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Skin Diseases: Molecular Targets for New Therapeutics

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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: closed (30 September 2023) | Viewed by 7911

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Dr. Katarzyna Walczak

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Guest Editor

Laboratory for Immunology of Skin Diseases, Chair and Department of Dermatology, Venerology and Paediatric Dermatology, Medical University of Lublin, Radziwillowska 11, 20080 Lublin, Poland
Interests: cancer cells; metabolism; proliferation; cell cycle; apoptosis; uv signaling pathways; tryptophan; kynurenic acid; kynurenine

Special Issue Information

Dear Colleagues,

Skin diseases are a growing problem worldwide, not only because of their prevalence in society and the growing number of patients, but also because of the rising cost of treatment and the insufficient effectiveness of currently available therapies. Importantly, the pathogenesis and molecular basis of skin diseases are often not fully understood. Therefore, extensive studies regarding new therapeutic approaches seem to be a priority, whereas an understanding of how drugs may modify or modulate the molecular mechanisms in the skin will be helpful in this process.

The Special Issue is focused on the molecular targets for new therapeutics in skin diseases including skin cancer, autoimmune skin diseases, and inflammatory skin diseases. Studies regarding the biological and molecular mechanisms of new compounds which may be used in the future in the therapy of skin disorders as well as clinical submissions with biomolecular experiments are welcomed.

This special issue is supervised by Dr. Katarzyna Walczak and assisted by our Topical Advisory Panel Member Dr. Anna Makuch-Kocka.

Dr. Katarzyna Walczak
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

melanoma
systemic sclerosis
psoriasis
skin diseases
angiogenesis
proliferation
cell cycle
signaling pathways
fibrosis
inflammation
cell death
melanogenesis

Published Papers (4 papers)

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Research

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16 pages, 3752 KiB

Open AccessArticle

Anhydrous Alum Inhibits α-MSH-Induced Melanogenesis by Down-Regulating MITF via Dual Modulation of CREB and ERK

by Kyu-Ree In, Mi Ae Kang, Su Dong Kim, Jinho Shin, Sung Un Kang, Tae Jun Park, Seung-Joo Kim and Jong-Soo Lee

Int. J. Mol. Sci. 2023, 24(19), 14662; https://doi.org/10.3390/ijms241914662 - 28 Sep 2023

Cited by 1 | Viewed by 1566

Abstract

Melanogenesis, the intricate process of melanin synthesis, is central to skin pigmentation and photoprotection and is regulated by various signaling pathways and transcription factors. To develop potential skin-whitening agents, we used B16F1 melanoma cells to investigate the inhibitory effects of anhydrous alum on melanogenesis and its underlying molecular mechanisms. Anhydrous alum (KAl(SO₄)₂) with high purity (>99%), which is generated through the heat-treatment of hydrated alum (KAl(SO₄)₂·12H₂O) at 400 °C, potentiates a significant reduction in melanin content without cytotoxicity. Anhydrous alum downregulates the master regulator of melanogenesis, microphthalmia-associated transcription factor (MITF), which targets key genes involved in melanogenesis, thereby inhibiting α-melanocyte-stimulating hormone (α-MSH)-induced melanogenesis. Phosphorylation of the cAMP response element-binding protein, which acts as a co-activator of MITF gene expression, is attenuated by anhydrous alum, resulting in compromised MITF transcription. Notably, anhydrous alum promoted extracellular signal-regulated kinase phosphorylation, leading to the impaired nuclear localization of MITF. Overall, these results demonstrated the generation and mode of action of anhydrous alum in B16F1 cells, which constitutes a promising option for cosmetic or therapeutic use. Full article

(This article belongs to the Special Issue Skin Diseases: Molecular Targets for New Therapeutics)

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14 pages, 1224 KiB

Open AccessArticle

Treatment with the Topical Antimicrobial Peptide Omiganan in Mild-to-Moderate Facial Seborrheic Dermatitis versus Ketoconazole and Placebo: Results of a Randomized Controlled Proof-of-Concept Trial

by Jannik Rousel, Mahdi Saghari, Lisa Pagan, Andreea Nădăban, Tom Gambrah, Bart Theelen, Marieke L. de Kam, Jorine Haakman, Hein E. C. van der Wall, Gary L. Feiss, Tessa Niemeyer-van der Kolk, Jacobus Burggraaf, Joke A. Bouwstra, Robert Rissmann and Martijn B. A. van Doorn

Int. J. Mol. Sci. 2023, 24(18), 14315; https://doi.org/10.3390/ijms241814315 - 20 Sep 2023

