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Background: Anti-IL-4 receptor α antibody (dupilumab) has demonstrated favorable sinonasal outcomes for chronic rhinosinusitis with nasal polyps (CRSwNP), which is mainly caused by type 2 inflammation. Although increased blood eosinophil levels and injection site symptoms are frequently observed as acute adverse events (AEs) of dupilumab, limited knowledge is available regarding the late AEs of dupilumab for CRSwNP. Objectives: We investigated the late AEs following the initiation of dupilumab treatment for CRSwNP. Material and methods: Fifty-one patients with CRSwNP treated with dupilumab for > 3 months were enrolled, and their clinical data were collected from their medical records. Results: Six (11.8%) patients experienced late AEs. One case of eczema with pruritus, one case of psoriasis-like dermatitis, two cases of severe rash, one case of malignant lymphoma, and one case of alopecia areata were observed. Skin disorders were the most common late AEs in this study. It is a Th1-inflammatory disease, and its mechanism is thought to be due to the immune imbalance caused by dupilumab. We could not confirm whether malignant lymphoma in our case was caused by dupilumab use. Conclusions and significance: Skin disorders are often late AEs associated with dupilumab; therefore, careful monitoring after dupilumab initiation should be considered. [ABSTRACT FROM AUTHOR]

In dry skin (DS), skin-barrier function is easily disturbed and moisturizing factors in the stratum corneum are reduced. Despite being a common condition, DS is often overlooked in patients with advanced age or comorbid diseases. In September 2022, specialists in dermatology and skin care met to discuss unmet needs and management of patients with DS with existing medical conditions or DS induced by ongoing pharmacological treatments. There was consensus about the need to improve the current understanding and management of DS in patients with comorbidities, including type 2 diabetes, chronic kidney disease, radiodermatitis, and photodamaged skin. Clinical guidance related to optimal treatment of DS in patients with advanced age or comorbid diseases is needed. Dexpanthenol-containing emollients have been shown to provide rapid relief from the symptoms and clinical signs of skin inflammation and are well-tolerated and effective in terms of moisturizing and soothing DS and maintaining skin-barrier function. Thus, dexpanthenol-containing emollients may play an important role in future management of DS. Further research is needed to elucidate the efficacy of dexpanthenol across the spectrum of DS, irrespective of comorbidity status or age. [ABSTRACT FROM AUTHOR]

Introduction: Adult dermatomyositis (DM) and juvenile dermatomyositis (JDM) are rare autoimmune diseases with characteristic skin rashes, weakness, and other systemic features. Upregulated interferon signaling has been consistently described in both adult and juvenile DM which makes janus kinase inhibitors (jakinibs) an attractive therapeutic agent that has a targeted mechanism of action. Areas covered: Herein is a review of the growing literature of jakinib use in adult and juvenile DM, including reports on specific disease features and safety of jakinibs in this population and a comparison between adult and juvenile DM. We performed a literature review using PubMed including all English-language publications before 1 February 2024 and abstracts from key recent rheumatology conferences. Expert opinion: Jakinibs are an exciting and promising treatment in both adult and juvenile DM. Current Phase 2 and 3 randomized placebo-controlled trials of jakinibs in both adult and JDM will provide significant insights into the efficacy of this class of medication as a potentially more mechanistically targeted treatment of both skin and muscle disease. In fact, these results will likely inform the treatment paradigm of dermatomyositis in that it may even be considered as first or second line. The next five years in the therapeutic landscape of both juvenile and adult DM is an exciting time for both patients and medical providers. [ABSTRACT FROM AUTHOR]

The two most common animal-based indicators used to evaluate leg health in broiler chickens are footpad dermatitis (FPD) and gait scoring, but these indicators are less explored in broiler breeders. This study is the first to investigate FPD and gait scoring in broiler breeders during their lifespan from rearing to end of life. In total, eight flocks were monitored (four Ross and four Hubbard) at five different timepoints, in rearing (5 and 15 weeks of age), during the production period (25 and 45 weeks of age) and at the end of the production period (approximately 60 weeks of age). At each visit, 50 hens and 25 roosters were gait scored (six-point scale) and footpads from another 50 hens and 25 roosters were evaluated (five-point scale) (total n = 3000 breeders, 2000 hens and 1000 roosters). Litter quality and air quality were measured at each visit. The results showed that the overall prevalence of FPD in rearing was low and that it increased towards the end of the production, with a mean FPD score of 2 out of a maximum 4 in the hens, indicating moderate lesions and 1.5 in the roosters. In all houses, the litter was dry and loose. FPD was not related to the litter quality, but to air quality, especially the ammonia concentration (P < 0.001). Overall, the gait score were good, and increased with age in both hens (P < 0.001) and roosters of both hybrids (P < 0.001). [ABSTRACT FROM AUTHOR]

Juvenile dermatomyositis (JDM) is a rare autoimmune disease most commonly with proximal weakness due to inflammation and characteristic skin rashes. Most patients have a chronic or polycyclic disease course on standard therapy so better treatments are needed. An interferon signature is well-established in key tissues of JDM. Janus kinase inhibitors (jakinibs), which can decrease IFN signaling, are therefore appealing as a targeted therapy. Herein is a review of the growing literature on JDM patients in jakinibs, including specifics of their jakinib exposure, summary of efficacy, disease features, and characteristics of patients treated, and safety parameters. The vast majority of refractory JDM patients respond to jakinib therapy, though they have varied features, doses, and previous/concurrent medications, and data is largely retrospective. Jakinibs are an exciting and promising treatment in JDM. Evaluation with larger prospective controlled studies is needed to answer remaining questions about jakinibs in JDM regarding dosing, which JDM patients to treat with jakinibs, potential biomarkers to use, and how best to monitor safety risks in JDM. [ABSTRACT FROM AUTHOR]

Skin exposure to noxious agents leads to cutaneous lesion marked by an increase in inflammation, cellular proliferation, and hyperplasiogenic reactions. Studies have demonstrated that these damages breach the skin integrity resulting in the aetiology of various cutaneous disorders like atopic dermatitis, eczema, psoriasis, and development of non-melanoma skin cancer. Celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, is an effective treatment for a variety of inflammatory diseases. Its importance in the therapy of skin problems, however, remains under appreciated. We tested efficacy of topically applied celecoxib in mitigating skin inflammation, cellular proliferation, and hyperplasia induced by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) in Swiss albino mice. Celecoxib (5 and 10 μmol) markedly reduced TPA (10 nmol) induced prostaglandin E2 (PGE2) production, oedema formation, myeloperoxidase (MPO) activity, and levels of pro-inflammatory cytokines such as tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6). It also resulted in a considerable decrease in ornithine decarboxylase (ODC) activity and the incorporation of [3H]-thymidine into DNA. In addition, there was a significant reduction in histoarchitectural abnormalities such as epidermal thickness, number of epidermal cell layers, neutrophil infiltration, intercellular oedema, and vasodilation. Our results demonstrate that topical celecoxib can reduce the inflammation, hyperproliferation, and hyperplasiogenic events of skin insults suggesting that it may prove to be a valuable management option for cutaneous lesion and associated illnesses such as atopic dermatitis, eczema, and psoriasis, as well as the emergence of non-melanoma cancer. [ABSTRACT FROM AUTHOR]

