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Interaction of skin-born mediators with the cutaneous microbiota and beyond 皮肤生成的介质与皮肤微生物群的相互作用及其他
Pub Date : 2024-08-22 DOI: 10.1016/j.coemr.2024.100545
Marc G.J. Feuilloley , Emilie Hadjiev , Lanyo J. Amegnona

Cutaneous microorganisms are growing in a microenvironment where skin hormones and neurohormones are present in abundance. These molecules are markers of the host physiology, and microorganisms have developed strategies for detecting host factors that can represent a threat for their survival. Until now, our knowledge of these mechanisms is limited to bacteria, although the skin microbiota also includes an abundance of yeasts, fungi, viruses, and even archaea. Several human hormones and neurotransmitters, including substance P, calcitonin gene-related peptides, natriuretic peptides, catecholamines, and even estradiol have been studied in this context. This was leading to the identification of original proteins, such as the thermo-unstable ribosomal elongation factor, the chaperone DnaK, or the enzyme AmiC, which have been developed by bacteria and have dual functions, in the cytoplasm where they were originally identified and in the bacterial membrane where they act as sensors for host factors. These sensors, designed as moonlighting proteins for their dual functions, are submitted to structural reorganizations and probably post-translational modifications. The occurrence of epigenetic mechanisms in the regulation of moonlighting proteins activity is a source of major complications since similar processes are activated during bacteria adaptation to the host physiology and even storage. Cutaneous bacterial endocrinology is a wide and complex emerging scientific field that requires a deep knowledge of both human and microbial physiology and careful experimental procedures.

皮肤微生物是在皮肤激素和神经激素大量存在的微环境中生长的。这些分子是宿主生理机能的标记,微生物已经开发出了检测宿主因素的策略,这些因素可能对它们的生存构成威胁。到目前为止,我们对这些机制的了解仅限于细菌,尽管皮肤微生物群还包括大量的酵母菌、真菌、病毒甚至古细菌。在这方面,我们已经研究了几种人体激素和神经递质,包括 P 物质、降钙素基因相关肽、利尿肽、儿茶酚胺,甚至雌二醇。研究还发现了一些新的蛋白质,如热不稳定性核糖体伸长因子、伴侣蛋白 DnaK 或酶 AmiC,这些蛋白质是由细菌开发的,具有双重功能:在细胞质中,它们是最初被发现的;在细菌膜上,它们是宿主因子的传感器。这些传感器被设计成具有双重功能的兼职蛋白,它们的结构会发生重组,很可能会发生翻译后修饰。表观遗传机制对月光蛋白活性的调控是一个重大复杂问题的根源,因为在细菌适应宿主生理甚至贮存过程中,类似的过程也会被激活。皮肤细菌内分泌学是一个广泛而复杂的新兴科学领域,需要对人类和微生物生理学有深入的了解,并需要谨慎的实验程序。
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引用次数: 0
Therapeutic treatments targeting communication between angiogenic and immune microenvironments in thyroid cancers 针对甲状腺癌血管生成和免疫微环境之间沟通的治疗方法
Pub Date : 2024-08-14 DOI: 10.1016/j.coemr.2024.100544
Alessandro Prete , Carmelo Nucera
Thyroid cancer treatment has recently been revolutionized by the introduction of specific targeted therapies (e.g. BRAFV600E or highly selective RET inhibitors), anti-angiogenic agents (e.g. tyrosine kinase inhibitors (TKIs)) and immune checkpoint inhibitors, which significantly ameliorate outcomes in selected groups of thyroid cancer patients. Targeted and anti-angiogenic treatments are characterized by transient and partial efficacy, due to primary or secondary tumor resistance mechanisms, and toxicity profile. Immune therapy-based approaches are producing preliminary results. Herein, we review and prospectively discuss the immune microenvironment in non-medullary and medullary thyroid cancers and its interplays with the angiogenic microenvironment (endothelial cells and pericytes). In addition, we discuss how these interactions might be targeted using combined therapies. Furthermore, we will review chimeric antigen receptor (CAR) T cells treatment that potentially may ensure a more durable and effective response in advanced thyroid cancers. In sum, angiogenic and immune microenvironments show functional connectivity in TCs. Therapies with anti-angiogenic and immune checkpoint inhibitors combined with specific targeted therapy inhibitors with a tolerable toxicity profile may overcome drug resistance and provide better clinical outcomes than single agents.
最近,特定靶向疗法(如 BRAFV600E 或高选择性 RET 抑制剂)、抗血管生成药物(如酪氨酸激酶抑制剂 (TKIs))和免疫检查点抑制剂的引入彻底改变了甲状腺癌的治疗,显著改善了部分甲状腺癌患者的预后。由于原发性或继发性肿瘤耐药机制和毒性特征,靶向治疗和抗血管生成治疗具有短暂和部分疗效的特点。基于免疫疗法的方法正在取得初步成效。在此,我们回顾并前瞻性地讨论了非髓样和髓样甲状腺癌的免疫微环境及其与血管生成微环境(内皮细胞和周细胞)的相互作用。此外,我们还将讨论如何利用联合疗法来针对这些相互作用进行治疗。此外,我们还将讨论嵌合抗原受体(CAR)T细胞疗法,这种疗法有可能确保晚期甲状腺癌患者获得更持久、更有效的治疗。总之,血管生成和免疫微环境在甲状腺癌中显示出功能性联系。抗血管生成抑制剂和免疫检查点抑制剂与毒性可耐受的特异性靶向治疗抑制剂相结合的疗法可以克服耐药性,并提供比单一药物更好的临床疗效。
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引用次数: 0
Timing of physical activity in the pursuit of fat mass loss and weight maintenance 把握体育锻炼的时机,减少脂肪量和保持体重
Pub Date : 2024-08-03 DOI: 10.1016/j.coemr.2024.100542
Milena Schönke , Patrick C.N. Rensen

