Background/Objectives: Skin cancer is becoming increasingly common due to increasing risk factors such as excessive UV radiation, genetic predisposition, fair skin, and a history of sunburn. Melanoma accounts for only 1% of cases but causes the majority of skin cancer deaths. Dysplastic nevi (DN) are important precursors of melanoma. The aim of this study was to investigate the influence of these risk factors on the pathogenesis, incidence, and stage of skin cancer.; Methods: The study included 591 patients aged 18 to 64 who visited the Clinic in 2022–2023 for skin examinations. Each patient completed a questionnaire regarding the risk factors for melanoma and atypical melanocytic nevi and then underwent a dermatoscopic examination of the whole body using a digital videodermatoscope. Statistical analysis of the collected data was performed.; Results: Dermatoscopic examination revealed a lesion suggestive of melanoma in 1,69% of the patients. Risk factors for developing melanoma included male gender, family history of melanoma, number of skin moles, sunburns in childhood, sun-dependent hobby, using tanning bed, using cream with low SPF, not avoiding sun exposure and co-occurrence of actinic keratosis.; Conclusions: Risk factors for melanoma and dysplastic nevi are still common among patients, but the situation has been improving over the years. Early intervention and education on sun safety can play pivotal roles in reducing the incidence of atypical moles and potentially preventing malignant transformations. Keywords: dysplastic nevum; melanoma; risk factors; dermoscopy; prevention

The management of skin cancer presents challenges in reconstructive surgery to achieve the best patient outcome and rapid wound healing. The most used antiseptic in pre and post operative care is Povidone Iodine solution. However, valid antiseptic alternatives should be considered. The primary endpoint of our study was to achieve the best healing in patients receiving fluorescein solution versus two comparator arms (Eosin and Povidone-Iodine).182 patients were enrolled and divided into three randomized groups according to the type of antiseptic solution received: Fluorescein (n = 63), Eosin (n= 60), and Povidone-Iodine (n = 59). To assess the endpoint of our study the ASEPSIS score was used to objectively evaluate graft healing. Results of the ASEPSIS score for each group were analyzed. The comparison demonstrated that there was no statistically significant difference among the three groups regarding the endpoint of our study, thus between fluorescein and povidone-iodine (p = 0.89), eosin and fluorescein (p = 0.54), and eosin and povidone-iodine (p = 0.81). Patients responded positively to the use of the Fluorescein antiseptic solution, although no more than the others. This study suggests that this type of antiseptic can be successfully used in skin graft management.

Melanin content significantly influences the skin-lightening effects of active ingredients, with inhibition of melanin synthesis contributing to skin-lightening effects. This study evaluates the effects of novel cyclopeptide CHP-9 as a safe and potent human tyrosinase inhibitor. CHP-9 showed a significant inhibition rate of approximately 28.57% at 1% concentration. The melanin formation assay, upon exposure to CHP-9 alone, resulted in a reduction of cellular melanin content from 30.90±1.13 μg/mL to 23.51±1.14 μg/mL. Additionally, in silico molecular docking experiments were conducted to verify the tyrosinase inhibitory activity of the cyclopeptide CHP-9 on tyrosinase and it was observed that hydrogen bonding is pivotal in the binding affinity of CHP-9 with the target enzyme in docking. These results suggest that the cyclopeptide CHP-9 may serve as a valuable bioactive compound for skin-lightening agents in cosmetics applications, specifically in reducing melanin production.

Skin cancer is one of the most prevalent cancers worldwide, with an increasing incidence. Skin cancer is typically classified as melanoma or non-melanoma skin cancer. Melanoma, despite being much less common than basal or squamous cell carcinomas, is the most deadly, with nearly 8,300 Americans expected to die from melanoma each year. Biopsies are currently the gold standard in diagnosing melanoma; however, they can be invasive and expensive and inaccessible to lower-income individuals. Currently, suspicious lesions are triaged with image-based technologies, such as dermatoscopy and confocal microscopy. While these techniques are useful, there is wide inter-user variability and minimal training for dermatology residents on how to properly use these devices. The use of artificial intelligence (AI)-based technologies in dermatology has emerged in recent years to assist in the diagnosis of melanoma that may be more accessible to all patients and more accurate than current methods of screening. This review explores the current status of the application of AI-based algorithms in the detection of melanoma, underscoring its potential to aid dermatologists in clinical practice. We will specifically focus on AI’s application in clinical imaging, dermoscopic evaluation, algorithms that can distinguish melanoma from non-melanoma skin cancers, and in-vivo skin imaging devices.

Cutaneous metastases from clear cell renal carcinoma (ccRC) are uncommon and often indicate a poor prognosis. These metastases typically occur on the scalp, face, and trunk, and they can be difficult to diagnose due to their resemblance to benign dermatological tumors. We report the case of a 56-year-old patient with a history of ccRC (TNM stage 4) who was referred to our Dermatology department with two rapidly enlarging, painful lesions on the left jawline and scalp, which had developed one month and one week earlier, respectively. On examination, the lesions appeared as well-defined, round to oval plaques with a central ulceration and a peripheral red rim. Dermoscopic examination revealed a structureless pink to orange pattern, atypical central vessels, and irregular linear vessels in a corona-like arrangement. Despite the patient's stable oncological treatment for six months, pain management had recently included paracetamol, tramadol, and NSAIDs. Given the recent medication changes and the clinical presentation, differential diagnoses initially included drug-induced eruptions such as erythema multiforme or fixed drug eruption. However, a biopsy of the facial lesion revealed immunohistochemical positivity for CD10, CAIX, and PAX8, confirming the diagnosis of metastatic ccRC with sarcomatoid differentiation. Unfortunately, despite continued targeted therapies and palliative care, the patient’s condition deteriorated rapidly, leading to death two months later. This case highlights the aggressive progression and poor prognosis associated with cutaneous metastases from renal cell carcinoma, particularly once the skin is involved.

Background: Fabry disease is a rare, X-linked, lysosomal disorder caused by pathogenic variants in GLA and consequent deficient activity of alpha-galactosidase A, resulting in glycosphingolipid storage. Although many systemic manifestations of the disease have been documented, the association between Fabry disease and erysipelas has not previously been reported. Objective: To describe a case series of thirteen patients with Fabry disease and erysipelas and identify potential predisposing factors in this population. Patients and Methods: We retrospectively studied a cohort of 223 French patients with a confirmed molecular and enzymatic diagnosis of Fabry disease. Results: Twelve of the 223 patients with Fabry disease had experienced one or more episodes of erysipelas for a total of 70. All 12 patients had classic Fabry disease. There were ten males and two females, one of whom had highly skewed X chromosome inactivation silencing the wild type GLA allele. Lymphedema of the lower legs (10/11), male gender (10/12), and clinically advanced classic Fabry disease (11/12) were the characteristics identified in patients who experienced erysipelas. No patient with the later-onset form of Fabry disease had any episode of erysipelas. Conclusion: Our findings suggest that clinicians should be aware of the risk of erysipelas in patients with Fabry disease and promptly prevent or treat any skin wound or infection in those with lower limbs lymphedema.

Non-melanoma skin cancers (NMSCs), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), are highly prevalent and a significant cause of morbidity. Image-guided su-perficial radiation therapy (IGSRT) uses integrated high-resolution dermal ultrasound to improve lesion visualization, but it is unknown whether efficacy varies by histology. This large retro-spective cohort study was conducted to determine the effect of tumor histology on freedom from recurrence in 20,069 biopsy-proven NMSC lesions treated with IGSRT, including 9,928 BCC (49.5%), 5,294 SCC (26.4%), 4,648 SCCIS (23.2%), and 199 lesions with ≥2 NMSCs (1.0%). Freedom from recurrence at 2, 4, and 6 years was 99.60%, 99.45%, and 99.45% in BCC; 99.58%, 99.49%, and 99.49% in SCC; and 99.96%, 99.80%, and 99.80% in SCCIS. Freedom from recurrence at 2, 4, and 6 years following IGSRT did not differ significantly comparing BCC vs. non-BCC or SCC vs. non-SCC but were slightly lower among SCCIS vs. non-SCCIS (p = 0.002). There were no significant differences in freedom from recurrence when stratifying lesions by histologic subtype. This study demonstrates that there is no significant effect of histology on freedom from recurrence in IGSRT-treated NMSC except in SSCIS. These findings support IGSRT as a first-line therapeutic option for NMSC regardless of histology.

Atopic dermatitis (AD) impacts various aspects of patients' lives. The most reported factors affecting clinical burden are itching and psychological disturbances (e.g., depression, anxiety or even suicidal thoughts). Also, AD affects school and work-related activities, even career advancement. Thus, AD patient management and decisions regarding advanced/systemic therapy are complex, requiring consideration of multiple disease-related factors: age; disease severity; patient medical history and comorbidities; previous topical therapy use and any adverse reactions; treatment efficacy concerns; patient preferences, expectations and fears; pregnancy planning; ability and willingness to adhere to the treatment regimen; impact on intimate and social relationships and work/school performance; and treatment-related risks and any associated psychological or psychiatric issues. Current guidelines and systematic reviews support the safety and efficacy of systemic therapy (conventional, biologics, JAK inhibitors) for treating AD. When topical therapy and phototherapy are insufficient, conventional systemic therapies (cyclosporine, methotrexate, azathioprine) are used, or advanced treatments can be introduced, like biologics and JAK inhibitors (baricitinib, upadacitinib, and abrocitinib), which have been approved for moderate to severe AD. Additional biologics being evaluated in clinical trials include lebrikizumab, nemolizumab, eblasakimab, and OX40/OX40L. Ultimately, there is great value in a personalized and multidisciplinary approach to AD management, as has been supported by numerous studies and clinical practice over time.

The human scalp is a common site of skin cancer in humans, with non-melanoma skin cancer being exceedingly common. In this review, two dermatologists with extensive experience in cutaneous oncology will discuss unique features of the epidemiology of cancer of the scalp. Clinical observations on these common skin cancers lead to insight into the pathogenesis and potential prevention and treatment of cutaneous scalp neoplasia. Our hypothesis is that the presence of hair protects against the development of skin cancer, but not by serving as a physical shield, but rather by providing a continuous IL-17 biased immunosurveillance. Loss of hair allow release from immunosurveillance, resulting in expansion of neoplastic cells towards skin cancer. Both hair follicles and metabolic changes in stroma allow permissiveness for tumor promotion.

This study reports a 50-year-old patient presented with eczematous drug-eruption induced by selpercatinib after the treatment of non-small cell lung cancer (NSCLC). The patient has symmetric erythematous papules and plaques all over the body with dry, scaly skin accompanied by severe pruritus and visible scarring. After systemic treatment with glucocorticoids, the skin lesions of the patient were well reduced. Currently, the medical literature on the incidence of selpercatinib-induced cutaneous eczematous reactions and their clinical management is scarce. Therefore, this study provides novel evidence for the treatment of selpercatinib-induced cutaneous eczematous reactions.

Ustekinumab is a fully human IgG1k monoclonal antibody that binds with high affinity and specificity to the p40 subunit of interleukins (IL-) 12 and 23, inhibiting their activity by preventing binding to their receptors. The European extension of the patent (Supplementary Protection Certificate) of ustekinumab expired on July 20, 2024. Biosimilar alternatives to ustekinumab are now an additional option for treating patients. The efficacy data for this drug in moderate-to-severe psoriasis, obtained both from clinical trials and indirect comparisons through meta-analyses, are superior to those of etanercept and adalimumab, and its safety profile is more favorable than that of tumor necrosis factor (TNF) inhibitors. Several ustekinumab biosimilars have already been approved by regulatory agencies: between October 2023 and July 2024, Wezlana® (Amgen ABP 654), Uzpruvo® (Alvotech AVT04) and Pyzchiva® (Samsung/Bioepis SB17) have been approved by both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). SteQeyma® (Celltrion Healthcare CT-P43) has been approved by the EMA in August 2024. Several other potential biosimilar candidates are under development, including FYB202 (Formycon), BAT2206 (Bio-Thera), DMB-3115 (Dong-A ST), QX001S (Qyuns Therapeutic), BFI-751 (BioFactura), NeuLara (Neuclone), ONS3040 (Oncobiologics), and BOW090 (Epirus Biopharmaceuticals). In most cases, these monoclonal antibodies are expressed in cell lines (e.g. Chinese Hamster Ovary, CHO) different from those used for the originator (Sp2/0 spleen cell murine myeloma); of note, the cell line of origin is not a requirement for biosimilarity in the totality-of-evidence comparison exercise and may facilitate the production and reduce the immunogenicity of biosimilars originated in CHO cultures. This narrative review will summarize the available data on characteristics of the full comparability exercises and comparative clinical trials of these drugs.

Species of the genus Kalanchoe have a long history of therapeutic use in ethnomedicine linked to their remarkable medical properties. One of them is Kalanchoe blossfeldiana succulents occurring in tropical regions. Despite the great interest in this plant, there are no reports about its therapeutic effects on the skin. In this study, the antioxidant properties and skin permeation of a topical hydrogel containing K. blossfeldiana ethanol extract was assessed. Additionally, the content of active compounds in the K. blossfeldiana extract was evaluated by UHPLC-MS and HPLC-UV. The extract was analysed with three antioxidant assays: ABTS, DPPH and FRAP. Furthermore, antielastase and antihialuronidase properties of the tested extract were assessed. The ex vivo penetration studies were performed using the Franz diffusion cells. The obtained results show that antioxidant properties of K. blossfeldiana extract were similar to ascorbic acid, while antielastase and antihialuronidase tests indicated strong antiaging and anti-inflammatory activity (IC50 was 26.8 ± 0.13 and 77.31 ± 2.44 µg/mL, respectively). Moreover, active ingredients contained in K. blossfeldiana extract penetrated through human skin and accumulate in it. In conclusion, the hydrogel containing K. blossfeldiana extract can be considered as an interesting and new alternative to dermatologic and cosmetic preparations.

The enormous diversity of hair fibers found in human population is striking, while the basic structure of human fibers is often the same! But why do some fibers curl? Curling is related to the machinery and processes that produce different keratin filament orientation in relation to the axis of hair growth, influenced by developmental and molecular control. It is established that a curly hair shaft is produced by a curved hair follicle that have an angulated dermal implantation, with a bulb bent in the shape of golf club, while the outer root sheath is dissymmetrical; have an outer side that is convex bulging and thin and a concave side in which the cells express alpha-smooth muscle protein reflecting internal mechanical force. Yet, the exact cause of hair curling is not known. All the previous studies were short of impacting curly hair treatment. My hypothesis is that the curling mechanical force is generated by a hypersensitive contracted Arrector Pili muscle (APM) of the hair follicle. In curly hair, each APM fiber is shortened; pulling its attachment spot upward towards the epidermis and obliquely or laterally; curling the outer root sheath to produce the curved follicle described above. This contraction has the influence at a time when the young hair root is being formed and keratin microfibrils are being oriented and packed. APM is a multi-unit muscle wherein each fiber contracts independently to create the enormous diversity of curly hair types. APM contraction can be modulated by oral administration of selective smooth muscle relaxing treatment that relax the curved follicle from within. Further studies are needed to confirm the role of APM in shaping curly hair follicle including AI studies, i.e., computer-aided target identification to demonstrate APM active site that can interact with herbal small molecules.