Hydroxychloroquine (HCQ) is a US Food and Drug Administration (FDA)-approved treatment for systemic lupus erythematosus (SLE) through inhibition of antigen presentation and subsequent reduction in T cell activation. Psoriasis relapse after antimalarial therapy have been reported in up to 18% of patients with psoriasis. Here, we explored the role of HCQ on exacerbating dermatitis utilizing an imiquimod (IMQ)-induced psoriasis-like dermatitis mouse model. Thirty-six C57BL/6 female mice were divided into six groups: wild-type control, IMQ-Only, pre-treat HCQ (30 mg/kg and 60 mg/kg HCQ), and co-treat HCQ with IMQ (30 mg/kg and 60 mg/kg HCQ). Besides control, all were topically treated with IMQ for 5 days. Pharmacological effects and mechanisms of HCQ were assessed by clinical severity of dermatitis, histopathology, and flow cytometry. HaCaT cells were co-treated with both HCQ and recombinant IL-17A, followed by the detection of proinflammatory cytokine expression and gene profiles through enzyme-linked immunosorbent assay and next-generation sequencing. In the pre-treated and co-treated HCQ groups, skin redness and scaling were significantly increased compared to the IMQ-Only group, and Th17 cell expression was also upregulated. Acanthosis and CD11b+IL23+ dendritic cell (DC) infiltration were observed in the HCQ treatment group. IL-6 overexpression was detected in both the HaCaT cells and skin from the experimental mice. Psoriasis-related genes were regulated after being co-treated with HCQ and recombinant IL-17A in HaCaT cells. HCQ exacerbates psoriasis-like skin inflammation by increasing the expression of IL-6, stimulating DC infiltration, and promoting Th17 expression in the microenvironment of the skin. This study provided possible mechanisms for inducing psoriasis during HCQ treatment through an animal model. [ABSTRACT FROM AUTHOR]

Vermicompost tea (VCT) is the effluent or leachate with a honeybrown colour collected during vermicomposting, an ecologically significant process essential to today's organic and regenerative agriculture. Dried earthworm, a.k.a. dilong (DL, meaning "earth dragon") in traditional Chinese herbal medicine, has long been used as a key component to treat diverse skin diseases, including eczema. In the present study, we hypothesized that VCT might have a positive influence on eczema therapy. It was found that the oral application of 50% VCT in mouse model reduced the ear allergic scores and alleviated the histological changes caused by eczema. Furthermore, the levels of Th2-associated and pro-inflammatory cytokines (namely IL-4 and IL-13 in serum) and IgE (in serum and ear tissues) were significantly reduced by VCT. Therefore, oral administration of 50% VCT exerts immunomodulatory effects on the development of eczema, suggesting its potential as a nutraceutical candidate for eczema treatment. [ABSTRACT FROM AUTHOR]

Dermatitis herpetiformis (DH) is a cutaneous manifestation of coeliac disease. Increased cardiovascular morbidity has been reported in coeliac disease, but in DH only little is known about this. In this cohort study with a long-term follow-up, the risk for vascular diseases in patients with dermatitis herpetiformis (DH) and coeliac disease was assessed. The study consisted of 368 DH and 1072 coeliac disease patients with biopsy-proven diagnosis performed between 1966 and 2000. For each DH and coeliac disease patient three matched reference individuals were obtained from the population register. Data regarding all outpatient and inpatient treatment periods between 1970 and 2015 were reviewed for diagnostic codes of vascular diseases from the Care Register for Health Care. Cox proportional hazard model was used to assess the risks for the diseases studied and the HRs were adjusted for diabetes mellitus (aHR). The median follow-up time of DH and coeliac disease patients was 46 years. The risk for cardiovascular diseases did not differ between DH patients and their references (aHR 1.16, 95% CI 0.91–1.47), but among coeliac disease patients, the risk was increased (aHR 1.36, 95% CI 1.16–1.59). The risk for cerebrovascular diseases was found to be decreased in DH patients when compared with references (aHR 0.68, 95% CI 0.47–0.99) and increased in coeliac disease patients (aHR 1.33, 95% CI 1.07–1.66). The risk for venous thrombosis was increased in coeliac disease patients (aHR 1.62, 95% CI 1.22–2.16) but not in DH. The risk for vascular complications appears to differ between DH and coeliac disease. In DH the risk for cerebrovascular diseases seems to be decreased, while in coeliac disease an elevated risk for cerebrovascular and cardiovascular diseases was observed. These differing vascular risk profiles between the two manifestations of the same disease merit further investigation. An increased risk for cardiovascular diseases was observed among patients with coeliac disease, but not among patients with dermatitis herpetiformis, a cutaneous manifestation of coeliac disease. The risk for cerebrovascular diseases was shown to be decreased in dermatitis herpetiformis patients, but conversely, an increased risk for cerebrovascular diseases was identified in coeliac disease patients. Coeliac disease, but not dermatitis herpetiformis, was shown to be associated with increased risk for venous thrombosis. [ABSTRACT FROM AUTHOR]

Macroautophagy/autophagy is a cellular recycling program regulating cell survival and controlling inflammatory responses in a context-dependent manner. Here, we demonstrate that keratinocyte-selective ablation of Atg16l1, an essential autophagy mediator, results in exacerbated inflammatory and neoplastic skin responses. In addition, mice lacking keratinocyte autophagy exhibit precocious onset of hair follicle growth, indicating altered activation kinetics of hair follicle stem cells (HFSCs). These HFSCs also exhibit expanded potencies in an autophagy-deficient context as shown by de novo hair follicle formation and improved healing of abrasion wounds. ATG16L1-deficient keratinocytes are markedly sensitized to apoptosis. Compound deletion of RIPK3-dependent necroptotic and CASP8-dependent apoptotic responses or of TNFRSF1A/TNFR1 reveals that the enhanced sensitivity of autophagy-deficient keratinocytes to TNF-dependent cell death is driving altered activation of HFSCs. Together, our data demonstrate that keratinocyte autophagy dampens skin inflammation and tumorigenesis but curtails HFSC activation by restraining apoptotic responses. Abbreviations: ATG16L1: autophagy related 16 like 1; DMBA: 2,4-dimethoxybenzaldehyde; DP: dermal papilla; EpdSCs: epidermal stem cells; Gas6: growth arrest specific 6; HF: hair follicle; HFSC: hair follicle stem cell; IFE: interfollicular epidermis; KRT5: keratin 5; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; PMK: primary mouse keratinocyte; RIPK3: receptor-interacting serine-threonine kinase 3; scRNAseq: single-cell RNA-sequencing; SG: sebaceous gland; TEWL: transepidermal water loss; TPA: 12-O-tetradecanoylphorbol-13-acetate; TNF: tumor necrosis factor; TNFRSF1A/TNFR1: tumor necrosis factor receptor superfamily, member 1a; UMAP: uniform manifold approximation and projection [ABSTRACT FROM AUTHOR]

