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Naunyn-Schmiedeberg's Archives of... Mar 2024Clostridium botulinum C3 exoenzyme (C3bot) exclusively inhibits RhoA, B and C by ADP-ribosylation and is therefore used as a cell-permeable tool for investigating the...
Clostridium botulinum C3 exoenzyme (C3bot) exclusively inhibits RhoA, B and C by ADP-ribosylation and is therefore used as a cell-permeable tool for investigating the cellular role of these Rho-GTPases. Rho-GTPases represent a molecular switch integrating different receptor signalling to downstream cascades including transcriptional cascades that regulate various cellular processes, such as regulation of actin cytoskeleton and cell proliferation. C3bot-induced inhibition of RhoA leads to reorganization of the actin cytoskeleton, morphological changes, and inhibition of cell proliferation as well as modulation of inflammatory response. In this study, we characterized the C3bot-mediated effects on a full-thickness skin model exhibiting a psoriasis-like phenotype through the addition of cytokines. Indeed, after the addition of cytokines, a decrease in epidermal thickness, parakeratosis, and induction of IL-6 was detected. In the next step, it was studied whether C3bot caused a reduction in the cytokine-induced psoriasis-like phenotypes. Basal addition of C3bot after cytokine induction of the full-thickness skin models caused less epidermal thinning and reduced IL-6 abundance. Simultaneous basal incubation with cytokines and C3bot, IL-6 abundance was inhibited, but epidermal thickness was only moderately affected. When C3bot was added apically to the skin model, IL-6 abundance was reduced, but no further effects on the psoriasis-like phenotype of the epidermis were observed. In summary, C3bot inhibits the cytokine-induced expression of IL-6 and thus may have an impact on the pro-inflammatory immune response in the psoriasis-like phenotype.
Topics: Humans; Clostridium botulinum; Botulinum Toxins; Interleukin-6; ADP Ribose Transferases; Phenotype; rho GTP-Binding Proteins; Psoriasis
PubMed: 37707681
DOI: 10.1007/s00210-023-02718-9 -
Clinics and Research in Hepatology and... Oct 2023The endoscopic workup of dysphagia can lead to the diagnosis of atypical esophagitis, with thickened esophageal mucosa, strictures, mucosal exudates, furrows, and...
BACKGROUND AND AIMS
The endoscopic workup of dysphagia can lead to the diagnosis of atypical esophagitis, with thickened esophageal mucosa, strictures, mucosal exudates, furrows, and sloughing. While these aspects suggest eosinophilic esophagitis, pathology might not report the presence of eosinophils, but rather chronic inflammation, with spongiosis, parakeratosis, and lymphocytic infiltrate. We aimed to report the management of this disease and assess the prevalence of associated dermatological conditions.
METHODS
We retrospectively evaluated the medical records of our patients with non-eosinophilic stricturing esophagitis for clinical, endoscopy, and pathology data. Patients were evaluated by a dermatologist. A blood immunoassay and skin biopsy were performed if needed.
RESULTS
Thirty-eight patients (twenty-six women) were included in the study. The median age at onset of symptoms was 56.5 years, with a median duration of symptoms of two years. Thirty-five patients presented with dysphagia at diagnosis and eighteen with weight loss. At endoscopy, a single esophageal stenosis was diagnosed in 19 patients, localized in the upper third in 22 patients. Thirty patients received endoscopic treatment (dilatation in 29/38 and local triamcinolone injection in 11/38 patients). In 21 patients, oral, skin or vulvo-anal lesions were found on dermatological examination. Nineteen patients received systemic treatment, including corticosteroids, immunosuppressive drugs and plasmapheresis. Five patients developed esophageal squamous cell carcinoma.
CONCLUSION
The management of non-eosinophilic chronic stricturing esophagitis is challenging, because of a low contribution of esophageal biopsies and the refractory nature of the strictures. In our experience, a dermatological evaluation helped in 55% of cases to introduce a systemic treatment, leading to limit the use of endoscopic dilatation. Endoscopic follow-up is needed, considering the significant risk of esophageal squamous cell carcinoma.
PubMed: 37657720
DOI: 10.1016/j.clinre.2023.102202 -
The New Zealand Medical Journal Jul 2023Intertriginous or flexural eruptions are common presenting problems in clinical practice, raising several differential diagnoses. A clinico-histopathological correlation...
Intertriginous or flexural eruptions are common presenting problems in clinical practice, raising several differential diagnoses. A clinico-histopathological correlation is important to establish a correct diagnosis when a clinical diagnosis cannot be ascertained. We here present a case of flaky erythematous eruptions in a female adult, with a final diagnosis of granular parakeratosis, involving nonflexural area mid-back (under bra cover) in addition to flexural zones of the groin, gluteal fold, inframammary fold and axilla. It seems that mechanism of pressure and friction as well as occlusion all play a part. Management with potent topical steroid and avoidance of inciting triggers offered resolution in 4 weeks in this case.
