Royal College of Surgeons

本文研究结果进一步证明了NLRP3炎性小体的生物钟时间或许依赖于机体线粒体的功能，并能通过昼夜节律基因Bmal1来进行驱动。 巨噬细胞是机体中一类能调节机体炎性过程的先天性免疫细胞，其在一天中的不同时间会发生不同的变化，这或许就确保了机体免疫反应与外部环境的适当生物学时机，NLRP3炎性小体能通过细胞焦亡（pyroptosis）介导IL-1家族性的细胞因子释放过程，线粒体在调节NLRP3炎性小体活性方面扮演着多方面的角色，此外，线粒体在一天中的不同时间能表现出不同的代谢变化，这往往受到了机体生物钟的影响，然而，巨噬细胞时钟是否能通过线粒体控制来调节NLRP3炎性小体的功能，目前研究人员并不清楚。 近日，一篇发表在国际杂志The FASEB Journal上题为“Time-of-day control of mitochondria regulates NLRP3 inflammasome activation in macrophages”的研究报告中，来自爱尔兰皇家外科医学院等机构的科学家们通过研究解释了机体的生物钟如何影响免疫系统的炎性过程，文章中，他们描述了巨噬细胞如何在一天中的不同时间发挥作用，有望为诸如关节炎等炎性疾病的定时靶向性治疗铺平道路。 文章中，研究人员深入揭示了机体免疫系统与生物钟之间的关联，巨噬细胞能作为在机体中检测并对有害物质产生反应的特殊免疫细胞，其能通过组装称之为炎性小体的大型复合物来诱发炎症作为一种防御性机制，炎性小体可以比作“烟雾探测器”（smoke detectors），其能向免疫系统发出危险警报。 生物钟影响IL-1家族的细胞因子释放和细胞死亡 研究者发现，称之为NLRP3的炎性小体的激活并不是在全天中恒定的，而是受到了机体24小时生物钟的调节，这种日常昼夜节律决定了巨噬细胞在什么时候能最有效地检测威胁以及什么时候其能量水平能达到峰值从而做出反应，本文研究还强调了线粒体在驱动机体免疫活性的这些日常变化中的关键作用。研究者Annie Curtis解释道，当巨噬细胞认为是早晨时，炎性小体的激活就会更快更强劲，这意味着机体免疫反应在一天中的早期时候会增强，而这时候我们是最清醒的，且更有可能遭遇环境挑战，比如受伤或感染。 这项研究对于理解和治疗诸如关节炎等炎性疾病具有重要意义，其中过度活跃的炎性小体在其中发挥着关键作用，诸如此类疾病的症状通常在早晨会加重，而这项研究也有助于解释这一点。基于这些研究发现，目前研究人员或有望改进炎性疾病的治疗方法，比如，如果在巨噬细胞的活性达到峰值的特定时间里进行治疗的话，针对炎性小体的新疗法或许更为有效。 综上，本文研究结果进一步证明了NLRP3炎性小体的生物钟时间或许依赖于机体线粒体的功能，并能通过昼夜节律基因Bmal1来进行驱动。（生物谷Bioon.com） 参考文献： James R. O'Siorain,Shannon L. Cox,Cloé Payet, et al. Time‐of‐day control of mitochondria regulates NLRP3 inflammasome activation in macrophages, The FASEB Journal (2024). DOI: 10.1096/fj.202400508RR.

