Pub Date : 2024-11-21DOI: 10.1186/s40779-024-00578-9
Mei-Han Guo, David Montero
{"title":"Hans Chinese consume less O<sub>2</sub> for muscular work than european-american.","authors":"Mei-Han Guo, David Montero","doi":"10.1186/s40779-024-00578-9","DOIUrl":"https://doi.org/10.1186/s40779-024-00578-9","url":null,"abstract":"","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"11 1","pages":"73"},"PeriodicalIF":16.7,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-18DOI: 10.1186/s40779-024-00575-y
Win Lwin Thuya, Janique Michelle Peyper, Tan Ti Myen, Nur Diana Anuar, Arif Anwar, Ranga Gudimella, Nurul Huda Rutt, Nurul Shielawati Mohamed Rosli, Noorul Hidayah Badri, Teh Norleila Abdul Rahman, Raja Nurashirin, Gautam Sethi, John Kit Chung Tam, Andrea Li-Ann Wong, Ross Soo, Jonathan M Blackburn, Lingzhi Wang, Boon Cher Goh
{"title":"Exosome autoantibody biomarkers for detection of lung cancer.","authors":"Win Lwin Thuya, Janique Michelle Peyper, Tan Ti Myen, Nur Diana Anuar, Arif Anwar, Ranga Gudimella, Nurul Huda Rutt, Nurul Shielawati Mohamed Rosli, Noorul Hidayah Badri, Teh Norleila Abdul Rahman, Raja Nurashirin, Gautam Sethi, John Kit Chung Tam, Andrea Li-Ann Wong, Ross Soo, Jonathan M Blackburn, Lingzhi Wang, Boon Cher Goh","doi":"10.1186/s40779-024-00575-y","DOIUrl":"10.1186/s40779-024-00575-y","url":null,"abstract":"","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"11 1","pages":"72"},"PeriodicalIF":16.7,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11571996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-28DOI: 10.1186/s40779-024-00574-z
Ting Gong, Qing-De Wang, Patricia A Loughran, Yue-Hua Li, Melanie J Scott, Timothy R Billiar, You-Tan Liu, Jie Fan
Background: Sepsis is often accompanied by lactic acidemia and acute lung injury (ALI). Clinical studies have established that high serum lactate levels are associated with increased mortality rates in septic patients. We further observed a significant correlation between the levels of cold-inducible RNA-binding protein (CIRP) in plasma and bronchoalveolar lavage fluid (BALF), as well as lactate levels, and the severity of post-sepsis ALI. The underlying mechanism, however, remains elusive.
Methods: C57BL/6 wild type (WT), Casp8-/-, Ripk3-/-, and Zbp1-/- mice were subjected to the cecal ligation and puncture (CLP) sepsis model. In this model, we measured intra-macrophage CIRP lactylation and the subsequent release of CIRP. We also tracked the internalization of extracellular CIRP (eCIRP) in pulmonary vascular endothelial cells (PVECs) and its interaction with Z-DNA binding protein 1 (ZBP1). Furthermore, we monitored changes in ZBP1 levels in PVECs and the consequent activation of cell death pathways.
Results: In the current study, we demonstrate that lactate, accumulating during sepsis, promotes the lactylation of CIRP in macrophages, leading to the release of CIRP. Once eCIRP is internalized by PVEC through a Toll-like receptor 4 (TLR4)-mediated endocytosis pathway, it competitively binds to ZBP1 and effectively blocks the interaction between ZBP1 and tripartite motif containing 32 (TRIM32), an E3 ubiquitin ligase targeting ZBP1 for proteasomal degradation. This interference mechanism stabilizes ZBP1, thereby enhancing ZBP1-receptor-interacting protein kinase 3 (RIPK3)-dependent PVEC PANoptosis, a form of cell death involving the simultaneous activation of multiple cell death pathways, thereby exacerbating ALI.
Conclusions: These findings unveil a novel pathway by which lactic acidemia promotes macrophage-derived eCIRP release, which, in turn, mediates ZBP1-dependent PVEC PANoptosis in sepsis-induced ALI. This finding offers new insights into the molecular mechanisms driving sepsis-related pulmonary complications and provides potential new therapeutic strategies.
