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Biomedicine & Pharmacotherapy =... Dec 2023Psoriasis is a chronic inflammatory skin disease characterized by thickening the epidermis with erythema, scaling, and proliferation. Noscapine (NOS) has several...
Preparation and characterization of solid lipid nanoparticles encapsulated noscapine and evaluation of its protective effects against imiquimod-induced psoriasis-like skin lesions.
Psoriasis is a chronic inflammatory skin disease characterized by thickening the epidermis with erythema, scaling, and proliferation. Noscapine (NOS) has several anti-inflammatory, anti-angiogenic, and anti-fibrotic effects, but its low solubility and large size results in its lower efficacy in the clinic. In this regard, solid lipid nanoparticles (SLN) encapsulated NOS (SLN-NOS) were fabricated using the well-known response surface method based on the central composite design and modified high-shear homogenization and ultrasound method. As a result, Precirol® was selected as the best lipid base for the SLN formulation based on Hildebrand-Hansen solubility parameters, in which SLN-NOS 1 % had the best zeta potential (-35.74 ± 2.59 mV), average particle size (245.66 ± 17 nm), polydispersity index (PDI, 0.226 ± 0.09), high entrapment efficiency (89.77 %), and ICH-based stability results. After 72 h, the SLN-NOS 1 % released 83.23 % and 58.49 % of the NOS at pH 5.8 and 7.4, respectively. Moreover, Franz diffusion cell's results indicated that the skin levels of NOS for SLN and cream formulations were 46.88 % and 13.5 % of the total amount, respectively. Our pharmacological assessments revealed that treatment with SLN-NOS 1 % significantly attenuated clinical parameters, namely ear thickness, length, and psoriasis area and severity index, compared to the IMQ group. Interestingly, SLN-NOS 1 % reduced the levels of interleukin (IL)-17, tumor necrosis factor-α, and transforming growth factor-β, while elevating IL-10, compared to the IMQ group. Histology studies also showed that topical application of SLN-NOS 1 % significantly decreased parakeratosis, hyperkeratosis, acanthosis, and inflammation compared to the IMQ group. Taken together, SLN-NOS 1 % showed a high potential to attenuate skin inflammation.
Topics: Humans; Imiquimod; Noscapine; Lipids; Skin; Psoriasis; Nanoparticles; Inflammation
PubMed: 37924792
DOI: 10.1016/j.biopha.2023.115823 -
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 -
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 -
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