Skin cancers, including melanoma, and non-melanoma- cutaneous basal cell carcinoma and cutaneous squamous cell carcinoma, are a diverse group of malignancies characterized by variations in their molecular and cellular features. Melanoma is a highly heterogenous tumor characterized by the dysregulation of a myriad of cell-cycle associated signaling pathways. In the non-melanoma skin cancers, such as cutaneous basal and cutaneous squamous cell carcinoma, the role of cyclin-dependent kinases and cyclins remains poorly understood with relatively limited investigation. Although revolutionary therapies against diverse molecular targets have been introduced over the last decade leading to significant prognostic benefit, advanced stages of melanoma remain exceptionally difficult to treat. The three cancers are united by evidence of stem-like, cancer initiating cell populations which dictate highly dynamic microenvironments and rely on disrupted cell cycle signaling to support treatment resistance and cancer progression. Potential of cell cycle targeting in skin cancer in underexplored in terms of identification of specific mechanisms supporting the maintenance of skin cancer stem cell pools and could offer potential targets to advance the therapy in these malignancies. In this review, we comprise the existing data on major cell of cell cycle regulators in skin cancer, the regulation of cancer stem cells and most recent developments and limitations surrounding cell cycle-targeted therapies, with a focus on the application of CDK inhibitors.

Introduction & Objectives: Blood cells-(BC)count derived parameters have been inves-tigated in systemic inflammation, cancer, and various cutaneous diseases. Little is known about their usefulness in trichology, especially as prognostic and therapeutic biomarkers. We conducted a retrospective study on patients with not-cicatricial alopecia to assess differences in BC-count. Materials & Methods: Patients with alopecia areata (AA), telogen effluvium (TE), androgenic alopecia (AGA), psoriasis and hidradenitis suppurativa (HS) were included in the study. Baseline complete BC-count and derived parameters (i.e. NLR, PLR, MLR, SII; PIV) were recorded and analyzed for each patient and at different timepoints for AA patients on systemic agents. Results: 170 patients fulfilled inclusion criteria. BC-count and derived values were similar across the not-cicatricial alopecia groups, while general differences were observed compared to psoriasis and HS. TE displayed a closer inflammatory signature to psoriasis with respect to CRP, NLR, MLR, SII and PIV. We also found a significant reduction in RBCs in severe versus patchy-AA and an increase of SII in acute versus chronic AA. Modulation of platelet number and volume could be used as therapeutic marker in AA. Conclusions: In our experience, the BC-count and its derived parameters could represent potential tools in AA and TE.

Background/Objectives: Pityriasis rosea (PR) is a self-limiting exanthematous disease associated with the endogenous reactivation of human herpesvirus (HHV)-6 and HHV-7. Classically, the lesions gradually resolve leaving no sequelae. Therefore, the best treatment is reassuring the patient and suggesting a resting period. However, atypical PR cases characterized by extensive, persistent lesions and systemic symptoms may impact the patient’s quality of life, and, therefore, a treatment can be prescribed. There is limited evidence on the comparative effectiveness of pharmacological treatments for PR, therefore we performed a network meta-analysis to compare these interventions. Methods: Overall, 12 randomized control trials (RCTs) were identified. The outcomes were itch resolution and rash improvement. Results were expressed as risk ratio (RR) and 95% confidence interval (CI). We also calculated the relative ranking of the interventions for achieving the aforementioned outcomes as their surface under the cumulative ranking (SUCRA). Results: On network meta-analysis, only oral steroids and the combination of oral steroids+antihistamine resulted significantly superior to the placebo in terms of itch resolution (RR 0.44, CI 0.27-0.72 and RR 0.47, CI 0.22-0.99). Oral steroids resulted as the best treatment (SUCRA 0.90) for itch resolution. In terms of rash improvement, only acyclovir and erythromycin resulted significantly superior to placebo (RR 2.55, CI 1.81-3.58 and RR 1.69, CI 1.23-2.33), and acyclovir outperformed all the other tested interventions. Consequently, acyclovir ranked as the best intervention (SUCRA score 0.92). Conclusions: Acyclovir represents the best option in PR patients with extensive, persistent lesions or systemic symptoms. Steroids and antihistamines seemed the best treatment for itch resolution.

Breast cancer remains a significant health concern worldwide, necessitating early detection and treatment. The rapid appearance or a change in the shape of skin lesion on the breast or just of the nipple-areola complex(NAC), especially if it is unilateral needs to be evaluated. Several primary or secondary tumours such as inflammatory skin lesions can affect this body area. Ultrasound, mammography, or magnetic resonance imaging (MRI) are the most used non-invasive diagnostic techniques for breast cancer, but in recent years reflectance confocal microscopy (RCM) and optical coherence tomography have emerged as additional tools to diagnose cases characterized by cutaneous changes.The introduction of new techniques such as reflectance confocal microscopy (RCM), may open new perspectives in the non-invasive diagnosis of mammary paget disease (MPD). RCM is a non-invasive diagnostic technique that allows high-resolution images of the skin at microscopic level in real time. It is non-invasive, painless and repeatable, making it a valuable tool in the early diagnosis and monitoring of skin diseases. We describe an atypical clinical presentation of mammary paget disease early diagnosed by reflectance confocal microscopy evaluation.

Facial artificial intelligence (AI) skincare applications offer patients simple and effective means of obtaining quantitative information regarding their skin characteristics. Advances in AI may facilitate dermatologic assessments by providing accurate and reliable scores for common skin concerns. The objective of our study was to assess the effect of different lighting on facial characteristic scores produced by an iPad-based AI skin analysis system. Participants were recruited from dermatology clinics. Images were captured using an AI skincare app in different lighting settings: below average lighting (L1), standard room lighting (L2), and enhanced studio lighting (L3). Raw scores produced for twenty facial characteristics were recorded. Higher raw scores indicated better skin health. Scores were compared between the three lighting conditions. Below average lighting had the highest mean raw scores for facial characteristics (79.67 ±10.56). Mean raw scores were lowest for enhanced studio lighting conditions (74.43 ±10.24). The difference in scores produced by the different lighting conditions was not statistically significant (p=0.79). Enhanced studio lighting did not appear necessary as scores were similar without the additional lighting. The application used in our study may serve as a cost-effective and convenient tool both within and outside clinical settings allowing enhanced quantitative analysis of facial characteristics.

Diabetic wound (DW) is the most devastating complication resulting in significant mortality and morbidity in diabetic patients. Although the pathophysiology of DWs is multifaceted, evidence revealed that prolonged inflammation with infections, extracellular matrix (ECM) degradation and unnecessary NETosis impair DW healing. This theoretical problem commands the necessity of developing a novel strategy focused on targeting the 'specific' molecular modalities of DW. The primary culprits, matrix metalloproteinase (MMP)-9 and protein kinase C (PKC)-βII, are responsible for impaired angiogenesis, NETosis, and ECM degradation. Thus, there is reinvigorated interest in identifying selective inhibitors for the effective management of DW. The current study exemplified human β-defensin-2 (HBD-2), a biological macromolecule as a dual-inhibitor of MMP-9 and PKC-βII using protein-protein docking and molecular dynamics simulation studies. Residue-residue interactions and binding affinity were investigated using Z-dock. Chemical bonding behavioral changes, structural dynamics, and functional changes were determined using GROMACS by analyzing RMSD, ROG, RMSF, SASA, FEL, and PCA. Overall, the data analysis revealed that HBD-2 possesses strong binding affinity and stability against MMP-9 and PKC-βII, which can be an ideal therapeutic for the accelerated healing of DW. The study provides valuable insights into the molecular mechanisms underlying hBD-2's potential therapeutic effects, offering new avenues for the development of innovative treatment strategies. The clinical relevance of our findings lies in their potential to inform the development of new approaches for diabetic wound management, addressing a significant healthcare concern.

To verify the efficacy of placental extracts (Pla-Ext) and human mesenchymal stem-cell-derived exosomes (hMSC-Exo) against human skin aging, we investigated the human dermal fibroblast (HDF) response following hMSC-Exo and Pla-Ext treatment and whether they elicited resistance to damage when HDFs were subjected to several types of aging stresses. The effect of hMSC-Exo alone, the combined effect of Pla-Ext and hMSC-Exo, and the effect of hMSC-Exo (Pla/MSC-Exo) recovered from cultures with Pla-Ext added to hMSC were verified using collagen, elastin, and hyaluronic acid synthase mRNA levels for each effect. Cells were subjected to photoaging (UV radiation), glycation (glycation end product stimulation), and oxidation (H2O2 stimulation) as HDF stressors. Pla-Ext did not significantly affect normal skin fibroblasts considering intracellular parameters; however, a pro-proliferative effect was observed. Pla-Ext induced resistance to several stresses in skin fibroblasts (UV irradiation, glycation stimulation, H2O2 stimulation) and inhibited reactive oxygen species accumulation following H2O2 stimulation. Although the combined efficacy of hMSC-Exo and Pla-Ext was unclear, some changes resulted in senescence stress resistance due to preconditioned hMSC-Exo stimulated by Pla-Ext. This suggests that Pla-Ext supplementation may cause some changes in the surface molecules or hMSC-Exo content (e.g., microRNA).

Background: The skin prick test (SPT) is used to diagnose sensitization to antigens. This study proposes a deep learning approach to infer wheal dimensions, aiming to reduce dependence on human interpretation. Methods: A dataset of SPT images (n=5844) was used to infer a convolutional neural network for wheal segmentation (ML model). Three methods for inferring wheal dimensions were evaluated: the ML model; the standard protocol (MA1); and approximation of the area as an ellipse using diameters measured by an allergist (MA2). The results were compared with assisted image segmentation (AIS), the most accurate method. Bland-Altman, distribution analyses, and correlation tests were applied to compare the methods. The study also compared the percentage deviation among these methods in determining the area of wheals with regular geometric shapes (n = 150) and with irregular shapes (n=150). Results: The Bland-Altman analysis showed that the difference between methods was not correlated with the absolute area. The ML model achieved a segmentation accuracy of 85.88% and a strong correlation with the AIS method (ρ=0.88), outperforming all other methods. Additionally, MA1 showed significant error (13.44±13.95%) for pseudopods. Conclusions: The ML protocol can potentially automate the reading of SPT, offering greater accuracy than the standard protocol.

The current research is focused on the discovery and optimization of an effective cosmetic carrier of alpha-bisabolol as a first step in the development of a cosmetic product with cleansing and antimicrobial action for facial skin hygiene. A micellar solution of Poloxamer 407 was selected as a cosmetic base because of the good washing ability, easy application, and high tolerability of this polymeric surfactant. The solubilization capacity of a 5% micellar solution with respect to α-bisabolol was investigated by applying varying solubilization techniques and increasing concentrations of the oily active substance. The test samples were subjected to an accelerated physical stability test, viscosimetry, dynamic light scattering (DLS), electrophoretic light scattering (ELS), foamability test, and antimicrobial screening. In the course of research, the advantage of the film-hydration method over direct solubilization was demonstrated by the narrower size distribution and smaller hydrodynamic size of the micellar nano-carriers (ranging from 29.02-116.5 nm) and the respective higher physical stability of the dispersions. The optimized composition was found to possess a suitable for application on large skin areas viscosity in the temperature range from 20°C to 40°C (3.4-2.3 mPa.s). Preservation of the washing capacity of the micellar solution in the presence of solubilized α-bisabolol was established. The active composition demonstrated inhibitory activity against Staphylococcus aureus and Escherichia coli, and fungicidal activity against Candida albicans. The study concludes that the optimal concentration of α-bisabolol to be solubilized in a 5% Poloxamer 407 micellar solution by the film-hydration technique is 1% considering the desirable physical endurance and antimicrobial activity.

Psoriasis is a multifactorial, chronic, and inflammatory disease that severely impacts patients’ quality of life. The disease is caused by genetic irregularities affected by the epigenetic and environmental factors. Some of these factors may include the seasonal changes, such as solar radiation, air pollution and humidity, and changes in circadian rhythm, especially in the temporal and polar zones. Thus, some psoriasis patients report seasonal variability of symptoms. Through a comprehensive review, we aim to delve deeper into the intricate interplay between seasonality, environmental factors, and the genetic and epigenetic landscape of psoriasis. By elucidating these complex relationships, we strive to provide insights that may inform targeted interventions and personalized management strategies for individuals living with psoriasis.

Ichthyosis is a genetic skin disorder marked by hyperkeratosis, pruritus, and scaling. This case study explores a potential association between ichthyosis and scalp paresthesia, a symptom not commonly linked with this dermatological condition. In a longstanding history of ichthyosis patients, we detail the therapeutic use of fluocinolone, a synthetic corticosteroid, in managing scalp paresthesia. The effectiveness of fluocinolone in reducing paresthesia episodes underscores its potential as a critical component in the symptomatic treatment of this complex interplay between skin and neurological symptoms. This case prompts a broader discussion on the need for increased awareness and education among healthcare providers regarding the diverse manifestations of ichthyosis. Enhanced understanding and recognition of these associations can lead to improved patient counseling, tailored management strategies, and, ultimately, better quality of life for individuals affected by ichthyosis.

Introduction Image Guided Superficial Radiation Therapy (IGSRT) is a novel technology which combines traditional superficial radiation therapy (SRT) with high resolution dermal ultrasound (HRDUS) to treat non-melanoma skin cancers (NMSC). Since development, IGSRT use has expanded dramatically in outpatient clinics. We review the IGSRT literature and state of the art operating principles in US dermatologic practices. Materials and Methods A literature search of electronic databases (Medline, Pubmed, Cochrane Library, Science Direct) combined with various authors’ published and unpublished documents, procedures and clinical experience with IGSRT were synthesized for this paper. Results Studies have demonstrated IGSRT consistently delivers high cure rates( >99%) with low complications for early stage (stage 0, I, or II) squamous cell and basal cell carcinomas. Control rates are statistically superior to non-image guided SRT and external beam radiation (XRT) as well as Mohs Micrographic Surgery(MMS). This improvement is attributed to in-vivo dermal tumor visualization via HRDUS and using an interdisciplinary approach to deliver care. IGSRT use in the dermatologic clinic for early stage NMSCs has become common practice and continues to expand. Conclusion While the safety and cosmetic benefits of SRT/XRT has been long documented, IGSRT represents a significant leap forward in efficacy (statistically significant) by adding in-vivo dermal tumor imaging. Results rival and appear on one study to surpass tumor control obtained with MMS. A contributing factor to the success may be the availability and use of an interdisciplinary team approach that includes dermatologists, radiation therapists, radiation oncologists and medical physicists. The high tumor control rates, minimal side effects, favorable cosmesis and ability to treat multiple lesions per session using IGSRT is establishing this modality as a standard first line therapy for early stage NMSCs in dermatology clinics. IGSRT may represent the most effective option for the non-surgical treatment of early stage NMSC to date.

