Macmillanfunch1710

Upon binding, Asp1116 assumed a conformation that altered the architecture of the bromodomain active site, thereby orienting the helices around the active site in a more compacted position. Interestingly, in addition to some specific structural perturbations mediated by Asp1116 on the dynamics of CBP, our study revealed that the strong hydrogen bond interaction (N-H⋯O) elicited in CBP-Y08197 sequestered Y08197 tightly into the CBP bromodomain active site. CONCLUSION Conclusively, the inhibition and selective pattern of Y08197 can be replicated in future structure-based CBP inhibitors and other bromodomain implicated in carcinogenesis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.BACKGROUND Activated inflammation and oxidant stress during cerebral ischemia reperfusion injury (IRI) lead to brain damage. Astaxanthin (ASX) is a type of carotenoid with a strong antioxidant effect. OBJECTIVE The aim of this study was to investigate the role of ASX on brain IRI. METHODS A total of 42 adult male Sprague-Dawley rats were divided into 3 groups as control (n=14) group, IRI (n=14) group and IRI + ASX (n=14) group. Cerebral ischemia was instituted by occluding middle cerebral artery for 120 minutes and subsequently, reperfusion was performed for 48 hours. oxidant parameter levels and protein degradation products were evaluated. Hippocampal and cortex cell apoptosis, neuronal cell count, neurological deficit score were evaluated. RESULTS In the IRI group, oxidant parameter levels and protein degradation products in the tissue were increased compared to control group. However, these values were significantly decreased in the IRI + ASX group (p less then 0.05). There was a significant decrease in hippocampal and cortex cell apoptosis and a significant increase in the number of neuronal cells in the IRI + ASX group compared to the IRI group alone (p less then 0.05). The neurological deficit score which was significantly lower in the IRI group compared to the control group was found to be significantly improved in the IRI + ASX group (p less then 0.05). selleckchem CONCLUSION Astaxanthin protects the brain from oxidative damage and reduces neuronal deficits due to IRI injury. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.AIM AND OBJECTIVE One of the challenges to conventional therapies against Mycobacterium tuberculosis is the development of multi-drug resistant pathogenic strains. This study was undertaken to explore new therapeutic targets for the revolutionary antivirulence therapy utilizing the pathogen's essential hypothetical proteins, serving as virulence factors, the essential first step in novel drug designing. METHODS Functional annotations of essential hypothetical proteins from Mycobacterium tuberculosis (H37Rv strain) were performed through domain annotation, Gene Ontology analysis, physicochemical characterization and prediction of subcellular localizations. Virulence factors among the essential hypothetical proteins were predicted, among which pathogen-specific drug target candidates, non-homologous to human and gut microbiota were identified. This was followed by druggability and spectrum analysis of the identified targets. RESULTS AND CONCLUSION The study successfully assigned functions of 83 essential hypothetical proteins of Mycobacterium tuberculosis, among which 25 were identified as virulence factors. Out of 25, 12 virulence factors were observed as potential pathogen-specific drug target candidates. Nine potential targets had druggable properties and rest three were considered as novel targets. Exploration of these targets provided new insights to future drug development. Characterization of subcellular localizations revealed most of the predicted targets were cytoplasmic that could be ideal for intracellular drugs, while two drug targets were membrane-bound, ideal for vaccines. Spectrum analysis identified one broad spectrum and 11 narrow spectrum targets. This study would, therefore, instigate in designing novel therapeutics for antivirulence therapy, which has the potential to bring revolutionary treatment over conventional antibiotic therapies to overcome the lethality of antibiotic-resistant strains. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.The most important activity of erythropoietin (EPO) is the regulation of erythrocyte production by activation of the erythropoietin receptor (EPO-R), which triggers the activation of antiapoptotic and proliferative responses of erythroid progenitor cells. Additionally, to erythropoietic EPO activity, an antiapoptotic effect has been described in a wide spectrum of tissues. EPO low levels are found in the central nervous system (CNS), while EPO-R is expressed in most CNS cell types. In spite of EPO-R high levels expressed during hypoxic-ischemic brain, insufficient production of endogenous cerebral EPO could be the cause of determined circuit alterations that lead to the loss of specific neuronal populations. In the heart, high EPO-R expression in cardiac progenitor cells appears to contribute to myocardial regeneration under EPO stimulation. Several lines of evidence have linked EPO to an antiapoptotic role in CNS and in heart tissue. In this review, we resume an antiapoptotic role of EPO/EPO-R system in both brain and heart under hypoxic conditions, such as epilepsy and sudden death (SUDEP). Additionally, their protective effects could be a new field of research and a novel therapeutic strategy for the early treatment of these conditions and avoid SUDEP. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.BACKGROUND Cancer is a set of diseases formed by abnormal growth of cells leading to the formation of the tumor. The diagnosis can be made through symptoms' evaluation or imaging tests, however the techniques are limited and the tumor detection may be late. Thus, pharmaceutical nanotechnology has emerged to optimize the cancer diagnosis through nanostructured contrast agent's development. OBJECTIVE This review aims to identify commercialized nanomedicines and patents for cancer diagnosis. METHODS The databases used for scientific articles research were Pubmed, Science Direct, Scielo and Lilacs. Research on companies' websites and articles for the recognition of commercial nanomedicines were performed. The Derwent tool was applied for patents research. RESULTS This article aimed on nanosystems based on nanoparticles, dendrimers, liposomes, composites and quantum dots, associated to imaging techniques. Commercialized products based on metal and composite nanoparticles, associated to magnetic resonance and computed tomography, have been observed.