Topics: Adult; Humans; Female; New Zealand; Parakeratosis; Diagnosis, Differential; Axilla
PubMed: 37501251
DOI: No ID Found -
Clinical, Cosmetic and Investigational... 2023Granular parakeratosis (GP) is a unique keratotic disorder that often affects the intertriginous areas. GP usually presents as erythematous or brownish hyperkeratotic...
Granular parakeratosis (GP) is a unique keratotic disorder that often affects the intertriginous areas. GP usually presents as erythematous or brownish hyperkeratotic papules or plaques and can be further classified into five types. GP of the eccrine ostium is a rare subtype; its pathological defects are mainly localized to the stratum corneum of the eccrine ostia. Due to its rarity, there is usually a delay in diagnosing GP, and these patients are often misdiagnosed with other dermatological conditions. In this report, we present the case of a 64-year-old Thai female who presented with recurrent pruritic erythematous rashes on her neck since approximately 40 years. She was previously diagnosed with eczema or folliculitis. Histopathological examination confirmed a final diagnosis of GP of the eccrine ostium. She was advised to avoid excessive heat and keep her intertriginous areas dry. Her condition improved significantly during the follow-up visit.
PubMed: 37469551
DOI: 10.2147/CCID.S421152 -
PeerJ 2023Psoriasis is an autoimmune skin disease characterized by immunocyte activation, excessive proliferation, and abnormal differentiation of keratinocytes. Signal...
BACKGROUND
Psoriasis is an autoimmune skin disease characterized by immunocyte activation, excessive proliferation, and abnormal differentiation of keratinocytes. Signal transducers and activators of transcription 3 (STAT3) play a crucial role in linking activated keratinocytes and immunocytes during psoriasis development. T helper (Th) 17 cells and secreted interleukin (IL)-17A contribute to its pathogenesis. IL-17A treated STAT3 overexpressing mouse model might serve as an animal model for psoriasis.
METHODS
In this study, we established a mouse model of psoriasiform dermatitis by intradermal IL-17A injection in STAT3 overexpressing mice. Transcriptome analyses were performed on the skin of wild type (WT), STAT3, and IL-17A treated STAT3 mice. Bioinformatics-based functional enrichment analysis was conducted to predict biological pathways. Meanwhile, the morphological and pathological features of skin lesions were observed, and the DEGs were verified by qPCR.
RESULTS
IL-17A treated STAT3 mice skin lesions displayed the pathological features of hyperkeratosis and parakeratosis. The DEGs between IL-17A treated STAT3 mice and WT mice were highly consistent with those observed in psoriasis patients, including S100A8, S100A9, Sprr2, and LCE. Gene ontology (GO) analysis of the core DEGs revealed a robust immune response, chemotaxis, and cornified envelope, et al. The major KEGG enrichment pathways included IL-17 and Toll-like receptor signaling pathways.
CONCLUSION
IL-17A exacerbates psoriasis dermatitis in a STAT3 overexpressing mouse.
Topics: Mice; Animals; Interleukin-17; Imiquimod; Psoriasis; Skin; Disease Models, Animal; Dermatitis
PubMed: 37465147
DOI: 10.7717/peerj.15727 -
Head and Neck Pathology Sep 2023Verruciform xanthoma (VX) is an uncommon, benign epithelial lesion of the oral mucosa. While this entity can also present extraorally, including on the skin and in...
BACKGROUND
Verruciform xanthoma (VX) is an uncommon, benign epithelial lesion of the oral mucosa. While this entity can also present extraorally, including on the skin and in anogenital areas, the variation in its histologic features in extraoral sites is not yet well defined. Differences in the demographics and morphologic features of oral versus extraoral VX were assessed to help facilitate the accurate diagnosis and management of this lesion.
METHODS
After obtaining IRB approval, 110 cases of diagnosed VX were retrospectively collected from our institutional archives spanning from 2000 to 2022. Patient age, gender, available medical history, lesion appearance, and duration were obtained for each case.
RESULTS
The median age was 55 years (range 13-86) with a male-to-female ratio of 1.2:1. The most common oral sites, in descending order, were the palate (n = 24, 22%), buccal mucosa (n = 18, 16%), gingiva (n = 16, 15%), and tongue (n = 13, 12%). Extraoral sites comprised 9% of all lesions, including the scrotum (9), vulva (2), cheek (1), wrist (1), gluteal region (1), and abdominal wall (1). The median size for all lesions was 6.0 mm, and extraoral lesions were associated with a 6.7 mm larger size compared to oral lesions (B ± SE: 6.7 ± 2.5 cm, p = 0.01). The lesions were most frequently pink or white in color and often described as papillary, pedunculated, verrucous, and/or exophytic. Microscopically, the presence of wedge-shaped parakeratosis, keratin projections above the epithelium/epidermis, and associated inflammation significantly differed between oral and extraoral lesions. Prominent wedge-shaped parakeratosis (p = 0.04) and keratin projections above the epithelium/epidermis (p < 0.001) were more prevalent in extraoral lesions. There was no significant link between keratin projections and epithelial atypia (p = 0.44).