{"title":"Mechanism of lactic acidemia-promoted pulmonary endothelial cells death in sepsis: role for CIRP-ZBP1-PANoptosis pathway.","authors":"Ting Gong, Qing-De Wang, Patricia A Loughran, Yue-Hua Li, Melanie J Scott, Timothy R Billiar, You-Tan Liu, Jie Fan","doi":"10.1186/s40779-024-00574-z","DOIUrl":"10.1186/s40779-024-00574-z","url":null,"abstract":"<p><strong>Background: </strong>Sepsis is often accompanied by lactic acidemia and acute lung injury (ALI). Clinical studies have established that high serum lactate levels are associated with increased mortality rates in septic patients. We further observed a significant correlation between the levels of cold-inducible RNA-binding protein (CIRP) in plasma and bronchoalveolar lavage fluid (BALF), as well as lactate levels, and the severity of post-sepsis ALI. The underlying mechanism, however, remains elusive.</p><p><strong>Methods: </strong>C57BL/6 wild type (WT), Casp8<sup>-/-</sup>, Ripk3<sup>-/-</sup>, and Zbp1<sup>-/-</sup> mice were subjected to the cecal ligation and puncture (CLP) sepsis model. In this model, we measured intra-macrophage CIRP lactylation and the subsequent release of CIRP. We also tracked the internalization of extracellular CIRP (eCIRP) in pulmonary vascular endothelial cells (PVECs) and its interaction with Z-DNA binding protein 1 (ZBP1). Furthermore, we monitored changes in ZBP1 levels in PVECs and the consequent activation of cell death pathways.</p><p><strong>Results: </strong>In the current study, we demonstrate that lactate, accumulating during sepsis, promotes the lactylation of CIRP in macrophages, leading to the release of CIRP. Once eCIRP is internalized by PVEC through a Toll-like receptor 4 (TLR4)-mediated endocytosis pathway, it competitively binds to ZBP1 and effectively blocks the interaction between ZBP1 and tripartite motif containing 32 (TRIM32), an E3 ubiquitin ligase targeting ZBP1 for proteasomal degradation. This interference mechanism stabilizes ZBP1, thereby enhancing ZBP1-receptor-interacting protein kinase 3 (RIPK3)-dependent PVEC PANoptosis, a form of cell death involving the simultaneous activation of multiple cell death pathways, thereby exacerbating ALI.</p><p><strong>Conclusions: </strong>These findings unveil a novel pathway by which lactic acidemia promotes macrophage-derived eCIRP release, which, in turn, mediates ZBP1-dependent PVEC PANoptosis in sepsis-induced ALI. This finding offers new insights into the molecular mechanisms driving sepsis-related pulmonary complications and provides potential new therapeutic strategies.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"11 1","pages":"71"},"PeriodicalIF":16.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11514876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-28DOI: 10.1186/s40779-024-00562-3
Guo-Hua Zeng, Wen Zhong, Giorgio Mazzon, Wei Zhu, Sven Lahme, Sanjay Khadgi, Janak Desai, Madhu Agrawal, David Schulsinger, Mantu Gupta, Emanuele Montanari, Juan Manuel Lopez Martinez, Shabir Almousawi, Vincent Emanuel F Malonzo, Seshadri Sriprasad, Otas Durutovic, Vimoshan Arumuham, Stefania Ferretti, Wissam Kamal, Ke-Wei Xu, Fan Cheng, Xiao-Feng Gao, Ji-Wen Cheng, Bhaskar Somani, Mordechai Duvdevani, Kah Ann Git, Christian Seitz, Norberto Bernardo, Tarek Ahmed Amin Ibrahim, Albert Aquino, Takahiro Yasui, Cristian Fiori, Thomas Knoll, Athanasios Papatsoris, Nariman Gadzhiev, Ulanbek Zhanbyrbekuly, Oriol Angerri, Hugo Lopez Ramos, Iliya Saltirov, Mohamad Moussa, Guido Giusti, Fabio Vicentini, Edgar Beltran Suarez, Margaret Pearle, Glenn M Preminger, Qing-Hui Wu, Otas Durutovic, Khurshid Ghani, Marcus Maroccolo, Marianne Brehmer, Palle J Osther, Marek Zawadzki, Azimdjon Tursunkulov, Monolov Nurbek Kytaibekovich, Abdusamad Abdukakhorovich Abuvohidov, Cesar Antonio Recalde Lara, Zamari Noori, Stefano Paolo Zanetti, Sunil Shrestha, Jean de la Rosette, John Denstedt, Zhang-Qun Ye, Kemal Sarica, Simon Choong
Over the past three decades, there has been increasing interest in miniaturized percutaneous nephrolithotomy (mPCNL) techniques featuring smaller tracts as they offer potential solutions to mitigate complications associated with standard PCNL (sPCNL). However, despite this growing acceptance and recognition of its benefits, unresolved controversies and acknowledged limitations continue to impede widespread adoption due to a lack of consensus on optimal perioperative management strategies and procedural tips and tricks. In response to these challenges, an international panel comprising experts from the International Alliance of Urolithiasis (IAU) took on the task of compiling an expert consensus document on mPCNL procedures aimed at providing urologists with a comprehensive clinical framework for practice. This endeavor involved conducting a systematic literature review to identify research gaps (RGs), which formed the foundation for developing a structured questionnaire survey. Subsequently, a two-round modified Delphi survey was implemented, culminating in a group meeting to generate final evidence-based comments. All 64 experts completed the second-round survey, resulting in a response rate of 100.0%. Fifty-eight key questions were raised focusing on mPCNLs within 4 main domains, including general information (13 questions), preoperative work-up (13 questions), procedural tips and tricks (19 questions), and postoperative evaluation and follow-up (13 questions). Additionally, 9 questions evaluated the experts' experience with PCNLs. Consensus was reached on 30 questions after the second-round survey, while professional statements for the remaining 28 key questions were provided after discussion in an online panel meeting. mPCNL, characterized by a tract smaller than 18 Fr and an innovative lithotripsy technique, has firmly established itself as a viable and effective approach for managing upper urinary tract stones in both adults and pediatrics. It offers several advantages over sPCNL including reduced bleeding, fewer requirements for nephrostomy tubes, decreased pain, and shorter hospital stays. The series of detailed techniques presented here serve as a comprehensive guide for urologists, aiming to improve their procedural understanding and optimize patient outcomes.