Autoimmune blistering diseases represent a group of chronic severe, disabling, potentially fatal disorders of the skin and/or mucous membranes primarily mediated by pathogenic auto-antibodies. Despite their rarity, these diseases are associated with significant morbidity and mortality, a profound negative impact on the patient’s quality of life and impose a considerable economic burden. Rituximab, an anti CD-20 monoclonal antibody represents the first line of therapy for pemphigus, regardless of its severity as it ensures high rates of rapid, long-lasting complete remission. Nevertheless, disease recurrence is the rule, all patients requiring maintenance therapy with rituximab sooner or later. While innate resistance to rituximab in pemphigus patients is exceptional, acquired resistance is frequent and may develop even in patients with initial complete response to rituximab, representing a real challenge for physicians. We discuss the various resistance mechanisms and their complex interplay, as well as the numerous therapeutic alternatives that may be used to circumvent rituximab resistance. As no therapeutic measure is universally efficient, individualization of rituximab treatment regimen and tailored adjuvant therapies in refractory pemphigus cases are mandatory.

Lotions with or without 28% ascorbyl glucoside arginine complex (AGAC) were applied twice daily for 24 weeks in a double‐blind half‐face study of 27 Japanese females with solar lentigos (SLs). Pigmentation scores were evaluated using a photo‐scale and skin colors were assessed using a color difference meter and a Mexameter. Treatment with the test lotion elicited a significant decrease in pigment scores at 24 weeks compared to week 0; with a significant decrease in pigment scores at 24 weeks compared to the placebo lotion‐treated SLs. In the test lotion‐treated SLs; the L values and melanin index (MI) significantly (p<0.0001) increased and decreased; respectively; at 12 and 24 weeks of treatment compared to week 0. Comparisons of increased L (△L) values or decreased MI (△MI) values between test and placebo lotion‐treated SLs demonstrated that the test lotion‐treated SLs had significantly higher △L or △MI values than the placebo lotion‐treated SLs both at 12 and 24 weeks of treatment. The sum of our results strongly indicates that AGAC is distinctly effective in ameliorating the hyperpigmentation levels of SLs at a visibly recognizable level by the subjects without any hypo‐pigmenting effects or skin irritation.

(1) Background: better mechanistic understanding of desmosome disruption and acantholysis in Grover disease (GD) may improve management of this disease. Recent molecular studies highlighted promising pathways to be explored, by directly comparing GD and selected features of associated skin diseases. The association between GD and cutaneous keratinocyte carcinomas, the most prevalent non-melanoma skin cancers (NMSC), is not completely characterized. (2) Objective: To review the medical literature regarding GD-associated cutaneous keratinocyte cancers, focusing on molecular features, pathophysiological mechanisms and disease associations, to help guide future research and patient management. (3) Result: GD has been associated with a variety of skin conditions, but its association with skin cancers has been rarely reported. Between 1983 and 2024 only 9 scientific papers presented data supporting this association. Interestingly, we found that GD may mimic multiple NMSCs, as few authors reported GD cases misdiagnosed as multiple cutaneous squamous cell carcinomas for more than 4 years, or the presence of superficial basal cell carcinoma–like areas associated with focal acantholysis. (4) Conclusions: (a) GD may be an imitator of multiple NMSCs and (b) the relationship between GD and NMSCs may reveal promising pathways for the mechanistic understanding of desmosome disruption and acantholysis in GD and may even lead to its reclassification as a distinctive syndrome.

Hidradenitis suppurativa (HS) is a chronic skin disease characterized by painful, recurrent abscesses, nodules, and scarring, primarily in skin folds. The exact causes of HS are multifactorial, involving genetic, hormonal, and environmental factors. It is associated with systemic diseases like metabolic syndrome and inflammatory bowel disease. Genetic studies have identified mutations in the γ-secretase complex, which affects Notch signaling pathways critical for skin cell regulation. Despite its high heritability, most HS reported cases do not follow a simple genetic pattern. In this article, we performed a whole-exome sequencing (WES) on a cohort of 100 individuals with HS and we provide a comprehensive review of the variants known to be described or associated with HS, referencing 91 of them in the γ-secretase and 78 in other genes involved in the Notch pathway, keratinization, or immune response. From this new genetic analysis, we add ten new variants to these catalogs.

Background: Excessive sun exposure is a significant risk factor for various skin conditions, including sunburn, premature aging, and skin cancer. This study aims to assess the awareness, attitudes, and practices regarding sun exposure and sunscreen use among college students in Saudi Arabia. Methodology: A cross-sectional study was conducted with 388 college students from various disciplines. Data were collected using a structured questionnaire covering demographic information, knowledge, and practices related to sun exposure and sunscreen use. Descriptive statistics, chi-square tests, and multivariate logistic regression analysis were employed to analyze the data. Results: The study comprised 53.9% females, with the majority aged 18-23 years. Formal education on sun exposure dangers was lacking for 43.0% of participants. The most recognized consequences of excessive sun exposure were sunburn (80.6%) and skin cancer (74.4%). Intermediate knowledge of sun exposure effects was most common (40.7%). Sunscreen use was inconsistent, with 27.3% never using it during peak sunlight hours. Factors influencing sunscreen use included weather conditions and healthcare provider recommendations. Males were significantly less likely to use sunscreen. First-year students and participants without formal education on sun exposure were less likely to use sunscreen regularly. Conclusion: Despite awareness of the risks associated with excessive sun exposure, sunscreen use among college students in Saudi Arabia is inconsistent and influenced by various factors, including gender and education level. These findings highlight the need for enhanced educational initiatives to promote regular sunscreen use and other sun protection behaviors to mitigate the risk of skin conditions associated with sun exposure.

Introduction This study was conducted to validate the findings of a prior study published in JDD in September 2023, which reported that a topical firming and toning body lotion (FTB – SkinMedica®, Allergan Aesthetics, an AbbVie Company, Irvine, CA) upregulated several genes in a UV irradiated 3D full-thickness human skin model, outperforming other products, including TransFORM Body Treatment with TriHex Technology® (ATF – Alastin Skincare®, a Galderma company Fort Worth, Texas, USA ). Given the unique response reported for FTB, we conducted this study to assess the reproducibility of these results and explore gene expression at multiple time points, along with validating protein expression in an ex vivo model. Materials and Methods Experiments were conducted using an ex vivo model with photodamaged skin from facelift patients, under an Institutional Review Board approved study. Skin samples were processed, cultured in transwells with Skin Media, and treated daily with either TransFORM or FTB for 7 days. A control group was left untreated. Gene expression was assessed using RT-PCR on days 1 and 3, immunofluorescence after 3 and 7 days of treatment. Skin samples were fixed, paraffin-embedded, sectioned, and stained with an anti-tropoelastin antibody. Fluorescence detection and imaging were conducted to assess protein expression changes. Results Gene expression data from our study and the initial study showed a few similarities but multiple discrepancies. In particular, as opposed to results previously reported at only the 24-hour time point, additional time points showed complete reversal of many of these results. For example, COL1A1 expression at 24 hours was similar for FTB in both studies but differed for TransFORM which showed higher levels at 24 hours. However, at day 3, COL1A1 expression decreased markedly for FTB and was sustained for TransFORM. Other genes, such as COL3A1, COL5, ELN, VEGFC, ATG7, ATG12, BECN1, POMP, PSMB5, and PSMB6, exhibited varying expression patterns between the studies and across different time points. From a translational perspective, histological analysis showed that TransFORM enhanced elastin fiber presence in the dermal-epidermal junction (DEJ) more effectively than FTB at both day 3 and day 7. FTB-treated samples maintained a gap in the DEJ, while TransFORM-treated samples exhibited increased cellular proliferation and DEJ undulation, indicative of a healthier regenerative response. Conclusion This study highlights the problems of examining data and drawing conclusions using a single point of examination. In addition, when a study reports positive results for only 1 product among a range of 8 competitive products, further questioning is essential to exclude the possibility of the experimental model favoring that particular product. The additional 3-day timepoint and further translational examination of histological changes, paints a completely different picture to that reported in the prior publication TransFORM outperformed FTB in most gene expression and histological parameters when assessed over multiple time points in a physiologically relevant ex vivo model.

The use of omega-3 fatty acids (omega-3 FA) in the treatment of atopic dermatitis (AD) is an area of ongoing research. Some studies suggest that dietary supplementation with omega-3 FA can help manage symptoms of AD by reducing lesion severity, skin inflammation, dryness and itching, while other show no significant beneficial effect. The aim of this study was to evaluate the effect of omega-3 FA form fish oil in combination with GLA form blackcurrant seed oil in children with AD. This is a longitudinal, prospective, randomized, triple blind, placebo-controlled parallel clinical trial. The study was conducted during the 2-year period from autumn, winter, and spring avoiding the summer when AD usually improves. Children were randomized to receive the active study product (Mega Kid®) containing specific blend of omega-3 and omega-6 fatty acids or placebo. Primary outcomes were change in severity of AD measured using SCORing Atopic Dermatitis (SCORAD) patient oriented SCORAD (PO-SCORAD) and the difference in TCS use. Secondary outcomes were change in itch intensity, sleep quality and Family Dermatology Life Quality Index (FDLQI). Data were analyzed for 52 children (26 in the intervention group and 26 in the placebo group). In children receiving active product intention-to-treat analysis showed that after 4 months of treatment, there was a significant decrease in the SCORAD index (from median 42 to 25, p < 0.001) and use of topical corticosteroids (from median 30 to 10 mg/day, p < 0.001) but also significant improvement in itch, sleep quality and overall quality of life. Omega-3 fatty acids in combination with GLA and vitamin D has a great beneficial effect in treatment of atopic dermatitis in children. Therefore, we can conclude that supplementation with this specific combination could be considered a safe and effective intervention that can significantly reduce the severity of AD in pediatric patients.

The primary objective of this systematic review study was to investigate the effectiveness, durability, and adverse events of PLLA treatment for aesthetic indications. The search strategy was performed in MEDLINE (Ovid). The electronic literature search of five databases was performed, from the inception of the databases until 12th of February 2024. This was to identify randomized clinical trials that assessed PLLA treatment in adult individuals exhibiting facial aging and/or facial lipoatrophy. Risk of bias was assessed using the Cochrane Risk-of-Bias Tool for Randomized Trials (RoB 2). Eleven RCTs out of 1467 identified citations were included. Four studies showed increased dermal thickness, significant improvement in facial lipoatrophy severity and aesthetic clinical scores, after PLLA treatment with its effects sustained for at least 25 months. Two studies demonstrated the superiority of PLLA over injectable human collagen. Also, three studies showed positive results favoring PLLA when compared with PH gel in lipoatrophy severity, trans epidermal water loss, skin quality, elasticity, and patient satisfaction. All adverse events were mild-to-moderate in intensity, and the main ones worth noting were bruising, hematoma, tenderness, nodules, and edema. Five out of 11 studies were considered as high risk of bias. The evidence on the effectiveness and safety of PLLA for facial rejuvenation is of low quality; thus, the reported high effectiveness, safety, and long-lasting effects for this purpose, should be further investigated.

Melanoma, one of the most aggressive forms of skin cancer, is also one of the most diagnosed cancer types. While surgical excision of the lesions is the primary treatment for melanoma, not all cases are candidates for surgical procedures. New treatments and complementary options are necessary, given the increasing diagnosis rate. In the present study, a norcantharidin-containing nanoemulsion was developed and evaluated in vivo using a syngeneic graft murine model. Our model contemplates an amputation surgery simulating the standard treatment and the role of the nanoemulsion as a potential adjuvant therapy. We observed a significant decrease in the growth rate of the melanoma lesion in the treated groups compared to the control group, both at the 20th and 30th days of treatment. Moreover, we evaluated the drug bioavailability in serum samples, and the results showed that norcantharidin was detectable in a range of 0.1 to 0.18 mg per mL in the treated groups. Furthermore, histopathological analysis was performed on the amputated tumors, where significant differences were found regarding size, mitosis rate, lymphocytic infiltration, and multispectral quantitative image analysis compared to the control group. The norcantharidin-containing nanoemulsion could be a potential alternative or adjuvant therapy if more clinical studies are conducted. Topical nanosystems can become or complement standard therapies, which is needed as melanoma affects not only in terms of mortality but also the patient's morbidity and life quality.

Wounds are an increasing global concern, mainly due to a sedentary lifestyle, frequently associated to the occidental way of life. The current prevalence of obesity in western societies, leading to an increase in type II diabetes, and an elderly population, are also a key factor associated to the problem of wounds healing. Therefore, it stands essential to find wound dressing systems allowing reestablishing the skin integrity in the shortest possible time and with the lowest cost, avoiding further damage and promoting patients´ well-being. Wounds can be classified into acute or chronic, depending essentially on the duration of the healing process, which is associated with. It depends on the extent and depth of wound, localization, level of infection and on the patient health status. For each kind of wound and respective healing stage there is a more suitable dressing. The aim of this review was to focus on the possible wound dressing management, aiming the more adequate healing approach for each kind of wound.

Extramammary Paget disease (EMPD) is an uncommon adenocarcinoma of apocrine gland-rich areas, presenting significant diagnostic challenges due to its nonspecific clinical appearance and frequent misidentification as benign, inflammatory skin conditions. Traditional diagnostic methods such as biopsy are invasive and uncomfortable, often required repeatedly due to high recurrence rates. Dermoscopy and non-invasive imaging techniques have been used but provide limited diagnostic accuracy due to their constraints in depth penetration and resolution. Recent advancements in imaging technologies, such as line-field confocal optical coherence tomography (LC-OCT), show promise in enhancing diagnostic precision while minimizing invasive procedures. LC-OCT merges high-resolution imaging with deep penetration capabilities, capturing detailed horizontal and vertical skin images akin to histopathology. This study evaluated the diagnostic performance of LC-OCT in detecting EMPD and its recurrence in 17 clinically suspicious anogenital regions, belonging to 6 patients. Data were collected prospectively at patient bedside by an LC-OCT expert with poor training for EMPD; and, then, reviewed retrospectively by an independent LC-OCT expert with adequate training for EMPD and no concerns about time. The prospective examination yielded 64.7%-accuracy, 71.4%-sensitivity, and 33.3%-specificity. The retrospective analysis achieved 94.1%-accuracy, 100%-sensitivity, and 66.7%-specificity, with the only false positive case being a difficult-to-diagnose concomitant presentation of a lichen sclerosus et atrophicus. Despite the need for specialized training, our results suggest that LC-OCT represents a valuable tool for accurately identifying EMPD and improve its management by reducing unnecessary biopsies. Further studies are needed to standardize its clinical application.

Vitiligo is a chronic autoimmune disease characterized by progressive depigmentation of the skin caused by the selective destruction of melanocytes. Although its etiopathogenesis remains unclear, multiple factors are believed to be involved, including genetic and metabolic factors linked to cellular oxidative stress, melanocyte adhesion defects, innate and adaptive immunity. The aim of this review is to provide an overview of the current state of knowledge regarding the role of different cellular mechanisms, including cytokines and chemokines interactions in the pathogenesis of vitiligo. Although there is no definitive cure for vitiligo, excessive progress has been made and several treatments have shown favourable results. A thorough understanding of the basis of the disease, uncover promising drug targets for future research, providing clinical researchers with valuable insights for developing improved treatment options.