1. A new assessment method for duck footpad dermatitis (FPD) evaluation was developed, combining visual and histological characters using the images and sections of 400 ducks' feet at 340 d of age. All ducks were graded as G0 (healthy), G1 (mild), G2 (moderate) and G3 (severe) according to the degree of FPD. 2. To reveal the potential biomarkers in serum related to duck FPD, non-targeted metabolomics and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were used to explore differential metabolites in each group. 3. There were 57, 91 and 210 annotated differential metabolites in groups G1, G2 and G3 compared with G0, which meant that the severity of FPD increased in line with the number of metabolites. Four metabolites, L-phenylalanine, L-arginine, L-leucine and L-lysine, were considered potential biomarkers related to FPD. 4. KEGG enrichment analysis showed that the FPD was mainly involved in glycolysis, the tricarboxylic acid (TCA) cycle, the pentose phosphate pathway and amino acid metabolism. These are related to production metabolism and can affect the physiological activities of ducks, which might explain the decrease in production performance. [ABSTRACT FROM AUTHOR]

The (macro)autophagy field is facing a paradigm shift after the recent discovery that cytosolic cargoes can still be selectively targeted to phagophores (the precursors to autophagosomes) even in the absence of LC3 or other Atg8-protein family members. Several in vitro studies have indeed reported on the existence of an unconventional selective autophagic pathway that involves the in-situ formation of an autophagosome around the cargo through the direct selective autophagy receptor-mediated recruitment of RB1CC1/FIP200, thereby bypassing the requirement of LC3. In an article recently published in Science, we demonstrate the physiological importance of this unconventional autophagic pathway in the context of TNF (tumor necrosis factor) signaling. We show that it promotes the degradation of the cytotoxic TNFRSF1A/TNFR1 (TNF receptor superfamily member 1A) complex II that assembles upon TNF sensing and thereby protects mice from TNFRSF1A-driven embryonic lethality and skin inflammation. Abbreviations: ATG: autophagy related; CASP: caspase; FIR: RB1CC1/FIP200-interacting region; LIR: LC3-interacting region; M1: linear; PAS: phagophore assembly site; PtdIns3K: phosphatidylinositol 3-kinase; TNF: tumor necrosis factor; TNFRSF1A: TNF receptor superfamily member 1A [ABSTRACT FROM AUTHOR]

The present work aims to formulate nanoemulgel of crisaborole (CB) and evaluate its effectiveness against 2,4-Di-nitrochlorobenzene induced (DNCB) atopic dermatitis (AD) in mice. AD is a chronic inflammation of the skin affecting the quality of life. CB is a topical PDE4 inhibitor marketed as a 2% ointment. It, however, possesses poor aqueous solubility. An o/w nanoemulsion shall exhibit an enhanced therapeutic effect owing to the increased solubility of CB and an augmented skin penetration. The addition of a gelling agent to form a nanoemulgel further provides ease of application to the patients. Nanoemulsion was prepared by aqueous titration method using caproyl PGMC, cremophore EL and propylene glycol as the oil, surfactant, and cosurfactant respectively. The formulations were characterized by their size, zeta potential and polydispersity index (PDI). 1% Carbopol 934 was used as the gelling agent to formulate nanoemulgel comprising of optimized nanoemulsion (NE 9). Ex vivo skin permeation of the CB nanoemulgel was compared with the CB ointment. Its therapeutic effect was evaluated in Balb/c mice. NE 9 comprised of 7.49% oil, 37.45% Smix (1:3) and water 55.06%. Its particle size, PDI and zeta potential were 15.45 ± 5.265 nm, 0.098 and −17.9 ± 8.00 mV respectively. The nanoemulgel exhibited a 3-fold higher permeation flux as compared to the ointment. In vivo studies demonstrated that the nanoemulgel provided better therapeutic effect than the ointment. We can thereby conclude that nanoemulgel formulation can be a successful drug delivery strategy for enhancing the therapeutic effect of CB. [ABSTRACT FROM AUTHOR]

T cells populate the skin to provide an effective immunosurveillance against external insults and to maintain tissue homeostasis. Most cutaneous T cells are αβ T cells, however, γδ T cells also exist although in much lower frequency. Different subsets of αβ T cells can be found in the skin, such as short-lived effector T cells, central memory T cells, effector memory T cells, and tissue-resident memory T cells. Their differential biology, function, and location provide an ample spectrum of immune responses in the skin. Foxp3+ memory regulatory T cells have a pivotal role in maintaining homeostasis in the skin and their dysregulation has been linked with different skin pathologies. The skin also contains populations of non-classical T cells, such as γδ T cells, NK T cells, and MR1-restricted T cells. Their role in skin homeostasis and response to pathogens has been well established in the past years, however, there is also growing evidence of their role in mediating allergic skin inflammation and promoting sensitization to allergens. In this review, we provide an updated overview on the different subsets of T cells that populate the skin with a specific focus on their role in allergic skin inflammation. [ABSTRACT FROM AUTHOR]

Herein, we developed an engineered extracellular vehicle (EV)-based method for ameliorating inflammatory responses in psoriasis. EVs, derived from annexin A1 (ANXA1) overexpressing T cells, were co-extruded with M2 macrophage membrane to obtain engineered EVs. In vitro, the effect of engineered EVs on macrophage polarization was evaluated by real-time PCR. In imiquimod (IMQ)-induced psoriasis-like mouse model, the efficacy of engineered EVs in ameliorating psoriatic inflammation was evaluated by Psoriasis Area and Severity Index (PASI) score and immunohistochemistry staining after subcutaneous injection of EVs. The engineered EVs not only preserved the high stability of M2 macrophage membrane but also retained the macrophage reprogramming potential of ANXA1 overexpressed in T cells. In the psoriasis-like mouse model, subcutaneous injection of engineered EVs successfully reduced the PASI score and the levels of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α. Along with high biosafety, the administration of EVs also rescued the histomorphological changes of spleen, liver, and kidney. The engineered EVs exhibited the potential to alleviate inflammation of psoriasis, providing new insights and potential strategies for the immunotherapies of psoriasis. [ABSTRACT FROM AUTHOR]

T-LAK-cell-originated protein kinase (TOPK), a novel member of the mitogen-activated protein kinase family, is considered an effective therapeutic target for skin inflammation. In this study, a series (A - D) of paeonol derivatives was designed and synthesised using a fragment growing approach, and their anti-inflammatory activities against lipopolysaccharide (LPS)-induced nitric oxide production in RAW264.7 cells were tested. Among them, compound B12 yielded the best results (IC50 = 2.14 µM) with low toxicity (IC50 > 50 mM). Preliminary mechanistic studies indicated that this compound could inhibit the TOPK-p38/JNK signalling pathway and phosphorylate downstream related proteins. A murine psoriasis-like skin inflammation model was used to determine its therapeutic effect. [ABSTRACT FROM AUTHOR]

Objectives. Hand block printing is a highly repetitive and precision job involving tasks such as hitting the wooden hand block with the hands as a hammer, causing chronic mechanical trauma to the ulnar side of the palm. This study aimed to determine the prevalence of work-related hand symptoms, to identify ergonomic risks and musculoskeletal disorders (MSDs) and evidence of mechanical trauma among artisans working in Bagh print of Madhya Pradesh. Methods. Occupational risk involved in the artisan's wrist area was identified using the modified Dutch musculoskeletal questionnaire (MDMQ) and modified Boston hand evaluation questionnaire. The Boston hand evaluation questionnaire helps in the measurement of the severity of the symptoms. A direct observation study was performed to identify the chronic effects of mechanical trauma (CEMT) on artisan's hands. Results. Symptoms like pain, weakness, numbness and tingling were highly prevalent among the artisans, those with experience <3 years were more likely to report pain during working hours (p < 0.001) and those with experience >13 years were more likely to report numbness (p < 0.001) and tingling (p < 0.001). Conclusion. This study supports the evidence that the new artisans are at higher risks of reporting pain and CEMT, including fever and body pain, ultimately causing job loss. [ABSTRACT FROM AUTHOR]

