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Molecular Basis and Treatment of Skin Diseases and Their Associated Complications

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: 20 February 2025 | Viewed by 10992

Special Issue Editors

Dr. Vincenzo Piccolo

E-Mail Website
Guest Editor
Department of Pharmacy, University of Naples Federico II, Via Domenico Montesano 49, 80131 Naples, Italy
Interests: biomarkers; mass spectrometry; metabolomics; nutraceuticals; natural products; chromatography; cutaneous comorbidities complication
Dr. Maria Maisto

E-Mail Website
Guest Editor
Department of Pharmacy, University of Naples Federico II, Via Domenico Montesano 59, 80131 Naples, Italy
Interests: nutraceuticals; bioactive compounds; antioxidant activity; mass spectrometry; chromatography
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The objective of this Special Issue is to explore present-day approaches to addressing the root cause of skin diseases and their related complications. Given the wide range of genes associated with these conditions and the mutations responsible for the diseases, a diverse array of phenotypic severities and clinical outcomes can be observed. The severity of the disease and its corresponding subtype are determined by the specific affected gene, the type of mutation, and the method of inheritance. At present, treatment methods primarily focus on providing relief from symptoms, including wound care and blister prevention, as definitive treatments are still in the preclinical phase. Common skin diseases include genodermatoses, atopic dermatitis, and recessive dystrophic epidermolysis bullosa (RDEB).

This Special Issue will focus on the molecular basis of various skin diseases, aiming to shed light on the underlying mechanisms behind these conditions. By investigating the molecular aspects of these skin diseases and highlighting potential therapeutic approaches, we hope to contribute to a broader understanding and improved management of these conditions, benefiting both patients and medical professionals in the field of dermatology.

Dr. Piccolo Vincenzo
Dr. Maria Maisto
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • diagnosis
  • biomarkers
  • imaging
  • histopathology
  • cutaneous comorbidities complication
  • therapy
  • management
  • clinical Trials

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Published Papers (7 papers)