Research in Kenya has demonstrated that the mortality rate following Paediatric surgical procedures can be 100 times higher than in high-income countries. PATA seeks to redefine surgical and anesthesia care in Africa. LUSAKA, Zambia, Sept. 29, 2023 /PRNewswire/ -- To bridge the gap for millions of African children lacking access to safe surgery and anesthesia care, the world's largest cleft organization, Smile Train has officially launched the Paediatric Anaesthesia Training in Africa (PATA) program in partnership with The ELMA Foundation and Vanderbilt University Medical Center. Continue Reading Dr. Maryrose Osazuwa (Program Director-PATA Nigeria) teaching pediatric resuscitation to fellows (Dr. Rukayya Abdullahi Sidi and Dr. Chinedu Onyeoji, both of Nigeria). The PATA Program will be implemented at three African institutions, namely the University of Zambia, National Hospital, Abuja in Nigeria and Makerere University, Kampala in Uganda. The training program, which has been endorsed by the World Federation of Societies of Anaesthesiologists (WFSA), seeks to increase access to safe surgery and anaesthesia care through intensive, year-long fellowships in Paediatric anaesthesia. Through collaboration with the Ministry of Health, the program will also enable the development of a Paediatric anaesthesia policy. Speaking during the launch, Smile Train Vice-President and Regional Director for Africa Mrs. Nkeiruka Obi acknowledged that PATA is intended to meet the urgent need to strengthen Paediatric surgical systems in the region and ensure the safety and quality of Paediatric anaesthesia. "Children in need of surgical treatment, such as those born with clefts or those who are injured, need timely surgery to live a productive life – but access to surgery means nothing if that surgery isn't safe and high-quality. In many African countries, there is a huge gap in skilled surgical and anesthesia providers, which compromises the quality of surgical services. As part of achieving Universal Health Coverage, PATA seeks to upskill more anesthesia providers in the local community by strengthening the Human Resources for Health," said Mrs. Obi. While endorsing the program, Zambia Ministry of Health Director of Clinical Care Dr. Kennedy Lishimpi added: "As part of Zambia's commitment to advancing Universal Health Coverage, we are pleased that the collaboration will strengthen Paediatric anesthesia care in the region. This program is aligned with The Government's endeavors to implement a National Paediatric Surgical and Anaesthesia Plan." Research by the Lancet Commission shows that approximately 143 million surgical procedures are needed yearly in the world which shows a significant burden facing the Paediatric population. In addition, approximately 85 percent of children may require some form of surgery before their 15th birthday. In Kenya, a recent study titled Paediatric Perioperative Mortality in Kenya revealed that the mortality rate of Paediatric procedures is 100 times higher than in high-income countries. In her remarks, Melissa Morrison, Director of Health Programs at ELMA Philanthropies noted, "We are proud to partner with Smile Train in launching the Paediatric Anaesthesia Training in Africa (PATA) program. A well-trained workforce is essential to ensuring that children across Africa have access to safe surgery and anesthesia care. The inequities in surgical access and poor outcomes for children in Africa compared to high-income countries is unacceptable, and the PATA graduates represent hope and a future for thousands of children." Other institutions collaborating on the implementation of the PATA program include African Mission Healthcare-Kenya, Boston Children's Hospital, Kids Operating Room, University of Nairobi, Global Institute of Children's Surgery, African Paediatric Fellowship in Africa, University of Cape Town, Royal College of Surgeons of Ireland, and Association of Anesthesiologists of Uganda (AAU). Media Contact: Smile Train Emily Manjeru PR & Communications Manager, Africa +254724 926 269 [email protected] Photo - Logo - SOURCE Smile Train

来自爱尔兰皇家外科医学院等机构的科学家们通过研究揭示了昼夜24小时机体时钟影响机体对疫苗所产生的免疫反应背后的分子机制。 树突细胞（dendritic cells）在加工并将抗原呈递给原始T细胞从而激发适应性免疫性方面扮演着关键角色，众所周知，昼夜节律能帮助调节机体免疫力的多个方面，然而其在树突细胞功能中所发挥的作用，研究人员并不清楚。近日，一篇发表在国际杂志Nature Communications上题为“The circadian clock influences T cell responses to vaccination by regulating dendritic cell antigen processing”的研究报告中，来自爱尔兰皇家外科医学院等机构的科学家们通过研究揭示了昼夜24小时机体时钟影响机体对疫苗所产生的免疫反应背后的分子机制。 文章中，研究人员分析了参与机体疫苗反应的关键免疫细胞中线粒体所发生的改变，这或许有助于帮助设计并改进未来疫苗的接种时间，从而最大限度地提高其接种有效性。此前研究结果表明，人类对某些疫苗的反应较大，这或许依赖于一天中疫苗所接种的时间，然而研究人员并不清楚其背后的原因；本文研究结果表明，机体的昼夜节律钟能改变树突细胞中线粒体的形状，线粒体结构的变化会影响树突细胞在一天中功能的发挥情况。 揭示昼夜节律钟影响机体疫苗反应的分子机制。 图片来源：Nature Communications (2022). DOI:10.1038/s41467-022-34897-z 研究者Annie Curtis教授说道，我们的研究发现解释了机体对疫苗产生反应的一个关键方面，并强调了昼夜节律钟在机体免疫力功能发挥中的重要性，为此研究人员就能在疫苗开发过程中应用这一认识，从而确保我们能得到来自疫苗接种最大的效益。树突细胞中的昼夜节律钟能控制线粒体是否会形成两种形状之一，即长串的网络状结构或破碎成效的点状碎片；正是在这种网络状形状的形成过程中，疫苗的接种是最有效的，因为树突细胞有着较好的能力能将疫苗分解成小块状从而与宿主机体的免疫细胞（T细胞）发生相互作用，这项研究中，研究人员利用了一种方法来诱导线粒体的网状化阶段，从而对于疫苗的设计具有重要意义，这样或许就能帮助优化机体的免疫反应，而不用考虑在一天中的接种时间。 研究者指出，近年来，线粒体的重要性已经超越了其作为“细胞能量工厂”的常见标签，尤其是在免疫系统细胞内，研究人员很高兴地揭示这种与机体免疫系统及疫苗反应相关的新关联。综上，本文研究结果表明，与树突细胞线粒体形态改变相关的线粒体钙质的节律性改变或许能帮助调节宿主机体抗原的呈递处理过程。（生物谷Bioon.com） 原始出处: Cervantes-Silva, M.P., Carroll, R.G., Wilk, M.M. et al. The circadian clock influences T cell responses to vaccination by regulating dendritic cell antigen processing. Nat Commun 13, 7217 (2022). doi：10.1038/s41467-022-34897-z