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Molecular Research in Chronic Dermatoses

A special issue of Current Issues in Molecular Biology (ISSN 1467-3045). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 12440

Special Issue Editors


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Guest Editor
Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, 50-368 Wroclaw, Poland
Interests: skin; allergic contact dermatitis; hidradenitis suppurativa; inflammatory skin disorders; psoriasis; atopic dermatitis; dermatosurgery; dermato-oncology; itch; skin biology; molecular biology; genetics
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Department of Dermatology, Hospital Manises, 46940 Valencia, Spain
Interests: melanoma; clinical dermatology; cancer biomarkers; basal cell carcinoma; psoriasis; dermatopathology; dermatosurgery; skin biology; cosmetology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Chronic inflammatory dermatoses are a group of skin disorders characterized by recurrent and debilitating course and destructive influence on patients’ quality of life. The pathogenesis of most of them is not fully understood. Therefore, treatment is challenging both for physicians and their patients, and the outcome is often unsatisfactory.

In recent years, outstanding progress in understanding the molecular mechanisms behind the pathogenesis of inflammatory dermatoses has been achieved. Studies have led to the development of new therapies, including biologics (chimeric, humanized, and human monoclonal antibodies) and their biosimilars, as well as systemic and topical small molecules (e.g., JAK inhibitors), which have revolutionized the management of patients suffering from chronic inflammatory dermatoses.

Nevertheless, there are still many unmet needs of currently available therapies. The insufficient availability and the high price of biologics impede their use in lower-income communities, while the adverse effects of JAK inhibitors may make physicians hesitant about their prolonged use. Therefore, there is still a significant need for future molecular research explaining the pathogenetic mechanisms leading to the development of skin lesions. In the future, these findings may build a foundation for new, targeted therapies, as well as for predicting disease course and its severity.

This Special Issue entitled “Molecular Research in Chronic Dermatoses” is now open for submission. Our aim is to publish state-of-the-art articles about the molecular mechanisms in, among others, hidradenitis suppurativa, psoriasis, atopic dermatitis, alopecia areata, vitiligo, and chronic spontaneous urticaria. This Special Issue will accept review articles, original research, and updated information on the pathophysiology and molecular pathways.

Dr. Piotr K. Krajewski
Dr. Antonio Martorell-Calatayud
Guest Editors

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. Current Issues in Molecular Biology is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). 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

  • dermatopathology
  • dermatosurgery
  • skin biology
  • molecular biology
  • genetics

Published Papers (7 papers)

