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Melanoma and non-melanoma skin cancers (NMSCs) are the most frequent cancers of the skin in white populations. An increased risk in the development of skin cancers has been associated with the combination of several environmental factors (i.e., ultraviolet exposure) and genetic background, including melanocortin-1 receptor (MC1R) status. In the last few years, advances in the diagnosis of skin cancers provided a great impact on clinical practice. Despite these advances, NMSCs are still the most common malignancy in humans and melanoma still shows a rising incidence and a poor prognosis when diagnosed at an advanced stage. Efforts are required to underlie the genetic and clinical heterogeneity of melanoma and NMSCs, leading to an optimization of the management of affected patients. The clinical implications of the impact of germline MC1R variants in melanoma and NMSCs’ risk, together with the additional risk conferred by somatic mutations in other peculiar genes, as well as the role of MC1R screening in skin cancers’ prevention will be addressed in the current review.

Skin aging is a multifactorial process driven by a combination of intrinsic genetic programming and extrinsic environmental exposures. Recent advances in epigenetics have illuminated how changes in DNA methylation, histone modifications, and non-coding RNAs regulate skin aging, with the epigenetic clock emerging as a powerful tool to quantify biological age. This review aims to synthesize current evidence on how environmental and lifestyle factors - particularly ultraviolet radiation, pollution, smoking, diet, and stress - accelerate skin aging through epigenetic mechanisms, while also evaluating the potential of skin-specific epigenetic clocks as biomarkers for early detection of premature aging and for guiding therapeutic interventions. We further discuss the expanding field of epigenetic-targeted therapies in dermatology, encompassing topical agents, energy-based devices, and systemic approaches that may reverse or delay visible signs of cutaneous aging. By integrating insights from molecular biology, environmental science, and clinical dermatology, this review positions skin aging not as an irreversible outcome but as a modifiable, biologically regulated process with promising avenues for personalized prevention and rejuvenation.

Melanoma, the most aggressive form of skin cancer, still represents a significant and growing public health concern. Ultraviolet radiation (UVR) is considered the primary driver of melanoma, although genetic predisposition also plays a critical role. This review explores the intricate molecular mechanisms by which UVR-induced photodamage contributes to melanoma development. We examine epidemiological evidence linking UV exposure to increased risk, detailing how UVR damage to DNA triggers inflammatory responses and impairs DNA repair mechanisms. Specifically, we discuss the roles of nucleotide excision repair (NER) and base excision repair (BER) in mitigating UV damage. The review further explores diagnostic and surgical implications for melanomas arising on sun-exposed skin. By synthesizing current evidence, this overview aims to deepen understanding of the complex relationship between UVR, photodamage, and melanoma, shedding light on the need for personalized preventive strategies to better stratify the risk and introduce behavioral changes to reduce skin photodamage.

Hydroxyurea (HU), a cornerstone treatment for myeloproliferative disorders, is associated with a wide range of cutaneous side effects, from xerosis and hyperpigmentation to more severe conditions like dermatomyositis-like eruptions (DM-LE) and nonmelanoma skin cancers (NMSC), particularly squamous cell carcinoma (SCC). In this review, we present a unique case of HU-induced DM-LE with histological evidence of keratinocyte dysplasia and p53 overexpression, followed by a systematic analysis of similar cases. Our findings reveal that the clinical presentation of DM-LE, while typically considered benign, shares clinical and histological features with hydroxyurea-associated squamous dysplasia (HUSD), a precancerous condition that may progress to SCC in chronically exposed patients. Key insights include the characteristic histopathological findings of DM-LE, the role of chronic HU therapy and UV-induced damage in promoting p53 overexpression, and the overlap between DM-LE and HUSD. Regular dermatologic monitoring, patient education on photoprotection, and the careful assessment of skin lesions in long-term HU users are essential for the early detection and prevention of malignancies. This review underscores the importance of distinguishing between DM-LE, HUSD, and SCC to optimize management and minimize risks associated with HU therapy.

Hyaluronic acid (HA) fillers and botulinum toxin remain among the most frequently requested non-surgical esthetic procedures, due to their favorable safety profile and ability to restore volume and improve skin quality. However, variability in product performance and the lack of objective measurement tools remain challenges in clinical practice. This prospective, single-arm, non-randomized pilot study aimed to assess the esthetic efficacy, tolerability, and duration of effect of Sofiderm® HA fillers in Caucasian patients with signs of facial aging, and to explore the correlation between subjective visual grading and instrumental imaging outcomes. Five patients with Griffiths photoaging scores ranging from 4 to 8 were treated with different Sofiderm® formulations. Standardized evaluations were performed at baseline, 2 months, and 9 months using VISIA-CR and PRIMOS 3D optical profilometry. All subjects experienced measurable improvements, with an average 2-point reduction in Griffiths scores at 2 months, maintained at 9 months in most cases. Objective imaging data confirmed enhancements in volume, texture, and surface regularity. No serious adverse events occurred. These findings suggest that Sofiderm® fillers may offer sustained esthetic benefits with a favorable safety profile and demonstrate how integrated digital imaging can enhance treatment evaluation in esthetic dermatology.