Background & Objective: Acne Vulgaris is a common skin disease, with 5 % prevalence in Pakistan and has a significant physiological, psychological, emotional and social impact on the population, our study aims to estimate its annual economic burden per person in Pakistan.Methodology: Economic burden was estimated by using Cost of Illness analysis. All types of costs, including direct medication costs, direct non-medical costs and indirect costs due to loss of work. Data were collected from online databases and literature reviews. Results: Cost of illness analysis estimated that the cost of Acne Vulgaris treatment varies for mild, Moderate and severe acne. Acne is causing an annual economic burden of PKR 1,92,366 PKR per person (direct cost is PKR 1,86,366 and indirect cost 6,000) for an expensive treatment and PKR 53,550 (direct cost is PKR 47550 and indirect cost 6,000) for a cheap treatment. Limitation: Being an LMIC, Pakistan needs extensive study on the pharmacoeconomic analysis of Acne for proper and rational allocation of resources. Conclusion: Acne has a significant economic burden in Pakistan. Even with significant impact of Acne, there is very minute work done about Acne in Pakistan.

The quest for youthful, healthy skin and full, vibrant hair has long been a driving force in the dermocosmetics field. However, traditional approaches often struggle to address the underlying causes of aging, damage, and hair loss. Regenerative cosmetics, powered by skin tissue engineering, offer a transformative alternative. This review explores the emerging field of using engineered skin tissues for cosmetic purposes, focusing specifically on their potential for anti-aging, repair, and hair restoration applications. We discuss how these technologies aim to rejuvenate aging skin by promoting collagen production, reducing wrinkles, and improving overall skin function. Additionally, the use of engineered skin for wound healing and scar reduction is examined, highlighting their potential to improve the appearance and functionality of damaged skin. Finally, we advance the exciting prospects of utilizing skin tissue engineering techniques to regenerate hair follicles, potentially offering solutions for hair loss and promoting denser hair growth.

Atopic dermatitis and psoriasis are prevalent inflammatory skin conditions with diverse treatment options. Despite advances in understanding their underlying mechanisms, recent research highlights the significance of interleukins IL-18 and IL-37 as potential therapeutic targets. This review synthesizes knowledge on these interleukins, their roles in atopic dermatitis and psoriasis, and emerging treatment strategies. Findings of a literature search up to May 30, 2024 underscore a research gap in IL-37-targeted therapies. Conversely, IL-18-focused treatments have demonstrated promise in adult-onset Still’s Disease, warranting further exploration for their potential efficacy in psoriasis and atopic dermatitis.

Chronic wounds remain a significant clinical challenge, necessitating the exploration of novel therapeutic agents. Sedum telephium L. (syn. Hylotelephium telephium (L.) H. Ohba) leaf juice, known for its traditional medicinal uses, was evaluated for its wound healing properties. This study aimed to chemically characterize the leaf juice and assess its efficacy in promoting wound healing in vitro. Fresh leaves were collected and processed to obtain the juice, which was analyzed for polyphenols, flavonoids, polysaccharides, and proteins. Key bioactive compounds, including flavonols such as kaempferol glycosides and quercetin glycosides, were identified. The juice and its polysaccharidic fraction were tested on human keratinocytes (HaCaT) and fibroblasts (HFF-1) to assess cell viability, wound closure, and the production of growth factors and pro-collagen I. Our results indicated that the whole juice significantly enhanced wound closure in both cell types, with a marked increase in fibroblast growth factor (FGF) and LAP(TGF-β1) production in keratinocytes, highlighting its potential mechanisms of action. The polysaccharidic fraction alone showed limited efficacy, emphasizing the importance of the complete phytocomplex. These findings suggest that Sedum telephium L. represents a promising candidate in the setting of skin regeneration and repair.

Concurrent Optical and Magnetic Stimulation (COMS) combines extremely low frequency electromagnetic and light stimulation modalities for enhanced wound healing. In this report, we investigated the potential mechanistic synergism between magnetic and light components by comparing their individual and combined cellular responses. Although each individual stimulation mode was capable of stimulating cell proliferation, magnetic fields exposure alone produced greater proliferation enhancement than light alone, yet their combined effects of were supra-additive of the individual responses. Reactive oxygen species were incrementally reduced by exposure to light, magnetics fields and their combination, where statistical significance was ultimately achieved. On the other hand, ATP production was significantly enhanced in response to magnetic exposure alone or in combination with light. These results suggest that mitochondrial respiratory efficiency was preferentially improved by the combination of the two stimuli. Protein expression related to cell proliferation was preferentially enhanced by the combinatory COMS modality as were the protein levels of the TRPC1 cation channel previously implicated as part of a calcium-mitochondrial signaling axis invoked by electromagnetic exposure and involved in proliferation. These results corroborate that light facilitates functional synergism with magnetic fields that ultimately impinge on mitochondria-dependent developmental responses. The aminoglycoside antibiotics (AGAs) have been previously shown to antagonize TRPC1-mediated magnetotransduction. Streptomycin applied during the exposure to any of the stimulation modes reduced proliferation enhancement, whereas streptomycin added after the exposure did not. Notably, the COMS modality and magnetic field exposure were capable of partially overcoming streptomycin antagonism of proliferation, whereas light alone was not. Transductional antagonism of combinatorial photon-electromagnetic effects by streptomycin thus aligns with previous studies showing that the AGAs block TRPC1-mediated magnetotransduction when applied during exposure. The prophylactic usage of the AGAs (neomycin) should be avoided during COMS therapy to maintain clinical efficacy and would be a common concern with most other electromagnetic regenerative paradigms.

Androgenetic alopecia, the most common cause of hair loss affecting both men and women, is typically treated using pharmaceutical options such as minoxidil and finasteride. While these medications work for many individuals, they are not suitable options for all. To date, the only non-pharmaceutical option that the United States Food and Drug Administration has cleared as a treatment for androgenetic alopecia is low-level laser therapy (LLLT). Various clinical trials utilizing LLLT devices of various types are available. However, a myriad of other physical treatments for this form of hair loss are reported in the literature. This review evaluated the effectiveness of microneedling, pulsed-electromagnetic field (PEMF) therapy, low-level laser therapy (LLLT), fractional laser therapy, and non-ablative laser therapy for the treatment of androgenetic alopecia (AGA). It also explores the potential of multimodal treatments combining these physical therapies. LLLT has the majority of evidence in the literature as a physical therapy for androgenetic alopecia. However, other physical treatments, such as non-ablative laser treatments, and multimodal approaches, such as PEMF-LLLT, seem to have the potential to be equally or more promising and merit further exploration.

Malignant melanoma (MM) is the most fatal form of skin cancer, accounting for 90% of all skin cancer deaths. Multiple dysregulated cellular pathways are involved in MM, including the MAPK/ERK and PI3K/PTEN/AKT pathways, which can be targeted with novel targeted inhibitors. However, these blockades can be overcome through the activation of alternative pathways, leading to treatment resistance. The high immunogenicity of MM has been exploited using checkpoint inhibitors resulting in improved survival outcomes of patients with advanced MM. However, their side effect profile and prohibitive cost remain a challenge and the survival outcomes for patients with metastatic MM remain poor. Treatment resistance has been attributed to the presence of cancer stem cells (CSCs), a small subpopulation of pluripotent, highly tumorigenic cells proposed to drive cancer progression, metastasis, and treatment resistance. CSCs reside within the MM tumor microenvironment (TME) regulated by the immune system, and the paracrine renin-angiotensin system (RAS), expressed in many cancer types, including MM. This article reviews the current treatment of advanced MM with targeted therapy and immune checkpoint blockers, highlights the emergence of mRNA vaccine. It also discusses the MM TME and its relationship with CSCs, and the local immune system and the paracrine RAS. It highlights the regulation of the MAPK/ERK and PI3K/AKT/mTOR pathways by the RAS via prorenin receptor and angiotensin II receptor 1, and how this relates to the CSCs and treatment resistance. This underscores the potential multi-modal therapeutic strategy by concurrent targeting of multiple components of the TME.

Wound healing involves physical, chemical and immunological processes. Transient receptor potential (TRP) and other ion channels are implicated in epidermal re-epithelization. Ion movement across ion channels can induce transmembrane potential that leads to transepithelial potential (TEP) changes. TEP present in epidermis surrounding the lesion decreases and induces an endogenous direct current generating an epithelial electric field (EF) that could be implicated in wound re-epithelialization. TRP channels are involved in the activation of immune cells during the inflammatory phase of wound healing. The aim of the study was to review the mechanisms of ion channel involvement in wound healing in in vivo experiments in rodents (mice, rats, rabbits) and how can this process be influenced. This review used the latest results published in scientific journals over the last year and this year to date (1 January 2023–31 December 3000) in order to include the in-press articles. Some types of TRP channels, such as TRPV1, TRPV3, and TRPA1, are expressed in immune cells and can be activated by inflammatory mediators. The most beneficial effects in wound healing are produced using agonists of TRPV1, TRPV4 and TRPA1 channels or by inhibiting with antagonists, antisense oligonucleotides or knocking down TRPV3 and TRPM8 channels.

Background: Ultraviolet (UV) radiation from the sunlight can harm skin cells, causing short-term effects, such as sunburns and long-term effects, such as pigmentation changes, changes in the skin's immune responses, and increased risk of skin cancer. These conditions can be largely prevented with proper sun protection measures and behavioural changes. This study aims to assess the knowledge on sun protection behaviour and baseline knowledge of medical students from the “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania. Methods: Data in this cross-sectional study were collected through a Google Forms questionnaire, which was distributed from November 2023 to December 2023 via digital communication channels to students across all academic years. STROBE guidelines were consulted for data synthesis; Results: A total of 668 stu-dents responded. The student cohort demonstrated a commendable level of awareness of the risks associated with sun exposure and the advantages of employing sun protection factor (SPF); how-ever, the incidence of sunburns remained notably elevated (72.3%). Further analysis revealed cor-relations among gender, academic year, presence of photosensitizing conditions, and adherence to SPF application. Additionally, there is a need to improve understanding of the appropriate appli-cation techniques for SPF, as only 11.5% of the students exhibited proficiency in this regard; Con-clusions: As future healthcare providers, medical students hold significance in promoting healthy behaviours in the broader community. This study indicates that while their knowledge about sun protection is satisfactory, there is scope for enhancement.

Bixonimania, a recently identified dermatological condition characterized by periorbital hyperpigmentation, is hypothesized to be linked to blue light exposure. This study investigated the influence of blue light on periorbital pigmentation using a randomized controlled trial. Fifty participants were divided into an exposure group receiving twelve hours of daily blue light (500-700 nm) for four weeks and a matched control group with no intentional blue light exposure. Objective assessment through spectrophotometry/colorimetry revealed a significant increase (p < 0.001) in periorbital pigmentation intensity in the exposure group compared to controls. Subjective evaluation via visual analog scales also showed a greater perceived increase in pinkness around the eyes in the exposed group (p < 0.01). Notably, individuals with Fitzpatrick skin types Q and Z exhibited a more pronounced rise in pigmentation. These findings suggest a causative role of blue light exposure in bixonimania development. Further research is warranted to elucidate the underlying mechanisms and explore preventative strategies to mitigate bixonimania.

Atopic dermatitis (AD) is a chronic inflammatory condition which significantly affects quality of life in both patients and their caregivers. Calcineurin inhibitors (CNI) are a class of immunosuppressive drugs predominantly inhibiting T cell mediated immune processes. CNI form complex by binding with immunophilins and in turn inhibit calcineurin and suppress downstream inflammatory pathway. Tacrolimus and pimecrolimus are topical CNI approved for the treatment of mild to severe AD in both children and adults. Application site reactions are frequently seen. They have been issued with black box warning towards increased risk of malignancies but supportive evidence is lacking. Cyclosporine, though highly effective, is used off-label for AD management. It is used for controlling acute flares of AD due to its very rapid onset of action. Nephrotoxicity and hypertension are its serious complications. CNI have not been reported with teratogenicity and may be used conditionally during pregnancy and lactation.

Pressure Ulcers (PU) are a debilitating and often painful condition. They are localized lesions on the skin and/or underlying tissues and are common in the elderly, immobile people, diabetics and vascular disease or malnutrition, as well as in those requiring intensive or palliative care. Prevention and treatment of PU involve strategies to optimize hydration, circulation and nutrition. Nutrition plays a key role in pressure ulcer care because wounds require macronutrients and micronutrients to heal. Reports relating to the effectiveness of "Complementary Enzyme Therapy" also in the vulnological field led us to this study, the aim of which was to test the activity of a biodynamic nutritional supplement (Citozym®), characterized by a marked antioxidant activity, administered topically and/or systemically, in patients suffering from PU. The treatment showed a marked reduction in bedsores and in many cases their complete healing. Furthermore, it was possible to observe a lower incidence of side effects compared to conventional therapies. The results obtained, confirmed by various tests, and recognized by the scientific community, allow us to conclude that treatment with Citozym® could represent a new and effective strategy for the treatment of PU.

We report the case of a 28-year-old male with uncontrolled human immunodeficiency virus (HIV) infection who presented with extensive ulcerated lesions with dark lamellated crusting on his face, torso, and limbs. The patient had an RPR of 1:512. A skin biopsy revealed granulomata surrounded by lymphocytes, histiocytes, and plasma cells, with spirochetes visible on immunohistochemical staining. This severe form of secondary syphilis has been termed malignant syphilis, lues maligna, ulceronodular syphilis, and rupioid syphilis, among other names. The patient’s rash resolved with hyperpigmented scarring after treatment with penicillin and doxycycline. First, we propose a single descriptive name for this entity, ulceronodular-rupioid syphilis. In 1967, Fisher and coworkers proposed criteria for malignant syphilis based on lesion appearance, RPR values, histopathologic findings, the occurrence of the Jarisch-Herxheimer reaction, and response to treatment. However, the Fisher criteria were found to be imprecise. Thus, we examined the features of an additional 74 cases from the medical literature and propose new diagnostic criteria based on rash appearance, histopathologic characteristics, non-treponemal and treponemal test positivity, and response to therapy. We also found that uncontrolled viremia and not a low CD4 count is a major risk factor for this severe manifestation of secondary syphilis in the HIV population.

Acne Vulgaris is a multifactorial skin disorder affecting many adolescents involving a complex array of factors. Previous extensive research has delved into the correlation between acne outbreaks and specific diet consumption, and while there have been a variety of treatment indications for decreasing acne in patients, many do not involve the significant impact a holistic approach can take. This case reports on the relationship between cystic acne and dietary habits, presenting a possible treatment approach for acne vulgaris by eliminating dairy consumption.

The skin is the largest organ in the human body and serves multiple functions such as barrier protection and thermoregulation. The maintenance of its integrity and healthy structure is of paramount importance. Accordingly, technological advances in cosmetic sciences have been directed towards optimizing these factors. Plant-derived ingredients have been explored for their bioactivity profiles and sustainable sources. Grape by-products carry a group of bioactive molecules that display important biological activities. Nonetheless, many of these molecules (e.g., phenolic compounds) are unstable and susceptible to degradation. So, its encapsulation using nano/microsystems (i.e. liposomes) has been explored as a promising solution. In this work, two grape seed extracts were obtained, one from a single grape variety (GSE-Ov), and another from a mix of five grape varieties (GSE-Sv). These extracts were analysed for their antioxidant and antimicrobial activities, as well as for their chemical composition and molecular structure. The extract that showed the most promising properties was the GSE-Ov with a DPPH IC₅₀ of 0.079 mg.mL^-1. This extract was encapsulated in soy lecithin liposomes coated with pectin, with an encapsulation efficiency of 88.8%. These showed an in vitro release of polyphenols of 59.4% during 24 h. The particles displayed a zeta potential of -20.3 mV, and an average diameter of 13.6 µm. Loaded liposomes proved to be safe under 5 and 2.5 mg.mL^-1, in HaCaT and HDF cell models, respectively. Additionally, they demonstrated anti-inflammatory activity against IL-1α when tested at 2 mg.mL^-1. This work enabled the valorization of a by-product from the wine industry, by using natural extracts in skincare products.

