China Medical University (Taiwan)

细胞凋亡是一种高度保守的过程，在我们日常生活中的生理和病理条件下都会发生。数十亿细胞每天都经历着凋亡，产生大量的凋亡小泡(Apov)，这对维持器官和身体的动态平衡至关重要。ApoV是细胞凋亡过程中释放的一种特殊类型的胞外小泡，包括1~5μm的凋亡小体、0.1~1μm的凋亡微泡和直径小于150 nm的凋亡外体，携带着从亲本细胞遗传来的蛋白质、核酸、脂类和其他分子。在细胞凋亡过程中，大量与核相关的成分，包括蛋白质和核酸，被包装成ApoVs，使它们有别于生理释放的细胞外囊泡。这些遗传的核材料在载脂蛋白中的作用尚未完全阐明。DNA损伤通常发生在人体内，由各种因素引起，如紫外线辐射、X射线、γ射线、化学试剂和活性氧物种(ROS)。DNA损伤的积累会导致衰老和癌症。众所周知，细胞具有一个复杂的DNA修复系统来处理DNA损伤，但是否有凋亡代谢参与DNA修复尚不清楚。辐射损伤被认为是一种严重的临床疾病，必须在战争中甚至在日常生活中预防，这一挑战预计在未来将变得越来越重要。然而，世界卫生组织(WHO)提供的2023年辐射和核紧急情况关键药物清单并不包括任何专门用于促进DNA损伤修复的药物。因此，迫切需要开发实用的治疗方法来修复DNA损伤。图片来源：https://doi-org.libproxy1.nus.edu.sg/10.1002/jev2.12428近日，来自中国医科大学的研究者们在J Extracell Vesicles杂志上发表了题为“Apoptotic vesicles are required to repair DNA damage and suppress premature cellular senescence”的文章，该研究揭示了细胞凋亡囊泡是修复DNA损伤和抑制细胞过早衰老所必需的。众所周知，DNA损伤会导致细胞凋亡。然而，细胞凋亡及其代谢产物是否有助于DNA修复在很大程度上是未知的。在这项研究中，研究者发现凋亡缺陷的Fasmut和BIM−/−小鼠表现出显著的DNA损伤和细胞过早衰老，同时16000g凋亡小泡(Apov)的数量显著减少。静脉输注骨髓间充质干细胞来源的16,000g载脂蛋白可以挽救Fasmut和BIM−/−小鼠的DNA损伤和过早衰老。此外，亚致死剂量的辐射暴露导致Fasmut小鼠出现比野生型小鼠更严重的DNA损伤、存活率下降和体重减轻，但这些都可以通过输注MSC-apov来恢复。凋亡缺陷的Fasmut小鼠表现出过早衰老和DNA损伤的表型图片来源：https://doi-org.libproxy1.nus.edu.sg/10.1002/jev2.12428从机制上讲，研究者证明了细胞凋亡可以将多种核DNA修复酶，如全长的PARP1，组装成16,000克的载脂蛋白。这些DNA修复成分通过16,000g apov直接转移到受体细胞，从而挽救DNA损伤并消除衰老细胞。最后，研究者证明了胚胎干细胞来源的16,000g载脂蛋白具有优越的DNA修复能力，因为它含有高水平的核DNA修复酶来拯救受到致命剂量辐射的小鼠。这项研究不仅揭示了凋亡囊泡在DNA保护方面的巨大作用，更展示了干细胞衍生囊泡在对抗辐射伤害上的无限潜力。细胞凋亡产生含有丰富DNA修复相关蛋白的apoV复合体图片来源：https://doi-org.libproxy1.nus.edu.sg/10.1002/jev2.12428综上所述，在本研究中，研究者证明ApoV数量的减少会导致显著的早衰和DNA损伤，而MSC-apov的输注可以改善这些疾病。同时，研究者首次揭示了细胞凋亡通过产生含有丰富DNA修复酶的DDR-apoV复合体来参与DNA修复。参考文献Zhiqing Huang et al. Apoptotic vesicles are required to repair DNA damage and suppress premature cellular senescence. J Extracell Vesicles. 2024 Apr;13(4):e12428. doi: 10.1002/jev2.12428.本文仅用于学术分享，转载请注明出处。若有侵权，请联系微信：bioonSir 删除或修改！