{"title":"International Alliance of Urolithiasis (IAU) consensus on miniaturized percutaneous nephrolithotomy.","authors":"Guo-Hua Zeng, Wen Zhong, Giorgio Mazzon, Wei Zhu, Sven Lahme, Sanjay Khadgi, Janak Desai, Madhu Agrawal, David Schulsinger, Mantu Gupta, Emanuele Montanari, Juan Manuel Lopez Martinez, Shabir Almousawi, Vincent Emanuel F Malonzo, Seshadri Sriprasad, Otas Durutovic, Vimoshan Arumuham, Stefania Ferretti, Wissam Kamal, Ke-Wei Xu, Fan Cheng, Xiao-Feng Gao, Ji-Wen Cheng, Bhaskar Somani, Mordechai Duvdevani, Kah Ann Git, Christian Seitz, Norberto Bernardo, Tarek Ahmed Amin Ibrahim, Albert Aquino, Takahiro Yasui, Cristian Fiori, Thomas Knoll, Athanasios Papatsoris, Nariman Gadzhiev, Ulanbek Zhanbyrbekuly, Oriol Angerri, Hugo Lopez Ramos, Iliya Saltirov, Mohamad Moussa, Guido Giusti, Fabio Vicentini, Edgar Beltran Suarez, Margaret Pearle, Glenn M Preminger, Qing-Hui Wu, Otas Durutovic, Khurshid Ghani, Marcus Maroccolo, Marianne Brehmer, Palle J Osther, Marek Zawadzki, Azimdjon Tursunkulov, Monolov Nurbek Kytaibekovich, Abdusamad Abdukakhorovich Abuvohidov, Cesar Antonio Recalde Lara, Zamari Noori, Stefano Paolo Zanetti, Sunil Shrestha, Jean de la Rosette, John Denstedt, Zhang-Qun Ye, Kemal Sarica, Simon Choong","doi":"10.1186/s40779-024-00562-3","DOIUrl":"10.1186/s40779-024-00562-3","url":null,"abstract":"<p><p>Over the past three decades, there has been increasing interest in miniaturized percutaneous nephrolithotomy (mPCNL) techniques featuring smaller tracts as they offer potential solutions to mitigate complications associated with standard PCNL (sPCNL). However, despite this growing acceptance and recognition of its benefits, unresolved controversies and acknowledged limitations continue to impede widespread adoption due to a lack of consensus on optimal perioperative management strategies and procedural tips and tricks. In response to these challenges, an international panel comprising experts from the International Alliance of Urolithiasis (IAU) took on the task of compiling an expert consensus document on mPCNL procedures aimed at providing urologists with a comprehensive clinical framework for practice. This endeavor involved conducting a systematic literature review to identify research gaps (RGs), which formed the foundation for developing a structured questionnaire survey. Subsequently, a two-round modified Delphi survey was implemented, culminating in a group meeting to generate final evidence-based comments. All 64 experts completed the second-round survey, resulting in a response rate of 100.0%. Fifty-eight key questions were raised focusing on mPCNLs within 4 main domains, including general information (13 questions), preoperative work-up (13 questions), procedural tips and tricks (19 questions), and postoperative evaluation and follow-up (13 questions). Additionally, 9 questions evaluated the experts' experience with PCNLs. Consensus was reached on 30 questions after the second-round survey, while professional statements for the remaining 28 key questions were provided after discussion in an online panel meeting. mPCNL, characterized by a tract smaller than 18 Fr and an innovative lithotripsy technique, has firmly established itself as a viable and effective approach for managing upper urinary tract stones in both adults and pediatrics. It offers several advantages over sPCNL including reduced bleeding, fewer requirements for nephrostomy tubes, decreased pain, and shorter hospital stays. The series of detailed techniques presented here serve as a comprehensive guide for urologists, aiming to improve their procedural understanding and optimize patient outcomes.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"11 1","pages":"70"},"PeriodicalIF":16.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11514913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-21DOI: 10.1186/s40779-024-00573-0
Yuan Xiong, Bo-Bin Mi, Mohammad-Ali Shahbazi, Tian Xia, Jun Xiao
Severe tissue defects present formidable challenges to human health, persisting as major contributors to mortality rates. The complex pathological microenvironment, particularly the disrupted immune landscape within these defects, poses substantial hurdles to existing tissue regeneration strategies. However, the emergence of nanobiotechnology has opened a new direction in immunomodulatory nanomedicine, providing encouraging prospects for tissue regeneration and restoration. This review aims to gather recent advances in immunomodulatory nanomedicine to foster tissue regeneration. We begin by elucidating the distinctive features of the local immune microenvironment within defective tissues and its crucial role in tissue regeneration. Subsequently, we explore the design and functional properties of immunomodulatory nanosystems. Finally, we address the challenges and prospects of clinical translation in nanomedicine development, aiming to propose a potent approach to enhance tissue regeneration through synergistic immune modulation and nanomedicine integration.
