60 research outputs found

    The HMGB1-RAGE axis mediates traumatic brain injury-induced pulmonary dysfunction in lung transplantation

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    Traumatic brain injury (TBI) results in systemic inflammatory responses that affect the lung. This is especially critical in the setting of lung transplantation, where more than half of donor allografts are obtained postmortem from individuals with TBI. The mechanism by which TBI causes pulmonary dysfunction remains unclear but may involve the interaction of high-mobility group box-1 (HMGB1) protein with the receptor for advanced glycation end products (RAGE). To investigate the role of HMGB1 and RAGE in TBI-induced lung dysfunction, RAGE-sufficient (wild-type) or RAGE-deficient (RAGE(-/-)) C57BL/6 mice were subjected to TBI through controlled cortical impact and studied for cardiopulmonary injury. Compared to control animals, TBI induced systemic hypoxia, acute lung injury, pulmonary neutrophilia, and decreased compliance (a measure of the lungs' ability to expand), all of which were attenuated in RAGE(-/-) mice. Neutralizing systemic HMGB1 induced by TBI reversed hypoxia and improved lung compliance. Compared to wild-type donors, lungs from RAGE(-/-) TBI donors did not develop acute lung injury after transplantation. In a study of clinical transplantation, elevated systemic HMGB1 in donors correlated with impaired systemic oxygenation of the donor lung before transplantation and predicted impaired oxygenation after transplantation. These data suggest that the HMGB1-RAGE axis plays a role in the mechanism by which TBI induces lung dysfunction and that targeting this pathway before transplant may improve recipient outcomes after lung transplantation

    World Congress Integrative Medicine & Health 2017: Part one

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    Inaugurating High‐Throughput Profiling of Extracellular Vesicles for Earlier Ovarian Cancer Detection

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    Abstract Detecting early cancer through liquid biopsy is challenging due to the lack of specific biomarkers for early lesions and potentially low levels of these markers. The current study systematically develops an extracellular‐vesicle (EV)‐based test for early detection, specifically focusing on high‐grade serous ovarian carcinoma (HGSOC). The marker selection is based on emerging insights into HGSOC pathogenesis, notably that it arises from precursor lesions within the fallopian tube. This work thus establishes murine fallopian tube (mFT) cells with oncogenic mutations and performs proteomic analyses on mFT‐derived EVs. The identified markers are then evaluated with an orthotopic HGSOC animal model. In serially‐drawn blood of tumor‐bearing mice, mFT‐EV markers increase with tumor initiation, supporting their potential use in early cancer detection. A pilot clinical study (n = 51) further narrows EV markers to five candidates, EpCAM, CD24, VCAN, HE4, and TNC. The combined expression of these markers distinguishes HGSOC from non‐cancer with 89% sensitivity and 93% specificity. The same markers are also effective in classifying three groups (non‐cancer, early‐stage HGSOC, and late‐stage HGSOC). The developed approach, for the first time inaugurated in fallopian tube‐derived EVs, could be a minimally invasive tool to monitor women at high risk of ovarian cancer for timely intervention

    Effect of oriental medicine music therapy on patients with Hwa-byung: a study protocol for a randomized controlled trial

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    <p>Abstract</p> <p>Background</p> <p>Hwa-byung, a Korean culture-bound syndrome with both psychological and somatic symptoms, is also known as ‘anger syndrome’. It includes various physical symptoms including anxiety, a feeling of overheating, a sensation of pressure on the chest, heart palpitations, respiratory stuffiness, insomnia, and anxiety.</p> <p>Methods/design</p> <p>The proposed study is a single-center, double-blind, randomized, controlled trial with two parallel arms: an oriental medicine music therapy (OMMT) group and a control music therapy (CMT) group. In total, 48 patients will be enrolled into the trial. The first visit will be the screening visit. At baseline (visit 2), all participants fulfilling both the inclusion and the exclusion criteria will be split and randomly divided into two equal groups: the OMMT and the CMT (n = 24 each). Each group will receive treatment sessions over the course of 4 weeks, twice per week, for eight sessions in total. The primary outcome is the State-Trait Anxiety Inventory (STAI), and the secondary outcomes are the Hwa-byung scale (H-scale), the Center for Epidemiologic Studies Depression Scale (CES-D), the Hwa-byung visual analogue scale (H-VAS) for primary symptoms, the World Health Organization Quality of Life scale, brief version (WHOQOL-BREF), and levels of salivary cortisol. Patients will be asked to complete questionnaires at the baseline visit (visit 2), after the last treatment session (visit 9), and at 4 weeks after the end of all trial sessions (visit 10). From the baseline (visit 2) through the follow-up (visit 10), the entire process will take a total of 53 days.</p> <p>Discussion</p> <p>This proposed study targets patients with Hwa-byung, especially those who have exhibited symptoms of anxiety. Therefore, the primary outcome is set to measure the level of anxiety. OMMT is music therapy combined with traditional Korean medicinal theories. Unlike previously reported music therapies, for which patients simply listen to music passively, in OMMT, patients actively move their bodies and play the music. Because Hwa-byung is caused by an accumulation of blocked emotions and anger inside the body, OMMT, because of its active component, is expected to be more efficacious than pre-existing music therapies.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN11939282</p
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