Translational research : the journal of laboratory and clinical medicine
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Following injury, the oral mucosa undergoes complex sequences of biological healing processes to restore homeostasis. While general similarities exist, there are marked differences in the genomics and kinetics of wound healing between the oral cavity and cutaneous epithelium. The lack of successful therapy for oral mucosal wounds has influenced clinicians to explore alternative treatments and potential autotherapies to enhance intraoral healing. ⋯ Studies were evaluated by injury models, therapy interventions, and outcome measures. The success of therapeutic approaches was assessed, and research outcomes were compared based on current hallmarks of oral wound healing. By leveraging therapeutic advancements, particularly within in cell-based biomaterials and immunoregulation, there is great potential for translational therapy in oral tissue regeneration.
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Diabetes mellitus is a costly disease and nearly one-third of these costs are attributed to management of diabetic foot disease including chronic, non-healing, diabetic foot ulcers. Therefore, much effort has been placed into understanding the pathogenesis of diabetic wounds and novel therapeutics. A relatively new area of interest has been macrophage polarization and its role in diabetic wound healing. ⋯ We reviewed factors known to affect macrophage polarization, mostly focused on those that contribute to M2 macrophage polarization, and potential treatments that at least in part target macrophage polarization in the diabetic wound bed. Much of the work has been aimed at reducing hyperglycemia and encouraging pro-inflammatory cytokine neutralization or decreased expression given this has a significant role in producing M1 macrophages. Treatment of diabetic wounds will likely require a multi-modal approach including management of underlying diabetes and control of hyperglycemia, topical therapeutics, and prevention of secondary infection and inflammation.
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Hypertrophic scars are the most common post-burn complications characterized by fibroblast proliferation and excessive extracellular matrix deposition. The intermediate-conductance Ca2+-activated K+ channel (KCa3.1) mediates fibroblast activation, resulting in several fibrotic diseases; however, this channel's role in the formation of post-burn hypertrophic skin scars remains unknown. Herein, we investigated the role of KCa3.1 and the therapeutic potential of TRAM-34, a selective inhibitor of KCa3.1, in hypertrophic skin scar formation following burn injury. ⋯ Anti-scarring molecular, histological, and visual effects of TRAM-34 were confirmed in murine burn models. Altered subcellular expression of KCa3.1 is a novel mechanism underlying the cellular response to burn injury. Our results suggest that selective inhibition of KCa3.1 by TRAM-34 has therapeutic potential against post-burn hypertrophic scar formation.
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Multicenter Study Clinical Trial
Circulating microRNA profiles predict the severity of COVID-19 in hospitalized patients.
We aimed to examine the circulating microRNA (miRNA) profile of hospitalized COVID-19 patients and evaluate its potential as a source of biomarkers for the management of the disease. This was an observational and multicenter study that included 84 patients with a positive nasopharyngeal swab Polymerase chain reaction (PCR) test for SARS-CoV-2 recruited during the first pandemic wave in Spain (March-June 2020). Patients were stratified according to disease severity: hospitalized patients admitted to the clinical wards without requiring critical care and patients admitted to the intensive care unit (ICU). ⋯ The discriminatory potential of the signature was higher than that observed for laboratory parameters such as leukocyte counts, C-reactive protein (CRP) or D-dimer [maximum AUC (95% CI) for these variables = 0.73 (0.55-0.92)]. miRNA levels were correlated with the duration of ICU stay. Specific circulating miRNA profiles are associated with the severity of COVID-19. Plasma miRNA signatures emerge as a novel tool to assist in the early prediction of vital status deterioration among ICU patients.
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Aberrant mesenchymal stem cells (MSCs) in multiple myeloma (MM) bone marrows (BM) promote disease progression and drug resistance. Here, we assayed the protein cargo transported from MM-MSCs to MM cells via microvesicles (MVs) with focus on ribosomal proteins (RPs) and assessment of their influence on translation initiation and design of MM phenotype. Proteomics analysis (mass spectrometry) demonstrated increased levels and repertoire of RPs in MM-MSCs MVs compared to normal donors (ND) counterparts (n = 3-8; P = 9.96E - 08). ⋯ MVs-mediated horizontal transfer of RPs between niche MSCs and myeloma cells is a systemic way to bestow pro-cancer advantages. This capacity also differentiates normal MSCs from the MM-modified MSCs and may mark their reprogramming. Future studies will be aimed at assessing the clinical and therapeutic potential of the increased RPs levels in MM-MSCs MVs.