{"title":"Microenvironment-responsive nanomedicines: a promising direction for tissue regeneration.","authors":"Yuan Xiong, Bo-Bin Mi, Mohammad-Ali Shahbazi, Tian Xia, Jun Xiao","doi":"10.1186/s40779-024-00573-0","DOIUrl":"10.1186/s40779-024-00573-0","url":null,"abstract":"<p><p>Severe tissue defects present formidable challenges to human health, persisting as major contributors to mortality rates. The complex pathological microenvironment, particularly the disrupted immune landscape within these defects, poses substantial hurdles to existing tissue regeneration strategies. However, the emergence of nanobiotechnology has opened a new direction in immunomodulatory nanomedicine, providing encouraging prospects for tissue regeneration and restoration. This review aims to gather recent advances in immunomodulatory nanomedicine to foster tissue regeneration. We begin by elucidating the distinctive features of the local immune microenvironment within defective tissues and its crucial role in tissue regeneration. Subsequently, we explore the design and functional properties of immunomodulatory nanosystems. Finally, we address the challenges and prospects of clinical translation in nanomedicine development, aiming to propose a potent approach to enhance tissue regeneration through synergistic immune modulation and nanomedicine integration.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"11 1","pages":"69"},"PeriodicalIF":16.7,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142469878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-27DOI: 10.1186/s40779-024-00570-3
Han Han, Hao Jia, Yi-Fan Wang, Jiang-Ping Song
The advancement in extraterrestrial exploration has highlighted the crucial need for studying how the human cardiovascular system adapts to space conditions. Human development occurs under the influence of gravity, shielded from space radiation by Earth's magnetic field, and within an environment characterized by 24-hour day-night cycles resulting from Earth's rotation, thus deviating from these conditions necessitates adaptive responses for survival. With upcoming manned lunar and Martian missions approaching rapidly, it is essential to understand the impact of various stressors induced by outer-space environments on cardiovascular health. This comprehensive review integrates insights from both actual space missions and simulated experiments on Earth, to analyze how microgravity, space radiation, and disrupted circadian affect cardiovascular well-being. Prolonged exposure to microgravity induces myocardial atrophy and endothelial dysfunction, which may be exacerbated by space radiation. Mitochondrial dysfunction and oxidative stress emerge as key underlying mechanisms along with disturbances in ion channel perturbations, cytoskeletal damage, and myofibril changes. Disruptions in circadian rhythms caused by factors such as microgravity, light exposure, and irregular work schedules, could further exacerbate cardiovascular issues. However, current research tends to predominantly focus on disruptions in the core clock gene, overlooking the multifactorial nature of circadian rhythm disturbances in space. Future space missions should prioritize targeted prevention strategies and early detection methods for identifying cardiovascular risks, to preserve astronaut health and ensure mission success.
