ARTICLE | doi:10.20944/preprints202309.1665.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: skin; COVID infection; cytokines; SARS-CoV-2
Online: 25 September 2023 (09:37:37 CEST)
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.
ARTICLE | doi:10.20944/preprints202309.1065.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: psoriasis; plasma cytokines; TNFα inhibitors; etanercept; infliximab; adalimumab
Online: 18 September 2023 (02:32:17 CEST)
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 < 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.
REVIEW | doi:10.20944/preprints202309.0375.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: Burn healing; anti-Gal antibody; -gal epitope; -gal nanoparticles; macrophage migration; -gal therapy; mesenchymal stem cells.
Online: 6 September 2023 (10:23:59 CEST)
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.
REVIEW | doi:10.20944/preprints202309.0059.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: Skin; Anti-aging; Health, Lifestyle Factors, Diet, Sleep, Exercise, Social interactions, Polyphenols, Vitamins
Online: 1 September 2023 (10:30:06 CEST)
Lifestyle health has been recognized as an evidence-based innovation that defines how daily habits and practices impact both the prevention and treatment of disease and provides an important adjunctive component to overall health. Specifically, an approach with small changes over time can have a dramatic impact on the health and well-being of individuals not only, in general, but also can be applied to skin health. However, lifestyle health factors to improve skin well-being have not been discussed extensively and/or well promulgated. The narrative for this overview focuses on providing a summary for topic background information, but more importantly, presents four lifestyle factors that can improve dermal health [i.e., factor 1: nutrition - diet; factor 2: rest (sleep); factor 3: movement/physical exercise, and factor 4: social and community associations]. This was accomplished by identifying previous journal articles and reviews with emphasis over the last five years (from January 2018 through July 2023; 156 out of 190 references cited or 82 %) using scientific search databases. The main conclusions of this overview encourage the concept that lifestyle health factors such as nutrition/diet, rest/sleep, movement/physical exercise, and community/social interactions support enhanced skin health and well-being with aging. Plus, social media interventions that aim to promote dietary, sleep and physical activity changes might be an application to improve skin health in the future.
COMMUNICATION | doi:10.20944/preprints202308.0827.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: psoriasis; NADH/NAD+ redox imbalance; NADH fluorescence; FMSF technique
Online: 10 August 2023 (07:12:46 CEST)
Mitochondrial dysfunction has been linked to psoriasis, and may be an important underlying factor contributing to this disease. However, a precise methodology for assessing mitochondrial dysfunction has yet to be developed. One promising approach is to measure NADH autofluorescence from affected skin areas. In this study, we show that Flow Mediated Skin Fluorescence (FMSF) can be used for non-invasive assessment of mitochondrial dysfunction in psoriasis. The fluorescence level at baseline and the half-time of ischemic growth (t1/2) derived from the FMSF traces can be used for non-invasive assessment of NADH/NAD+ redox imbalance in psoriatic lesions compared to unaffected skin. These results are supported by analysis of the key FMSF parameters, Reactive Hyperemia Response (RHR) and Hypoxia Sensitivity (HS). This method not only contributes to understanding of the biochemical processes involved in the etiopathogenesis of psoriasis, but also provides a basis for identifying new drug targets and improving the treatment process.
ARTICLE | doi:10.20944/preprints202308.0569.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: Keratinocytes; alpha-mangostin; TRPV3; skin inflammation; dermatitis
Online: 8 August 2023 (03:42:33 CEST)
The TRPV3 calcium ion channel is vital for maintaining skin health and has been associated with various skin-related disorders. Since TRPV3 is involved in the development of skin inflammation, inhibiting TRPV3 could be a potential treatment strategy. Alpha-mangostin isolated from Garcinia mangostana L. extract exhibits diverse positive effects on skin health; however, the underlying mechanisms remain obscure. This study investigated the TRPV3-inhibitory properties of alpha-mangostin on TRPV3 hyperactive mutants associated with Olmsted syndrome and its impact on TRPV3-induced cytokine secretion and cell death. Our findings demonstrate that alpha-mangostin effectively inhibits TRPV3, with an IC50 of 0.077 ± 0.013 μM, showing inhibitory effects on both wild-type and mutant TRPV3. TRPV3 inhibition with alpha-mangostin decreased calcium influx and cytokine release, protecting cells from TRPV3-induced death. These results indicate that alpha-mangostin reduced inflammation in TRPV3-activated skin keratinocytes, suggesting that alpha-mangostin could be potentially used for improving inflammatory skin conditions such as dermatitis.
REVIEW | doi:10.20944/preprints202308.0582.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: forehead; temple reconstruction; frontalis myocutaneous trasposition flap; preauricular skin advancement flap; glabela; eyebrows
Online: 8 August 2023 (02:51:03 CEST)
The forehead and temporal region are a frequent area of skin cancer development. After tumor removal, reconstruction must be performed maintaining the frontal-temporal line of the scalp and the symmetry of the eyebrows, trying to hide the scars in these marks or in natural folds and wrinkles. Second wound healing and skin grafts generally do not produce an acceptable cosmetic result. When direct closure is not possible, the technique of choice is skin flaps. In the midfrontal line, continuation of the glabella, there is a remnant of skin to be used as a donor area for local flaps; similarly, it occurs in the preauricular cheek, which can move towards the temple. In addition to the classic advancement and rotation flaps, the frontalis myocutaneous transposition flap is an excellent technique for closing defects which are wider than higher on the forehead. Its design is very versatile and can be done between the two pupil lines at different heights depending on the location of the defect. On the other hand, the preauricular skin advancement flap with an infralobular Burow's triangle is also an excellent option for reconstructing tumors in the temporal area.
ARTICLE | doi:10.20944/preprints202308.0511.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: psoriasis; psoriatic arthritis (PsA); overweight; obesity; cardiovascular disease (CVD); miR-22-3p; miR-133a-3p; miR-146a-5p; miR-369-3p; Let-7b-5p
Online: 7 August 2023 (11:50:50 CEST)
Psoriasis is nowadays recognized as a multifactorial systemic disease with complex and still not fully understood pathogenesis. In psoriatic patients the increased cardiovascular disease (CVD) risk and frequent comorbidities like obesity are observed. The aim of this study was to investigate differences in miRNA (miR-22-3p, miR-133a-3p, miR-146a-5p, miR-369-3p and Let-7b-5p) involved in CVD risk among psoriatic patients with overweight/obesity and with normal weight. The study comprised 28 male psoriatic patients and 16 male healthy controls. miRNA isolated from peripheral blood mononuclear cells was reverse-transcribed and RT-qPCR was performed. We have found the decreased levels of miR-22, miR-133a, miR-146a, and miR-369 among the psoriatic patients. There was a statistically significant difference in miR-22 and miR-146a levels between psoriatic patients with overweight/obesity and with normal weight. There were positive correlations between miR-22 and miR-146a levels and psoriatic arthritis (PsA) in psoriatic patients with normal weight and between miR-133a level and PsA in the overweight/obese patients. The decreased levels of selected miRNA are consistent with their levels observed in CVD indicating their impact in the CVD risk in psoriatic patients. miR-22 and miR-146 may be recognized as one of the contributing factors in the obesity-CVD-psoriasis network.
ARTICLE | doi:10.20944/preprints202308.0463.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: alopecia areata; androgenetic alopecia; genetic test; DNA analysis
Online: 7 August 2023 (10:13:57 CEST)
Background: Androgenetic alopecia (AGA) and alopecia areata (AA) are most common types of non-cicatricial alopecia. Both diseases have limited effective therapeutic options and affect patients' quality of life. Pharmacogenetic tests can help predict the most appropriate treatment option by evaluating the single nucleotide polymorphisms (SNPs) corresponding to genes related to alopecia. The objective of the study was to evaluate and compare selected SNPs and genes in AA and AGA patients from Romania and Brazil. Materials and methods: We investigated associations between AA and AGA and 45 tag SNPs of 13 genes in 287 Romanian and 882 Brazilian patients. The DNA samples were extracted from saliva using qPCR technique. Results: GR-alpha gene, GPR44-2 gene, SULT1A1 gene and CRABP2 gene were statistically significantly different in Brazil compared to Romania. Minoxidil may be recommended in half of the cases of AGA and AA. Patients with AGA and high expression of SRD5A1 or PTGFR-2 may benefit from Dutasteride, respectively Latanoprost treatment. Most of the studied genes showed no differences between the two population. Conclusion: The DNA analysis of the patients with alopecia may contribute to a successful treatment.
ARTICLE | doi:10.20944/preprints202308.0347.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: psoriasis; neutrophil/lymphocyte ratio; platelet/lymphocyte ratio; neutrophil/monocyte ratio; systemic immune-inflammation index
Online: 4 August 2023 (07:52:53 CEST)
Background: Psoriasis is a chronic immune-mediated skin disease in which systemic inflammation plays an important role in the pathogenesis. In recent years, neutrophil-to-lymphocyte ratio (NLR), neutrophil-to-monocyte ratio (NMR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) have been shown to be important indicators of inflammation. In this study, our aim is to investigate NLR, NMR, PLR, and SII levels in psoriasis patients treated with biologic agents. Method: Clinical and biochemical data of 209 patients who received systemic therapy for psoriasis were obtained by retrospectively reviewing their medical records. NLR, NMR, PLR, and SII values were calculated from the hemogram values of the patients. Results: In the third month of follow-up, the mean CRP, NLR, NMR, PLR, and SII values were significantly decreased compared to the baseline values. SII values showed strong positive correlations with NLR, NMR and PLR. Adalimumab, etanercept, and infliximab, which are TNF-α blockers, were observed to be more effective on PLR and NLR and especially NMR. Conclusion: NLR, NMR, PLR, and SII, which are data obtained from routine blood tests, can be used in the monitoring of treatment of psoriasis, especially with TNF- α blockers.
ARTICLE | doi:10.20944/preprints202308.0361.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: skin aging; polymorpysms; laboratory analysis
Online: 3 August 2023 (14:42:49 CEST)
We conducted a research study to create groundwork for personalized solutions within skin aging segment. This test utilises genetic and general laboratory data to predict individual susceptibility of weak skin characteristics, leveraging on the research on genetic polymorphisms related to skin functional properties. A cross-sectional study was conducted in collaboration between the Private Clinic Medicina Practica Laboratory (Vilnius, Lithuania) and the Public Institution Lithuanian University of Health Sciences (Kaunas, Lithuania). 370 participants agreed to participate in the project. The median age of respondents was 40, with a range of 19 to 74 years. After the literature search, we selected 15 polymorphisms of the genes related to skin aging subsequently distributed for different skin functions: SOD2(rs4880), GPX1(rs1050450), NQO1(rs1800566), CAT (rs1001179), TYR (rs1126809), SLC45A2 (rs26722), SLC45A2 (rs16891982), MMP1(rs1799750), ELN (rs7787362), COL1A1(rs1800012), AHR (rs2066853), IL6 (rs1800795), IL1Beta (rs1143634), TNF-α (rs1800629), AQP3(rs17553719). RT genotyping, blood count and immunochemistry results have been analysed using statistical methods. Obtained results showed significant associations among genotyping models and routine blood screens. These findings demonstrate the personalized medicine approach for aging segment and further add onto the growing field of literature. Further investigation is warranted to fully understand the complex interplay between genetic factors, environmental influences, and skin aging.
ARTICLE | doi:10.20944/preprints202308.0150.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: nanoemulsion; wound healing effect; essential oil
Online: 2 August 2023 (08:29:35 CEST)
This study develops an efficient, low-temperature process for formulating a nanoemulsion-based gel encapsulating Pituranthos tortuosus's essential oil, investigating its wound healing potential. The novel process ensured stable encapsulation of the medicinal plant's oil. The nanoemulsion was characterized using dynamic light scattering and transmission electron microscopy, followed by in vitro and in vivo tests to examine wound healing efficacy. Results revealed the gel's excellent stability, high encapsulation efficiency, and significant wound-healing effects. This research provides a new method for formulating Pituranthos tortuosus's essential oil nanoemulsion-based gel, emphasizing the potential role of plant-based therapies in healthcare advancement, and invites further exploration into the therapeutic applications of essential oil-encapsulating nanoemulsions.
COMMUNICATION | doi:10.20944/preprints202308.0124.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: amniotic membrane stem cell; exosome-rich conditioned medium (ERCM); growth factor; neurotrophic factor; wound healing; keratinocyte proliferation; collagen synthesis
Online: 2 August 2023 (07:32:13 CEST)
Tissue regeneration is an essential requirement for wound healing and recovery of organs’ dysfunction. 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. 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 a concentration-dependent manner. 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 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. The results indicate that ERCM from AMSCs containing a large amount of GFs and NFs improve wound healing through tissue regeneration not only by facilitating keratinocyte proliferation for skin repair, but also activating fibroblasts for extracellular matrix production.
REVIEW | doi:10.20944/preprints202307.2097.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: Skin injuries; Therapy; Caring; Natural Materials; Regulatory Issues; ISO
Online: 31 July 2023 (10:38:44 CEST)
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.
REVIEW | doi:10.20944/preprints202307.1499.v1
Online: 21 July 2023 (10:27:08 CEST)
Psoriasis is considered an immune-mediated disease involving the innate and adaptative immune system triggered by environmental risk factors in genetically susceptible individuals. However, its physiopathology is not fully understood yet. Recent technological advances, specially genome and epigenome-wide studies, have allowed a more sensitive study of the genetic and epigenetic mechanisms, allowing an enhanced understanding of its physiopathology and facilitating the development of new drugs. In this review, we aim to summarize the current evidence on genetic and epigenetic mechanisms of psoriasis.
ARTICLE | doi:10.20944/preprints202307.0998.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: acne vulgaris; insulin resistance; HOMA-IR; resistant acne
Online: 14 July 2023 (11:12:45 CEST)
Acne vulgaris has multifactorial pathogenesis which may include insulin resistance. To investigate whether insulin resistance is a causative factor in acne vulgaris development, this study and a systematic review were conducted. 41 acne vulgaris patients and 47 healthy BMI-matched controls were involved. Glucose and insulin fasting serum levels were obtained, HOMA-IR was calculated, insulin resistance was diagnosed in cases with HOMA-IR value over 2.1. The mean±SD values for glucose fasting serum level were as follows: 94.88±7.731 [mg/dl] in study group and 79.51±7.175 [mg/dl] in controls (p<0.001). The mean±SD insulin fasting serum levels were 14.47±6.394 [µIU/mL and 11.83±4.309 [µIU/mL](p=0.059), respectively. The HOMA-IR mean±SD value calculated for the study group was 3.4±1.49 and in the control group 2.34±0.909 (p<0.001).Out of 41 patients 32 were diagnosed with insulin resistance (78%) and 26 of the 47 controls 26 were diagnosed with IR (55%) (p=0.026). Insulin resistance diagnosis was statistically more common among the acne patients compared to the controls. In the articles reviewed insulin resistance was found to be more frequent in acne vulgaris patients. Both our study and the papers analysed indicate that insulin resistance might be an independent factor in acne vulgaris development and should be considered when diagnosing and treating acne.
CASE REPORT | doi:10.20944/preprints202307.0971.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: atopic dermatitis; emollient plus cream; topical corticosteroids; topical calcineurin inhibitors; case report
Online: 14 July 2023 (09:18:55 CEST)
Atopic dermatitis (AD) is a chronic skin disease marked by inflammation, erythema, dryness and pruritic lesions. Due to the intermittent nature of the disease, management strategies for AD focus on flare prevention following remission. A 24-year-old patient with mild-to-moderate AD lesions, previously non-responsive to topical corticosteroids (TCS), was treated with pimecrolimus for 12 days and emollient plus cream (EC) every day. After the initial 12-day treatment course, the patient was advised to use pimecrolimus if his symptoms reoccured. AD symptoms improved substantially between Weeks 0 and 12 with daily use of EC. However, by Week 12, his symptoms had relapsed, necessitating retreatment with pimecrolimus. Overall, the patient experienced flare-free periods between Weeks 3 and 12 and between Weeks 13 and 16. No tolerability issues were reported. This case report demonstrates the use of a complementary approach of daily administration of maintenance EC and intermittent application of pimecrolimus for flare management, which was effective for treating a patient with mild-to-moderate AD resistant to TCS.
