Biomedical Journal最新文献_第8页

Effect of SARS-CoV2 S protein on red blood cells parameters. Some comments SARS-CoV2 S蛋白对红细胞参数的影响一些评论。

IF 4.1 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomedical Journal

Pub Date : 2025-06-01 DOI: 10.1016/j.bj.2025.100857

Geir Bjørklund , Umberto Tirelli , Salvatore Chirumbolo , Luigi Valdenassi

引用次数: 0

Rhythms under tension: Circadian clocks in an Unsynced Society 紧张下的节奏：不同步社会中的生物钟。

IF 4.1 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomedical Journal

Pub Date : 2025-06-01 DOI: 10.1016/j.bj.2025.100873

Aila Akosua Kattner

This special issue of the Biomedical Journal centers on circadian rhythms, examining the molecular mechanisms of the circadian clock, the consequences of circadian disruption, and their implications for health and disease. Featured topics include blue light therapy for sleep disorders in myocardial infarction patients; sex-specific links between clock genes and colorectal cancer; the impact of social jetlag on blood pressure; and how irregular light-dark cycles and misaligned eating patterns affect circadian stability. A study on Stenabolic (SR9009) in mice investigates its potential to mitigate weight gain, insulin resistance, and white fat accumulation under constant light exposure. Additional reviews address the role of purinoreceptors in extracellular vesicle-mediated communication, the evolving understanding of pseudogenes and their functional derivatives, and future prospects for hyperpolarized magnetic resonance imaging. Original research highlights the influence of corticosterone on white adipose tissue expansion in mice and challenges the assumed protective role of pentoxifylline against diabetic retinopathy in patients with chronic kidney disease and diabetes. A novel application of peripheral magnetic stimulation as a treatment for overactive bladder is also explored. Two studies on hidradenitis suppurativa are included: one linking the condition to an increased risk of migraine in women, and another examining its association with alopecia areata. The issue concludes with two letters to the editor on the effects of the SARS-CoV-2 spike protein on erythrocyte biology, along with a request for further clarification, which is addressed in detail.

本期《生物医学杂志》特刊以昼夜节律为中心，探讨昼夜节律钟的分子机制、昼夜节律紊乱的后果及其对健康和疾病的影响。专题包括心肌梗死患者睡眠障碍的蓝光疗法；时钟基因与结直肠癌之间的性别特异性联系社会时差对血压的影响；以及不规则的明暗周期和不一致的饮食模式如何影响昼夜节律的稳定性。一项关于小鼠窄代谢（SR9009）的研究探讨了其在持续光照下减轻体重增加、胰岛素抵抗和白色脂肪积累的潜力。其他综述涉及嘌呤受体在细胞外囊泡介导的通讯中的作用，对假基因及其功能衍生物的不断发展的理解，以及超极化磁共振成像的未来前景。原始研究强调了皮质酮对小鼠白色脂肪组织扩张的影响，并挑战了己酮茶碱对慢性肾病和糖尿病患者糖尿病视网膜病变的保护作用。外周磁刺激作为治疗膀胱过度活动的新应用也进行了探讨。其中包括两项关于化脓性汗腺炎的研究：一项将这种疾病与女性偏头痛风险增加联系起来，另一项则研究了它与斑秃的关系。这期杂志最后给编辑写了两封信，内容是关于SARS-CoV-2刺突蛋白对红细胞生物学的影响，并要求进一步澄清，详细说明了这一点。

{"title":"Rhythms under tension: Circadian clocks in an Unsynced Society","authors":"Aila Akosua Kattner","doi":"10.1016/j.bj.2025.100873","DOIUrl":"10.1016/j.bj.2025.100873","url":null,"abstract":"<div><div>This special issue of the <em>Biomedical Journal</em> centers on circadian rhythms, examining the molecular mechanisms of the circadian clock, the consequences of circadian disruption, and their implications for health and disease. Featured topics include blue light therapy for sleep disorders in myocardial infarction patients; sex-specific links between clock genes and colorectal cancer; the impact of social jetlag on blood pressure; and how irregular light-dark cycles and misaligned eating patterns affect circadian stability. A study on Stenabolic (SR9009) in mice investigates its potential to mitigate weight gain, insulin resistance, and white fat accumulation under constant light exposure. Additional reviews address the role of purinoreceptors in extracellular vesicle-mediated communication, the evolving understanding of pseudogenes and their functional derivatives, and future prospects for hyperpolarized magnetic resonance imaging. Original research highlights the influence of corticosterone on white adipose tissue expansion in mice and challenges the assumed protective role of pentoxifylline against diabetic retinopathy in patients with chronic kidney disease and diabetes. A novel application of peripheral magnetic stimulation as a treatment for overactive bladder is also explored. Two studies on hidradenitis suppurativa are included: one linking the condition to an increased risk of migraine in women, and another examining its association with alopecia areata. The issue concludes with two letters to the editor on the effects of the SARS-CoV-2 spike protein on erythrocyte biology, along with a request for further clarification, which is addressed in detail.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"48 3","pages":"Article 100873"},"PeriodicalIF":4.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

