Snail extract for skin: A review of uses, projections, and limitations.

BACKGROUND: Snail mucin is becoming increasingly popular for its wide range of ingredients and potential benefits. Snail extract's widespread appearance in cosmetic formulations encourages an investigation into the medical and cosmetic benefits. AIMS: This study aims to explore current literature on the variety of snail mucin applications. Specifically, we present a review of the uses, global market estimates and projects, and limitations to snail mucin. METHODS: A literature search was conducted on PubMed reviewing snail mucin and their application in medical and dermatologic fields examining their uses. Economic reports were also investigated for Global Market estimates. RESULTS: The therapeutic use of snail mucin in medical fields has been studied as antimicrobial agents, drug delivery vehicles, antitumor agents, wound healing agents, and biomaterial coatings among others. Additionally, the use in cosmetic fields includes antiaging, hydrating, anti-acne, scarring, and hyperpigmentation treatments. It is important to highlight that most studies conducted were preclinical or small clinical studies, stressing the need for additional large-scale clinical trials to support these claims. Investigations into the global market found estimates ranging from $457 million to $1.2 billion with upward projections in the upcoming decade. Limitations include ethical habitats for collection, allergy investigation, and missing clinical studies. CONCLUSIONS: The findings presented here emphasize the expanding uses of snail mucin and its ingredients alongside a growing market cosmetic industry should consider. We also emphasize the need for appropriate clinical trials into the stated benefits of snail mucin to ensure consumer safety and ethical extraction of mucin.

Selective inhibition of overactive warmth-sensitive Ca2+-permeable TRPV3 channels by antispasmodic agent flopropione for alleviation of skin inflammation.

The temperature-sensitive Ca2+-permeable TRPV3 ion channel is robustly expressed in the skin keratinocytes, and its gain-of-function mutations are involved in the pathology of skin lesions. Here, we report the identification of an antispasmodic agent flopropione that alleviates skin inflammation by selective inhibition of TRPV3. In whole-cell patch clamp recordings, flopropione selectively inhibits macroscopic TRPV3 currents in a concentration-dependent manner with an IC50 value of 17.8 ± 3.5 µM. At the single-channel level, flopropione inhibits TRPV3 channel open probability without alteration of its unitary conductance. In an in vivo mouse model of skin inflammation induced by the skin sensitizer DNFB, flopropione also alleviates dorsal skin lesions and ear skin swelling. Further molecular docking combined with site-directed mutagenesis reveals that two residues E501 and I505 in the channel S2-helix are critical for flopropione-mediated inhibition of TRPV3. Taken together, our findings demonstrate that the spasmolytic drug flopropione as a selective inhibitor of TRPV3 channel not only provides a valuable tool molecule for understanding of TRPV3 channel pharmacology but also holds repurposing potential for therapy of skin disorders, such as dermatitis and pruritus.

Discovery of a structural class of antibiotics with explainable deep learning.

The discovery of novel structural classes of antibiotics is urgently needed to address the ongoing antibiotic resistance crisis1-9. Deep learning approaches have aided in exploring chemical spaces1,10-15; these typically use black box models and do not provide chemical insights. Here we reasoned that the chemical substructures associated with antibiotic activity learned by neural network models can be identified and used to predict structural classes of antibiotics. We tested this hypothesis by developing an explainable, substructure-based approach for the efficient, deep learning-guided exploration of chemical spaces. We determined the antibiotic activities and human cell cytotoxicity profiles of 39,312 compounds and applied ensembles of graph neural networks to predict antibiotic activity and cytotoxicity for 12,076,365 compounds. Using explainable graph algorithms, we identified substructure-based rationales for compounds with high predicted antibiotic activity and low predicted cytotoxicity. We empirically tested 283 compounds and found that compounds exhibiting antibiotic activity against Staphylococcus aureus were enriched in putative structural classes arising from rationales. Of these structural classes of compounds, one is selective against methicillin-resistant S. aureus (MRSA) and vancomycin-resistant enterococci, evades substantial resistance, and reduces bacterial titres in mouse models of MRSA skin and systemic thigh infection. Our approach enables the deep learning-guided discovery of structural classes of antibiotics and demonstrates that machine learning models in drug discovery can be explainable, providing insights into the chemical substructures that underlie selective antibiotic activity.