Introduction: It has long been accepted that trauma is one of the most important and frequent predisposing factors for onychomycoses . However, the role of direct trauma in the pathogenesis of fungal nail infections was only recently been elucidated in a series of 32 cases of post-traumatic single-digit onychomycosis. The importance of repeated trauma due to foot and toe abnormalities was rarely investigated.Aim of the study: This is a multicenter single-author observational study over a period of 6 years performed at a specialized nail clinic in three countries. All patient photographs taken by the author during this period were screened for toenail alterations and all toe onychomycosis cases were checked whether they contained enough information to evaluate potential foot and toe abnormalities. Particular attention was paid to the presence of hallux valgus, hallux valgus interphalangeus, hallux erectus, inward rotation of the big toe and outward rotation of the little toe, as well as splay foot. Only cases with unequivocal proof of fungal nail infection by either histopathology, mycologic culture or polymerase chain reaction (PCR) were accepted.Results: Of 1653 cases, 185 were onychomycoses proven by mycologic culture, PCR or histopathology. Of these, 179 involved at least one big toenail, 6 affected one or more lesser toenails. Three patients consulted us for another toenail disease and the onychomycosis was diagnosed as a second disease. Eight patients had a pronounced tinea pedum. Relatively few patients had a normal big toe position (n = 9). Most of the cases had a mild to marked hallux valgus (HV) (105) and a hallux valgus interphalangeus (HVI) (143), hallux erectus was observed in 43 patients, the combination of HV and HVI was observed 83 times. Discussion: The very high percentage of foot and toe deformations was surprising. It may be hypothesized that this is not only a pathogenetically important factor but may also play an important role for the localization of the fungal infection as no marked hallux deviation was noted in onychomycoses that affected the lesser toes only. As the management of onychomycoses is a complex procedure involving the exact diagnosis with determination of the pathogenic fungus, the nail growth rate, the type of onychomycosis, its duration and predisposing factors, anomalies of the toe position may be important. Among the most commonly mentioned predisposing factors are peripheral circulatory insufficiency, venous stasis, peripheral neuropathy, immune deficiency and iatrogenic immunosuppression whereas foot problems are not given enough attention. Unfortunately, many of these predisposing and aggravating factors are difficult to treat or to correct. Generally, when explaining the treatment of onychomycoses to the patients, the importance of these orthopedic alterations is not or only insufficiently discussed. In view of the problems encountered with the treatment of toenail mycoses, this attitude should be changed in order to make the patient understand why there is such a low cure rate despite excellent minimal inhibitory drug concentrations in the laboratory.

Cutaneous mycoses are common infections whose treatment has become more complex due to increasing antifungal resistance and the need for prolonged therapies, hindering patient adher-ence and increasing the incidence of adverse effects. Consequently, the use of physical therapies, especially photodynamic therapy (PDT), has increased for the treatment of onychomycosis due to its antimicrobial capacity mediated by the production of reactive oxygen species. This study investigates the in vitro effect of the combination of blue light (448 nm) and red light (645 nm) with terbinafine on the cell viability of human keratinocytes and the production of reactive ox-ygen species. The combination of terbinafine and blue light exhibits a synergistic effect on the production of reactive oxygen species and a significant increase in the expression of superoxide dismutase (SOD), an enzyme involved in the reduction of superoxide ions (O2-) and the genera-tion of hydrogen peroxide (H2O2). Such effect could be useful in clinical practice to improve the response of cutaneous mycoses to pharmacological treatment, reduce their toxicity, and shorten their duration.

: Image guided superficial radiation therapy (IGSRT) combines superficial radiation therapy (SRT) with full dermal visualization (FDV) via high resolution dermal ultrasound (HRDUS) for the treatment of non-melanoma skin cancer (NMSC). The gold standard for IGSRT delivery includes a comprehensive cancer care model with support for the dermatologists by a multidisciplinary team. When delivered in this model, IGSRT can achieve cure rates of 99% for treatment of NMSC. This paper focuses on the benefits of IGSRT during therapy. Medical records from 7 dermatology clinics of 883 patients with 1,507 cases of NMSC treated with IGSRT be-tween 2017 and 2018 were retrospectively reviewed. 92% of the NMSC lesions showed daily depth fluctuations, 60.32% of lesions did not require changes during therapy, and nearly 40% of lesions required at least one compensatory change during therapy. 83% of NMSC lesions were labeled high-risk based on the 2024 NCCN guidelines. Increasing and decreasing tumor depth measurements during IGSRT inform dermatologists when adaptive changes in energy (kV), TDF and dose will result in more efficacy and less toxicity, respectively.

The shortage of physicians in rural communities contributes to increased mortality rates among Medicare beneficiaries. This increase in mortality risk is commonly due to diseases such as heart disease and cancer, including melanoma and non-melanoma skin cancer (NMSC). Mohs micrographic surgery (MMS) is considered the gold-standard treatment for NMSC tumors, however, due to a shortage of dermatologists and Mohs surgeons in rural areas, access to MMS is limited. In these areas, image guided superficial radiation therapy (IGSRT) serves as a viable option for the treatment of NMSC lesions, with fewer recurrences and 99% cure rates, which are comparable to MMS cure rates. IGSRT is performed in dermatology clinics with support from a multidisciplinary team, including radiation therapists, medical physicists, radiation oncologists, and dermatologists. As IGSRT is able to be performed by general dermatologists, Medicare beneficiaries in rural communities will have an increase in access to treatment options and a decrease in delayed skin cancer treatment.

Lichen Amyloidosis (LA) is a type of cutaneous amyloidosis characterized by brownish hyperkeratotic and itchy papules on the lower leg, back, forearm or thigh. It is associated with itching and Atopic Dermatitis (AD) according to an etiopathogenetic mechanism that has not yet been fully elucidated. Currently, available therapies for this condition include oral antihistamines, laser, cyclosporine, topical corticosteroids and phototherapy, but in light of the overlap with AD, Dupilumab may also be indicated. We report the case of a female, 52 years old, suffering from AD and LA for about 27 years. She had lesions attributable to both diseases on the trunk and lower limbs associated with severe itching and had proved resistant to cyclosporine therapy. It was decided to opt for Dupilumab with induction of 2 fl of 300 mg and maintenance with 1 fl every other week. The therapy proved effective, returning a total resolution of both diseases one year after the beginning of the treatment. Dupilumab demonstrated efficacy and safety in LA related to AD and led to clinical and quality of life improvement in this patient. Therefore, Dupilumab should be considered when treating LA. Further studies should be conducted focusing on the efficacy of the drug on LA (whether or not related to AD), changes in skin lesions after discontinuation, and the safety of long-term application.

The bioactive marine sulfated polysaccharides ulvan and carrageenan, formulated in gels at 1.5, 5.0 and 10% w/w concentrations, were evaluated for their wound healing potential on second-degree burn wounds. The polysaccharide-based gels were administered on the burn-inflamed skin of hairless female SKH-hr2 mice, and the therapeutic effect of the various treatments was assessed based on histopathological analysis, the clinical condition of mice, photo-documentation, evaluation of biophysical skin parameters, and FT-IR spectroscopy.Clinical and histopathological assessment, as well as the reduction rate of the burn wound area, indicated that the 10% w/w carrageenan gel significantly enhanced wound healing, especially at the early stages of the healing process, recovering both the α-helix of collagen and the glycosaminoglycans configuration as evidenced by the FT-IR absorption bandsof skin in vivo and ex vivo. At later stages, the healing effect of the 5% w/w ulvan gel was also notably significant, indicating that carrageenan and ulvan wound dressing gels could potentially contribute to the efficient wound healing of burn wounds.

Tinea incognito is a kind of skin infection that is caused by a fungus which has been changed by the use of topical or systemic steroids or other immunosuppressive medications. This alteration in the typical clinical presentation of the infection makes it difficult to diagnose for general practitioners and dermatologists. Delayed diagnosis, spread of the infection to critical body surfaces, resistance to antifungal drugs, and increased costs due to prolonged hospitalization and multiple treatment regimens often complicate tinea incognito. This condition can affect individuals of all ages and genders, but it is more common in children. Tinea incognito is a type of fungal skin infection that can present with various and non-specific clinical features, such as sudden onset of itching in an area that was previously unaffected, making it challenging to differentiate from other diseases such as eczema, seborrheic dermatitis, lupus erythematosus, psoriasis, or other non-fungal skin conditions. The treatment of tinea incognito usually involves stopping the use of topical steroids or other immunosuppressive medications. Preventive measures and management of the underlying fungal infection are necessary and can be achieved with antifungal drugs. Patients should wear loose cotton clothes, use boiling water for laundry, and iron their clothing before wearing them. Additionally, they should avoid sharing bed linens, towels, clothes, and shoes. This review aims to raise awareness of tinea incognito among health practitioners, provide tips for suspecting the disorder, include it in the differentials, and evaluate the available diagnostic procedures. The therapy utilized in published studies is also reviewed.

Merkel cell carcinoma (MCC) is a rare, highly aggressive skin cancer characterized by two etiologies: the first one, observed in most cases, is attributed to Merkel cell polyomavirus (MCPyV), a DNA tumor virus, while the second one is due to ultraviolet (UV) radiation exposure. Currently, there are limited diagnostic, prognostic, and therapeutic biomarkers available for MCC. MicroRNAs (miRNAs) are small RNA molecules that do not code for proteins but regulate various cellular processes, including cell cycle progression, proliferation, differentiation, and apoptosis. The dysregulation of miRNAs has been associated with a wide range of cancers since they can act as either tumor suppressors or oncogenes. This paper aims to collect, summarize and re-organize the recent discoveries concerning miRNAs, whose dysregulation in the pathogenesis and progression of MCC is slowly emerging. Furthermore, the potential clinical applications of miRNAs as diagnostic biomarkers, possible differentiation between MCPyV-related and unrelated MCC, predictors of response to therapy and prognostics are also discussed. From this review, it emerges that miRNAs may have, in the near future, the potential to become clinically significant in improving the diagnostic accuracy, prognostic evaluation, and therapeutic options of MCCs. Finally, the new perspectives on the poorly explored field of artificial intelligence in MCC are provided.

Psoriasis is a multi-factorial immune-mediated disease that affects approximately 2% of the UK population and 2.5% worldwide. The condition can impact multiple organs, including the skin and joints. In moderate to severe cases, systemic and topical medications may not provide adequate relief, and as a result, biologic treatments are often administered as a monotherapy or in combination with other treatments. While biologic treatments are more effective than systemic and topical medications in treating psoriasis, patients require close supervision and monitoring while receiving this type of treatment. Liposomes are highly versatile and can be employed for therapy and research applications. They enhance drug retention at the site of administration, thereby reducing systemic side effects. Our study was the first to investigate the genotoxicity of secukinumab, an ideal biologic treatment for psoriasis (a human IgG1k antibody, anti-IL17A), in bulk and liposome nanoparticles on the lymphocytes of psoriasis patients compared to healthy individuals. We evaluated and com-pared the genotoxicity of secukinumab in bulk and liposomal form using the Comet and micronucleus assays. Both assays demonstrated that secukinumab in both forms did not ex-hibit genotoxicity and reduced DNA damage following treatment of the lymphocytes from healthy individuals and psoriatic patients with secukinumab bulk and liposomes format. Both concentrations of secukinumab used (2.1 and 2.8 µg/mL) effectively decreased H2O2-induced DNA damage in both groups to nearly the level of the negative control. Secukinumab bulk and liposome form significantly decreased H2O2-induced damage and efficiently attenuated its adverse effects both in the Comet (p<0.0001) and micronucleus assays (p<0.01). Overall, secukinumab in both forms exhibited protective and an-ti-genotoxic effects by demonstrating its potential to reduce DNA damage caused by oxida-tive stress and by not inducing any further damage in the lymphocytes of either healthy in-dividuals or patients.

Photobiomodulation (PBM) is a procedure that uses light to modulate cellular functions and bio-logical processes. Over the past decades, PBM has gained considerable attention for its potential in various medical applications due to its non-invasive nature and minimal side effects. This narrative review article examines the existing literature on PBM, encompassing research studies, clinical trials, and technological developments. This review highlights the mechanisms of action underlying PBM, including the interaction with cellular chromophores and the activation of in-tracellular signaling pathways. The evidence from clinical trials and experimental studies to evaluate the efficacy of PBM in clinical practice is summarized with a special emphasis on der-matology. Furthermore, advancements in PBM technology, such as novel light sources and treat-ment protocols, are discussed in the context of optimizing therapeutic outcomes and improving patient care. This narrative review underscores the promising role of PBM as a non-invasive therapeutic approach with broad clinical applicability. Despite the need for further research to develop standard protocols, PBM holds great potential for addressing a wide range of medical conditions and enhancing patient outcomes in modern healthcare practice.

Xanthone derivatives, a class of natural compounds abundantly found in plants such as mangosteen (Garcinia mangostana) and certain herbs, have garnered substantial interest due to their diverse pharmacological properties, including antioxidant, anti-inflammatory, and anti-cancer activities. Recent investigations have unveiled their potential as modulators of enzymatic activity, prompting exploration into their effects on hyaluronidase-mediated HA degradation, and their effects in topical treatment of telangiectasia and rosacea. Telangiectasia and rosacea are common dermatological conditions characterized by chronic skin inflammation, vascular abnormalities, and visible blood vessels, resulting in significant cosmetic concerns and impaired quality of life for affected individuals. This review aims to provide a comprehensive overview of the current understanding regarding the interplay between mechanisms of action by which xanthone derivatives exert their therapeutic effects, including the inhibition of pro-inflammatory cytokines, modulation of oxidative stress pathways, and regulation of vascular endothelial growth factors. Furthermore, we will discuss the implications of harnessing xanthone derivatives as therapeutic agents for mitigating vascular dysfunction and its associated pathologies, thereby offering insights into future research directions and therapeutic strategies in the field of vascular biology.

Melasma is a challenging skin condition which involves both structural and functional skin alterations. Despite the availability of various treatment options, the management remains complex. This is the first study to investigate topical application of Rosa Damascena stem cell exosomes when used concomitantly with microneedling in women and men with facial melasma. We recruited 20 subjects with Fitzpatrick skin types I-III, exhibiting melasma of varying severity. The modified Melasma Area and Severity Index (mMASI) and Global Aesthetic Improvement Scale (GAIS) were utilized to evaluate treatment response. The treatment protocol involved microneedling followed by exosome application over four or five sessions, at 4-week intervals. Ninety percent of subjects demonstrated a significant improvement in mMASI scores, while only 10% showed no change. GAIS assessment further supports overall improvement, with just 10% categorized as "not changed". Tolerability was favorable, with mild, transient side effects. Our findings suggest promising outcomes with this combined therapy, underscoring its potential as a safe and effective approach for treating melasma, particularly in severe and moderate cases. However, further research with larger sample sizes and control arms is warranted to validate these findings and explore long-term efficacy.