High-fat diet-induced increase in glucocorticoids contributes to adipogenesis in obese mice 高脂饮食引起的糖皮质激素增加有助于肥胖小鼠的脂肪生成。

IF 4.1 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomedical Journal

Pub Date : 2025-06-01 DOI: 10.1016/j.bj.2024.100772

Sheng-Feng Tsai , Pei-Ling Hsu , Mei-Chen Yeh , Hao-Chang Hung , Monica Meng-Chun Shih , Bon-chu Chung , Chia-Yih Wang , Chih-Jen Chang , Yu-Min Kuo

Background

This study was designed to examine how glucocorticoids (GCs) induced by a long-term ingestion of high-fat diet (HFD) mediate the HFD-induced adipose expansion and obesity.

Material and methods

To address this goal, we used a unique L/L mouse model that fails to induce its corticosterone (CORT) level, a major type of GCs in rodents, after prolonged exposure to an HFD.

Results

We found that, after receiving a 12-week HFD feeding, the L/L mice show less weight gain, milder adipose expansion, and higher plasma levels of triglycerides than the wild-type mice. These changes were reversed by replenishing CORT to L/L mice. When examining the expression levels of various molecules linked to lipid uptake and de novo lipogenesis in CORT-induced adipose expansion, we observed a reduction in the expression of adipose preadipocyte factor 1 (Pref-1), a key regulator in adipogenesis. In 3T3-L1 preadipocyte-like cells, dexamethasone, an agonist of the glucocorticoid receptor, also reduced expressions of Pref-1 and facilitated intracellular accumulation of lipids.

Conclusions

Our results suggest that fat ingestion-induced release of CORT contributes to adipose expansion and development of obesity and highlight the pathogenic role of CORT-mediated downregulation of adipose Pref-1 in diet-induced obesity.

背景：本研究旨在探讨长期摄入高脂饮食（HFD）诱导的糖皮质激素（GCs）如何介导HFD诱导的脂肪膨胀和肥胖：为了实现这一目标，我们使用了一种独特的 L/L 小鼠模型，该模型在长期摄入高脂饮食后不能诱导皮质酮（CORT）水平，而皮质酮是啮齿类动物体内的一种主要 GCs：结果：我们发现，与野生型小鼠相比，L/L 型小鼠在摄入 12 周高密度脂蛋白后体重增加较少，脂肪膨胀较轻，血浆甘油三酯水平较高。给L/L小鼠补充CORT后，这些变化被逆转。在研究 CORT 诱导的脂肪膨胀过程中与脂质摄取和新脂肪生成相关的各种分子的表达水平时，我们观察到脂肪前脂肪细胞因子 1（Pref-1）的表达减少，而 Pref-1 是脂肪生成的一个关键调节因子。在 3T3-L1 类前脂肪细胞中，糖皮质激素受体激动剂地塞米松也会降低 Pref-1 的表达，并促进脂质在细胞内的积累：我们的研究结果表明，脂肪摄入诱导的 CORT 释放有助于脂肪膨胀和肥胖的发生，并强调了 CORT 介导的脂肪 Pref-1 下调在饮食诱导肥胖中的致病作用。

