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Search Results (2,276)

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2 pages, 168 KB  
Abstract
Image Analysis Criteria for the Macroscopic Assessment of Skin Healing in Atlantic Salmon
by João Leça, Bruna Henriques, Filipe Soares, Cláudia Magalhães, Rui Rocha and Paulo Rema
Proceedings 2026, 146(1), 105; https://doi.org/10.3390/proceedings2026146105 (registering DOI) - 22 Jun 2026
Abstract
Introduction: Fish skin is the first line of defense against the aquatic environment, acting as a physical, chemical, and immunological barrier. In addition to preventing pathogen entry, the skin and its mucus contribute to osmoregulation, innate immunity, and redox balance. Skin lesions—caused by [...] Read more.
Introduction: Fish skin is the first line of defense against the aquatic environment, acting as a physical, chemical, and immunological barrier. In addition to preventing pathogen entry, the skin and its mucus contribute to osmoregulation, innate immunity, and redox balance. Skin lesions—caused by mechanical damage, parasites, environmental stress, or handling—disrupt this barrier, increasing susceptibility to infections, inflammation, and production losses. Thus, efficient skin regeneration is essential for fish welfare and performance. Nutrition plays a key role in this process by providing substrates for epithelial repair, immune function, and antioxidant defense. Among dietary factors, zinc (Zn) is particularly important due to its involvement in cell proliferation, enzymatic activity, and maintenance of skin integrity. Objective: Our objective is to assess the effectiveness of image-based analysis in quantifying the skin healing process in Atlantic salmon fed diets supplemented with zinc. Methodology: The trial comprised three dietary treatments: a control diet with 42 mg Zn per kg (D1), and two diets supplemented up to 120 mg/kg of zinc, derived from inorganic (D2) or organic (D3) forms. Pit-tagged fish with an initial body weight (78 ± 0.1 g) were fed the diets for 75 days. After 15 days of experimental feeding, a standardized wound lesion (2.5 mm diameter × 0.5 mm depth) was inflicted in deeply anesthetized fish, with a disposable biopsy punch, in the dorsal area. After wound infliction, the fish resumed their normal feeding regime for the rest of the trial days. The progression of skin wound healing was assessed using standardized digital image analysis. High-resolution photographs of individual wounds were collected 8, 16, 24 and 32 days post-wounding. All images were acquired under standardized conditions with the inclusion of ArUco identifiers to enable a subsequent computer-assisted comparison. Morphometric parameters (wound width, diameter, perimeter and area) were used to assess wound contraction and closure over time. In parallel, a semi-quantitative visual scoring system was applied to each wound image to capture qualitative aspects of healing that are not fully described by morphometric data alone. Results: Full data analysis is currently underway, but the first results show beneficial effects of dietary zinc supplementation on the skin regenerative process. Conclusions: The combined use of objective digital measurements and standardized visual scoring enabled a comprehensive evaluation of wound healing progress, bridging quantitative tissue remodeling with biologically relevant phenotypic outcomes. This image-based framework provides a sensitive and reproducible approach for assessing dietary interventions targeting skin regeneration and barrier restoration in Atlantic salmon. Full article
(This article belongs to the Proceedings of The XI Iberian Congress of Ichthyology)
19 pages, 5420 KB  
Review
Usnic Acid and Its Topical Use—A Concise Review
by Gabriela Siedlarczyk, Irma Podolak and Agnieszka Galanty
Molecules 2026, 31(12), 2183; https://doi.org/10.3390/molecules31122183 (registering DOI) - 22 Jun 2026
Abstract
Usnic acid (UA), a prominent lichen secondary metabolite, exhibits a unique dual therapeutic profile in dermatology, though its clinical translation is limited by systemic hepatotoxicity and poor solubility. This review comprehensively evaluates the topical efficacy, molecular mechanisms, and advanced formulation strategies of UA [...] Read more.
