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Cutaneous Biology, Molecular Dermatology and Dermatopathology

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 30 December 2024 | Viewed by 16406

Special Issue Editor

Dr. Bijan Safai

E-Mail Website
Guest Editor
1. Chairman and Professor of Dermatology, New York Medical College, Valhalla, NY 10595, USA
2. Dermatology Department, NYC Health + Hospitals/Metropolitan, New York, NY 10029, USA
3. Dermatology Department, NYC Health + Hospitals/Coney Island, New York, NY 11235, USA
Interests: molecular dermatology; targeted therapy; cutaneous oncology; immunodermatology; cutaneous biology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The past few decades have witnessed considerable advancements in the field of molecular technology. Dermatology has benefited from these new developments more than most other medical disciplines. Dermatology has become one of the fastest-growing fields in medicine and is at the forefront of disciplines utilizing these new advances. Much has been learned about the pathogenic mechanisms and diagnostic tools applied in this field, and many targeted therapies have been discovered for the treatment of various inflammatory and neoplastic disorders.

The advances in molecular technologies have opened new research avenues, specifically in the area of immunohistochemistry and the identification of cellular biomarkers. Other molecular techniques—such as enzyme-linked immunosorbent assays, blotting techniques, flow cytometry, and mass spectrometry—have been employed in dermatology in order to improve our understanding of the pathogenic mechanisms of dermatologic diseases and their diagnosis. More importantly, we have recently witnessed the onset of the application of whole-genomic sequencing, together with CRISPR and mRNA sequencing, in dermatology. While these technologies are in their early phases of development, they can provide many new insights into the biology of skin disorders.

Led by Dr. Bijan Safai, with the assistance of our Topical Advisory Panel Member Dr. Banu Farabi (New York Medical College-Metropolitan Hospital), this publication highlights some very exciting and informative areas of dermatology and their impacts on diagnosis and treatment approaches.

Dr. Bijan Safai
Guest Editor

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Keywords

  • molecular dermatology
  • targeted therapy
  • cutaneous oncology
  • immunodermatology
  • cutaneous biology

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Published Papers (7 papers)

