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Skin Diseases: From Accurate Diagnosis to Novel Therapeutic Approaches, in...
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Skin Diseases: From Accurate Diagnosis to Novel Therapeutic Approaches, in the Light of Molecular Medicine

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 20219

Special Issue Editor

Dr. Olga Simionescu

E-Mail Website
Guest Editor
Chief of the First Clinic of Dermatology, Department of Dermatology, “Carol Davila” University of Medicine and Pharmacy, Colentina Hospital, 020125 Bucharest, Romania
Interests: skin cancer; dermoscopy; melanom; psoriasis; connective tissue diseases; venereology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Medicine in general, and dermatology in particular, has recently made significant progress. A greater understanding of the molecular mechanisms led eventually to better and more accurate reclassifications in dermatology, the medical specialty that undoubtedly consists of the highest number and variety of diseases.

 In dermoscopy, the great interest moved the field forward and provided certainty and accuracy in tumoral diagnosis. Nowadays, this diagnostic method allows for rapid global interconnection between people within different continents. 

In psoriasis, we are currently experiencing a spring in novel therapeutic approaches that are life-changing for our patients. Although psoriasis remains a problem, great steps forward have been made in understanding this genetic, inflammatory, immunological, proliferative disorder of keratinization.

The efficiency of monoclonal antibodies in bullous diseases and melanoma has started a new era in our understanding of a tailor-made approach to the dermatological/rheumatological patient.

Human skin is indeed a powerful and amazing immune organ. Cutaneous resident cells are fully equipped to provide the best protection of the other human cells' DNA. For example, if we analyse the keratinocyte, we will realize how diligent it can be during its turnover while participating in both acquired and innate immunity, and we may understand more about the complexity of the pathways involved in pathophysiology.

Dr. Olga Simionescu
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. Biomedicines 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 2600 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

  • skin cancer
  • dermoscopy
  • melanoma
  • psoriasis
  • connective tissue diseases
  • venereology

Published Papers (6 papers)

