37 research outputs found

    Hypoxia-Induced Mitogenic Factor (HIMF/FIZZ1/RELMα) Recruits Bone Marrow-Derived Cells to the Murine Pulmonary Vasculature

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    . and localized to the media layer of the vessels. This finding suggests that these cells are of mesenchymal origin and differentiate toward myofibroblast and vascular smooth muscle. Structural location in the media of small vessels suggests a functional role in the lung vasculature. To examine a potential mechanism for HIMF-dependent recruitment of mesenchymal stem cells to the pulmonary vasculature, we performed a cell migration assay using cultured human mesenchymal stem cells (HMSCs). The addition of recombinant HIMF induced migration of HMSCs in a phosphoinosotide-3-kinase-dependent manner.These results demonstrate HIMF-dependent recruitment of BMD mesenchymal-like cells to the remodeling pulmonary vasculature

    Ectosome biogenesis and release processes observed by using live-cell dynamic imaging in mammalian glial cells.

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    BackgroundEctosomes are recognized as shedding from the plasma membranes into the extracellular environment. Recent research has demonstrated that ectosomes are surrounded by phospholipid membranes containing lipid rafts and caveolae. Some ectosomes contain cytokines in the lumen and have high levels of phosphatidylserine exposed to the outer membrane. Intracellular vesicles share both characters with ectosomes. Why the plasma membrane-derived ectosomes have the same characteristics as intracellular vesicles remain largely unknown.MethodsUsing live-cell dynamic imaging, we recorded the process of ectosome biogenesis and release in primary cultured neural cells.ResultsOur results show two different ectosome release methods: slow-releasing and fast-releasing. In the slow-releasing, multiple ectosomes emerge almost simultaneously on the cell surface and are released by outward budding from the plasma membrane. In the fast releasing, ectosomes squeeze out of the membrane domain and pinch off from a cell's surface. Using ER-tracker for live-cell imaging, we directly observed the process that intracellular vesicles jump out of the plasma membrane for release. This type of ectosomes has a reverse array of membrane proteins and phospholipids compared to the plasma membrane. So ectosomes should be divided into two groups: plasma membrane-derived and intracellular membrane-derived ectosomes.ConclusionsBoth slow releasing and fast releasing EVs imply mechanisms of human diseases and for diagnostics and drug delivery

    Breathing Signature as Vitality Score Index Created by Exercises of Qigong: Implications of Artificial Intelligence Tools Used in Traditional Chinese Medicine

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    Rising concerns about the short- and long-term detrimental consequences of administration of conventional pharmacopeia are fueling the search for alternative, complementary, personalized, and comprehensive approaches to human healthcare. Qigong, a form of Traditional Chinese Medicine, represents a viable alternative approach. Here, we started with the practical, philosophical, and psychological background of Ki (in Japanese) or Qi (in Chinese) and their relationship to Qigong theory and clinical application. Noting the drawbacks of the current state of Qigong clinic, herein we propose that to manage the unique aspects of the Eastern ‘non-linearity’ and ‘holistic’ approach, it needs to be integrated with the Western “linearity” “one-direction” approach. This is done through developing the concepts of “Qigong breathing signatures,” which can define our life breathing patterns associated with diseases using machine learning technology. We predict that this can be achieved by establishing an artificial intelligence (AI)-Medicine training camp of databases, which will integrate Qigong-like breathing patterns with different pathologies unique to individuals. Such an integrated connection will allow the AI-Medicine algorithm to identify breathing patterns and guide medical intervention. This unique view of potentially connecting Eastern Medicine and Western Technology can further add a novel insight to our current understanding of both Western and Eastern medicine, thereby establishing a vitality score index (VSI) that can predict the outcomes of lifestyle behaviors and medical conditions

    Hypoxia-induced mitogenic factor (HIMF/FIZZ1/RELMα) in chronic hypoxia- and antigen-mediated pulmonary vascular remodeling

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    <p>Abstract</p> <p>Background</p> <p>Both chronic hypoxia and allergic inflammation induce vascular remodeling in the lung, but only chronic hypoxia appears to cause PH. We investigate the nature of the vascular remodeling and the expression and role of hypoxia-induced mitogenic factor (HIMF/FIZZ1/RELMα) in explaining this differential response.</p> <p>Methods</p> <p>We induced pulmonary vascular remodeling through either chronic hypoxia or antigen sensitization and challenge. Mice were evaluated for markers of PH and pulmonary vascular remodeling throughout the lung vascular bed as well as HIMF expression and genomic analysis of whole lung.</p> <p>Results</p> <p>Chronic hypoxia increased both mean pulmonary artery pressure (mPAP) and right ventricular (RV) hypertrophy; these changes were associated with increased muscularization and thickening of small pulmonary vessels throughout the lung vascular bed. Allergic inflammation, by contrast, had minimal effect on mPAP and produced no RV hypertrophy. Only peribronchial vessels were significantly thickened, and vessels within the lung periphery did not become muscularized. Genomic analysis revealed that HIMF was the most consistently upregulated gene in the lungs following both chronic hypoxia and antigen challenge. HIMF was upregulated in the airway epithelial and inflammatory cells in both models, but only chronic hypoxia induced HIMF upregulation in vascular tissue.</p> <p>Conclusions</p> <p>The results show that pulmonary vascular remodeling in mice induced by chronic hypoxia or antigen challenge is associated with marked increases in HIMF expression. The lack of HIMF expression in the vasculature of the lung and no vascular remodeling in the peripheral resistance vessels of the lung is likely to account for the failure to develop PH in the allergic inflammation model.</p
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