{"title":"High-fat diet-induced increase in glucocorticoids contributes to adipogenesis in obese mice","authors":"Sheng-Feng Tsai , Pei-Ling Hsu , Mei-Chen Yeh , Hao-Chang Hung , Monica Meng-Chun Shih , Bon-chu Chung , Chia-Yih Wang , Chih-Jen Chang , Yu-Min Kuo","doi":"10.1016/j.bj.2024.100772","DOIUrl":"10.1016/j.bj.2024.100772","url":null,"abstract":"<div><h3>Background</h3><div>This study was designed to examine how glucocorticoids (GCs) induced by a long-term ingestion of high-fat diet (HFD) mediate the HFD-induced adipose expansion and obesity.</div></div><div><h3>Material and methods</h3><div>To address this goal, we used a unique L/L mouse model that fails to induce its corticosterone (CORT) level, a major type of GCs in rodents, after prolonged exposure to an HFD.</div></div><div><h3>Results</h3><div>We found that, after receiving a 12-week HFD feeding, the L/L mice show less weight gain, milder adipose expansion, and higher plasma levels of triglycerides than the wild-type mice. These changes were reversed by replenishing CORT to L/L mice. When examining the expression levels of various molecules linked to lipid uptake and <em>de novo</em> lipogenesis in CORT-induced adipose expansion, we observed a reduction in the expression of adipose preadipocyte factor 1 (Pref-1), a key regulator in adipogenesis. In 3T3-L1 preadipocyte-like cells, dexamethasone, an agonist of the glucocorticoid receptor, also reduced expressions of Pref-1 and facilitated intracellular accumulation of lipids.</div></div><div><h3>Conclusions</h3><div>Our results suggest that fat ingestion-induced release of CORT contributes to adipose expansion and development of obesity and highlight the pathogenic role of CORT-mediated downregulation of adipose Pref-1 in diet-induced obesity.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"48 3","pages":"Article 100772"},"PeriodicalIF":4.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141756990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Role of purinoreceptors in the release of extracellular vesicles and consequences on immune response and cancer progression 嘌呤受体在细胞外囊泡释放中的作用及其对免疫反应和癌症进展的影响。

IF 4.1 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomedical Journal

Pub Date : 2025-06-01 DOI: 10.1016/j.bj.2024.100805

Thomas Duret , Mohammed Elmallah , Jérôme Rollin , Philippe Gatault , Lin-Hua Jiang , Sébastien Roger

Cell-to-cell communication is a major process for accommodating cell functioning to changes in the environments and to preserve tissue and organism homeostasis. It is achieved by different mechanisms characterized by the origin of the message, the molecular nature of the messenger, its speed of action and its reach. Purinergic signalling is a powerful mechanism initiated by extracellular nucleotides, such as ATP, acting on plasma membrane purinoreceptors. Purinergic signalling is tightly controlled in time and space by the action of ectonucleotidases. Recent studies have highlighted the critical role of purinergic signalling in controlling the generation, release and fate of extracellular vesicles and, in this way, mediating long-distance responses. Most of these discoveries have been made in immune and cancer cells. This review is aimed at establishing the current knowledge on the way which purinoreceptors control extracellular vesicle-mediated communications and consequences for recipient cells.

细胞间通信是细胞功能适应环境变化、保持组织和机体平衡的主要过程。它是通过不同的机制实现的，这些机制的特点是信息的来源、信使的分子性质、作用速度和影响范围。嘌呤能信号是一种由细胞外核苷酸（如 ATP）作用于质膜嘌呤感受器而启动的强大机制。嘌呤能信号在时间和空间上都受到外切核苷酸酶的严格控制。最近的研究突显了嘌呤能信号在控制细胞外囊泡的生成、释放和归宿方面的关键作用，并以这种方式介导远距离反应。这些发现大多是在免疫细胞和癌细胞中发现的。本综述旨在介绍嘌呤受体如何控制细胞外囊泡介导的通讯及其对受体细胞的影响。

引用次数: 0

Circadian rhythmicity and human health 昼夜节律与人类健康。

IF 4.1 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomedical Journal

Pub Date : 2025-06-01 DOI: 10.1016/j.bj.2025.100855

Jan Martel , David M. Ojcius , John D. Young

Our modern lifestyle involves irregular eating habits and extended periods spent indoors under artificial lighting. This lifestyle contrasts with the body's circadian rhythms and likely contributes to an increase of chronic diseases worldwide. This special issue on the circadian rhythm contains articles that deepen our understanding of the biological rhythmicity associated with health and disease. Research articles include studies on the effects of light therapy in patients with myocardial infarction and 24-h ambulatory blood pressure monitoring in Japanese women. Review articles cover the roles of micro-RNAs in colorectal cancer, the influence of light, electromagnetic fields and water on biological rhythms, and the effects of eating patterns on metabolic diseases. These studies and review articles highlight the importance of maintaining circadian rhythms and provide practical tips to improve human health.

我们的现代生活方式包括不规律的饮食习惯和长时间呆在室内的人工照明下。这种生活方式与人体的昼夜节律相反，可能会导致全球慢性疾病的增加。这个关于昼夜节律的特刊包含了加深我们对与健康和疾病相关的生物节律的理解的文章。研究文章包括光疗对心肌梗死患者的影响的研究，24小时动态血压监测日本妇女和接受五种抗高血压药物之一的患者。综述文章涵盖了微rna在结直肠癌中的作用，光、电磁场和水对生物节律的影响，以及饮食模式对代谢性疾病的影响。这些研究和评论文章强调了维持昼夜节律的重要性，并提供了改善人类健康的实用技巧。