CONCLUSIONS
Familiarity with the broad morphological spectrum of VX, including the presence and degree of wedge-shaped parakeratosis, keratin projections above the epithelium/epidermis, and associated underlying inflammation, will be helpful in diagnosing it in unusual locations.
Topics: Humans; Male; Female; Adolescent; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Retrospective Studies; Parakeratosis; Mouth Diseases; Xanthomatosis; Keratins; Genitalia
PubMed: 37420145
DOI: 10.1007/s12105-023-01568-4 -
Computers in Biology and Medicine Sep 2023Generative adversarial networks (GANs) and their variants as an effective method for generating visually appealing images have shown great potential in different medical...
Generative adversarial networks (GANs) and their variants as an effective method for generating visually appealing images have shown great potential in different medical imaging applications during past decades. However, some issues remain insufficiently investigated: many models still suffer from model collapse, vanishing gradients, and convergence failure. Considering the fact that medical images differ from typical RGB images in terms of complexity and dimensionality, we propose an adaptive generative adversarial network, namely MedGAN, to mitigate these issues. Specifically, we first use Wasserstein loss as a convergence metric to measure the convergence degree of the generator and the discriminator. Then, we adaptively train MedGAN based on this metric. Finally, we generate medical images based on MedGAN and use them to build few-shot medical data learning models for disease classification and lesion localization. On demodicosis, blister, molluscum, and parakeratosis datasets, our experimental results verify the advantages of MedGAN in model convergence, training speed, and visual quality of generated samples. We believe this approach can be generalized to other medical applications and contribute to radiologists' efforts for disease diagnosis. The source code can be downloaded at https://github.com/geyao-c/MedGAN.
Topics: Humans; Education, Medical; Learning; Radiologists; Software; Image Processing, Computer-Assisted
PubMed: 37364533
DOI: 10.1016/j.compbiomed.2023.107119 -
Journal of Ethnopharmacology Dec 2023Liangxue Jiedu formula (LXJDF) is an effective traditional Chinese medicine (TCM) formula for treating psoriasis of blood-heat syndrome and has been used in clinics for...
Liangxue Jiedu formula improves imiquimod-induced psoriasiform dermatitis with circadian desynchrony by regulating Th17 cell differentiation based on network pharmacological analysis.
ETHNOPHARMACOLOGICAL RELEVANCE
Liangxue Jiedu formula (LXJDF) is an effective traditional Chinese medicine (TCM) formula for treating psoriasis of blood-heat syndrome and has been used in clinics for decades.
AIM OF THE STUDY
This study aimed to discover the mechanism of LXJDF in psoriasis and the circadian clock by network pharmacology and experimental studies.
MATERIALS AND METHODS
The compounds of LXJDF were obtained from the TCMSP and BATMAN-TCM databases. The genes related to psoriasis and circadian rhythm/clock were identified by the OMIM and GeneCards databases. Then, target genes were integrated by Venn and analyzed by the String, CytoNCA, DAVID (GO and KEGG) databases, and the network was constructed using Cytoscape. Mice were raised under light disturbance for fourteen days. On the eighth day, mouse dorsal skin was shaved and smeared with 62.5 mg 5% imiquimod at 8:00 (ZT0) for six successive days. Mice were randomly divided into the model, LXJDF-H (49.2 g/kg·bw), LXJDF-L (24.6 g/kg·bw), and positive drug (dexamethasone) groups. Other mice were smeared with Vaseline under the normal light cycle as the control. The drug of each group was administered at 10:00 (ZT2) and 22:00 (ZT14). The skin lesions were observed, and PASI was scored daily. HE and immunofluorescence were used to measure pathological morphology. Th17 cytokines in serum and skin were measured by flow cytometry and qPCR. Circadian clock gene and protein expression levels were determined by qPCR and Western blotting.
RESULTS
We found 34 potential targets of LXJDF in the treatment of psoriasis and circadian rhythm and confirmed their importance by topology analysis. KEGG pathway analysis revealed that the two major pathways were Th17 cell differentiation and the HIF-1 signaling pathway. At ZT2 and ZT14, LXJDF improved IMQ-induced light disturbance mouse skin lesions, including alleviating scales, erythema, and infiltration, reducing PASI, and inhibiting keratinocyte hyperproliferation and parakeratosis. LXJDF reduced IL-17A, IL-17F, TNF-α, and IL-6 in serum at ZT2 and increased IL-10 at ZT2 and ZT14. LXJDF downregulated the expression of IL-17A and IL-17F in skin. At ZT2, LXJDF significantly upregulated CLOCK and REV-ERBα expression and downregulated HIF-1α expression. At ZT14, LXJDF decreased HIF-1α and RORγt expression and significantly increased REV-ERBα expression.
CONCLUSION
LXJDF improves psoriasis dermatitis with circadian rhythm disorders by regulating Th17 cell differentiation.
Topics: Animals; Mice; Interleukin-17; Imiquimod; Skin; Psoriasis; Cell Differentiation; Dermatitis; Disease Models, Animal; Th17 Cells; Mice, Inbred BALB C
PubMed: 37331449
DOI: 10.1016/j.jep.2023.116807