates the extravasation of T cells and their possible redistribution to lymph nodes. Moreover, such studies revealed a selectively enhancing influence of sleep on cytokines promoting the interaction between antigen presenting cells and T helper cells, like interleukin-12. Sleep on the night after experimental vaccinations against hepatitis A produced a strong and persistent increase in the number of antigen-specific Th cells and antibody titres. Together these findings indicate a specific role of sleep in the formation of immunological memory. This role appears to be associated in particular with the stage of slow wave sleep and the accompanying pro-inflammatory endocrine milieu that is hallmarked by high growth hormone and prolactin levels and low cortisol and catecholamine concentrations.
4New challenges in modern vaccinology.PubMed
Mireille Centlivre, Béhazine Combadière
Vaccination has been a major advance for health care, allowing eradication or reduction of incidence and mortality of various infectious diseases. However, there are major pathogens, such as Human Immunodeficiency Virus (HIV) or the causative agent of malaria, for which classical vaccination approaches have failed, therefore requiring new vaccination strategies. The development of new vaccine strategies relies on the ability to identify the challenges posed by these pathogens. Understanding the pathogenesis and correlates of protection for these diseases, our ability to accurately direct immune responses and to vaccinate specific populations are such examples of these roadblocks. In this respect, the use of a robust, cost-effective and predictive animal model that recapitulates features of both human infection and vaccination is currently a much-needed tool. We discuss here the major limitations faced by modern vaccinology and notably, the development of humanized mice for assessing the immune system, along with their potential as vaccine models.
5From trade-off to synergy: microbial insights into enhancing plant growth and immunity.PubMed
Yee-Shan Ku, Yi-Jun Liao, Shian-Peng Chiou, et al.
The reduction in crop yield caused by pathogens and pests presents a significant challenge to global food security. Genetic engineering, which aims to bolster plant defence mechanisms, emerges as a cost-effective solution for disease control. However, this approach often incurs a growth penalty, known as the growth-defence trade-off. The precise molecular mechanisms governing this phenomenon are still not completely understood, but they generally fall under two main hypotheses: a "passive" redistribution of metabolic resources, or an "active" regulatory choice to optimize plant fitness. Despite the knowledge gaps, considerable practical endeavours are in the process of disentangling growth from defence. The plant microbiome, encompassing both above- and below-ground components, plays a pivotal role in fostering plant growth and resilience to stresses. There is increasing evidence which indicates that plants maintain intimate associations with diverse, specifically selected microbial communities. Meta-analyses have unveiled well-coordinated, two-way communications between plant shoots and roots, showcasing the capacity of plants to actively manage their microbiota for balancing growth with immunity, especially in response to pathogen incursions. This review centers on successes in making use of specific root-associated microbes to mitigate the growth-defence trade-off, emphasizing pivotal advancements in unravelling the mechanisms behind plant growth and defence. These findings illuminate promising avenues for future research and practical applications.
6Reproduction-Immunity Trade-Offs in Insects.PubMed
Robin A Schwenke, Brian P Lazzaro, Mariana F Wolfner
Immune defense and reproduction are physiologically and energetically demanding processes and have been observed to trade off in a diversity of female insects. Increased reproductive effort results in reduced immunity, and reciprocally, infection and activation of the immune system reduce reproductive output. This trade-off can manifest at the physiological level (within an individual) and at the evolutionary level (genetic distinction among individuals in a population). The resource allocation model posits that the trade-off arises because of competition for one or more limiting resources, and we hypothesize that pleiotropic signaling mechanisms regulate allocation of that resource between reproductive and immune processes. We examine the role of juvenile hormone, 20-hydroxyecdysone, and insulin/insulin-like growth factor-like signaling in regulating both oogenesis and immune system activity, and propose a signaling network that may mechanistically regulate the trade-off. Finally, we discuss implications of the trade-off in an ecological and evolutionary context.
7Respiratory viral infections awaken metastatic breast cancer cells in lungs.PubMed
Shi B Chia, Bryan J Johnson, Junxiao Hu, et al.