Hair cosmetics are in fashion. Numerous products are commonly used in combination. Frequent allergens are present in hair cosmetics, which, added to almost daily use, increase the risk of sensitization. Familiarity with the clinical distribution of the eczematous rash is necessary to seriously consider patch testing. There are haptens on the market, although not all of them. It is necessary to know how to patch your own products. When avoidance of the allergen cannot be possible, new treatments are being evaluated to combat allergic contact dermatitis, mainly of the occupational type. In this manuscript, a complete and practical review of the main allergens and contact sources of hair cosmetic origin has been carried out.

Introduction: Wound healing is a complex cascade involving the orchestration of inflammatory cells, skin fibroblasts, keratinocytes, and endothelial cells. These cells achieve tissue repair through an interchange of cytokines and growth factors through a controlled inflammation, angiogenesis, and remodeling process. Disruptions in the wound-healing process by comorbid conditions lead to significant morbidity and mortality. Stem cell therapy has emerged as a new strategy to facilitate the wound healing process. Stem cells harvested from different sources can be used for wound repair and regeneration (endothelial progenitor cells, bone marrow, adipose tissue, dermal and inducible pluripotent stem cells). We aimed to review clinical, translational, and primary literature on stem cell therapies in chronic wounds and summarize practical clinical applications to dermatological care. Materials and Methods: A comprehensive search of Pubmed, Embase, Web of Science, Google Scholar, and Cochrane Library was conducted for studies relating to stem cells and wound healing. Duplicate results were removed using Covidence. Titles and abstracts were screened by two independent researchers (BF and KR), with discrepancies resolved through discussion and mutual agreement. Articles were excluded if they were review-type or commentary-type articles. Results: A total of 22,454 articles were retrieved from the search. Deduplication removed 905, and automation removed an additional 18,363 articles. After an initial screening of titles and abstracts, 170 articles remained. Full-text screening resulted in an additional 126 articles being removed, leaving 44 included studies. Discussion: Stem cells used for wound repair and regeneration include endothelial progenitor stem cells and adult stem cells, in the forms of bone marrow-derived mesenchymal stem cells, adipose tissue stem cells, and inducible pluripotent stem cells. Among these sources, adipose tissue-derived mesenchymal stem cells (AD-MSCs) are ideally used due to the abundant supply of fat tissue, ease of isolation, extensive proliferative capacities ex vivo, and their ability to secrete pro-angiogenic factors. AD-MSCs have been used to enhance wound healing in peripheral arterial disease, diabetic wounds, hypertensive ulcers, bullous diabeticorum, venous ulcers, and postsurgical wounds after Mohs micrographic surgery. These cells have been delivered to the tissue topically, with scaffolds, combined with plasma-rich proteins, and through atelocollagen in various human studies. These approaches, when combined with local wound care practices, resulted in decreased pain, shorter wound healing times, and better cosmesis. Conclusions: Stem cell transplantation is a potential therapeutic approach in the wound healing process. Transplanted stem cells do not only differentiate into multiple skin cell types but also provide cytokine and growth factors required for wound healing resulting in increased angiogenesis. Thus, this approach may be regarded as an attractive option for intractable wounds that cause major clinical problems, especially chronic lower leg wounds. It can also be used after Mohs micrographic surgery for defects left to heal by secondary intention. Stem cell application may reduce the overall cost burden on the healthcare system and improve the quality of life for patients.

To better understand anogenital warts (AGW) natural history and dynamic of HPV6/11 infection in regional hairs, 32 newly diagnosed AGW male patients and 32 age-matched healthy controls were closely followed. During enrollment and six follow-up visits (every 2.6 months) 43 AGW tissue and 1,232 anogenital and eyebrow hair samples were collected. This represents the closest longitudinal monitoring of AGW patients to date. Patients were treated according to standard-of-care. HPV6/11 prevalence was 19.9% in patients’ hair samples (HPV6 B1 in 87.5%) and 0% in controls. The highest HPV6/11 prevalence was found in pubic hairs (29.0%) and lowest in eyebrows (7.1%). Odds for HPV6/11-positive hairs increased with smoking, shaving anogenital region and age. A close association between HPV6/11 presence in hairs and clinically visible AGW was observed. The proportion of patients with visible AGW and HPV6/11-positive hairs declined during follow-up with similar trends. No particular HPV6/11 variant was linked with increased AGW recurrence, but sublineage HPV6 B1 showed significantly higher clearance from hairs. Despite treatment, 78.1% and 62.5% of AGW patients experienced one and two/more post-initial AGW episodes, respectively. Patients having HPV6/11-positive hairs or visible AGW at preceding visit demonstrated substantially higher odds for presenting with visible AGW in subsequent visit.

Cutaneous T-cell lymphomas (CTCLs), encompassing mycosis fungoides (MF) and Sézary syndrome (SS), present a complex landscape influenced by cytokines and cellular responses. In this work, the intricate relationship between these inflammatory proteins and disease pathogenesis is examined, focusing on what is known at a clinical and therapeutic level regarding the most well-known inflammatory mediators. An in-depth look has been given to their possible alterations caused by novel immunomodulatory drugs and how they may alter disease progression.From this narrative review of the actual scientific landscape, Interferon-gamma (IFN-γ) emerges as a central player, demonstrating a dual role in both promoting and inhibiting cancer immunity, but the work navigates through all the major Interleukins known in inflammatory environments.Immunotherapeutic perspectives are elucidated, highlighting the crucial role of the cutaneous microenvironment in shaping dysfunctional cell trafficking, antitumor immunity, and angiogenesis in MF, showcasing advancements in understanding and targeting the immune phenotype in CTCL.In summary, this manuscript aims to comprehensively explore the multifaceted aspects of CTCL, from the immunopathogenesis and cytokine dynamics centred around TNF-α and IFN-γ to evolving therapeutic modalities. Including all the major known and studied cytokines in this analysis broadens our understanding of the intricate interplay influencing CTCL, paving the way for improved management of this complex lymphoma.

In dermatological practice, disturbances of the skin microbiome are found in various infectious and inflammatory dermatoses featuring one or more skin lesions with loss of tissue, directly exposing skin layers to microbial invasions. Literature data on the incidence of cutaneous-onset sepsis are, however, scarce. This retrospective observational study assessed hospital admissions for primary skin lesions with vs. without bacterial infections and sepsis during 2020-2022 in the largest emergency hospital in NE Romania. Of 509 patients 441 had infected lesions, 78 had sepsis caused by venous ulcers microbial eczema cellulitis, superinfected bullous dermatoses, erysipelas, erythroderma. Cultured samples revealed S. aureus, P. aeruginosa, E. coli, with K. pneumoniae, S. β-hemolytic associated with sepsis even if rarer. Clinical manifestations included ulcerations, erosions, fissures, excoriations, bullae, vesicles, pruritus, tumefaction, edema, fever, chills, pain, adenopathy, mildly altered mental status. Underlying chronic heart failure, atrial fibrillation, anemia, type-1 diabetes mellitus were comorbidities associated with infection and sepsis. Significant associations and risk factors, including their combined effects, are discussed to draw attention to the need for further research and adequate management to prevent sepsis in adult patients of any age presenting with infected skin lesions (especially cellulitis) and comorbidities (especially type 1 diabetes mellitus and anemia).

The management of wounds is a significant issue that impacts individuals, healthcare systems, and society at large. This study evaluates Rigemed D (RD), a novel compound extracted from Bovine Colostrum with a unique combination of 20 different growth factors and exosomes, known for its exceptional properties in promoting cell proliferation and regeneration. This study aims to determine the effects of different doses of RD on cell survival (using CCK8) and to assess its antioxidant effect using the Comet assay in the presence of hydrogen peroxide (H2O2) on two human cell types, fibroblasts and immortalised keratinocytes (HaCat cell line). The study results revealed that RD, at doses of 1, 1.5, and 2 % v/v, significantly improved cell viability four, six, and 12 times, respectively, compared to the control group (p < 0.00001). Furthermore, the Comet assay showed a two-fold reduction in DNA damage in RD-treated cells at 2% v/v without and with H2O2 (p < 0.001). The effect of RD on cell proliferation and migration was evaluated using a scratch assay on fibroblasts and HaCat cells. The findings demonstrated a four-fold increase in cell proliferation and migration at 1 and 24 hours (p < 0.001). Immunohistochemistry confirmed this claim (p < 0.001). Also, angiogenesis induction of RD was assessed on human vein umbilical endothelial cells (HUVEC), showing that RD significantly enhanced the proliferation of endothelial HUVEC cells (p < 0.0001). In conclusion, RD is a promising vitalising compound with exceptional capabilities in promoting cell proliferation, migration, and regeneration. It also shows a significant antioxidant effect and has the potential to support all phases of wound healing involving cell proliferation, re-epithelialisation, angiogenesis, and tissue maturation. Hence, the present formulation presents a promising foundation for developing a 3D bio-printed membrane, potentially expediting the wound healing process.

Background: Atopic dermatitis (AD), a common dermatological condition, is often associated with significant economic and social burdens. Despite extensive studies globally, there is a gap in understanding the comprehensive impact of this condition in Romania. Objectives:This study evaluated the economic burden and quality of life impact of AD in Romania, considering both direct and indirect costs. Materials & Methods: A mixed methods cost of illness study was conducted from April to October 2023. A patient survey, expert reviews, and national health data analysis were used to assess direct medical costs (treatments, medical services), direct non-medical costs (transportation, accommodation), and indirect costs (productivity losses). Quality of life was evaluated using the EuroQol EQ-5D-5L instrument. Results: In 2022, the total cost of atopic dermatitis in Romania was 32.983.498 EUR for adults and 31.573.968 EUR for children. Adult costs included 24.534.603 EUR in direct and 8.429.884 EUR in indirect medical costs, with an average annual cost per patient of 447 EUR. Pediatric costs involved 15.026.781 EUR in direct and 16.516.410 EUR in indirect costs, averaging 290 EUR per patient annually. Conclusion: Care expenditure with AD management in Romania is substantially lower than in other countries, posing a significant economic burden, primarily driven by indirect costs. This study provides a foundation for future policy interventions and highlights the need for targeted management strategies for AD.

Background: Alopecia areata is a skin disease that affects patients’ quality of life and social participation. Objective: To quantify the economic burden of alopecia areata and to map health services utilization among patients with alopecia areata.Materials and methods: Prospective and retrospective data sources, using both top-down and bottom-up approaches to estimate direct and indirect costs and to map health service utilization associated with alopecia areata in Romania in 2022.Results: In our study, the total cost of alopecia areata in Romania for 2022 was estimated at 46.289 million EUR for adult patients and 1.89 million EUR for pediatric patients, encompassing both mild and severe cases. The breakdown reveals that both mild and severe cases incurred the highest costs due to associated expenses, medical services, and treatment. As for children, the highest alopecia-related expenses were represented by associated expenses and treatment costs (for both severity levels).Conclusion: This is the first study to quantify the burden of alopecia areata in Romania. Additional studies are needed due to a low sample size. However, considering our estimations based on external data sources, alopecia areata should be considered when planning health service distribution.

The introduction of biologic therapies has led to dramatic improvements in the management of moderate-to-severe psoriasis. Even though the efficacy and safety of the newer biologic agents are difficult to match, oral administration is considered an important advantage by many patients. Current research is focused on development of oral therapies with improved efficacy and safety compared to available alternatives, as exemplified by deucravacitinib, the first oral allosteric Tyk2 inhibitor approved for the treatment of moderate-to-severe psoriasis in adults. Recent advances in our knowledge of psoriasis pathogenesis have also led to the development of targeted topical molecules, mostly focused on intracellular signaling pathways, such as AhR, PDE-4 and Jak-STAT. Topical tapinarof, an AhR modulator, and roflumilast, a PDE-4 inhibitor, have exhibited favorable efficacy and safety outcomes have been approved by the FDA for the topical treatment of plaque psoriasis. This revision focuses on the most recent oral and topical therapies available for psoriasis and specially on those that are currently under evaluation and development for the treatment of psoriasis.

Background: Laser therapies can cause hyper- and hypopigmentation of the skin. There is little evidence in the literature of effective treatments for these types of problems in Fitzpatrick IV-VI skin phototypes. The main aim of this retrospective study is to evaluate the effects of a new therapy combining the application of electromagnetic fields and vacuum on a subject with Fitzpatrick VI skin phototype, presenting an extensive, laser-induced facial dyschromia. The secondary aim is to test the effectiveness of a free imaging software for assessing skin pigmentation. Methods: The level of improvement after the therapy was evaluated, with a 5-point Likert scale, one month after the end of the treatment by both the subject, and the doctor who performed the treatment, and by two blinded dermatologists. With the free software, a three-dimensional reconstruction of the area treated and the evaluation of colour distribution were performed. Results: Both the subject and the doctors involved in the study positively evaluated the effects of the treatment. The image analysis highlighted the homogenization of the skin colour in the treated area. Conclusions: The combination of electromagnetic fields and vacuum for dyschromia treatments appears promising. The new method of assessing melanin levels resulted particularly efficient.

Diagnosing skin lesions can be a challenging task. Dermatologic lesions are hard to differentiate especially for an untrained eye. However, carefully analyzing every aspect of the lesion can help clinicians reach an accurate diagnosis. If diagnosed correctly with the naked eye, many lesions can be treated without the need for further histopathology or investigations. Those aspects include morphology, color, distribution, configuration and arrangement, texture and consistency, and any evolutions or changes within the lesion. Clinicians must also contextualize those lesions into the patient’s history and overall systemic symptoms and signs. Risk factors should be taken into consideration and whether there are evolutionary changes in the lesions. Clinicians should also look for patterns as they might be the key to diagnosis. If definitive diagnosis is still not reached, biopsy, dermatoscopy, cultures, skin scrapings, patch testing, blood tests, and imaging studies may be necessary for confirmation. Integrating these methods with clinical judgment and patient history significantly enhances the accuracy of diagnosis in dermatology. Treatment for dermatologic lesions varies depending on the underlying cause.

(1) Background: Various cutaneous adverse drug reactions (ADRs) are observed with the development of mRNA COVID-19 vaccines. To gain insight into the clinicopathologic features, we analyzed the correlation of histological and clinical data in 48 patients with these ADRs.; (2) Methods: Single-center retrospective study in patients with ADRs post-mRNA COVID-19 vaccination (mRNA-1273 and BNT162b2 vaccines).; (3) Results: Distant generalized ADRs prevailed (91%), often appearing clinically as spongiotic dermatitis or maculo-papular exanthema. Histopathological analysis revealed spongiotic changes (46%) and dermal superficial perivascular lympho-histiocytic infiltrates (17%). Eosinophils were found in 66% of biopsies, neutrophils in 29%, and plasma cells only in 8% of biopsies. Most ADRs occurred post-second vaccine dose (44%). Histologically spongiotic changes were associated with clinical features of spongiotic dermatitis in only 50% and maculo-papular exanthema in the remaining patients. ADRs represented an aggravation of preexisting skin disease in 23% of patients. ADRs regressed within 28 days or less in 53% of patients and persisted beyond a month in the remaining patients.; (4) Conclusions: Our study demonstrates a diverse spectrum of generalized ADRs, revealing correlations between histology and clinical features but also instances of divergence. The majority of ADRs are self-limited with a few extending beyond a month.