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Research

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17 pages, 13647 KiB  
Article
Single-Nuclei Transcriptome Profiling Reveals Intra-Tumoral Heterogeneity and Characterizes Tumor Microenvironment Architecture in a Murine Melanoma Model
by Sushant Parab, Valery Sarlo, Sonia Capellero, Luca Palmiotto, Alice Bartolini, Daniela Cantarella, Marcello Turi, Annamaria Gullà, Elena Grassi, Chiara Lazzari, Marco Rubatto, Vanesa Gregorc, Fabrizio Carnevale-Schianca, Martina Olivero, Federico Bussolino and Valentina Comunanza
Int. J. Mol. Sci. 2024, 25(20), 11228; https://doi.org/10.3390/ijms252011228 - 18 Oct 2024
Viewed by 883
Abstract
Malignant melanoma is an aggressive cancer, with a high risk of metastasis and mortality rates, characterized by cancer cell heterogeneity and complex tumor microenvironment (TME). Single cell biology is an ideal and powerful tool to address these features at a molecular level. However, [...] Read more.
Malignant melanoma is an aggressive cancer, with a high risk of metastasis and mortality rates, characterized by cancer cell heterogeneity and complex tumor microenvironment (TME). Single cell biology is an ideal and powerful tool to address these features at a molecular level. However, this approach requires enzymatic cell dissociation that can influence cellular coverage. By contrast, single nucleus RNA sequencing (snRNA-seq) has substantial advantages including compatibility with frozen samples and the elimination of a dissociation-induced, transcriptional stress response. To better profile and understand the functional diversity of different cellular components in melanoma progression, we performed snRNA-seq of 16,839 nuclei obtained from tumor samples along the growth of murine syngeneic melanoma model carrying a BRAFV600E mutation and collected 9 days or 23 days after subcutaneous cell injection. We defined 11 different subtypes of functional cell clusters among malignant cells and 5 different subsets of myeloid cells that display distinct global transcriptional program and different enrichment in early or advanced stage of tumor growth, confirming that this approach was useful to accurately identify intratumor heterogeneity and dynamics during tumor evolution. The current study offers a deep insight into the biology of melanoma highlighting TME reprogramming through tumor initiation and progression, underlying further discovery of new TME biomarkers which may be potentially druggable. Full article
(This article belongs to the Special Issue Molecular Basis and Treatment of Skin Diseases and Their Associated Complications)
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13 pages, 1490 KiB  
Article
Markers of Metabolic Abnormalities in Vitiligo Patients
by Federica Papaccio, Monica Ottaviani, Mauro Truglio, Andrea D’Arino, Silvia Caputo, Alessia Pacifico, Paolo Iacovelli, Anna Di Nardo, Mauro Picardo and Barbara Bellei
Int. J. Mol. Sci. 2024, 25(18), 10201; https://doi.org/10.3390/ijms251810201 - 23 Sep 2024
Viewed by 1021
Abstract
While vitiligo is primarily caused by melanocyte deficiency or dysfunction, recent studies have revealed a notable prevalence of metabolic syndrome (MetS) among patients with vitiligo. This suggests shared pathogenic features between the two conditions. Individuals with vitiligo often exhibit variations in triglyceride levels, [...] Read more.
While vitiligo is primarily caused by melanocyte deficiency or dysfunction, recent studies have revealed a notable prevalence of metabolic syndrome (MetS) among patients with vitiligo. This suggests shared pathogenic features between the two conditions. Individuals with vitiligo often exhibit variations in triglyceride levels, cholesterol, and blood pressure, which are also affected in MetS. Given the similarities in their underlying mechanisms, genetic factors, pro-inflammatory signalling pathways, and increased oxidative stress, this study aims to highlight the common traits between vitiligo and metabolic systemic disorders. Serum analyses confirmed increased low-density lipoprotein (LDL) levels in patients with vitiligo, compared to physiological values. In addition, we reported significant decreases in folate and vitamin D (Vit D) levels. Oxidative stress is one of the underlying causes of the development of metabolic syndromes and is related to the advancement of skin diseases. This study found high levels of inflammatory cytokines, such as interleukin-6 (IL-6) and chemokine 10 (CXCL10), which are markers of inflammation and disease progression. The accumulation of insulin growth factor binding proteins 5 (IGFBP5) and advanced glycation end products (AGEs) entailed in atherosclerosis and diabetes onset, respectively, were also disclosed in vitiligo. In addition, the blood-associated activity of the antioxidant enzymes catalase (Cat) and superoxide dismutase (SOD) was impaired. Moreover, the plasma fatty acid (FAs) profile analysis showed an alteration in composition and specific estimated activities of FAs biosynthetic enzymes resembling MetS development, resulting in an imbalance towards pro-inflammatory n6-series FAs. These results revealed a systemic metabolic alteration in vitiligo patients that could be considered a new target for developing a more effective therapeutic approach. Full article
(This article belongs to the Special Issue Molecular Basis and Treatment of Skin Diseases and Their Associated Complications)
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19 pages, 7968 KiB  
Article
Chronic Gut Inflammation and Dysbiosis in IBS: Unraveling Their Contribution to Atopic Dermatitis Progression
by Jae-Hwan Jang, Sun-Young Jang, Sora Ahn, Ju-Young Oh, Mijung Yeom, Seok-Jae Ko, Jae-Woo Park, Soon-Kyeong Kwon, Kyuseok Kim, In-Seon Lee, Dae-Hyun Hahm and Hi-Joon Park
Int. J. Mol. Sci. 2024, 25(5), 2753; https://doi.org/10.3390/ijms25052753 - 27 Feb 2024
Cited by 1 | Viewed by 2073
Abstract
Emerging evidence suggests a link between atopic dermatitis (AD) and gastrointestinal disorders, particularly in relation to gut microbial dysbiosis. This study explored the potential exacerbation of AD by gut inflammation and microbial imbalances using an irritable bowel syndrome (IBS) mouse model. Chronic gut [...] Read more.
