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Pharmaceutics Jun 2022Recently, various types of in vitro-reconstructed 3D skin models have been developed for drug testing and disease modeling. Herein, we structurally and functionally...
Recently, various types of in vitro-reconstructed 3D skin models have been developed for drug testing and disease modeling. Herein, we structurally and functionally validated a self-assembled reconstructed skin equivalent (RSE) and developed an IL-17a-induced in vitro psoriasis-like model using a self-assembled RSE. The tissue engineering approach was used to construct the self-assembled RSE. The dermal layer was generated using fibroblasts secreting their own ECM, and the epidermal layer was reconstructed by seeding keratinocytes on the dermal layer. To generate the psoriatic model, IL-17A was added to the culture medium during the air-liquid interface culture period. Self-assembled RSE resulted in a fully differentiated epidermal layer, a well-established basement membrane, and dermal collagen deposition. In addition, self-assembled RSE was tested for 20 reference chemicals according to the Performance Standard of OECD TG439 and showed overall sensitivity, specificity, and accuracy of 100%, 90%, and 95%, respectively. The IL-17a-treated psoriatic RSE model exhibited psoriatic epidermal characteristics, such as epidermal hyperproliferation, parakeratosis, and increased expression of KRT6, KRT17, hBD2, and S100A9. Thus, our results suggest that a self-assembled RSE that structurally and functionally mimics the human skin has a great potential for testing various drugs or cosmetic ingredients and modeling inflammatory skin diseases.
PubMed: 35745784
DOI: 10.3390/pharmaceutics14061211 -
Postepy Dermatologii I Alergologii Oct 2021Reflectance confocal microscopy (RCM) is abbreviated as skin three-dimensional computed tomography, which can help clearly observe the structure of the epidermis and... (Review)
Review
Reflectance confocal microscopy (RCM) is abbreviated as skin three-dimensional computed tomography, which can help clearly observe the structure of the epidermis and superficial dermis. It is a non-invasive skin disease examination method and provides fast access to real-time, dynamic skin micro-anatomical images. Therefore, RCM is widely used in the clinical diagnosis of skin diseases. For example, the RCM features of vitiligo are as follows: pigment loss or partial pigment loss in the lesion area, loss of the basal layer pigment ring. The RCM findings of Riehl melanosis are as follows: basal cell liquefaction and degeneration. The RCM results for verruca plana show: the Rose-like structure. The characteristics of psoriasis under RCM include: hyperkeratosis, parakeratosis, thickening of the spinous layer, capillary dilatation and hyperaemia, peripheral inflammatory cell infiltration. Epidermal brain-like structure was observed under RCM of seborrheic keratosis. With RCM, image acquisition and preservation of the skin is convenient, and the technique is convenient for comparing the development of lesions during long-term follow-up observation. Therefore, it helps to understand disease development in real time and dynamically and can be used to evaluate the curative effect. In this article, we briefly review the technical principles, diagnostic criteria for RCM application and RCM-related research progress in the diagnosis of pigmentary diseases, inflammatory diseases, skin tumours, and other common skin diseases.
PubMed: 34849113
DOI: 10.5114/ada.2021.110077 -
Veterinary Sciences Aug 2022The plasticity of the genome is an evolutionary factor in all animal species, including canines, but it can also be the origin of diseases caused by hereditary genetic... (Review)
Review
The plasticity of the genome is an evolutionary factor in all animal species, including canines, but it can also be the origin of diseases caused by hereditary genetic mutation. Genetic changes, or mutations, that give rise to a pathology in most cases result from recessive alleles that are normally found with minority allelic frequency. The use of genetic improvement increases the consanguinity within canine breeds and, on many occasions, also increases the frequency of these recessive alleles, increasing the prevalence of these pathologies. This prevalence has been known for a long time, but mutations differ according to the canine breed. These genetic diseases, including skin diseases, or genodermatosis, which is narrowly defined as monogenic hereditary dermatosis. In this review, we focus on genodermatosis , i.e., monogenic, and hereditary dermatosis, in addition to the clinical features, diagnosis, pathogeny, and treatment. Specifically, this review analyzes epidermolytic and non-epidermolytic ichthyosis, junctional epidermolysis bullosa, nasal parakeratosis, mucinosis, dermoid sinus, among others, in canine breeds, such as Golden Retriever, German Pointer, Australian Shepherd, American Bulldog, Great Dane, Jack Russell Terrier, Labrador Retriever, Shar-Pei, and Rhodesian Ridgeback.