{"title":"Cardiovascular adaptations and pathological changes induced by spaceflight: from cellular mechanisms to organ-level impacts.","authors":"Han Han, Hao Jia, Yi-Fan Wang, Jiang-Ping Song","doi":"10.1186/s40779-024-00570-3","DOIUrl":"https://doi.org/10.1186/s40779-024-00570-3","url":null,"abstract":"<p><p>The advancement in extraterrestrial exploration has highlighted the crucial need for studying how the human cardiovascular system adapts to space conditions. Human development occurs under the influence of gravity, shielded from space radiation by Earth's magnetic field, and within an environment characterized by 24-hour day-night cycles resulting from Earth's rotation, thus deviating from these conditions necessitates adaptive responses for survival. With upcoming manned lunar and Martian missions approaching rapidly, it is essential to understand the impact of various stressors induced by outer-space environments on cardiovascular health. This comprehensive review integrates insights from both actual space missions and simulated experiments on Earth, to analyze how microgravity, space radiation, and disrupted circadian affect cardiovascular well-being. Prolonged exposure to microgravity induces myocardial atrophy and endothelial dysfunction, which may be exacerbated by space radiation. Mitochondrial dysfunction and oxidative stress emerge as key underlying mechanisms along with disturbances in ion channel perturbations, cytoskeletal damage, and myofibril changes. Disruptions in circadian rhythms caused by factors such as microgravity, light exposure, and irregular work schedules, could further exacerbate cardiovascular issues. However, current research tends to predominantly focus on disruptions in the core clock gene, overlooking the multifactorial nature of circadian rhythm disturbances in space. Future space missions should prioritize targeted prevention strategies and early detection methods for identifying cardiovascular risks, to preserve astronaut health and ensure mission success.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"11 1","pages":"68"},"PeriodicalIF":16.7,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11429428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Sexual dimorphism in the relationship between BMI and recent suicidal attempts in first-episode drug-naïve patients with major depressive disorder.","authors":"Ze-Zhi Li, Yu-Ping Chen, Xiao-Cui Zang, Denise Zheng, Xiao-E Lang, Yong-Jie Zhou, Feng-Chun Wu, Xiang-Yang Zhang","doi":"10.1186/s40779-024-00572-1","DOIUrl":"https://doi.org/10.1186/s40779-024-00572-1","url":null,"abstract":"","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"11 1","pages":"66"},"PeriodicalIF":16.7,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11425971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-26DOI: 10.1186/s40779-024-00564-1
Babu Santha Aswani, Mangala Hegde, Ravichandran Vishwa, Mohammed S Alqahtani, Mohamed Abbas, Hassan Ali Almubarak, Gautam Sethi, Ajaikumar B Kunnumakkara
Nuclear receptors (NRs) function as crucial transcription factors in orchestrating essential functions within the realms of development, host defense, and homeostasis of body. NRs have garnered increased attention due to their potential as therapeutic targets, with drugs directed at NRs demonstrating significant efficacy in impeding chronic disease progression. Consequently, these pharmacological agents hold promise for the treatment and management of various diseases. Accumulating evidence emphasizes the regulatory role of exosome-derived microRNAs (miRNAs) in chronic inflammation, disease progression, and therapy resistance, primarily by modulating transcription factors, particularly NRs. By exploiting inflammatory pathways such as protein kinase B (Akt)/mammalian target of rapamycin (mTOR), nuclear factor kappa-B (NF-κB), signal transducer and activator of transcription 3 (STAT3), and Wnt/β-catenin signaling, exosomes and NRs play a pivotal role in the panorama of development, physiology, and pathology. The internalization of exosomes modulates NRs and initiates diverse autocrine or paracrine signaling cascades, influencing various processes in recipient cells such as survival, proliferation, differentiation, metabolism, and cellular defense mechanisms. This comprehensive review meticulously examines the involvement of exosome-mediated NR regulation in the pathogenesis of chronic ailments, including atherosclerosis, cancer, diabetes, liver diseases, and respiratory conditions. Additionally, it elucidates the molecular intricacies of exosome-mediated communication between host and recipient cells via NRs, leading to immunomodulation. Furthermore, it outlines the implications of exosome-modulated NR pathways in the prophylaxis of chronic inflammation, delineates current limitations, and provides insights into future perspectives. This review also presents existing evidence on the role of exosomes and their components in the emergence of therapeutic resistance.