Usnic acid (UA), a prominent lichen secondary metabolite, exhibits a unique dual therapeutic profile in dermatology, though its clinical translation is limited by systemic hepatotoxicity and poor solubility. This review comprehensively evaluates the topical efficacy, molecular mechanisms, and advanced formulation strategies of UA enantiomers and UA-rich extracts. A literature search across PubMed, Scopus, and Google Scholar identified 36 original publications focusing on anti-melanoma activity, photoprotection, and tissue regeneration. In vitro studies demonstrate that UA induces apoptosis in resistant melanoma cell lines (A375, HTB-140) via extrinsic/intrinsic pathways, with (−)-UA effectively overcoming doxorubicin resistance. Conversely, in non-cancerous models, low concentrations of UA accelerate wound and burn healing by upregulating vascular endothelial growth factor (VEGF), stimulating fibroblast proliferation, and optimizing extracellular matrix remodeling while preventing hypertrophic scarring. To mitigate skin sensitization and systemic risks, advanced drug delivery systems—including liposomes, nanoemulsions, chitosan nanogels, and electrospun scaffolds—have been developed, significantly enhancing skin permeability and localized dermal retention. Ultimately, the development of bio-functionalized smart dressings and targeted nano-formulations represents the most viable path toward unlocking the full clinical potential of UA in modern dermatological and oncological care. Full article
(This article belongs to the Special Issue Chemistry and Biological Activities of Lichens and Fungi)
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11 pages, 871 KB  
Review
Circulating Tumor DNA in Merkel Cell Carcinoma: A Precision Biomarker for Recurrence Detection and Therapeutic Guidance
by Joshua E. Chan and Lisa C. Zaba
J. Pers. Med. 2026, 16(6), 330; https://doi.org/10.3390/jpm16060330 (registering DOI) - 20 Jun 2026
Viewed by 113
Abstract
Background/Objectives: Merkel cell carcinoma (MCC) is a rare but aggressive skin cancer with a 40% recurrence rate. However, reliable biomarkers for early recurrence detection or treatment guidance are lacking, especially for virus-negative tumors. Circulating tumor DNA (ctDNA), a fragment of tumor-derived cell-free DNA [...] Read more.
Background/Objectives: Merkel cell carcinoma (MCC) is a rare but aggressive skin cancer with a 40% recurrence rate. However, reliable biomarkers for early recurrence detection or treatment guidance are lacking, especially for virus-negative tumors. Circulating tumor DNA (ctDNA), a fragment of tumor-derived cell-free DNA in blood, has emerged across multiple cancers as a minimally invasive precision biomarker to detect minimal residual disease (MRD); predict recurrence; and monitor treatment response. This review’s objective was to summarize recent advances in ctDNA as a tool for therapeutic decision-making in MCC, contextualized by findings in other malignancies. Methods: A comprehensive literature review was performed, focusing on studies published between 2016 and 2026 that evaluate ctDNA in MCC and other cancers. Key prospective trials, observational studies, and case reports were identified through PubMed and relevant conference proceedings. Data on ctDNA assay methods (tumor-informed vs. tumor-agnostic), clinical sensitivity, lead time for recurrence detection, and predictive value for therapy response were extracted and synthesized. Results: Across cancers such as colorectal, lung, and melanoma, ctDNA positivity after curative treatment predicts relapse months in advance of imaging and can guide adjuvant therapy decisions. In MCC, recent studies demonstrate that ctDNA levels correlate with MCC tumor burden and exhibit high sensitivity and specificity for clinically evident disease. Stage I-III MCC patients who were ctDNA-positive within four months of treatment had a 7.4-fold higher recurrence risk within the subsequent 12–18 months of follow-up. Serial ctDNA monitoring may enable earlier intervention in otherwise asymptomatic ctDNA-positive MCC cases, helping distinguish responders from non-responders. Conclusions: ctDNA is an emerging precision biomarker that offers significant prognostic and surveillance utility in MCC. It enables earlier detection of recurrence, potentially allowing treatment to begin before clinical disease manifests. It also helps stratify patients by risk and treatment response, informing personalized surveillance intensity and therapeutic choices. Integrating ctDNA monitoring into MCC management could improve outcomes by guiding timely interventions, although prospective trials are needed to confirm that ctDNA-guided decisions translate to improved patient survival. Formal cost-effectiveness analyses have not yet been conducted and represent an important area for future investigation. Full article
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14 pages, 5367 KB  
Article
Anti-Inflammatory Activity of a Phycocyanin–Protein Complex in THP-1 Cells: Implications for Dermocosmetic Applications
by Fidel Delgado, Mario Blanco-Vieites, María Álvarez-Gil, Víctor Casado-Bañares and Eduardo Rodríguez
BioTech 2026, 15(2), 45; https://doi.org/10.3390/biotech15020045 - 16 Jun 2026
Viewed by 152
Abstract
Phycocyanin, a phycobiliprotein derived from the cyanobacterium Limnospira (Arthrospira) platensis (commonly known as Spirulina), is recognized for its antioxidant, immunomodulatory, and bioactive properties. This research aims to develop a new cosmetic ingredient based on phycocyanin incorporated into a high-lipid matrix, such [...] Read more.