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Research

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17 pages, 10256 KiB  
Article
Actualities in the Morphology and Immunohistochemistry of Cutaneous and Ocular Melanoma: What Lies Ahead? A Single-Centre Study
by Andreea Cătălina Tinca, Raluca Moraru, Iuliu Gabriel Cocuz, Mihaela Cornelia Șincu, Raluca Niculescu, Adrian Horațiu Sabău, Diana Maria Chiorean, Andreea Raluca Szoke, Silviu-Horia Morariu and Ovidiu Simion Cotoi
Biomedicines 2022, 10(10), 2500; https://doi.org/10.3390/biomedicines10102500 - 7 Oct 2022
Cited by 4 | Viewed by 1778
Abstract
Melanoma is the most aggressive melanocytic tumor whose incidence is continuously increasing worldwide. Methods: We highlight the morphological, immunohistochemistry, and particularities of various melanoma types based on the cases diagnosed in our department from 2017 to 2021. Results: We present 100 melanoma cases [...] Read more.
Melanoma is the most aggressive melanocytic tumor whose incidence is continuously increasing worldwide. Methods: We highlight the morphological, immunohistochemistry, and particularities of various melanoma types based on the cases diagnosed in our department from 2017 to 2021. Results: We present 100 melanoma cases and one capsular nevus case. The most common type was nodular melanoma. The immunohistochemistry markers used were SRY-box transcription factor 10 (SOX10), S100 protein, human melanoma black 45 (HMB45), and melanoma antigen recognized by T cells 1 (Melan-A). Uveal melanoma and conjunctival melanoma represent particular tumors with independent prognostic factors. Uveal melanoma requires assessment of macrophages, microvascularisation, and mitoses. Sentinel lymph node metastases are essential targets that provide staging tools. Conjunctival melanoma and capsular nevi are diagnostic pitfalls. Conclusion: Melanoma can appear in various forms, and sometimes the diagnosis might be unclear. Today, immunohistochemistry remains the most important tool in confirming the diagnosis and prognosis for this type of neoplasia. Full article
(This article belongs to the Special Issue Skin Diseases: From Accurate Diagnosis to Novel Therapeutic Approaches, in the Light of Molecular Medicine)
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12 pages, 3158 KiB  
Article
IL-33 Enhances ACE2 Expression on Epidermal Keratinocytes in Atopic Dermatitis: A Plausible Issue for SARS-CoV-2 Transmission in Inflamed Atopic Skin
by En-Cheng Lin and Chien-Hui Hong
Biomedicines 2022, 10(5), 1183; https://doi.org/10.3390/biomedicines10051183 - 20 May 2022
Cited by 6 | Viewed by 2449
Abstract
Background: Interleukin-33 (IL-33) is an important cytokine in the pathophysiology of atopic dermatitis (AD) and in the progression of COVID-19. Angiotensin converting enzyme 2 (ACE2), the entry receptor for SARS-CoV-2, is expressed in epidermal keratinocytes. Whether IL-33 could regulate the expression of ACE2 [...] Read more.
Background: Interleukin-33 (IL-33) is an important cytokine in the pathophysiology of atopic dermatitis (AD) and in the progression of COVID-19. Angiotensin converting enzyme 2 (ACE2), the entry receptor for SARS-CoV-2, is expressed in epidermal keratinocytes. Whether IL-33 could regulate the expression of ACE2 mechanistically in keratinocytes warrants investigation. Objective: We questioned whether the ACE2 expression is increased in AD skin. We also questioned whether ACE2 is expressed in keratinocytes; if so, would its expression be enhanced mechanistically by IL-33. Methods: We measured and compared the expression of ACE2 in skin from patients with AD, patients with psoriasis, and healthy controls using immunohistochemistry. Flow cytometry, immunofluorescent exam, and quantitative RT-PCR were used for measuring the ACE2 expression in cultured keratinocytes treated with IL-33 and IL-17. Blocking antibodies were utilized to study the intracellular signaling pathways governing the ACE2 expression using cytokines. Results: The results showed that the ACE2 expression is increased in AD compared with that in healthy skin and psoriasis. In primary epidermal keratinocytes, ACE2 is constitutively expressed. IL-33 induces a time-dependent increase in ACE2 expression in cultured keratinocytes through quantitative PCR, flow cytometry, and immunofluorescent examinations. Furthermore, pretreatment of an ERK inhibitor, but not a STAT3 inhibitor, eliminated the increases in ACE2 by IL-33 in keratinocytes, indicating that IL-33 enhances ACE2 expression through ERK on epidermal keratinocytes. Conclusion: This is the first study to reveal that IL-33 enhances ACE2 expression on keratinocytes via ERK. Although further mechanistic studies are required, the increased ACE2 expression in IL-33 might have a biological implication on the transmission of SARS-CoV-2 in patients with AD. Full article
(This article belongs to the Special Issue Skin Diseases: From Accurate Diagnosis to Novel Therapeutic Approaches, in the Light of Molecular Medicine)
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13 pages, 1150 KiB  
Article
Significantly Altered Serum Levels of NAD, AGE, RAGE, CRP, and Elastin as Potential Biomarkers of Psoriasis and Aging—A Case-Control Study
by Adam Karas, Drahomira Holmannova, Pavel Borsky, Zdenek Fiala, Ctirad Andrys, Kvetoslava Hamakova, Tereza Svadlakova, Vladimir Palicka, Jan Krejsek, Vit Rehacek, Monika Esterkova, Helena Kovarikova and Lenka Borska
Biomedicines 2022, 10(5), 1133; https://doi.org/10.3390/biomedicines10051133 - 13 May 2022
Cited by 10 | Viewed by 3648
Abstract
Background: This study aims to investigate potential markers of psoriasis and aging, and to elucidate possible connections between these two processes. Methods: The serum samples of 60 psoriatic patients and 100 controls were analysed, and the levels of four selected parameters (AGEs, RAGE, [...] Read more.
Background: This study aims to investigate potential markers of psoriasis and aging, and to elucidate possible connections between these two processes. Methods: The serum samples of 60 psoriatic patients and 100 controls were analysed, and the levels of four selected parameters (AGEs, RAGE, NAD, and elastin) were determined using commercial ELISA kits. Serum C-reactive protein was assayed using an immune-nephelometry method. Findings: Among the patients, the levels of CRP, AGEs, and RAGE were all increased, while the levels of NAD were reduced when compared to the control group. A negative correlation between the levels of AGEs and NAD was found. A negative correlation between age and the NAD levels among the control group was observed, however among the patients the relationship was diminished. While there was no difference in the levels of native elastin between the patients and the controls, a positive correlation between the levels of native elastin and age and a negative correlation between the levels of native elastin and the severity of psoriasis were found. Conclusions: The results of our study support the notion of psoriasis and possibly other immune-mediated diseases accelerating the aging process through sustained systemic damage. The serum levels of CRP, NAD, AGEs, and RAGE appear to be promising potential biomarkers of psoriasis. The decrease in the serum levels of NAD is associated with (pro)inflammatory states. Our analysis indicates that the levels of native elastin might strongly reflect both the severity of psoriasis and the aging process. Full article
(This article belongs to the Special Issue Skin Diseases: From Accurate Diagnosis to Novel Therapeutic Approaches, in the Light of Molecular Medicine)
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Review