核受体(NRs)是协调人体发育、宿主防御和体内平衡等重要功能的关键转录因子。NRs 因其作为治疗靶点的潜力而受到越来越多的关注,针对 NRs 的药物在阻碍慢性疾病进展方面具有显著疗效。因此,这些药理制剂有望治疗和控制各种疾病。不断积累的证据强调了外泌体衍生的微小核糖核酸(miRNA)在慢性炎症、疾病进展和耐药性中的调控作用,主要是通过调节转录因子,特别是 NRs。通过利用蛋白激酶 B(Akt)/哺乳动物雷帕霉素靶标(mTOR)、核因子卡巴-B(NF-κB)、转录信号转导和激活因子 3(STAT3)以及 Wnt/β-catenin 信号转导等炎症通路,外泌体和 NRs 在发育、生理和病理全景中发挥着关键作用。外泌体的内化会调节 NRs 并启动多种自分泌或旁分泌信号级联,影响受体细胞的各种过程,如存活、增殖、分化、新陈代谢和细胞防御机制。这篇综合性综述细致研究了外泌体介导的 NR 调节参与动脉粥样硬化、癌症、糖尿病、肝病和呼吸系统疾病等慢性疾病的发病机制。此外,它还阐明了外泌体介导的宿主和受体细胞之间通过 NRs 进行交流并导致免疫调节的复杂分子机制。此外,它还概述了外泌体调控的 NR 通路在预防慢性炎症方面的意义、目前的局限性,并提供了对未来前景的见解。本综述还介绍了关于外泌体及其成分在治疗耐药性出现中的作用的现有证据。
{"title":"Tackling exosome and nuclear receptor interaction: an emerging paradigm in the treatment of chronic diseases.","authors":"Babu Santha Aswani, Mangala Hegde, Ravichandran Vishwa, Mohammed S Alqahtani, Mohamed Abbas, Hassan Ali Almubarak, Gautam Sethi, Ajaikumar B Kunnumakkara","doi":"10.1186/s40779-024-00564-1","DOIUrl":"https://doi.org/10.1186/s40779-024-00564-1","url":null,"abstract":"<p><p>Nuclear receptors (NRs) function as crucial transcription factors in orchestrating essential functions within the realms of development, host defense, and homeostasis of body. NRs have garnered increased attention due to their potential as therapeutic targets, with drugs directed at NRs demonstrating significant efficacy in impeding chronic disease progression. Consequently, these pharmacological agents hold promise for the treatment and management of various diseases. Accumulating evidence emphasizes the regulatory role of exosome-derived microRNAs (miRNAs) in chronic inflammation, disease progression, and therapy resistance, primarily by modulating transcription factors, particularly NRs. By exploiting inflammatory pathways such as protein kinase B (Akt)/mammalian target of rapamycin (mTOR), nuclear factor kappa-B (NF-κB), signal transducer and activator of transcription 3 (STAT3), and Wnt/β-catenin signaling, exosomes and NRs play a pivotal role in the panorama of development, physiology, and pathology. The internalization of exosomes modulates NRs and initiates diverse autocrine or paracrine signaling cascades, influencing various processes in recipient cells such as survival, proliferation, differentiation, metabolism, and cellular defense mechanisms. This comprehensive review meticulously examines the involvement of exosome-mediated NR regulation in the pathogenesis of chronic ailments, including atherosclerosis, cancer, diabetes, liver diseases, and respiratory conditions. Additionally, it elucidates the molecular intricacies of exosome-mediated communication between host and recipient cells via NRs, leading to immunomodulation. Furthermore, it outlines the implications of exosome-modulated NR pathways in the prophylaxis of chronic inflammation, delineates current limitations, and provides insights into future perspectives. This review also presents existing evidence on the role of exosomes and their components in the emergence of therapeutic resistance.</p>","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"11 1","pages":"67"},"PeriodicalIF":16.7,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11426102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-19DOI: 10.1186/s40779-024-00571-2
Dong-Dong Yang, Meng Zhao, Jia-Xiu Du, Yu Shi
<p>Traumatic brain injury (TBI) remains a prominent global cause of mortality and disability, accounting for an estimated 69 million new cases annually [1]. Both civilian and military populations face substantial health challenges due to TBI, particularly in military settings, where combat-related injuries introduce unique considerations for prevalence and management [2]. Despite notable advancements in acute care, our comprehension of the complex pathophysiological mechanisms underlying the long-term effects of TBI remains inadequate [3]. Although the initial mechanical impact triggers the cascade of injury, it is often the subsequent neuroinflammatory processes that propel progressive neuronal damage and lead to long-term neurological impairments [4, 5].</p><p>Neutrophils, the most prevalent circulating leukocytes and first-line defenders against pathogens, have long been recognized as key players in the acute inflammatory response following TBI [6]. Although their rapid infiltration into the injured cerebral tissue is crucial for debris clearance and the initiation of repair mechanisms, excessive or prolonged activation of neutrophils may exacerbate tissue damage and lead to poorer clinical outcomes.</p><p>The groundbreaking research conducted by Zhou et al. [7] published in <i>Military Medical Research</i> unveiled novel insights into the dual role of neutrophils in TBI. They identified a distinct subpopulation of neutrophils characterized by elevated expression of the transcription factor forkhead box protein O1 (FOXO1). This FOXO1-high neutrophil subpopulation predominates during the acute neuroinflammatory response and, unexpectedly, persists into the chronic phase, thereby challenging the traditional perception of neutrophils as short-lived effector cells. These cells exhibit unique characteristics that contribute to both acute and chronic TBI pathologies. In the acute phase, they exacerbate immediate cerebral damage. Conversely, in the chronic phase, FOXO1-high neutrophils disrupt iron homeostasis with oligodendrocytes through the FOXO1-transferrin receptor axis, resulting in myelin loss and depression-like behaviors. This innovative perspective on neutrophil-oligodendrocyte interactions illuminates the intricate crosstalk between immune responses and nervous system functions following TBI, thus emphasizing the multifaceted role of neutrophils in chronic neuroinflammation.