Auricular keloids pose significant aesthetic and functional challenges, and traditional treatments often fall short in addressing these issues. Our study presents an innovative combined approach of ablative CO2 and dye laser therapy for improved keloid management. This treatment protocol was applied to 15 patients with auricular keloids after an initial multispectral analysis to assess keloid composition. The laser sequence was tailored per patient based on this analysis. Evaluations using the Vancouver Scar Scale and Patient and Observer Scar Assessment Scale were carried out at baseline and at 3-week intervals post-treatment. The results showed a significant reduction in these scores at the final follow-up (p < 0.05), suggesting improvements in keloid color, texture, and pliability, with minimal adverse events. Additionally, no recurrence of keloids was observed. Our findings indicate that this novel methodology of multispectral analysis followed by tailored laser therapy may offer a safe and effective solution for auricular keloids, promising enhanced keloid treatment and prevention of recurrence. However, further investigations, including randomized controlled trials, are needed to confirm and optimize this treatment protocol.

Pigmentary disorders of the face present a significant challenge in dermatology, impacting the confidence and well-being of affected individuals. Various approaches have been developed to address these concerns, including microneedling and topical vitamin C products. This study involved 15 participants undergoing three treatment sessions over 12 weeks, assessing the efficacy of a combined microneedling and CE Ferulic® serum approach. Clinical evaluation and statistical analysis were conducted before and after the intervention. Significant improvement of akin hyperpigmentation was observed, particularly on the side treated with microneedling and CE Ferulic® serum compared to microneedling alone. The integrated treatment protocol demonstrated a synergistic effect in improving skin texture and appearance. Integrated treatment protocols, such as combining microneedling with CE Ferulic® serum, show promise in managing facial hyperpigmentation disorders. Further research with larger cohorts is warranted to validate these findings and optimize treatment strategies, highlighting the potential of combined therapeutic modalities for achieving optimal clinical outcomes in pigmentary disorder management.

Laser treatments have become popular in Dermatology. In parallel to technologic development enabling the availability of different laser wavelengths, non-invasive skin imaging techniques, such as reflectance confocal microscopy (RCM), have been used to explore morphologic and qualitative skin characteristics. Specifically, RCM can be applied to cosmetically sensitive skin areas such as the face, without the need for skin biopsies. For these reasons, apart from its current use in skin cancer diagnosis, our systematic review reveals how RCM can be employed in the field of laser treatment monitoring, being particularly suitable for the evaluation of variations in epidermis and dermis, and pigmentary and vascular characteristics of the skin. This systematic review article aims to provide an overview on current applications of RCM laser treatment monitoring, while describing RCM features identified for different applications. Studies on human subjects treated with laser treatments, monitored with RCM, were included in the current systematic review. Five groups of treatments were identified and described: skin rejuvenation, scar tissue, pigmentary disorders, vascular disorders and other. Interestingly, RCM can assist treatments with lasers targeting all chromophores in the skin and exploiting laser induced optical breakdown. Treatment monitoring encompasses assessment at baseline and examination of changes after treatment, therefore revealing details in morphologic alterations underlying different skin conditions and mechanisms of actions of laser therapy, as well as objectify results after treatment.

Hyaluronic acid (HA) fillers represent the most frequently performed minimally invasive procedures for facial rejuvenation, yet their overall safety profile is critically influenced by the cross-linking technology employed. Polyethylene glycol diglycidyl ether (PEGDE) has recently been introduced as an alternative to 1,4-butanediol diglycidyl ether (BDDE). The present prospective observational study was undertaken to evaluate the safety of a PEGDE-crosslinked HA filler for the correction of severe nasolabial folds. A total of 60 patients received bilateral injections of 1 mL per side and were monitored over a six-month period. Safety assessment included systematic documentation of adverse events and non-invasive biophysical and imaging techniques, specifically corneometry, sebumetry, and high-frequency ultrasound (HFUS). The treatment was well tolerated: 15% of patients reported only mild and transient adverse events, such as pain, swelling, bruising, or discomfort, while no serious adverse events, vascular compromise, or ocular complications were observed. Corneometry demonstrated a statistically significant increase in cutaneous hydration, sebumetry confirmed stability of sebaceous activity, and HFUS documented correct placement, homogeneous distribution, and progressive integration of the filler without nodules or granulomatous reactions. These findings support the favorable short-term safety and local tolerance of PEGDE-crosslinked HA fillers in the treatment of severe nasolabial folds.

Background Melanoma cells develop adaptive responses in order to cope with particular conditions of tumor microenvironment, characterized by stress conditions and deregulated proliferation. Recently, the interplay between the stress response and the gene expression programs leading to metastatic spread has been reported. Methods We evaluated levels and localization of eIF2α/peIF2α in V600BRAF and wtBRAF metastatic melanoma cell lines by means of western blot and confocal microscopy analyses. Furthermore, we performed a sequence analyses and structure and dynamics studies of eIF2α protein to reveal the role of eIF2α and its correlations in different pathways involved in the invasive phase of melanoma. Results We found peIF2α both in cytoplasm and nucleus. Nuclear localization was more represented in V600BRAF melanoma cell lines. Our studies on eIF2α protein sequence indicated the presence of a predicted bipartite NLS as well as a nuclear export signal NES and an S1 domain, typical of RNA interacting proteins. Furthermore, we found high levels of transcription factor EB (TFEB), a component of the MiT/TFE family, and low β-catenin levels in V600BRAF cells. Conclusions Based on our results, we suggest that peIF2α nuclear localization can be crucial in ER stress response and in driving the metastatic spread of melanoma, through lysosomal signaling and Wnt/β-catenin pathway. In conclusion, this is the first evidence of nuclear localization of peIF2α, representing a possible target for future therapeutic approaches for metastatic melanoma.