Vegetable as a Source of Bioactive Compounds with Photoprotective Properties: Implication in the Aging Process.

The skin, as an external organ, protects the entire body against harmful external factors. One of these factors is ultraviolet (UV) radiation, which in excessive amounts can lead to premature skin aging, DNA damage, and even skin cancer. Therefore, it is worth supporting skin protection not only with commercially available preparations, but also with a proper diet. Consuming certain vegetables and applying them topically may reduce the effects of UV radiation. The aim of the review was to collect information on the effects of vegetables and their compounds on the skin when used externally or included in the diet. This review summarizes studies on vegetables, such as broccoli, cucumber, kale, tomato, and carrot, which have shown significant activity in skin photoprotection. Additionally, it outlines the bioactive substances present in these vegetables and their effects.

Dersimelagon in Erythropoietic Protoporphyrias.

BACKGROUND: Erythropoietic protoporphyria and X-linked protoporphyria are inborn errors of heme biosynthesis that cause elevated circulating levels of metal-free protoporphyrin and phototoxicity. Both disorders are characterized by excruciating phototoxic attacks after exposure to visible light. Dersimelagon is a new, orally administered, selective melanocortin 1 receptor agonist that increases levels of skin eumelanin. METHODS: We conducted a randomized, placebo-controlled, phase 2 trial to investigate the efficacy and safety of dersimelagon with respect to the time to onset and the severity of symptoms associated with sunlight exposure in patients with erythropoietic protoporphyria or X-linked protoporphyria. Patients 18 to 75 years of age were randomly assigned in a 1:1:1 ratio to receive placebo or dersimelagon at a dose of 100 or 300 mg once daily for 16 weeks. The primary end point was the change from baseline to week 16 in the time to the first prodromal symptom associated with sunlight exposure. Patients recorded daily sunlight exposure and symptom data in an electronic diary. Quality of life and safety were also assessed. RESULTS: Of the 102 patients (93 with erythropoietic protoporphyria and 9 with X-linked protoporphyria) who underwent randomization, 90% completed the treatment period. The mean daily time to the first prodromal symptom associated with sunlight exposure increased significantly with dersimelagon: the least-squares mean difference from placebo in the change from baseline to week 16 was 53.8 minutes in the 100-mg dersimelagon group (P = 0.008) and 62.5 minutes in the 300-mg dersimelagon group (P = 0.003). The results also suggest that quality of life improved in patients receiving dersimelagon as compared with placebo. The most common adverse events that occurred or worsened during treatment were nausea, freckles, headache, and skin hyperpigmentation. CONCLUSIONS: At both doses evaluated, dersimelagon significantly increased the duration of symptom-free sunlight exposure in patients with erythropoietic protoporphyria or X-linked protoporphyria. (Funded by Mitsubishi Tanabe Pharma; Endeavor ClinicalTrials.gov number, NCT03520036.).

Combining topical dermal infused exosomes with injected calcium hydroxylapatite for enhanced tissue biostimulation.