引用次数: 0

Advancements, challenges, and future prospects in clinical hyperpolarized magnetic resonance imaging: A comprehensive review 临床超极化磁共振成像的进展、挑战和未来前景：全面回顾。

IF 4.1 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomedical Journal

Pub Date : 2025-06-01 DOI: 10.1016/j.bj.2024.100802

Ching-Yi Hsieh , Ying-Chieh Lai , Kuan-Ying Lu , Gigin Lin

Hyperpolarized (HP) magnetic resonance imaging (MRI) is a groundbreaking imaging platform advancing from research to clinical practice, offering new possibilities for real-time, non-invasive metabolic imaging. This review explores the latest advancements, challenges, and future directions of HP MRI, emphasizing its transformative impact on both translational research and clinical applications. By employing techniques such as dissolution Dynamic Nuclear Polarization (dDNP), Parahydrogen-Induced Polarization (PHIP), Signal Amplification by Reversible Exchange (SABRE), and Spin-Exchange Optical Pumping (SEOP), HP MRI achieves enhanced nuclear spin polarization, enabling in vivo visualization of metabolic pathways with exceptional sensitivity. Current challenges, such as limited imaging windows, complex pre-scan protocols, and data processing difficulties, are addressed through innovative solutions like advanced pulse sequences, bolus tracking, and kinetic modeling. We highlight the evolution of HP MRI technology, focusing on its potential to revolutionize disease diagnosis and monitoring by revealing metabolic processes beyond the reach of conventional MRI and positron emission tomography (PET). Key advancements include the development of novel tracers like [2–¹³C]pyruvate and [1–¹³C]-alpha-ketoglutarate and improved data analysis techniques, broadening the scope of clinical metabolic imaging. Future prospects emphasize integrating artificial intelligence, standardizing imaging protocols, and developing new hyperpolarized agents to enhance reproducibility and expand clinical capabilities particularly in oncology, cardiology, and neurology. Ultimately, we envisioned HP MRI as a standardized modality for dynamic metabolic imaging in clinical practice.

超极化（HP）磁共振成像（MRI）是一个突破性的成像平台，正从研究走向临床实践，为实时、无创的代谢成像提供了新的可能性。这篇综述探讨了高压磁共振成像的最新进展、挑战和未来方向，强调了它对转化研究和临床应用的变革性影响。通过采用溶解动态核极化 (dDNP)、对氢诱导极化 (PHIP)、可逆交换信号放大 (SABRE) 和自旋交换光学泵浦 (SEOP) 等技术，HP MRI 实现了增强的核自旋极化，从而能以超高的灵敏度实现代谢途径的体内可视化。通过先进的脉冲序列、栓剂跟踪和动力学建模等创新解决方案，目前所面临的挑战，如有限的成像窗口、复杂的预扫描方案和数据处理困难等，都得到了解决。我们着重介绍了 HP MRI 技术的发展，重点是通过揭示传统 MRI 和正电子发射断层扫描 (PET) 无法实现的代谢过程，该技术有望彻底改变疾病诊断和监测。主要进展包括开发了新型示踪剂，如[2-13C]丙酮酸和[1-13C]-α-酮戊二酸，并改进了数据分析技术，扩大了临床代谢成像的范围。未来的前景强调整合人工智能、标准化成像方案以及开发新的超极化制剂，以提高可重复性并扩展临床能力，尤其是在肿瘤学、心脏病学和神经学领域。最终，我们希望 HP MRI 成为临床实践中动态代谢成像的标准化模式。

{"title":"Advancements, challenges, and future prospects in clinical hyperpolarized magnetic resonance imaging: A comprehensive review","authors":"Ching-Yi Hsieh , Ying-Chieh Lai , Kuan-Ying Lu , Gigin Lin","doi":"10.1016/j.bj.2024.100802","DOIUrl":"10.1016/j.bj.2024.100802","url":null,"abstract":"<div><div>Hyperpolarized (HP) magnetic resonance imaging (MRI) is a groundbreaking imaging platform advancing from research to clinical practice, offering new possibilities for real-time, non-invasive metabolic imaging. This review explores the latest advancements, challenges, and future directions of HP MRI, emphasizing its transformative impact on both translational research and clinical applications. By employing techniques such as dissolution Dynamic Nuclear Polarization (dDNP), Parahydrogen-Induced Polarization (PHIP), Signal Amplification by Reversible Exchange (SABRE), and Spin-Exchange Optical Pumping (SEOP), HP MRI achieves enhanced nuclear spin polarization, enabling in vivo visualization of metabolic pathways with exceptional sensitivity. Current challenges, such as limited imaging windows, complex pre-scan protocols, and data processing difficulties, are addressed through innovative solutions like advanced pulse sequences, bolus tracking, and kinetic modeling. We highlight the evolution of HP MRI technology, focusing on its potential to revolutionize disease diagnosis and monitoring by revealing metabolic processes beyond the reach of conventional MRI and positron emission tomography (PET). Key advancements include the development of novel tracers like [2–<sup>13</sup>C]pyruvate and [1–<sup>13</sup>C]-alpha-ketoglutarate and improved data analysis techniques, broadening the scope of clinical metabolic imaging. Future prospects emphasize integrating artificial intelligence, standardizing imaging protocols, and developing new hyperpolarized agents to enhance reproducibility and expand clinical capabilities particularly in oncology, cardiology, and neurology. Ultimately, we envisioned HP MRI as a standardized modality for dynamic metabolic imaging in clinical practice.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"48 3","pages":"Article 100802"},"PeriodicalIF":4.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The clockwork macrophage: timing in innate immunity. 生物钟巨噬细胞：先天免疫中的定时。

