The cardiovascular system is a complex and well-organized system in which glycosylation plays a vital role. The heart and vascular wall cells are constituted by an array of specific receptors; most of them are N- glycosylated and mucin-type O-glycosylated. There are also intracellular signaling pathways regulated by different post-translational modifications, including O-GlcNAcylation, which promote adequate responses to extracellular stimuli and signaling transduction. Herein, we provide an overview of N-glycosylation and O-glycosylation, including O-GlcNAcylation, and their role at different levels such as reception of signal, signal transduction, and exogenous molecules or agonists, which stimulate the heart and vascular wall cells with effects in different conditions, like the physiological status, ischemia/reperfusion, exercise, or during low-grade inflammation in diabetes and aging. Furthermore, mutations of glycosyltransferases and receptors are associated with development of cardiovascular diseases. The knowledge on glycosylation and its effects could be considered biochemical markers and might be useful as a therapeutic tool to control cardiovascular diseases.
Chagas disease, caused by the parasite Trypanosoma cruzi, affects millions of people in South America. The current treatments are limited, have severe side effects, and are only partially effective. Drug repositioning, defined as finding new indications for already approved drugs, has the potential to provide new therapeutic options for Chagas. In this work, we conducted a structure-based drug repositioning approach with over 130,000 3D protein structures to identify drugs that bind therapeutic Chagas targets and thus represent potential new Chagas treatments. The screening yielded over 500 molecules as hits, out of which 38 drugs were prioritized following a rigorous filtering process. About half of the latter were already known to have trypanocidal activity, while the others are novel to Chagas disease. Three of the new drug candidates—ciprofloxacin, naproxen, and folic acid—showed a growth inhibitory activity in the micromolar range when tested ex vivo on T. cruzi trypomastigotes, validating the prediction. We show that our drug repositioning approach is able to pinpoint relevant drug candidates at a fraction of the time and cost of a conventional screening. Furthermore, our results demonstrate the power and potential of structure-based drug repositioning in the context of neglected tropical diseases where the pharmaceutical industry has little financial interest in the development of new drugs.
Background Serious games have been used as supportive therapy for traditional rehabilitation. However, most are designed without a systematic process to guide their development from the phases of requirement identification, planning, design, construction, and evaluation, which reflect the lack of adaptation of rehabilitation requirements and thus the patient’s needs. Objective The aim of this study was to propose a conceptual framework with standardized elements for the development of information systems by using a flexible and an adaptable process centered on the patient’s needs and focused on the creation of serious games for physical rehabilitation. Methods The conceptual framework is based on 3 fundamental concepts: (1) user-centered design, which is an iterative design process focused on users and their needs at each phase of the process, (2) generic structural activities of software engineering, which guides the independent development process regardless of the complexity or size of the problem, and (3) gamification elements, which allow the transformation of obstacles into positive and fun reinforcements, thereby encouraging patients in their rehabilitation process. Results We propose a conceptual framework to guide the development of serious games through a systematic process by using an iterative and incremental process applying the phases of context identification, user requirements, planning, design, construction of the interaction devices and video game, and evaluation. Conclusions This proposed framework will provide developers of serious games a systematic process with standardized elements for the development of flexible and adaptable software with a high level of patient commitment, which will effectively contribute to their rehabilitation process.
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