REVIEW | doi:10.20944/preprints202307.0996.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: hereditary angioedema guidelines; treatment; prophylaxis; management
Online: 14 July 2023 (08:49:28 CEST)
Hereditary angioedema (HAE) is a very rare and potentially life-threatening genetic disease characterized by low levels of C1-INH inhibitor esterase and involving recurrent attacks of non-pruritic angioedema that do not leave subcutaneous or mucosal wells without the presence of hives. It occurs worldwide in 1 in 50,000 to 150,000 individuals and accounts for approximately 2% of clinical angioedema. It affects both sexes equally and can affect all races without ethnic differences. Methods: We conducted a review in Pubmed regarding this disease using keywords such as: hereditary angioedema, guideline, treatment, prophylaxis, management. Results: We analysed 195 articles and we focused our study on 17 reviews about type I of HAE published in English in the last 10 years. Conclusions: Screening among the family members of affected individuals (even if symptoms are absent) is mandatory, since it is a life-threatening condition. Moreover, advances in diagnosis and management have significantly improved the outcomes and quality of life of patients with hereditary angioedema.
REVIEW | doi:10.20944/preprints202307.0554.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: alopecia; cicatricial alopecia; follicular cycle; follicle histopathology; hair; hair loss; noncicatricial alopecia; nonscarring alopecia; scarring alopecia
Online: 10 July 2023 (08:53:59 CEST)
Accurately diagnosing specific variants of alopecia remains challenging for pathologists, potentially delaying appropriate therapeutic decisions by dermatologists. Issues such as limited knowledge on optimal biopsy types and processing methods add complexity. Understanding the normal histology of hair follicles and their changes throughout the follicular cycle further complicates microscopic evaluation. This paper aims to summarize these characteristics and highlight essential diagnostic clues for pathologists to confidently suggest a diagnosis, therefore playing a key role in alopecia diagnosis. Ongoing education, collaboration with dermatologists, and staying updated on advancements is crucial for accurate diagnosis and effective management of different types of alopecia.
REVIEW | doi:10.20944/preprints202307.0397.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: Rosacea; inflammation; inflammatory skin disease; pathogenesis; therapeutic strategies; treatment options
Online: 6 July 2023 (09:02:30 CEST)
Rosacea is a chronic inflammatory skin disease characterized by recurrent erythema, flushing, telangiectasia, papules, pustules, and phymatous changes in the central area of the face. Patients with this condition often experience a significant negative impact on their quality of life, self-esteem, and overall well-being. Despite its prevalence, the pathogenesis of rosacea is not yet fully understood. Recent research advances are reshaping our understanding of the underlying mechanisms of rosacea, and treatment options based on the pathophysiological perspective hold promise to improve patient outcomes and reduce incidence. In this comprehensive review, we investigate the pathogenesis of rosacea in-depth, with a focus on emerging and novel mechanisms, and provide an up-to-date overview of therapeutic strategies that target the diverse pathogenic mechanisms of rosacea. Lastly, we discuss potential future research directions aimed at enhancing our understanding of the condition and developing effective treatments.
REVIEW | doi:10.20944/preprints202306.1811.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: advanced melanoma; pembrolizumab; immunotherapy
Online: 26 June 2023 (12:07:15 CEST)
Introduction: pembrolizumab showed to increase survival in patients with metastatic melanoma, Con-sidering the numerous oncoming studies, we decided to conduct a narrative review of the latest efficacy evidence regarding the use of pembrolizumab, alone or in combination, in patients with metastatic melanoma. (2) Methods: A search was conducted on Pubmed using "pembrolizumab," and "metastatic melanoma" as keywords, considering studies from 2022 onward. (3) results: we reviewed pembroli-zumab and associations, cost-effectiveness, virus, advanced acral melanoma, long-term outcomes, re-al-life data, biomarkers, obesity, and vaccines (4) Conclusions: pembrolizumab is a fundamental op-tion in the therapy of metastatic melanoma. However, a certain group of patients do not respond and therefore new combination options need to be evaluated. In particular, the use of vaccines tailored to tumor epitopes could represent a breakthrough in the treatment of resistant forms. Further studies with larger sample numbers are needed to confirm preliminary results.
ARTICLE | doi:10.20944/preprints202306.1726.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: Gut Microbiota (GM); Psoriasis (Ps); Psoriatic Arthritis (PsA); Mendelian randomization(MR); Causal effect
Online: 25 June 2023 (08:26:05 CEST)
Background: Numerous investigations have shed light on the intriguing interplay between gut microbiota(GM) and psoriasis (Ps) as well as psoriatic arthritis (PsA). However, the precise nature of the causal relationship between them remains an area of active investigation. Methods: For the purpose of our investigation, we meticulously curated a collection of genetic variants (P < 1 × 10−5) associated with GM (n = 18,340) derived from the MiBioGen study. To explore the intricate relationship between GM and Ps as well as PsA, we harnessed the comprehensive resources of the FinnGen database, encompassing a vast cohort of individuals, including 4,510 Ps cases and 212,242 controls, and 1,637 PsA cases and 212,242 controls. Even complementary MR methods were implemented, including an inverse variance weighting method, followed by a sensitivity analysis to verify the robustness of the results. Results: In this study, we found that certain bacterial taxa, such as Lactococcus, Ruminiclostridium 5, and Eubacterium fissicatena, were identified as risk factors. Conversely, Alloprevotella and Odoribacter demonstrated a protective effect against Ps. In the case of PsA, our results revealed a distinct set of risk factors and protective factors among the gut bacterial taxa. Lactococcus, Verrucomicrobiales, Akkermansia, Coprococcus 1, Lachnospiraceae, and Verrucomicrobiaceae were identified as risk factors for PsA. On the other hand, Odoribacter, Rikenellaceae, Clostridium innocuum, and Marvinbryantia exhibited a protective effect against the development of PsA. Conclusion: Our findings shed light on the distinctive disease characteristics and onset features between Ps and PsA. Notably, certain intestinal flora were implicated in the pathogenesis of PsA, suggesting their potential role as early diagnostic indicators. Furthermore, we identified several bacterial flora that exhibit a potential protective effect against the occurrence of Ps and PsA. These discoveries lay a solid foundation for future endeavors in the prevention and treatment of these conditions.
REVIEW | doi:10.20944/preprints202306.1647.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: Polypodium leucotomos; Fernblock®; photoprotection; photodermatoses; photoaging; hyperpigmentation
Online: 23 June 2023 (08:58:58 CEST)
Exposure to sun radiation leads to higher risk of sunburn, pigmentation, immunosuppression, photoaging and skin cancer. In addition to ultraviolet radiation (UVR), recent research indicates that infrared radiation (IR) and visible light (VIS) can play an important role in the pathogenesis of some of these processes. Detrimental effects associated to sun exposure are well known, but new studies have shown that DNA damage continues to occur long after exposure to solar radiation has ended. Regarding photoprotection strategies, natural substances are emerging for topical and oral photoprotection. In this sense, Fernblock®, a standardized aqueous extract of the fern Polypodium Leucotomos (PLE), has been widely administered both topically and orally with a strong safety profile. Thus, this extract has been used extensively in clinical practice, including as a complement to photodynamic therapy (PDT) for treating actinic keratoses (AKs) and field cancerization. It has also been used to treat skin diseases such as photodermatoses, photoaggravated inflammatory conditions and pigmentary disorders. This review examines the most recent developments in the clinical application of Fernblock® and assesses how newly investigated action mechanisms may influence its clinical use.
REVIEW | doi:10.20944/preprints202306.1290.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: psoriasis; genetics; biologics; cytokines; interleukins; small molecules; JAK-STAT
Online: 19 June 2023 (04:59:13 CEST)
Genetic susceptibility in psoriasis is a topic of interest in the initiative to improve targeted treatment strategies. In this review, we discuss genes linked to psoriasis and the available treatment options in context of targeting respective gene products implicated in the pathogenesis of psoriasis. In order to identify relevant genetic markers and treatments, we developed a literature search utilizing PubMed, Google Scholar, MEDLINE, and Web of Science with keywords, including genetic susceptibility to psoriasis, genetics and psoriasis, psoriasis treatments, biologics treatments in psoriasis. Articles in English from database inception to 1/1/23, were included. Case reports and series were excluded. Gene variant forms commonly implicated in the pathogenesis of psoriasis include those encoding for interleukins, interferons, and other mediators involved in inflammatory pathways, such as JAK/STAT, NFk-B, and others. Most commonly utilized treatments for psoriasis include drugs that target inflammatory markers like IL23, IL12, IL17, and TNF-a. TYK2 inhibition has been discussed as an emerging treatment strategy. Multiple genes are linked to the pathogenesis of psoriasis. This understanding may provide an avenue for further development of pharmacologic strategies targeting underlying genetic pathways. Genetically guided treatment may also allow for greater understanding in the selection of biologics.
ARTICLE | doi:10.20944/preprints202306.1248.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: Auricular keloids, CO2 laser therapy, Dye laser therapy, Multispectral analysis; scar; Vancouver scar scale; Patient and Observer Scar Assessment Scale
Online: 16 June 2023 (13:46:19 CEST)
Auricular keloids pose significant aesthetic and functional challenges, and traditional treatments often fall short in ad-dressing these. 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 multispec-tral analysis to assess keloid composition. The laser sequence was tailored per patient based on this analysis. Evalua-tions 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 recur-rence 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.
ARTICLE | doi:10.20944/preprints202306.0583.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: cosmetics; skin microbiota; Staphylococcus epidermidis; lactic acid; PCA
Online: 8 June 2023 (04:09:58 CEST)
Cosmetics have various characters, but there have been no studies which classified the properties of cosmetics based on their effects on skin-domesticated bacteria. In this study, we established an anaerobic culture and short-chain fatty acid measurement system using Staphylococcus epidermidis, a representative bacterium of indigenous skin bacteria. Furthermore, this system was used to extract and classify the characteristics of 9 cosmetics. Cosmetics containing ferments of rice and soy were clustered in the vicinity, although one cosmetic containing soy ferment was clustered distant from other similar cosmetics. Cosmetics from South Asia and those containing natural plant extracts were clustered in the vicinity. These results show that this method can be utilized as a cosmetics pattern map, and will provide a method to prevent growth of opportunistic bacteria.
ARTICLE | doi:10.20944/preprints202306.0301.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: pruritus; 3D-accellerometer; monitoring; allergic skin disease; canine atopic dermatitis
Online: 5 June 2023 (10:13:20 CEST)
Medical management of chronic canine pruritic dermatologic conditions is challenging and often frustrating. This is a report that shows one way of aiding the management of pruritic dogs using a remote monitoring device. It is often difficult for veterinarians to get dog owners to return to the clinic once a dog is treated. It is possible that a 3-D accelerometer device could provide information to the clinic staff on the success or failure of a pruritus treatment plan while the dog was cared for at home. Eighty-seven dogs and their owners came to a Florida dermatology specialty clinic or its general practice hospital to be evaluated and treated for pruritus. An ANIMO® 3-D accelerometer was placed on the collar of dogs diagnosed and treated for pruritus. Dogs that completed the study were monitored for 120 days (4 months). The ANIMO app monitored a dog’s daily scratching, shaking, sleeping, activity, resting, barking and calories consumed and summarized this information in a daily report visible on the pet owner’s smart phone. An additional variable (grooming minutes per day) could be seen by the Sure Petcare R&D Team that was not yet available in the app. The use of a 3-D accelerometer enabled veterinarians to continuously monitor dogs at home when they were being treated for itching. Clinic staff kept in touch with the owners by phone and could change therapy or bring the dog back for a recheck if problems were seen. Daily reports were combined into line charts that showed plots of scratching, shaking, grooming and sleeping over four months. Veterinarians were able to remotely monitor dogs that had been treated for pruritus for up to four months through the use of a collar-borne monitoring device. Dog owners and clinic staff used the daily summaries which were accessible through a smart phone app. Dogs seemed to tolerate the device well because of its small size and unobtrusive nature.
ARTICLE | doi:10.20944/preprints202306.0257.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: wound dressing; drug delivery; organ culture, infection models, ciprofloxacin, infected wounds
Online: 5 June 2023 (08:09:29 CEST)
Bacterial infections are a constant challenge in the management of acute and chronic wounds. Chronic wounds, like diabetic foot ulcers, have increased significantly in the last years due to the rise of an aging population. A better understanding of the infectious pathophysiological mechanisms is urgently needed along with new options for the treatment of wound infections and wound healing disorders. New advances in the preparation of biocompatible dressing materials that can be loaded with antimicrobial drugs may improve the topical treatment of infected wounds. In this study, we investigated the antimicrobial activity of polyvinylpyrrolidone (PVP) foils loaded with ciprofloxacin (Cipro-foils) in the presence of acetic acid as co-solvent. We used ex vivo human wounds that were infected with two bacterial strains: Methicillin-Resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa (PAO1). The effectiveness of the treatment was demonstrated by the quantification of the living bacteria extracted from the wound and the detection of released immunological mediators in skin extracts and in the skin culture media. We found that Cipro-foils effectively treated the infection with both PAO1 and MRSA. Other than PAO1, MRSA had not proteolytic effects. MRSA infections increased cytokines expression and release. Interestingly, treatment with Cipro-foils could partially counteract these effects.
ARTICLE | doi:10.20944/preprints202306.0016.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: psoriasis; psoriatic arthritis; IFIH1; MDA5; polymorphism; genetic association
Online: 1 June 2023 (03:40:11 CEST)
The melanoma differentiation-associated protein 5 (MDA5; encoded by the IFIH1 gene) mediates the activation of the interferon pathway in response to viral infection. This protein is also upregulated in autoimmune diseases and psoriasis skin lesions. IFIH1 gene variants that increased the MDA5 activity have been associated with increased risk for immune mediated diseases, including psoriasis. Our aim was to determine the association between three IFIH1 variants (rs35337543, intron8 +1G>C; rs35744605, Glu627Stop; and rs1990760, Ala946Thr) and the main clinical findings in a cohort of Spanish patients with psoriatic disease (N=572; 77% early-onset). Early-onset psoriasis (EOPs) had a significant higher frequency of severe disease and Cw6+. Carriers of the 946Thr variant were more common in EOPs (p<0.001), and the effect was more pronounced among Cw6-negatives. This variant was also associated with an increased risk of psoriatic arthritis (PsA) independently of other factors (OR=1.62, 95%CI=1.11-2.37). The rs3533754 and rs35744605 have been reported as risk factors for viral infection and protective for autoimmune diseases, but we did not find significant differences between the two onset age or PsA groups. However, due to the reduced frequency of the two variants (<0.02) the size of our cohort was too low to conclude a significant effect. In conclusion, the common IFIH1 rs1990760 T allele that has been linked to increased gene expression was significantly more frequent in EOPs patients. This variant was also an independent risk factor for PsA in our cohort. This risk allele was in linkage disequilibrium with other variants previously associated with the risk of psoriasis and PsA. Our study reinforces the widely reported role of IFIH1 gene variants on psoriatic disease and other immune mediated diseases.
ARTICLE | doi:10.20944/preprints202305.2058.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: Dermoscopy; high magnification; super-high magnification; keratinocyte; melanocyte; melanoma.
Online: 30 May 2023 (06:04:10 CEST)
Super-high (x400) magnification dermoscopy (D400) is a new non-invasive imaging technique that has been shown to add information for the differential diagnosis of melanocytic lesions in a pilot study. Our study aimed to confirm if D400 can add details for the discrimination of clinically atypical nevus and melanoma. This is a retrospective observational, multicentric study enrolling patients who received an x20 (D20) and x400 (D400) magnification dermoscopic examination of pigmented skin lesions. Dermoscopic images were retrospectively evaluated by three observers for the presence/absence of nine D20 and twenty D400 dermoscopic features defined in the previous pilot study. Univariate and multivariate analyses were carried out to find predictors of benign and malignant behaviors. At D20 atypical pigment network, blue-whitish veil, atypical vascular pattern, regression, and homogenous pattern were more frequent in melanoma than in nevi (p<0.001). At D400 melanoma showed more frequently than benign lesions melanocytes with an irregular arrangement and irregular in shape and size (p<0.001). Network with edged papillae was more frequent in benign lesions than melanomas (p<0.001). Our study confirms that D400 can identify melanocytes with an irregular arrangement and irregular in shape and size in melanomas, adding information to the conventional D20 examination.