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Research

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18 pages, 5535 KiB  
Article
An In Vitro Strategy to Evaluate Ketoprofen Phototoxicity at the Molecular and Cellular Levels
by Klaudia Banach, Justyna Kowalska, Mateusz Maszczyk, Zuzanna Rzepka, Jakub Rok and Dorota Wrześniok
Int. J. Mol. Sci. 2024, 25(23), 12647; https://doi.org/10.3390/ijms252312647 - 25 Nov 2024
Viewed by 313
Abstract
Phototoxicity is a significant problem that occurs in a large part of the population and is often caused by commonly used pharmaceuticals, including over-the-counter drugs. Therefore, testing drugs with photosensitizing potential is very important. The aim of this study is to analyze the [...] Read more.
Phototoxicity is a significant problem that occurs in a large part of the population and is often caused by commonly used pharmaceuticals, including over-the-counter drugs. Therefore, testing drugs with photosensitizing potential is very important. The aim of this study is to analyze the cytotoxicity and phototoxicity of ketoprofen towards human melanocytes and fibroblasts in three different treatment schemes in order to optimize the study. Cytometric tests (studies of viability, proliferation, intracellular thiol levels, mitochondrial potential, cell cycle, and DNA fragmentation), Western blot analysis (cytochrome c and p44/p42 protein levels), and confocal microscopy imaging were performed to assess the impact of the developed treatments on skin cells. Research on experimental schemes may help reduce or eliminate the risk of phototoxic reactions. In the case of ketoprofen, we found that the strongest phototoxic potential was exhibited in the treatment where the drug was present in the solution during the irradiation of cells, both pigmented and non-pigmented cells. These results indicate that the greatest risk of photosensitivity reactions related to ketoprofen occurs after direct contact with the drug and UV exposure. Full article
(This article belongs to the Special Issue Cutaneous Biology, Molecular Dermatology and Dermatopathology)
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20 pages, 14484 KiB  
Article
Liver Fluke-Derived Molecules Accelerate Skin Repair Processes in a Mouse Model of Type 2 Diabetes Mellitus
by Anna Kovner, Yaroslav Kapushchak, Oxana Zaparina, Dmitry Ponomarev and Maria Pakharukova
Int. J. Mol. Sci. 2024, 25(22), 12002; https://doi.org/10.3390/ijms252212002 - 8 Nov 2024
Viewed by 387
Abstract
Chronic nonhealing wounds, such as diabetic ulcers, are among the most serious complications of diabetes mellitus. Consequently, the search for new therapeutic strategies remains highly relevant. Based on our previous data on acute wounds, bioactive molecules derived from the liver fluke Opisthorchis felineus [...] Read more.
Chronic nonhealing wounds, such as diabetic ulcers, are among the most serious complications of diabetes mellitus. Consequently, the search for new therapeutic strategies remains highly relevant. Based on our previous data on acute wounds, bioactive molecules derived from the liver fluke Opisthorchis felineus hold promise as a novel approach to wound healing. The aim of this study was to investigate the wound-healing properties of excretory–secretory products (ESP) and inactivated eggs of O. felineus in a model of type 2 diabetes mellitus. Two-month-old mice of the BKS.Cg + Leprdb/+Leprdb/OlaHsd (db/db) strain were inflicted with superficial wounds of 5 mm in diameter. Mouse groups included several controls (methylcellulose as the vehicle and human recombinant PDGF as the positive control) and specific-treatment groups (ESP and inactivated O. felineus eggs). Histopathological, immunohistochemical, and RT-PCR studies using markers for M1/M2 polarization, angiogenesis, and extracellular matrix remodeling were carried out. Additionally, an image analysis of Masson’s trichrome-stained skin sections was performed. The proliferation of HaCaT cells under ESP and egg treatment was also assessed. The present study reveals a significant increase in the percentage of wound healing in ESP- and egg-treated groups, which significantly exceeded the control values after 14 days. Wound treatment with either ESP or worm eggs resulted in (i) a reduction in inflammation with a canonical M1-to-M2 polarization shift, (ii) the modulation of the vascular response, and (iii) dermal extracellular matrix remodeling. All results are comparable to those of the positive control group treated with PDGF. This study also reveals that ESP, but not O. felineus eggs, stimulated keratinocyte proliferation in vitro. The results indicate the high wound-healing potential of liver fluke bioactive molecules and open prospects for further research on these new promising therapeutic approaches. Full article
