Author: Hu, Junjie ; Zhang, Di ; Yan, Jiayun ; Guo, Yingjie ; Yu, Fan ; Chen, Quan ; Shen, Birong ; Zhang, Yue ; Liu, Haiyang ; Guo, Xiangyang ; Zhou, Bing ; Liu, Lei ; Liu, Ronghe ; Kong, Deling ; Zhang, Huan ; Sun, Sha ; Yuan, Yun ; Lv, He ; Zhang, Yaoyao ; Yan, Chen ; Hao, Xiaojiang ; Liu, Yang ; Li, Wenlei ; Yang, Jie-Feng ; Zhang, Qianping ; Zhong, Ya-Ting ; Qin, Jiangyu ; Gao, Song ; Wang, Zhaoxia

Membrane dynamics are important to the integrity and function of mitochondria. Defective mitochondrial fusion underlies the pathogenesis of multiple diseases. The ability to target fusion highlights the potential to fight life-threatening conditions. Here we report a small molecule agonist, S89, that specifically promotes mitochondrial fusion by targeting endogenous MFN1. S89 interacts directly with a loop region in the helix bundle 2 domain of MFN1 to stimulate GTP hydrolysis and vesicle fusion. GTP loading or competition by S89 dislodges the loop from the GTPase domain and unlocks the molecule. S89 restores mitochondrial and cellular defects caused by mitochondrial DNA mutations, oxidative stress inducer paraquat, ferroptosis inducer RSL3 or CMT2A-causing mutations by boosting endogenous MFN1. Strikingly, S89 effectively eliminates ischemia/reperfusion (I/R)-induced mitochondrial damage and protects mouse heart from I/R injury. These results reveal the priming mechanism for MFNs and provide a therapeutic strategy for mitochondrial diseases when additional mitochondrial fusion is beneficial.

01 Dec 2000·Diabetes Technology & TherapeuticsQ2 · MEDICINE

Office Logistics: Implementation of the Continuous Glucose Monitoring System in Clinical Practice

Q2 · MEDICINE

Article

Author: Einhorn, Daniel ; Sadler, Christopher E.

S-89 THE CONTINUOUS GLUCOSE MONITORING SYSTEM (CGMS) provides important information for the management of diabetes mellitus, but its implementation requires training staff and educating patients for its proper use. This article discusses the practical aspects of utilizing CGMS cost-effectively in a busy office practice. We draw on the experience of using this valuable new technology in our practice, which has six satellite offices, three endocrinologists, a nurse practitioner-certified diabetes educator (CDE), an RN-CDE, a physician’s assistant– CDE, and multiple medical assistants. Although each clinical practice is unique, certain principles of CGMS implementation can be applied in many settings.

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Indication	Highest Phase	Country/Location	Organization	Date
Mitochondrial Diseases	Preclinical	CN	Kunming Institute of Botany	15 Jan 2023
Mitochondrial Diseases	Preclinical	CN	Institute of Biophysics of Chinese Academy of Sciences	15 Jan 2023
Mitochondrial Diseases	Preclinical	CN	Nankai University	15 Jan 2023

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