IF 4.1 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomedical Journal

Pub Date : 2025-05-21 DOI: 10.1016/j.bj.2025.100872

Siyu Chen, Nick Ciccone, David Ray

The circadian clock enables organisms to predict daily environmental changes and synchronize their physiology and behaviour accordingly. Macrophages, key sensor cells in the innate immune system, exhibit cell-autonomous circadian rhythmicity. This circadian rhythmic behaviour is synchronised to the central clock in the hypothalamus as a result of neural, and hormonal signals. Macrophage rhythms and responses involve sensing temporal cues, integrating information from tissue-specific environments, and initiating context-appropriate, time-gated responses. On a broader scale, monocytes and macrophages communicate and synchronize with other immune cells, migrate throughout the body, and infiltrate tissues, collectively contributing to circadian regulation in both health and disease. While the field of macrophage circadian biology is rapidly advancing, it is equally important to reflect on its historical development, which has been shaped by over two centuries of accumulating knowledge and technological progress. This review traces key milestones in macrophage and circadian research, examining how recent discoveries have refined our understanding of early foundational questions and setting the stage for future inquiries. Notably, many intriguing questions remain unresolved, including the circadian regulation of macrophage function under steady-state conditions, the tissue-specific heterogeneity of macrophage circadian rhythms, and the role of macrophage circadian clocks in disease pathogenesis and their potential clinical implications.

生物钟使生物体能够预测每天的环境变化，并相应地同步它们的生理和行为。巨噬细胞是先天免疫系统中的关键感知细胞，具有细胞自主的昼夜节律性。作为神经和激素信号的结果，这种昼夜节律行为与下丘脑的中央时钟同步。巨噬细胞节律和反应涉及感知时间线索，整合来自组织特异性环境的信息，并启动上下文适当的时间门控反应。在更广泛的范围内，单核细胞和巨噬细胞与其他免疫细胞交流和同步，在全身迁移，并渗透到组织中，共同促进健康和疾病的昼夜节律调节。虽然巨噬细胞昼夜生物学领域正在迅速发展，但同样重要的是要反思其历史发展，这是由两个多世纪的知识积累和技术进步所形成的。这篇综述追溯了巨噬细胞和昼夜节律研究的关键里程碑，研究了最近的发现如何改进了我们对早期基础问题的理解，并为未来的研究奠定了基础。值得注意的是，许多有趣的问题仍未解决，包括稳态条件下巨噬细胞功能的昼夜调节，巨噬细胞昼夜节律的组织特异性异质性，巨噬细胞昼夜节律时钟在疾病发病机制中的作用及其潜在的临床意义。

{"title":"The clockwork macrophage: timing in innate immunity.","authors":"Siyu Chen, Nick Ciccone, David Ray","doi":"10.1016/j.bj.2025.100872","DOIUrl":"https://doi.org/10.1016/j.bj.2025.100872","url":null,"abstract":"<p><p>The circadian clock enables organisms to predict daily environmental changes and synchronize their physiology and behaviour accordingly. Macrophages, key sensor cells in the innate immune system, exhibit cell-autonomous circadian rhythmicity. This circadian rhythmic behaviour is synchronised to the central clock in the hypothalamus as a result of neural, and hormonal signals. Macrophage rhythms and responses involve sensing temporal cues, integrating information from tissue-specific environments, and initiating context-appropriate, time-gated responses. On a broader scale, monocytes and macrophages communicate and synchronize with other immune cells, migrate throughout the body, and infiltrate tissues, collectively contributing to circadian regulation in both health and disease. While the field of macrophage circadian biology is rapidly advancing, it is equally important to reflect on its historical development, which has been shaped by over two centuries of accumulating knowledge and technological progress. This review traces key milestones in macrophage and circadian research, examining how recent discoveries have refined our understanding of early foundational questions and setting the stage for future inquiries. Notably, many intriguing questions remain unresolved, including the circadian regulation of macrophage function under steady-state conditions, the tissue-specific heterogeneity of macrophage circadian rhythms, and the role of macrophage circadian clocks in disease pathogenesis and their potential clinical implications.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"100872"},"PeriodicalIF":4.1,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144131901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Overview: PAI-1 inhibitors and clinical applications 综述：PAI-1抑制剂及其临床应用。

