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2 results on '"Michael Demczuk"'

1. Topical application of synthetic melanin promotes tissue repair

Author

Dauren Biyashev, Zofia E. Siwicka, Ummiye V. Onay, Michael Demczuk, Dan Xu, Madison K. Ernst, Spencer T. Evans, Cuong V. Nguyen, Florencia A. Son, Navjit K. Paul, Naneki C. McCallum, Omar K. Farha, Stephen D. Miller, Nathan C. Gianneschi, and Kurt Q. Lu

Subjects
Medicine
Abstract

Abstract In acute skin injury, healing is impaired by the excessive release of reactive oxygen species (ROS). Melanin, an efficient scavenger of radical species in the skin, performs a key role in ROS scavenging in response to UV radiation and is upregulated in response to toxic insult. In a chemical injury model in mice, we demonstrate that the topical application of synthetic melanin particles (SMPs) significantly decreases edema, reduces eschar detachment time, and increases the rate of wound area reduction compared to vehicle controls. Furthermore, these results were replicated in a UV-injury model. Immune array analysis shows downregulated gene expression in apoptotic and inflammatory signaling pathways consistent with histological reduction in apoptosis. Mechanistically, synthetic melanin intervention increases superoxide dismutase (SOD) activity, decreases Mmp9 expression, and suppresses ERK1/2 phosphorylation. Furthermore, we observed that the application of SMPs caused increased populations of anti-inflammatory immune cells to accumulate in the skin, mirroring their decrease from splenic populations. To enhance antioxidant capacity, an engineered biomimetic High Surface Area SMP was deployed, exhibiting increased wound healing efficiency. Finally, in human skin explants, SMP intervention significantly decreased the damage caused by chemical injury. Therefore, SMPs are promising and effective candidates as topical therapies for accelerated wound healing, including via pathways validated in human skin.

Published
2023
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2. A novel treatment for skin repair using a combination of spironolactone and vitamin D3

Author

Kurt Q. Lu, Dauren Biyashev, Prarthana Dalal, Spencer Evans, U. Onay, Jose-Marc Techner, and Michael Demczuk

Subjects
0301 basic medicine, Chemokine, Inflammation, vitamin D, Apoptosis, Pharmacology, Spironolactone, General Biochemistry, Genetics and Molecular Biology, Proinflammatory cytokine, 03 medical and health sciences, Mice, 0302 clinical medicine, Immune system, Mineralocorticoid receptor, History and Philosophy of Science, medicine, Nyasphys1560, Animals, Mechlorethamine, Cholecalciferol, Skin, Skin repair, Nyasdrug6499, Wound Healing, biology, integumentary system, Chemistry, General Neuroscience, Macrophages, Interleukin, nitrogen mustard, Original Articles, 030104 developmental biology, RAW 264.7 Cells, Gene Expression Regulation, 030220 oncology & carcinogenesis, biology.protein, Wounds and Injuries, Original Article, Female, skin injury, medicine.symptom, Wound healing
Abstract

Injury of the skin from exposure to toxic chemicals leads to the release of inflammatory mediators and the recruitment of immune cells. Nitrogen mustard (NM) and other alkylating agents cause severe cutaneous damage for which there are limited treatment options. Here, we show that combined treatment of vitamin D3 (VD3) and spironolactone (SP), a mineralocorticoid receptor antagonist, significantly improves the resolution of inflammation and accelerates wound healing after NM exposure. SP enhanced the inhibitory effect of VD3 on nuclear factor‐kB activity. Combined treatment of NM‐exposed mice with VD3 and SP synergistically inhibited the expression of iNOS in the skin and decreased the expression of matrix metallopeptidase‐9, C‐C motif chemokine ligand 2, interleukin (IL)‐1α, and IL‐1β. The combined treatment decreased the number of local proinflammatory M1 macrophages resulting in an increase in the M2/M1 ratio in the wound microenvironment. Apoptosis was also decreased in the skin after combined treatment. Together, this creates a proresolution state, resulting in more rapid wound closure. Combined VD3 and SP treatment is effective in modulating the immune response and activating anti‐inflammatory pathways in macrophages to facilitate tissue repair. Altogether, these data demonstrate that VD3 and SP may constitute an effective treatment regimen to improve wound healing after NM or other skin chemical injury., Our results demonstrate that vitamin D3 in combination with spironolactone treatment improves wound healing after nitrogen mustard (NM) exposure by modulating the immune response and activating anti‐inflammatory pathways. In addition to supportive treatment, this may expand the currently limited treatment options to improve clinical outcomes for NM injury.

Published
2020

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