ARTICLE | doi:10.20944/preprints202305.1369.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: UVA radiation; oxidative stress; dermal fibroblasts; apoptosis; antioxidant; Amaranthus cruentus seed oil; sun-protective substance; pharmacy; cosmetology
Online: 19 May 2023 (03:49:20 CEST)
UVA radiation inducing oxidative stress is harmful for the skin cells. The most sensitive are dermal fibroblasts. Exposure of the cells to prolonged UVA radiation induces apoptosis. Although, skin cells have a number of defense mechanisms that protect them against UV-induced oxidative stress, they are insufficient during long-lasting UV exposure. Therefore, there is a need for effective skin protection compounds with cytoprotective and antioxidant properties. One of their sources is Amaranthus cruentus L. seed oil, rich in unsaturated fatty acids, squalene, vitamin E derivatives, and phytosterols. The aim of this study was to evaluate whether Amaranthus cruentus seed oil evokes protective effect on the apoptosis stimulated by UVA radiation in human skin fibroblasts. UVA radiation at an applied dose of 10 J/cm2 caused a significant reduction in the survival of human skin fibroblasts and directed them into apoptosis pathway. Increased expression of p53, caspase 3, and caspase 9 and PARP proteins in UVA-treated fibroblasts suggests the intrinsic mechanism of apoptosis. The application of Amaranthus cruentus seed oil at 0.1% and 0.15% concentrations to UVA-treated cells decreased the expression of these proteins, which was accompanied by increased cell survival. Similarly, the UVA-dependent decrease in expression of p-Akt and mTOR proteins was restored, under the effect of studied oil. The molecular mechanism of this phenomenon is related to the stimulation of antioxidant processes through activation of Nrf2. This suggests that Amaranthus cruentus seed oil stimulate the antioxidant system in fibroblast cells and prevent the effects of UVA-induced oxidative stress and may find application in pharmacy and cosmetology as a sun- protective substance.
ARTICLE | doi:10.20944/preprints202305.1290.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: cutaneous T-cell lymphoma; ultraviolet; mutation signatures; malignant melanoma, whole exome sequencing
Online: 18 May 2023 (07:36:55 CEST)
Ultraviolet (UV) radiation is a strong environmental carcinogen responsible for the pathogenesis of most skin cancers, such as malignant melanoma (MM) and non-melanoma (keratinocyte) skin cancers. The carcinogenic role of UV was firmly established based on epidemiological evidence and molecular findings of the characteristic mutation signatures which occur during excision repair of cyclobutane pyrimidine dimers and 6,4-photoproducts. The role of UV in the pathogenesis of mycosis fungoides (MF), the most common primary cutaneous T-cell lymphoma, remains controversial. Here, we performed whole exome sequencing of 61 samples of MF cells microdissected from the cutaneous lesions, and compared their mutational signatures to 340 MM. The vast majority of MM mutations had a typical UV mutational signature (SBS 7, SBS 38, DSB 1) underscoring the key role of ultraviolet as a mutagen. In contrast, the SBS 7 signature in MF comprised <5% of all mutations. SBS 7 was higher in the intraepidermal MF cells (when compared to the dermal cells) and in the cells from tumors as compared to early-stage plaques. In conclusion, our data do not support the pathogenic role of UV in the pathogenesis of MF and suggest that the UV mutations are the result of the cumulative, environmental ultraviolet exposure of cutaneous lesions, rather than an early mutagenic event.
REVIEW | doi:10.20944/preprints202305.0628.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: atopic dermatitis; skin inflammation; natural products; nanotechnology; topical delivery
Online: 9 May 2023 (09:45:26 CEST)
Atopic dermatitis (AD) is a chronic eczematous inflammatory disease that may arise from environmental, genetic and immunological factors. Despite the efficacy of current treatment options like corticosteroids, such approaches are mainly focused on symptoms relief, and may present certain undesirable side effects. In recent years, investigation regarding isolated natural compounds, oils, mixtures and/or extracts, have gained scientific attention because of their high efficiency and moderate to low toxicity. Despite their promising therapeutic effects, the applicability of such natural health care solutions is somehow limited by their instability, poor solubility, and low bioavailability. Therefore, novel nanoformulation-based systems have been designed to overpass these limitations, thus enhancing the therapeutic potential, by promoting the capacity of these natural drugs to properly exert their action in AD-like skin lesions. For the best of our knowledge, this is the first literature review that focused on summarizing the last nanoformulation-based solutions loaded with natural ingredients, and specifically for the management of AD. We suggest that future studies should focus on robust clinical trials that may confirm the security and effectiveness of such natural-based nanosystems, thus paving the way for more reliable AD treatments.
ARTICLE | doi:10.20944/preprints202305.0461.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: Psoriasis; genetic susceptibility; oxidative stress; glutathione; glutamate cysteine ligase; GCLC; single nucleotide polymorphism; cigarette smoking; alcohol abuse; gene–environment interactions
Online: 8 May 2023 (08:03:11 CEST)
The aim of this pilot study was to investigate whether single nucleotide polymorphisms (SNP) in the gene encoding the catalytic subunit of glutamate cysteine ligase (GCLC) are associated with the risk and clinical features of psoriasis. A total of 944 unrelated individuals, including 474 patients with a diagnosis of psoriasis and 470 healthy controls, were recruited for the study. Six common SNPs in the GCLC gene were genotyped using the MassArray-4 system. Polymorphisms rs648595 (OR=0.56 95%CI 0.35-0.90, Pperm=0.017) and rs2397147 (OR=0.54 95%CI 0.30-0.98, Pperm=0.05) were associated with susceptibility to psoriasis in males. In the male group, diplotype rs2397147-C/C×rs17883901-G/G was associated with decreased risk of psoriasis (FDR-adjusted P=0.014), whereas diplotype rs6933870-G/G×rs17883901-G/G (FDR-adjusted P=0.045) showed association with increased disease risk in females. Joint effects of SNPs with tobacco smoking (rs648595 and rs17883901) and alcohol abuse (rs648595 and rs542914) on the risk of psoriasis were observed (Pperm≤0.05). Furthermore, we found multiple sex-independent associations between GCLC gene polymorphisms and various clinical features such as earlier disease onset, the psoriatic triad, and specific localizations of skin lesions. The present study is the first to show that polymorphisms of the GCLC gene are significantly associated with the risk of psoriasis and related to its clinical features.
COMMUNICATION | doi:10.20944/preprints202305.0357.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: ABCB5; cell therapy; mesenchymal stromal cells; recessive dystrophic epidermolysis bullosa; wound healing
Online: 5 May 2023 (10:49:57 CEST)
Recessive dystrophic epidermolysis (RDEB) is a rare, inherited and currently incurable skin blistering disorder characterized by cyclically recurring wounds coexisting with chronic non-healing wounds. In a recent clinical trial three intravenous infusions of skin-derived ABCB5+ mesenchymal stromal cells (MSCs) to 14 patients with RDEB improved healing of wounds that were present at baseline. Since in RDEB even minor mechanical forces perpetually provoke the development of new or recurrent wounds, a post-hoc analysis of patient photographs was performed to specifically assess the effects of ABCB5+ MSCs on new or recurrent wounds by evaluating 174 wounds that occurred after baseline. During 12 weeks of systemic treatment with ABCB5+ MSCs the number of newly occurring wounds declined. When compared to the previously reported healing responses of the wounds present at baseline, the newly occurring wounds healed faster, and a greater portion of healed wounds remained stably closed. These data suggest a previously undescribed skin-stabilizing effect of treatment with ABCB5+ MSCs and support repeated dosing of ABCB5+ MSCs in RDEB to continuously slow the wound development and accelerate the healing of new or recurrent wounds before they become infected or progress to a chronic, difficult-to-heal stage.
ARTICLE | doi:10.20944/preprints202304.1261.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: Ingrown toenail; onychocryptosis; hypergranulation tissue; proud flesh; sharp resection
Online: 30 April 2023 (04:48:26 CEST)
Ingrown toenails are a commonly occurring foot complaint. The condition occurs when the nail plate pierces the sulcus, giving rise to pain, inflammation and infection. As the skin attempts to heal itself, hypergranulation tissue may form. This is a case report of phenolic nail surgery treatment for a bilateral presentation with sharp resection of hypergranulation tissue performed in only one (the lateral) of the two affected sulci. Sharp resection of the residual medial hypergranulation tissue was performed two months after the index procedure when this had not settled. The case highlights the potential role of sharp resection in the overall improvement of treatment outcomes.
CASE REPORT | doi:10.20944/preprints202304.0775.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: facial rejuvenation; Stromal Vascular Fraction; adipose derived mesenchymal stem cells; autologous adipose tissue graft; Superficial Enhanced Fluid Fat Injection; clinical regeneration applications
Online: 23 April 2023 (05:01:28 CEST)
Background: The ageing process starts in the center of the face, in the periocular region and around the mouth, with a combination of volume loss and tissue descent, wrinkles deepen, and loss of skin structure and quality. Recently, several studies proved the efficacy of therapies based on the autologous adipose tissue grafting that leverages the properties of stromal vascular fraction (SVF) and adipose derived mesenchymal stem cells (ADSCs) to accelerate the regenerative processes of the skin. This study aimed to verify the ability of the guided Superficial Enhanced Fluid Fat Injection (SEFFI) in the facial area to correct volume loss and skin aging and proved the very low rate of complications of this standardized procedure . Methods: we retrospectively collected data from 2,365 procedures performed in Italian centers between 2019 and 2021. Guided SEFFI was performed alone or combined with cosmetic treatments, including the use of hyaluronic acid filler, suspension threads, synthetic calcium hydroxylapatite, botulin toxin, and microneedling. Results: SEFFI was used alone in more than 60% of the patients, and in all face areas. In about one tenth of patients SEFFI was combined with botulin toxin treatment or hyaluronic acid filling. Other procedures were used more rarely. Ecchymosis in the donor or injection sites was the most frequent event, and yet observed in only 14.2% and 38.6% of patients, respectively. Conclusions: The SEFFI technique is standardized and minimally invasive, leading to very few complications. It can be a promising antiaging medical treatment that combines effectiveness, safety, and simplicity.
ARTICLE | doi:10.20944/preprints202304.0630.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: Hidradenitis Suppurativa; Adalimumab (Humira); Hurley Stages; Arabs and Jews
Online: 20 April 2023 (08:14:30 CEST)
Background: Hidradenitis Suppurativa (HS) is characterized by inflamed lesions that appear in apocrine rich flexural areas. Although studies have reported clinical and epidemiological data from western countries, data from the Middle East are scarce. The aim of this study is to characterize the differences in the clinical characteristics of patients with HS of Arab and Jewish ancestry and to review the clinical characteristics, the course of the disease, the comorbidities and the response to treatment. Methods: This is a retrospective study. We collected clinical and demographic data from patient files at the Rambam Healthcare Campus dermatology clinic – a tertiary hospital located at the north of Israel. between 2015-2018. Our results were compared to those of a previously published Israeli control group registered in clalit health services. Results: Of the 164 patients with HS, 96 (58.5%) were men and 68 (41.5%) were women. The average age at diagnosis was 27.5 years and the latency between the onset and diagnosis of the disease was 4 years. we found a higher adjusted prevalence of HS in Arab patients (56%) than in their Jewish counterparts (44%). Gender, smoking and obesity, as well as axilla and buttock lesions, were risk factors for severe HS, with no differences between ethnicities. No differences were documented in comorbidities and in response to Adalimumab, with a high overall response rate of 83%. Conclusions: Our findings revealed differences between Arab and Jewish patients with HS in terms of incidence and gender predominance, while no differences were documented in comorbidities and response to Adalimumab.
ARTICLE | doi:10.20944/preprints202304.0617.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: Psoriasis; erythema; infiltration; desquamation; itching; PASI; SBA
Online: 20 April 2023 (07:34:29 CEST)
Introduction: Psoriasis is an inflammatory skin disease. The objective was to elaborate a cream with natural products and salicylic acid. Hypothesis: ¿Will the topical cream made from natural products reduce the characteristic clinical signs of psoriasis? Methodology: Quasi-experimental clinical trial, in 100 healthy volunteer subjects, five formulations of the new product were prepared and applied to each 20 healthy subjects. The universe was 270 patients with different type of dermatology disease, 120 volunteer patients were selected with Psoriasis, of which he creams was applied to 60 volunteer patients with mild and moderate psoriasis were no randomly administered the full formulation of the new product at TMC Hospital. The database for this study is in the Figshare and Dryad repository. Outcome: In healthy subjects showed that 99% had no side effects. In psoriasis patient mild and moderate psoriasis at TMC Hospital was evaluated the results before and after treatment with the new formulation, Using T Student for paired tests, in the clinical variables, as well as the PASI index and the SBA, the alternative hypothesis was proved, the new formula is effective in the control post treatment of psoriasis (p=0.000). Discussion: The new formulation showed greater efficacy after 10 days treatment. This cream is recommended as an alternative and complementary therapy for psoriasis, since it did not show secondary reactions in healthy subjects, so its effectiveness was demonstrated in this study. A new population study is recommended by regions in Ecuador: coast, highlands, Amazon and Galapagos Island, to evaluate the response to treatment.
ARTICLE | doi:10.20944/preprints202304.0545.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: Paullinia cupana; natural products; nanoparticles; stability; cytotoxicity; cell culture
Online: 19 April 2023 (04:52:31 CEST)
The objective of this study was to analyze the in vitro stability and toxicity of liposomes containing guarana in skin cell lines. The liposomes were produced by the reverse phase evaporation method containing 1 mg/mL guarana. The stability of the liposomes was evaluated by physical-chemical parameters for up to 90 d using three different storage conditions. The cytotoxicity of guarana (GL), liposomes (B-Lip), and guarana-loaded liposomes (G-Lip) was evaluated on spontaneously immortalized human keratinocyte cell lines (HaCaT), murine swiss albino fibroblasts (3T3), and human fibroblast (1BR.3.G). The evaluation was performed using cellular viability analysis. The techniques used were 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and neutral red capturing (NRU) and the analyses were conducted after 24, 48, and 72 h exposure of these cells to the different treatments. The G-Lip exhibited physical-chemical stability for 60 d when the samples were stored in a refrigerator. The GL, B-Lip, and G-Lip demonstrated low cytotoxicity in the three cell cultures tested since a low reduction in cell viability was only observed at the highest concentrations. In addition, greater cell damage was observed for B-Lip; however, guarana protects cells from this damage. Thus, G-Lip structures can be considered as promising systems for topical applications.
ARTICLE | doi:10.20944/preprints202304.0395.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: cassipourea flanaganii; hypermelanosis; melasma; toxicity
Online: 17 April 2023 (04:11:14 CEST)
The conventional use of medicinal plants is in part based on the widespread belief that plant crude extracts are non-toxic. In South Africa, traditional preparations of Cassipourea flanaganii used to treat hypermelanosis have accordingly been regarded by many as non-toxic. Whether so, impacts on the potential of bark extracts to be developed as a commercial drug to treat melasma, given their documented capacity to inhibit tyrosinase activity. Our study investigated the acute and subacute toxicity of the methanol extract of C. flanaganii bark in rats. Wistar rats were randomly assigned into different treatment groups. The rats received daily oral gavage of crude extract for acute and sub-acute toxicity tests. Haematological, biomechanical, clinical and histopathology examinations were carried out to evaluate possible toxicity of C. flanaganii. Results were subjected to the Student’s t-test and ANOVA. For both acute and subacute toxicity, there was no statistical difference between groups. There were no clinical or behavioral signs of toxicity observed in the rats. No treatment-related gross pathology lesions as well as no histopathology was observed. The findings of this study demonstrate the absence of acute or subacute toxicity after oral treatment with C. flanaganii bark extracts in Wistar rats at the levels administered.
REVIEW | doi:10.20944/preprints202303.0164.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: mucosal barrier; cholangiocarcinoma; gut-liver-axis; primay biliary cholangitis; primay sclerosing cholangitis
Online: 9 March 2023 (03:12:39 CET)
The “Gut-Liver Axis” refers to physiological bidirectional interplay between the gut and its microbiota and the liver which, in health, occurs thanks to a condition of immune tolerance. In recent years, several studies have shown that, in case of modifications of gut bacterial homeostasis or impairment of intestinal barrier functions, cholangiocytes, which are the epithelial cells lining the bile ducts, activate innate immune responses against gut-derived microorganisms or bacterial products that reach the liver via enterohepatic circulation. Intestinal dysbiosis or impaired intestinal barrier functions expose cholangiocytes to an increasing amount of microorganisms and may exacerbate inflammatory responses thus leading to fibrotic remodeling of the organ. The present review focuses on the role of the gut liver axis in the pathogenesis of cholangiopathies.