IF 4.4 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomedical Journal

Pub Date : 2025-05-20 DOI: 10.1016/j.bj.2025.100874

Toshio Miyata

Plasminogen activator inhibitor-1 (PAI-1) is a protein involved in the fibrinolytic system and has been reported to be involved in various pathologies such as fibrosis and inflammation. We have developed small molecule inhibitors of human PAI-1 for clinical applications. A clinical candidate compound (TM5509) was finally identified among over 1400 derivatives of a hit compound (TM5275) searched by the X-ray crystal structure information of human PAI-1 and the in silico approach on a big virtual chemical library. From pre-clinical studies using our PAI-1 inhibitors, new therapeutic concepts for clinical applications, such as anti-cancer and anti-aging, have been conceived, some oh which have been tested in various investigator-initiated clinical trials.

纤溶酶原激活物抑制剂-1 （PAI-1）是一种参与纤溶系统的蛋白，据报道与多种病理如纤维化和炎症有关。我们已经开发了用于临床应用的人PAI-1小分子抑制剂。利用人PAI-1的x射线晶体结构信息和大型虚拟化学文库的计算机方法，从候选化合物TM5275的1400多个衍生物中最终鉴定出临床候选化合物TM5509。从使用我们的PAI-1抑制剂的临床前研究，新的临床应用治疗概念，如抗癌和抗衰老，已经被设想出来，其中一些已经在各种研究者发起的临床试验中进行了测试。

引用次数: 0

Autophagy-induced osteoblast-derived exosomes maintain bone formation and prevent osteoporosis by remodeling gut microbiota-metabolism. 自噬诱导的成骨细胞来源的外泌体通过重塑肠道微生物代谢来维持骨形成和预防骨质疏松症。

IF 4.4 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomedical Journal

Pub Date : 2025-05-06 DOI: 10.1016/j.bj.2025.100870

Lin Chen, Liesheng Lu, Chunyi Fan, Xiaonan Zhu, Ling Pan, Shanshan Tang, Yufan Wang, Yongde Peng, Li You

Background: Osteoporosis is a chronic disease of bone metabolism with high incidence rates. Recently, exosome therapy has emerged as a promising avenue for the treatment of osteoporosis. However, the role of autophagy-induced osteoblast-derived exosomes (Auto-exo) in osteoporosis has yet to be elucidated.

Methods: The effect of Auto-exo on bone formation was assessed in vivo. The composition of gut microbiota was determined through 16S rDNA sequencing, and metabolite profiles were analyzed using liquid chromatography-mass spectrometry (LC-MS). Cell experiments were conducted to explore the role of bilirubin in bone formation.

Results: Auto-exo were successfully isolated and identified. Auto-exo promoted bone formation and alleviated osteoporosis progression in a mouse model of osteoporosis. 16S rDNA sequencing revealed that Auto-exo changed diversity and composition of gut microbiota in osteoporotic mice, with a notable increase in Lactobacillus and a decrease in Dubosiella and Faecalibaculum. LC-MS analysis indicated that Auto-exo treatment reduced the elevated levels of bilirubin in osteoporotic mice. Cell experiments uncovered that bilirubin remarkably inhibited osteoblast differentiation. Furthermore, Auto-exo promoted osteoblast differentiation via inhibiting bilirubin production.

Conclusions: Our findings demonstrated that Auto-exo promoted bone formation by modulating the gut microbiota-metabolite bilirubin axis, thereby alleviating osteoporosis progression. This discovery provides a novel perspective on the mechanism underlying the therapeutic effects of Auto-exo on osteoporosis.