Breast cancer is the second most common cancer globally, with most deaths caused by metastatic disease, often following long periods of clinical dormancy. Understanding the mechanisms that disrupt the quiescence of dormant disseminated cancer cells (DCCs) is crucial for addressing metastatic progression. Infections caused by respiratory viruses such as influenza and SARS-CoV-2 trigger both local and systemic inflammation. Here we demonstrate, in mice, that influenza and SARS-CoV-2 infections lead to loss of the pro-dormancy phenotype in breast DCCs in the lung, causing DCC proliferation within days of infection and a massive expansion of carcinoma cells into metastatic lesions within two weeks. These phenotypic transitions and expansions are interleukin-6 dependent. We show that DCCs impair lung T cell activation and that CD4 T cells sustain the pulmonary metastatic burden after the influenza infection by inhibiting CD8 T cell activation and cytotoxicity. Crucially, these experimental findings align with human observational data. Analyses of cancer survivors from the UK Biobank (all cancers) and Flatiron Health (breast cancer) databases reveal that SARS-CoV-2 infection substantially increases the risk of cancer-related mortality and lung metastasis compared with uninfected cancer survivors. These discoveries underscore the huge impact of respiratory viral infections on metastatic cancer resurgence, offering new insights into the connection between infectious diseases and cancer metastasis.
8Exercise and the immune system: regulation, integration, and adaptation.PubMed
B K Pedersen, L Hoffman-Goetz
Stress-induced immunological reactions to exercise have stimulated much research into stress immunology and neuroimmunology. It is suggested that exercise can be employed as a model of temporary immunosuppression that occurs after severe physical stress. The exercise-stress model can be easily manipulated experimentally and allows for the study of interactions between the nervous, the endocrine, and the immune systems. This review focuses on mechanisms underlying exercise-induced immune changes such as neuroendocrinological factors including catecholamines, growth hormone, cortisol, beta-endorphin, and sex steroids. The contribution of a metabolic link between skeletal muscles and the lymphoid system is also reviewed. The mechanisms of exercise-associated muscle damage and the initiation of the inflammatory cytokine cascade are discussed. Given that exercise modulates the immune system in healthy individuals, considerations of the clinical ramifications of exercise in the prevention of diseases for which the immune system has a role is of importance. Accordingly, drawing on the experimental, clinical, and epidemiological literature, we address the interactions between exercise and infectious diseases as well as exercise and neoplasia within the context of both aging and nutrition.
9Evolution of the immune system in humans from infancy to old age.PubMed
A Katharina Simon, Georg A Hollander, Andrew McMichael
This article reviews the development of the immune response through neonatal, infant and adult life, including pregnancy, ending with the decline in old age. A picture emerges of a child born with an immature, innate and adaptive immune system, which matures and acquires memory as he or she grows. It then goes into decline in old age. These changes are considered alongside the risks of different types of infection, autoimmune disease and malignancy.
10Trade-Off Regulation in Plant Growth and Stress Responses Through the Role of Heterotrimeric G Protein Signaling.PubMed
Horim Lee
Unlike animals, plants are sessile organisms that cannot migrate to more favorable conditions and must constantly adapt to a variety of biotic and abiotic stresses. Therefore, plants exhibit developmental plasticity to cope, which is probably based on the underlying trade-off mechanism that allocates energy expenditure between growth and stress responses to achieve appropriate growth and development under different environmental conditions. Plant heterotrimeric G protein signaling plays a crucial role in the trade-off involved in the regulation of normal growth and stress adaptation. This review examines the composition and signaling processes of heterotrimeric G proteins in plants, detailing how they balance growth and adaptive responses in plant immunity and thermomorphogenesis through recent advances in the field. Understanding the trade-offs associated with plant G protein signaling will have significant implications for agricultural innovation, particularly in the development of crops with improved resilience and minimal growth penalties under environmental stress.
11Heme and iron toxicity in the aged spleen impairs T cell immunity through iron deprivation.PubMed
David Ezuz, Heba Ombashe, Lana Watad, et al.
Mechanisms of T cell aging involve cell-intrinsic alterations and interactions with immune and stromal cells. Here we found that splenic T cells exhibit greater functional decline than lymph node T cells within the same aged mouse, prompting investigation into how the aged spleen contributes to T cell aging. Proteomic analysis revealed increased expression of heme detoxification in aged spleen-derived lymphocytes. Exposure to the heme- and iron-rich aged splenic microenvironment induced aging phenotypes in young T cells, including reduced proliferation and CD39 upregulation. T cells survived this hostile niche by maintaining a low labile iron pool, at least in part, via IRP2 downregulation to resist ferroptosis but failed to induce sufficient iron uptake for activation. Iron supplementation enhanced antigen-specific T cell responses in aged mice. This study identifies the aged spleen as a source of hemolytic signals that systemically impair T cell function, underscoring a trade-off between T cell survival and function and implicating iron metabolism in immune aging.