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Research

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9 pages, 793 KiB  
Communication
The NLRP3 Inflammasome Gene Is Overexpressed in Hidradenitis Suppurativa Lesions: A Preliminary Study on the Role of Pyroptosis in Disease Pathogenesis
by Piotr K. Krajewski, Weronika Szukała and Jacek C. Szepietowski
Curr. Issues Mol. Biol. 2024, 46(3), 2544-2552; https://doi.org/10.3390/cimb46030161 - 16 Mar 2024
Viewed by 624
Abstract
Hidradenitis suppurativa (HS) is a debilitating inflammatory skin disorder, and its pathogenesis remains incompletely understood. This study aimed to investigate the role of the P2X7 receptor (P2X7R) and NLRP3 inflammasome in HS pathogenesis. RNA sequencing and real-time PCR were performed to assess the [...] Read more.
Hidradenitis suppurativa (HS) is a debilitating inflammatory skin disorder, and its pathogenesis remains incompletely understood. This study aimed to investigate the role of the P2X7 receptor (P2X7R) and NLRP3 inflammasome in HS pathogenesis. RNA sequencing and real-time PCR were performed to assess the gene expression levels of P2X7R and NLRP3 in the skin biopsies of HS patients and healthy controls (HC). The results of our study revealed a significantly increased expression of the NLRP3 gene in both the lesional and perilesional skin of HS patients compared to healthy controls. Moreover, the mRNA levels of NLRP3 were significantly higher in lesional skin compared to non-lesional skin in HS patients, indicating the spread of inflammation to adjacent tissues. In contrast, no significant differences in P2X7R gene expression were observed between the three groups. These findings suggest the involvement of NLRP3 inflammasomes in HS pathogenesis, while P2X7R may not play a significant role in the disease. This research sheds light on the complex inflammatory pathways in HS, highlighting the potential of NLRP3 as a therapeutic target. Understanding the molecular mechanisms underlying HS is crucial for the development of targeted treatment modalities for this debilitating condition. Full article
(This article belongs to the Special Issue Molecular Research in Chronic Dermatoses)
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15 pages, 2210 KiB  
Article
Increase in Double Negative B Lymphocytes in Patients with Systemic Lupus Erythematosus in Remission and Their Correlation with Early Differentiated T Lymphocyte Subpopulations
by Eleni Moysidou, Georgios Lioulios, Michalis Christodoulou, Aliki Xochelli, Stamatia Stai, Myrto Iosifidou, Artemis Iosifidou, Sophia Briza, Dimitria Ioanna Briza, Asimina Fylaktou and Maria Stangou
Curr. Issues Mol. Biol. 2023, 45(8), 6667-6681; https://doi.org/10.3390/cimb45080421 - 13 Aug 2023
Cited by 2 | Viewed by 1072
Abstract
B and T lymphocytes demonstrate important alterations in patients with systemic lupus erythematous (SLE), with a significant upregulation of double negative (DN) B cells. The aim of this study was to evaluate the correlation of T cell immunity changes with the distinct B-cell-pattern [...] Read more.
B and T lymphocytes demonstrate important alterations in patients with systemic lupus erythematous (SLE), with a significant upregulation of double negative (DN) B cells. The aim of this study was to evaluate the correlation of T cell immunity changes with the distinct B-cell-pattern SLE. In the present study, flow cytometry was performed in 30 patients in remission of SLE and 31 healthy controls to detect DN B cells (CD19+IgD-CD27-) and a wide range of T lymphocyte subpopulations based on the presence of CD45RA, CCR7, CD31, CD28, and CD57, defined as naive, memory, and advanced differentiated/senescent T cells. Both B and T lymphocytes were significantly reduced in SLE patients. However, the percentage of DN B cells were increased compared to HC (12.9 (2.3–74.2) vs. 8 (1.7–35), p = 0.04). The distribution of CD4 and CD8 lymphocytes demonstrated a shift to advanced differentiated subsets. The population of DN B cells had a significant positive correlation with most of the early differentiated T lymphocytes, CD4CD31+, CD4CD45RA+CD28+, CD4CD45RA+CD57-, CD4CD45RA-CD57-, CD4CD28+CD57-, CD4CD28+CD57+, CD4 CM, CD8 CD31+, CD8 NAÏVE, CD8CD45RA-CD57-, CD8CD28+CD57-, and CD8CD28+CD57+. Multiple regression analysis revealed CD4CD31+, CD8CD45RA-CD57-, and CD8CD28+CD57- cells as independent parameters contributing to DN B cells, with adjusted R2 = 0.534 and p < 0.0001. The predominance of DN B cells in patients with SLE is closely associated with early differentiated T lymphocyte subsets, indicating a potential causality role of DN B cells in T lymphocyte activation. Full article