背景：骨质疏松症是一种发病率较高的慢性骨代谢疾病。最近，外泌体疗法已成为治疗骨质疏松症的一个有前途的途径。然而，自噬诱导的成骨细胞衍生外泌体（Auto-exo）在骨质疏松症中的作用尚未阐明。方法：在体内观察Auto-exo对骨形成的影响。通过16S rDNA测序确定肠道菌群组成，并使用液相色谱-质谱（LC-MS）分析代谢物谱。通过细胞实验探讨胆红素在骨形成中的作用。结果：成功分离鉴定了Auto-exo。在骨质疏松小鼠模型中，Auto-exo促进骨形成并减轻骨质疏松进展。16S rDNA测序结果显示，Auto-exo改变了骨质疏松小鼠肠道菌群的多样性和组成，乳酸杆菌显著增加，Dubosiella和Faecalibaculum显著减少。LC-MS分析表明，Auto-exo治疗降低了骨质疏松小鼠胆红素的升高水平。细胞实验发现胆红素显著抑制成骨细胞分化。此外，Auto-exo通过抑制胆红素的产生促进成骨细胞分化。结论：我们的研究结果表明，Auto-exo通过调节肠道微生物代谢产物胆红素轴促进骨形成，从而缓解骨质疏松症的进展。这一发现为Auto-exo治疗骨质疏松症的机制提供了一个新的视角。

{"title":"Autophagy-induced osteoblast-derived exosomes maintain bone formation and prevent osteoporosis by remodeling gut microbiota-metabolism.","authors":"Lin Chen, Liesheng Lu, Chunyi Fan, Xiaonan Zhu, Ling Pan, Shanshan Tang, Yufan Wang, Yongde Peng, Li You","doi":"10.1016/j.bj.2025.100870","DOIUrl":"10.1016/j.bj.2025.100870","url":null,"abstract":"<p><strong>Background: </strong>Osteoporosis is a chronic disease of bone metabolism with high incidence rates. Recently, exosome therapy has emerged as a promising avenue for the treatment of osteoporosis. However, the role of autophagy-induced osteoblast-derived exosomes (Auto-exo) in osteoporosis has yet to be elucidated.</p><p><strong>Methods: </strong>The effect of Auto-exo on bone formation was assessed in vivo. The composition of gut microbiota was determined through 16S rDNA sequencing, and metabolite profiles were analyzed using liquid chromatography-mass spectrometry (LC-MS). Cell experiments were conducted to explore the role of bilirubin in bone formation.</p><p><strong>Results: </strong>Auto-exo were successfully isolated and identified. Auto-exo promoted bone formation and alleviated osteoporosis progression in a mouse model of osteoporosis. 16S rDNA sequencing revealed that Auto-exo changed diversity and composition of gut microbiota in osteoporotic mice, with a notable increase in Lactobacillus and a decrease in Dubosiella and Faecalibaculum. LC-MS analysis indicated that Auto-exo treatment reduced the elevated levels of bilirubin in osteoporotic mice. Cell experiments uncovered that bilirubin remarkably inhibited osteoblast differentiation. Furthermore, Auto-exo promoted osteoblast differentiation via inhibiting bilirubin production.</p><p><strong>Conclusions: </strong>Our findings demonstrated that Auto-exo promoted bone formation by modulating the gut microbiota-metabolite bilirubin axis, thereby alleviating osteoporosis progression. This discovery provides a novel perspective on the mechanism underlying the therapeutic effects of Auto-exo on osteoporosis.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"100870"},"PeriodicalIF":4.4,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

SLC7A11-HSPB1 axis: A novel mechanism for hepatocellular carcinoma progression and ferroptosis regulation. SLC7A11-HSPB1轴：肝细胞癌进展和铁下垂调控的新机制

IF 4.4 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomedical Journal

Pub Date : 2025-05-06 DOI: 10.1016/j.bj.2025.100869

Yan An, Weilong Liu, Yuliang Deng, Wanqiu Huang, Jian Huang

Background: SLC7A11, a plasma membrane protein, has been implicated as an oncogene in various cancers, including hepatocellular carcinoma (HCC). Its role in HCC pathogenesis, particularly in relation to ferroptosis, is not well understood. This study aims to investigate the function of SLC7A11 with ferroptosis and its interaction in development of HCC.

Methods and materials: Clinical HCC tissue samples were used to analyze the expression of SLC7A11 by RT-PCR. The impact of SLC7A11 on HCC cell viability, proliferation, and migration was assessed by CCK-8, AlamarBlue and Transwell. Protein-protein interactions were explored using co-immunoprecipitation and immunofluorescence. The effect of SLC7A11 on ferroptosis was evaluated by iron levels, ROS, and GSH. The impact of sorafenib and doxorubicin (DOX) on HCC cells was analyzed using cell viability assay.

Results: SLC7A11 was found to be highly expressed in HCC tissues and was correlated with tumor size and poor prognosis. Overexpression of SLC7A11 in HCC cells promoted cell viability, proliferation, and migration. Additionally, SLC7A11 overexpression mitigated erastin-induced ferroptosis, as evidenced by decreased ROS levels and increased GSH levels. We also discovered that SLC7A11 interacted with HSPB1. HSPB1 inhibited erastin-induced ferroptosis. Furthermore, a portion of the cell death induced by sorafenib and DOX is attributed to ferroptosis, with HSPB1 and SLC7A11 inhibiting the death induced by the two drugs, respectively.