BACKGROUND: Exosome research continues to flourish. Subsequent knowledge surrounding indications, dose-response, safety, efficacy, and the ability to combine exosome treatment as a "skin primer"-for biostimulation modalities such as calcium hydroxylapatite (CaHA), platelet-rich plasma (PRP), and platelet-rich fibrin matrix (PRFM) is growing rapidly. The objective of this study was to develop safe, reproducible methods of improving topical exosome absorption to enhance the quality of skin either by themselves, or in combination with injectable CaHA. METHODS: Under IRB Approval (International Cell Surgical Society: ICSS-2022-007), 40 patients were enrolled in this study. Twenty patients underwent facial biostimulatory dermal infusion alone, to determine if this method allowed adequate exosome absorption. Five patients underwent facial biostimulatory infusion followed immediately by Dilute CaHA injection (1:1 dilution) to the face. Five patients underwent exosome biostimulatory dermal infusion followed immediately by hyperdilute CaHA (dilution 1:4) injection to the neck. Five patients underwent Facial Dilute CaHA injection (1:1 dilution) alone, without dermal infusion. Five patients underwent neck hyperdilute CaHA injection (1:4 dilution) alone, without dermal infusion. All patients had pretreatment Quantificare 3-D photo-documentation and skin analysis (Quantificare, France). In all patients, the skin was first cleansed with a gentle glycolic acid facial wash (Gregory MD). To induce a "homing inflammatory environment" for the exosomes, sea salt exfoliation was performed (SaltFacial®, SaltMed, Cardiff, CA). A nitric oxide-generating serum (N101 Pneuma Nitric Oxide, Austin, TX) was then applied to act as an enhanced vehicle for absorption. A 3 MHz ultrasound (SaltFacial®, SaltMed, Cardiff, CA) was then utilized to further deepen the absorption of the nitric oxide serum. A topical emulsion containing equal volumes (1.0 cc containing 1 million) of exosomes (Kimera Labs, Miramar, FL), 25 units of botulinum toxin (Xeomin, Merz Aesthetics, Raleigh, NC) and hyaluronic acid (Belatero, Merz Aesthetics, Raleigh, NC) was mixed via back-and-forth propulsion in a 3-cc syringe. When adequately mixed, the emulsion was then applied to the treatment areas. The cavitating ultrasound was then used to aid in the absorption of the emulsion. The patients were then treated with high-intensity LED therapy (SaltFacial®, SaltMed, Cardiff, CA), utilizing the collagen restoration preset program of combination red (660 nm) near-infrared (930 nm) wavelength for 20 min. Post-treatment Quantificare analysis was performed at 15 and 30 days after treatment. RESULTS: Without exception, all dermal infusion alone and CaHA injection alone patients showed an improvement in the tone, quality, and texture of their skin. Quantificare results showed consistent improvement in wrinkles, pores, skin evenness, improved vascularity, and a reduction in oiliness and unwanted pigment. When employed as a skin primer prior to injections (CaHA), enhanced and more rapid results were seen. CONCLUSIONS: Biostimulatory dermal infusion can be achieved utilizing topical placental mesenchymal stem cell-derived exosomes. These exosomes can be used alone, or mixed with ancillary ingredients such as botulinum toxin, hyaluronic acid dermal filler, and CaHA to customize and personalize treatments based upon individual patient needs. Topical absorption is enhanced with sea salt exfoliation, a topical nitric oxide-generating serum, and 3 MHz cavitating ultrasound. Post-absorption activity is enhanced with high-intensity LED treatment. The addition of CaHA injections after the topical exosome "priming of the skin" yielded enhanced skin quality faster than exosomes or CaHA alone.

Tolerability and efficacy assessment of an oral collagen supplement for the improvement of biophysical and ultrasonographic parameters of skin in middle eastern consumers.

BACKGROUND: Topical skin care products often do not reach the deeper layers of the skin, and oral hydrolyzed collagen is one of the newest and most popular systemic supplementations for skin rejuvenation. However, there are limited information in case of Middle Eastern consumers OBJECTIVE: The purpose of this study was to evaluate the tolerability and efficacy of an oral collagen supplement for improvement of skin elasticity, hydration, and roughness in Middle Eastern consumers. METHODS AND MATERIALS: It was a 12-week, before-after clinical study, conducted on 20 participants (18 women and 2 men) aged 44.15 ± 5.36 years with skin type III-IV. Skin elasticity parameters (R0, R2, R5, and R7), skin hydration and friction, as well as the thickness and echo density of the dermis, were measured after six and 12 weeks daily intake of the study product, as well as 4 weeks after stopping its use (week 16). Participants' satisfaction was assessed on the basis of their answers to the standard questionnaire, and tolerability of the product was assessed by monitoring the adverse effects. RESULTS: A significant improvement was detected in R2, R5, and skin friction at week 12 (p-values 0.041, 0.012 and <0.01, respectively). At week 16, the values remained at an increased level, which indicates the persistence of the results. The increase of dermis density in week 16 was also significant (p-value = 0.03). Moderate overall satisfaction was reported with the treatment, and a few gastrointestinal complications were reported. CONCLUSION: The study demonstrated that oral collagen peptides could significantly improve the skin elasticity, roughness, and dermis echo density, and they also proved to be safe and well-tolerated.

