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.
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]
Project description:Acupuncture is recommended by the World Health Organization (WHO) as an alternative and complementary strategy for stroke treatment and for improving stroke care. Clinical trial and meta-analysis findings have demonstrated the efficacy of acupuncture in improving balance function, reducing spasticity, and increasing muscle strength and general well-being post-stroke. The mechanisms underlying the beneficial effects of acupuncture in stroke rehabilitation remain unclear. The aim of this study was to conduct a literature review, summarize the current known mechanisms in ischemic stroke rehabilitation through acupuncture and electroacupuncture (EA) therapy, and to detail the frequently used acupoints implicated in these effects. The evidence in this review indicates that five major different mechanisms are involved in the beneficial effects of acupuncture/EA on ischemic stroke rehabilitation: (1) Promotion of neurogenesis and cell proliferation in the central nervous system (CNS); (2) Regulation of cerebral blood flow in the ischemic area; (3) Anti-apoptosis in the ischemic area; (4) Regulation of neurochemicals; and, (5) Improvement of impaired long-term potentiation (LTP) and memory after stroke. The most frequently used acupoints in basic studies include Baihui (GV20), Zusanli (ST36), Quchi (LI11), Shuigou (GV26), Dazhui (GV14), and Hegu (LI4). Our findings show that acupuncture exerts a beneficial effect on ischemic stroke through modulation of different mechanisms originating in the CNS.
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.
Project description:In the past century there have been incredible advances in the field of medical research, but what hinders translation of this knowledge into effective treatment for human disease? There is an increasing focus on the failure of many research breakthroughs to be translated through the clinical trial process and into medical practice. In this mini review, we will consider some of the reasons that findings in basic medical research fail to become translated through clinical trials and into basic medical practices. We focus in particular on the way that human disease is modeled, the understanding we have of how our targets behave in vivo, and also some of the issues surrounding reproducibility of basic research findings. We will also look at some of the ways that have been proposed for overcoming these issues. It appears that there needs to be a cultural shift in the way we fund, publish and recognize quality control in scientific research. Although this is a daunting proposition, we hope that with increasing awareness and focus on research translation and the hurdles that impede it, the field of medical research will continue to inform and improve medical practice across the world.
Project description:Pompe disease is a rare and deadly muscle disorder. As a clinical entity, the disease has been known for over 75 years. While an optimist might be excited about the advances made during this time, a pessimist would note that we have yet to find a cure. However, both sides would agree that many findings in basic science-such as the Nobel prize-winning discoveries of glycogen metabolism, the lysosome, and autophagy-have become the foundation of our understanding of Pompe disease. The disease is a glycogen storage disorder, a lysosomal disorder, and an autophagic myopathy. In this review, we will discuss how these past discoveries have guided Pompe research and impacted recent therapeutic developments.
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.
Project description:PURPOSE OF REVIEW:Orthobiologics, including amniotic products, have been gaining interest in the past decade for the treatment of various orthopedic conditions including osteoarthritis. However, the use of biologics is varied and is currently available with minimal oversight or regulation. This review will assess the current state of research that utilizes amniotic products both in vitro and in vivo. RECENT FINDINGS:Amniotic tissue derivatives have been shown to have positive effects in animal models for a variety of conditions. Clinical trials are limited with mixed outcomes, yet some recent studies suggest the rationale for continued investigation. While amniotic products appear promising in numerous animal studies, human clinical trials are still lacking. Future studies are needed to assess whether amniotic products have a role in the treatment of osteoarthritis and other orthopedic pathologies.
Project description:Background: This study intends to summarize the causes, clinical examination, and treatments of scapular dyskinesis (SD) and to briefly investigate whether alteration can be managed by a precision rehabilitation protocol planned on the basis of features derived from clinical tests. Methods: We performed a comprehensive search of PubMed, Cochrane, CINAHL and EMBASE databases using various combinations of the keywords "Rotator cuff", "Scapula", "Scapular Dyskinesis", "Shoulder", "Biomechanics" and "Arthroscopy". Results: SD incidence is growing in patients with shoulder pathologies, even if it is not a specific injury or directly related to a particular injury. SD can be caused by multiple factors or can be the trigger of shoulder-degenerative pathologies. In both cases, SD results in a protracted scapula with the arm at rest or in motion. Conclusions: A clinical evaluation of altered shoulder kinematics is still complicated. Limitations in observing scapular motion are mainly related to the anatomical position and function of the scapula itself and the absence of a tool for quantitative SD clinical assessment. High-quality clinical trials are needed to establish whether there is a possible correlation between SD patterns and the specific findings of shoulder pathologies with altered scapular kinematics.