Obesity is a significant global burden for individuals and healthcare systems with its array of associated chronic cardiometabolic diseases. While lifestyle modifications such as dietary interventions and increased physical activity are effective in weight management, recent investigations highlight the critical role of timing these interventions in accordance with our body's circadian clock. Over the past decade, multiple studies and meta analyses have investigated how the timing of exercise training influences white adipose tissue (WAT) biology, fat mass loss, and obesity, but physical activity guidelines have not yet adopted a recommendation for exercise timing due to conflicting conclusions. This review aims to summarize the latest findings in this field and touches upon contributing factors such as sex disparities and nutrition timing.

肥胖症是个人和医疗保健系统的一个重大全球性负担,会引发一系列相关的慢性心脏代谢疾病。虽然饮食干预和增加体育锻炼等生活方式的改变能有效控制体重,但最近的研究强调了根据人体昼夜节律来安排这些干预措施的时间的关键作用。在过去的十年中,多项研究和荟萃分析调查了运动训练的时机如何影响白色脂肪组织(WAT)生物学、脂肪量减少和肥胖,但由于结论相互矛盾,体育锻炼指南尚未采纳关于运动时机的建议。本综述旨在总结该领域的最新研究成果,并探讨性别差异和营养时机等诱因。
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引用次数: 0
Fasting-regulated mechanisms in inter-organ crosstalk 器官间串扰的快速调节机制
Pub Date : 2024-07-17 DOI: 10.1016/j.coemr.2024.100540
Ana Jimena Alfaro , Stephan Herzig

The adaptation to changing environmental cues represents a key prerequisite for the survival of an organism. Mammals, including humans, have evolved intricate endocrine signals to convey information about the nutritional status to individual organs, cells, and eventually the cell nucleus, to trigger appropriate molecular-metabolic responses. To this end, mounting a proper fasting response is determined by not only intra-organ adaptations but also inter-tissue crosstalk mechanisms that orchestrate whole-body energy homeostasis under nutrient-deprived conditions. Here, we shortly summarize recent advances in our current understanding of the key processes driving the adaptive response to fasting with a focus on the crosstalk between the adipose tissue and liver ketogenesis.