Two Phase 3 Trials of Lebrikizumab for Moderate-to-Severe Atopic Dermatitis.

BACKGROUND: Lebrikizumab, a high-affinity IgG4 monoclonal antibody targeting interleukin-13, prevents the formation of the interleukin-4Rα-interleukin-13Rα1 heterodimer receptor signaling complex. METHODS: We conducted two identically designed, 52-week, randomized, double-blind, placebo-controlled, phase 3 trials; both trials included a 16-week induction period and a 36-week maintenance period. Eligible patients with moderate-to-severe atopic dermatitis (adults [≥18 years of age] and adolescents [12 to <18 years of age, weighing ≥40 kg]) were randomly assigned in a 2:1 ratio to receive either lebrikizumab at a dose of 250 mg (loading dose of 500 mg at baseline and week 2) or placebo, administered subcutaneously every 2 weeks. Outcomes for the induction period were assessed up to 16 weeks and are included in this report. The primary outcome was an Investigator's Global Assessment (IGA) score of 0 or 1 (indicating clear or almost clear skin; range, 0 to 4 [severe disease]) with a reduction (indicating improvement) of at least 2 points from baseline at week 16. Secondary outcomes included a 75% improvement in the Eczema Area and Severity Index score (EASI-75 response) and assessments of itch and of itch interference with sleep. Safety was also assessed. RESULTS: In trial 1, the primary outcome was met in 43.1% of 283 patients in the lebrikizumab group and in 12.7% of 141 patients in the placebo group (P<0.001); an EASI-75 response occurred in 58.8% and 16.2%, respectively (P<0.001). In trial 2, the primary outcome was met in 33.2% of 281 patients in the lebrikizumab group and in 10.8% of 146 patients in the placebo group (P<0.001); an EASI-75 response occurred in 52.1% and 18.1%, respectively (P<0.001). Measures of itch and itch interference with sleep indicated improvement with lebrikizumab therapy. The incidence of conjunctivitis was higher among patients who received lebrikizumab than among those who received placebo. Most adverse events during the induction period were mild or moderate in severity and did not lead to trial discontinuation. CONCLUSIONS: In the induction period of two phase 3 trials, 16 weeks of treatment with lebrikizumab was effective in adolescents and adults with moderate-to-severe atopic dermatitis. (Funded by Dermira; ADvocate1 and ADvocate2 ClinicalTrials.gov numbers, NCT04146363 and NCT04178967, respectively.).

Reduction of wrinkles: From a computational hypothesis to a clinical, instrumental, and biological proof.

BACKGROUND: Facial wrinkles are clear markers of the aging process, being chronological, photo-induced, or reflecting repetitive facial expressions. The aim of this study is to provide new insights into the biophysical and biological mechanisms involved in the formation, prevention, or elimination of the expression wrinkles. MATERIALS AND METHODS: We use a computational model to get a better understanding of the wrinkle mechanical behavior and evolution after skin softening and suggesting a possible antiaging mechanism. Then, we provide a clinical demonstration of the anti-wrinkle effect of a long-term application of a 20% glycerol in a moisturizer formula (GBM) versus its vehicle on crow's feet. Skin hydration, elasticity, and wrinkles visibility were evaluated by a combination of clinical and instrumental in vivo data, inverse finite element analysis, and proteomic data. RESULTS: The computational model shows a predominantly compressive stress beneath the wrinkle and its significant decrease by the softening of stratum corneum. The associated clinical study confirmed a significant increase of skin hydration and elasticity as well as a decrease of wrinkle visibility after 2 and 4 months as application for both formulas; this effect being stronger for GBM. A softening effect on stratum corneum and dermis was also observed for the GBM. Furthermore, proteomic data revealed an effect of upregulation of four proteins associated with desquamation, cell-glycan extracellular interactions, and protein glycation/oxidation, functions related to the tissue mechanics and adhesion. CONCLUSIONS: We provide an in vivo demonstration of the anti-ageing benefit of glycerol at high dose (20%) reflected by a cumulative skin surface softening effect. The use of high moisturizing potent formulations should bring additional performance to other conventional moisturizing formulations.