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18 pages, 742 KiB  
Review
Current Concepts of Vitiligo Immunopathogenesis
by Nika Hlača, Tina Žagar, Marija Kaštelan, Ines Brajac and Larisa Prpić-Massari
Biomedicines 2022, 10(7), 1639; https://doi.org/10.3390/biomedicines10071639 - 8 Jul 2022
Cited by 16 | Viewed by 5611
Abstract
Vitiligo is an acquired immune-mediated disorder of pigmentation clinically characterized by well-defined depigmented or chalk-white macules and patches on the skin. The prevalence of vitiligo varies by geographical area, affecting 0.5% to 2% of the population. The disease imposes a significant psychological burden [...] Read more.
Vitiligo is an acquired immune-mediated disorder of pigmentation clinically characterized by well-defined depigmented or chalk-white macules and patches on the skin. The prevalence of vitiligo varies by geographical area, affecting 0.5% to 2% of the population. The disease imposes a significant psychological burden due to its major impact on patients’ social and emotional aspects of life. Given its autoimmune background, vitiligo is frequently associated with other autoimmune diseases or immune-mediated diseases. Vitiligo is a multifaceted disorder that involves both genetic predisposition and environmental triggers. In recent years, major predisposing genetic loci for the development of vitiligo have been discovered. The current findings emphasize the critical role of immune cells and their mediators in the immunopathogenesis of vitiligo. Oxidative-stress-mediated activation of innate immunity cells such as dendritic cells, natural killer, and ILC-1 cells is thought to be a key event in the early onset of vitiligo. Innate immunity cells serve as a bridge to adaptive immunity cells including T helper 1 cells, cytotoxic T cells and resident memory T cells. IFN-γ is the primary cytokine mediator that activates the JAK/STAT pathway, causing keratinocytes to produce the key chemokines CXCL9 and CXCL10. Complex interactions between immune and non-immune cells finally result in apoptosis of melanocytes. This paper summarizes current knowledge on the etiological and genetic factors that contribute to vitiligo, with a focus on immunopathogenesis and the key cellular and cytokine players in the disease’s inflammatory pathways. Full article
(This article belongs to the Special Issue Skin Diseases: From Accurate Diagnosis to Novel Therapeutic Approaches, in the Light of Molecular Medicine)
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22 pages, 7680 KiB  
Review
Stem Cell-Based Therapy: A Promising Treatment for Diabetic Foot Ulcer
by Racha El Hage, Uwe Knippschild, Tobias Arnold and Irene Hinterseher
Biomedicines 2022, 10(7), 1507; https://doi.org/10.3390/biomedicines10071507 - 25 Jun 2022
Cited by 14 | Viewed by 4107
Abstract
Diabetic foot ulcer (DFU) is a severe complication of diabetes and a challenging medical condition. Conventional treatments for DFU have not been effective enough to reduce the amputation rates, which urges the need for additional treatment. Stem cell-based therapy for DFU has been [...] Read more.
Diabetic foot ulcer (DFU) is a severe complication of diabetes and a challenging medical condition. Conventional treatments for DFU have not been effective enough to reduce the amputation rates, which urges the need for additional treatment. Stem cell-based therapy for DFU has been investigated over the past years. Its therapeutic effect is through promoting angiogenesis, secreting paracrine factors, stimulating vascular differentiation, suppressing inflammation, improving collagen deposition, and immunomodulation. It is controversial which type and origin of stem cells, and which administration route would be the most optimal for therapy. We reviewed the different types and origins of stem cells and routes of administration used for the treatment of DFU in clinical and preclinical studies. Diabetes leads to the impairment of the stem cells in the diseased patients, which makes it less ideal to use autologous stem cells, and requires looking for a matching donor. Moreover, angioplasty could be complementary to stem cell therapy, and scaffolds have a positive impact on the healing process of DFU by stem cell-based therapy. In short, stem cell-based therapy is promising in the field of regenerative medicine, but more studies are still needed to determine the ideal type of stem cells required in therapy, their safety, proper dosing, and optimal administration route. Full article
(This article belongs to the Special Issue Skin Diseases: From Accurate Diagnosis to Novel Therapeutic Approaches, in the Light of Molecular Medicine)
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Other