Phycocyanin, a phycobiliprotein derived from the cyanobacterium Limnospira (Arthrospira) platensis (commonly known as Spirulina), is recognized for its antioxidant, immunomodulatory, and bioactive properties. This research aims to develop a new cosmetic ingredient based on phycocyanin incorporated into a high-lipid matrix, such as shea butter. A comprehensive characterization of the cytotoxicity and anti-inflammatory activity of this new bioactive phycocyanin–protein complex in human THP-1 monocytic cells was performed. For this purpose, cytocompatibility was evaluated using MTT assays at concentrations ranging from 10 to 0.0006% v/v. Anti-inflammatory activity was measured under LPS-induced inflammatory stress by measuring IL-6 and IL-8 secretion using ELISA in PMA-differentiated THP-1 cells treated with non-cytotoxic concentrations (0.04, 0.02, and 0.01% v/v). A crucial finding was the absence of anti-inflammatory activity at 0.01% v/v, indicating a minimum effective concentration threshold and, consequently, effective doses. The results of this research indicate that the phycocyanin and shea butter ingredients demonstrate strong cytocompatibility at relevant cosmetic doses and significant anti-inflammatory activity, supporting their suitability for formulations targeting skin sensitivity, erythema reduction, and post-inflammatory recovery. Full article
(This article belongs to the Section Medical Biotechnology)
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20 pages, 3942 KB  
Article
A Competent Antiviral, Antimicrobial, Nontoxic Nanostructured Lipid Carrier System for Safe Use as a Hand Sanitizer: In Vitro and In Vivo Studies
by Eman Samy Shalaby, Mohamed Azab El-Liethy, Sherif Abd-Elmaksoud, Corrado Tagliati, Rawia Mohamed Khalil and Said Ibrahim Shalaby
Biomolecules 2026, 16(6), 886; https://doi.org/10.3390/biom16060886 - 16 Jun 2026
Viewed by 210
Abstract
Effective hand washing takes time and hand sanitizers that contain alcohol have a number of drawbacks, and frequent use of alcohol may cause skin damage. The objective of this study is to formulate nanostructured lipid carrier systems containing chlorhexidine digluconate to be applied [...] Read more.
Effective hand washing takes time and hand sanitizers that contain alcohol have a number of drawbacks, and frequent use of alcohol may cause skin damage. The objective of this study is to formulate nanostructured lipid carrier systems containing chlorhexidine digluconate to be applied topically for hand hygiene, especially for people sensitive to alcohol. A cytotoxicity experiment was conducted to ascertain the safe dosage for each of the three nano-cream formulas (F1, F2 and F3). Following each treatment, the viral titer was assessed using tissue culture infectious dose50 and standard plaque assays. The selected formulation was characterized rheologically. Furthermore, fifteen volunteers of various ages and genders participated in the vivo antimicrobial test of the selected formulation as a hand sanitizer. All of the formulas were found to be safe. Using the disc diffusion method, the three formulations exhibited in vitro antimicrobial effects against different microbes. F1 showed biphasic release, reasonable skin deposition and spherical droplets under a microscope. F1 exhibited a non-Newtonian shear thinning flow behavior. After 30 min, the reduction values for rotavirus and Phix-174 were 21 and 4%, respectively. Additionally, the impact of F1 was assessed on the infectivity of simian rotavirus sa-11 (ds RNA) and Phix-174 (ss DNA) bacteriophage. According to the findings of the in vivo study, the percentage of total bacterial counts that were removed varied from 91 to 100%. Moreover, the range of the removal percentage of total fungi was 95.38 to 100%. In summary, F1 can be used as an economic, safe, and effective hand antiseptic. It can also completely replace alcohol in the market. Full article
(This article belongs to the Special Issue Advances in Nano-Based Drug Delivery Systems)
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15 pages, 3358 KB  
Systematic Review
SUDOSCAN for the Early Detection of Diabetic Neuropathy: A Systematic Review of the Diagnostic Performance and Clinical Utility
by Monica Annemarie Selefon, Claudiu Cobuz, Corina Vernic, Dragos Catalin Jianu, Oana Milas and Adrian Vlad
Diabetology 2026, 7(6), 115; https://doi.org/10.3390/diabetology7060115 - 16 Jun 2026
Viewed by 196
Abstract
Background: Diabetic neuropathy (DN) is a common complication of diabetes mellitus that remains frequently undetected by conventional diagnostic methods. Sudomotor dysfunction, reflecting small-fiber impairment, has emerged as a potential early marker. SUDOSCAN, a rapid and non-invasive device measuring electrochemical skin conductance (ESC), has [...] Read more.