(This article belongs to the Special Issue Molecular Research in Chronic Dermatoses)
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13 pages, 5052 KiB  
Article
The Skin-Whitening and Antioxidant Effects of Protocatechuic Acid (PCA) Derivatives in Melanoma and Fibroblast Cell Lines
by Jaehoon Cho, Hyeonbi Jung, Dong Young Kang, Nipin Sp, Wooshik Shin, Junhak Lee, Byung Gyu Park, Yoon A Kang, Kyoung-Jin Jang and Se Won Bae
Curr. Issues Mol. Biol. 2023, 45(3), 2157-2169; https://doi.org/10.3390/cimb45030138 - 6 Mar 2023
Cited by 3 | Viewed by 2657
Abstract
The skin is the most voluminous organ of the human body and is exposed to the outer environment. Such exposed skin suffers from the effects of various intrinsic and extrinsic aging factors. Skin aging is characterized by features such as wrinkling, loss of [...] Read more.
The skin is the most voluminous organ of the human body and is exposed to the outer environment. Such exposed skin suffers from the effects of various intrinsic and extrinsic aging factors. Skin aging is characterized by features such as wrinkling, loss of elasticity, and skin pigmentation. Skin pigmentation occurs in skin aging and is caused by hyper-melanogenesis and oxidative stress. Protocatechuic acid (PCA) is a natural secondary metabolite from a plant-based source widely used as a cosmetic ingredient. We chemically designed and synthesized PCA derivatives conjugated with alkyl esters to develop effective chemicals that have skin-whitening and antioxidant effects and enhance the pharmacological activities of PCA. We identified that melanin biosynthesis in B16 melanoma cells treated with alpha-melanocyte-stimulating hormone (α-MSH) is decreased by PCA derivatives. We also found that PCA derivatives effectively have antioxidant effects in HS68 fibroblast cells. In this study, we suggest that our PCA derivatives are potent ingredients for developing cosmetics with skin-whitening and antioxidant effects. Full article
(This article belongs to the Special Issue Molecular Research in Chronic Dermatoses)
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11 pages, 2204 KiB  
Article
Iris Pallida Extract Alleviates Cortisol-Induced Decrease in Type 1 Collagen and Hyaluronic Acid Syntheses in Human Skin Cells
by Jung Ha Choo, Hong Gu Lee, So Young Lee and Nae Gyu Kang
Curr. Issues Mol. Biol. 2023, 45(1), 353-363; https://doi.org/10.3390/cimb45010025 - 1 Jan 2023
Cited by 1 | Viewed by 2294
Abstract
Excessive endogenous or exogenous levels of the stress hormone cortisol have negative effects on various tissues, including the skin. Iris pallida (IP), used in traditional medicine and perfumes, exhibits biological activities, such as antioxidant and anti-inflammatory activities. In this study, we aimed to [...] Read more.
Excessive endogenous or exogenous levels of the stress hormone cortisol have negative effects on various tissues, including the skin. Iris pallida (IP), used in traditional medicine and perfumes, exhibits biological activities, such as antioxidant and anti-inflammatory activities. In this study, we aimed to investigate the inhibitory effect of IP extract (IPE) on cortisol activity in human skin cells. We found that IPE alleviated the cortisol-induced decrease in the levels of procollagen type 1 and hyaluronic acid (HA), which were significantly recovered by 106% and 31%, respectively, compared with cortisol-induced reductions. IPE also rescued the suppression of the gene expression of COL1A1 and the HA synthases HAS2 and HAS3 in cortisol-exposed cells. Moreover, IPE blocked the cortisol-induced translocation of the glucocorticoid receptor (GR) from the cytoplasm to the nucleus as effectively as the GR inhibitor mifepristone. Analysis using a high-performance liquid chromatography–diode-array detector system revealed that irigenin, an isoflavone, is the main component of IPE, which restored the cortisol-induced reduction in collagen type 1 levels by 82% relative to the cortisol-induced decrease. Our results suggest that IPE can act as an inhibitor of cortisol in human skin cells, preventing cortisol-induced collagen and HA degradation by blocking the nuclear translocation of the GR. Therefore, IPE may be used as a cosmetic material or herbal medicine to treat stress-related skin changes. Full article
(This article belongs to the Special Issue Molecular Research in Chronic Dermatoses)
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Review

