Stroke Literature Synopses: Basic Science (2018/May)
Ontology highlight
ABSTRACT:
SUBMITTER: Arai K
PROVIDER: S-EPMC6247919 | biostudies-literature | 2018 Jun
REPOSITORIES: biostudies-literature
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Project description:Cell therapy is emerging as a viable therapy to restore neurological function after stroke. Many types of stem/progenitor cells from different sources have been explored for their feasibility and efficacy for the treatment of stroke. Transplanted cells not only have the potential to replace the lost circuitry, but also produce growth and trophic factors, or stimulate the release of such factors from host brain cells, thereby enhancing endogenous brain repair processes. Although stem/progenitor cells have shown a promising role in ischemic stroke in experimental studies as well as initial clinical pilot studies, cellular therapy is still at an early stage in humans. Many critical issues need to be addressed including the therapeutic time window, cell type selection, delivery route, and in vivo monitoring of their migration pattern. This review attempts to provide a comprehensive synopsis of preclinical evidence and clinical experience of various donor cell types, their restorative mechanisms, delivery routes, imaging strategies, future prospects and challenges for translating cell therapies as a neurorestorative regimen in clinical applications.
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Project description:ProblemUnderstanding and communicating medical advances driven by basic research, and acquiring foundational skills in critically appraising and communicating translational basic research literature that affects patient care, are challenging for medical students to develop.ApproachThe authors developed a mandatory course from 2012 to 2018 at Texas A&M University College of Medicine to address this problem. Medical Student Grand Rounds (MSGR) trains first-year students to find, critically assess, and present primary research literature about self-selected medically relevant topics. With basic science faculty mentoring, students completed milestones culminating in oral presentations. Students learned to search literature databases and then choose a clinical subject using these skills. They outlined the clinical subject area background and a mechanistic research topic into a clinical problem based on deeper evaluation of primary research literature. "Mechanistic" was defined in this context as providing experimental evidence that explained the "how" and "why" underlying clinical manifestations of a disease. Students received evaluations and feedback from mentors about discerning the quality of information and synthesizing information on their topics. Finally, students prepared and gave oral presentations, emphasizing the primary literature on their topics.OutcomesIn the early stages of the course development, students had difficulty critically assessing and evaluating research literature. Mentored training by research-oriented faculty, however, dramatically improved student perceptions of the MSGR experience. Mentoring helped students develop skills to synthesize ideas from basic research literature. According to grades and self-evaluations, students increased proficiency in finding and interpreting research articles, preparing and delivering presentations, and understanding links among basic and translational research and clinical applications.Next stepsThe authors plan to survey fourth-year students who have completed MSGR about their perceptions of the course in the context of clinical experiences in medical school to guide future refinements.
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Project description:Background Many HIV databases and applications focus on a limited domain of HIV knowledge. Since even a “simple” organism like HIV represents a very complex system with many interacting elements, the fractured structure of existing databases and applications likely limits our ability to investigate and understand HIV. To facilitate research, therefore, we have built HIVToolbox, which integrates much of the knowledge about HIV proteins and presents the data in an interactive web application. HIVToolbox allows quick and convenient hypotheses generation, experiment interpretation, and potential new drug structure creation. Methods HIVToolbox was built as a standard three-tier J2EE web application, consisting of 1) an underlying relational MySQL database, 2) a set of standard Java data access objects that pull data from the database, and 3) a set of dynamic web pages the user interacts with. HIV-1 data from external sources such as the Protein Data Bank, NCBI, Los Alamos, etc. was collected, curated, and stored in the HIVToolbox database. Additional data, such as homology and position statistics matrices, was generated from existing data. Since version 1, drug binding site and drug resistant mutation data has also been added. Results HIVToolbox was used to create several new hypotheses about HIV-1 integrase, including predicting the location of a CK2 phosphorylation site, which was later confirmed by experiment. A new version of HIVToolbox support display of the 3D locations of drug resistant mutations on surface plots of HIV proteins and the drug binding sites for structures of complexes of HIV proteins with drugs. Conclusion HIVToolbox is an open-access web application that allows virologists and structural biologists to access detailed information about HIV-1 proteins, such as sequence, structure, functional sites and relationships, homology, drug binding sites, and drug resistant mutations, and to immediately see the relationships between any or all of them. Weblink: [http://hivtoolbox.bio-toolkit.com]
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Project description:Tendinopathy is a common clinical problem with athletes and in many occupational settings. Tendinopathy can occur in any tendon, often near its insertion or enthesis where there is an area of stress concentration, and is directly related to the volume of repetitive load to which the tendon is exposed. Recent studies indicate tendinopathy is more likely to occur in situations that increase the "dose" of load to the tendon enthesis - including increased activity, weight, advancing age, and genetic factors. The cells in tendinopathic tendon are rounder, more numerous, and show evidence of oxidative damage and more apoptosis. These cells also produce a matrix that is thicker and weaker with more water, more immature and cartilage-like matrix proteins, and less organization. There is now evidence of a population of regenerating stem cells within tendon. These studies suggest prevention of tendinopathy should be directed at reducing the volume of repetitive loads to below that which induces oxidative-induced apoptosis and cartilage-like genes. The management strategies might involve agents or cells that induce tendon stem cell proliferation, repair and restoration of matrix integrity.
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Project description:Diverse insults to the optic nerve result in partial to total vision loss as the axons of retinal ganglion cells are destroyed. In glaucoma, axons are injured at the optic nerve head; in other optic neuropathies, axons can be damaged along the entire visual pathway. In all cases, as mammals cannot regenerate injured central nervous system cells, once the axons are lost, vision loss is irreversible. However, much has been learned about how retinal ganglion cells respond to axon injuries, and many of these crucial discoveries offer hope for future regenerative therapies. Here we review the current understanding regarding the temporal progression of axonal degeneration. We summarize known survival and regenerative mechanisms in mammals, including specific signaling pathways, key transcription factors, and reprogramming genes. We cover mechanisms intrinsic to retinal ganglion cells as well as their interactions with myeloid and glial cell populations in the retina and optic nerve that affect survival and regeneration. Finally, we highlight some non-mammalian species that are able to regenerate their retinal ganglion cell axons after injury, as understanding these successful regenerative responses may be essential to the rational design of future clinical interventions to regrow the optic nerve. In the end, a combination of many different molecular and cellular interventions will likely be the only way to achieve functional recovery of vision and restore quality of life to millions of patients around the world.
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