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Looking into the Skin in Health and Disease: From Microscopy Imaging Techniques to Molecular Analysis

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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 (15 March 2023) | Viewed by 22563

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Special Issue Editors

Dr. Mihaela Adriana Ilie

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Guest Editor

Dermatology Department, Kalmar County Hospital, Kalmar, Sweden
Interests: skin cancer; skin inflammation; in vivo reflectance confocal microscopy; skin diagnostic techniques; skin physiology
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Monica Neagu

E-Mail Website1 Website2
Co-Guest Editor

1. Department of Pathology, Colentina University Hospital, 020125 Bucharest, Romania
2. Immunology Department, “Victor Babes” National Institute of Pathology, 050096 Bucharest, Romania
Interests: immuno-oncology; biomarkers; inflammation; melanoma
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Constantin Caruntu

E-Mail Website1 Website2
Co-Guest Editor

Department of Physiology, The “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
Interests: physiology and physiopathology of the skin and oral mucosa; dermato-oncology; in vivo reflectance confocal microscopy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Skin constantly adapts in response to various physiological and pathological states. Moreover, skin is the most accessible organ of the human body and, in recent years, prodigious amounts of research have been done in the fields of imaging correlated with cellular and molecular biology techniques. This technological armamentarium has recently led to massive progress in the diagnosis, targeted treatment and investigation of pathophysiology of skin conditions. Nevertheless, new discoveries are in the research pipeline and many more are needed as there are still patients that develop skin diseases with no clear pathogenesis, nor an effective treatment.

With this Special Issue, we aim to expand our understanding and to emphasize new research directions related to investigation of various aspects of the physiology and pathology of the skin with emphasis on the cellular and molecular mechanisms. Therefore, we invite you to submit your interesting results related to the topic in the forms of original research, review articles or short communications.

Dr. Mihaela Adriana Ilie
Dr. Teodora Monica Neagu
Prof. Dr. Constantin Caruntu
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.

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

skin imaging
molecular analysis
skin physiology
dermatopathology
skin cancer
skin inflammation
molecular biology

Published Papers (9 papers)

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Editorial

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8 pages, 260 KiB

Open AccessEditorial

Looking into the Skin in Health and Disease: From Microscopy Imaging Techniques to Molecular Analysis

by Constantin Caruntu, Mihaela Adriana Ilie and Monica Neagu

Int. J. Mol. Sci. 2023, 24(18), 13737; https://doi.org/10.3390/ijms241813737 - 06 Sep 2023

Viewed by 1020

Abstract

The skin is a complex organ that includes a wide variety of tissue types with different embryological origins [...] Full article

(This article belongs to the Special Issue Looking into the Skin in Health and Disease: From Microscopy Imaging Techniques to Molecular Analysis)

Research

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15 pages, 2779 KiB

Open AccessArticle

Transcriptomic Study on Human Skin Samples: Identification of Two Subclasses of Actinic Keratoses

by Hélène Dubois-Pot-Schneider, Grégoire Khairallah, Cyril Brzenczek, François Plénat, Frédéric Marchal and Marine Amouroux

Int. J. Mol. Sci. 2023, 24(6), 5937; https://doi.org/10.3390/ijms24065937 - 21 Mar 2023

Cited by 2 | Viewed by 1399

Abstract

Actinic keratoses (AKs) are sun-damaged skin areas that affect 20% of the European adult population and more than 50% of people aged 70 years and over. There are currently no clinical or histological features allowing us to identify to which clinical class (i.e., regression or progression) an AK belongs. A transcriptomic approach seems to be a robust tool for AK characterization, but there is a need for additional studies, including more patients and elucidating the molecular signature of an AK. In this context, the present study, including the largest number of patients to date, is the first aiming at identifying biological features to objectively distinguish different AK signatures. We highlight two distinct molecular profiles: AKs featuring a molecular profile similar to squamous cell carcinomas (SCCs), which are called “lesional AKs” (AK_Ls), and AKs featuring a molecular profile similar to normal skin tissue, which are called “non-lesional AKs” (AK_NLs). The molecular profiles of both AK subclasses were studied, and 316 differentially expressed genes (DEGs) were identified between the two classes. The 103 upregulated genes in AK_L were related to the inflammatory response. Interestingly, downregulated genes were associated with keratinization. Finally, based on a connectivity map approach, our data highlight that the VEGF pathway could be a promising therapeutic target for high-risk lesions. Full article

(This article belongs to the Special Issue Looking into the Skin in Health and Disease: From Microscopy Imaging Techniques to Molecular Analysis)