REVIEW | doi:10.20944/preprints202303.0110.v1
Online: 6 March 2023 (15:23:52 CET)
The relative paucity of donor livers suitable for transplantation has sparked innovations to preserve and recondition organs to expand the pool of transplantable organs. Currently, machine perfusion techniques have led to the improvement of the quality of marginal livers and to prolonged cold ischemia time and allowed for the prediction of graft function through analysis of the organ during perfusion, improving the rate of organ use. In the future, the implementation of organ modulation might expand the scope of machine perfusion beyond its current usage. The aim of this review was to provide an overview of the current clinical use of machine perfusion devices in liver transplantation and provide a perspective for future clinical use, including therapeutic interventions in perfused donor liver grafts.
REVIEW | doi:10.20944/preprints202303.0039.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: metabolic disorders; nitric oxide; obesity; ultraviolet; vitamin D
Online: 2 March 2023 (09:44:53 CET)
Ultraviolet (UV) radiation has both harmful and beneficial effects on human health. It can cause skin damage and cancer, but also provides the primary source of vitamin D. Additionally, UV radiation affects energy metabolism in mice with metabolic diseases and has protective effects on hypertension and cardiovascular diseases.Metabolic Syndrome is a collection of metabolic dysfunctions such as dyslipidemia, hypertension, hyperglycemia, abdominal/central obesity, and insulin resistance. Chronic UVR exposure suppressed obesity and type 2 diabetes in high-fat diet-fed mice, while vitamin D supplementation did not replicate these effects. On the other hand, topical application of nitric oxide (NO) donors replicated UV effects on mice, and NO scavengers prevented the positive impact of UV. UVR may prevent the development of obesity and metabolic syndrome through mechanisms that depend on UVR-induced NO, not vitamin D. Exposure to sunshine has a protective impact on blood pressure and cardiovascular disease. Although lower vitamin D concentration is linked to increased hypertension and the incidence of CVD, oral vitamin D supplementation does not decrease blood pressure or the risk of CVD, indicating that vitamin D may not mediate the beneficial effects of sun exposure. Instead, NO plays a crucial role as an endogenous vasodilator, produced by the vascular endothelium. Solar UVA may release nitrogen oxides from skin storage into the bloodstream, lowering blood pressure and cardiovascular mortality.In conclusion, UVR exposure could be a promising non-pharmacological intervention for metabolic syndrome, hypertension, and CVD prevention, and NO may play a crucial role in mediating these effects. Further research is needed to explore the precise mechanisms and identify the optimal doses and exposure times of UVR.
ARTICLE | doi:10.20944/preprints202303.0035.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: breast cancer; radiodermatitis; radiotherapy; primary prevention
Online: 2 March 2023 (06:33:07 CET)
INTRODUCTION: Radiation dermatitis is a common sequela of radiotherapy (RT) that can affect up to 95% of patients, developing moderate to severe skin reactions in up to 30% of them. Variation in fractionation or administration methods may reduce the incidence and severity of radiation dermatitis. It is considered that topical use of preparations holding certain preservatives, surfactants, additives, oils, and impurities should be avoided in cancer patients. In clinical practice, creams of different compositions are used, with and without Epidermal Growth Factor (EFG). OBJECTIVE: To analyze the effectiveness of three creams of different compositions for the control of symptoms and skin side effects of RT.METHODS: A pilot study comparing three treatment groups (HR, HU, and RS creams) during the RT program and with a follow-up of 2 weeks thereafter. Study variables: fractionation, Patient-Observer scale, Maxidex (elasticity, hydration, melanin, erythema).RESULTS: The pilot study sample included 15 patients (5 for each group), so the results were not statistically significant. There were no undesirable side effects to the application of the creams under study and compliance and tolerance were excellent.Regardless of fractionation, RS cream appears to be more effective in controlling symptoms during RT, while HU cream may control them more effectively after the RT regimen is completed.During RT, in hypofractionated therapies, the RS cream seems to preserve elasticity, hydration, and hyperpigmentation allowing erythema that could increase skin repair processes. After the RT is finished, the HR cream further improves elasticity and allows the appearance of erythema.In normofractionated therapies during RT all creams seem to have comparable results in the four cutaneous components analyzed; after completion of RT, HR cream appears to better control hydration and hyperpigmentation.CONCLUSIONS: All the creams analyzed have good control of symptoms and the appearance of the skin during and after RT. The prescription of one or another composition should be done individually according to the cutaneous and clinical particularities of each patient. A study with experimental design is needed to analyze the statistical significance of the differences between the creams analyzed.
REVIEW | doi:10.20944/preprints202302.0458.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: atopic eczema; dermatitis; allergy; itch; skin disease; treatment; prevention; epidemiology; ethnic differences; cellular; molecular; immunological; physiological therapeutic
Online: 27 February 2023 (08:30:54 CET)
Atopic dermatitis (AD) is a common chronic inflammatory skin disease with high prevalence worldwide, including countries from Asia, Africa and Latin America, and in different ethnic groups. In recent years, more attention on AD heterogeneity associated on multiple factors, including patient’s ethnic background, has been posed, resulting in an increasing body of clinical, genetic, epidemiologic, and immune-phenotypic evidence that delineate differences among racial groups with AD. Filaggrin (FLG) mutations, the strongest genetic risk factor for the development of AD, are detected in up to 50% of European and 27% of Asian AD patients, while very rarely in Africans. The Th2 activation is a common attribute of all ethnic groups, though the Asian endotype of AD is also characterized by an increased Th17-mediated signal whereas African Americans own a strong Th2/Th22 signature and the absence of Th1/Th17 skewing. In addition, the ethnic heterogeneity may own important therapeutic implications as the genetic predisposition may affect treatment response and, thereby, a tailored strategy that better targets the dominant immunologic pathways in each ethnic subgroup may be envisaged. Nevertheless, white patients with AD represent the largest ethnicity enrolled and tested in clinical trials and the most treated in a real-world setting, limiting the investigation about safety and efficacy across different ethnicities. The purpose of this review is to describe the heterogeneity of pathophysiology across ethnicities and its potential therapeutic implications.
REVIEW | doi:10.20944/preprints202302.0429.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: RNA therapeutics; skin; mRNA therapeutics; siRNA therapeutics; antisense oligonucleotide ther-apeutics; ASO; melanoma; hypertrophic scars; wound healing; dermatology
Online: 27 February 2023 (01:53:06 CET)
Despite being under development for decades, RNA therapeutics have only recently emerged as viable platform technologies. The COVID-19 mRNA vaccines have demonstrated the promise and power of the platform technology. In response, novel RNA drugs are entering clinical trials at an accelerating rate. As the skin is the largest and most accessible organ, it has always been a preferred target for drug discovery. This holds true for RNA therapies as well, and multiple candidate RNA-based drugs are currently in development for an array of skin conditions. In this mini review, we catalog the RNA therapies currently in clinical trials for different dermatological diseases. We summarize the main types of RNA-related drugs and use examples of drugs currently in development to illustrate their key mechanism of action.
ARTICLE | doi:10.20944/preprints202302.0351.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: liver fibrosis; liver cirrhosis; bile duct ligation; animal model
Online: 21 February 2023 (04:21:07 CET)
Liver fibrosis is based on complex interactions between extracellular matrix-producing hepatic stellate cells and is defined as excessive matrix deposition and an abundance of infiltrating cells in the liver. Studying these processes requires in vitro and in vivo experimental work on animals. In fibrosis research, experimental work in rodents is currently the gold standard for confirming a proposed disease-associated mechanism. Bile duct ligation (BDL) induces obstructive jaundice resulting in cholestasis. BDL is useful for preclinical research studies of liver injury due to extrahepatic cholestasis such as apoptosis and fibrosis. Here we provide a stepwise surgical approach to resect the common bile duct and monitor in situ hepatic metabolism by microdialysis.
CONCEPT PAPER | doi:10.20944/preprints202302.0297.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: Helicobacter pylori; peptic ulcer; etiology; illusion; philosophy; African enigma
Online: 17 February 2023 (06:33:15 CET)
Currently, peptic ulcers are widely considered an infectious disease caused by Helicobacter pylori due to 3 supporting evidences, and this etiology may explain 3 other observations. However, it cannot withstand the challenges of all the 15 major characteristics and the other 75 observations/phenomena of peptic ulcers. To address these challenges, a recently published Complex Causal Relationship with its accompanying methodologies was applied to analyze the existing data. Peptic ulcers are identified as a psychosomatic disease triggered by psychological stress, where Helicobacter pylori plays a secondary role in the late phase of ulceration. This new etiology addresses all the characteristics, observations/phenomena, controversies, and mysteries of peptic ulcers in a series of 6 articles. This sixth article focuses on the controversies associated with Helicobacter pylori. In-depth analyses find that all the 3 supporting evidences are illusions, and all the 3 explainable observations are misinterpreted, indicating that none of the 15 characteristics and 81 observations/phenomena of peptic ulcers can be elucidated by the etiology based on Helicobacter pylori. Moreover, the definitions of ‘etiological factor’, controversies on H. pylori, epidemiological studies, characteristics of the disease, and historical observations suggest ‘peptic ulcers are an infectious disease caused by Helicobacter pylori’ is an illusion and thus, the African enigma, a mystery derived from the illusion, does not exist. Similar illusions widely exist in medical research, resulting in direct interference with the true understanding of diseases. A full understanding of the pathogenesis of peptic ulcers highlights the guiding role of philosophy in life science and medical research.
ARTICLE | doi:10.20944/preprints202302.0271.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: peptic ulcer; seasonal variation; superposition mechanism; climate; work; vacation; psychosomatic disease; psychological stress
Online: 16 February 2023 (04:52:59 CET)
Although 13 etiological theories, including the most recent Theory of Helicobacter pylori, have been proposed to explain the pathogenesis of peptic ulcers, the seasonal variation of the disease has remained an unsolved mystery for ≥90 years. Additionally, the major characteristics and observations/phenomena of peptic ulcers have never been fully understood. To address these challenges, a recently published Complex Causal Relationship with its accompanying methodologies was applied to analyze the existing data. Peptic ulcers were identified as a psychosomatic disease triggered by psychological stress, where Helicobacter pylori plays a secondary role in only the late phase of ulceration. This etiology addresses all the characteristics, observations/phenomena, controversies, and mysteries of peptic ulcers in a series of 6 articles. This fourth article focuses exclusively on the seasonal variation of peptic ulcers. The seasonal changes on the earth periodically alter multiple environmental/social factors, each of which induces psychological stress in a proportion of individuals and result in a monthly incidence of peptic ulcers. The superposition of the monthly incidences caused by climate, work, and vacation reproduces 3 typical fluctuation curves of the seasonal variation. Further discussion suggests that surrounding psychological stress, multiple environmental and social factors, such as tradition, climate, industry, vacation, and well-being policies, work together to cause the diversity of the seasonal variation. A full understanding of the seasonal variation suggests that peptic ulcers are not an infectious disease caused by Helicobacter pylori, but a psychosocial disease associated with multiple environmental/social factors, further validating the etiology identified by the Complex Causal Relationship.
ARTICLE | doi:10.20944/preprints202302.0193.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: peptic ulcers; birth-cohort phenomenon; superposition mechanism; psychosomatic disease; psy-chological stress; crucial events
Online: 13 February 2023 (02:06:22 CET)
Background: The birth-cohort phenomenon of peptic ulcers has remained an unresolved mystery for 60 years since it was first reported in 1962. Currently, peptic ulcers are widely studied as an infectious disease caused by Helicobacter pylori, but this etiology cannot explain this phenomenon. A recently published etiological theory identified peptic ulcers as a psychosomatic disease triggered by psychological stress. This new theory addresses all the characteristics, observations/phenomena, controversies, and mysteries of the disease in a series of 6 articles. Methods: In this fourth article of the series, all the possible causes of peptic ulcers collected from literatures were classified into 3 categories, and the mortality rates caused by these categories were superposed to reproduce the fluctuation curves in the birth-cohort phenomenon. Results: The fluctuation curves in the birth-cohort phenomenon were successfully reproduced, with all the details of the phenomenon elucidated. Psychological stress induced by the First World War accounted for the increasing mortality rates in the early 1910s. The high mortality rates between 1910s and 1940s were maintained by a succession of crucial events that led to extensive psychological stress in the population. The end of the Second World War and continuous improvements in living conditions explained the fall in the early 1950s and afterwards. Conclusions: The birth-cohort phenomenon cannot be fully understood unless peptic ulcers are considered a psychosomatic disease triggered by psychological stress. A full explanation of the birth-cohort phenomenon exemplifies the application of a brand-new methodological concept, superposition mechanism, which can be universally applied to understand any life phenomenon and human disease.
ARTICLE | doi:10.20944/preprints202212.0364.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: Phaseolus angularis seed extract (PASE); anti-aging; health skin, cosmetic products
Online: 20 December 2022 (09:03:36 CET)
Skin photoaging is caused by prolonged exposure to ultraviolet (UV) radiation from sunlight. UV-exposed skin appears rough, thick, dry, loose, and shows deep wrinkles, and thickening. Our previous research showed that a Phaseolus angularis seed extract (PASE) effectively inhibits photoaging through UVB protection in HaCaT cells. However, its efficacy has not been evaluated in clinical trials so far. In this single-centered, randomized, double-blind study, we investigated the anti-aging effect of PASE in eye wrinkle areas. To these 21 healthy adult women aged 30 to 65, a PASE cream was applied to the right eye wrinkle area and a placebo to the left eye wrinkle area twice a day (morning and evening) for 12 weeks. The change in thick, deep crease wrinkles around the eyes was confirmed by visual evaluation, skin measurements, and a questionnaire. As a result, the R1 (surface roughness), R2 (maximum roughness), R3 (average roughness), R4 (smoothness depth), and R5 (arithmetic mean roughness) values in the group using the PASE cream all decreased. Particularly, R1, R4, and R5 significantly decreased by 18.1%, 18.6%, and 25.0%. In addition, no participants reported side effects. Our study showed that PASE led to clinically significant levels of wrinkle improvement. In conclusion, as PASE is a natural food, safe, and with few side effects, it can be a good resource for natural anti-wrinkle cosmetics in the future.
REVIEW | doi:10.20944/preprints202212.0315.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: Melasma; Treatment; Darker skin types; Fitzpatrick skin types IV-VI; mapping review
Online: 19 December 2022 (03:45:26 CET)
Melasma is a challenging chronic skin condition associated with hyperpigmentation and un-known etiology. This scoping review mapped evidence of available treatments and their effectiveness in darker skin types. A comprehensive, systematic online search was conducted in Scopus, PubMed, CINAHL Complete, Cochrane, ScienceDirect, and Web of Science Core Collection. All eligible titles were exported to an Endnote20 library. Thematic content analysis was performed to summarise data on current melasma treatments for darker skin types. The quality of included articles was appraised using the Mixed Methods Appraisal Tool (MMAT) 2018 version. A total of 2863 articles were retrieved from the databases, and 10 met the eligibility criteria following abstract and full-text screening. Our findings demonstrate that topical treatments, chemical peels, lasers, and tranexamic acid are common treatment modalities used in darker skin types. Although these treatments may be effective in the short term, they bring about un-desirable side effects and sometimes worsen or result in reoccurrences of melasma. Based on the evidence mapped, current treatment modalities are not suitable for darker skin types. There are very few studies conducted on individuals of African descent. Further research is necessary to investigate treatment interventions which may be user-friendly when dealing with darker skin types.
REVIEW | doi:10.20944/preprints202211.0345.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: Tungiasis; Tunga penetrans; neglected tropical diseases; epidemiology
Online: 18 November 2022 (02:48:20 CET)
Tungiasis is a neglected parasitic skin disease caused by the permanent penetration of the female sand flea (Tunga penetrans) in the skin of the host, mainly the lower extremities.This gradually, it can lead to severe limb deformities.To date it is a health issue mainly in sub-Saharan Africa, the Caribbean, Latin and South America. It occurs mainly in poor rural populations and a major problem for children and the elderly. In diurnal zones, the incidence can reach over 73%. Over the past 20 years, studies in endemic areas on tungiasis have clarified to some extent the scientific community's knowledge for some problems of the disease. In this review, the current data on epidemiology, risk factors and prevention options are examinedof Tungiasis, as well as the expected steps of the international medical community to combat the disease.