Background: Diabetic neuropathy (DN) is a common complication of diabetes mellitus that remains frequently undetected by conventional diagnostic methods. Sudomotor dysfunction, reflecting small-fiber impairment, has emerged as a potential early marker. SUDOSCAN, a rapid and non-invasive device measuring electrochemical skin conductance (ESC), has been proposed as a screening tool for early DN. The objective of this study was to systematically evaluate the diagnostic performance and clinical utility of SUDOSCAN in the early detection of DN. Methods: A systematic review was conducted in accordance with the PRISMA 2020 guidelines. Studies assessing SUDOSCAN-derived ESC in adults with diabetes were included. Data on diagnostic accuracy, correlations with established neuropathy measures, and clinical applicability were extracted. Where feasible, pooled sensitivity and specificity were estimated using a random-effects model. Results: Fifteen studies (n = 7343 participants) were included in the qualitative synthesis, with five of them contributing to the quantitative analysis. Reduced ESC values were consistently associated with DN, including early and asymptomatic cases. Pooled sensitivity and specificity for detecting DN were 0.81 (95% CI 0.73–0.87) and 0.73 (95% CI 0.57–0.85), respectively. ESC values correlated with neuropathy severity scores and autonomic dysfunction measures. However, substantial heterogeneity was observed due to variability in diagnostic criteria, ESC thresholds, and study populations. Conclusions: SUDOSCAN is a feasible, rapid, and non-invasive tool for detecting DN, particularly in the early-stage or small-fiber disease. It shows promise as a screening and adjunctive diagnostic modality, especially when combined with established clinical tools. Nevertheless, the lack of standardized thresholds limits its standalone use. Full article
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21 pages, 21638 KB  
Systematic Review
Prophylactic Use of Tranexamic Acid to Prevent Postpartum Hemorrhage in High-Risk Cesarean Deliveries: A Systematic Review and Meta-Analysis
by Xochitl Sandoval López, Hazel C. García, Cesar M. Gavidia, Karina V. Alam, Zaida I. Álvarez, Mirna E. Meléndez and David A. Tejada
J. Clin. Med. 2026, 15(12), 4630; https://doi.org/10.3390/jcm15124630 - 15 Jun 2026
Viewed by 571
Abstract
Background/Objective: Postpartum hemorrhage is a leading cause of maternal morbidity and mortality, particularly among high-risk women undergoing cesarean section. This systematic review and meta-analysis evaluated the efficacy and safety of prophylactic tranexamic acid in high-risk cesarean sections. Methods: A systematic review [...] Read more.
Background/Objective: Postpartum hemorrhage is a leading cause of maternal morbidity and mortality, particularly among high-risk women undergoing cesarean section. This systematic review and meta-analysis evaluated the efficacy and safety of prophylactic tranexamic acid in high-risk cesarean sections. Methods: A systematic review and meta-analysis of randomized controlled trials was conducted. Risk of bias was assessed using RoB 2.0 and certainty of evidence was evaluated with GRADE. Random-effects meta-analyses, subgroup analyses and sensitivity analyses were performed. PROSPERO: CRD420251087054. Results: Nine randomized controlled trials involving 1776 participants were included. Tranexamic acid reduced total blood loss (MD −300.78; 95% CI −459.78 to −157.77), with greater efficacy when administered 15–20 min before incision (SMD −0.61; 95% CI −0.82 to −0.39). It also reduced intraoperative blood loss (MD −256.71 mL; 95% CI −375.04 to −138.39), blood loss >1000 mL (RR 0.24; 95% CI 0.14 to 0.41), additional uterotonics (RR 0.37; 95% CI 0.24 to 0.58), blood transfusions (RR 0.30; 95% CI 0.22 to 0.40), and complementary surgical interventions (RR 0.35; 95% CI 0.16 to 0.78). Conclusions: Prophylactic tranexamic acid may reduce blood loss in high-risk cesarean deliveries, particularly when administered 15–20 min before skin incision. It may decrease total and intraoperative blood loss and blood loss exceeding 1000 mL. It also likely reduces the postoperative decline in hemoglobin, the need for additional uterotonics, blood transfusions, and complementary surgical interventions; however, its effect on hematocrit remains uncertain. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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21 pages, 2229 KB  
Article
Bacterial Cellulose Dressings from Mango Pulp Agro-Waste Functionalized with Grapefruit Seed Oil for Diabetic Wound Healing
by Mayra E. García-Sánchez, Alfonso Barajas-Cervantes, Inés Jiménez-Palomar, José M. Acosta-Cuevas and Erick O. Cisneros-López
Polysaccharides 2026, 7(2), 69; https://doi.org/10.3390/polysaccharides7020069 - 15 Jun 2026
Viewed by 252
Abstract
Bacterial cellulose (BC) is an emerging biopolymer for skin tissue regeneration; however, its functionalization with natural antimicrobial agents remains limited. This study reports the preclinical evaluation of a BC-based dressing for diabetic wounds. BC membranes were obtained from mango pulp agro-waste by Komagataeibacter [...] Read more.