</p><p>Zhou et al. [7] also elucidated the molecular mechanisms that underpin the distinctive characteristics of FOXO1-high neutrophils in TBI pathogenesis. Mechanistically, their research revealed that FOXO1 directly enhances both the anti-apoptotic capacity and interleukin-6 production in neutrophils by upregulating the novel target gene <i>versican</i> (<i>VCAN</i>) during the acute phase. Additionally, they demonstrated that FOXO1 induces a metabolic shift from glycolysis to aerobic oxidation in neutrophils. This metabolic reprogramming may contribute to the altered
作者及工作单位河南中医药大学第五临床医学院(郑州市人民医院)神经内科,郑州,450000杨冬冬,赵萌&;杜家秀南方医科大学珠江医院康复科,广州,510282、中国Yu Shi作者Dong-Dong Yang查看作者发表的论文您也可以在PubMed Google Scholar中搜索该作者Meng Zhao查看作者发表的论文您也可以在PubMed Google Scholar中搜索该作者Jia-Xiu Du查看作者发表的论文您也可以在PubMed Google Scholar中搜索该作者Yu Shi查看作者发表的论文您也可以在PubMed Google Scholar中搜索该作者ContributionsDDY、MZ、JXD和YS起草了原稿。开放获取本文采用知识共享署名 4.0 国际许可协议进行许可,该协议允许以任何媒介或格式使用、共享、改编、分发和复制,只要您适当注明原作者和来源,提供知识共享许可协议的链接,并说明是否进行了修改。本文中的图片或其他第三方材料均包含在文章的知识共享许可协议中,除非在材料的署名栏中另有说明。如果材料未包含在文章的知识共享许可协议中,且您打算使用的材料不符合法律规定或超出许可使用范围,您需要直接从版权所有者处获得许可。如需查看该许可的副本,请访问 http://creativecommons.org/licenses/by/4.0/。创意共享公共领域专用免责声明(http://creativecommons.org/publicdomain/zero/1.0/)适用于本文提供的数据,除非在数据的信用行中另有说明。转载与授权引用本文Yang, DD., Zhao, M., Du, JX. et al. FOXO1-expressing neutrophils: a double-edged sword in traumatic brain injury.军事医学研究 11, 65 (2024). https://doi.org/10.1186/s40779-024-00571-2Download citationReceived:30 July 2024Accepted:05 September 2024Published: 19 September 2024DOI: https://doi.org/10.1186/s40779-024-00571-2Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative Keywords创伤性脑损伤(TBI)FOXO1-高表达中性粒细胞神经炎症急性脑损伤
{"title":"FOXO1-expressing neutrophils: a double-edged sword in traumatic brain injury","authors":"Dong-Dong Yang, Meng Zhao, Jia-Xiu Du, Yu Shi","doi":"10.1186/s40779-024-00571-2","DOIUrl":"https://doi.org/10.1186/s40779-024-00571-2","url":null,"abstract":"<p>Traumatic brain injury (TBI) remains a prominent global cause of mortality and disability, accounting for an estimated 69 million new cases annually [1]. Both civilian and military populations face substantial health challenges due to TBI, particularly in military settings, where combat-related injuries introduce unique considerations for prevalence and management [2]. Despite notable advancements in acute care, our comprehension of the complex pathophysiological mechanisms underlying the long-term effects of TBI remains inadequate [3]. Although the initial mechanical impact triggers the cascade of injury, it is often the subsequent neuroinflammatory processes that propel progressive neuronal damage and lead to long-term neurological impairments [4, 5].</p><p>Neutrophils, the most prevalent circulating leukocytes and first-line defenders against pathogens, have long been recognized as key players in the acute inflammatory response following TBI [6]. Although their rapid infiltration into the injured cerebral tissue is crucial for debris clearance and the initiation of repair mechanisms, excessive or prolonged activation of neutrophils may exacerbate tissue damage and lead to poorer clinical outcomes.</p><p>The groundbreaking research conducted by Zhou et al. [7] published in <i>Military Medical Research</i> unveiled novel insights into the dual role of neutrophils in TBI. They identified a distinct subpopulation of neutrophils characterized by elevated expression of the transcription factor forkhead box protein O1 (FOXO1). This FOXO1-high neutrophil subpopulation predominates during the acute neuroinflammatory response and, unexpectedly, persists into the chronic phase, thereby challenging the traditional perception of neutrophils as short-lived effector cells. These cells exhibit unique characteristics that contribute to both acute and chronic TBI pathologies. In the acute phase, they exacerbate immediate cerebral damage. Conversely, in the chronic phase, FOXO1-high neutrophils disrupt iron homeostasis with oligodendrocytes through the FOXO1-transferrin receptor axis, resulting in myelin loss and depression-like behaviors. This innovative perspective on neutrophil-oligodendrocyte interactions illuminates the intricate crosstalk between immune responses and nervous system functions following TBI, thus emphasizing the multifaceted role of neutrophils in chronic neuroinflammation.</p><p>Zhou et al. [7] also elucidated the molecular mechanisms that underpin the distinctive characteristics of FOXO1-high neutrophils in TBI pathogenesis. Mechanistically, their research revealed that FOXO1 directly enhances both the anti-apoptotic capacity and interleukin-6 production in neutrophils by upregulating the novel target gene <i>versican</i> (<i>VCAN</i>) during the acute phase. Additionally, they demonstrated that FOXO1 induces a metabolic shift from glycolysis to aerobic oxidation in neutrophils. This metabolic reprogramming may contribute to the altered","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"49 1","pages":""},"PeriodicalIF":21.