This study explores the innovative use of CO2 laser technology in frenuloplasty, a significant shift from traditional methods like scalpel surgery or electrocautery, towards a minimally invasive approach. The research involved 15 patients aged 25 to 50, undergoing frenuloplasty with a CO2 laser system equipped with a 7-inch defocused handpiece, set at 20Hz and 0.3W. This method diverges from conventional laser techniques, focusing on controlled laser passes combined with manual traction to elongate the fibrous tissue of the frenulum. The results demonstrated that the CO2 laser technique allowed for a precise and progressive modification of the frenulum, significantly reducing the risks of hemorrhage and secondary in-tention fibrosis. The healing process was notably expedited, with patients reporting satisfactory outcomes within a two-week period. Statistically significant improvements were observed in pa-tient-reported outcomes, as evidenced by the increases in the Short Form Health Survey (SF-12) scores, with the mean Physical Component Summary (PCS) score rising from 32.5 to 47.5 and the mean Mental Component Summary (MCS) score from 39.3 to 52.3 (p < 0.001 for both). The study concludes that CO2 laser frenuloplasty is an effective and safe technique, offering sub-stantial benefits in terms of reduced healing time and enhanced patient satisfaction. The signifi-cant improvements in SF-12 scores underscore the positive impact on patient quality of life, ad-vocating for the broader application of this technique in clinical practice. Further research is warranted to explore its potential in a wider clinical context.

Kojic acid (KA) has emerged as a prominent tyrosinase inhibitor with considerable potential in cosmetic applications; however, its susceptibility to instability during storage poses a challenge to its widespread use. This review explores the advancements in addressing this limitation through the development of various KA derivatives, focusing on the modification of the C-7 hydroxyl group. Strategies such as esterification, hydroxy-phenyl ether formation, glycosylation, and incorporation into amino acid or tripeptide derivatives have been employed to enhance stability and efficacy. Among these derivatives, Kojic Acid Dipalmitate (KDP), a palmitic ester derivative of KA, stands out for its notable improvements in stability, permeability, and low toxicity. Recent developments indicate a growing utilization of KDP in cosmetic formulations, with over 132 available products on the market, encompassing various formulations. Additionally, three patents and seven advanced system deliveries of KDP further underscore its significance. Despite its increasing prevalence, the literature on KDP remains limited. This comprehensive review aims to bridge this gap by providing insights into the synthesis process, physicochemical properties, pharmaceutical preparation, diverse applications of KDP in cosmetic products, and recent nanotechnology formulations of KDP. This review paper seeks to explore the recent developments in the use of KDP in cosmetics. The goal is to enhance stability, permeability, and reduce the toxicity of KA, with the intention of promoting future research in this promising sector.

Superficial mycoses, encompassing a range of fungal infections affecting the outer layers of the skin, hair, and nails, have become increasingly prevalent in recent years. While these infections are generally non-life-threatening, the emergence of antifungal resistance poses a growing threat to effective treatment strategies. In this article we explore the escalating specter of antifungal resistance in superficial mycoses, focusing on the underlying mechanisms driving resistance, the clinical implications, and potential avenues for mitigation. The rise of antifungal resistance in superficial mycoses is multifactorial. Consequently, the efficacy of conventional treatments is diminishing, leading to persistent or recurrent infections. Understanding the molecular mechanisms underlying antifungal resistance is crucial for developing targeted therapeutic approaches. Research efforts aimed at unraveling these mechanisms are essential for identifying new drug targets and designing innovative treatment strategies to combat resistant strains. In response to the escalating threat of antifungal resistance, a multifaceted approach is required. This includes enhanced surveillance of antifungal susceptibility patterns, the development of novel antifungal agents, and the implementation of stringent guidelines for antifungal use. Additionally, educational initiatives targeting healthcare professionals and the public are essential to promote responsible antifungal use, reduce the risk of resistance emergence, and improve treatment outcomes.

Background: We previously reported that human keratinocytes express protease-activated receptor (PAR)-2 and play an important role in activated protein C (APC)-induced cutaneous wound healing. This study investigated the involvement of PAR-2 in the production of gelatinolytic matrix metalloproteinases (MMP)-2 and -9 by APC during cutaneous wound healing. Methods: Full-thickness excisional wounds were made on the dorsum of male C57BL/6 mice. Wounds were treated with APC on days 1, 2, and 3 post-wounding. Cultured neonatal foreskin keratinocytes were treated with APC with or without intact PAR-2 signalling to examine the effects on MMP-2 and MMP-9 production. Murine dermal fibroblasts from PAR2 knock-out (KO) mice were also assessed. MMP-2 and -9 were measured by gelatin zymography, fluorometric assay, and immunohistochemistry. Results: APC accelerated wound healing in WT mice, but had negligible effect in PAR-2 KO mice. APC stimulated murine cutaneous wound healing was associated with differential 0temporal production of MMP-2 and MMP-9, with the latter peaking on Day 1 and the former on Day 6. In-hibition of PAR-2 in human keratinocytes reduced APC-induced MMP-2 activity 25~50, but had little effect on MMP-9. Similarly, APC-induced MMP-2 activation was reduced by 40% in cultured dermal fibroblasts derived from PAR-2 KO mice. Conclusion: This study shows for the first time that PAR-2 is essential for APC-induced MMP-2 production. Considering the important role of MMP-2 in wound healing, this work helps explain the underlying mechanisms of action of APC to promote wound healing through PAR2.

Background and Objectives: Inflammatory bowel disease (IBD) may affect organs outside the intestines, it is called extraintestinal manifestations of IBD. Data on the prevalence of mucocutaneous manifestations in IBD patients are very limited, therefore, the aim of this study was to assess the prevalence of skin and mucosal lesions and to determine the relationship with demographic factors, clinical features, and systemic treatment. Materials and Methods: Prospective study included 162 out-patients with IBD who were managed in the tertiary care center. Ulcerative colitis (UC) was diagnosed in 117 patients, Crohn's disease (CD) in 45. Patients completed the questionnaire containing demographic and IBD data, questions about mucocutaneous lesions (in past or present state). Results: Skin lesions were reported by 40.7% of patients, oral mucosal lesions were reported by 16.7%, without significant differences between sexes or IBD types. In 47 (29%) of patients, skin lesions appeared together with IBD or during the course of the disease. The most common skin lesions were psoriasis (8.0%), erythema nodosum (5.6%), pyoderma gangrenosum and acne (3.7% each). UC patients mostly reported about psoriasis (9.4%), while CD patients – erythema nodosum (11.1%). There were more frequent skin lesions in patients with more extensive UC type (p = 0.01), while no difference was noticed between different types of CD. The average duration of IBD in patients with skin lesions was similar to those without lesions (9.3±6.7 vs. 9.4±6.7 years). Conclusions: Mucocutaneous lesions were reported by 48.8% of inflammatory bowel disease patients. The frequency of mucocutaneous lesions does not differ significantly between UC and CD, and a longer duration of illness is not a predictive factor for the appearance of lesions. More extensive UC is related to higher frequency of skin lesions.

(1) Background: This manuscript introduces the "Lines and Dots" (LAD) technique, a novel method for administering Botulinum Toxin Type A (BoNT-A) in treating horizontal forehead lines. This technique emphasizes precision in targeting nerve endplates, considering individual anatomical variations, and optimizing treatment efficacy. (2) Methods: The LAD technique focus on using the frontalis muscle contraction dynamics to identify the specific distribution of the supraorbital and supratrochlear nerves It involves creating a grid of predetermined lines and points on the forehead that align with nerve paths and motor endplate zones. (3) Results: By targeting injections along these precise lines and points, the LAD technique ensures more effective utilization of BoNT-A. This approach not only enhances the toxin's effect but also allows for a reduction in the overall dosage. The strategic placement of injections results in a more natural, symmetrical, and sustained therapeutic effect, ensuring an improved aesthetic outcome. (4) Conclusions: The LAD technique represents a significant advancement in the realm of cosmetic injectables. It offers a tailored, patient-specific approach, maximizing the effectiveness of BoNT-A injections for treating forehead lines while minimizing risks and enhancing patient satisfaction. This method underscores the importance of a deep anatomical understanding and precision in cosmetic procedures.

Wounds are breaks in the continuity of the skin and the underlying tissues, due to external causes, such as cuts, blows and impacts, or even, during surgical interventions. Millions of people suffer minor or serious injuries, sometimes ending in death. Today, there are many commercially available products that promote healing from wounds. The high demand from the healthcare industry has created a huge market that continues to grow, fueling research and development of new wound healing products. In the present article, we review recent advances in wound healing products based on natural biopolymers, stem cells, and microRNAs. We analyze the advances of both, the commercial products and the products that are still in research phase, and we also include an overview of the opportunities, barriers, and regulatory issues for the commercialization of these products in the European, American, and Asian markets.

Since atopic dermatitis (AD) is a heterogeneous condition, subtyping of AD is a crucial issue. The classical subtypes of AD are represented by extrinsic and intrinsic subtypes, European American and Asian subtypes, and adult and pediatric subtypes. While subtyping of AD was historically conducted based on the phenotype, recent findings on the mechanisms of AD have revealed importance of the endotype, which can characterize individual patients more accurately. Considering the current development of AD therapies, AD endotyping is prerequisite for personalized therapeutic choice. Endotypes of AD can be stratified from different viewpoints, including cytokine expression patterns, allergen properties, epidermal barrier conditions, ceramide variation, involvement of innate immunity, and serum biomarkers. Among them, the cytokine-based endotype seems to be the most useful one and is categorized into type 2 cytokine (IL-4, IL-13 and IL-31)-high, type 1 cytokine (interferon-g)-high, and/or type 3 cytokine (IL-22 and IL-17)-high, or mixed subtypes. The recently biomarker-proposed endotyping aims at individualized treatment options, although the daily clinical use of endotypes is a future issue. To better understand the endotypes for clinicians, attempts to adjust each of the classical subtypes to the endotypes are required. This review will discuss the correspondence of the classical subtypes to the various endotypes that have recently been proposed.

Adherence with multidrug therapy (MDT) is one of the keys to successful treatment of leprosy. In order to understand the treatment behavior, reasons for non-adherence, and efforts to improve medication adherence, it is necessary to use a valid and reliable instrument to measure adherence to MDT in multibacillary leprosy patients on regular basis. This study used a mixed method de-sign. The instrument development phase involved 10 experts using 4 rounds of Delphi method. Assessment items that are considered relevant are those that meet 4-5 Likert scale by a minimum of 75% of experts or meet assessment score >3.75. We did the pilot testing and the questionnaire was revised if invalid. After obtaining a valid and reliable instrument, it was tested to 100 sub-jects in 4 health centers. For internal validity test, 9 valid assessment items were obtained, with the correlation coefficient values of each item >0.3, and -Cronbach's reliability of 0.723. The instru-ment produced had sensitivity of 88.46% and specificity of 78.37%. From 100 subjects enrolled, 61% had good adherence and 39% had poor adherence based on questionnaire assessment. A valid and reliable questionnaire for evaluating adherence with MDT in Indonesian patients has been composed.

Tissue regeneration is an essential requirement for wound healing and recovery of organs’ function. It has been demonstrated that wound healing can be facilitated by activating paracrine signaling mediated by exosomes secreted from stem cells, since exosomes deliver many functional molecules including growth factors (GFs) and neurotrophic factors (NFs) effective for tissue regeneration. In this study, an exosome-rich conditioned medium (ERCM) was collected from human amniotic membrane stem cells (AMSCs) by cultivating the cells under a low oxygen tension (2% O2 and 5% CO2). The contents of GFs and NFs including keratinocyte growth factor, epidermal growth factor, fibroblast growth factor 1, transforming growth factor-β, and vascular endothelial growth factor responsible for skin regeneration were much higher (10-30 folds) in the ERCM than in normal conditioned medium (NCM). In was found that CM-DiI-labeled exosomes readily entered keratinocytes and fibroblasts, and that ERCM not only facilitated the proliferation of keratinocytes in normal condition, but also protected against H2O2 cytotoxicity. In cell-migration assay, the scratch wound in keratinocyte culture dish was rapidly closed by treatment with ERCM. Such wound-healing effects of ERCM were confirmed in a rat whole skin-excision model: i.e., the wound closure was significantly accelerated, remaining minimal crusts, by topical application of ERCM solution (4 x 109 exosome particles/100 μL) at 4-day intervals. In the wounded skin, the deposition of collagens was enhanced by treatment with ERCM, which was supported by the increased production of collagen-1 and collagen-3. In addition, enhanced angiogenesis in ERCM-treated wounds was confirmed by increased von Willebrand factor (vWF)-positive endothelial cells. The results indicate that ERCM from AMSCs with high concentrations of GFs and NFs improves wound healing through tissue regeneration not only by facilitating keratinocyte proliferation for skin repair, but also activating fibroblasts for extracellular matrix production, in addition to the regulation of angiogenesis and scar tissue formation.

Background and Objectives: Previous studies revealed anti-angiogenic, antiproliferative and anti-inflammatory effects of Vitamin D on cancer cells. Although this body of evidence supported the correlation of high Vitamin D levels with reduced incidence rates for various malignancies, contradictory results were reported regarding non-melanoma skin cancer (NMSC). Aim of this overview was to summarize the available evidence from the existing pool of systematic reviews and meta-analyses, focusing on Vitamin D serum status, dietary intake, and Vitamin D receptor (VDR) polymorphisms in correlation to NMSC incidence. Materials and Methods: A literature search in electronic databases was conducted from inception to January 2023. Inclusion criteria were systematic reviews and meta-analyses published in peer-reviewed journals, evaluating Vitamin D serum levels, dietary and/or supplementary intake, or VDR gene polymorphisms, and reporting data on NMSC. Results: A total of 10 studies were included in the data analysis models. A positive association between Vitamin D serum levels and NMSC is highlighted. However, dietary/supplementation of Vitamin D doesn’t exhibit a likewise strong linkage to NMSC. Despite the contradictory findings, VDR polymorphisms may play a crucial role in the intricate NMSC pathogenesis. Conclusions: This umbrella review showed that high Vitamin D levels are associated with increased NMSC incidence, potentially due to its direct correlation with increased sun exposure. Further research on VDR polymorphisms is suggested to explore their true effect size on NMSC risk.

In Caucasians, basal cell carcinoma, a type of non-melanoma skin cancer, is most often found on the nose. This presents challenges for surgeons due to anatomical, functional, and aesthetic concerns. The study aimed to evaluate the distribution of tumor localization, size, morphological subtypes, surgical outcomes, radicality levels, and their correlation with recurrence rates. The research utilized data from the Hygiene Institute Health Information Centre. A retrospective analysis encompassed 343 cases of nasal skin cancer over a four-year period from January 1, 2019, to December 31, 2022. The research cohort comprised 252 female and 91 male participants, averaging 75,2 years old. Tumors were most found on the left sidewall of the nose (25.4%) and the dorsum (24.8%). The infiltrative morphological subtype was predominant (70.8%). Standard surgical excision with fasciocutaneous plastic was the preferred surgical procedure. Radical excision was achieved in 79.0% of lesions, while 16.9% were incompletely excised. Non-radically excised tumors exhibited a significantly higher recurrence rate (24.1%) compared to those with radical excision (6.3%). In nasal reconstruction, diverse surgical techniques are essential for precise adaptation based on factors like tumor characteristics and patient needs. Despite surgeons' careful adherence to excision guidelines, the potential for non-radical procedures cannot be entirely eliminated.