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12 pages, 3557 KiB

Open AccessArticle

Organophosphorus Flame Retardant TCPP Induces Cellular Senescence in Normal Human Skin Keratinocytes: Implication for Skin Aging

by Jian-Xiang Liu, Dao-Lei Cui, Dan-Lei Yang, Jing-Ya Li, Zi-Yue Yang, Jin-Zhou Su, Cai-Xia Ren, You-Ya Niu and Ping Xiang

Int. J. Mol. Sci. 2022, 23(22), 14306; https://doi.org/10.3390/ijms232214306 - 18 Nov 2022

Cited by 6 | Viewed by 1512

Abstract

Tris (1-chloro-2-propyl) phosphate (TCPP) is one of the most frequently detected organophosphorus flames in the environment. Continuous daily exposure to TCPP may harm human skin. However, little is known about the adverse effects of TCPP on human skin. In this study, we first evaluated the detrimental effects and tried to uncover the underlying mechanisms of TCPP on human skin keratinocytes (HaCaT) after 24 h exposure. We found that TCPP caused a concentration-dependent decrease in HaCaT cell viability after exposure to 1.56–400 μg/mL for 24 h, with an IC₅₀ of 275 μg/mL. TCPP also promoted the generation of intracellular reactive oxygen species (ROS) and triggered DNA damage, evidenced by an increase of phosphorylated histone H2A.X (γH2A.X) in the nucleus. Furthermore, the cell cycle was arrested at the G1 phase at 100 μg/mL by upregulation of the mRNA expression of p53 and p21 and downregulation of cyclin D1 and CDK4 expression. Additionally, both the senescence-associated-β-galactosidase activity and related proinflammatory cytokine IL-1β and IL-6 were elevated, indicating that TCPP exposure caused cellular senescence may be through the p53-dependent DNA damage signal pathway in HaCaT cells. Taken together, our data suggest that flame-retardant exposure may be a key precipitating factor for human skin aging. Full article

(This article belongs to the Special Issue Looking into the Skin in Health and Disease: From Microscopy Imaging Techniques to Molecular Analysis)

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Graphical abstract

14 pages, 1812 KiB

Open AccessArticle

Computer Aided Diagnosis of Melanoma Using Deep Neural Networks and Game Theory: Application on Dermoscopic Images of Skin Lesions

by Arthur Cartel Foahom Gouabou, Jules Collenne, Jilliana Monnier, Rabah Iguernaissi, Jean-Luc Damoiseaux, Abdellatif Moudafi and Djamal Merad

Int. J. Mol. Sci. 2022, 23(22), 13838; https://doi.org/10.3390/ijms232213838 - 10 Nov 2022

Cited by 6 | Viewed by 2151

Abstract

Early detection of melanoma remains a daily challenge due to the increasing number of cases and the lack of dermatologists. Thus, AI-assisted diagnosis is considered as a possible solution for this issue. Despite the great advances brought by deep learning and especially convolutional neural networks (CNNs), computer-aided diagnosis (CAD) systems are still not used in clinical practice. This may be explained by the dermatologist’s fear of being misled by a false negative and the assimilation of CNNs to a “black box”, making their decision process difficult to understand by a non-expert. Decision theory, especially game theory, is a potential solution as it focuses on identifying the best decision option that maximizes the decision-maker’s expected utility. This study presents a new framework for automated melanoma diagnosis. Pursuing the goal of improving the performance of existing systems, our approach also attempts to bring more transparency in the decision process. The proposed framework includes a multi-class CNN and six binary CNNs assimilated to players. The players’ strategies is to first cluster the pigmented lesions (melanoma, nevus, and benign keratosis), using the introduced method of evaluating the confidence of the predictions, into confidence level (confident, medium, uncertain). Then, a subset of players has the strategy to refine the diagnosis for difficult lesions with medium and uncertain prediction. We used EfficientNetB5 as the backbone of our networks and evaluated our approach on the public ISIC dataset consisting of 8917 lesions: melanoma (1113), nevi (6705) and benign keratosis (1099). The proposed framework achieved an area under the receiver operating curve (AUROC) of 0.93 for melanoma, 0.96 for nevus and 0.97 for benign keratosis. Furthermore, our approach outperformed existing methods in this task, improving the balanced accuracy (BACC) of the best compared method from 77% to 86%. These results suggest that our framework provides an effective and explainable decision-making strategy. This approach could help dermatologists in their clinical practice for patients with atypical and difficult-to-diagnose pigmented lesions. We also believe that our system could serve as a didactic tool for less experienced dermatologists. Full article

(This article belongs to the Special Issue Looking into the Skin in Health and Disease: From Microscopy Imaging Techniques to Molecular Analysis)

