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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 -
Iranian Journal of Microbiology Jun 2023HPV infections cause a wide spectrum of pathological changes in lower anogenital epithelium. The aim of this study was to investigate the HPV DNA status and histological...
BACKGROUND AND OBJECTIVES
HPV infections cause a wide spectrum of pathological changes in lower anogenital epithelium. The aim of this study was to investigate the HPV DNA status and histological findings in cervical biopsy specimens diagnosed as flat condyloma.
MATERIALS AND METHODS
This study included 20 cervical biopsy specimens diagnosed as flat condyloma. The histopathological criteria and presence of HPV DNA were evaluated. HPV genotyping was determined in HPV-positive specimens using BioEdit software and the results were analyzed in SPSS software.
RESULTS
HPV DNA was not found in 30% of specimens and relative frequency of HPV genotypes was: 15% HPV6, 15% HPV11, 5% HPV16, 5% HPV18, 5% HPV53, 5% HPV68, 5% HPV84, 10% HPV45. Relative frequency of histopathological criteria was as below: 100% of specimens had koilocytosis, 100% acanthosis, 15% nuclear immaturity, 100% atypia, 15% mitotic activity, 50% dyskeratosis, 35% parakeratosis and 10% hyperkeratosis.
CONCLUSION
There were significant differences between HPV positivity and two pathologic criteria; multinucleation and hyperkeratosis (P Value: 0.02). Nuclear immaturity was significantly more prevalent in high risk HPV-positive specimens (P Value: 0.03).
PubMed: 37448682
DOI: 10.18502/ijm.v15i3.12909 -
International Journal of Molecular... Jun 2023Psoriasis is the most common chronic inflammatory skin disease with a genetic basis. It is characterised by keratinocyte hyperproliferation, parakeratosis and... (Review)
Review
Psoriasis is the most common chronic inflammatory skin disease with a genetic basis. It is characterised by keratinocyte hyperproliferation, parakeratosis and inflammatory cell infiltration. Psoriasis negatively affects a patient's physical and emotional quality of life. Sirtuins (SIRTs; silent information regulators) are an evolutionarily conserved group of enzymes involved in the post-translational modification of proteins, including deacetylation, polyADP-ribosylation, demalonylation and lipoamidation. SIRTs are involved in a number of cellular pathways related to ageing, inflammation, oxidative stress, epigenetics, tumorigenesis, the cell cycle, DNA repair and cell proliferation, positioning them as an essential component in the pathogenesis of many diseases, including psoriasis. Activation of SIRT1 counteracts oxidative-stress-induced damage by inhibiting the mitogen-activated protein kinases (MAPK), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and signal transducer and activator of transcription 3 (STAT3) pathways and may mitigate pathological events in psoriasis. There is a significant reduction in the expression of SIRT1, SIRT2, SIRT3, SIRT4 and SIRT5 and an increase in the expression of SIRT6 and SIRT7 in psoriasis. The aim of the review is to draw the attention of physicians and scientists to the importance of SIRTs in dermatology and to provide a basis and impetus for future discussions, research and pharmacological discoveries to modulate SIRT activity. In light of the analysis of the mode of action of SIRTs in psoriasis, SIRT1-SIRT5 agonists and SIRT6 and SIRT7 inhibitors may represent new therapeutic options for the treatment of psoriasis.
Topics: Humans; Sirtuin 1; Sirtuins; Quality of Life; Aging; Psoriasis; Skin Diseases
PubMed: 37445960
DOI: 10.3390/ijms241310782 -
Clinical, Cosmetic and Investigational... 2023Pretibial pruritic papular dermatitis (PPPD) is a distinctive skin disorder in response to persistent pretibial manipulation. Clinically, it manifests as multiple...
Pretibial pruritic papular dermatitis (PPPD) is a distinctive skin disorder in response to persistent pretibial manipulation. Clinically, it manifests as multiple discrete, pruritic, flesh-colored-to-erythematous papules and plaques confined to the pretibial area. The histological hallmark of PPPD comprises irregular epidermal psoriasiform hyperplasia with parakeratosis and spongiosis, dermal fibrosis, and lymphohistiocytic infiltration. Due to its rarity and underrecognition, the prevalence and standard treatment of the disease have yet to be well elucidated. Here, we present a case of PPPD in a 60-year-old female presenting with numerous pruritic, erythematous-to-brownish papules and plaques on bilateral pretibial areas for 1.5 years. The lesions were significantly improved after 1 month of additional treatment with oral pentoxifylline. In this report, we aim to raise awareness in recognizing PPPD since it manifests unique clinical, dermoscopic, and histological features, representing pretibial skin's response to chronic rubbing. In addition, we proposed a novel effective therapy for the disease using pentoxifylline.
PubMed: 37366429
DOI: 10.2147/CCID.S420726 -
Clinical, Cosmetic and Investigational... 2023Various laser- and light-based devices have been introduced as complementary or alternative treatment modalities for dermatophytosis, particularly for finger or toenail...
BACKGROUND
Various laser- and light-based devices have been introduced as complementary or alternative treatment modalities for dermatophytosis, particularly for finger or toenail onychomycosis.
OBJECTIVE
This study aimed to comparatively evaluate the antifungal effects of 405-nm and 635-nm dual-band diode lasers using an in vivo guinea pig model of dermatophytosis.
MATERIALS AND METHODS
A guinea pig model was developed by the repetitive application of fungal spore preparations to the back skin of guinea pigs. Dual-diode laser treatment was delivered to the guinea pig skin at a power of 24 mW at a wavelength of 405 nm and 18 mW at 635 nm for 12 min. The treatments were administered three times weekly for 2 weeks, and a mycological study was performed.
RESULTS
Mycological studies using scraped samples obtained from treatment groups A (N = 8) and B (N = 8) after dual-diode laser treatment revealed that seven of eight (87.5%) samples in each group had negative results for direct potassium hydroxide microscopy and fungal culture studies. Skin specimens from each infected laser-untreated guinea pig exhibited spongiotic psoriasiform epidermis with parakeratosis. Meanwhile, skin specimens from infected laser-treated guinea pigs in groups A and B demonstrated thinner epidermal thickness than those from infected untreated controls but thicker than those from uninfected treated controls without noticeable inflammatory cell infiltration in the dermis.
CONCLUSION
The guinea pig dermatophytosis model can be used to comparatively evaluate the efficacy and safety of various treatment modalities, including dual-diode lasers, for superficial fungal skin infection.
PubMed: 37351065
DOI: 10.2147/CCID.S415679