Bacterial cellulose (BC) is an emerging biopolymer for skin tissue regeneration; however, its functionalization with natural antimicrobial agents remains limited. This study reports the preclinical evaluation of a BC-based dressing for diabetic wounds. BC membranes were obtained from mango pulp agro-waste by Komagataeibacter xylinus cultivation (6.32 g/L) and functionalized with grapefruit seed oil (GSO) at three v/v ratios (1:100, 1:200 and 1:500). FTIR spectroscopy confirmed GSO incorporation into the BC matrix through physical interactions, with a dose-dependent loading. Antimicrobial activity of the BC/GSO dressings was screened against Staphylococcus aureus, Escherichia coli and Candida albicans by agar diffusion, showing dose-dependent inhibition zones. Following the minimum effective dose principle, the BC/GSO 1:500 (v/v) formulation was selected for comprehensive biocompatibility evaluation (cytotoxicity, mutagenicity, pyrogenicity and sensitization) and for in vivo wound-healing testing in a streptozotocin-induced diabetic Wistar rat model. Cell viability above 70% was achieved from membrane-extract dilution 1:100,000, while mutagenicity, pyrogenicity and sensitization assays confirmed the absence of adverse biological responses. In vivo, BC/GSO 1:500 (v/v) dressings supported wound closure comparable to nitrofurazone, with no clinical signs of infection. Overall, these results position BC/GSO dressings as a sustainable, biocompatible and antimicrobial candidate for early-stage diabetic wound regeneration and demonstrate the technical feasibility of valorizing mango pulp agro-waste into a high-value biomedical biopolymer. Full article
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18 pages, 4051 KB  
Article
Preparation of High Elongation and Low Hysteresis Conductive Hydrogels Strain Sensor Using Flake-like PEDOT Particles as Conductive Fillers
by Xiyuan Duan, Shimin Wang, Daheng Wang, Yu Gong and Ziwei Jiang
Gels 2026, 12(6), 536; https://doi.org/10.3390/gels12060536 - 15 Jun 2026
Viewed by 190
Abstract
Conductive hydrogel strain sensors using poly(3,4-ethylenedioxythiophene) (PEDOT) as fillers are rapidly advancing and are emerging as candidates for monitoring devices such as wearable electronic skin. However, due to limitations such as low elongation and high hysteresis, it is difficult to fully leverage its [...] Read more.
Conductive hydrogel strain sensors using poly(3,4-ethylenedioxythiophene) (PEDOT) as fillers are rapidly advancing and are emerging as candidates for monitoring devices such as wearable electronic skin. However, due to limitations such as low elongation and high hysteresis, it is difficult to fully leverage its promising sensor properties in practical applications. In this study, we synthesized flake-like PEDOT particles (FP particles) and used Polyacrylamide (PAM) as the hydrogel matrix to fabricate a conductive hydrogel strain sensor. These particles were obtained by grinding PEDOT particles prepared via a template-free method. After swelling with ethylene glycol (EG) and assembly with polyvinyl alcohol (PVA), the FP particles become porous and contain many hydroxyl groups. This design enables the adsorption of acrylamide (AM) monomers within FP particles, facilitating the in situ polymerization of PAM onto the PEDOT/PVA chains, thereby yielding a dual-network structure with strong entanglements. This gives the sensor high elongation and very low hysteresis. In addition, it offers favorable sensor performance, including high sensitivity, high repeatability, and reliability. This strain sensor can be used in wearable electronic skin applications for facial monitoring and motion detection. Full article
(This article belongs to the Special Issue Research on the Applications of Conductive Hydrogels)
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19 pages, 7615 KB  
Article
A Rapid 3D Melanoma–Skin Organoid for High-Throughput Assessment of Tumor Dynamics and Drug Response
by Gemma Nomdedeu-Sancho, Nicholas Edenhoffer, Anastasiya Gorkun-Roeder, Ola A. Gaser, Carlos Kengla, Allie Benton, David W. Mullins, Anthony Atala and Shay Soker
Int. J. Mol. Sci. 2026, 27(12), 5314; https://doi.org/10.3390/ijms27125314 - 12 Jun 2026
Viewed by 349
Abstract
Melanoma is the most aggressive type of skin cancer, driven by early invasion, phenotypic plasticity, and frequent resistance to targeted therapies. Although genomic profiling informs treatment selection, genotype alone often fails to predict therapeutic response, underscoring the need for rapid and physiologically relevant [...] Read more.