Researchers have developed a web-based platform that offers an unprecedented view of the human body at the cellular level. The aim is to create an invaluable resource for researchers worldwide to increase knowledge about human health and disease. Researchers at Karolinska Institutet have developed a web-based platform that offers an unprecedented view of the human body at the cellular level. The aim is to create an invaluable resource for researchers worldwide to increase knowledge about human health and disease. The study is published in Genome Biology. Simultaneous measurement of numerous biomolecular variables, known as multi-omics, enables deep and comprehensive profiling of human biology. The new Single Cell Atlas (SCA) is based on analyses of thousands of human tissue samples from 125 different adult and fetal tissues. The researchers combined eight cutting-edge omics technologies, including single-cell RNA sequencing, whole-genome sequencing, and spatial transcriptomics to map and localise genes expressed in the tissue. The platform provides unique insights into individual cell properties and their interactions within tissues. The extensive collection of data is freely accessible through the platform's website. "The Single Cell Atlas not only saves time and resources but also fosters a collaborative environment for scientists from diverse fields, paving the way for new discoveries and innovations," says the study's first author Lu Pan, researcher at the Institute of Environmental Medicine, Karolinska Institutet, Sweden. Looking ahead, the team plans to refine the SCA by introducing more detailed analyses and annual updates. These enhancements will fill gaps in tissue representation and expand the sample size, allowing for more precise research. "The creation of the SCA marks a significant step forward in biomedical research," says the study's last author Xuexin Li, researcher at the Department of Physiology and Pharmacology (previously at the Department of Medical Biochemistry and Biophysics), Karolinska Institutet. "Our goal is to continually enrich the atlas, making it an invaluable resource for understanding human health and disease." The research was done in collaboration with China Medical University and several other international collaboration partners in The Single Cell Atlas Consortium. The study was financed by Karolinska Institutet and the KI Network Medicine Global Alliance (KI NMA). Coauthor Volker Lauschke is CEO and shareholder of HepaPredict AB, co-founder and shareholder of PersoMedix AB, and discloses consultancy work for Enginzyme AB. The other authors declare that they have no competing interests.

City of Hope's Richard T. Lee, M.D. treats a patient using acupuncture. He's been tapped to head the newly announced Cherng Family Center for Integrative Oncology, which will take an evidence-based approach to employing Eastern cultures' healing traditions alongside cancer treatments more typical in the West. A new $100 million donation will help cancer research and treatment organization City of Hope establish a new evidence-based “integrative oncology” program that blends Eastern and Western medicine, the Los Angeles organization announced Tuesday. The gift, which is the single largest philanthropic contribution in City of Hope’s history, comes from the co-founders and co-CEOs of food chain Panda Express, Andrew and Peggy Cherng. Their money will help kick off the Cherng Family Center for Integrative Oncology at City of Hope and its work to explore unique treatments, oncology fellowships and other cancer research that could be scaled across the organization’s national system, according to the announcement. “Innovative and holistic care is part of our culture and mission; we are committed to supporting and treating the whole patient—not just the cancer,” City of Hope CEO Robert Stone said in a statement thanking the Cherngs for their gift. “I am honored that our cancer expertise, world-class research environment, national patient population, robust clinical trials program and compassionate ethos have prepared City of Hope to lead this work.” Integrative medicine therapies pull from non-pharmacologic interventions to improve quality of life, such as by lessening pain or relieving anxiety. The organizations pointed to data suggesting an estimated 40% of cancer patients turn to these approaches to help manage their condition. Research has also outlined the benefits practices like music therapy, acupuncture, mindfulness meditation and massage therapy could bring patients. More research on traditional Chinese medicine and other Eastern healing traditions often tapped into integrative medicine “could result in evidence-based insights that fuel the development of more effective cancer medicines and care,” the organizations said in their announcement. Few organizations, particularly cancer centers, currently provide access to these whole-person practices under physician supervision, they said. In addition to accelerating research on these approaches as part of cancer care, the Cherng Family Center for Integrative Oncology will develop education and training programs for cancer care providers. City of Hope said it plans to have an oncologist-led fellowship in place “within the next year.” Leading the new center will be Richard T. Lee, M.D., a City of Hope researcher and practitioner who serves as medical director of the organization’s Integrative Medicine Program. Lee’s practice “augments the latest in cancer care” with acupuncture, meditation and yoga, traditional medicine approaches he was exposed to during a post-residency Fulbright scholarship to China Medical University in Taiwan. Though the integrative oncology programs will be piloted at City of Hope Los Angeles and across California’s Orange County, the organization said it plans to develop a platform to track clinical data and other scalable infrastructure to eventually expand the programs to City of Hope’s nationwide footprint. “The Cherng Family Center for Integrative Oncology will be the epicenter of translational research, new drug development and holistic care that meets a pressing need for patients and enhances our connection to the diverse communities we serve,” Edward S. Kim, M.D., vice physician-in-chief for City of Hope National Medical Center, said in the announcement. The Cherng’s Panda Charitable Family Foundation has long supported City of Hope with funds for research into natural cancer therapies and other sponsorships and donations supporting pediatric patients, according to the announcement. The organization has raised over $329 million since 1999, including more than $150 million for pediatric care charity Children’s Miracle Network Hospitals, according to its website. “Panda Restaurant Group began 50 years ago with a vision to bring the best of Eastern and Western flavors and cultures together through food,” Peggy Cherng said in the announcement. “In the same spirit, we hope the Cherng Family Center of Integrative Oncology becomes a model of bringing the best of Eastern and Western medicine together to unlock holistic healing for our communities.”