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The burden of common urologic diseases, including benign prostatic hyperplasia (BPH), urinary tract infections (UTI), urolithiasis, bladder cancer, kidney cancer, and prostate cancer, varies both geographically and within specific regions. It is essential to conduct a comprehensive and precise assessment of the global burden of urologic diseases. We obtained data on incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) for the aforementioned urologic diseases by age, sex, location, and year from the Global Burden of Disease (GBD) 2021. We analyzed the burden associated with urologic diseases based on socio-demographic index (SDI) and attributable risk factors. The trends in burden over time were assessed using estimated annual percentage changes (EAPC) along with a 95% confidence interval (CI). In 2021, BPH and UTI were the leading causes of age-standardized incidence rate (ASIR) and age-standardized prevalence rate (ASPR), with rates of 5531.88 and 2782.59 per 100,000 persons, respectively. Prostate cancer was the leading cause of both age-standardized mortality rate (ASMR) and age-standardized DALYs rate (ASDR), with rates of 12.63 and 217.83 per 100,000 persons, respectively. From 1990 to 2021, there was an upward trend in ASIR, ASPR, ASMR, and ASDR for UTI, while urolithiasis showed a downward trend. The middle and low-middle SDI quintile levels exhibited higher incidence, prevalence, mortality, and DALYs related to UTI, urolithiasis, and BPH, while the high and high-middle SDI quintile levels showed higher rates for the three cancers. The burden of these six urologic diseases displayed diverse age and sex distribution patterns. In 2021, a high body mass index (BMI) contributed to 20.07% of kidney cancer deaths worldwide, while smoking accounted for 26.48% of bladder cancer deaths and 3.00% of prostate cancer deaths. The global burden of 6 urologic diseases presents a significant public health challenge. Urgent international collaboration is essential to advance the improvement of urologic disease management, encompassing the development of effective diagnostic screening tools and the implementation of high-quality prevention and treatment strategies.
{"title":"Global burden of benign prostatic hyperplasia, urinary tract infections, urolithiasis, bladder cancer, kidney cancer, and prostate cancer from 1990 to 2021","authors":"Hao Zi, Meng-Yang Liu, Li-Sha Luo, Qiao Huang, Peng-Cheng Luo, Hang-Hang Luan, Jiao Huang, Dan-Qi Wang, Yong-Bo Wang, Yuan-Yuan Zhang, Ren-Peng Yu, Yi-Tong Li, Hang Zheng, Tong-Zu Liu, Yu Fan, Xian-Tao Zeng","doi":"10.1186/s40779-024-00569-w","DOIUrl":"https://doi.org/10.1186/s40779-024-00569-w","url":null,"abstract":"The burden of common urologic diseases, including benign prostatic hyperplasia (BPH), urinary tract infections (UTI), urolithiasis, bladder cancer, kidney cancer, and prostate cancer, varies both geographically and within specific regions. It is essential to conduct a comprehensive and precise assessment of the global burden of urologic diseases. We obtained data on incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) for the aforementioned urologic diseases by age, sex, location, and year from the Global Burden of Disease (GBD) 2021. We analyzed the burden associated with urologic diseases based on socio-demographic index (SDI) and attributable risk factors. The trends in burden over time were assessed using estimated annual percentage changes (EAPC) along with a 95% confidence interval (CI). In 2021, BPH and UTI were the leading causes of age-standardized incidence rate (ASIR) and age-standardized prevalence rate (ASPR), with rates of 5531.88 and 2782.59 per 100,000 persons, respectively. Prostate cancer was the leading cause of both age-standardized mortality rate (ASMR) and age-standardized DALYs rate (ASDR), with rates of 12.63 and 217.83 per 100,000 persons, respectively. From 1990 to 2021, there was an upward trend in ASIR, ASPR, ASMR, and ASDR for UTI, while urolithiasis showed a downward trend. The middle and low-middle SDI quintile levels exhibited higher incidence, prevalence, mortality, and DALYs related to UTI, urolithiasis, and BPH, while the high and high-middle SDI quintile levels showed higher rates for the three cancers. The burden of these six urologic diseases displayed diverse age and sex distribution patterns. In 2021, a high body mass index (BMI) contributed to 20.07% of kidney cancer deaths worldwide, while smoking accounted for 26.48% of bladder cancer deaths and 3.00% of prostate cancer deaths. The global burden of 6 urologic diseases presents a significant public health challenge. Urgent international collaboration is essential to advance the improvement of urologic disease management, encompassing the development of effective diagnostic screening tools and the implementation of high-quality prevention and treatment strategies.","PeriodicalId":18581,"journal":{"name":"Military Medical Research","volume":"33 1","pages":""},"PeriodicalIF":21.1,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}