Morel mushrooms, Morchella species are highly nutritious and excellently edible wild mushrooms abundantly growing in Kashmir Himalayas. The free radical scavenging, anti-inflammatory, and arthritis edema-inhibiting properties of bioactive extract of Morchella elata (EAE) were evaluated. EAE inhibited 53.2% formalin-induced paw edema at a dose of 500 mg/kg b.wt and 75.0% croton oil-induced skin inflammation at a dose of 50 mg topical application. EAE exhibited 51.8% COX inhibiting activity at a concentration of 100 µg/ml when assayed using LPS-stimulated RAW 264.7 cells exposed to the extract. NF-kB inhibiting activity of EAE was assayed using Lentix-293T P65 Ds Red stable cell line. High-throughput fluorescent imaging and flow cytometry showed profound ability of EAE to inhibit NF-kB activity. HPTLC analysis revealed that EAE is composed of several chemical components. The mushroom is a source of therapeutically useful functional food that can provide relief in arthritis. [ABSTRACT FROM AUTHOR]

We aimed to find active substances to help relieve the symptoms caused by increased photosensitivity after alpha hydroxy acid (AHA) peeling. A questionnaire survey was provided to 66 patients who received AHA peeling therapy to understand if increased photosensitivity existed and its specific symptoms. We verified increased photosensitivity after AHA peeling by monitoring cell viability to detect the combined toxicity of glycolic acid (GA) and UVB in HaCaT cells. The ELISA method was used to determine the expression of KLK7, FLG, IL-1β, and IL-8 to correlate damage to the skin barrier and inflammation induced by GA and UVB and the relieving effects of Portulaca oleracea extract. Our survey results showed that 6.06% of people were more sensitive to sunlight after AHA peeling than before. Experiments at the cellular level showed that UVB induced cytotoxicity on HaCaT cells pre-treated with GA. Combined exposure of GA and UVB induced up-regulation of KLK7 and down-regulation of FLG and increased inflammatory cytokines of IL-1β and IL-8. P. oleracea extract inhibited the reduction of FLG and increased KLK7, IL-1β, and IL-8 expression caused by combined exposure. Our study found that combined exposure to GA and UV disrupted the skin barrier and induced significant inflammation. These results provided a theoretical basis for increased photosensitivity after chemical peeling. P. oleracea extract ameliorated GA and UVB-induced impaired skin barrier function and inflammation in HaCaT cells and may have the potential to relieve photosensitivity after AHA peeling. [ABSTRACT FROM AUTHOR]

Transient eosinophilia is not uncommon in patients with moderate-to-severe atopic dermatitis (AD) treated with dupilumab. A retrospective, single center, observational study was conducted to assess the difference in terms of absolute eosinophil count (AEC) change at 4 months and at 12 months, relative to the baseline, in predefined subgroups of patients affected by moderate-to-severe AD treated with dupilumab. Complete data for 373, 289 and 210 patients were available at the baseline, 4 months and 12 months, respectively. Patients with a history of conjunctivitis (n = 152) had greater increases in AEC at 4 months as compared with those (n = 137) who did not (+16%vs0%,p = 0.01). Patients with food allergies (n = 46) showed similar increases (+39%vs + 5%, p = 0.01). Patients experiencing facial redness dermatitis on dupilumab (n = 46) had greater increases in AEC at 4 months than those (n = 243) who did not (+40%vs + 5%, p = 0.03). Patients that had dupilumab-induced ocular surface disease (n = 44) had greater increases in AEC at 4 months than those (n = 245) who did not (+43%vs + 5%, p = 0.01). Atopic comorbidities are associated with a paradoxical increase in AEC at 4 months in AD patients treated with dupilumab. Patients experiencing dupilumab-related ocular surface disease or facial redness dermatitis also have remarkable increases in AEC at 4 months. [ABSTRACT FROM AUTHOR]

Shiitake mushrooms (Lentinus edodes) are an edible fungus, initially grown in Japan and China that are increasingly marketed in Europe. We previously presented 15 shiitake dermatitis cases reported to Poison Control Centres (PCCs) in France from January 2000 to December 2013. The aim of this study was to describe changes in the number of shiitake dermatitis cases since 2014, and to better describe the clinical characteristics and risk factors of this reaction. This observational study is a retrospective review of cases in the French PCCs database between 1 January 2014 and 31 December 2019. Out of 125 shiitake exposures, we identified 59 cases of dermatitis: sex ratio of 1.80 M/F; ages ranging from 19 to 69 years (median: 39 years). Dermatitis occurred after raw or undercooked shiitake consumption (e.g., from the wok, in soup, or on pizza). The rash appeared 1–168 h (median: 48 h) after shiitake ingestion. Linear, erythematous, urticarial papules and plaques developed across the trunk, arms, and legs within a few hours and persisted for 1–40 d (median 10 d). The amount of shiitake eaten (low vs. medium vs. high) significantly increased the duration of dermatitis (median days 4 vs. 7 vs. 15, respectively; p =.007). In all, 38 patients received corticosteroids, antihistamine drugs, or both without demonstrated benefit. All patients made a complete recovery. The mechanism of shiitake dermatitis is thought to involve lentinan, a heat-labile polysaccharide component. Inadequate cooking clearly seems to be a driver of the occurrence of shiitake dermatitis. This study highlighted a dose-dependent response, suggesting a partial toxic mechanism or a th1-type hypersensitivity mechanism. Treatment is focused on symptom management. Health professionals and the general population should be aware of both the risk associated with inadequately cooked shiitake consumption and the favourable prognosis of this still poorly known toxic dermatitis. [ABSTRACT FROM AUTHOR]

1. Footpad dermatitis (FPD) can be used as an important indicator of animal welfare and for economic evaluation; however, human scoring is subjective, biased and labour intensive. This paper proposes a novel deep learning approach that can automatically determine the severity of FPD based on images of chicken's feet. 2. This approach first determined the areas of the FPD lesion, normal parts of each foot and the background, using a deep segmentation model. The proportion of the FPD for the chicken's two feet was calculated by dividing the number of FPD pixels by the number of feet pixels. The proportion was then categorised using a five-point score for FPD. The approach was evaluated from 244 images of the left and right footpads using five-fold cross-validation. These images were collected at a commercial slaughter plant and scored by trained observers. 3. The result showed that this approach achieved an overall accuracy and a macro F1-score of 0.82. The per-class F1-scores from all FPD scores (scores 0 to 4) were similar (0.85, 0.80, 0,80, 0,80, and 0.87, respectively), which demonstrated that this approach performed equally well for all classes of scores. 4. The results suggested that image segmentation and a deep learning approach can be used to automate the process of scoring FPD based on chicken foot images, which can help to minimise the subjective bias inherent in manual scoring. [ABSTRACT FROM AUTHOR]