Conclusions: SLC7A11 plays a significant role in HCC progression by inhibiting ferroptosis, and its interaction with HSPB1 is a critical pathway in this process. Targeting the SLC7A11-HSPB1 axis may provide a novel therapeutic strategy for HCC treatment, highlighting the importance of understanding the mechanisms of ferroptosis in cancer cells.

背景：SLC7A11是一种质膜蛋白，已被认为是多种癌症的致癌基因，包括肝细胞癌（HCC）。它在HCC发病机制中的作用，特别是与铁下垂有关的作用，尚不清楚。本研究旨在探讨SLC7A11在铁下垂中的功能及其在HCC发生中的相互作用。方法与材料：采用RT-PCR方法对临床HCC组织样本进行SLC7A11的表达分析。通过CCK-8、AlamarBlue和Transwell评估SLC7A11对HCC细胞活力、增殖和迁移的影响。利用共免疫沉淀和免疫荧光研究蛋白-蛋白相互作用。通过铁水平、ROS和GSH评估SLC7A11对铁下垂的影响。采用细胞活力法分析索拉非尼和阿霉素（DOX）对HCC细胞的影响。结果：SLC7A11在HCC组织中高表达，与肿瘤大小及预后不良相关。SLC7A11在HCC细胞中的过表达促进了细胞活力、增殖和迁移。此外，SLC7A11过表达减轻了erasastin诱导的铁下垂，这可以通过降低ROS水平和增加GSH水平来证明。我们还发现SLC7A11与HSPB1相互作用。HSPB1抑制erastin诱导的铁下垂。此外，索拉非尼和DOX诱导的部分细胞死亡归因于铁凋亡，HSPB1和SLC7A11分别抑制两种药物诱导的死亡。结论：SLC7A11通过抑制铁下垂在HCC进展中发挥重要作用，其与HSPB1的相互作用是这一过程的关键途径。靶向SLC7A11-HSPB1轴可能为HCC治疗提供一种新的治疗策略，强调了了解癌细胞铁凋亡机制的重要性。

{"title":"SLC7A11-HSPB1 axis: A novel mechanism for hepatocellular carcinoma progression and ferroptosis regulation.","authors":"Yan An, Weilong Liu, Yuliang Deng, Wanqiu Huang, Jian Huang","doi":"10.1016/j.bj.2025.100869","DOIUrl":"10.1016/j.bj.2025.100869","url":null,"abstract":"<p><strong>Background: </strong>SLC7A11, a plasma membrane protein, has been implicated as an oncogene in various cancers, including hepatocellular carcinoma (HCC). Its role in HCC pathogenesis, particularly in relation to ferroptosis, is not well understood. This study aims to investigate the function of SLC7A11 with ferroptosis and its interaction in development of HCC.</p><p><strong>Methods and materials: </strong>Clinical HCC tissue samples were used to analyze the expression of SLC7A11 by RT-PCR. The impact of SLC7A11 on HCC cell viability, proliferation, and migration was assessed by CCK-8, AlamarBlue and Transwell. Protein-protein interactions were explored using co-immunoprecipitation and immunofluorescence. The effect of SLC7A11 on ferroptosis was evaluated by iron levels, ROS, and GSH. The impact of sorafenib and doxorubicin (DOX) on HCC cells was analyzed using cell viability assay.</p><p><strong>Results: </strong>SLC7A11 was found to be highly expressed in HCC tissues and was correlated with tumor size and poor prognosis. Overexpression of SLC7A11 in HCC cells promoted cell viability, proliferation, and migration. Additionally, SLC7A11 overexpression mitigated erastin-induced ferroptosis, as evidenced by decreased ROS levels and increased GSH levels. We also discovered that SLC7A11 interacted with HSPB1. HSPB1 inhibited erastin-induced ferroptosis. Furthermore, a portion of the cell death induced by sorafenib and DOX is attributed to ferroptosis, with HSPB1 and SLC7A11 inhibiting the death induced by the two drugs, respectively.</p><p><strong>Conclusions: </strong>SLC7A11 plays a significant role in HCC progression by inhibiting ferroptosis, and its interaction with HSPB1 is a critical pathway in this process. Targeting the SLC7A11-HSPB1 axis may provide a novel therapeutic strategy for HCC treatment, highlighting the importance of understanding the mechanisms of ferroptosis in cancer cells.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"100869"},"PeriodicalIF":4.4,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0