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7 pages, 671 KiB  
Brief Report
Non-Canonical WNT/Wnt5a Pathway Activity in Circulating Monocytes of Untreated Psoriatic Patients: An Exploratory Study of Its Association with Inflammatory Cytokines and Cardiovascular Risk Marker-ADAMTS7
by Claudio Karsulovic, Khanty Loyola, Raul Cabrera, Claudio Perez and Lia Hojman
Biomedicines 2023, 11(2), 577; https://doi.org/10.3390/biomedicines11020577 - 16 Feb 2023
Cited by 1 | Viewed by 1275
Abstract
The leading cause of death in psoriasis is cardiovascular disease. The determinants that induce the increase in this risk are not known. The systemic inflammatory process is dependent on lymphocytes and monocytes, as has been proposed. However, adaptation modules such as mTOR have [...] Read more.
The leading cause of death in psoriasis is cardiovascular disease. The determinants that induce the increase in this risk are not known. The systemic inflammatory process is dependent on lymphocytes and monocytes, as has been proposed. However, adaptation modules such as mTOR have recently been mentioned as having a role. Other factors, such as WNT and its non-canonical WNT5a-inducing pathway, are relevant in inflammation, cell migration, and neoangiogenesis. Thus, we studied circulating monocytes from untreated severe psoriatic patients and characterized inflammatory cytokines, chemokines, mTOR activity, and the cardiovascular risk marker ADAMTS7. Peripheral blood from ten severely psoriatic patients (Psoriasis severity index greater than 10) was extracted and age- and sex-matched with healthy subjects. Surface and intracellular flow cytometry were performed for cytokine, chemokine receptors, and mTOR activity. ADAMTS7 was measured using ELISA. Psoriatic patients had a higher frequency of WNT5a+ cells in monocytes, which also had higher levels of IL-1β, IL-6, CXCR3, CCR2, and phosphorylated S6R protein. We found that M1 monocytes are dominant in the WNT5a+ cell group, and intracellular levels of WNT5a were also augmented. Levels of WNT5a were correlated with ADAMTS7, a blood marker related to the pathogenesis of atheromatosis. WNT5a could be relevant to the cardiovascular risk of psoriatic patients considering its association with higher levels of inflammatory cytokines, chemokine receptors and the pro-atherogenic profile of circulating monocytes. Full article
(This article belongs to the Special Issue Skin Diseases: From Accurate Diagnosis to Novel Therapeutic Approaches, in the Light of Molecular Medicine)
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