Javier Ganz,1,2,3,8,9 Lovelace J. Luquette,4,8 Sara Bizzotto,1,2,3,5,8 Michael B. Miller,1,3,6 Zinan Zhou,1,2,3 Craig L. Bohrson,4
Hu Jin,4 Antuan V. Tran,4 Vinayak V. Viswanadham,4 Gannon McDonough,6 Katherine Brown,6 Yasmine Chahine,1
Brian Chhouk,1 Alon Galor,4 Peter J. Park,4,7,* and Christopher A. Walsh1,2,3,10,*
1 Division of Genetics and Genomics, Manton Center for Orphan Disease Research, Department of Pediatrics, and Howard Hughes Medical Institute, Boston Childrens Hospital, Boston, MA 02115, USA
2 Departments of Pediatrics and Neurology, Harvard Medical School, Boston, MA 02115, USA
3 Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
4 Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA
5 Sorbonne Universite´ , Institut du Cerveau (Paris Brain Institute) ICM, Inserm, CNRS, Hoˆ pital de la Pitie´ Salpeˆ trie`re, 75013 Paris, France
6 Department of Pathology, Brigham and Womens Hospital, Harvard Medical School, Boston, MA 02115, USA
7 Division of Genetics, Brigham and Womens Hospital, Boston, MA 02115, USA
8 These authors contributed equally
9 Present address: Merck Research Laboratories, Cambridge, MA 02142, USA
10 Lead contact
*Correspondence: 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (P.J.P.), 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (C.A.W.)
https://doi.org/10.1016/j.cell.2024.02.025
SUMMARY
Characterizing somatic mutations in the brain is important for disentangling the complex mechanisms of aging, yet little is known about mutational patterns in different brain cell types. Here, we performed wholegenome sequencing (WGS) of 86 single oligodendrocytes, 20 mixed glia, and 56 single neurons from neurotypical individuals spanning 0.4–104 years of age and identified >92,000 somatic single-nucleotide variants (sSNVs) and small insertions/deletions (indels). Although both cell types accumulate somatic mutations linearly with age, oligodendrocytes accumulated sSNVs 81% faster than neurons and indels 28% slower than neurons. Correlation of mutations with single-nucleus RNA profiles and chromatin accessibility from the same brains revealed that oligodendrocyte mutations are enriched in inactive genomic regions and are distributed across the genome similarly to mutations in brain cancers. In contrast, neuronal mutations are enriched in open, transcriptionally active chromatin. These stark differences suggest an assortment of active mutagenic processes in oligodendrocytes and neurons.
an Yang1 Xinyuan Zhang2 Hua Wang1 Miao Guo1 Jinlong Zhang1 Xuejiao Feng3 Jiayi Yu3 Jiahui Yang3 Jinjin Zhu4 Yiyu Wang3
1 Research & Development Center, Mageline Biology Tech Co., Ltd, Wuhan, Hubei, China
2 Shanghai Skinshield Clinical Testing and Technological Research Ltd., Shanghai, China
3 Department of Dermatology, Air Force Medical Center, PLA, Beijing, China
4 Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, China
Correspondence
Jinjin Zhu, Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, 430022, China.
Email: 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。
Yiyu Wang, Department of Dermatology, Air Force Medical Center, PLA, Beijing, China.
Abstract
Background: The delicate periorbital region is susceptible to skin dehydration, wrinkles, and loss of elasticity. Thus, targeted and effective anti-aging interventions are necessary for the periorbital area.
Aim: To evaluate the efficacy and safety of a new anti-aging eye cream formulated with the active complex (Yeast/rice fermentation filtrate, N-acetylneuraminic acid, palmityl tripeptide-1, and palmitoyl tetrapeptide-7).
Methods: The cell viability and expressions of key extracellular matrix (ECM) components of the active complex were evaluated using a human skin fibroblast model. In the 12-week clinical trial, skin hydration, elasticity, facial photographs, and collagen density following eye cream application were assessed using Corneometer, Cutometer, VISIA, and ultrasound device, respectively. Dermatologists and participants evaluated clinical efficacy and safety at baseline, and after 4, 8, and 12 weeks.
Results: PCR and immunofluorescent analyses revealed that the active complex significantly stimulated fibroblast proliferation (p < 0.05) and markedly promote the synthesis of collagen and elastin. Clinical findings exhibited a substantial enhancement in skin hydration (28.12%), elasticity (18.81%), and collagen production (54.99%) following 12 weeks of eye cream application. Dermatological evaluations and participants’ assessments reported a significant improvement in skin moisture, roughness, elasticity, as well as fine lines and wrinkles by week 8.
Conclusion: The new anti-aging eye cream, enriched with the active complex, demonstrates comprehensive rejuvenating effects, effectively addressing aging concerns in the periorbital area, coupled with a high safety profile.
KEYWORDS
anti-aging, collagen, elastin, extracellular matrix, eye cream, wrinkle
原创: 十六点五 中山二院糖尿病足中心
糖尿病足部的慢性溃疡是否存在感染,好像应该是没有多少疑问的,但在所谓的“神经性溃疡”的表面是否存在有临床意义的感染,一直有争议。
对于外周血管病变的介入治疗,较IWGDF指南较有关OFFLOADING的细节描述,有关介入治疗的部分实在是比较粗慥,目前糖尿病外周血管病变介入治疗的热点问题大部分都没有涉及
对于糖尿病外周血管病变的治疗,2019年版IWGDF指南讲的比较少,无论是内科治疗还是介入治疗,这版的指南都讲得比较少(其实之前版本的IWGDF指南有关血管病变方面的内容更少),而国内糖尿病足指南,提到有关糖尿病外周血管病变治疗,一般都会用比较大的篇幅谈到其内科治疗。
人们对于糖尿病外周血管病变越来越关注,一方面,它是糖尿病足形成的最重要的原因;另一方面,它也是糖尿病进展到一定程度的标志,严重的糖尿病外周血管病变,往往标志着糖尿病进展到晚期,心、肾、脑、眼底等重要脏器的血管也存在严重的问题,而糖尿病足长期的皮肤溃疡不愈合,其产生的大量炎症因子,也会加重这些血管病变,因此,如何评价(诊断)及治疗糖尿病外周血管病变,成为了糖尿病诊断和治疗的最重要的领域。
伤口世界平台生态圈,以“关爱人间所有伤口患者”为愿景,连接、整合和拓展线上和线下的管理慢性伤口的资源,倡导远程、就近和居家管理慢性伤口,解决伤口专家的碎片化时间的价值创造、诊疗经验的裂变复制、和患者的就近、居家和低成本管理慢性伤口的问题。
2019广东省医疗行业协会伤口管理分会年会
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