12Impact of Childhood Cancer on Growth.PubMed
Tomoko Yoshida, Angela Delaney
Along with improvements in cancer treatment over time, the number of childhood cancer survivors has been growing. Survivors are at risk for serious medical complications, and growth impairment is among the most common. There are multiple factors that may cause impaired growth among survivors. In this article, we review the impact of cancer on growth in children and adolescents. We first provide an overview of growth disturbance among childhood cancer patients and survivors due to nonhormonal causes, including a recent understanding of the effect of targeted cancer therapies (eg, tyrosine kinase inhibitors and immune checkpoint inhibitors) on growth. Then we describe the hormonal causes of growth impairment among survivors, focusing on growth hormone deficiency, including the prevalence, risk factors, and treatment. Lastly, we briefly summarize overgrowth and tall stature in childhood cancer. It is critical to assess the linear growth of children and adolescents, especially in cancer survivors who are at risk for growth disturbance, since growth is an important measure of their health.
13Growth hormone and fish immune system.PubMed
Takashi Yada
This paper reviews the immunomodulatory effects, extra-pituitary expression and paracrine action of growth hormone (GH), and a possible role of GH/insulin-like growth factor-I (IGF-I) axis in the immune system of teleost fish. In some euryhaline fish, the activation of immune functions observed during seawater acclimation appears to be associated with the osmoregulatory action of GH. Administration of GH enhances many aspects of immune functions including non-specific defences; cytotoxic, phagocytic, haemolytic and lysozyme activities. GH also activates immunoglobulin production as a specific defense and increases ceruloplasmin levels as an acute-phase protein. The GH gene is also expressed in many extra-pituitary tissues of fish, especially in lymphoid organs and cells. Several endocrine factors appear to act on immune function through modification of GH secretion from fish leucocytes. Exposure of phagocytic leucocytes of tilapia to IGF-I in vitro stimulated proliferation and superoxide production associated with phagocytosis. Exposure to GH had no significant effect on IGF-I secretion from tilapia leucocytes, despite of the fact that they secreted significant amounts of IGF-I. GH and IGF-I appear to act in a paracrine manner in the regulation of the teleostean immune system. Further studies are necessary to characterize the interactions of GH with other endocrine and paracrine factors.
14Trade-off between growth and immunity: role of brassinosteroids.PubMed
Rosa Lozano-Durán, Cyril Zipfel
A balance between growth and immunity exists in plants. Recently, the growth-promoting hormones brassinosteroids (BR) have emerged as crucial regulators of the growth-immunity trade-off, although the molecular mechanisms underlying this role remained unclear. New evidence obtained from the model plant Arabidopsis thaliana points at an indirect crosstalk between BR signaling and immunity, mediated by the transcription factors BZR1 and HBI1, which suppress immunity upon BR perception. The core transcriptional cascade formed by BZR1 and HBI1 seems to act as a regulatory hub on which multiple signaling inputs impinge, ensuring effective fine-tuning of the trade-off between growth and immunity in a timely and cost-efficient manner.
15How Might Bromodomain and Extra-Terminal (BET) Inhibitors Operate in Cardiovascular Disease?PubMed
C Mary Schooling, Jie V Zhao
Bromodomain and extra-terminal (BET) inhibitors, acting via epigenetic mechanisms, have been developed recently as potential new treatments for cancer, including prostate cancer, and inflammatory conditions. Some BET inhibitors, such as RVX-208, also raise high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-1 levels. A recent meta-analysis of three small trials (n = 798) found that RVX-208 protected against major adverse cardiovascular events (MACE), raising the question as to whether this protective effect was an artefact, a chance finding, or mediated by HDL-C, anti-inflammatory pathways, or other factors. Notably, the effect of RVX-208 on MACE was largely driven by revascularizations, but fewer interventions in the treatment arm could have arisen accidently from favorable effects of RVX-208 on HDL-C and C-reactive protein influencing decisions about patient care. A larger (n = 2400) trial of RVX-208, BETonMACE (NCT02586155), with a more restricted definition of MACE, excluding hospitalizations, will shortly provide clarity. A successful BETonMACE trial would raise the question as to whether RVX-208 operates via lipids, inflammation, or other means, because several previous HDL-C modulators and anti-inflammatories have not provided effective means of treating cardiovascular disease and reducing overall mortality. Re-conceptualizing cardiovascular disease within the well-established evolutionary biology theory that growth and specifically reproduction trade-off against longevity might provide a more comprehensive explanation. Drivers of the gonadotropic axis, particularly androgens, suppress both HDL-C and the immune system while promoting ischemic heart disease and stroke. As such, any effects of RVX-208 on cardiovascular disease might be the result of reducing androgens, of which higher HDL-C and reduced inflammation are biomarkers. Notably, several other effective treatments for cardiovascular disease, such as statins and spironolactone, are known anti-androgens. Results of the BETonMACE trial, and corresponding insight about the mechanism of BET inhibitors in cardiovascular disease, are eagerly awaited.