REVIEW | doi:10.20944/preprints202211.0340.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: Tungiasis; Tunga penetrans; neglected tropical diseases; epidemiology
Online: 17 November 2022 (12:53:26 CET)
Tungiasis is a neglected parasitic skin disease caused by the permanent penetration of the female sand flea (Tunga penetrans) in the skin of the host, mainly the lower extremities.This gradually, it can lead to severe limb deformities.To date it is a health issue mainly in sub-Saharan Africa, the Caribbean, Latin and South America. It occurs mainly in poor rural populations and a major problem for children and the elderly. In diurnal zones, the incidence can reach over 73%. Over the past 20 years, studies in endemic areas on tungiasis have clarified to some extent the scientific community's knowledge for some problems of the disease. In this review, the current data on epidemiology, risk factors and prevention options are examinedof Tungiasis, as well as the expected steps of the international medical community to combat the disease.
ARTICLE | doi:10.20944/preprints202211.0137.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: Mushroom tyrosinase; Melanogenesis; Tyrosinase inhibitor; Multi-spectroscopic techniques; Natural compounds; tyrosinase inhibitor
Online: 8 November 2022 (02:23:25 CET)
This research work focuses on the potential application of an organic compound, santalol obtained from santalum album in the inhibition of the enzyme tyrosinase which is actively involved in the biosynthesis of the melanin pigment. Over-production of melanin causes undesirable pigmentation in humans as well as other organisms that significantly downgrade their aesthetic value. The study is designed to explain the purification of tyrosinase from the mushroom Agaricus bisporus, followed by activity assay and enzyme kinetic to give insight into the santalol modulated tyrosinase inhibition in a dose dependent manner. The multi-spectroscopic techniques like UV-vis, fluorescence, and isothermal calorimetry are employed to deduce the efficiency of santalol as potential candidate against the tyrosinase enzyme activity. Experimental results are further verified by molecular docking. Santalol derived from the essential oils of santalum album, is widely used as remedy for skin disorders and potion for fair complexion since ancient times. Based on enzyme kinetics and biophysical characterization, this is the first scientific evidence where santalol inhibits tyrosinase, which may be employed in agriculture, food, and cosmetic industries by prevent excess melanin formation or browning.
ARTICLE | doi:10.20944/preprints202211.0133.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: skin infection; antibiotics; quinolone; S. aureus; geriatrics
Online: 8 November 2022 (01:57:03 CET)
INTRODUCTION: Superficial cutaneous bacterial infections have a high incidence in geriatric patients. The most implicated pathogens are gram-positive cocci (Staphylococcus aureus, Streptococcus pyogenes) while gram-negative germs are also implicated. Resistances to common topical antibiotics (mupirocin, fusidic acid) require alternatives to gram-positive and gram-negative microorganisms.Ozenoxacin cream for topical use (non-fluorinated bactericidal quinolone), in other countries and with other galenics, is indicated in children older than 6 months and in adults as a treatment of superficial bacterial infections, such as acne. In Spain, ozenoxacin cream is indicated only for non-bullous impetigo; scientific evidence show effectiveness also in other superficial skin bacterial infections.A cases series of clinical use of ozenoxacin in bacterial superficial skin infections in geriatric patients (institutionalized or community dwelling) is presented.METHODS: Multicenter case series (March-August 2022) of bacterial superficial skin infections treated with ozenoxacin cream (10mg/g every 12h, 5days); data from medical records (controls: 1-3-5 days), after obtaining informed consent (use of data and images).RESULTS: Series of 28 patients (mean age: 84,79) from nine nursing homes and one outpatient geriatric service, including acute and subacute/chronic cases.In all cases treatment was ozenoxacin 10mg/g topical cream applied every 12 hours for 5 days according to medical prescription (except for one case in which 3 days were enough for complete healing and another case treated for 10 days).Results showed complete healing in all 20 acute cases and significant clinical improvement in all subacute/chronic cases (with complete healing in one of them). Professionals scored the effectiveness in acute cases as a mean 4.5 points (maximum score: 5, p<.0001) and in subacute/chronic cases as 3.8 points (p=.010).There was no skin irritation or other adverse effects in anyone of the patients, and clinical improvement of pain, itching and other symptoms was observed, suggesting an anti-inflammatory effect. DISCUSSION AND CONCLUSIONS: Our results seem to demonstrate the effectiveness and tolerability of ozenozacin cream in bacterial infections other than non-bullous impetigo. Ozenoxacin cream is indicated only for the treatment of non-bullous impetigo; however, it is also shown to be effective, both in the scientific evidence and in our case series, for other superficial bacterial skin infections, both acute and subacute/chronic, suggesting the opportunity for clinical studies with an experimental design to evaluate the findings of clinical practice and to be able to have a therapeutic alternative to compensate for the complications of the appearance of resistance.
REVIEW | doi:10.20944/preprints202211.0099.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: Clothing; Health Promotion; Skin Cancer Prevention; Sport; Ultraviolet Radiation
Online: 7 November 2022 (02:06:38 CET)
Australia and New Zealand have the highest incidence of skin cancer. Sport is a fundamental part of Australasian culture, beginning in childhood, often with life-long participation. Participating in outdoor sports can contribute significantly to the lifetime ultraviolet radiation (UVR) dose individuals receive and their risk of developing skin cancer. This systematic scoping review explores the use of sun-protection by outdoor sporting participants in Australasia and considers how sun-protection practices may be better evaluated and improved in the community. A search of electronic databases using the search strategy “sun protection” AND “sport” AND “Australia” yielded 17 studies published in English from January 1992 to August 2021. Study methods included using UV-dosimeters to measure individual UVR-exposure; remote estimates of clothing-adjusted UVR-exposure; direct observation of sun-protection practices; and self-reported sun-exposure and sun-protection. Despite 40-years of ‘Slip Slop Slap’ campaigns in Australia, the use of sun-protection in most outdoor sports is inadequate. The paucity of comparable data limited our analyses, demonstrating a need for standardized, objective evaluation tools. Such tools, if used across a range of sports, should inform the development of workable recommendations that sporting clubs could implement and adopt into policy, thus empowering them to better protect the health of their participants.
ARTICLE | doi:10.20944/preprints202209.0317.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: Bibliometric analysis; Scopus database; Syphilis; Sexually Transmitted Infections; Public Health; Research; Global
Online: 21 September 2022 (07:14:19 CEST)
Sexually transmitted infections encompass considerable effects on human sexual and reproductive health. Its presence is ubiquitous despite decades of prevention and management. The present study has been conducted to provide an insightful bibliometric analysis of syphilis based on the Scopus repository. Therefore, given the dearth of a consolidated bibliometric analysis on Syphilis, this investigation aimed to compile the literature of the last century (1921-2021) to gain insight into the publications pertinent to the burden, diagnosis, treatment, and management of Syphilis. In this study, we have provided the year-wise, and subject-wise publications, type of articles, country, funding organizations, institutions, citations, and H-index. The data obtained from the Scopus database was exported to CSV file format and then converted to Microsoft Excel version for analysis to curtail the chances of error in the information. It has been evidenced that the USA possesses the highest track of proven publications. Therefore, this study considerably contributes to the future leaders, researchers & specialists/ clinicians of the domain
REVIEW | doi:10.20944/preprints202209.0303.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: Ultraviolet irradiation; Dead Sea; psoriasis; photoclimatotherapy
Online: 20 September 2022 (10:23:03 CEST)
The Dead Sea basin is the lowest terrestrial site on the globe and is internationally recognized as a photoclimatotherapy center. Since the last century, questions raised regarding the possible presence of a unique incident ultraviolet irradiation, allowing successful treatment of psoriasis, atopic dermatitis and other dermatological diseases. Aim: Determine the characteristics of the solar ultraviolet irradiation and understand the mechanism of action of photoclimatotherapy while applying the results to clinical protocols of treatment. Methods: A meteorological station was established at the Dead Sea basin to continuously measure global, UVB and UVA irradiation. The same irradiation parameters are also being monitored continuously by a set of identical ultraviolet irradiation instruments installed on the campus of the Ben-Gurion University of the Negev, in Beer Sheva. Results: This study details the results of these long-term measurements, ae well as their correlation with the success obtained by clinicians treating psoriasis patients. Conclusions: A database of more than 25 years has enabled the medical staff to establish tailor-made protocols for sun-exposure time intervals as a function of particular month and hour of day. The availability of such information has significantly improved the results of photoclimatotherapy for psoriasis and at the same time increasing the safety of sun-exposure at the Dead Sea.
ARTICLE | doi:10.20944/preprints202207.0449.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: CKD-aP; ion channels; action potential; hyperpolarization; RT-PCR
Online: 29 July 2022 (04:50:39 CEST)
Expression levels of Cav3.2, BKCa, and anoctamin 1 were previously found to be significantly elevated in patients with chronic kidney disease–associated pruritus (CKD-aP). On the other hand, the expression of TRPV1 was significantly reduced. We further compared CKD patients with and without CKD-aP in terms of the expression levels of several ion channels in the skin, including in peripheral nerve endings。Based on CKD-aP severity, subjects were divided into two groups: non-CKD-aP (no or slight pruritus; n = 16) and CKD-aP (mild, moderate, or severe pruritus; n = 16). Skin samples were obtained from the forearm or elbow during arteriovenous fistula surgery. We used quantitative real-time polymerase chain reaction to measure the skin expression levels of the following ion channels in the skin: Nav1.7, Kv7.2, TREK1, HCN2, TrkA, and Piezo2. RT-PCR analyses showed that CKD-aP patients had significantly higher levels of TREK1 and Piezo2 transcripts and significantly lower levels of HCN2 transcripts than non–CKD-aP patients. No significant differences were noted between groups in the expression of Nav1.7 or TrkA. Moreover, Kv7.2 transcripts were not detected in either group. In skin samples collected from CKD-aP patients, ion channel expression patterns were altered to enhance hyperpolarization of pruriceptive neurons.
ARTICLE | doi:10.20944/preprints202206.0367.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: rosmarinic acid; anti-inflammatory activity; comet assay; sunscreen; skin biocompatibility
Online: 27 June 2022 (13:22:01 CEST)
The skin acts as a protective barrier, guarding the body against microorganisms, chemicals, and several environmental factors. Accordingly, this all-important organ must be kept healthy to maintain its optimal functionality. One approach to maintain skin health is the application of multifunction bioactive sunscreens containing antioxidant molecule(s). Rosmarinic acid (RA), a phenolic compound, is known for its antioxidant activity. Herein, the safety and efficacy of a multifunction prototype sunscreen were investigated, aiming to probe putative synergies of this polyphenol with two known and widely used UV filters (bemotrizinol and octyl p-methoxycinnamate). Samples protected the DNA fragmentation compared to UV control, by the comet assay, and showed good skin compatibility in subjects. Formulations F1 and F3 were able to increase skin hydration, and, possibly, the RA interfered with this attribute. An increase in transepidermal water loss was observed for formulations F1, F2 and F4, which may be related to vehicle containing or not the RA. No decreases were observed in the inflammatory reaction caused by the ethyl nicotinate with any of the evaluated formulations. As a perspective, we suggest trials with a greater number of subjects or protocol modifications. Altering the vehicle qualitative and quantitative composition is also a pertinent perspective.
ARTICLE | doi:10.20944/preprints202205.0356.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: Teledermatology; Teledermoscopy; skin cancer diagnosis
Online: 26 May 2022 (07:53:54 CEST)
Background Due to the COVID-19 pandemic, teledermoscopy has been increasingly used in the remote diagnosis of skin cancers. In a study conducted in 2020, we demonstrated a potential role of an inexpensive device (NurugoTM Derma) as a first triage to select the skin lesions that require a face-to-face consultation with dermatologists. Herein, we report the results of a novel study that aims to better investigate the performance of NurugoTM. Objectives i) verify whether the NurugoTM can be a communication tool between the General Practitioner (GP) and dermatologist in the first assessment of skin lesions; ii) analyze the degree of diagnostic-therapeutic agreement between dermatologists; iii) estimate the number of potentially serious diagnostic errors. Methods One hundred forty-four images of skin lesions were collected at the Dermatology Outpatient Clinic in Novara using a conventional dermatoscope (instrument F), the NurugoTM (instrument N), and the latter with the interposition of a laboratory slide (instrument V). The images were evaluated in-blind by four dermatologists, and each was asked to make a diagnosis and to specify a possible treatment. Results: Our data show that F gave higher agreement values for all dermatologists, concerning the real clinical diagnosis. Nevertheless, a medium/moderate agreement value was obtained also for N and V instruments and that can be considered encouraging and indicate that all examined tools can potentially be used for the first screening of skin lesions. The total amount of misclassified lesions was limited (especially with the V tool), with up to nine malignant lesions wrongly classified as benign. Conclusions NurugoTM, with adequate training, can be used to build a specific support network between GP and dermatologist or between dermatologists. Furthermore, its use could be extended to the diagnosis and follow-up of other skin diseases, especially for frail patients in emergencies such as the current pandemic context.
REVIEW | doi:10.20944/preprints202205.0128.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: systemic lupus erythematosus; anifrolumab; interferon; cutaneous lupus erythematosus
Online: 10 May 2022 (07:45:29 CEST)
Systemic lupus erythematosus (SLE) is a clinically heterogeneous autoimmune disease, and organ manifestations, such as lupus nephritis (LN) or skin disease, may be refractory to standard treatment. Therefore, new agents are required to allow for a more personalized therapeutic approach. Recently, several new therapies have been approved internationally, including voclosporine for LN and anifrolumab for moderately to severely active SLE. Here, we report a case of SLE with a predominant and refractory cutaneous manifestation despite treatment with glucocorticoids, hydroxychloroquine, mycophenolate mofetil, and belimumab. Belimumab was switched to anifrolumab, and the patient responded quickly after two infusions (eight weeks) with a reduction of the Cutaneous Lupus Assessment and Severity Index (CLASI) from 17 to 7. In addition, we review the available clinical trial data for anifrolumab with a focus on cutaneous outcomes. Based on phase II and III clinical trials investigating the intravenous administration, a consistent CLASI improvement was observed at 12 weeks. Interestingly, in a phase II trial of subcutaneous anifrolumab application, CLASI response was not different from placebo at 12 weeks but numerically different at 24 and 52 weeks, respectively. Thus, anifrolumab emerges as an attractive new therapeutic option suggesting a possible domain-based approach.
REVIEW | doi:10.20944/preprints202205.0056.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: tetracyclines; doxycycline; limecycline; minocycline; pleiotrophy; non-antibiotic properties
Online: 6 May 2022 (03:34:44 CEST)
Tetracyclines are a group of antibiotics whose first representative was discovered over 70 years ago. Since then, they have been of great interest in dermatology. In addition to their antibacterial activity, they are able to inhibit metalloproteinases and exhibit anti-inflammatory, anti-apoptotic and antioxidant effects. The side effects have been thoroughly studied over the years. The most characteristic and important in daily dermatolgical practice are: phototoxicity, hyperpigmentation, onycholysis, photoonycholysis, induced lupus erythematosus, idiopathic intracranial hypertension. In this article, we summarize the use of tetracyclines in infectious diseases and inflammatory dermatoses, and further discuss indications where the efficacy and safety of tetracyclines have been highlighted over the past few years.
REVIEW | doi:10.20944/preprints202205.0037.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: Melanoma; Chemo-thermo-immuno-therapy; Melanogenesis; Magnetite nanoparticle; Drug delivery system; Heat shock protein; In situ vaccine therapy; Immune checkpoint inhibitor
Online: 5 May 2022 (12:23:27 CEST)
A major advance of drug discovery and targeted therapy directed to cancer cells may be achieved by exploitation and immunomodulation of their unique biological property. This re-view summarizes our efforts to develop novel chemo-thermo-immuno-therapy (CTI therapy) by conjugating a melanogenesis substrate, N-propionyl cysteaminylphenol (NPrCAP: amine analog of tyrosine), with magnetite nanoparticles (MNP). In our approach, NPrCAP provides a unique drug delivery system (DDS) because of its selective incorporation into melanoma cells. It also functions as a melanoma-targeted therapeutic drug because of its production of highly reactive free radicals (melanoma-targeted chemotherapy). Moreover, utilization of MNP is a platform to develop thermo-immunotherapy because of heat shock protein (HSP) generation upon exposure to an alternating magnetic field (AMF). The feasibility of our approach was successfully shown in experimental in vivo and in vitro mouse melanoma models and in preliminary clinical trials to a limited number of advanced melanoma patients.