Nanotechnological products have been used as strategies to optimize the therapy and minimize the side effects of topical corticoids. The objective of this study was to develop hydrogels by the addition of sclerotium gum to the suspensions of desonide-loaded açai oil-based nanocapsules and to study their biological effect using an animal model of acute skin inflammation. The hydrogels presented a pH compatible with topical application (4.4 to 5.0), nanometric mean diameter (131 to 165 nm), pseudoplastic behavior, and stability under room conditions during 30 days. The in vitro skin permeation/penetration study demonstrated that a higher amount of desonide (p < 0.05) was retained in the epidermis from the nanotechnological-hydrogels (0.33 to 0.36 µg.cm2) in comparison to the commercial gel cream (0.16 µg.cm2). In the dermis, the nanostructured hydrogels promoted a lower DES retention compared to the non-nanostructured formulations (p < 0.05). This result may indicate a smaller amount of drug reaching the bloodstream and, thus, fewer side effects can be expected. Concerning the anti-inflammatory effect, the developed hydrogels reduced both ear edema and inflammatory cell infiltration, showing an effect comparable to the commercially available formulation, which presents twice the drug concentration. The hydrogels developed may be considered a promising approach to treat dermatological disorders. [ABSTRACT FROM AUTHOR]

Psoriasis is chronic incurable skin inflammation. The anti-inflammatory properties of mesenchymal stem cells (MSCs) have been put forward to be involved in several inflammatory diseases. However, little was known about the role of human adipose tissue-derived stem cells (hAD-MSCs) in psoriasis. We sought to explore the feasibility of using hAD-MSCs infusion as a therapeutic approach in psoriatic mice. We constructed the psoriasis-like model by IMQ implication, treated with hAD-MSCs by subcutaneous injection. To evaluate the efficacy, we examined the histology, CD45 and ROS positive cells by HE and flow cytometry respectively. We also tested the key cytokines with PCR. Moreover, to achieve a better therapeutic effect, we treated the model by combing with vitamin E application. We found that the classic histological symptoms of psoriasis were relieved after treatment with hAD-MSCs, also, the splenic index, the infiltration of immune cells and several pro-inflammatory cytokines were decreased. Interestingly, we also found that hAD-MSCs could inhibit ROS generation. Moreover, the combination therapy of hAD-MSCs and vitamin E could promote the curative effect with greater ROS inhibition. These results suggested that hAD-MSCs could be useful for treating psoriasis by negatively regulating ROS. [ABSTRACT FROM AUTHOR]

'Soak and smear' method, water soaking to induce skin hydration followed by topical corticoids application suggests effectiveness in clinical dermatological practice. We investigate one possible mechanism of soaking times effect on drug partitioning and diffusion rates in skin and its proposed efficacy. Utilizing an in vitro flow-through diffusion system to evaluate efficacy of the 'soak and smear' method following 0.5, 8, and 20 min water soaking and [14C]-hydrocortisone topical application on human skin to probe the possibility of percutaneous penetration enhancement. In water-soak groups, more [14C]-hydrocortisone was absorbed and retained in stratum corneum and epidermis, whereas, in the control (no soak) more was in the deep skin–dermis and receptor fluid. These differences between water-soak groups and the control are statistically significant (p <.05). Effect of 'soak and smear' on skin absorption and penetration depends on interaction of individual drug's physicochemical property, stratum corneum hydration, and stratum corneum–epidermoid barrier status. Water soaking ( ≤ 20 min) induced skin hydration increases [14C]-hydrocortisone absorption and retention into the upper skin layer but not deep layers. This could support the proposed hypothesis of clinical dermatological treatment of hydrocortisone to local skin inflammations should the epidermis be found to be a key target for atopic dermatitis therapy. [ABSTRACT FROM AUTHOR]

Therapeutic drug monitoring (TDM) may lead to more rational use of biologics. Still, TDM is largely underexplored in psoriasis. Little is known about the dosing behavior of biologics by dermatologists, and their attitude toward TDM. Exploration of the awareness and need for the concept of TDM in psoriasis amongst (inter)national dermatologists. A survey was distributed at the Belgian Dermatology Days 2019 and Skin Inflammation & Psoriasis International Network (SPIN) Congress 2019. Next, an online survey version was launched amongst the SPIN Scientific Committee members. We collected physician's characteristics, prescription behavior of biologics, data regarding clinical response to biologics and attitude toward TDM. A total of 107 surveys were included for analysis. Most dermatologists were Belgium-based (54.2%), others from European (23.4%) or non-European countries (19.6%). Seventy percent performed either dose increase (64.8%), time interval shortening (74.6%), dose lowering (16.9%) or time interval extension (33.8%). The majority who performed dose adaptations acknowledged the need for TDM. This study showed most dermatologists perform dose adaptations empirically. The need for TDM was indicated by the majority, implying the need for effective communication regarding availability, utility and implementation of TDM assays in daily dermatology practice. [ABSTRACT FROM AUTHOR]

Present investigation was aimed to develop aspasomal gel of Mometasone Furoate for the treatment of Psoriasis that are biologically active and deliver drug at controlled rate and decrease dosing frequency. The vesicles were fabricated using film hydration method and optimized using 32 factorial Design. Prepared formulations were evaluated for percent drug loading, vesicle size, Zeta potential, polydispersity index and morphological studies. Gel was prepared using carbopol by loading optimized drug loaded asposomes and was evaluated for drug content, pH, viscosity and spreadability. The drug release study from the gel was done using dialysis membrane and goat skin. Anti- oxidant potency of the prepared aspasomal gel was determined by Ferric Reducing Assay whereas, in-vivo performance for inflammation and skin irritation was carried out using Wistar rats. Optimized aspasomes demonstrated desired properties for entrapment efficiency (74.72 ± 1.8), vesicle size (282.9 ± 1.7), polydispersity index (0.2), zeta potential (−20.2 mV) with spherical shape. The results recorded for drug release from the optimized aspasomal gel exhibited sustained release (24h) compared to the marketed cream (5h). Depot formation of Mometasone furoate loaded aspasomal gel in the epidermis was confirmed by ex vivo skin penetration study by using fluorescent marker. In-vivo study revealed no any irritation and inflammation to the skin promoting drug delivery system to treat psoriasis. In conclusion, Mometasone furoate loaded aspasomal gel releases the drug for longer duration of time and reduce dosing frequency, providing the new dimension for the treatment of psoriasis. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is characterized by progressive skin inflammation. In addition, sulforaphane is an isothiocyanate organosulfur compound from cruciferous vegetables. Sulforaphane was reported to ameliorate inflammatory responses. Therefore, this study was conducted to evaluate the protective effects of sulforaphane in AD through affecting the balance between pro-inflammatory and anti-inflammatory cytokines and to evaluate its effect on AD-induced activation of the apoptotic pathway. The method of repeated rubbing of 2,4-dinitrochlorobenzene (DNCB) on shaved dorsal skin and ears of mice was used for induction of AD. After the development of AD, part of the mice was injected with 1 mg/kg sulforaphane, subcutaneously three times weekly. Samples of skin were isolated for assessment of gene and protein expression of 8-hydroxy2′-deoxyguanosine, IgE, NFκB, TNF-α, IL-1β, IL-4, IL-10, Nrf2, and caspase-3. In addition, skin sections from different groups were stained with anti-caspase-3 antibodies. Mice in the AD group were characterized by increased gene and protein expression of 8-hydroxy2′-deoxyguanosine, IgE, NFκB, TNF-α, IL-1β, and caspase-3 associated with reduced expression of Nrf2, IL-4, and IL-10. Treatment of AD mice with sulforaphane significantly reduced the number of scratches, dermatitis score, and ear thickness. In addition, sulforaphane significantly attenuated the gene and protein expressions produced by AD. Therefore, sulforaphane alleviated AD induced in mice through inhibition of oxidative stress, oxidative DNA damage, inflammation, and apoptosis. Atopic dermatitis is a chronic relapsing inflammatory disease. Sulforaphane is an isothiocyanate organosulfur compound obtained from cruciferous vegetables. Sulforaphane alleviated AD induced in mice. Sulforaphane inhibits oxidative stress, oxidative DNA damage, inflammation, and apoptosis. [ABSTRACT FROM AUTHOR]