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14 pages, 4504 KiB

Open AccessArticle

3D Molecular Imaging of Stratum Corneum by Mass Spectrometry Suggests Distinct Distribution of Cholesteryl Esters Compared to Other Skin Lipids

by Peter Sjövall, Sebastien Gregoire, William Wargniez, Lisa Skedung and Gustavo S. Luengo

Int. J. Mol. Sci. 2022, 23(22), 13799; https://doi.org/10.3390/ijms232213799 - 09 Nov 2022

Cited by 4 | Viewed by 1718

Abstract

The crucial barrier properties of the stratum corneum (SC) depend critically on the design and integrity of its layered molecular structure. However, analysis methods capable of spatially resolved molecular characterization of the SC are scarce and fraught with severe limitations, e.g., regarding molecular specificity or spatial resolution. Here, we used 3D time-of-flight secondary ion mass spectrometry to characterize the spatial distribution of skin lipids in corneocyte multilayer squams obtained by tape stripping. Depth profiles of specific skin lipids display an oscillatory behavior that is consistent with successive monitoring of individual lipid and corneocyte layers of the SC structure. Whereas the most common skin lipids, i.e., ceramides, C24:0 and C26:0 fatty acids and cholesteryl sulfate, are similarly organized, a distinct 3D distribution was observed for cholesteryl oleate, suggesting a different localization of cholesteryl esters compared to the lipid matrix separating the corneocyte layers. The possibility to monitor the composition and spatial distribution of endogenous lipids as well as active drug and cosmetic substances in individual lipid and corneocyte layers has the potential to provide important contributions to the basic understanding of barrier function and penetration in the SC. Full article

(This article belongs to the Special Issue Looking into the Skin in Health and Disease: From Microscopy Imaging Techniques to Molecular Analysis)

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17 pages, 5515 KiB

Open AccessArticle

Automatic Segmentation of Laser-Induced Injury OCT Images Based on a Deep Neural Network Model

by Tianxin Gao, Shuai Liu, Enze Gao, Ancong Wang, Xiaoying Tang and Yingwei Fan

Int. J. Mol. Sci. 2022, 23(19), 11079; https://doi.org/10.3390/ijms231911079 - 21 Sep 2022

Cited by 5 | Viewed by 1533

Abstract

Optical coherence tomography (OCT) has considerable application potential in noninvasive diagnosis and disease monitoring. Skin diseases, such as basal cell carcinoma (BCC), are destructive; hence, quantitative segmentation of the skin is very important for early diagnosis and treatment. Deep neural networks have been widely used in the boundary recognition and segmentation of diseased areas in medical images. Research on OCT skin segmentation and laser-induced skin damage segmentation based on deep neural networks is still in its infancy. Here, a segmentation and quantitative analysis pipeline of laser skin injury and skin stratification based on a deep neural network model is proposed. Based on the stratification of mouse skins, a laser injury model of mouse skins induced by lasers was constructed, and the multilayer structure and injury areas were accurately segmented by using a deep neural network method. First, the intact area of mouse skin and the damaged areas of different laser radiation doses are collected by the OCT system, and then the labels are manually labeled by experienced histologists. A variety of deep neural network models are used to realize the segmentation of skin layers and damaged areas on the skin dataset. In particular, the U-Net model based on a dual attention mechanism is used to realize the segmentation of the laser-damage structure, and the results are compared and analyzed. The segmentation results showed that the Dice coefficient of the mouse dermis layer and injury area reached more than 0.90, and the Dice coefficient of the fat layer and muscle layer reached more than 0.80. In the evaluation results, the average surface distance (ASSD) and Hausdorff distance (HD) indicated that the segmentation results are excellent, with a high overlap rate with the manually labeled area and a short edge distance. The results of this study have important application value for the quantitative analysis of laser-induced skin injury and the exploration of laser biological effects and have potential application value for the early noninvasive detection of diseases and the monitoring of postoperative recovery in the future. Full article

(This article belongs to the Special Issue Looking into the Skin in Health and Disease: From Microscopy Imaging Techniques to Molecular Analysis)

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14 pages, 4015 KiB

Open AccessArticle

High-Intensity Focused Ultrasound Induces Adipogenesis via Control of Cilia in Adipose-Derived Stem Cells in Subcutaneous Adipose Tissue

by Seyeon Oh, Hyoung Moon Kim, Sosorburam Batsukh, Hye Jin Sun, Taehui Kim, Donghwan Kang, Kuk Hui Son and Kyunghee Byun

Int. J. Mol. Sci. 2022, 23(16), 8866; https://doi.org/10.3390/ijms23168866 - 09 Aug 2022