16Air pollution and children's health-a review of adverse effects associated with prenatal exposure from fine to ultrafine particulate matter.PubMed
Natalie M Johnson, Aline Rodrigues Hoffmann, Jonathan C Behlen, et al.
BACKGROUND: Particulate matter (PM), a major component of ambient air pollution, accounts for a substantial burden of diseases and fatality worldwide. Maternal exposure to PM during pregnancy is particularly harmful to children's health since this is a phase of rapid human growth and development. METHOD: In this review, we synthesize the scientific evidence on adverse health outcomes in children following prenatal exposure to the smallest toxic components, fine (PM) and ultrafine (PM) PM. We highlight the established and emerging findings from epidemiologic studies and experimental models. RESULTS: Maternal exposure to fine and ultrafine PM directly and indirectly yields numerous adverse birth outcomes and impacts on children's respiratory systems, immune status, brain development, and cardiometabolic health. The biological mechanisms underlying adverse effects include direct placental translocation of ultrafine particles, placental and systemic maternal oxidative stress and inflammation elicited by both fine and ultrafine PM, epigenetic changes, and potential endocrine effects that influence long-term health. CONCLUSION: Policies to reduce maternal exposure and health consequences in children should be a high priority. PM levels are regulated, yet it is recognized that minority and low socioeconomic status groups experience disproportionate exposures. Moreover, PM levels are not routinely measured or currently regulated. Consequently, preventive strategies that inform neighborhood/regional planning and clinical/nutritional recommendations are needed to mitigate maternal exposure and ultimately protect children's health.
17Therapeutic Benefits of Laughter in Mental Health: A Theoretical Review.PubMed
JongEun Yim
In modern society, fierce competition and socioeconomic interaction stress the quality of life, causing a negative influence on a person's mental health. Laughter is a positive sensation, and seems to be a useful and healthy way to overcome stress. Laughter therapy is a kind of cognitive-behavioral therapies that could make physical, psychological, and social relationships healthy, ultimately improving the quality of life. Laughter therapy, as a non-pharmacological, alternative treatment, has a positive effect on the mental health and the immune system. In addition, laughter therapy does not require specialized preparations, such as suitable facilities and equipment, and it is easily accessible and acceptable. For these reasons, the medical community has taken notice and attempted to include laughter therapy to more traditional therapies. Decreasing stress-making hormones found in the blood, laughter can mitigate the effects of stress. Laughter decreases serum levels of cortisol, epinephrine, growth hormone, and 3,4-dihydrophenylacetic acid (a major dopamine catabolite), indicating a reversal of the stress response. Depression is a disease, where neurotransmitters in the brain, such as norepinephrine, dopamine, and serotonin, are reduced, and there is something wrong in the mood control circuit of the brain. Laughter can alter dopamine and serotonin activity. Furthermore, endorphins secreted by laughter can help when people are uncomfortable or in a depressed mood. Laughter therapy is a noninvasive and non-pharmacological alternative treatment for stress and depression, representative cases that have a negative influence on mental health. In conclusion, laughter therapy is effective and scientifically supported as a single or adjuvant therapy.
18Alternative splicing of a potato disease resistance gene maintains homeostasis between growth and immunity.PubMed
Biying Sun, Jie Huang, Liang Kong, et al.