适应不断变化的环境线索是生物生存的关键前提。包括人类在内的哺乳动物已经进化出复杂的内分泌信号,将有关营养状况的信息传递给各个器官、细胞,并最终传递到细胞核,以触发适当的分子代谢反应。为此,做出适当的禁食反应不仅取决于器官内部的适应性,还取决于组织间的串联机制,这些机制可在营养缺乏的条件下协调全身能量平衡。在此,我们简要总结了我们目前对驱动禁食适应性反应的关键过程的理解的最新进展,重点是脂肪组织和肝脏酮体生成之间的串联。
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引用次数: 0
Attenuation of adipose tissue inflammation by pro-resolving lipid mediators 促溶解脂质介质缓解脂肪组织炎症
Pub Date : 2024-07-16 DOI: 10.1016/j.coemr.2024.100539
Madison Clark , Bianca E. Suur , Matúš Soták , Emma Börgeson

Adipose tissue inflammation drives systemic pathophysiology, for instance, obesity-related cardiometabolic disease. Specialized pro-resolving lipid mediators are a superfamily of endogenously produced lipids that promote the resolution of inflammation, an actively regulated process. New evidence suggests that such lipids (e.g. lipoxins) could resolve adipose tissue inflammation and, thus, subvert obesity-related diseases. A key feature of pro-resolving lipids is their ability to promote an M2-like macrophage phenotype and enhance efferocytosis while avoiding adverse side-effects typically associated with anti-inflammatory drugs, such as increased sensitivity to infections. This brief review discusses the therapeutic potential of pro-resolving lipid mediators in mitigating systemic disease fueled by adipose tissue inflammation in both experimental and human disease models.

脂肪组织炎症是全身性病理生理学的驱动因素,例如与肥胖有关的心脏代谢疾病。专门的促进消炎脂质介质是内源性产生的脂质超家族,可促进消炎这一主动调节过程。新的证据表明,这类脂质(如脂毒素)可以解决脂肪组织的炎症,从而减少与肥胖有关的疾病。促进消炎脂质的一个主要特点是,它们能够促进类似 M2 的巨噬细胞表型并增强排泄功能,同时避免通常与抗炎药物相关的不良副作用,如增加对感染的敏感性。这篇简短的综述讨论了促溶解脂质介质在减轻实验和人体疾病模型中由脂肪组织炎症引发的全身性疾病方面的治疗潜力。
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引用次数: 0
Genetics of cortisol-secreting bilateral macro- and micronodular adrenal hyperplasias 分泌皮质醇的双侧大和小结节性肾上腺皮质增生症的遗传问题
Pub Date : 2024-07-16 DOI: 10.1016/j.coemr.2024.100541
Stéphanie Larose, Stéfanie Parisien-La Salle, Isabelle Bourdeau, André Lacroix

Bilateral adrenal cortex hyperplasias can present in various forms and are divided as either macronodular or micronodular. This review presents the recent identifications of the genetic alterations responsible for the various forms of cortisol-secreting adrenal hyperplasias. These include the tumor suppressor genes ARMC5 in bilateral primary macronodular adrenal hyperplasia (PBMAH) and KDM1A in GIP-dependent PBMAH with Cushing’s syndrome. Other genetic alterations are found in PBMAH associated with rare syndromic forms and various cAMP/PKA pathway gene mutations are involved in both macronodular and micronodular adrenal hyperplasias. We present as well certain clinical recommendations for each genetic etiology, including that ARMC5 or KDM1A genetic testing should be offered to all patients with PBMAH, depending on the Cushing syndrome’s GIP-dependence or not.