Cited by 7 | Viewed by 3218

Abstract

During skin aging, the volume of subcutaneous adipose tissue (sWAT) and the adipogenesis potential of adipose-derived stem cells (ASCs) decrease. It is known that the shortening of cilia length by pro-inflammatory cytokines is related to the decreased adipogenic differentiation of ASCs via increase in Wnt5a/β-catenin. High-intensity focused ultrasound (HIFU) is known to upregulate heat shock proteins (HSP), which decrease levels of pro-inflammatory cytokines. In this study, we evaluated whether HIFU modulates the cilia of ASCs by upregulating HSP70 and decreasing inflammatory cytokines. HIFU was applied at 0.2 J to rat skin, which was harvested at 1, 3, 7, and 28 days. All results for HIFU-applied animals were compared with control animals that were not treated. HIFU increased expression of HSP70 and decreased expression of NF-κB, IL-6, and TNF-α in sWAT. HIFU decreased the expression of cilia disassembly-related factors (AurA and HDAC9) in ASCs. Furthermore, HIFU increased the expression of cilia assembly-related factors (KIF3A and IFT88), decreased that of WNT5A/β-catenin, and increased that of the adipogenesis markers PPARγ and CEBPα in sWAT. HIFU increased the number of adipocytes in the sWAT and the thickness of sWAT. In conclusion, HIFU could selectively increase sWAT levels by modulating the cilia of ASCs and be used for skin rejuvenation. Full article

(This article belongs to the Special Issue Looking into the Skin in Health and Disease: From Microscopy Imaging Techniques to Molecular Analysis)

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Review

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58 pages, 13600 KiB

Open AccessReview

Skin Cancer Pathobiology at a Glance: A Focus on Imaging Techniques and Their Potential for Improved Diagnosis and Surveillance in Clinical Cohorts

by Elena-Georgiana Dobre, Mihaela Surcel, Carolina Constantin, Mihaela Adriana Ilie, Ana Caruntu, Constantin Caruntu and Monica Neagu

Int. J. Mol. Sci. 2023, 24(2), 1079; https://doi.org/10.3390/ijms24021079 - 05 Jan 2023

Cited by 6 | Viewed by 3710

Abstract

Early diagnosis is essential for completely eradicating skin cancer and maximizing patients’ clinical benefits. Emerging optical imaging modalities such as reflectance confocal microscopy (RCM), optical coherence tomography (OCT), magnetic resonance imaging (MRI), near-infrared (NIR) bioimaging, positron emission tomography (PET), and their combinations provide non-invasive imaging data that may help in the early detection of cutaneous tumors and surgical planning. Hence, they seem appropriate for observing dynamic processes such as blood flow, immune cell activation, and tumor energy metabolism, which may be relevant for disease evolution. This review discusses the latest technological and methodological advances in imaging techniques that may be applied for skin cancer detection and monitoring. In the first instance, we will describe the principle and prospective clinical applications of the most commonly used imaging techniques, highlighting the challenges and opportunities of their implementation in the clinical setting. We will also highlight how imaging techniques may complement the molecular and histological approaches in sharpening the non-invasive skin characterization, laying the ground for more personalized approaches in skin cancer patients. Full article

(This article belongs to the Special Issue Looking into the Skin in Health and Disease: From Microscopy Imaging Techniques to Molecular Analysis)

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21 pages, 1317 KiB

Open AccessReview

Mechanical Stretch Induced Skin Regeneration: Molecular and Cellular Mechanism in Skin Soft Tissue Expansion

by Yaotao Guo, Yajuan Song, Shaoheng Xiong, Tong Wang, Wei Liu, Zhou Yu and Xianjie Ma

Int. J. Mol. Sci. 2022, 23(17), 9622; https://doi.org/10.3390/ijms23179622 - 25 Aug 2022

Cited by 10 | Viewed by 4803

Abstract

Skin soft tissue expansion is one of the most basic and commonly used techniques in plastic surgery to obtain excess skin for a variety of medical uses. However, skin soft tissue expansion is faced with many problems, such as long treatment process, poor skin quality, high retraction rate, and complications. Therefore, a deeper understanding of the mechanisms of skin soft tissue expansion is needed. The key to skin soft tissue expansion lies in the mechanical stretch applied to the skin by an inflatable expander. Mechanical stimulation activates multiple signaling pathways through cellular adhesion molecules and regulates gene expression profiles in cells. Meanwhile, various types of cells contribute to skin expansion, including keratinocytes, dermal fibroblasts, and mesenchymal stem cells, which are also regulated by mechanical stretch. This article reviews the molecular and cellular mechanisms of skin regeneration induced by mechanical stretch during skin soft tissue expansion. Full article

(This article belongs to the Special Issue Looking into the Skin in Health and Disease: From Microscopy Imaging Techniques to Molecular Analysis)

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