Unparallel improvement patterns of dynamic wrinkles and skin quality after botulinum toxin type A treatment on the upper face.

BACKGROUND: Botulinum toxin type A (BoNT-A) can not only reduce the dynamic wrinkles but also improve the skin quality. This study aims to quantitaively and comprehensively assess the improvement of dynamic wrinkles and skin quality following BoNT-A treatment on the upper face. METHODS: Patients were recruited to receive BoNT-A treatment of the glabellar, frontal, and lateral periorbital wrinkles. Antera 3D camera was used to evaluate the skin quality and dynamic wrinkle severity. Follow-up visits were at 1 week, 1 month, 3 months, and 6 months after treatment. Different filters were utilized to quantitatively detect the severity of fine wrinkles (FWS), the volume of pores (PV), the roughness of skin texture (STR), and the severity of dynamic wrinkles (DWS). RESULTS: Twenty-four participants (average 30.5 ± 7.2 years) were recruited. The significant improvement of PV, FWS, and STR in different areas usually maintained from 1 to 6 months after injections but of DWS only existed within 3 months. For each area, the improvement rates of FWS, PV, and STR peaked at 3 months or 6 months after treatment while the maximal improvement of DWS was observed at 1 month posttreatment. CONCLUSION: After BoNT-A treatment for dynamic wrinkles on the upper face, the skin quality of target regions can also be ameliorated. The improvement of skin quality and dynamic wrinkles presented unparallel patterns. The former is with a slower onset but longer duration while the latter exhibits a more rapid onset but shorter duration.

Skin mucus metabolomics provides insights into the interplay between diet and wound in gilthead seabream (Sparus aurata).

The molecular processes underlying skin wound healing in several fish species have been elucidated in the last years, however, metabolomic insights are scarce. Here we report the skin mucus metabolome of wounded and non-wounded gilthead seabream (Sparus aurata) fed with silk fibroin microparticles, a functional additive considered to accelerate the wound healing process. The three experimental diets (commercial diet enriched with 0 mg (control), 50 mg or 100 mg of silk fibroin microparticles Kg-1) were administered for 30 days and thereafter, a skin wound was inflicted. Skin mucus was collected on day 30 of feeding and 7 days post-wounding and subjected to metabolomic analysis by Ultra Performance Liquid Chromatography coupled with a high-resolution quadrupole-orbitrap mass spectrometry. The most enriched metabolite class was amino acids and derivatives, followed by nucleotides, nucleosides and analogues and carbohydrates and their derivatives. Metabolomic profiles revealed that the diet had a more profound effect than wounding in skin mucus. Metabolic pathway analysis of significantly affected metabolites revealed perturbations in the aminoacyl t-RNA biosynthesis in the skin. In particular, skin wound resulted in a decreased methionine level in mucus. Further, silk fibroin supplementation increased methionine level in skin mucus, which correlated with several wound morphometric parameters that characterized the epithelial healing capacity in seabream. The results provided new insight into the physiological consequences of skin wounds and how these processes could be influenced by dietary manipulation.

Succinoglycan riclin relieves UVB-induced skin injury with anti-oxidant and anti-inflammatory properties.

Excessive UVB exposure increases the production of reactive oxygen species (ROS), which causes oxidative damage and epidermal inflammation. Previous studies have identified that the succinoglycan riclin has potent anti-inflammatory properties. The current study aims to investigate whether riclin protects against UVB-induced photodamage. In vitro, riclin demonstrated excellent moisture-preserving properties, along with antioxidant potential by scavenging superoxide anions, hydroxyl and DPPH radicals. Riclin increased Col1α1 and Col3α1 expression in NIH3T3 cells, inhibited oxidation and melanin synthesis by B16F10 cells upon UVB irradiation. In vivo, topical application of riclin effectively attenuated UVB-induced skin damage in C57BL6 mice, which was characterized by erythema, epidermal hyperplasia, hydroxyproline loss and ROS production in skin tissue. Riclin suppressed skin inflammation by the elevation of TNF-α, IL-6, IL-ß, and alleviated UVB-induced immune cell up-regulation. Moreover, treatment with a Dectin-1 inhibitor reversed the protective effect of riclin in THP-1 cells.