Melanoma is the most aggressive type of skin cancer, driven by early invasion, phenotypic plasticity, and frequent resistance to targeted therapies. Although genomic profiling informs treatment selection, genotype alone often fails to predict therapeutic response, underscoring the need for rapid and physiologically relevant functional testing platforms. Here, we present a three-dimensional melanoma–skin organoid (mSO) model that integrates primary skin cells with melanoma cell lines in a self-assembling, high-throughput format. The spherical mSOs recapitulate native human skin architecture, including a stratified epidermis and a dermal–hypodermal core, while supporting melanoma growth within an appropriate tissue microenvironment. In this niche, melanoma cells display epidermal spreading in radial growth-like patterns, outward invasion, and transcriptional shifts toward a pro-invasive phenotype. Using live confocal imaging coupled with a custom automated image analysis pipeline, we quantitatively measured tumor growth, migration beyond the organoid boundary, and interactions between melanoma cells and normal melanocytes. The mSOs also captured genotype-specific drug responses: BRAF-mutant melanoma cells were sensitive to BRAF and MEK inhibition, whereas NRAS-mutant, BRAF–wild-type cells were resistant to BRAF inhibition but remained responsive to MEK inhibition. Altogether, our mSO platform combines architectural and functional complexity with experimental scalability, providing a robust framework for modeling melanoma progression and evaluating targeted therapeutic responses within a relevant skin microenvironment. In the future, adaptation of this system to include patient-derived tumor cells could support personalized therapeutic decision-making in melanoma. Full article
(This article belongs to the Special Issue Tumor Organoids Uncovered: A Molecular Lens on Cancer Complexity)
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19 pages, 1577 KB  
Article
Validation of the Electrophilic Allergen Screening Assay for Detection of Key Event 1 of the Skin Sensitization Adverse Outcome Pathway
by Emily N. Reinke, Elijah J. Petersen, John D. Gordon, Rick Uhl, Valerie H. Adams, Diego Rua, Victor J. Johnson, Gary R. Burleson, Judy Strickland, Robert Gutierrez, Catherine S. Sprankle, Tripp LaPratt, David M. Lehmann, Dori R. Germolec and Nicole C. Kleinstreuer
Toxics 2026, 14(6), 511; https://doi.org/10.3390/toxics14060511 - 11 Jun 2026
Viewed by 417
Abstract
The electrophilic allergen screening assay (EASA) uses small-molecule probes as surrogates for skin proteins to measure hapten protein carrier complex formation, Key Event (KE) 1 in the adverse outcome pathway for skin sensitization. Although multiple assays are accepted for this purpose, the EASA [...] Read more.
The electrophilic allergen screening assay (EASA) uses small-molecule probes as surrogates for skin proteins to measure hapten protein carrier complex formation, Key Event (KE) 1 in the adverse outcome pathway for skin sensitization. Although multiple assays are accepted for this purpose, the EASA has higher throughput and needs less specialized equipment than other commonly used KE1 assays. This validation study assessed transferability of the EASA to naïve laboratories and within- and between-laboratory reproducibility. The predictive capacity of the assay in relation to reference data both from the murine local lymph node assay (LLNA) and, where available, human predictive patch tests, was estimated. The validation study was conducted using performance standards developed for methods that are under evaluation for inclusion in relevant test guidelines. The within- and between-laboratory reproducibility were cumulatively 96% and 85%, respectively. These scores exceeded the performance standard thresholds of 80%. Compared to reference LLNA data, the cumulative EASA results from the four laboratories had an overall sensitivity of 87%, specificity of 76%, and accuracy of 83%. The consensus results among the four laboratories had an overall sensitivity of 85%, specificity of 80%, and accuracy of 83%. For human reference data, the cumulative EASA results had an overall sensitivity of 81%, specificity of 76%, and accuracy of 70%. The EASA predicted sensitizers very well, although it had a slightly higher rate of misclassifying some negative test chemicals as positive with a specificity below the performance standards criterion of 80%. Our findings support further exploring use of the EASA in defined approaches to identify potential skin sensitizers. Full article
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16 pages, 19516 KB  
Article
Interpretable Skin Cancer Identification Using a Hybrid Deep Learning and XAI Framework on HAM10000
by Bhagyashri S. Sonune, R. Udaya Kumar, K. Sankar, Puja S. Agrawal, Shon G. Nemane, Dhiraj P. Tulaskar, Manish Bhaiyya and Madhusudan B. Kulkarni
Bioengineering 2026, 13(6), 677; https://doi.org/10.3390/bioengineering13060677 - 11 Jun 2026
Viewed by 440
Abstract
Deep learning-based automated classification of dermatoscopic skin lesions has exhibited promising potential in diagnostics. However, two prominent issues need to be addressed before achieving high-quality diagnostic tools: inconsistent performance in the case of imbalanced classes and poor clinical interpretability of models. Even though [...] Read more.