双侧肾上腺皮质增生症的表现形式多种多样,可分为大结节型和小结节型。本综述介绍了最近发现的导致各种皮质醇分泌型肾上腺皮质增生症的基因改变。其中包括双侧原发性大结节性肾上腺增生症(PBMAH)中的肿瘤抑制基因 ARMC5 和库欣综合征 GIP 依赖性 PBMAH 中的 KDM1A。在与罕见综合征形式相关的 PBMAH 中还发现了其他基因改变,各种 cAMP/PKA 通路基因突变均涉及大结节性和小结节性肾上腺增生症。我们还针对每种遗传病因提出了一些临床建议,包括应根据库欣综合征是否依赖 GIP,对所有 PBMAH 患者进行 ARMC5 或 KDM1A 基因检测。
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引用次数: 0
Editorial overview: Genetics of endocrine tumors 编辑综述:内分泌肿瘤的遗传学
Pub Date : 2024-06-29 DOI: 10.1016/j.coemr.2024.100538
Ali S. Alzahrani, Noha Mukhtar
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引用次数: 0
How human hormones regulate human microbiota: Where are we in the middle of this terra incognita? 人体荷尔蒙如何调节人体微生物群:我们在这个未知领域的中间处于什么位置?
Pub Date : 2024-06-24 DOI: 10.1016/j.coemr.2024.100537
Andrei V. Gannesen , Sergey V. Mart'yanov, Vladimir K. Plakunov

Human organism is tightly interconnected with its microbiota on physiological and signaling levels. Microbial endocrinology as an interdisciplinary area of studying host–microbiota interactions can focus on either player: how the microbiota affects the host via synthesis of host-targeted humoral factors and how the host-derived molecules regulate the microbial community homeostasis. The present mini-review presents the authors' perspective on the impact of human hormones on the microbiota. It discusses known effects, but especially outlines existing complications in this research area, and proposes directions for future investigation.

人类机体与其微生物群在生理和信号水平上密切相关。微生物内分泌学作为研究宿主与微生物群相互作用的一个跨学科领域,可以关注其中任何一方:微生物群如何通过合成宿主靶向的体液因子影响宿主,以及宿主衍生的分子如何调节微生物群落的平衡。本微型综述从作者的角度阐述了人类激素对微生物群的影响。它讨论了已知的影响,特别是概述了这一研究领域现有的复杂情况,并提出了未来研究的方向。
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引用次数: 0
Type 1 diabetes mellitus and host–bacterial interactions in the oral cavity 1 型糖尿病与口腔中宿主与细菌的相互作用
Pub Date : 2024-06-13 DOI: 10.1016/j.coemr.2024.100536
Ulvi Kahraman Gürsoy , Neslihan Yilmaz , Dogukan Yilmaz , Sanni Grönroos , Mervi Gürsoy

Type 1 diabetes mellitus (T1DM) is an autoimmune disease which is characterized by the destruction of insulin-producing pancreatic β-cells. Current evidence supports the contribution of T-cells, macrophages, B-cells, and dendritic cells to the pathogenesis of T1DM as well. T1DM-associated risk factors, including defects in host immune response, socioeconomic conditions, and environmental factors create a dysbiotic environment in the oral cavity, which support the growth of pathogenic microbial biofilms. Changes in microbial composition, together with the diminished immune response, lead to the development of two most common oral diseases, caries and periodontal diseases. In the present review, we summarized the current evidence on oral manifestations of T1DM and described the shifts in oral microbial composition and oral immune response.

1 型糖尿病(T1DM)是一种自身免疫性疾病,其特征是产生胰岛素的胰岛β细胞遭到破坏。目前有证据表明,T 细胞、巨噬细胞、B 细胞和树突状细胞也是 T1DM 的致病因素。与 T1DM 相关的风险因素包括宿主免疫反应缺陷、社会经济条件和环境因素,这些因素在口腔中造成了一种菌群失调的环境,支持了致病微生物生物膜的生长。微生物组成的变化,加上免疫反应的减弱,导致了两种最常见的口腔疾病--龋齿和牙周病的发生。在本综述中,我们总结了目前有关 T1DM 口腔表现的证据,并描述了口腔微生物组成和口腔免疫反应的变化。
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引用次数: 0
Editorial board page 编辑委员会页面
Pub Date : 2024-06-01 DOI: 10.1016/S2451-9650(24)00028-0
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引用次数: 0
期刊
Current Opinion in Endocrine and Metabolic Research
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