CD147/Basigin, a transmembrane glycoprotein belonging to the immunoglobulin super family, is a multifunctional molecule with various binding partners. CD147 binds to monocarboxylate transporters (MCTs) and supports their expression on plasma membranes. MCTs play an important role in glycolysis, the enzymatic conversion of glucose to pyruvate and adenosine triphosphate (ATP). Pyruvate is further converted to lactic acid which is exported from the cytoplasm by MTC-1 and MCT-4 to maintain intracellular pH and a stable metabolic state. Under physiological conditions, cellular energy production is induced by mitochondrial oxidative phosphorylation. Glycolysis usually occurs under anaerobic conditions, whereas cancer cells depend on glycolysis under aerobic conditions. T cells also require glycolysis for differentiation, proliferation, and activation. Human malignant melanoma cells expressed higher levels of MCT-1 and MCT-4, co-localized with CD147 on the plasma membrane and showed an increased glycolysis rate compared to normal human melanocytes. Silencing of CD147 by siRNA abrogated the membrane expression of MCT-1 and MCT-4 and disrupted glycolysis, inhibiting cancer cell activity. The differentiation of CD4+ T cells into Th17 cells is a pivotal process in the development of various immune disorders, including psoriasis. Studies using CD147-deficient mice demonstrated the involvement of CD147 in psoriasis. MCT-1 was absent on CD4+ T cells in CD147-deficient mice. Naïve CD4+ T-cells from CD147-deficient mice show low potential for differentiation into Th17 cells. Imiquimod-induced skin inflammation was significantly milder in CD147-deficient mice than in wild-type mice. These findings indicate that CD147/Basigin is involved in the development of malignant tumors and T cell mediated immunological disorders via regulation of glycolysis.

Myeloid neoplasms and acute leukemias include different entities that have been recently re-classify taking into account molecular and clinicopathological features. The myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) category comprises a heterogeneous group of hybrid neoplastic myeloid diseases characterized by the co-occurrence of clinical and pathologic features of both myelodysplastic and myeloproliferative neoplasms. The most frequent entity in this category is chronic myelomonocytic leukemia (CMML) which is, after acute myeloid leukemia (AML), the main myeloid disorder prone to develop cutaneous manifestations. Skin lesions associated with myelodysplastic and myeloproliferative neoplasms include a broad clinical, histopathological and molecular spectrum of lesions, poorly understood and without a clear-cut classification in the current medical literature. The aim of this review is to describe and classify the main clinical, histopathological and molecular patterns of cutaneous lesions in the setting of MDS/MPN in order to improve the diagnostic skills of dermatologists, hematologist and pathologist who deal with these patients.

Psoriasis is a common chronic immune-mediated disease with many comorbidities and impacts on quality of life. Among the treatment options for psoriasis, phosphodiesterase-4 (PDE4) inhibi-tors are emerging with expanding options. PDE4 inhibitors play a pivotal role in the inflamma-tory cascade by degrading cyclic adenosine monophosphate (cAMP), contributing to pro-inflammatory mediator production. Apremilast, an oral PDE4 inhibitor, is an approved class for psoriasis. While effective, its adverse effects can limit its utility. Roflumilast, a topical PDE4 inhibitor, was recently also approved for psoriasis and shows promise in clinical trials. Crisaborole, approved for atopic dermatitis, has also been studied in psoriasis. This updated re-view summarizes evidence from randomized clinical trials regarding the efficacy and safety of PDE4 inhibitors in psoriasis treatment. By highlighting their potential benefits and limitations, this review provides valuable insights for clinicians and researchers aiming to optimize psoriasis therapy.

The practice of voluntary depigmentation is still prevalent in Africa, with a wide range of lightening cosmetics used. Our objective was to research and quantify three regulated and/or prohibited depigmenting ingredients present in lightening cosmetics sold in Ouagadougou. Twenty-nine lightening cosmetic samples were collected from vendors and HPLC analysis was subsequently conducted to identify and measure the concentrations of hydroquinone, clobetasol propionate, and kojic acid. The presence of hydroquinone was indicated on the label of 13.79% of the products, while 51.72% contained it after analysis. Furthermore, none of the products mentioned a concentration of hydroquinone exceeding 2.00%, even though 27.58% of them contained high concentrations. For clobetasol propionate, its presence was stated on the labels of 13.79% of the products, while 31.03% contained it. One sample had a clobetasol content exceeding 0.05%, although none mentioned a concentration higher than this value. Finally, while 24.13% of the samples claimed to contain kojic acid, only 17.24% did. We also observed that 41.38% of the samples contained combinations of two depigmenting ingredients investigated, with a predominance of the hydroquinone + clobetasol propionate (27.38%). These results demonstrate that manufacturers' declarations regarding the compositions of active ingredients in lightening cosmetics can sometimes be deceptive.

Seaweeds have been the target of much attention due to the known bioactivities of some of their compounds. Although many studies about the application of seaweeds in various areas are available, these data are mostly about the raw extracts and not about specific compounds, such as seaweeds pigments. Moreover, the fungal infections of the skin, nails and hair caused by dermatophytes, are the most common fungal infections in humans. These pathologies require long periods of topical and/or systemic treatment that are associated with adverse effects and contraindications. This study had two objectives, the first was to evaluate the possibility of isolating and characterizing the pigments of Calliblepharis jubata and Fucus vesiculosus; the second was to assess their antifungal activity. The extraction of pigments was performed using a method of extraction by exhaustion; the purification was carried out by column chromatography. Three techniques were used to characterize the pigments, thin layer chromatography (TLC), UV-visible spectrophotometry and Fourier-transform infrared spectroscopy (FTIR). The antifungal activity was evaluated using the micro-dilution method, following the EUCAST international standards, on three dermatophytes, Trichophyton rubrum, Trichophyton mentagrophytes and Microsporum canis. It was possible to observe that the extract obtained from the seaweed C. jubata and F. vesiculosus, corresponding to the purified pigment phycobiliprotein, and the crude extract, an enriched extract, obtained from the seaweed C. jubata showed antifungal activity against the three fungal agents of human skin infection.

Dermal pigmentation is a challenging condition due to relative resistance to medical treatment and requirement of multiple sessions with modalities like chemical peels and lasers. There is inadequate literature regarding the efficacy and safety of lasers for dermal pigmentation in Indian skin. One hundred and twenty two patients were enrolled and divided into 4 groups: a) Dermal melasma b) Acquired dermal macular hyperpigmentation c) Nevus and d) Tattoo. Sequential combination of various lasers were used with different protocols for 4 different groups like ablative pixel Er:YAG, intense pulse light based technologies, Q-Switched and Alma Hybrid lasers for treatment of dermal pigmentation. A total of 4-10 sessions were conducted at three weekly intervals. Results were evaluated by comparing photographs at baseline, one month after the last session and then at 6 months interval to assess the relapse. All groups showed a statistically significant reduction in pigmentation. The mean treatment duration was 5-7 months for tattoo, lichen planus pigmentosus and melasma with 6-8 number of sessions. The mean treatment duration for nevus was 7-9 months with 8-10 sessions. Lasers are safe and effective modalities in Indian skin type for treatment of dermal pigmentation. Treatment period and relapse of dermal pigmentation may be reduced by combining resurfacing and chromophore selective lasers along with adequate dietary and lifestyle modifications to minimize complications and recurrence rates.

This review provides information on acne transcriptomics allowing deeper insights into acne pathogenesis and isotretinoin´s mode of action. Puberty-induced insulin-like growth factor 1 (IGF-1), insulin and androgen signaling activate the kinase AKT and mechanistic target of rapamycin complex 1 (mTORC1). Western diet (hyperglycemic carbohydrates, milk/dairy products) as well co-stimulate AKT/mTORC1 signaling. AKT-mediated phosphorylation of nuclear FoxO1 and FoxO3 results in their extrusion into the cytoplasm, a critical switch, which enhances the transactivation of lipogenic and proinflammatory transcription factors including androgen receptor (AR), sterol regulatory element-binding transcription factor 1 (SREBF1), peroxisome proliferator-activated receptor γ (PPARγ), and signal transducer and activator of transcription 3 (STAT3) but reduces FoxO1-dependent expression of GATA binding protein 6 (GATA6), the key transcription factor of infundibular keratinocyte homeostasis. AKT-mediated phosphorylation of the p53-binding protein MDM2 promotes the degradation of p53. In contrast, isotretinoin enhances the expression of p53, FoxO1 and FoxO3 in sebaceous glands of acne patients. Overexpression of these proapoptotic transcription factors explains isotretinoin´s desired sebum-suppressive effect via induction of sebocyte apoptosis but also its adverse effects including teratogenicity (neural crest cell apoptosis), reduced ovarian reserve (granulosa cell apoptosis), risk of depression (apoptosis of hypothalamic neurons), VLDL hyperlipidemia, intracranial hypertension and dry skin.

Dermal penetration is considered to mainly occur via passive diffusion. Therefore, a high concentration gradient of dissolved active ingredient between formulation and skin is needed to achieve an effective dermal penetration. The concentration gradient between formulation and skin can be changed by changing the amount of dissolved active ingredient in the formulation. In case of poorly soluble active ingredients this can be achieved by using nanosized drug material instead of larger sized material. The smaller size and the resulting larger surface increase the kinetic solubility and thus increase the concentration gradient of dissolved active ingredient between formulation and skin, which then results in an increased dermal penetration. In this study we demonstrated that the concentration gradient between formulation and skin can also be influenced by the number of particles being present in the formulation and by the dose (volume of formulation) applied to the skin. Particles of undissolved active ingredient are known to act as a reservoir by releasing dissolved molecules in the liquid phase of the formulation. It could now be demonstrated that the particles - once the liquid in which they are dispersed evaporates - can connect to the skin via an aqueous meniscus. The aqueous meniscus contains dissolved active ingredient and therefore creates a small local spot with a locally high concentration gradient and improved dermal penetration. Therefore, the dermal penetration can be increased with formulations that contain high amounts of particles. This can be achieved by applying formulations with high numbers of particles and/or by applying larger volumes of particle containing formulations to the skin.

The patient was a 44-year-old woman with suspected Stevens-Johnson syndrome due to Baktar® (sulfamethoxazole trimethoprim) medication received at our outpatient dermatology clinic. Histopathological examination of the epidermis, dermis, and subcutaneous adipose tissue samples showed numerous necrotic keratinocytes in the epidermis. Apoptotic nuclei were visualized as diaminobenzidine brown deposits with immunoperoxidase staining for cleaved caspase-3. Cleaved-caspase3-positive findings were consistent with eosinophilic material that appeared to be necrotic cells within the epidermis. Therefore, these eosinophilic materials must be apoptotic bodies. Generally speaking, and especially in Japan, these materials are considered necrotic keratinocytes. To our best knowledge, no studies have used apoptotic immunohistochemical markers to examine whether these structures are apoptotic.

Background: There have been few reports of cutaneous skin lesions in severe COVID-19 hospitalized patients which exhibit different behavior compared to outpatients. Furthermore, a notable lack of rigorous studies exits. In this study we included patients with generalized rash during the first wave of the pandemic for characterization.Methods: Hospitalized patients with severe confirmed pulmonary COVID-19 infection and a generalized cutaneous rash during the first wave in March-May 2020 were included. The study received approval from the ethics committee. Clinical presentation, histo-logical examination, blood test, and complete blood interleukin profile were assessed. Special immunohistochemical investigations were conducted. Long term follow-up of the patient was performed throuhg a phone call 24 months later. Results: A total 28 patients were studied and classified by histological examination into three groups: G1: perivascular dermatitis (18/28, 64%); G2: Drug reaction (7/28, 25%); and G3: Generalized exanthema and chilblain (3/28, 11%). The virus was not detected in the skin, by PCR and by immunohistochemical analysis, and the interleukin expression in the skin were undetectable results. Vascular cell adhesion molecule 1 (VCAM1), E-selectine, and IT Galpha 5 were unspecific. G1 exhibited the least inflammation, G2 the most in-flammatory, and G3 had previous inflammation. Discussion: Our data suggest that generalized exanthemas during severe SARS-Cov-2 infection exhibit unspecific finding and are similar to other rashes caused by inflammation. Drug reaction should be considered, as they accounted for 25% of the rashes. Further studies including higher number of patients are necessary.

An analysis of the relationship between plasma cytokines and the effectiveness of treatment with TNFαinhibitors was performed in 81 patients with moderate-to-severe psoriasis. Treatment efficacy was assessed by PASI score, and patients were classified into a positive effect (PASI≥75) and no effect group (PASI≤50). A positive effect was reached in 11 (41%) patients for etanercept, 14 (52%) for adalimumab, and 26 (96%) for infliximab. Data analysis did not show  differences in baseline TNFα levels and subsequent treatment effectiveness. The CART algorithm showed that at the baseline level of VEGF ≥ 32 pg/ml and IL17F &lt; 26 pg/ml, there was an 83% probability of a positive effect. Random forest analysis showed the importance of VEGF, ICAM1, sCD40L, IL17F and IL31 baseline levels in the prediction of treatment effectiveness.   Significant differences between the groups before/after the treatment were found only for TNFα: the median values were more than 50 times higher in no effect compared with positive effect group. There were differences before/after therapy in the levels of IL20, ICAM1, IL22, IL23 in the no effect group. The treatment affected the cytokine profile in most cases regardless of the effectiveness of therapy.

Macrophages play a pivotal role in the process of healing burns. One of the major risks in the course of burns healing, in the absence of regenerating epidermis, is infections which greatly contribute to morbidity and mortality in such patients. Therefore, it is widely agreed that accelerating recruitment of macrophages into burns may contribute to faster regeneration of the epidermis and thus, decreasing the risk of infections. This review describes a unique method for rapid recruitment of macrophages into burns and activation of these macrophages to mediate accelerated regrowth of the epidermis and healing of burns. The method is based on application of bio-degradable “alpha-gal” nanoparticles to burns. These nanoparticles present multiple alpha-gal epitopes (Gal alpha1-3Gal beta1-4GlcNAc-R) which bind the abundant natural anti-Gal antibody that constitutes ~1% of immunoglobulins in humans. Anti-Gal/alpha-gal nanoparticles interaction activates the complement system, resulting in localized production of the complement cleavage-peptides C5a and C3a that are highly effective chemotactic factors for monocytes derived macrophages. The macrophages recruited into the alpha-gal nanoparticles treated burns are activated following interaction between the Fc portion of anti-Gal coating the nanoparticles and the multiple Fc receptors on macrophages cell membranes. The activated macrophages secrete a variety of cytokines/growth factors that accelerate the regrowth of the epidermis and regeneration of the injured skin, thereby cutting the healing time by half. Studies on healing of thermal injuries in the skin of anti-Gal producing mice, demonstrated a much faster recruitment of macrophages into burns treated with alpha-gal nanoparticles than in control burns treated with saline and healing of the burns within 6 days, whereas healing of control burns takes ~12 days. alpha-Gal nanoparticles are non-toxic, and do not cause chronic granulomas or keloids. These findings suggest that alpha-gal nanoparticles treatment may harness anti-Gal for inducing similar accelerated burn healing effects also in humans.