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Metabolic (re)programming in skeletal stem cell populations 骨骼干细胞群的代谢(再)编程
Pub Date : 2024-09-17 DOI: 10.1016/j.coemr.2024.100548
Milica Rajković , Nikola Bogosavljević , Marko Vujačić , Drenka Trivanović
Current findings imply that skeletal stem cell (SSC) populations intermittently utilize glycolysis and oxidative phosphorylation to satisfy energetic demands and accomplish their lineage specification, or even dedifferentiation. Metabolic reprogramming is one of the earliest processes that governs adult bone regeneration. Increasing numbers of findings indicate that SSCs reside in bone and bone marrow compartments and contribute to different phases of bone homeostasis, remodeling, and repair. All these processes have distinct microenvironmental landscapes imposing specific metabolic requirements to SSCs. Although glucose has been considered as the main source of energy for skeleton, novel findings emphasize the importance of still challenging metabolic profiling of SSCs at different stages of bone development, homeostasis, and repair for delicate control of stem cell-guided bone regeneration.
目前的研究结果表明,骨骼干细胞(SSC)群体间歇性地利用糖酵解和氧化磷酸化来满足能量需求,并完成其血统规范,甚至是去分化。代谢重编程是支配成体骨再生的最早过程之一。越来越多的研究结果表明,造血干细胞存在于骨骼和骨髓中,并在骨骼稳态、重塑和修复的不同阶段发挥作用。所有这些过程都有不同的微环境,对造血干细胞提出了特定的代谢要求。虽然葡萄糖一直被认为是骨骼的主要能量来源,但新发现强调了在骨骼发育、平衡和修复的不同阶段对造血干细胞进行新陈代谢分析的重要性,这对精细控制干细胞引导的骨骼再生仍具有挑战性。
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引用次数: 0
Local and systemic impact of adipocyte senescence-associated secretory profile 脂肪细胞衰老相关分泌特征对局部和全身的影响
Pub Date : 2024-09-13 DOI: 10.1016/j.coemr.2024.100547
Yi Ching Esther Wan, Jeremy Dufau, Kirsty L. Spalding
Obesity has become one of the most prevalent diseases worldwide. The accumulation of fat mass is associated with an increased risk of numerous comorbidities. Despite this, the precise mechanisms by which unhealthy fat cells contribute to the dysfunction of various tissues throughout the body remain poorly understood. Recently, cellular senescence in adipocytes has emerged as a significant factor in the pathological consequences of obesity. Here we review current knowledge regarding senescence in adipose tissue and adipocytes. We highlight the known mechanisms driving cellular senescence in mature adipocytes during obesity and summarize the deleterious crosstalk between senescent adipocytes and neighboring cells (as well as distant organs) as mediated by the senescence-associated secretory phenotype.
肥胖症已成为全球最普遍的疾病之一。脂肪的积累与多种并发症的风险增加有关。尽管如此,人们对不健康的脂肪细胞导致全身各种组织功能障碍的确切机制仍然知之甚少。最近,脂肪细胞的细胞衰老已成为肥胖症病理后果的一个重要因素。在此,我们回顾了目前有关脂肪组织和脂肪细胞衰老的知识。我们强调了已知的肥胖过程中成熟脂肪细胞细胞衰老的驱动机制,并总结了衰老脂肪细胞与邻近细胞(以及远处器官)之间由衰老相关分泌表型介导的有害串扰。
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引用次数: 0
Cholinergic signaling in adipose tissue 脂肪组织中的胆碱能信号传递
Pub Date : 2024-09-11 DOI: 10.1016/j.coemr.2024.100546
Vladimir S. Shavva , Laura Tarnawski , Ting Liu , Osman Ahmed , Peder S. Olofsson
Until recently, the role of direct cholinergic regulation of adipose tissue function was unclear. With the identification of the α2 nicotinic acetylcholine receptor as a key regulator of adaptive thermogenesis in white adipose tissue, there is evidence of direct cholinergic regulation of adipocyte physiology. As in the spleen and the bone marrow, there is a local source of nonneuronal acetylcholine in adipose tissue: Macrophages release acetylcholine in response to a multiplicity of stimuli including cold, norepinephrine, and fibroblast growth factor 21, integrating cholinergic signaling in the adipose tissue microenvironment. The recent insights on this cholinergic signaling provides a useful framework for further mapping of the physiology of cholinergic signaling in adipose tissue.
直到最近,胆碱能对脂肪组织功能的直接调节作用仍不明确。随着α2 尼古丁乙酰胆碱受体被确认为白色脂肪组织适应性产热的关键调节因子,有证据表明胆碱能直接调节脂肪细胞的生理机能。与脾脏和骨髓一样,脂肪组织中也有非神经元乙酰胆碱的局部来源:巨噬细胞会在寒冷、去甲肾上腺素和成纤维细胞生长因子 21 等多种刺激下释放乙酰胆碱,从而将胆碱能信号整合到脂肪组织微环境中。最近对这种胆碱能信号传导的深入研究为进一步绘制脂肪组织中胆碱能信号传导的生理学图谱提供了一个有用的框架。
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引用次数: 0
Editorial board page 编辑委员会页面
Pub Date : 2024-09-01 DOI: 10.1016/S2451-9650(24)00049-8
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引用次数: 0
Bacterial gene expression in response to catecholamine stress hormones 细菌基因表达对儿茶酚胺应激激素的反应
Pub Date : 2024-09-01 DOI: 10.1016/j.coemr.2024.100543
Meryem Boujnane, Amine Mohamed Boukerb, Nathalie Connil

Bacteria–host communication plays a crucial role in symbiosis and pathogenesis. Investigations of pathogenic bacterial responses to host neurotransmitters, including catecholamines, have been the subject of several studies. Both Epinephrine (Epi) and Norepinephrine (NE) catecholamines can modulate bacterial physiology, affecting growth, motility, biofilm formation, virulence, and interactions with eukaryotic cells. This has been widely described in Gram-negative bacteria and mostly for pathogens (i.e. Escherichia coli, Campylobacter jejuni, Salmonella enterica, and Vibrio cholerae). In this review, we focused on whole and targeted bacterial gene expression that have been modulated upon exposure to Epi and NE catecholamines. A wide range of these genes were involved in various physiological aspects (i.e. general metabolism, stress responses, uptake/transport, motility, biofilm, and virulence).

细菌与宿主的交流在共生和致病过程中起着至关重要的作用。病原细菌对宿主神经递质(包括儿茶酚胺)的反应是多项研究的主题。肾上腺素(Epi)和去甲肾上腺素(NE)儿茶酚胺都能调节细菌的生理机能,影响其生长、运动、生物膜形成、毒力以及与真核细胞的相互作用。这在革兰氏阴性细菌中得到了广泛的描述,并且主要针对病原体(即大肠杆菌、空肠弯曲杆菌、肠炎沙门氏菌和霍乱弧菌)。在这篇综述中,我们重点讨论了暴露于 Epi 和 NE 儿茶酚胺后受到调控的细菌全基因和靶基因表达。这些基因广泛涉及各种生理方面(即一般新陈代谢、应激反应、吸收/转运、运动、生物膜和毒力)。
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引用次数: 0
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
期刊
Current Opinion in Endocrine and Metabolic Research
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