ARTICLE | doi:10.20944/preprints202202.0131.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: AD; allergy; skin; DNCB; Panax ginseng; red ginseng marc; fermentation
Online: 9 February 2022 (10:26:55 CET)
Atopic dermatitis (AD) is a chronic and allergic skin disease, however, there is no cure for the disease. Many studies have shown anti-AD potentials of red ginseng, while red ginseng marc (RGM) remained after the ginseng extraction is discarded as industrial waste. However, it is recently reported that RGM, particularly fermented RGM (fRGM), still contains the bioactive properties. Thus, anti-allergic effects of fRGM were examined in 2,4-dinitrochlorobenzene-induced AD-like mice model. The model was topically treated with distilled water (control), dexamethasone, or fRGM for six weeks. The treatments of fRGM alleviated the skin lesions and reduced serum IgE levels, compared with the control. The fRGM also reduced skin levels of lipid peroxidation and superoxide anion, however, increased glutathione contents, with down-regulated gene expressions for inflammatory mediators. The histopathological analyses demonstrated that fRGM suppressed the epidermal thickening, collagen deposition, and inflammatory cell and mast cell infiltration, which involved the anti-inflammatory, anti-oxidant, and anti-apoptotic effects. Further, fRGM suppressed hypertrophic changes and inflammatory responses in the spleen and lymph node. The beneficial effects were observed in the dexamethasone and fRGM groups, however, the antioxidant effects were evident only in the fRGM treatments. These provide useful information for developing fRGM as therapeutic sources for AD.
REVIEW | doi:10.20944/preprints202111.0086.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: acetylcholine; acne vulgaris; botulinum toxins; cholinergic receptors; non-neuronal cholinergic system; oily skin; sebaceous glands; sebum
Online: 3 November 2021 (14:26:33 CET)
Intradermal injection of botulinum neurotoxin is a frequently performed procedure in aesthetic dermatology to improve facial skin tone, texture, fine wrinkles, and enlarged pores. In practice, botulinum neurotoxin type A is also used to reduce skin oiliness of the face. There is increasing evidence that acetylcholine plays specific roles in sebum production, suggesting that botulinum neurotoxin type A may reduce sebum production by interfering with cholinergic transmission between sebaceous glands and autonomic nerve terminals. Botulinum neurotoxins can also inhibit several pathogenetic components of acne development, suggesting that botulinum neurotoxins can be used as a safe and effective treatment modality for acne and other skin disorders related to the overactivity of sebaceous glands. This review aims to explore the current evidence behind the treatment of oily skin and acne with botulinum neurotoxin type A.
REVIEW | doi:10.20944/preprints202111.0043.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: Skin Aging; Rejuvenation; Skin Cream; Retinoid formulation; RetileX-A; Vercilex
Online: 2 November 2021 (10:55:27 CET)
Skin ageing is a progressive but modifiable, multi-factorial disorder that involves all skin tissues. Pertaining to its wide range of physiological and psychosocial complications, skin ageing requires rigorous clinical attention. Topical retinoids and per-oral proteoglycans are promising, non-invasive, therapeutic modalities. To overcome the low bioavailability of conventional free retinoids, Nourella® cream with Retilex-A® (Pharma Medico, Aarhus, Denmark) was developed using a proprietary nano-encapsulation technology. The nano-encapsulation is a sophisticated ‘permeation/penetration enhancer’ that optimises topical drug delivery by increasing surface availability and net absorption ratio. Treatment adherence is also improved by minimising skin irritation. Interventional evidence supports the higher efficacy of Retilex-A® in improving skin thickness and elasticity compared with conventional free forms. It is also reported that the rejuvenating efficacy of Retilex-A® and tretinoin are comparable. Another skin anti-ageing approach is proteoglycan replacement therapy (PRT) with Vercilex®. Vercilex® in Nourella® tablet has the potential to ameliorate proteoglycan dysmetabolism in the aged skin by activating skin cells and improving collagen/elastin turnover. Replicated clinical trials evidenced that PRT can significantly enhance the density, elasticity and thickness of both intrinsically aged and photoaged skin. Evidently, Vercilex® and Retilex-A® share a range of bioactivities, which underlies their synergistic activity observed in a clinical trial. Dual therapy with Nourella® tablets and cream produced higher effect sizes on skin characteristics than monotherapy with each of the two treatments. In conclusion, Nourella® cream and tablets are safe and effective treatments for skin ageing; however, combining the two in a ‘dual skin rejuvenation system’ significantly improves treatment outcomes.
Subject: Medicine And Pharmacology, Dermatology Keywords: topical steroid withdrawal; topical steroids; eczema; atopic dermatitis; skin microbiome; gut mi-crobiome; microbiome; biodiversity; skin allergy epidemic;
Online: 8 September 2021 (20:19:35 CEST)
We set up this preliminary study to evaluate one main question: could strengthening the microbiome have potential benefits for patients suffering with adverse effects after stopping long term topical steroid use? We aim to turn it into a much larger study if the results show promise. After commonly being prescribed for eczema, cessation of topical steroid use, especially after long periods of inappropriate use, can leave lasting adverse effects on the body and skin, known by some as topical steroid withdrawal (TSW). Furthermore, the subsequent withdrawal the body experiences when coming off the drug can leave lasting adverse effects on the body and skin, known by some as topical steroid withdrawal (TSW). This preliminary study involved seven human participants suffering with skin problems associated with TSW who approached Dr. Anja Gijsberts-Veens of their own volition because they were interested in more natural recovery methods. Five completed the study in full. Progress in skin condition was tracked by self-assessed symptom severity questionnaires filled out at the beginning and end of the study. The skin microbiome was addressed by using a 100% natural product shown in previous work to significantly increase skin microbiome biodiversity. Three participants implemented dietary changes and supplementation in response to guidance after fecal sample analysis to improve their gut health and biodiversity. The average improvement in skin symptoms for all participants was 40% and average symptom improvement ranged from 14% for Patient 5 to 92% for Patient 1. On average, the participants saw an improvement in 85% of their symptoms and a stagnation or regression in 11% and 4% respectively. We believe these results show enough promise to warrant expansion of this research to use a larger sample size, preferably 50+ participants, in future work. We also aim to swab the skin of participants to assess the effect on the skin microbiome from skin and gut treatments, as well as including more in-depth analysis of skin and gut microbiomes.
REVIEW | doi:10.20944/preprints202103.0061.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: vitamin D3, D2, calcitriol, oral, topical, serum 25-hydroxyvitamin D, psoriasis, skin diseases, UVB, phototherapy, sunshine, COVID-19, regulatory T lymphocytes
Online: 2 March 2021 (09:44:17 CET)
Vitamin D, sunshine and UVB phototherapy were first reported in the early 1900s to control psoriasis, cure rickets and cure tuberculosis (TB). Vitamin D also controlled asthma and rheumatoid arthritis with intakes ranging from 60,000 to 600,000 International Units (IU)/day. In the 1980s interest in treating psoriasis with vitamin D rekindled. Since 1985 four different oral forms of vitamin D (D2, D3, 1-hydroxyvitaminD3 (1(OH)D3) and 1,25-dihydroxyvitaminD3 (calcitriol)) and several topical formulations have been reported safe and effective treatments for psoriasis—as has UVB phototherapy and sunshine. In this review we show that many pre-treatment serum 25(OH)D concentrations fall within the current range of normal, while many post-treatment concentrations fall outside the upper limit of this normal (100 ng/ml). Yet, psoriasis patients showed significant clinical improvement without complications using these treatments. Current estimates of vitamin D sufficiency appear to underestimate serum 25(OH)D concentrations required for optimal health in psoriasis patients, while concentrations associated with adverse events appear to be much higher than current estimates of safe serum 25(OH)D concentrations. Based on these observations, the therapeutic index for vitamin D needs to be reexamined in the treatment of psoriasis and other diseases strongly linked to vitamin D deficiency, including COVID-19 infections, which may also improve safely with sufficient vitamin D intake or UVB exposure.
ARTICLE | doi:10.20944/preprints202009.0239.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: Cutaneous Melanoma; Immunotherapy; Lymphocytes; Monocytes; Macrophages; RNAseq; tumor immune microenvironment
Online: 11 September 2020 (04:02:03 CEST)
Background: Cutaneous Melanoma (SKCM) is characterized by significant heterogeneity in its molecular, genomic, and immunologic characteristics. Methods: Whole transcriptome RNAseq data from The Cancer Genome Atlas of SKCM (n=328) was utilized. The immune microenvironment was characterized using CIBERSORTX to identify immune cell type composition. Unsupervised hierarchical clustering was performed based on immune cell type content. Samples were separated into those obtained from the primary tumor site and regional skin or soft tissue (locoregional), or distant metastasis and regional lymph node (metastatic). Analysis of overall survival (OS) was performed using Kaplan-Meier estimates and Cox-regression multivariable analyses. Results: Four immune clusters were identified, largely defined by lymphocyte:monocyte (L:M) ratio, monocyte-enrichment, and M0-macrophage-enrichment (L:MLow, MonocyteHigh, M0High; L:MLow, MonocyteMid, M0Low; L:MMid, MonocyteLow, M0Low; L:MHigh, MonocyteLow, M0Low). The L:MLow, MonocyteHigh, M0High cluster demonstrated significantly worse OS than clusters 2-4 in the locoregional group (HR 2.804, 95% CI 1.262–6.234, p=0.0114). Membership in the L:MLow, MonocyteHigh, M0High cluster was an independently poor prognostic factor for survival (HR 3.03, 95% CI 1.12–8.20, p=0.029). The L:MLow, MonocyteHigh, M0High cluster correlated with higher rates of metastasis and decreased predicted response to immune checkpoint blockade compared to the other clusters as determined by the Tumor Immune Dysfunction and Exclusion tool (TIDE). Conclusion: Distinct tumor immune clusters with a M0-macrophage-enriched, L:M ratio low phenotype in the primary melanoma tumor site independently characterize an aggressive phenotype that may differentially respond to treatment.
ARTICLE | doi:10.20944/preprints202009.0227.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: keratin 1; keratin 2; keratin 10; epidermolytic ichthyosis; keratinopathic ichthyoses; congenital reticular ichthyosiform erythroderma; ichthyosis en confetti; revertant mosaicism; epidermolytic nevus, mosaicism
Online: 10 September 2020 (07:52:13 CEST)
Mutations in KRT1 (keratin 1) or KRT10 (keratin 10) underlie a spectrum of diseases known as keratinopathic ichthyoses. Epidermolytic ichthyosis (EI) is caused by heterozygous missense mutations in the genes KRT1 or KRT10, mutations in the gene KRT2 (keratin 2) lead to superficial epidermolytic ichthyosis, and congenital reticular ichthyosiform erythroderma is caused by frameshift mutations in the genes KRT10 or KRT1, which lead to the phenomenon of revertant mosaicism. Epidermolytic ichthyosis is also present in a mosaic pattern known as epidermolytic (acantholytic) nevus, isolated or diffuse. In the latter case, gonadic involvement is possible, leading to a rare pedigree in which a parent with diffuse epidermolytic nevus (linear EI) gives birth to a child affected by EI. We present here an update on the phenotypic presentations of keratinopathic ichthyoses and their molecular mechanisms.
ARTICLE | doi:10.20944/preprints201909.0166.v3
Subject: Medicine And Pharmacology, Dermatology Keywords: Acne Vulgaris; Hair tissue samples; Discrimination; FTIR-ATR
Online: 4 August 2020 (08:21:22 CEST)
Acne vulgaris is a chronic skin disease, which occurs due to inflammation of the hair follicles and sebum producing (sebaceous) glands of the skin called pilosebaceous unit and the anaerobic propionic acne bacterium, P.acne. Human sebum is dominantly made up of 57.5% of triglycerides and fatty acids, 26%wax esters, 12% Squalene and 4.5% Cholesterol. The increased level Androgen hormone, sebum lipid composition, P.acne over growth which induces monocytes and pro inflammatory cytokines attracts neutrophils, basophils, and T cells to the pilosebaceous unit and drive epithelial hyper proliferation i.e., Acne vulgaris. The actual biomolecular changes due to acne vulgaris disease are present in the blood, in the sebum, and in the noninvasive sample of human scalp hair follicles. The main objectives of the present study are to analyze human scalp hair follicles samples using FTIR-ATR spectroscopy to compare and discriminate the spectral signatures of acne vulgaris and healthy scalp hair tissue samples through acne biomarkers Protein, Amide I, Amide II and Squalene (LDL), using the method of internal ratio parameters. This work represents a first step in the development of an analytical tool for future drug development.
ARTICLE | doi:10.20944/preprints202006.0166.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: Tattoo; Tattoo ink; Oxidative stress; Phthalocyanine; Skin
Online: 14 June 2020 (04:13:53 CEST)
Introduction: Tattooing has been extensively discussed in the literature in the context of hygiene and infectious diseases. On the other hand, pathophysiological effects of tattoo inks in the human body are yet to be elucidated. Oxidative stress is considered to be the most important mediator of potential adverse effects of tattooing, however at the moment there is no experimental evidence for tattoo ink-related oxidative stress in the human body. The aim of this study was to examine the effect of a blue tattoo on skin redox regulatory network (RRN) parameters in a single human subject. Materials and Methods: A blue tattoo on my left forearm was used in the research. Tattooed skin surface oxidation-reduction potential (ORP) experiment was done by a PH60F flat probe. Capillary blood from the tattoo and the control area was extracted and analyzed with I2/KI-stabilized microORP, nitrocellulose redox permanganometry (NRP), carbonato-cobaltate (III) formation-derived H2O2 dissociation rate assay, 1,2,3-Trihydroxybenzene autoxidation assay, thiobarbituric reactive substances (TBARS) assay and 5,5,’-dithio-bis-(2-nitrobenzoic acid) (DTNB)-based determination of free thiol content in low molecular weight and protein precipitate fraction. Results: Surface ORP analysis revealed a greater antioxidant capacity of tattooed skin in comparison with the control (CTR). Capillary blood analysis confirmed slightly greater reductive capacity in the tattoo sample both by microORP (-4.33mV vs CTR) and NRP (+1.1%). Hydrogen peroxide dissociation rate (+11.8%), superoxide dismutase activity (+0.7%), and protein sulfhydryl content (+8.5%) were all increased, and lipid peroxidation (-15%) and low molecular weight thiols (-2.8%) were reduced in a tattoo sample in comparison with the CTR. Conclusion: In this N-of-1 study RRN of tattooed skin was shifted towards a more reductive state with most of the parameters indicating reduced levels of oxidative stress in comparison with nontattooed skin. Local antioxidant effect of copper(II) phthalocyanine provides one possible explanation of the observed effects.
ARTICLE | doi:10.20944/preprints202005.0500.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: skin microbiome; skincare; cosmetic products; ecobiology; microbiome friendly
Online: 31 May 2020 (20:12:40 CEST)
Background: Skincare products are used daily to maintain a healthy skin (cleansing, moisturizing, protecting…), but their impact on this first layer, which corresponds to the skin microbiome, is still poorly understood. Preserving natural resources and mechanisms of the skin ecosystem is essential; an original approach based on these premises, called ecobiology, has recently emerged in skincare. Ecobiology considers the skin as an ever-evolving ecosystem which hosts human and microbial cells that interact together with their environment. In this context, we evaluated the impact on the skin microbiome of three types of leave-on face skincare products: a hydrophilic sterile solution, a micellar solution, and an oil-in-water emulsion. Materials and Methods: The individual microbial profiles of 20 Caucasian females were investigated. Samples were obtained twenty-four hours and four days following a daily application of the skincare products versus control area where no product was applied. To analyze the bacterial diversity and abundance of skin microbiome, a 16SrRNA gene sequencing was performed using the Illumina MiSeq platform. Results: Our results confirm the overall diversity of skin microbiome as previously observed and notably reveal the prevalence of Cutibacterium spp. and Staphylococcus spp. on sebaceous site (the back). Bacterial diversity and abundance were not affected by the products either twenty-four hours or four days after application, as indicated by comparison with the control. Moreover, no dissimilarity was observed between the three products versus their control, neither between each product. Conclusions: These preliminary results demonstrated for the first time that three different types of leave-on face skincare products such as a hydrophilic sterile solution, a micellar solution, and an emulsion have no impact on skin microbiome and can be considered as “microbiome friendly”.