Emerging evidence suggests a link between atopic dermatitis (AD) and gastrointestinal disorders, particularly in relation to gut microbial dysbiosis. This study explored the potential exacerbation of AD by gut inflammation and microbial imbalances using an irritable bowel syndrome (IBS) mouse model. Chronic gut inflammation was induced in the model by intrarectal injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS), followed by a 4-week development period. We noted significant upregulation of proinflammatory cytokines in the colon and evident gut microbial dysbiosis in the IBS mice. Additionally, these mice exhibited impaired gut barrier function, increased permeability, and elevated systemic inflammation markers such as IL-6 and LPS. A subsequent MC903 challenge on the right cheek lasting for 7 days revealed more severe AD symptoms in IBS mice compared to controls. Further, fecal microbial transplantation (FMT) from IBS mice resulted in aggravated AD symptoms, a result similarly observed with FMT from an IBS patient. Notably, an increased abundance of Alistipes in the feces of IBS mice correlated with heightened systemic and localized inflammation in both the gut and skin. These findings collectively indicate that chronic gut inflammation and microbial dysbiosis in IBS are critical factors exacerbating AD, highlighting the integral relationship between gut and skin health. Full article
(This article belongs to the Special Issue Molecular Basis and Treatment of Skin Diseases and Their Associated Complications)
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15 pages, 11630 KiB  
Article
Topical Skin Application of Small-Molecule Antiplatelet Agent against Pressure Injury in Rat Models
by Yuan Yuan, En Takashi, Ping Hou, Akio Kamijo, Daiji Miura and Hirotomo Ten
Int. J. Mol. Sci. 2024, 25(3), 1639; https://doi.org/10.3390/ijms25031639 - 29 Jan 2024
Viewed by 1186
Abstract
Due to prolonged forced positioning, the incidence of intraoperative pressure injuries is high. This study aimed to explore the impact of small-molecule antiplatelet drugs on pressure injuries by locally applying them before an injury occurs. In the first part of this study, water-soluble [...] Read more.
Due to prolonged forced positioning, the incidence of intraoperative pressure injuries is high. This study aimed to explore the impact of small-molecule antiplatelet drugs on pressure injuries by locally applying them before an injury occurs. In the first part of this study, water-soluble tracers with different molecular weights were applied to normal and early-stage pressure-injured skin. Through digital cameras, spectrophotometers, and histological observations, the penetration of tracers into the epidermis was clarified. In the second part of this study, a water-soluble antiplatelet drug called Trapidil (molecular weight = 205 Da) was applied to the left side of the back of a rat before, during, and after compression, and the contralateral side served as a non-intervention control group. The differences in pressure injuries between the two groups were observed through a digital camera, an ultraviolet camera, and temperature measurement, and skin circulation and perfusion were assessed via an intravenous injection of Evans Blue. The first part of this study found that water-soluble tracers did not easily penetrate normal skin but could more easily penetrate pressure-damaged skin. The smaller the molecular weight of the tracer, the easier it penetrated the skin. Therefore, in the next step of research, water-soluble drugs with smaller molecular weights should be selected. The second part of this study found that, compared with the control group, the occurrence rates and areas of ulcers were lower, the gray value was higher, and the skin temperature was lower in the Trapidil group (p < 0.05). After the intravenous Evans Blue injection, skin circulation and perfusion in the Trapidil group were found to be better. In conclusion, this study found that the topical skin application of a small-molecule antiplatelet agent may have significant effects against pressure injuries by improving post-decompression ischemia, providing new insights into the prevention and treatment of intraoperative pressure injuries. Full article
(This article belongs to the Special Issue Molecular Basis and Treatment of Skin Diseases and Their Associated Complications)
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13 pages, 65086 KiB  
Article
Dysregulated Hippo Signaling Pathway and YAP Activation in Atopic Dermatitis: Insights from Clinical and Animal Studies
by Ga Hee Jeong and Ji Hyun Lee
Int. J. Mol. Sci. 2023, 24(24), 17322; https://doi.org/10.3390/ijms242417322 - 10 Dec 2023
Cited by 3 | Viewed by 2019
Abstract
The yes-associated protein (YAP) of the Hippo pathway regulates a variety of target genes involved in cell proliferation, survival, and inflammation. YAP and transcription activator with a PDZ-binding motif (TAZ) proteins act as mediators of the inflammatory response. Still, their role in atopic [...] Read more.
The yes-associated protein (YAP) of the Hippo pathway regulates a variety of target genes involved in cell proliferation, survival, and inflammation. YAP and transcription activator with a PDZ-binding motif (TAZ) proteins act as mediators of the inflammatory response. Still, their role in atopic dermatitis (AD)—particularly, the association with the nuclear factor kappa-B and Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathways—is not fully understood. In this study, we found that YAP, is upregulated in AD patients and NC/Nga mouse model of AD. In addition, inhibition of YAP significantly reduced epidermal cell proliferation by 58% and mast cell numbers by 51% and attenuated the upregulation of both Th1- and Th2-associated cytokines. Among the JAK-STAT family proteins, the expressions of JAK1 and JAK2 and those of STAT1, STAT2, and STAT3 were also downregulated. These findings may explain the role of YAP in AD and suggest YAP inhibitors as promising therapeutic agents for AD. Full article
(This article belongs to the Special Issue Molecular Basis and Treatment of Skin Diseases and Their Associated Complications)
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Review