(This article belongs to the Special Issue Cutaneous Biology, Molecular Dermatology and Dermatopathology)
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20 pages, 5011 KiB  
Article
Human Beta Defensin-2 mRNA and Proteasome Subunit β Type 8 mRNA Analysis, Useful in Differentiating Skin Biopsies from Atopic Dermatitis and Psoriasis Vulgaris Patients
by Agnieszka Terlikowska-Brzósko, Ryszard Galus, Piotr Murawski, Justyna Niderla-Bielińska, Izabela Młynarczuk-Biały, Elwira Paluchowska and Witold Owczarek
Int. J. Mol. Sci. 2024, 25(17), 9192; https://doi.org/10.3390/ijms25179192 - 24 Aug 2024
Viewed by 646
Abstract
(1): Atopic dermatitis and psoriasis vulgaris are chronic, inflammatory diseases. Clinical presentation usually leads to a proper diagnosis, but sometimes neither clinical examination nor histopathological evaluation can be conclusive. Therefore, we aimed to build up a novel diagnostic tool and check it for [...] Read more.
(1): Atopic dermatitis and psoriasis vulgaris are chronic, inflammatory diseases. Clinical presentation usually leads to a proper diagnosis, but sometimes neither clinical examination nor histopathological evaluation can be conclusive. Therefore, we aimed to build up a novel diagnostic tool and check it for accuracy. The main objective of our work was to differentiate between healthy skin (C), atopic dermatitis (AD) and psoriasis vulgaris (PV) biopsies on the base of involucrin (IVL) and human β-defensin-2 (hBD-2) concentrations and their mRNA, as well as mRNA for TPP2 and PSMB8. (2): ELISA for IVL and hBD-2 proteins and Real-time PCR for the relative expression of mRNA for: IVL (IVL mRNA), hBD-2 (hBD-2 mRNA), PSMB8 (PSMB8 mRNA) and TPP2 (TPP2 mRNA), isolated from skin biopsies taken from AD and PV patients and healthy volunteers were performed. (3): hBD-2 mRNA and PSMB8 mRNA correlated with some parameters of clinical assessment of inflammatory disease severity. hBD-2 mRNA expression, exclusively, was sufficient to distinguish inflammatory skin biopsies from the healthy ones. (4): hBD-2 mRNA and PSMB8 mRNA analysis were the most valuable parameters in differentiating AD and PV biopsies. Full article
(This article belongs to the Special Issue Cutaneous Biology, Molecular Dermatology and Dermatopathology)
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16 pages, 2396 KiB  
Article
Arsenic Impairs Wound Healing Processes in Dermal Fibroblasts and Mice
by Sara R. Dresler, Bronson I. Pinto, Matthew C. Salanga, Catherine R. Propper, Savannah R. Berry and Robert S. Kellar
Int. J. Mol. Sci. 2024, 25(4), 2161; https://doi.org/10.3390/ijms25042161 - 10 Feb 2024
Viewed by 1571
Abstract
Inorganic arsenic (NaAsO2) is a naturally occurring metalloid found in water resources globally and in the United States at concentrations exceeding the U.S. Environmental Protection Agency Maximum Contamination Level of 10 ppb. While exposure to arsenic has been linked to cancer, [...] Read more.
Inorganic arsenic (NaAsO2) is a naturally occurring metalloid found in water resources globally and in the United States at concentrations exceeding the U.S. Environmental Protection Agency Maximum Contamination Level of 10 ppb. While exposure to arsenic has been linked to cancer, cardiovascular disease, and skin lesions, the impact of arsenic exposure on wound healing is not fully understood. Cultured dermal fibroblasts exposed to NaAsO2 displayed reduced migration (scratch closure), proliferation, and viability with a lowest observable effect level (LOEL) of 10 µM NaAsO2 following 24 h exposure. An enrichment of Matrix Metalloproteinase 1 (MMP1) transcripts was observed at a LOEL of 1 µM NaAsO2 and 24 h exposure. In vivo, C57BL/6 mice were exposed to 10 µM NaAsO2 in their drinking water for eight weeks, then subjected to two full thickness dorsal wounds. Wounds were evaluated for closure after 6 days. Female mice displayed a significant reduction in wound closure and higher erythema levels, while males showed no effects. Gene expression analysis from skin excised from the wound site revealed significant enrichment in Arsenic 3-Methyltransferase (As3mt) and Estrogen Receptor 2 (Esr2) mRNA in the skin of female mice. These results indicate that arsenic at environmentally relevant concentrations may negatively impact wound healing processes in a sex-specific manner. Full article
(This article belongs to the Special Issue Cutaneous Biology, Molecular Dermatology and Dermatopathology)
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Review

