Drug Repurposing in Neurological Disorders: Implications for Neurotherapy in Traumatic Brain Injury
Authors: Shakkour, Zaynab; Habashy, Karl John; Berro, Moussa; Takkoush, Samira; Abdelhady, Samar; Koleilat, Nadia; Eid, Ali H.; Zibara, Kazem; Obeid, Makram; Shear, Deborah; Mondello, Stefania; Wang, Kevin K.; Kobeissy, Firas
Traumatic brain injury (TBI) remains a significant leading cause of death and disability among adults and children globally. To date, there are no Food and Drug Administration-approved drugs that can substantially attenuate the sequelae of TBI. The innumerable challenges faced by the conventional de novo discovery of new pharmacological agents led to the emergence of alternative paradigm, which is drug repurposing. Repurposing of existing drugs with well-characterized mechanisms of action and human safety profiles is believed to be a promising strategy for novel drug use. Compared to the conventional discovery pathways, drug repurposing is less costly, relatively rapid, and poses minimal risk of the adverse outcomes to study on participants. In recent years, drug repurposing has covered a wide range of neurodegenerative diseases and neurological disorders including brain injury. This review highlights the advances in drug repurposing and presents some of the promising candidate drugs for potential TBI treatment along with their possible mechanisms of neuroprotection. Edaravone, glyburide, ceftriaxone, levetiracetam, and progesterone have been selected due to their potential role as putative TBI neurotherapeutic agents. These drugs are Food and Drug Administration-approved for purposes other than brain injuries; however, preclinical and clinical studies have shown their efficacy in ameliorating the various detrimental outcomes of TBI.
Enhancing effect of FSH on follicular development through yolk formation and deposition in the low-yield laying chickens
Authors: Ma, Yanfen; Yao, Jinwei; Zhou, Shuo; Mi, Yuling; Tan, Xun; Zhang, Caiqiao
Healthy and efficient development of ovarian follicles largely determines poultry laying performance. In low-yield laying chickens, retarded follicle progression resulted in decreased prehierarchical follicles. In this study the extenuating effect of follicle-stimulating hormone (FSH) on delayed follicular development was investigated in the low-yield chickens. Results showed that FSH administration in vivo accelerated development of prehierarchical follicles, with increased expression of steroidogenic enzymes and follicular angiogenesis through elevating plasma levels of 17 beta-estradiol, progesterone, luteinizing hormone and the expression of vascular endothelial growth factor and its receptor as well as angiopoietins. Furthermore, treatment with FSH raised expression of lipid uptake and adipogenesis-related proteins and decreased tight junctions between granulosa cells. Meanwhile, the results of the in vivo studies were confirmed by the in vitro studies as FSH promoted development of the cultured prehierarchical follicles with increased angiogenesis, cell proliferation, steroid hormones synthesis and yolk deposition. These results indicated FSH enhanced follicular development in the low-yield laying chickens involving increased follicular angiogenesis. (C) 2020 Elsevier Inc. All rights reserved.