PubMed: 36006348
DOI: 10.3390/vetsci9080433 -
The International Journal of... 2022The epidermis is a stratified epithelium that forms the barrier between the organism and its environment. It is mainly composed of keratinocytes at various stages of...
The epidermis is a stratified epithelium that forms the barrier between the organism and its environment. It is mainly composed of keratinocytes at various stages of differentiation. The stratum corneum is the outermost layer of the epidermis and is formed of multiple layers of anucleated keratinocytes called corneocytes. We aim to highlight the roles of epidermal differentiation and proteolysis in skin diseases. Skin biopsies isolated from mice, the established model of Netherton syndrome (NS), and from patients with NS, seborrheic dermatitis (SD) and psoriasis, as well as healthy controls, were analyzed by histology and immunohistochemistry. Our results showed that NS, SD, and psoriasis are all characterized by abnormal epidermal differentiation, manifested by hyperplasia, hyperkeratosis, and parakeratosis. At the molecular level, abnormal differentiation is accompanied by increased expression of involucrin and decreased expression of loricrin in NS and psoriasis. Increased epidermal proteolysis associated with increased kallikrein-related peptidases (KLKs) expression is also observed in both NS and psoriatic epidermis. Furthermore, reduced expression of desmosomal proteins is observed in NS, but increased in psoriasis. Since desmosomal proteins are proteolytic substrates and control keratinocyte differentiation, their altered expression directly links epidermal proteolysis to differentiation. In conclusion, abnormal cellular differentiation and proteolysis are interconnected and underlie the pathology of NS, SD and psoriasis.
Topics: Animals; Cell Differentiation; Epidermis; Humans; Keratinocytes; Mice; Peptide Hydrolases; Proteolysis; Psoriasis
PubMed: 34881788
DOI: 10.1387/ijdb.210161gs -
Journal of Inflammation Research 2022As a multifunctional cytokine, lipocalin 2 is weakly expressed in skin and serum under normal conditions. However, it is over-expressed by neutrophils and keratinocytes... (Review)
Review
As a multifunctional cytokine, lipocalin 2 is weakly expressed in skin and serum under normal conditions. However, it is over-expressed by neutrophils and keratinocytes in the skin lesions and sera in several skin diseases. Recent studies demonstrated that lipocalin 2 participates in the pathogenesis of psoriasis by exerting versatile effects on skin resident cells and infiltrating immune cells. Lipocalin 2 inhibits the synthesis of keratin, involucrin, and loricrin in keratinocytes, leading to epidermal parakeratosis via the Tcf7l1-lipocalin 2 signaling axis. It also recruits inflammatory cells such as T cells and neutrophils into skin lesions via the IL-23/IL17, p38-MAPK, and ERK-1/2 signaling pathways. Additionally, lipocalin 2 and other cytokines such as IL-17 have the synergetic effects on skin cells. The neutralization of lipocalin 2 or relevant cytokines can alleviate psoriasis, verifying that lipocalin 2 is an effective interfering target for psoriasis. In this review, we summarize the roles of lipocalin 2 in the processes of psoriatic inflammation and the promising therapeutic strategies based on lipocalin 2-related molecules.
PubMed: 35386225
DOI: 10.2147/JIR.S358492 -
Indian Journal of Pathology &... Mar 2024Darier disease (DD) is a rare genodermatosis. Literature on this topic is overwhelmingly dominated by case reports with rare clinical presentations, which have mentioned...