The aim of our study was to characterize the group of patients suffering from dermatitis herpetiformis Duhring (DH) and to make the statistical analysis of monitored parameters. We retrospectively analysed the data of 122 patients with DH (age, gender, the severity of DH, tissue transglutaminase antibodies IgA (IgA-TGA) level and dapsone dose). The mild form of DH was recorded in 69 patients (56.6%), the moderate form in 48 patients (39.3%) and the severe form in 5 patients (4.1%); 118 patients (96.7%) are on dapsone therapy, 3.2% of patients are only on gluten-free diet. The median of average IgA-TGA in the mild form is 6.25 U/ml, in the moderate form 14.45 U/ml and in the severe form 10.33 U/ml. Although the significant relation of the IgA-TGA to the disease severity was not confirmed, there is some trend in the increase of the IgA-TGA level from mild to moderate and severe form of DH. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus is a skin commensal microorganism commonly colonizing healthy humans. Nevertheless, S. aureus can also be responsible for cutaneous infections and contribute to flare-up of inflammatory skin diseases such as atopic dermatitis (AD), which is characterized by dysbiosis of the skin microbiota with S. aureus as the predominant species. However, the role of major virulence factors of this pathogen such as phenol-soluble modulin (PSM) toxins in epidermal inflammation remains poorly understood. Stimulation of primary human keratinocytes with sublytic concentrations of synthetic and purified PSM α3 resulted in upregulation of a large panel of pro-inflammatory chemokine and cytokine gene expression, including CXCL1, CXCL2, CXCL3, CXCL5, CXCL8, CCL20, IL-1α, IL-1β, IL-6, IL-36γ and TNF-α, while inducing the release of CXCL8, CCL20, TNF-α and IL-6. In addition, using S. aureus culture supernatant from mutants deleted from genes encoding either α-type PSMs or all PSM production, PSMs were shown to be the main factors of S. aureus secretome responsible for pro-inflammatory mediator induction in human keratinocytes. On the other hand, α-type PSM-containing supernatant triggered an intense induction of pro-inflammatory mediator expression and secretion during both topical and basal layer stimulation of an ex vivo model of human skin explants, a physiologically relevant model of pluristratified epidermis. Taken together, the results of this study show that PSMs and more specifically α-type PSMs are major virulence factors of S. aureus inducing a potent inflammatory response during infection of the human epidermis and could thereby contribute to AD flare-up through exacerbation of skin inflammation. [ABSTRACT FROM AUTHOR]

Epicutaneous exposure to allergenic proteins is an important sensitization route for skin diseases like protein contact dermatitis, immunologic contact urticaria, and atopic dermatitis. Environmental allergen sources such as house dust mites contain proteases, which are frequent allergens themselves. Here, the dependency of T-helper (TH) cell recall responses on allergen protease activity in the elicitation phase in mice pre-sensitized via distant skin was investigated. Repeated epicutaneous administration of a model protease allergen, i.e. papain, to the back skin of hairless mice induced skin inflammation, serum papain-specific IgE and TH2 and TH17 cytokine responses in the sensitization sites, and antigen-restimulated draining lymph node cells. In the papain-sensitized but not vehicle-treated mice, subsequent single challenge on the ear skin with papain, but not with protease inhibitor-treated papain, up-regulated the gene expression of TH2 and TH17/TH22 cytokines along with cytokines promoting these TH cytokine responses (TSLP, IL-33, IL-17C, and IL-23p19). Up-regulation of IL-17A gene expression and cells expressing RORγt occurred in the ear skin of the presensitized mice even before the challenge. In a reconstructed epidermal model with a three-dimensional culture of human keratinocytes, papain but not protease inhibitor-treated papain exhibited increasing transdermal permeability and stimulating the gene expression of TSLP, IL-17C, and IL-23p19. This study demonstrated that allergen protease activity contributed to the onset of cutaneous TH2 and TH17/TH22 recall responses on allergen re-encounter at sites distant from the original epicutaneous sensitization exposures. This finding suggested the contribution of protease-dependent barrier disruption and induction of keratinocyte-derived cytokines to the recall responses. [ABSTRACT FROM AUTHOR]

Sasa coreana Nakai (SCN) is a medicinal plant commonly used against inflammation. However, the underlined mechanisms against skin inflammation is poorly understood. The present study investigated the effects of SCN leave extract on ear inflammation. To this aim, six-week-old male ICR mice was subjected to 12-O-tetradecanoyl-phorbol-13-acetate induce ear edema, which were then topically treated with the leave extract of SCN. Ear thickness, weight, and morphological changes were recorded to ensure the induction of ear edema. Further, histological analysis and protein expression for inflammatory markers were also recorded to validate the study. Topical treatment with SCN repressed TPA-induced ear edema in a dose-dependent manner. Further, SCN treatment significantly antagonized the protein expression of MAP kinase signaling pathway and reduced the effect of TPA-induced NF-κB activation, sequentially, deactivated its transcriptional targets in a dose-dependent manner. Collectively, the study suggested that SCN could be a useful therapeutic agent against skin inflammation. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the effect of liraglutide on obesity diabetic mice with psoriasiform skin inflammation. Wild-type mice and db/db mice were randomly divided into five groups (n = 6): including the control group which received Vaseline, the imiquimod (IMQ)-induction group and the liraglutide-treatment group. The advanced treatment with liraglutide (0.3 mg/kg/d) for 4 weeks before IMQ induced psoriatic skin inflammation in the db/db + IMQ + Lira group. Basic parameters of diabetes, PASI, histopathology of skin, the expression of IL-17A, IL-23, IL-22, and TNF-α in the skin of back were measured. After IMQ induction, the psoriatic skin inflammation and pathological changes in the db/db + IMQ group were more serious than those in the WT + IMQ group. The glucose metabolism and insulin resistance of in the db/db + IMQ + Lira group were significantly improved, Psoriasis Area and Severity Index (PASI) was significantly reduced, and the protein and mRNA expressions of IL-23, IL-17, IL-22, and TNF-α in the back skin tissues were decreased. Liraglutide can improve psoriasis skin lesions of obese diabetic mice, and the mechanism may be related to the inhibition of the expression of IL-23, IL-17, IL-22, and TNF-α through the IL-23/Th-17 pathway. [ABSTRACT FROM AUTHOR]