Cuadros cutáneo-mucosos asociados al consumo de cocaína / Cutaneous and Mucosal Conditions Associated With Cocaine Use

El consumo de cocaína, junto con algunos de sus adulterantes más frecuentes como el levamisol, puede provocar múltiples procesos cutáneos y mucosos, ya sean de índole isquémico, dermatosis neutrofílicas, lesiones destructivas de la línea media y vasculitis asociadas a ANCA, entre otros. Generalmente no se asocia clínica sistémica llamativa.Todos estos cuadros pueden presentar anticuerpos antinucleares, antifosfolípido y contra distintos antígenos de los neutrófilos, en ocasiones con un patrón característico. El estudio histológico suele mostrar cambios vasculares como vasculitis leucocitoclástica, necrosis de la pared y trombos. En este artículo revisamos las características clínicas, serológicas e histológicas de estas entidades, junto con los mecanismos fisiopatológicos implicados, el diagnóstico diferencial y su tratamiento. (AU)

Cocaine and some of its main adulterants, such as levamisole, can cause multiple cutaneous and mucosal manifestations, including ischemic complications, neutrophilic dermatoses, midline destructive lesions, and vasculitis associated with antineutrophil cytoplasmic antibodies (ANCAs). Striking systemic symptoms are generally not seen.In all these conditions, positive test results may be observed for antinuclear antibodies, antiphospholipid antibodies, and various ANCAs, sometimes with characteristic staining patterns. Histology typically shows vascular changes, such as leukocytoclastic vasculitis, necrotizing vasculitis, and thrombi. We review the clinical, serologic, and histologic features of cutaneous and mucosal conditions associated with the use of cocaine and also look at pathophysiologic mechanisms, differential diagnoses, and treatments. (AU)

[Translated article] Cutaneous and Mucosal Conditions Associated With Cocaine Use / Cuadros cutáneo-mucosos asociados al consumo de cocaína

Cocaine and some of its main adulterants, such as levamisole, can cause multiple cutaneous and mucosal manifestations, including ischemic complications, neutrophilic dermatoses, midline destructive lesions, and vasculitis associated with antineutrophil cytoplasmic antibodies (ANCAs). Striking systemic symptoms are generally not seen. In all these conditions, positive test results may be observed for antinuclear antibodies, antiphospholipid antibodies, and various ANCAs, sometimes with characteristic staining patterns. Histology typically shows vascular changes, such as leukocytoclastic vasculitis, necrotizing vasculitis, and thrombi. We review the clinical, serologic, and histologic features of cutaneous and mucosal conditions associated with the use of cocaine and also look at pathophysiologic mechanisms, differential diagnoses, and treatments. (AU)

El consumo de cocaína, junto con algunos de sus adulterantes más frecuentes como el levamisol, puede provocar múltiples procesos cutáneos y mucosos, ya sean de índole isquémico, dermatosis neutrofílicas, lesiones destructivas de la línea media y vasculitis asociadas a ANCA, entre otros. Generalmente no se asocia clínica sistémica llamativa. Todos estos cuadros pueden presentar anticuerpos antinucleares, antifosfolípido y contra distintos antígenos de los neutrófilos, en ocasiones con un patrón característico. El estudio histológico suele mostrar cambios vasculares, como vasculitis leucocitoclástica, necrosis de la pared y trombos. En este artículo revisamos las características clínicas, serológicas e histológicas de estas entidades, junto con los mecanismos fisiopatológicos implicados, el diagnóstico diferencial y su tratamiento. (AU)

Topical gel containing Polysiloxanes and hyaluronic acid for skin scar: Formulation design, characterization, and In vivo activity.