BRIEF REPORT | doi:10.20944/preprints202004.0150.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: actinic keratosis; cutaneous squamous cell carcinoma; cytoplams; skin cancer; heat shock protein
Online: 9 April 2020 (12:21:19 CEST)
Background: Cutaneous squamous skin cell carcinoma (SCC) is the second most frequent type of non- melanoma skin cancer and the second cause of death by skin cancer in caucasian population. However, at present it is difficult to predict patients with worst SCC prognosis. Objective: To identify proteins whose expression level could predict SCC infiltration in SCC arising from actinic keratosis (AC). Methods: A total of 20 biopsies of 20 different patients were studied, 10 were from SCC-AK samples and 10 from normal skin. Early infiltrated SCC-AK were selected on histological examination and to determine the expression of proteins fresh skin samples were processed by 2DE-electrophoresis Results: The expression levels of three proteins namely alpha-hemoglobin, heat shock protein (Hsp)-27 and 70 were significantly increased in SCC-AK samples with respect to normal control skin. However, only the expression level of Hsp70 protein positively correlated with the level of SCC-AK dermis infiltration. Immnunohistological examination suggested that the increased expression of Hsp70 proteins seems to mainly occur in the keratinocytes cytoplasm. The increased cytoplasmic Hsp70 expression in SCC-AK was confirmed by Western-blot experiments. Conclusion: Cytoplasmic expression of Hsp70 could be potential biomarker of early infiltration of SCC arising from an AK. Keywords: actinic keratosis, cutaneous squamous cell carcinoma; cytoplasm, skin cancer; heat shock protein.
CASE REPORT | doi:10.20944/preprints201912.0170.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: sphingomonas; gram-negative bacterial infection; skin disease; bacterial
Online: 12 December 2019 (10:01:35 CET)
Sphingomonas paucimobilis is an opportunist pathogen bacillus gram-negative aerobic with a rare occurrence. We present a case in an immunocompetent man successfully treated by surgical debridement, purulent drainage and with an associated course of antibiotics. A large necrotic infection, approximately 5 cm x 3 cm, in a 74-year-old man was identified. Empirical antibiotic therapy with ciprofloxacin 400mg EV 12/12 hours, associated with clindamycin 600mg EV 6/6 hours and pain control was done through dipyrone 1gr, tramadol 400 mg. Deep venous thrombosis was prevented through the prescription of enoxaparin 40mg subcutaneous once a day during hospitalization. The case was well illustrated with pictures throughout treatment. Complete healing was achieved after 90 days. Herein, we present a case of cutaneous contamination. The presented case is the third cutaneous contamination case reported in the literature and the first reported case in the Amazonia region in Brazil.
ARTICLE | doi:10.20944/preprints201911.0171.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: ulmus parvifolia; wound healing; matrix metalloproteinase; transforming growth factor; skin rejuvernation
Online: 15 November 2019 (04:05:45 CET)
Ulmus species have been widely used in Korean folk medicine because of their anti-inflammatory and antimicrobial properties. We intended to investigate the wound healing effect of the powder of Ulmus parvifolia (UP) root bark in a mouse wound healing model. We also determined the mechanisms of effects of Ulmus parvifolia (UP) in skin and skin wound healing effect using keratinocyte model. in vivo experiments showed that the wound lesions in the mice decreased by U. parvifolia with 200 mesh size of root bark powder and significantly reduced by treatment with UP, compared with those treated with U. macrocarpa (UM). Results from in vitro experiments also revealed that UP extract promoted the migration of human skin keratinocytes. UP powder treatment upregulated the expression of the matrix metalloproteinase-2 and -9 protein and significantly increased transforming growth factor (TGF)-β levels. We confirmed that topical administration of the bark powder of exerted a significant effect on skin wound healing by upregulating the expression of MMP and transforming growth factor-β. TGF-β In, Our study suggests that U. parvifolia may be a potential candidate for skin wound healing including epidermal skin rejuvernation.
ARTICLE | doi:10.20944/preprints201909.0091.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: fisetin; psoriasis; normal human epidermal keratinocyte; cell signaling; cell differentiation; proliferation; inflammatory cytokine; PBMC; CD4+ T lymphocyte; 3D psoriasis-like skin disease model
Online: 9 September 2019 (07:48:26 CEST)
Psoriasis is a chronic immune-mediated skin disease that involves interaction of both immune and skin cells, and is characterized by cytokine-driven epidermal hyperplasia, deviant differentiation, inflammation and angiogenesis. Because available treatments for psoriasis have significant limitations, dietary products are potential natural sources of therapeutic molecules, which can rescind molecular defects associated with psoriasis and could be developed for its management. Fisetin (3,7,3′,4′- tetrahydroxyflavone), a phytochemical naturally found in pigmented fruits and vegetables has demonstrated pro-apoptotic and antioxidant effects in several malignancies. This study utilized biochemical, cellular, pharmacological and tissue-engineering tools to characterize the effects of fisetin on normal human epidermal keratinocytes (NHEKs), peripheral blood mononuclear cells (PBMC) and CD4+ T lymphocytes in 2D and 3D psoriasis-like disease models. Fisetin treatment of NHEKs dose and time-dependently induced differentiation and inhibited interleukin-22-induced proliferation, as well as activation of the PI3K/Akt/mTOR pathway. Fisetin treatment of TNF-α-stimulated NHEKs significantly inhibited the activation of p38 and JNK, but had no effect on ERK1/2. In addition, fisetin treatment significantly decreased the secretion of Th1/Th-17 pro-inflammatory cytokines, particularly IFNγ and IL-17A by 12-O- tetradecanolylphorbol 13-acetate (TPA)-stimulated NHEKs and anti-CD3/CD28-activated human PBMCs. Furthermore, we established the in-vivo relevance of fisetin functions, using a 3D full-thickness human skin model of psoriasis (FTRHSP) that closely mimics in-vivo human psoriatic skin-lesions. Herein, fisetin significantly ameliorated psoriasis-like disease features, and decreased the production of IL-17 by CD4+ T lymphocytes co-cultured with FTRHSP. Collectively, our data identify pro-differentiative, anti-proliferative and anti-inflammatory effects of fisetin, via modulation of PI3K-Akt-mTOR and p38/JNK pathways and the production of cytokines in 2D and 3D human skin model of psoriasis. These results suggest that fisetin has a great potential to be developed as an effective and inexpensive agent for the treatment of psoriasis and other related inflammatory skin disorders.
Subject: Medicine And Pharmacology, Dermatology Keywords: skin melanoma, KIT mutation, Sanger sequencing
Online: 6 August 2019 (12:33:31 CEST)
Data on the KIT mutation rate in skin melanoma in the central European region is missing. Accordingly, in a cohort of 79 double wild type (BRAF/NRAS) skin melanoma KIT mutation was assessed by Sanger sequencing of exons 9,11,13,17 and 18. In this skin melanoma cohort KIT mutation frequency was found to be 34/79 (43%) with a significantly higher rate in acrolentiginous melanoma (ALM) as compared to UV-induced common variants (20/34, 58.8% versus 14/45, 31.1%, p=0.014). Exon 11 was the most frequent mutation site (44.7%) followed by exon 9 (21.1%) equally characterizing UV-induced common histotypes and ALM tumors. KIT mutation hotspots were identified in exon 9 (c491/492), in exon 11 (c559,c572, c570), in exon 13 (c642), in exon 17 (c822) and in exon 18 (c853). The relatively high KIT mutation rate in skin melanoma in this central-European cohort justifies regular testing of this molecular target.
ARTICLE | doi:10.20944/preprints201907.0018.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: atopic dermatitis; AD; dermatology; target identification; pathway identification; bioinformatics; protein-protein networks
Online: 1 July 2019 (12:47:49 CEST)
The exploration and identification of targets and pathways for Atopic dermatitis (AD) treatment and diagnosis are critical for AD control. The conventional target exploration approach such as the literature review is not satisfying in terms of efficiency and accuracy. Recently, the bioinformatic approach is drawing attention for its unique advantage of high-volume data analysis for target and pathway exploration; Open Targets Platform is the targets source for this study to extract top 200 high-rank proteins from 3122 AD associated proteins. STRING, Cytoscape, CytoHubba, ClueGo, and CluePedia function had been applied for data analysis. The KEGG Mapper search & colour pathway was the pathway map resource for identified pathways; 23 key hub genes (VDR, KIT, BCL2L11, NFKBIA, KRAS, IL13, JAK2, STAT3, IL21, IL4R, REL, PDGFRB, FOXP3, RARA, RELB, EGFR, IL21R, MYC, CREBBP, NR3C1, IL2, JAK1, and KITLG). Additionally, 8 correlated pathways and the biological process had been identified; Through this study, a viable approach for target and pathway exploration had been presented. The identified AD targets and pathways will be tested for upcoming research for traditional Chinese medicinal herb interactions
REVIEW | doi:10.20944/preprints201904.0327.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: sunscreen; sunburn; UV Radiation; melanoma; photoaging
Online: 30 April 2019 (11:18:23 CEST)
The sunscreen industry is achieving remarkable worldwide prominence by responding to the growing need for skin protection with fast-paced innovation. Increased consumer awareness of the harmful effects of sunlight has fueled the demand for improved photo protection. The need for broad-spectrum protection from both UVA and UVB rays has inspired scientists worldwide to research new cosmetic formulations and delivery systems. More effective sunscreen actives, emollients and novel cosmetic and functional ingredients have been regularly added to the formulator’s repertoire. Creativity in innovation has been hindered only by regulatory agencies and patent restrictions worldwide. Familiarity with the current restrictive regulations and patent law infringements has become integral to any research effort attempting to provide improved protection to individuals affected by the sun’s damaging effects. The increasing incidence of skin cancers and photo damaging effects caused by ultraviolet radiation has increased the use of sun screening agents, which have shown beneficial effects in reducing the symptoms and reoccurrence of these problems. Unlike the situation in Europe where sunscreen ingredients are considered under cosmetics guidelines, the FDA is required to define sunscreens as drugs since they are advertised to prevent sunburn and, more recently, the risk of skin cancer. In the USA, the FDA has been regulating this industry since August 25, 1978, with the publication of the Advance Notice of Proposed Rulemaking. Sunscreens are considered drugs and cosmetics and therefore must be governed by the FDA-OTC monograph. With the variety of sunscreen agents used in cosmetic and UV protection products, Australia, Canada, and the European Union (EU) have also developed regulatory protocols on safe sunscreen product use. Unlike the USA though, Australia has approved 34 active sunscreen ingredients and the EU has approved 28 of these ingredients. Current FDA regulations allow labeling of sunscreen products to a maximum of 30þ, despite the many products currently available with numbers as high as 100. From a cosmetic formulation point of view, increasing the SPF number in a product is governed by simple chemical principles.
COMMUNICATION | doi:10.20944/preprints201812.0257.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: atopic; dermatitis; emollient; moisturizer; epidermal barrier; filaggrin
Online: 21 December 2018 (07:37:32 CET)
Atopic dermatitis (AD) is a chronic cutaneous inflammatory disorder, characterized by skin barrier disruption. Dermacare is a new cosmetic formulation which enhances moisturization, reinforces and repairs the skin barrier and prevents cutaneous microbiota imbalance. To demonstrate its safety and efficacy a prospective, open-label and multicenter study was carried out on patients diagnosed with mild to moderate AD. Transepidermal water loss (TEWL), clinical severity, Desquamation Index, Patient/Investigator Global Assessments, quality of life index and tolerance were assessed. Adverse events were recorded. Daily application of the new treatment was well tolerated, and adverse events were absent. After 14 days, TEWL showed a 36.7% significant decrease (p = 0.035). At the end of the 28-day Dermacare treatment, the Desquamation Index showed a reduction in 70% of patients; Eczema Area and Severity Index were reduced by 70.4% (p = 0.002); and skin irritation showed a significant reduction (p = 0.024). Likewise, Patient and Investigator Global Assessments reported a significant improvement in conditions and an overall global worsening when patients restarted their normal treatment. Parent’s Index of Quality of Life Index significantly increased by 36.4% (p < 0.05) with Dermacare. In conclusion, Dermacare’s regular use helped reduce the risk of relapse and extend the steroid-free treatment periods.
REVIEW | doi:10.20944/preprints201812.0140.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: acne; polymorphism; genetics; CYP17; ethnicity
Online: 12 December 2018 (05:30:43 CET)
Acne vulgaris is one of the most common skin diseases and genetic relationships have been documented. The aim was to evaluate the association of CYP17 (T-34C) polymorphism related to the risk of acne in a meta-analysis study. The databases (Scopus, Web of Science, PubMed, and Cochrane Library) were searched until September 2018 to check the relationship between acne risk and CYP17 (T-34C) polymorphism and impact of this polymorphism on severity of acne. We used Review Manager 5.3 software to analyze the data using OR and 95% CI to check this relationship. Four studies were included and analyzed in the meta-analysis. The OR in analysis of C versus T in acne patients compared to the healthy controls was 1.42 (P=0.02), in CC vs. TT was 1.54 (P=0.04), in TC vs. TT was 1.46 (P=0.12), in TC + CC vs. TT was 1.55 (P=0.04), and in CC vs. TT + TC was 1.39 (P=0.06). There was no acne risk related to CYP17 (T-34C) in none of genetic models in Caucasian ethnicity, whereas in Asian ethnicity, there was higher acne risk related to CYP17 (T-34C) without heterogeneity. The results of the present meta-analysis showed the presence of C allele and CC genotype of CYP17 polymorphism can be risk factors for acne, mainly in the Asian ethnicity.
REVIEW | doi:10.20944/preprints201810.0772.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: Marine algae; Carbohydrates; Oligosaccharides; Monosaccharides; Skin health; Cosmeceuticals
Online: 1 November 2018 (18:19:37 CET)
Marine algae have been considered as abundant source of bioactive compounds with cosmeceutical potential. Recently, a great deal of interest has focused on the health-promoting effects of marine bioactive compounds. Carbohydrate is a major and abundant constitute of marine algae that have been utilized in cosmetic formulations, such as moisturizing and thickening agents. In addition, marine carbohydrates have been suggested as promising bioactive biomaterials for various skin beneficial properties, such as anti-oxidant, anti-melanogenic and anti-skin aging. Therefore, marine algae carbohydrates have potential of skin health benefits for value-added cosmeceutical application. The present review focused on the various biological capacities and potential skin health benefits of bioactive marine carbohydrates.
ARTICLE | doi:10.20944/preprints201810.0667.v1
Online: 29 October 2018 (09:54:28 CET)
Visfatin, a member of the adipokine family, plays an important role in many metabolic and stress responses. The mechanisms underlying the direct therapeutic effects of visfatin on wound healing have not been reported yet. In this study, we examined the effects of visfatin on wound healing in vitro and in vivo. Visfatin enhanced the proliferation and migration of human dermal fibroblasts (HDFs) and keratinocytes, and significantly increased the expression of wound healing-related vascular endothelial growth factor (VEGF) in vitro and in vivo. Treatment of HDFs with visfatin induced activation of both extracellular signal-regulated kinases 1 and 2 (ERK1/2) and c-Jun N-terminal kinases 1 and 2 (JNK1/2) in a time-dependent manner. Inhibition of ERK1/2 and JNK1/2 led to a significant decrease in visfatin-induced proliferation and migration of HDFs. Importantly, blocking VEGF with its neutralizing antibodies suppressed the visfatin-induced proliferation and migration of HDFs and human keratinocytes, indicating that visfatin induces the proliferation and migration of HDFs and human keratinocytes via increased VEGF expression. Moreover, visfatin effectively improved wound repair in vivo, which was comparable to the wound healing activity of epidermal growth factor (EGF). Taken together, we demonstrate that visfatin promotes the proliferation and migration of HDFs and human keratinocytes by inducing VEGF expression and can be used as a potential novel therapeutic agent for wound healing.