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17 pages, 458 KiB  
Review
The Efficacy of Stem Cells in Wound Healing: A Systematic Review
by Banu Farabi, Katie Roster, Rahim Hirani, Katharine Tepper, Mehmet Fatih Atak and Bijan Safai
Int. J. Mol. Sci. 2024, 25(5), 3006; https://doi.org/10.3390/ijms25053006 - 5 Mar 2024
Cited by 4 | Viewed by 6851
Abstract
Wound healing is an intricate process involving coordinated interactions among inflammatory cells, skin fibroblasts, keratinocytes, and endothelial cells. Successful tissue repair hinges on controlled inflammation, angiogenesis, and remodeling facilitated by the exchange of cytokines and growth factors. Comorbid conditions can disrupt this process, [...] Read more.
Wound healing is an intricate process involving coordinated interactions among inflammatory cells, skin fibroblasts, keratinocytes, and endothelial cells. Successful tissue repair hinges on controlled inflammation, angiogenesis, and remodeling facilitated by the exchange of cytokines and growth factors. Comorbid conditions can disrupt this process, leading to significant morbidity and mortality. Stem cell therapy has emerged as a promising strategy for enhancing wound healing, utilizing cells from diverse sources such as endothelial progenitor cells, bone marrow, adipose tissue, dermal, and inducible pluripotent stem cells. In this systematic review, we comprehensively investigated stem cell therapies in chronic wounds, summarizing the clinical, translational, and primary literature. A systematic search across PubMed, Embase, Web of Science, Google Scholar, and Cochrane Library yielded 22,454 articles, reduced to 44 studies after rigorous screening. Notably, adipose tissue-derived mesenchymal stem cells (AD-MSCs) emerged as an optimal choice due to their abundant supply, easy isolation, ex vivo proliferative capacities, and pro-angiogenic factor secretion. AD-MSCs have shown efficacy in various conditions, including peripheral arterial disease, diabetic wounds, hypertensive ulcers, bullous diabeticorum, venous ulcers, and post-Mohs micrographic surgery wounds. Delivery methods varied, encompassing topical application, scaffold incorporation, combination with plasma-rich proteins, and atelocollagen administration. Integration with local wound care practices resulted in reduced pain, shorter healing times, and improved cosmesis. Stem cell transplantation represents a potential therapeutic avenue, as transplanted stem cells not only differentiate into diverse skin cell types but also release essential cytokines and growth factors, fostering increased angiogenesis. This approach holds promise for intractable wounds, particularly chronic lower-leg wounds, and as a post-Mohs micrographic surgery intervention for healing defects through secondary intention. The potential reduction in healthcare costs and enhancement of patient quality of life further underscore the attractiveness of stem cell applications in wound care. This systematic review explores the clinical utilization of stem cells and stem cell products, providing valuable insights into their role as ancillary methods in treating chronic wounds. Full article
(This article belongs to the Special Issue Cutaneous Biology, Molecular Dermatology and Dermatopathology)
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24 pages, 6142 KiB  
Review
Understanding Type 3 Innate Lymphoid Cells and Crosstalk with the Microbiota: A Skin Connection
by Thao Tam To, Nicole Chizara Oparaugo, Alexander R. Kheshvadjian, Amanda M. Nelson and George W. Agak
Int. J. Mol. Sci. 2024, 25(4), 2021; https://doi.org/10.3390/ijms25042021 - 7 Feb 2024
Viewed by 2932
Abstract
Innate lymphoid cells (ILCs) are a diverse population of lymphocytes classified into natural killer (NK) cells, ILC1s, ILC2s, ILC3s, and ILCregs, broadly following the cytokine secretion and transcription factor profiles of classical T cell subsets. Nonetheless, the ILC lineage does not have rearranged [...] Read more.
Innate lymphoid cells (ILCs) are a diverse population of lymphocytes classified into natural killer (NK) cells, ILC1s, ILC2s, ILC3s, and ILCregs, broadly following the cytokine secretion and transcription factor profiles of classical T cell subsets. Nonetheless, the ILC lineage does not have rearranged antigen-specific receptors and possesses distinct characteristics. ILCs are found in barrier tissues such as the skin, lungs, and intestines, where they play a role between acquired immune cells and myeloid cells. Within the skin, ILCs are activated by the microbiota and, in turn, may influence the microbiome composition and modulate immune function through cytokine secretion or direct cellular interactions. In particular, ILC3s provide epithelial protection against extracellular bacteria. However, the mechanism by which these cells modulate skin health and homeostasis in response to microbiome changes is unclear. To better understand how ILC3s function against microbiota perturbations in the skin, we propose a role for these cells in response to Cutibacterium acnes, a predominant commensal bacterium linked to the inflammatory skin condition, acne vulgaris. In this article, we review current evidence describing the role of ILC3s in the skin and suggest functional roles by drawing parallels with ILC3s from other organs. We emphasize the limited understanding and knowledge gaps of ILC3s in the skin and discuss the potential impact of ILC3-microbiota crosstalk in select skin diseases. Exploring the dialogue between the microbiota and ILC3s may lead to novel strategies to ameliorate skin immunity. Full article
(This article belongs to the Special Issue Cutaneous Biology, Molecular Dermatology and Dermatopathology)
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30 pages, 1494 KiB  
Review
Skin Cancer Microenvironment: What We Can Learn from Skin Aging?
by Andrea D’Arino, Silvia Caputo, Laura Eibenschutz, Paolo Piemonte, Pierluigi Buccini, Pasquale Frascione and Barbara Bellei
Int. J. Mol. Sci. 2023, 24(18), 14043; https://doi.org/10.3390/ijms241814043 - 13 Sep 2023
Cited by 4 | Viewed by 2717
Abstract
Aging is a natural intrinsic process associated with the loss of fibrous tissue, a slower cell turnover, and a reduction in immune system competence. In the skin, the continuous exposition of environmental factors superimposes extrinsic damage, mainly due to ultraviolet radiation causing photoaging. [...] Read more.
Aging is a natural intrinsic process associated with the loss of fibrous tissue, a slower cell turnover, and a reduction in immune system competence. In the skin, the continuous exposition of environmental factors superimposes extrinsic damage, mainly due to ultraviolet radiation causing photoaging. Although not usually considered a pathogenic event, photoaging affects cutaneous biology, increasing the risk of skin carcinogenesis. At the cellular level, aging is typified by the rise of senescence cells a condition characterized by reduced or absent capacity to proliferate and aberrant hyper-secretory activity. Senescence has a double-edged sword in cancer biology given that senescence prevents the uncontrolled proliferation of damaged cells and favors their clearance by paracrine secretion. Nevertheless, the cumulative insults and the poor clearance of injured cells in the elderly increase cancer incidence. However, there are not conclusive data proving that aged skin represents a permissive milieu for tumor onset. On the other hand, tumor cells are capable of activating resident fibroblasts onto a pro-tumorigenic phenotype resembling those of senescent fibroblasts suggesting that aged fibroblasts might facilitate cancer progression. This review discusses changes that occur during aging that can prime neoplasm or increase the aggressiveness of melanoma and non-melanoma skin cancer. Full article
(This article belongs to the Special Issue Cutaneous Biology, Molecular Dermatology and Dermatopathology)
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