Darier disease (DD) is a rare genodermatosis. Literature on this topic is overwhelmingly dominated by case reports with rare clinical presentations, which have mentioned the histopathologic features briefly. The aim of this study was to document the histopathology of DD. Skin biopsies diagnosed as Darier disease based on clinicopathologic correlation over 12 years were reviewed for various epidermal and dermal features. There were 16 patients included, who most commonly presented in the third decade, with slight female predilection. The most common clinical presentation was hyperpigmented, hyperkeratotic, papules and plaques (91%), with 69% affecting the trunk. In addition to the classic suprabasal acantholytic clefts, we noted some unusual features: absence of parakeratosis (19%), a cornoid lamella-like pattern (62%), follicular acantholysis (13%) and multiple foci of involvement within a single biopsy (63%). Features such as the presence of dyskeratotic cells and minimal dermal lymphocytic infiltrates were concordant with previous literature. The limitation of this study was the small sample size. To conclude, pathologists must be aware of the variations in histopathology of Darier's disease, especially when challenged with atypical clinical presentations. The Darier-like pattern is met within several acantholytic diseases, and clinicopathologic correlation has the last word in arriving at a diagnosis.
PubMed: 38563701
DOI: 10.4103/ijpm.ijpm_610_23 -
Journal of Clinical Medicine Jan 2023Psoriasis is a common chronic, inflammatory skin disease characterised by keratinocyte hyperproliferation, parakeratosis, and T-cell infiltration. Adipose tissue has an...
Psoriasis is a common chronic, inflammatory skin disease characterised by keratinocyte hyperproliferation, parakeratosis, and T-cell infiltration. Adipose tissue has an endocrine function, producing an abundance of cytokines and adipokines. It has also been described that the major adipokines, leptin, resistin, and adiponectin, may be involved in the pathogenesis of psoriasis. The aim of the study was to examine the plasma levels of adiponectin, leptin, and resistin in patients with psoriasis and their correlations with disease activity parameters: Psoriasis Activity Severity Index (PASI), Dermatology Life Quality Index (DLQI), and Body Surface Area (BSA) index, as well as selected clinical parameters. The study included 53 patients with the plaque type and 31 healthy controls. The plasma concentrations of adiponectin were significantly lower in patients with psoriasis (p < 0.001) than in the control group. The plasma concentrations of leptin were higher in patients with psoriasis, however, due to high intra-patient variability of leptin plasma concentrations these differences did not reach statistical significance (p = 0.2). The plasma concentrations of resistin were significantly increased in patients with psoriasis compared to healthy controls (p = 0.02). There were no statistically significant correlations between adiponectin and leptin plasma concentrations and values of PASI, DLQI, and BSA. The resistin plasma concentrations correlated significantly with DLQI values. Additionally, we examined the correlations between adiponectin, leptin, and resistin plasma concentrations, and selected clinical parameters. Plasma concentrations of adiponectin correlated significantly with CRP values and ALT values. Leptin plasma concentrations correlated significantly with creatinine values. The results of our study confirm the role of adiponectin, leptin, and resistin in the pathogenesis of psoriasis.
PubMed: 36675592
DOI: 10.3390/jcm12020663 -
Dermatology Online Journal Feb 2021Epidermolytic ichthyosis (EI, OMIM 113800) is a rare autosomal dominant keratinization disorder that is caused by keratin 1 or 10 gene mutation. It can be classified...
Epidermolytic ichthyosis (EI, OMIM 113800) is a rare autosomal dominant keratinization disorder that is caused by keratin 1 or 10 gene mutation. It can be classified clinically based on the presence of palmoplantar hyperkeratosis involvement and extent of skin involvement. The diagnosis is made by clinical and histopathological examinations that can be confirmed by genetic testing. We present a 2-year-old girl who presented with erythematous and thick scaling skin. Her condition began at birth as multiple flaccid blisters that would easily break into erosions. There was no history of similar condition nor consanguinity within her family. Skin examination revealed diffuse erythematous skin covered with thick scales and erosion, predominantly on her face, extremities, palms, and soles. The skin histopathology examination showed diffuse parakeratosis with vacuolar and granular degeneration within granular and spinous layers along the epidermis. She was diagnosed with generalized EI with palmoplantar hyperkeratosis based on the clinical and histopathological examinations. Clinical improvement was observed after a one-month treatment with mupirocin cream, sodium bicarbonate bath, and moisturizer after bathing.