BACKGROUND: Scar formation is undesirable both cosmetically and functionally. It shows that silicone gel is effective in preventing and improving scars formed due to a wound formation after injury. OBJECTIVES: This study investigates whether a silicone gel composition based on a novel concept of infusing a biologically active material such as hyaluronic acid and/or salts with various polysiloxane derivatives in a specific proportion to achieve desired viscosity range and their action has a synergistic beneficial effect on skin scar after injury. METHODS: We have developed a topical gel utilizing a combination of emulsifiers, sodium hyaluronate, polysiloxane, and its derivatives. The method of preparation comprises mixing of aqueous phase dispersion and polysiloxanes blend under stirring at room temperature. RESULTS: It results in the formation of a homogenous smooth gel formulation. The developed topical gel formulation was characterized for physicochemical properties, rheology, stability, and anti-scar activity in Wistar rats. It was found that the developed formulation system consists of desirable attributes for skin applications. In vivo investigation of developed polysiloxane gel formulation for anti-scar activity shown promising outcomes compared to marketed product (Kelo-cote scar gel). Furthermore, a histopathology study of healed skin tissues observed the formation of microscopic skin structures compared to the Kelo-cote scar gel. CONCLUSIONS: It indicates that the combination of polysiloxanes and sodium hyaluronate resulting an improvement in anti-scar activity compared to the marketed product containing polysiloxanes alone.

"It's Like You Stuck a Pin in It:" African American/Black Patients Describe Cutaneous Toxicity From Epidermal Growth Factor Receptor Inhibitors.

Background: Epidermal growth factor receptor (EGFR) inhibitors cause cutaneous toxicity in over 90% of patients. Conceivably, healthcare providers could overlook such toxicity in African American/Black patients because of a darker complexion. This qualitative study sought to learn about such cutaneous signs and symptoms and, if present, to report them in patients' own words. Methods: Any patient who self-identified as African American/Black and who had been prescribed an EGFR inhibitor was eligible. The current report focuses on patients' responses to the following question, "What have you noticed since starting your cancer treatment (the EGFR inhibitor), any particular symptoms or reactions, positive or negative?" All interview data were audio-recorded, transcribed, and then independently coded and analyzed by two investigators. Results: Fifteen patients are the focus of this report, and all described cutaneous toxicity. Patients appeared troubled by the cosmetic aspect of these drug-induced skin changes, including their acneiform appearance, describing "little pimples with little, little pus in it." Notable were comments on hyperpigmentation, "I'm a black person but…. became darker." Furthermore, patients experienced physical symptoms: "it itches;" "it's like you stuck a pin in it;" "stinging;" and "burning;". Conclusion: Although cutaneous toxicity from EGFR inhibitors might be more difficult to visualize among darkly complected patients, the graphic descriptions offered in this qualitative study underscore the need for clinicians to heighten their awareness of such toxicity in African American/Black patients.

Impact of defensins-containing body cream on skin composition.

BACKGROUND AND AIMS: Defensins are peptides capable of reactivating latent LGR6 stem cells in the basal layer. When applied topically, these peptides can reduce signs of skin aging and increase dermal thickness. This study investigates the effects of a topical defensin formulation on extremity skin composition. METHODS: An open label, single arm clinical trial was conducted on participants with dry, photoaged, or dull skin. A defensin-containing hand and body cream was applied twice daily for 6 weeks to the hands, forearms, elbows, and knees. Photographs and objective measurements of skin hydration, viscoelasticity (VE), retraction time (RT), thickness, density/transepidermal water loss (TEWL), as well as self-evaluation of skin quality and characteristics were obtained pre- and post- intervention. RESULTS: After the study period, RT decreased by 56% across all body sites (p < 0.001) and VE improved at the elbow (125%, p = 0.009) and knee (110%, p < 0.001). Skin density also increased in all 4 body sites (40%, p < 0.001), while skin thickness increased at the elbow (29%, p = 0.03) and knee (17%, p = 0.04). Skin hydration increased at the elbow, knee, and forearm by 99%, 28%, and 16%, respectively (p < 0.05), while TEWL improved at the elbow only (-39%, p = 0.02). Patients' self-evaluations showed improvements in overall skin quality and in the domains of dryness, ashiness, wrinkling, pigmentation, redness, roughness, and discomfort (p < 0.05). CONCLUSIONS: Following 6-week use of a defensin-containing cream, subjects reported significant improvement across many subjective skin domains. Similarly, objective measurements demonstrated significant improvement in skin architecture at select sites.