Deep learning-based automated classification of dermatoscopic skin lesions has exhibited promising potential in diagnostics. However, two prominent issues need to be addressed before achieving high-quality diagnostic tools: inconsistent performance in the case of imbalanced classes and poor clinical interpretability of models. Even though some studies have attempted to leverage both deep and shallow learning by combining pretrained convolutional neural networks (CNNs)-based feature extraction with classical machine learning (ML) models, very few of them systematically explore several model combinations based on various clinically important metrics, such as F1-score, precision, recall, accuracy, etc., and utilize decision threshold calibration techniques. In this research, we present an evaluation of a systematic framework with threshold calibration for the comparison of several hybrid models on seven-class skin lesion classification (multi-class) on the HAM10000 dataset. In particular, we used deep features extracted from three pretrained CNN architectures, i.e., DenseNet201, InceptionV3 and EfficientNet-B4. These deep features were used as inputs for six different classical classifiers. As a result, we obtained 18 comparable hybrid models that were then systematically compared by multiple clinically relevant metrics: accuracy, macro-precision, macro-recall, macro-F1, ROC-AUC, Precision-Recall-AUC, and log loss. Also, fold-wise optimization of decision thresholds was performed, which was based on the maximization of the macro-F1 score. Finally, we found out that DenseNet201 with an SVM-RBF classifier yielded the highest performance among all 18 tested models, showing 90.88% accuracy, 90.7% macro-precision, and 0.921 ROC-AUC. To analyze the clinical plausibility, top-performing models were further explained with explainable artificial intelligence (XAI) techniques: Grad-CAM, LIME and Occlusion Sensitivity. Results show that the most successful models concentrated mostly on lesion-specific areas. Overall, this study contributes a reproducible hybrid-XAI model-selection framework rather than a single black-box classifier, supporting more transparent and clinically meaningful skin lesion diagnosis. Full article
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22 pages, 1891 KB  
Article
Systematic Failure of Vision Transformers in Imbalanced Skin Lesion Classification
by Serra Aksoy, Pinar Demircioglu and Ismail Bogrekci
Dermato 2026, 6(2), 22; https://doi.org/10.3390/dermato6020022 - 11 Jun 2026
Viewed by 148
Abstract
Background/Objectives: Vision Transformers (ViTs) have demonstrated impressive performance in dealing with large-scale natural image datasets. They have started to be used in medical image classification problems as well. However, how they behave under real-world conditions, such as data scarcity and extreme class imbalance, [...] Read more.
Background/Objectives: Vision Transformers (ViTs) have demonstrated impressive performance in dealing with large-scale natural image datasets. They have started to be used in medical image classification problems as well. However, how they behave under real-world conditions, such as data scarcity and extreme class imbalance, has not been well investigated. In this study, we examine the feasibility of using a standard Vision Transformer Base model that learned from scratch how to classify skin lesion images into multiple classes using the ISIC 2019 dataset. Methods: The Vision Transformer architecture was trained from scratch using stratified splitting of the data, class-balanced cross-entropy loss, multi-seed initialization, and control of hyperparameters such as patch size and dropout rate. The evaluation of the Vision Transformer architecture was performed using a hold-out test set with metrics such as accuracy, macro-F1, weighted-F1, and analysis of the confusion matrix. Results: Across all configurations, the training exhibited substantial instability and consistent overfitting behavior, with an average accuracy gap between validation and test sets of 22.7%. Test accuracy ranged from 8.0% to 37.8%, showing high sensitivity to initialization. For minority classes, the F1-score remained very low (F1 < 0.05) even though the classes were balanced in the loss function. Conclusions: The results indicate that a standard ViT-Base model trained from scratch can exhibit pronounced instability and a tendency toward majority-class bias when applied to multi-class skin lesion classification under conditions of extreme class imbalance and data scarcity. The findings point to the limitations of using simple transformer models without pre-training or other forms of inductive bias in scarce data settings. Full article
(This article belongs to the Special Issue Melanoma: Updates and Path Forward)
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13 pages, 15008 KB  
Article
Immunohistochemical Analysis of pH-Sensitive TRPV5 in Common Skin Tumors
by Sophia Victoria Weiß, Judith Heider, Dennis Niebel, Katja Evert, Florian Zeman, Marietta von Süßkind-Schwendi, Daniel Schiltz, Tobias Ettl, Christoph Brochhausen and Stephan Schreml
Int. J. Mol. Sci. 2026, 27(12), 5287; https://doi.org/10.3390/ijms27125287 - 11 Jun 2026
Viewed by 217
Abstract
Transient receptor potential vanilloid 5 (TRPV5) is a calcium- and pH-sensitive ion channel. It plays a role in tumor biology and cellular calcium homeostasis. Due to the inverse pH gradient in solid tumors (extracellular acidosis and increased intracellular pH), TRPV5 is interesting as [...] Read more.