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10 pages, 1015 KiB  
Review
Pivotal Role of mTOR in Non-Skin Manifestations of Psoriasis
by Ka Joo, Claudio Karsulovic, Milisa Sore and Lia Hojman
Int. J. Mol. Sci. 2024, 25(12), 6778; https://doi.org/10.3390/ijms25126778 - 20 Jun 2024
Cited by 1 | Viewed by 1432
Abstract
Psoriasis is a chronic inflammatory condition affecting 2% of the Western population. It includes diverse manifestations influenced by genetic predisposition, environmental factors, and immune status. The sustained activation of mTOR is a key element in psoriasis pathogenesis, leading to an uncontrolled proliferation of [...] Read more.
Psoriasis is a chronic inflammatory condition affecting 2% of the Western population. It includes diverse manifestations influenced by genetic predisposition, environmental factors, and immune status. The sustained activation of mTOR is a key element in psoriasis pathogenesis, leading to an uncontrolled proliferation of cytokines. Furthermore, mTOR activation has been linked with the transition from psoriasis to non-skin manifestations such as psoriatic arthritis and cardiovascular events. While therapies targeting pro-inflammatory cytokines have shown efficacy, additional pathways may offer therapeutic potential. The PI3K/Akt/mTOR pathway, known for its role in cell growth, proliferation, and metabolism, has emerged as a potential therapeutic target in psoriasis. This review explores the relevance of mTOR in psoriasis pathophysiology, focusing on its involvement in cutaneous and atheromatous plaque proliferation, psoriatic arthritis, and cardiovascular disease. The activation of mTOR promotes keratinocyte and synovial cell proliferation, contributing to plaque formation and joint inflammation. Moreover, mTOR activation may exacerbate the cardiovascular risk by promoting pro-inflammatory cytokine production and dysregulation lipid and glucose metabolism. The inhibition of mTOR has shown promise in preclinical studies, reducing skin inflammation and plaque proliferation. Furthermore, mTOR inhibition may mitigate cardiovascular risk by modulating cholesterol metabolism and attenuating atherosclerosis progression. Understanding the role of mTOR in psoriasis, psoriatic arthritis, and cardiovascular disease provides insight into the potential treatment avenues and sheds light on the complex interplay of the immune and metabolic pathways in these conditions. Full article
(This article belongs to the Special Issue Molecular Basis and Treatment of Skin Diseases and Their Associated Complications)
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12 pages, 631 KiB  
Review
Paediatric Atopic Dermatitis: The Unexpected Impact on Life with a Specific Look at the Molecular Level
by Silvia Artusa, Giorgia Mazzuca, Giorgio Piacentini, Riccardo Castagnoli, Gian Luigi Marseglia, Angelo Pietrobelli and Luca Pecoraro
Int. J. Mol. Sci. 2024, 25(9), 4778; https://doi.org/10.3390/ijms25094778 - 27 Apr 2024
Viewed by 1219
Abstract
Atopic dermatitis (AD) is a condition with a multifactorial aetiology that affects the skin. It most often begins at preschool age and involves the skin. The disease’s main symptom is intense itching, which occurs especially at night and affects the child’s sleep, negatively [...] Read more.
Atopic dermatitis (AD) is a condition with a multifactorial aetiology that affects the skin. It most often begins at preschool age and involves the skin. The disease’s main symptom is intense itching, which occurs especially at night and affects the child’s sleep, negatively impacting the quality of life of affected children and, consequently, their families. The difficulty in resting during the night leads to many problems during the day, particularly behavioural disorders and difficulties in paying attention at school, which results in learning impairment. The unexpected symptoms of AD are caused by pathophysiological processes that include many molecular pathways and inflammatory cytokines such as IL-31, IL-1, IL-2, TNF-a, and IL-6. Drawing on a comprehensive review of the literature in PubMed/MedLine, our review offers an in-depth exploration of both the psychosocial impacts of AD and the molecular processes that contribute to this disorder. Full article
(This article belongs to the Special Issue Molecular Basis and Treatment of Skin Diseases and Their Associated Complications)
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