Isotretinoin treatment upregulates the expression of p53 in the skin and sebaceous glands of patients with acne vulgaris.

The transcriptomic regulation induced by isotretinoin (13-cis retinoic acid) is still a matter of debate as short-term exposures of immortalized sebocytes with isotretinoin produced conflicting results. Based on translational evidence, it has been hypothesized that oral isotretinoin treatment upregulates the expression of the transcription factor p53. Twenty-five patients suffering from acne vulgaris were treated with isotretinoin (0.6 mg/kg body weight) for 6 weeks. Biopsies from back skin were taken before and after isotretinoin treatment for the determination of p53 expression by immunohistochemical staining, quantification of p53 protein concentration by enzyme-linked immunosorbent assay and TP53 gene expression by quantitative reverse transcription real time PCR. Fifteen socio-demographically cross-matched healthy volunteers served as controls. Isotretinoin treatment significantly increased the nuclear expression of p53 in sebaceous glands of treated patients compared to pre-treatment levels and p53 levels of untreated controls. Furthermore, the p53 protein and gene expression significantly increased in the skin after treatment. The magnitude of p53 expression showed an inverse correlation to acne severity score and body mass index. Under clinical conditions, isotretinoin induced the expression of p53, which controls multiple transcription factors involved in the pathogenesis of acne vulgaris including FoxO1, androgen receptor and critical genes involved in the induction of autophagy and apoptosis. Increased p53-FoxO1 signalling enhanced by systemic isotretinoin treatment explains the underlying transcriptomic changes causing sebum suppression but also the adverse effects associated with systemic isotretinoin therapy.

Uso de hidroxiapatita de cálcio no tratamento da dermatoporose / Use of calcium hydroxyapatite in the treatment of dermatoporosis

A dermatoporose é a síndrome de fragilidade cutânea. Acomete principalmente indivíduos acima de 60 anos, com maior prevalência no sexo feminino. Os principais fatores de risco são: envelhecimento, exposição solar intensa e uso de corticoterapia tópica e sistêmica. Se manifesta clinicamente por atrofia cutânea, púrpuras senis, pseudo cicatrizes estrelares e lacerações, podendo evoluir com hematomas dissecantes e infecções graves. Trata-se de uma doença com grande impacto na qualidade de vida dos pacientes e, até o presente momento, não há terapias com resultados satisfatórios. Hidratação, vitamina C tópica e oral, luz intensa pulsada foram algumas das terapêuticas estudadas. A hidroxiapatita de cálcio é um bioestimulador de colágeno composto por microesferas em um veículo de carboximetilcelulose (Radiesse®). Tem sido usada para estimular a produção endógena de colágeno e consequentemente melhorar a qualidade e espessura da pele. Este efeito do produto poderia melhorar o quadro clínico da dermatoporose. O estudo teve como objetivo avaliar a melhora das lesões purpúricas e da atrofia da pele após aplicação de Radiesse® no antebraço de 5 pacientes portadores de dermatoporose no setor de Dermatologia do Hospital do Servidor Público Municipal de São Paulo. Os 5 pacientes foram submetidos a aplicação de Radiesse® nos antebraços e foram avaliadas 45 e 90 dias após o procedimento, o número de lesões purpúricas, grau de atrofia da pele através do teste de pinçamento e realizado comparação fotográfica. Após o tratamento, observou-se melhora do número das lesões purpúricas, melhora da atrofia da pele e melhora da qualidade de pele quando comparada fotograficamente. Dessa forma, o tratamento com Radiesse® mostrou-se promissor, com resultados satisfatórios e com um bom perfil de segurança. Palavras-chave: Dermatoporose. Púrpura senil. Radiesse. Bioestimulador. Tratamento.