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Large congenital melanocytic nevi (lCMN) management is based exclusively on iterative surgical procedures in the absence of validated medical therapy. The aim of our study was to develop an intra-lesional medical treatment for lCMN. Seventeen patients harboring NRAS-mutated lCMN were included. Nevocytes obtained from lCMN displayed an overactivation of MAPK and AKT pathways. MEK and AKT inhibitors reduced nevosphere diameter in sphere-forming assays, as well as cell viability and proliferation in in vitro assays.
Inherited skin disorders have been recently reported to have sporadic normal-looking areas, where a portion of the keratinocytes have recovered from causative gene mutations (revertant mosaicism, or “RM”). We observed a case of recessive dystrophic epidermolysis bullosa (RDEB) treated with cultured epidermal autografts (CEAs), whose CEA-grafted site remained epithelized for 16 years. We proved that the CEA product and the grafted area included cells with RM. Based on these findings, we conducted an investigator-initiated clinical trial of CEAs from clinically revertant skin for RDEB.
Adjuvant use of immunohistochemical (IHC) stains enhance the Mohs surgeon’s ability to identify high-risk keratinocytic skin cancer cells on frozen section slides. However, no guidelines for its use during MMS treatment of BCC currently exist. High recurrence risk features, as defined by the National Comprehensive Cancer Network (NCCN), may provide guidance for the use of IHC for BCC. This study evaluated whether the use of AE1/AE3 cytokeratin IHC staining during the treatment of 7,104 BCCs between 2010-2018 correlated with NCCN high-risk features.
Microbiota and allergens drive specialized tissue-specific resident memory T (Trm) cells to colonize cutaneous barriers. Chronic exposure in adult atopic dermatitis leads to complex cutaneous Th2 cell hypersensitivity responses with variable contributions of additional cellular subsets. A pathogenic role for CD8 cells has become evident, with skin-homing CD8 IL-13-secreting T cells (Tc2) found to correlate with severity. There is pressing need to study Th2 and Tc2 T cell adaptation as it occurs at the level of the cutaneous microenvironment.
Natural amino acids are incorporated into topical cosmetic formulas as building blocks for collagen and elastin synthesis, for moisture retention, enhancing the skin barrier, reduction in sebaceous gland activity, and others. However, the use of non-proteogenic amino acids has received little attention in cosmetics and limited, to for the most part, to imparting hydrolytic stability to functional peptides in formulas. Non-proteogenic amino acids, are not incorporated into proteins during new protein synthesis, and therefore, their potential for topical application should be evaluated in order to functionally and quantitatively determine their benefits in terms of improvement in skin firming and wrinkle appearance.
Psoriasis is a common inflammatory skin disease that has limited topical treatment options. Several mouse models have been created to mimic psoriasis-like skin. In particular, the imiquimod (IMQ)-induced psoriasis-like skin model has been a useful tool to test therapeutic applicability of various topical agents. Despite its widespread use in research, the IMQ mouse model itself has not been well characterized and researchers would benefit from a better understanding of the induction, expected duration, and re-induction of topically-applied IMQ on mouse skin.
Psoriasis is a complex chronic immune-mediated inflammatory cutaneous disease that affects 2–3% of the global population. Various 3D skin models have been developed to mimic psoriatic pathogenesis and help develop drugs, but these models are very low throughput and expensive. Here, we established a cost-effective, high throughput system for disease modeling and drug development, using spheroid approach. We plated 1x105 cells primary fibroblasts in 96-well plates for 2-5 days before addition of 5x104 primary keratinocytes.
In recent years, automated image analysis has been gaining traction for dermatological clinical applications. In order to provide clinicians with a real-time disease quantification, knowing what is the minimal image resolution necessary for an accurate clinical assessment would improve computational efficiency, as well as help standardize image capture and alleviate future storage needs. Focusing on cases of alopecia, we address this question in order to capture the presence of the main characteristics needed to quantify alopecia in clinic: 1) abnormal hair density; 2) scarring (i.e.
The high frequency and extremely aggressive behavior of squamous cell carcinoma from recessive dystrophic epidermolysis bullosa patients (RDEB-cSCC), as well as the lack of an appropriate preclinical mouse model recapitulating the RDEB-cSCC phenotype for testing effective therapies/drugs, creates an urgent need for generating such a model. Here, we established a novel mouse model for RDEB-cSCC, in which we generated 3D cSCC skin constructs (SCs) using RDEB-cSCC and RDEB fibroblasts (FB), which were then grafted onto immunocompromised mice.
Guttate psoriasis is an eruptive form of psoriasis that occurs in young adults, is self-limiting, and frequently follows streptococcal pharyngitis. Approximately 1/3 of guttate patients develop chronic plaque psoriasis. To date, no studies have systematically characterized the molecular and histologic profiles of guttate psoriasis compared to plaque psoriasis. We prospectively collected lesional and non-lesional skin biopsies from guttate (n= 16) and plaque (n= 16) psoriasis patients for direct comparison of the microarray gene expression profile.
Sezary Syndrome (SS) and lymphocyte variant hypereosinophilic syndrome (L-HES) are mature T cell lymphoproliferations with similar manifestations of skin inflammation, pruritus, and eosinophilia. SS is a cutaneous lymphoma, while L-HES is a lymphoproliferation that can become malignant. Both show Th2 biased, and suggest developmental commonalities. Thus comparing their gene expression may shed light on genes important for Th2 manifestions and malignant transformation. Transcriptome profiles from Affymetrix U133 Plus 2 microarrays were compared: SS vs.
Induced pluripotent stem cells (iPSCs) for autologous skin regeneration can treat genetic skin diseases such as recessive dystrophic epidermolysis bullosa (RDEB) which is characterized by type VII collagen (C7) deficiency. iPSCs have unlimited proliferative potential and have the potency to differentiate into different cell lineages. However, lacking is a reproducible and scalable platform to produce clinical grade iPSC-derived tissue stem cells. Here, we employ one-step reprogramming and gene-correction on primary fibroblasts to generate iPSCs followed by a novel defined differentiation method to produce functional keratinocyte (iKC) progenitors.
With the hypothesis that new biomarker discovery will lead to better classification of individuals with psoriasis and aid in targeting of their primary disease and associated comorbidities, we are undertaking an endotype analysis of broadly-enrolled psoriasis and psoriatic arthritis (PsA) patients using a systems biology approach. Here we report our first findings using whole blood collected from psoriasis patients (n=33 including 7 with PsA; mean PASI=6.8 (range 0-29.6)) and 5 healthy controls.