Topics: Child, Preschool; Female; Humans; Hyperkeratosis, Epidermolytic; Keratoderma, Palmoplantar
PubMed: 33818988
DOI: No ID Found -
Journal of Cosmetic Dermatology Aug 2021Baboon syndrome is a rare, type IV hypersensitivity reaction causing a maculopapular rash. Tamoxifen is an antineoplastic agent, working as an estrogen receptor...
BACKGROUND
Baboon syndrome is a rare, type IV hypersensitivity reaction causing a maculopapular rash. Tamoxifen is an antineoplastic agent, working as an estrogen receptor antagonist, also called a selective estrogen receptor modulator. A variety of rashes were reported with Tamoxifen use to-date except baboon syndrome. The Tamoxifen-induced baboon syndrome seems to be reversible, as discontinuation of the drug improves clinical outcomes.
AIM
Herein, we present the first case of Tamoxifen-induced baboon syndrome which occurred 8 years after initiation of Tamoxifen use.
PATIENTS
A 44-year-old woman presented with papulovesicular eruption on her body and erythema on her face for a duration of 6 months. There was no evidence of ocular or mucosal involvement. She was diagnosed with breast cancer and treated with tamoxifen 10 mg twice daily over the past 8 years. She was not taking other medications or over-the-counter supplements at the time of presentation. The patient underwent urgent skin biopsies of two lesions on her buttock and thigh. No organisms were seen on Gram stain. The patient's skin biopsy revealed extensive hyperorthokeratosis, minimal parakeratosis, hypergranulosis, and lichenoid interface dermatitis in the irregularly acanthotic epidermis supporting diagnosis of fixed drug eruption. Following a multidisciplinary discussion, the patient was diagnosed with baboon syndrome or symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) associated with Tamoxifen.
RESULTS
Hence, Tamoxifen was immediately discontinued and treated with oral steroid along with topical agents. She showed improvement of clinical abnormalities within days after discontinuation of Tamoxifen.
CONCLUSIONS
Given the widespread use of Tamoxifen in the management of patients with breast cancer, it is important that healthcare professionals monitor for rare, however clinically significant, and potentially life-threatening dermatological manifestations of Tamoxifen use, such as baboon syndrome.
Topics: Adult; Animals; Drug Eruptions; Exanthema; Female; Humans; Papio; Syndrome; Tamoxifen
PubMed: 33253493
DOI: 10.1111/jocd.13863 -
Cureus Aug 2023Esophagitis dissecans superficialis (EDS) is a rare esophageal lesion characterized by sloughing of the esophageal mucosa. Typically asymptomatic and histopathologically...
Esophagitis dissecans superficialis (EDS) is a rare esophageal lesion characterized by sloughing of the esophageal mucosa. Typically asymptomatic and histopathologically nonspecific, diagnosis relies on endoscopic appearance. We report a case of an 81-year-old female who presented with an 8-pound weight loss in two weeks. Upper endoscopy showed severe mucosal changes with sloughing in the lower esophagus, consistent with EDS. Histopathology confirmed the diagnosis. No offending agents were identified, and high-dose proton pump inhibitors (PPIs) were initiated, resulting in symptom improvement. EDS remains poorly understood; it is associated with medication use, esophageal motility disorders, and autoimmune conditions. EDS should be considered in unexplained weight loss cases, with treatment focused on the discontinuation of culprits and PPI therapy.
PubMed: 37779763
DOI: 10.7759/cureus.44372