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14 pages, 1628 KiB  
Review
Pathological and Therapeutical Implications of Pyroptosis in Psoriasis and Hidradenitis Suppurativa: A Narrative Review
by Piotr K. Krajewski, Maria Tsoukas and Jacek C. Szepietowski
Curr. Issues Mol. Biol. 2024, 46(1), 663-676; https://doi.org/10.3390/cimb46010043 - 11 Jan 2024
Viewed by 1205
Abstract
This manuscript explores the role of pyroptosis, an inflammatory programmed cell death, in the pathogenesis of two chronic dermatoses, psoriasis and hidradenitis suppurativa (HS). The diseases, though clinically diverse, share common pathogenetic pathways involving the unbalanced interaction between the adaptive and innate immune [...] Read more.
This manuscript explores the role of pyroptosis, an inflammatory programmed cell death, in the pathogenesis of two chronic dermatoses, psoriasis and hidradenitis suppurativa (HS). The diseases, though clinically diverse, share common pathogenetic pathways involving the unbalanced interaction between the adaptive and innate immune systems. This review focuses on the molecular changes in psoriatic and HS skin, emphasizing the activation of dendritic cells, secretion of interleukins (IL-17, IL-22, and TNF-α), and the involvement of inflammasomes, particularly NLRP3. This manuscript discusses the role of caspases, especially caspase-1, in driving pyroptosis and highlights the family of gasdermins (GSDMs) as key players in the formation of pores leading to cell rupture and the release of proinflammatory signals. This study delves into the potential therapeutic implications of targeting pyroptosis in psoriasis and HS, examining existing medications like biologics and Janus kinase inhibitors. It also reviews the current limitations and challenges in developing therapies that selectively target pyroptosis. Additionally, the manuscript explores the role of pyroptosis in various inflammatory disorders associated with psoriasis and HS, such as inflammatory bowel disease, diabetes mellitus, and cardiovascular disorders. The review concludes by emphasizing the need for further research to fully elucidate the pathomechanisms of these dermatoses and develop effective, targeted therapies. Full article
(This article belongs to the Special Issue Molecular Research in Chronic Dermatoses)
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28 pages, 1075 KiB  
Review
Bitter Phytochemicals as Novel Candidates for Skin Disease Treatment
by Teodora-Cristiana Grădinaru, Adelina Vlad and Marilena Gilca
Curr. Issues Mol. Biol. 2024, 46(1), 299-326; https://doi.org/10.3390/cimb46010020 - 30 Dec 2023
Viewed by 1736
Abstract
Skin diseases represent a global healthcare challenge due to their rising incidence and substantial socio-economic burden. While biological, immunological, and targeted therapies have brought a revolution in improving quality of life and survival rates for certain dermatological conditions, there remains a stringent demand [...] Read more.
Skin diseases represent a global healthcare challenge due to their rising incidence and substantial socio-economic burden. While biological, immunological, and targeted therapies have brought a revolution in improving quality of life and survival rates for certain dermatological conditions, there remains a stringent demand for new remedies. Nature has long served as an inspiration for drug development. Recent studies have identified bitter taste receptors (TAS2Rs) in both skin cell lines and human skin. Additionally, bitter natural compounds have shown promising benefits in addressing skin aging, wound healing, inflammatory skin conditions, and even skin cancer. Thus, TAS2Rs may represent a promising target in all these processes. In this review, we summarize evidence supporting the presence of TAS2Rs in the skin and emphasize their potential as drug targets for addressing skin aging, wound healing, inflammatory skin conditions, and skin carcinogenesis. To our knowledge, this is a pioneering work in connecting information on TAS2Rs expression in skin and skin cells with the impact of bitter phytochemicals on various beneficial effects related to skin disorders. Full article
(This article belongs to the Special Issue Molecular Research in Chronic Dermatoses)
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17 pages, 1372 KiB  
Review
Genomic, Epigenomic, Transcriptomic, Proteomic and Metabolomic Approaches in Atopic Dermatitis
by Dalia Bratu, Daniel Boda and Constantin Caruntu
Curr. Issues Mol. Biol. 2023, 45(6), 5215-5231; https://doi.org/10.3390/cimb45060331 - 20 Jun 2023
Cited by 2 | Viewed by 2058
Abstract
Atopic dermatitis (AD) is a chronic inflammatory skin disease with a high prevalence in the developed countries. It is associated with atopic and non-atopic diseases, and its close correlation with atopic comorbidities has been genetically demonstrated. One of the main roles of genetic [...] Read more.
Atopic dermatitis (AD) is a chronic inflammatory skin disease with a high prevalence in the developed countries. It is associated with atopic and non-atopic diseases, and its close correlation with atopic comorbidities has been genetically demonstrated. One of the main roles of genetic studies is to comprehend the defects of the cutaneous barrier due to filaggrin deficit and epidermal spongiosis. Recently, epigenetic studies started to analyze the influence of the environmental factors on gene expression. The epigenome is considered to be a superior second code that controls the genome, which includes alterations of the chromatin. The epigenetic changes do not alter the genetic code, however, changes in the chromatin structure could activate or inhibit the transcription process of certain genes and consequently, the translation process of the new mRNA into a polypeptide chain. In-depth analysis of the transcriptomic, metabolomic and proteomic studies allow to unravel detailed mechanisms that cause AD. The extracellular space and lipid metabolism are associated with AD that is independent of the filaggrin expression. On the other hand, around 45 proteins are considered as the principal components in the atopic skin. Moreover, genetic studies based on the disrupted cutaneous barrier can lead to the development of new treatments targeting the cutaneous barrier or cutaneous inflammation. Unfortunately, at present, there are no target therapies that focus on the epigenetic process of AD. However, in the future, miR-143 could be an important objective for new therapies, as it targets the miR-335:SOX axis, thereby restoring the miR-335 expression, and repairing the cutaneous barrier defects. Full article
(This article belongs to the Special Issue Molecular Research in Chronic Dermatoses)
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