Cited by 1 | Viewed by 1694

Abstract

Facial seborrheic dermatitis (SD) is an inflammatory skin disease characterized by erythematous and scaly lesions on the skin with high sebaceous gland activity. The yeast Malassezia is regarded as a key pathogenic driver in this disease, but increased Staphylococcus abundances and barrier dysfunction are implicated as well. Here, we evaluated the antimicrobial peptide omiganan as a treatment for SD since it has shown both antifungal and antibacterial activity. A randomized, patient- and evaluator-blinded trial was performed comparing the four-week, twice daily topical administration of omiganan 1.75%, the comparator ketoconazole 2.00%, and placebo in patients with mild-to-moderate facial SD. Safety was monitored, and efficacy was determined by clinical scoring complemented with imaging. Microbial profiling was performed, and barrier integrity was assessed by trans-epidermal water loss and ceramide lipidomics. Omiganan was safe and well tolerated but did not result in a significant clinical improvement of SD, nor did it affect other biomarkers, compared to the placebo. Ketoconazole significantly reduced the disease severity compared to the placebo, with reduced Malassezia abundances, increased microbial diversity, restored skin barrier function, and decreased short-chain ceramide Cer[NSc34]. No significant decreases in Staphylococcus abundances were observed compared to the placebo. Omiganan is well tolerated but not efficacious in the treatment of facial SD. Previously established antimicrobial and antifungal properties of omiganan could not be demonstrated. Our multimodal characterization of the response to ketoconazole has reaffirmed previous insights into its mechanism of action. Full article

(This article belongs to the Special Issue Skin Diseases: Molecular Targets for New Therapeutics)

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19 pages, 5179 KiB

Open AccessArticle

Low P-Selectin Glycoprotein Ligand-1 Expression in Neutrophils Associates with Disease Activity and Deregulated NET Formation in Systemic Lupus Erythematosus

by Antonio Muñoz-Callejas, Elena González-Sánchez, Javier Silván, Esther San Antonio, Rafael González-Tajuelo, Alejandra Ramos-Manzano, Inés Sánchez-Abad, Isidoro González-Alvaro, Javier García-Pérez, Eva G. Tomero, Rosario García de Vicuña, Esther F. Vicente-Rabaneda, Santos Castañeda and Ana Urzainqui

Int. J. Mol. Sci. 2023, 24(7), 6144; https://doi.org/10.3390/ijms24076144 - 24 Mar 2023

Cited by 2 | Viewed by 1918

Abstract

Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by the generation of anti-DNA autoantibodies due to exposure of immune cells to excessive amounts of extracellular DNA. Lack of P-selectin in mice induces the development of a lupus-like syndrome and patients with cutaneous lupus have reduced P-selectin expression in skin vessels. Using flow cytometry we analyzed in healthy donors and patients the expression of P-selectin Glycoprotein Ligand-1 (PSGL-1) in circulating neutrophils and the implication of PSGL-1/P-selectin interaction in neutrophil extracellular traps (NETs) generation. We found a statistical significance that neutrophils from active SLE patients have a reduced expression of PSGL-1 and low levels of PSGL-1 in neutrophils from SLE patients associated with the presence of anti-dsDNA antibodies, clinical lung involvement, Raynaud’s phenomenon, and positive lupus anticoagulant. PSGL-1 is present along the DNA in the NET. In healthy donors, neutrophil interaction with immobilized P-selectin triggers Syk activation, increases the NETs percentage and reduces the amount of DNA extruded in the NETs. In active SLE patients, neutrophil interaction with P-selectin does not activate Syk or reduce the amount of DNA extruded in the NETs, that might contribute to increase the extracellular level of DNA and hence, to disease pathogenesis. Full article

(This article belongs to the Special Issue Skin Diseases: Molecular Targets for New Therapeutics)

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Review

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21 pages, 3426 KiB

Open AccessReview

Silver, Its Salts and Application in Medicine and Pharmacy

by Dominik Żyro, Joanna Sikora, Małgorzata Iwona Szynkowska-Jóźwik and Justyn Ochocki

Int. J. Mol. Sci. 2023, 24(21), 15723; https://doi.org/10.3390/ijms242115723 - 29 Oct 2023

Cited by 1 | Viewed by 2117

Abstract

The healing properties of silver have been used since ancient times. The main aim of the study was to collect and review the literature on the clinical potential of silver, its salts and complex compounds. The second goal was to present an outline of the historical use of silver in medicine and pharmacy, taking into account the possibility of producing pharmaceutical drug forms on the premises of pharmacies. In the context of the growing resistance of microorganisms to available, widely used antibiotics, silver plays a key role. There is only one known case of bacterial resistance to silver—the Pseudomonas stutzeri strain, which naturally occurs in silver mines. The development of research in the field of coordination chemistry offers great opportunities in the design of new substances in which silver ions can be incorporated. These substances exhibit increased potency and often an extended antimicrobial spectrum. Silver-based compounds are, however, only limited to external applications, as opposed to their historic oral administration. Advanced studies of their physicochemical, microbiological, cytotoxic and genotoxic properties are ongoing and full of challenges. The improvement of the methods of synthesis gives the possibility of applying the newly synthesized compounds ex tempore, as was the case with the complex of metronidazole with silver (I) nitrate. Some of these experimental efforts performed in vitro are followed with clinical trials. The third and final goal of this study was to present the possibility of obtaining an ointment under the conditions of an actual pharmacy using silver (I) salts and a ligand, both of which are active substances with antimicrobial properties. Full article

(This article belongs to the Special Issue Skin Diseases: Molecular Targets for New Therapeutics)

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