Browsing by Subject "Diabetic wound healing"

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    Driving adult tissue repair via re-engagement of a pathway required for fetal healing
    (Elsevier, 2023) Ghatak, Subhadip; Khanna, Savita; Roy, Sashwati; Thirunavukkarasu, Mahesh; Pradeep, Seetur R.; Wulff, Brian C.; El Masry, Mohamed S.; Sharma, Anu; Palakurti, Ravichand; Ghosh, Nandini; Xuan, Yi; Wilgus, Traci A.; Maulik, Nilanjana; Yoder, Mervin C.; Sen, Chandan K.; Surgery, School of Medicine
    Fetal cutaneous wound closure and repair differ from that in adulthood. In this work, we identify an oxidant stress sensor protein, nonselenocysteine-containing phospholipid hydroperoxide glutathione peroxidase (NPGPx), that is abundantly expressed in normal fetal epidermis (and required for fetal wound closure), though not in adult epidermis, but is variably re-induced upon adult tissue wounding. NPGPx is a direct target of the miR-29 family. Following injury, abundance of miR-29 is lowered, permitting a prompt increase in NPGPx transcripts and protein expression in adult wound-edge tissue. NPGPx expression was required to mediate increased keratinocyte migration induced by miR-29 inhibition in vitro and in vivo. Increased NPGPx expression induced increased SOX2 expression and β-catenin nuclear localization in keratinocytes. Augmenting physiologic NPGPx expression via experimentally induced miR-29 suppression, using cutaneous tissue nanotransfection or targeted lipid nanoparticle delivery of anti-sense oligonucleotides, proved to be sufficient to overcome the deleterious effects of diabetes on this specific pathway to enhance tissue repair.
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    The NIDDK Diabetic Foot Consortium
    (Sage, 2023) Jones, Teresa L. Z.; Holmes, Crystal M.; Katona, Aimee; Martin, Catherine L.; Niewczas, Monika A.; Pop-Busui, Rodica; Schmidt, Brian M.; Sen, Chandan K.; Tomic-Canic, Marjana; Veves, Aristidis; Medicine, School of Medicine
    The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Diabetic Foot Consortium (DFC) was established in September 2018 by the NIDDK to build an organization to facilitate the highest quality of clinical research on diabetic foot ulcers (DFUs) that will answer clinically significant questions to improve DFU healing and prevent amputations. The initial focus of the DFC is to develop and validate biomarkers for DFUs that can be used in clinical care and research. The DFC consists of a data coordinating center (DCC) for operational oversight and statistical analysis, clinical sites for participant recruitment and evaluation, and biomarker analysis units (BAUs). The DFC is currently studying biomarkers to predict wound healing and recurrence and is collecting biosamples for future studies through a biorepository. The DFC plans to address the challenges of recruitment and eligibility criteria for DFU clinical trials by taking an approach of “No DFU Patient Goes Unstudied.” In this platform approach, clinical history, DFU outcome, wound imaging, and biologic measurements from a large number of patients will be captured and the in-depth longitudinal data set will be analyzed to develop a computational-based DFU risk factor profile to facilitate scientifically sound clinical trial design. The DFC will expand its platform to include studies of the role of social determinants of health, such as food insecurity, housing instability, limited health literacy, and poor social support. The DFC is starting partnerships with the broad group of stakeholders in the wound care community.