Plants possess a robust and sophisticated innate immune system against pathogens and must balance growth with rapid pathogen detection and defense. The intracellular receptors with nucleotide-binding leucine-rich repeat (NLR) motifs recognize pathogen-derived effector proteins and thereby trigger the immune response. The expression of genes encoding NLR receptors is precisely controlled in multifaceted ways. The alternative splicing (AS) of introns in response to infection is recurrently observed but poorly understood. Here we report that the potato (Solanum tuberosum) NLR gene RB undergoes AS of its intron, resulting in 2 transcriptional isoforms, which coordinately regulate plant immunity and growth homeostasis. During normal growth, RB predominantly exists as an intron-retained isoform RB_IR, encoding a truncated protein containing only the N-terminus of the NLR. Upon late blight infection, the pathogen induces intron splicing of RB, increasing the abundance of RB_CDS, which encodes a full-length and active R protein. By deploying the RB splicing isoforms fused with a luciferase reporter system, we identified IPI-O1 (also known as Avrblb1), the RB cognate effector, as a facilitator of RB AS. IPI-O1 directly interacts with potato splicing factor StCWC15, resulting in altered localization of StCWC15 from the nucleoplasm to the nucleolus and nuclear speckles. Mutations in IPI-O1 that eliminate StCWC15 binding also disrupt StCWC15 re-localization and RB intron splicing. Thus, our study reveals that StCWC15 serves as a surveillance facilitator that senses the pathogen-secreted effector and regulates the trade-off between RB-mediated plant immunity and growth, expanding our understanding of molecular plant-microbe interactions.
19Salicylic acid-mediated competitive regulation of xylem vessel formation and defense responses in Arabidopsis thaliana.PubMed
Ya Ma, Rune Kurokawa, Chaokun Huang, et al.
In vascular plants, xylem vessels transport water and contribute to structural integrity. As part of vessel formation, xylem cells deposit secondary cell walls (SCWs), which are composed of cellulose, hemicellulose, and lignin polymers. Under environmental challenges such as pathogen attack, a growth-defense trade-off limits xylem vessel development. Understanding the mechanism regulating this trade-off has implications for understanding of plant strategy to utilize their carbon resources because SCWs contain large amounts of densely packed high-carbon compounds. Here, we investigated the effect of pathogen responses induced by the peptide defense elicitor flagellin22 (flg22) on VASCULAR-RELATED NAC-DOMAIN7 (VND7)-dependent xylem vessel formation in Arabidopsis (Arabidopsis thaliana). Treatment with flg22 decreased xylem transport and delayed ectopic xylem vessel differentiation, including SCW deposition, in plants with a dexamethasone-inducible VND7 system, suggesting that the plant prioritized defense responses over xylem formation. Consistent with this, transcriptome analysis revealed that flg22 treatment suppressed SCW-related genes and activated immune-related genes. Salicylic acid (SA) treatment had a similar inhibitory effect on VND7-dependent xylem vessel formation, and the sid2-2 and npr1-1 mutants, which are defective in SA biosynthesis and signaling, respectively, did not exhibit flg22-induced inhibition of xylem transport activity; these highlight the role of SA, which is biosynthesized from phenylalanine during immune responses, as a key mediator of the competition between xylem vessel formation and immune responses. These findings provide insights into how plants flexibly regulate xylem development under biotic stress to optimize their development.
20Impact of Pituitary Autoimmunity and Genetic Disorders on Growth Hormone Deficiency in Children and Adults.PubMed
Giuseppe Bellastella, Maria Ida Maiorino, Miriam Longo, et al.
Growth hormone (GH), mostly through its peripheral mediator, the insulin-like growth factor 1(IGF1), in addition to carrying out its fundamental action to promote linear bone growth, plays an important role throughout life in the regulation of intermediate metabolism, trophism and function of various organs, especially the cardiovascular, muscular and skeletal systems. Therefore, if a prepubertal GH secretory deficiency (GHD) is responsible for short stature, then a deficiency in adulthood identifies a nosographic picture classified as adult GHD syndrome, which is characterized by heart, muscle, bone, metabolic and psychic abnormalities. A GHD may occur in patients with pituitary autoimmunity; moreover, GHD may also be one of the features of some genetic syndromes in association with other neurological, somatic and immune alterations. This review will discuss the impact of pituitary autoimmunity on GHD and the occurrence of GHD in the context of some genetic disorders. Moreover, we will discuss some genetic alterations that cause GH and IGF-1 insensitivity and the arguments in favor and against the influence of GH/IGF-1 on longevity and cancer in the light of the papers on these issues that so far appear in the literature.