ARTICLE | doi:10.20944/preprints201809.0490.v1
Online: 25 September 2018 (15:43:11 CEST)
Background: Melatonin is a potent mitochondrial, cytoprotective and antioxidant molecule with potentially strong anti-aging properties. Topical melatonin has shown to improve the clinical signs of skin aging. Melatosphere™ is a new lipid-based delivery system able to improve stability and skin penetration of melatonin when used in topical formulations. No clinical studies, using objective instrumental data, are available so far regarding the positive effect of Melatosphere™ in improving wrinkles in women with mild-to-moderate skin aging. Study Aim: We evaluate, in an open prospective, evaluator-blinded trial, the effects on skin texture of 2 months treatment with a Melatosphere™ based cream. Subjects and Methods: 15 women aged >45 years with mild to moderate facial skin aging (Glogau score ≥2) participated in the trial, after their informed consent. An ANTERA 3D computer-assisted skin analysis evaluation for the assessment of coarse and fine wrinkles of the periorbital area and melanin content was performed at baseline and after two months of treatment. An evaluator-blinded Investigator Global assessment of skin elastosis, roughness, level of dyscromia, skin dryness and presence of actinic damage was also performed at the same time points using a 4-grade score from 0 (no sign) to 3 (severe sign). Results: At baseline the mean (SD) IGA score was 8.2(1.0). After 2 months the IGA score significantly decrease to 4.2(1.4) (49% reduction) (P=0.0007). ANTERA 3D evaluations showed a significant reduction in skin coarse and fine wrinkles volume in the target area of -31% and -18%, respectively. Melanin content was reduced significantly by -17%. Conclusion: Topical melatonin carried in Melatosphere improves in the short-term signs of skin aging evaluated clinically and by ANTERA 3D device in women with mild to moderate skin aging.
REVIEW | doi:10.20944/preprints201809.0215.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: gut microbiota; skin microbiota; inflammation; psoriasis; psoriatic arthritis; dysbiosis
Online: 12 September 2018 (07:49:33 CEST)
Psoriasis is a chronic inflammatory disease characterized by skin lesions. Psoriasis development has been associated both with genetic and environmental factors. Though skin and gut microbiota has been implicated in number of pathologies including atopic dermatitis, inflammatory bowel disease, Crohn’s disease, allergy, obesity, its role has been poorly studied in psoriatic disease, which incorporates both psoriasis and psoriatic arthritis. This literature review summarizes the most recent and major findings on microbiota features in psoriatic disease as well as gives immune system role in the given condition. Despite conflicting findings, psoriasis patients were frequently found to have distinct microbial composition in both skin and guts especially in the major bacterial phyla, Firmicutes, Bacteroidetes, and Akkermansia. Furthermore, bacterial DNA has been found in psoriatic patients both locally and systemically, and altogether suggesting role of bacteria in the chronic disease and future studies in this field.
REVIEW | doi:10.20944/preprints201807.0615.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: onchodermatitis; onchocercal skin disease; onchocerciasis; ivermectin
Online: 31 July 2018 (09:47:34 CEST)
Onchocerciasis causes debilitating pruritus and rashes as well as visual impairment and blindness . Prior to control measures, eye disease was particularly prominent in savanna areas of sub-Saharan Africa whilst skin disease was more common across rainforest regions of tropical Africa. Mass drug distribution with ivermectin is changing the global scene of onchocerciasis. There has been successful progressive elimination in Central and Southern American countries and the World Health Organization has set a target for elimination in Africa of 2025. This literature review was conducted to examine progress regarding onchocercal skin disease. PubMed searches were performed using keywords "onchocerciasis", "onchodermatitis" and "onchocercal skin disease" over the past eight years. Articles in English, or with an English abstract, were assessed for relevance, including any pertinent references within the articles. Recent progress in awareness of, understanding and treatment of onchocercal skin disease is reviewed with particular emphasis on publications within the past 5 years. The global burden of onchodermatitis is progressively reducing and is no longer seen in children in many formerly endemic foci.
REVIEW | doi:10.20944/preprints201807.0425.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: hyperpigmentation; palpebral region; geographic skin differences; ethnic predisposition; skin disorder;
Online: 23 July 2018 (12:56:47 CEST)
POH (Peri Orbital Hyperpigmentation) represents a minor clinical entity that attracts immense aesthetic damages and it generates social integration difficulties. This review focuses on the etiopathogenic causes of this entity, differentiating and reclassifying this defect as having, on the one hand, genetic causes of melanic hyperproduction – for Fitzpatrick cutaneous phototypes IV and V – and, on the other hand, both genetic and acquired vascular causes, in individuals with light-coloured skin phototypes. Hence, there is a big difference in the field of pathogenic treatment, for the two entities. In addition, this study notes the direct relationship between skin aging and POH, especially for aquired vascular causes. In this reasoning, other aesthetic deficiencies of the skin in the palpebral area should be also considered, like: blepharochalasis, wrinkles, the anatomical causes of the lower eyelid shading, symmetrical or asymmetric suborbital oedema. All of these issues will complicate the therapeutic decision and subsidiary, the pharmaceutical advice. In this context, the review shows the guidelines for a honest councelling of the patients, pointing the efficiency limit for the topical pharmaceutical medication (depigmentants, exfoliants) versus the necessity of minimally invasive or/ and surgical treatments (in blefarochalasis).
ARTICLE | doi:10.20944/preprints201806.0020.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: Annona muricata; apoptosis; basal cell carcinoma; cutaneous squamous cell carcinoma; graviola; Hedgehog signaling pathway; natural products chemistry; non-melanoma skin cancer
Online: 1 June 2018 (13:00:02 CEST)
Non-melanoma skin cancers (NMSCs) are the leading cause of skin cancer-related morbidity and mortality. Effective strategies are needed to control NMSC occurrence and progression. Non-toxic, plant-derived extracts have been shown to exert multiple anti-cancer effects. Graviola (Annona muricata), a tropical fruit-bearing plant, has been used in traditional medicine against multiple human diseases including cancer. The current study investigated the effects of graviola leaf and stem extract (GLSE) and its solvent-extracted fractions on two human NMSC cell lines, UW-BCC1 and A431. GLSE was found to: i) dose-dependently suppress UW-BCC1 and A431 cell growth, motility, wound closure, and clonogenicity; ii) induce G0/G1 cell cycle arrest by downregulating cyclin/cdk factors while upregulating cdk inhibitors, and (iv) induce apoptosis as evidenced by cleavage of caspases-3, -8 and PARP. Further, GLSE suppressed levels of activated hedgehog (Hh) pathway components Smo, Gli 1/2, and Shh while inducing SuFu. GLSE also decreased the expression of pro-apoptotic protein Bax while decreasing the expression of the anti-apoptotic protein Bcl-2. We determined that these activities were concentrated in an acetogenin/alkaloid-rich dichloromethane subfraction of GLSE. Our data identify graviola extracts and their constituents as promising sources for new chemopreventive and therapeutic agent(s) to be further developed for the control of NMSCs
ARTICLE | doi:10.20944/preprints201805.0260.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: melatonin; UVB; HaCaT keratinocytes; collagen; ROS; Hedgehog; Cox-2; MMP-1
Online: 18 May 2018 (08:51:37 CEST)
Though melatonin is known to improve ultraviolet B (UVB)-induced oxidative damage and inflammatory conditions via blockade of nuclear factor (NF)-κB, interleukin (IL)-6, there is no report on anti-wrinkle effect of melatonin to date. Hence in the present study, anti-wrinkle mechanism of melatonin was elucidated in UVB treated HaCaT keratinocytes and hairless mice. Herein melatonin protected against a radical initiator tert-Butyl hydroperoxide (t-BOOH) induced reactive oxygen species (ROS) production, matrix metalloprotease 1 (MMP-1) and cytotoxicity in HaCaT keratinocytes. Also, melatonin suppressed the expression of sonic hedgehog (SHH) and GLI for hedgehog signaling, p-NF-kB, cyclooxygenase (COX-2), p-ERK for inflammatory responses in UVB treated HaCaT keratinocytes. Furthermore, melatonin protected skin from wrinkle formation, transdermal water loss in hairless mice irradiated by UVB for 8 weeks. Notably, melatonin prevented against epidermal thickness and dermal collagen degradation in UVB irradiated hairless mice by Hematoxylin & Eosin and Masson’s trichrome staining. Taken together, these findings suggest that melatonin reduces wrinkle formation via inhibition of ROS/SHH and inflammatory proteins such as NF-kB/COX-2/ERK/MMP1.
REVIEW | doi:10.20944/preprints201805.0158.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: celiac disease; dermatitis herpetiformis; alopecia areata; cutaneous vasculitis; urticaria; atopic dermatitis; psoriasis; recurrent aphtous ulceration; chronic ulcerative stomatitis; gluten-free diet
Online: 10 May 2018 (08:04:40 CEST)
Celiac disease (CD) is an immune-mediated gluten-induced enteropathy that affects predisposed individuals of all ages. Many patients with CD do not report gastrointestinal symptoms making it difficult to reach an early diagnosis. On the other hand, CD is related to a wide spectrum of extra-intestinal manifestations, being dermatitis herpetiformis (DH) the best characterized. These associated conditions may be the clue for reaching the diagnosis of CD. Over the last years, there have been multiple reports of the association between CD and several cutaneous manifestations that may improve with a gluten-free diet (GFD). The presence of some of these skin diseases, even in absence of gastrointestinal symptoms, should give rise to an appropriate screening for CD. The aim of this paper is to describe the different cutaneous manifestations that have been associated to CD and the possible mechanisms involved.
REVIEW | doi:10.20944/preprints201801.0001.v2
Subject: Medicine And Pharmacology, Dermatology Keywords: Aboriginal; Australia; control; diagnosis; identification; prevention; scabies; sarcoptes scabiei; Torres Strait Islander; treatment
Online: 8 January 2018 (16:00:59 CET)
Background: Scabies is an unfortunately neglected tropical skin disease. Scabies occurs in Australia, however it is drastically more common amongst select socioeconomically disadvantaged groups. Amongst these, Aboriginal and Torres Strait Islander communities are affected particularly severely, likely secondary to rampant overcrowding. Methods: This literature review has comprehensively explored the relevant evidence available since the year 2000. Objectives: The objective of this article is to provide updates on the identification, management, and control of scabies in Aboriginal and Torres Strait Islander communities. The article also aims to reveal issues with these factors that may be contributing to the inflated prevalence of scabies amongst these groups. Conclusions: Diagnosis currently depends upon clinical examination, dermatoscopy, and skin scraping microscopy; all of which are prone to error. In Australia, topical permethrin remains first-line treatment, however resistance is developing. Other management aspects to consider are environmental measures and treating secondary infections. Scabies prevention is far more cost-effective than managing advanced individual cases, typically ensured through mass drug administration of permethrin or ivermectin. Sustained prevention can prove troublesome for some communities. In order to address the status of scabies as a neglected tropical disease, these issues must be managed first.
ARTICLE | doi:10.20944/preprints201710.0136.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: keloids; fibroproliferative disorder; HtrA1; inflammation
Online: 20 October 2017 (06:22:35 CEST)
1) Background: Keloids occur after the failure during the wound-healing process, persist the inflammation and are refractory to various treatments. The pathogenesis of keloids is still unclear. We previously analyzed the gene expression profiles in keloid tissue using microarray and Northern blot analysis and found that HtrA1 was markedly upregulated in the keloid lesions. HtrA1 is a member of the HtrA family of serine protease, has been suggested to play a role in the pathogenesis of various diseases including age-related macular degeneration and osteoarthritis by modulating proteins in extracellular matrix or cell surface. We focused on HtrA1, analyzed the localization and the role in keloid pathogenesis. 2) Methods: Twenty seven keloid patients and seven unrelated patients were enrolled in this study. We performed in situ hybridization analysis, immunohistochemical analysis, western blot analysis and cell proliferation assay. 3) Results: First, the fibroblast-like cells expressed HtrA1 higher in the active keloid lesions than in the surrounding lesions in situ hybridization. Second, the proportion of HtrA1-positive cells in keloid was higher than that of in normal skin significantly in immunohistochemical analysis. Third, HtrA1 protein was up-regulated, relative to normal skin tissue samples in western blot analysis. Finally, silencing of HtrA1 gene expression suppressed the cell proliferation significantly. 4) Conclusion: HtrA1 was highly expressed in keloid tissues and the suppression of HtrA1 gene inhibited the proliferation of keloid-derived fibroblasts. HtrA1 may promote keloid development through accelerating cell proliferation and remodeling keloid-specific extracellular matrix or cell surface molecules. HtrA1 is suggested to have an important role in keloid pathogenesis.
ARTICLE | doi:10.20944/preprints201703.0227.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: biodiversity; skin allergy; benchmark skin health values; effect of synthetic cosmetics on skin; 21st century skin ailments; measure skin health; healthy skin ecosystem; healthy skin bacteria; damaged skin bacteria; perfect skin
Online: 31 March 2017 (08:52:14 CEST)
There is a skin allergy epidemic in the western world, and the rate of deterioration has increased significantly in the past 5-10 years. It is probable that there are many environmental contributing factors, yet some studies have linked it primarily to the rise in the use of synthetic chemical ingredients in modern cosmetics. Our challenge, therefore, was to find a mechanism to determine the effect these substances have on skin health, and whether they really are a primary cause of long term damage to the skin. The first problem is the lack of any definitive way to measure skin health. Motivated by the overwhelming evidence for a link between deficient gut flora and ill health, we decided to look at whether our skin microbiota could similarly be used as an indicator of skin health. Our research illustrates how it is microbiota diversity alone that can predict whether skin is healthy or not, after we revealed a complete lack of conclusive findings linking the presence or abundance of particular species of microbe to skin problems. This phenomenon is replicated throughout nature, where high biodiversity always leads to healthy ecosystems. ‘Caveman’ skin, untouched by modern civilisation, was far different to ‘western’ skin and displayed unprecedented levels of bacterial diversity. The less exposed communities were to western practices, the higher the skin diversity, which is clear evidence of an environmental factor in the developed world damaging skin. For the first time we propose benchmark values of diversity against which we can measure skin to determine how healthy it is. This gives us the ability to be able to predict which people are more likely to be prone to skin ailments, and start to test whether cosmetic ingredients and products are a main cause of the skin allergy epidemic.
ARTICLE | doi:10.20944/preprints201612.0121.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: antibacterial activity, cinnamon, honey, checkerboards method, synergistic activity
Online: 23 December 2016 (18:37:59 CET)
Propionibacterium acnes and Staphylococcus epidermidis are the major skin bacteria that cause the formation of acne. The present study was conducted to investigate antibacterial activity of ethanolic extract of cinnamon bark, honey and their combination against acne bacteria. The antibacterial activity of extract of cinnamon bark and honey were investigated against P. acnes and S. epidermidis using disc diffusion method. Minimum Inhibitory Concentration (MIC) and minimal bactericidal concentration (MBC) were performed using Clinical and Laboratory Standard Institute (CLSI) methods. The interaction combination between extract of cinnamon bark and honey was determined by using a checkerboards method. The results showed that he MIC of extract of cinnamon bark and honey against P. acne were 256 µg/mL and 50% v/v, respectively, while against S. epidermidis were 1024 µg/mL and 50% v/v, respectively. The MBC of extract of cinnamon against P. acnes and S. epidermidis were more than 2048 µg/mL, whereas the MBC for honey against P. acnes and S. epidermidis were 100%. The combination of cinnamon bark extract and honey against against P. acnes and S. epidermidis, showed additive activity with the FICI value 0.625. Therefore, the combination of extract of cinnamon bark and honey has potential activity against acne causing bacteria.
COMMUNICATION | doi:10.20944/preprints201608.0228.v1
Online: 30 August 2016 (04:27:17 CEST)
Anderson-Fabry disease is a rare X-linked lysosomal storage disorder caused by deficient or absent activity of the enzyme alfa-galactosidase A. This defect enzyme leads to accumulation of glycolipids, primarily globotriaosylceramide (Gb3), in the vascular endothelium of several organs, including the skin, kidneys, nervous system, and heart. The characteristic early clinical features of Fabry disease include acroparaesthesia, angiokeratoma, heat intolerance, hypohidrosis, cornea verticillata and gastrointestinal symptoms. Later complications occur with the disease progression and include progressive renal failure, hypertrofic cardiomyopathy, cerebrovascular disease and reduced life expectancy. Anderson Fabry disease is therefore a disabling and systemic disease which requires a timely diagnosis. The purpose of our study is to define sweat glands morphological abnormalities in children and adolescents with Fabry disease with minimal symptoms and in patients affected by variants of Fabry disease in which biopsy is essential, to establish a baseline morphological diagnosis of the disease before to undergo to kidney or endomyocardial biopsy or when the classical approach is not possible because of some complications, with minimal discomfort for patients.