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1.
J Biol Chem ; 299(8): 105030, 2023 08.
Article in English | MEDLINE | ID: mdl-37442239

ABSTRACT

Human growth hormone (hGH) is a pituitary-derived endocrine protein that regulates several critical postnatal physiologic processes including growth, organ development, and metabolism. Following adulthood, GH is also a regulator of multiple pathologies like fibrosis, cancer, and diabetes. Therefore, there is a significant pharmaceutical interest in developing antagonists of hGH action. Currently, there is a single FDA-approved antagonist of the hGH receptor (hGHR) prescribed for treating patients with acromegaly and discovered in our laboratory almost 3 decades ago. Here, we present the first data on the structure and function of a new set of protein antagonists with the full range of hGH actions-dual antagonists of hGH binding to the GHR as well as that of hGH binding to the prolactin receptor. We describe the site-specific PEG conjugation, purification, and subsequent characterization using MALDI-TOF, size-exclusion chromatography, thermostability, and biochemical activity in terms of ELISA-based binding affinities with GHR and prolactin receptor. Moreover, these novel hGHR antagonists display distinct antagonism of GH-induced GHR intracellular signaling in vitro and marked reduction in hepatic insulin-like growth factor 1 output in vivo. Lastly, we observed potent anticancer biological efficacies of these novel hGHR antagonists against human cancer cell lines. In conclusion, we propose that these new GHR antagonists have potential for development towards multiple clinical applications related to GH-associated pathologies.


Subject(s)
Human Growth Hormone , Receptors, Prolactin , Humans , Carrier Proteins/chemistry , Cell Line , Human Growth Hormone/antagonists & inhibitors , Human Growth Hormone/chemistry , Prolactin/chemistry , Receptors, Prolactin/antagonists & inhibitors , Receptors, Prolactin/chemistry , Receptors, Somatotropin/chemistry , Polyethylene Glycols/chemistry
2.
Int Sch Res Notices ; 2016: 9754845, 2016.
Article in English | MEDLINE | ID: mdl-27382644

ABSTRACT

Nursing in Ghana is a crucial subject that permeates almost every issue in the society especially the field of hospital care. To a large extent, the frontiers of nursing have expanded since the time of Florence Nightingale. Globally some studies have been done to study nursing icons like her. The values in nursing practice however continue to preoccupy our minds. The need to accentuate the gains made by historical figures in nursing in present times as well as the nature of interactions between practitioners and patients continues to be of paramount concern to many across the globe and Ghana in particular. This study does an analysis of existing literature on Florence Nightingale and the nature of nursing in Ghana from the colonial times. Additionally, it analyzes responses concerning the activities of nurses and their interactions with patients in Kumasi. The varied information has been thematically pieced together to make inferences that are of great interest to nursing practitioners, policy makers, administrators, and educators among others. The findings to the study suggest among other things that the challenges faced by the nursing institution in modern times are similar to those of the earlier period. The study calls for the emulation of the positive ideas of Florence Nightingale to promote the interest of patients, a core objective championed by a revered nurse.

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