Permanent make-up tattooing as a cosmetic procedure is gaining popularity especially among women. Although it is considered a relatively safe intervention, the ink used can rarely be a trigger of sarcoidosis. Uveitis can occur as part of this inflammatory process. In this study, we describe two ladies presented with tattoo-associated uveitis as the first manifestations of systemic sarcoidosis. They developed intermediate uveitis shortly after skin inflammation several months after permanent make-up tattooing of eyebrows. Lung involvement, high ACE levels, and negative PPD were present. Skin granuloma formation was diffuse over the area of tattoo in one patient and localized in the other one. This is the first report of uveitis following make-up tattoo. [ABSTRACT FROM AUTHOR]

Psoriasis is an autoimmune inflammatory skin disorder consists of hyperkeratosis, abnormal keratinization, acanthosis, and infiltration of inflammatory cells in the dermis. Topical pharmacotherapy with conventional molecules and formulations is associated with toxicity, low efficacy, and poor skin penetration. Lipid-based nanoparticles can be introduced as a new strategy for improving the efficacy of psoriasis treatment by increasing drug localization. Metformin-loaded liposomes were prepared by thin-layer hydration technique and characterized for particle size, entrapment efficiency, and release profiles. The optimized formulations including metformin and two concentrations of ginger were further evaluated in ex vivo skin permeation and localization, and in vivo psoriasis treatment in an imiquimod-induced psoriatic skin model. Optimized liposome has indicated its ability in localization of metformin at the skin may by improving the impaired psoriatic skin barrier. Co-administration of metformin and ginger loaded in liposome completely treated the psoriatic lesions after 21 days of treatment and significantly decreased IL-22 and TNF-α compared with untreated skin and skin treated by betamethasone as a positive control. In conclusion, metformin and ginger loaded in liposomes have shown perfect results in providing effective treatment of psoriasis. [ABSTRACT FROM AUTHOR]

The sand flea, Tunga penetrans, causes tungiasis, the detrimental skin inflammation with the potential for bacterial co-infections. It is a neglected tropical disease common among the rural poor, especially communities along the coastlines in Southwest Nigeria. There are very few studies on T. penetrans infestation in Nigeria, and no records of infestation along the sandy coastal areas of Ondo State. Therefore, the current study was carried out to examine the prevalence of T. penetrans infestation in the coastal communities of Zion Igbokoda, Kofawe and Laranda in the region of Igbokoda, Ondo State. Hands and feet of selected household members were examined, whereas fleas on different types of floors were sampled by sweeping and beating, soil collection, and extraction by tullgren funnel methods. The prevalence of tungiasis was 35.8% of the total population studied with infection more prevalent in males within 0–4 years (46.9%), 5–9 years (60.2%), 10–14 years (60%) and 60 years and above (28.1%) age groups than in females (p = 0.015). Infestation prevalence was in the order of 43.9%, 34.6% and 29.0% for Zion Igbokoda, Kofawe and Laranda, respectively. The number of flea-infested floors was 81 out of 363 examined with the greatest percentage infestation in houses that had earthen floored rooms and verandas. The high prevalence recorded in this study is capable of affecting the socio-economic well-being of the Igbokoda community. Therefore, a well-designed intervention measure involving concrete flooring of houses is suggested in order to ameliorate infestation burdens. [ABSTRACT FROM AUTHOR]

The current experiment was designed to evaluate the effects of dietary supplementations of zinc oxide nanoparticles (ZONPs) on some behavioural, performance, welfare and histopathological changes in broilers exposed to multidrug resistant Staphylococcus aureus (MRSA)-induced footpad dermatitis (FPD). Eighty-four male Indian River (IR) broilers were randomly allotted to six different dietary treatments as follows: C−ve, C+ve, 10, 20, 30 and 40 ppm ZONPs from 7 to 49d of age. At day 28, broilers (n = 70) were sub-cutaneously injected with 0.5 ml of saline containing 5.3 × 107 CFU/ml of S. aureus (MRSA) in each metatarsal foot pad. Control (non-infected) broilers were given 0.5 ml of saline (n = 14). Results clarified that non-infected birds and ZONPs-fed birds had significantly higher standing and feeding activities and lower resting activities in comparison with the infected group. Also, the S. aureus infected group had significantly lower body weight gain (BWG) and higher feed conversion ratio (FCR) than the non-infected group. In addition, the non-infected birds and ZONPs groups had significantly lower object crossing and tonic immobility times (TI) and gait scores (GS) in comparison with the S. aureus group. Only ZONPs 30, 40 ppm and non-infected groups had a significantly higher latency to lie time (LLT) and lower serum cortisol level in comparison with the S. aureus group. Moreover, there were significant changes in the gross lesion score and histopathological lesions between the different groups. In conclusion, the dietary supplementation of ZONPs can reduce S. aureus-induced negative effects of FPD in broilers. [ABSTRACT FROM AUTHOR]

Cutaneous T-cell lymphoma (CTCL) may pose a diagnostic challenge for physicians, as clinical presentation and histologic analysis may mimic benign dermatologic conditions. The authors present a case of recurrent CTCL in which the recurrence was limited to the eyelid and misdiagnosed as a contact dermatitis. To the best of the authors' knowledge, this is the first reported case of recurrent CTCL that has presented solely as dermatitis of the eyelid. [ABSTRACT FROM AUTHOR]

Introduction: Atopic dermatitis (AD) is a heterogeneous, chronic, inflammatory skin disease with a non-negligible prevalence at present. Its pathogenesis is complex, but mainly characterized by constitutive T helper type 2 (Th2)-cell activation. Systemic therapies for moderate-to-severe AD can be associated with adverse events that encumber their satisfactory long-term use. Several drugs targeting relevant molecules in the immunopathogenesis of AD have been approved or are under clinical development for the treatment of moderate to severe AD. To elaborate this review, literature searches were performed in PubMed on 29 August 2020. Areas covered: This narrative literature review is focused on the pivotal role of IL-13 in the immunopathogenesis of AD and other skin diseases. Expert opinion: Dupilumab has demonstrated the central role of IL-13 and IL-4 in the pathogenesis of AD, asthma, and other diseases in the atopic spectrum. In addition, phase III randomized clinical trials (RCTs) evaluating specific blockade of IL-13 with tralokinumab for treatment of AD also demonstrated favorable results, and phase III RCT evaluating lebrikizumab are ongoing. The role of IL-13 in other skin diseases should be further investigated. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus is a skin commensal microorganism commonly colonizing healthy humans. Nevertheless, S. aureus can also be responsible for cutaneous infections and contribute to flare-up of inflammatory skin diseases such as atopic dermatitis (AD), which is characterized by dysbiosis of the skin microbiota with S. aureus as the predominant species. However, the role of major virulence factors of this pathogen such as phenol-soluble modulin (PSM) toxins in epidermal inflammation remains poorly understood. Stimulation of primary human keratinocytes with sub-lytic concentrations of synthetic and purified PSM a3 resulted in upregulation of a large panel of pro-inflammatory chemokine and cytokine gene expression, including CXCL1, CXCL2, CXCL3, CXCL5, CXCL8, CCL20, IL-1α, IL-1β, IL-6, IL-36γ and TNF-α, while inducing the release of CXCL8, CCL20, TNF-α and IL-6. In addition, using S. aureus culture supernatant from mutants deleted from genes encoding either α-type PSMs or all PSM production, PSMs were shown to be the main factors of S. aureus secretome responsible for pro-inflammatory mediator induction in human keratinocytes. On the other hand, α-type PSM-containing supernatant triggered an intense induction of pro-inflammatory mediator expression and secretion during both topical and basal layer stimulation of an ex vivo model of human skin explants, a physiologically relevant model of pluristratified epidermis. Taken together, the results of this study show that PSMs and more specifically α-type PSMs are major virulence factors of S. aureus inducing a potent inflammatory response during infection of the human epidermis and could thereby contribute to AD flare-up through exacerbation of skin inflammation. [ABSTRACT FROM AUTHOR]