Transient receptor potential vanilloid 5 (TRPV5) is a calcium- and pH-sensitive ion channel. It plays a role in tumor biology and cellular calcium homeostasis. Due to the inverse pH gradient in solid tumors (extracellular acidosis and increased intracellular pH), TRPV5 is interesting as a signaling molecule in tumors, as the altered pH in the tumor microenvironment (TME) impacts tumor growth and metastasis. This is the first study to analyze the expression of TRPV5 in common skin cancers, i.e., basal cell carcinomas (BCC), squamous cell carcinomas (SCC), malignant melanomas (MM) and melanocytic nevi (MCN). The results showed a significantly lower expression of TRPV5 in BCC than in all other tumor entities analyzed. While less than half of the BCC were positive for TRPV5, SCC, MM, and MCN exhibited a high level of positive staining results. These results suggest that TRPV5 may especially help as a novel marker in the differentiation of SCC from BCC. The low expression of TRPV5 in BCC, a rarely metastatic tumor, may also point to a role of TRPV5 in the progression of epithelial skin tumors. Further functional studies, however, are needed to clarify the exact role of TRPV5 in skin tumors. Full article
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Article
Sensitive Skin Improvement Through Bioinformatics-Identified Cosmetic Ingredients That Regulate Transcriptome-Derived Biomarkers
by Seo Hyeong Kim, Ji Hye Kim, Ji Min Shin, Yoon Mi Choi, Da Som Kim, Su Min Seo, Eun Young Jang, Sung Jae Lee, Jin-Muk Lim, Minsoo Han, Do Hyeon Jeong and Kwang Hoon Lee
Biomolecules 2026, 16(6), 843; https://doi.org/10.3390/biom16060843 - 9 Jun 2026
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Abstract
Sensitive skin is characterized by hypersensitivity to normal stimuli, and objective diagnostic tools and treatments are still limited. Currently, cosmetics for sensitive skin are developed through the exclusion of known irritants rather than investigation into the underlying mechanisms of sensitivity. In this study, [...] Read more.
Sensitive skin is characterized by hypersensitivity to normal stimuli, and objective diagnostic tools and treatments are still limited. Currently, cosmetics for sensitive skin are developed through the exclusion of known irritants rather than investigation into the underlying mechanisms of sensitivity. In this study, we developed an integrated pipeline combining transcriptome analysis via microneedle-based skin sampling (MISSM), bioinformatics, in vitro validation, and clinical assessment to identify sensitive skin-associated inflammatory biomarkers and cosmetic ingredients that regulate them. Candidate biomarkers and matched cosmetic ingredients were identified from transcriptomic data and validated in lactic acid-stimulated HaCaT and human dermal fibroblasts via qRT-PCR. A prototype emulsion was developed and evaluated in a 4-week open-label pilot clinical trial with longitudinal molecular monitoring via MISSM. After lactic acid stimulation, sensitive skin-associated biomarkers (MCOLN1, CYR61, PMAIP1, PTGS2, and HMGB2) were significantly upregulated in both cell types, and cosmetic ingredients that regulate these biomarkers were confirmed in vitro. The emulsion prototype demonstrated hypoallergenicity in a primary irritation test. In the pilot clinical trial, target biomarker expression was significantly reduced in MISSM-derived samples, with improvements in skin hydration, barrier function, redness, and sensory reactivity also observed. This integrated pipeline will enable the discovery of inflammatory biomarker-regulating cosmetic ingredients, with potential applicability to various inflammatory skin conditions. Full article
(This article belongs to the Section Molecular Biomarkers)
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