The natural products derived from Capparis ecuadorica H.H. Iltis (Capparaceae) could have great potential for anti-inflammation since they inhibited the inflammatory response in lipopolysaccharide (LPS)‐stimulated RAW 264.7 cells. This study investigated the anti-inflammatory effects and related mechanism of methanol extract of C. ecuadorica leaves (MCE) during atopic dermatitis (AD) responses. Alterations in the phenotypical markers for AD, luciferase signal, iNOS‐mediated COX‐2 induction pathway, and inflammasome activation were analysed in non-Tg (n = 5) and 15% phthalic anhydride (PA) treated IL-4/Luc/CNS-1 transgenic (Tg) HR1 mice (n = 5 per group), subsequent to treatment with acetone-olive oil (AOO), vehicle (DMSO) and two dose MCE (20 and 40 mg/kg) three times a week for 4 weeks. MCE treatment reduced the intracellular ROS level (48.2%), NO concentration (7.1 mmol/L) and inflammatory cytokine expressions (39.1%) in the LPS-stimulated RAW264.7 cells. A significant decrease was detected for ear thickness (16.9%), weight of lymph node (0.7 mg), IgE concentration (1.9 µg/mL), and epidermal thickness (31.8%) of the PA + MCE treated Tg mice. MCE treatment induced the decrease of luciferase signal derived from the IL-4 promoter and the recovery of the IL-4 downstream regulator cytokines. PA + MCE treated Tg mice showed decreasing infiltration of mast cells (42.5%), iNOS-mediated COX‐2 induction pathway, MAPK signalling pathway and inflammasome activation in the ear tissue. These findings provide the first evidence that MCE may have great potential to suppress chemical-induced skin inflammation through the suppression of IL-4 cytokine and the iNOS-mediated COX‐2 induction pathway, and activation of inflammasome. [ABSTRACT FROM AUTHOR]

To assess the role of CCR10 in innate lymphoid cells (ILCs) response in radiation-induced skin damage. CCR10+/− and CCR10−/− mice were treated with either a single dose of 5 Gy or 5 Gy everyday for 6 days with a total dose of 30 Gy with X-ray. ILCs from the skin were isolated and analyzed by flow cytometry 3 and 10 days after irradiation. A mouse model of radio-dermatitis was used to assess the skin damage 10 days after 6 × 5 Gy irradiation. Skin ILCs were decreased in both CCR10+/− and CCR10−/− mice 3 days after single irradiation (p <.05). However, the skin inflammation disappeared and ILCs returned to normal levels 10 days after single irradiation. ILCs of both genotypes were also decreased after 6 × 5 Gy irradiation, but the percentage of skin ILCs in CCR10−/− mice was lower than that in CCR10+/− mice 10 days after irradiation. The immunohistochemistry results showed that CCR10−/− mice had more severe skin inflammation than CCR10+/− mice. CCR10−/− mice had lower percentages of ILCs and more skin damage than CCR10+/− mice after irradiation. These findings indicate that skin ILCs are regulated by CCR10, which might be a potential target for reducing the radio-dermatitis. [ABSTRACT FROM AUTHOR]

Fish oil (FO) is a natural source of omega-3 fatty acids, with well-established beneficial effects in inflammatory diseases when FO is orally administered. This study investigated the effects of a topically applied FO preparation (FOP) on phenol-induced ear edema and evaluated the percutaneous penetration of FOP in ear tissue. After applying phenol, groups of mice received FOP on the ear. After 1 h, ear tissue was collected to determine the percent inhibition of edema, myeloperoxidase activity, and to perform photoacoustic spectroscopy (PAS). Treatment with FOP did not reduce edema, but reduced myeloperoxidase activity. The FOP decreased the area of bands that characterize inflamed tissue and penetrated into the tissue. These results indicated an inhibitory effect of FOP on leukocyte recruitment in phenol-induced ear edema. These data support the applicability of PAS as a non-destructive method for evaluating the inflammatory response, percutaneous penetration and antiinflammatory activity of compounds. [ABSTRACT FROM AUTHOR]

Oxidative stress and Th17 cytokines are important mediators of inflammation. Treatment with beta-adrenoceptor (ADRB) antagonists (beta-blockers) is associated with induction or aggravation of psoriasis-like skin inflammation, yet the underlying mechanisms are poorly understood. Herein, we identify lysosomotropic beta-blockers as critical inducers of IL23A in human monocyte-derived Langerhans-like cells under sterile-inflammatory conditions. Cytokine release was not mediated by cAMP, suggesting the involvement of ADRB-independent pathways. NFKB/NF-κB and MAPK14/p38 activation was required for propranolol-induced IL23A secretion whereas the NLRP3 inflammasome was dispensable. MAPK14 regulated recruitment of RELB to IL23A promoter regions. Without affecting the ubiquitin-proteasome pathway, propranolol increased lysosomal pH and induced a late-stage block in macroautophagy/autophagy. Propranolol specifically induced reactive oxygen species production, which was critical for IL23A secretion, in Langerhans-like cells. Our findings provide insight into a potentially crucial immunoregulatory mechanism in cutaneous dendritic cells that may explain how lysosomotropic drugs regulate inflammatory responses. ATF: activating transcription factor; DC: dendritic cell; ChIP: chromatin immunoprecipitation; gDNA: genomic DNA; IL: interleukin; LAMP1: lysosomal associated membrane protein 1; LC: Langerhans cell; LPS: lipopolysaccharide; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAPK: mitogen-activated protein kinase; MoDC: monocyte-derived DC; MoLC: monocyte-derived Langerhans-like cell; mtDNA: mitochondrial DNA; NAC: N-acetyl-L-cysteine; NLRP3: NLR family pyrin domain containing 3; PBMC: peripheral blood mononuclear cell; PI: propidium iodide; PYCARD/ASC: PYD and CARD domain containing; qRT-PCR: quantitative real-time PCR; ROS: reactive oxygen species; SQSTM1/p62: sequestosome 1; TLR: Toll-like receptor; TRAF6: TNF receptor associated factor 6; TNF: tumor necrosis factor; Ub: ubiquitin. [ABSTRACT FROM AUTHOR]

Chronic inflammatory skin disorders are frequently associated with impaired skin barrier function. Selective phosphodiesterase-4 (PDE4) inhibition constitutes an effective therapeutic strategy for the treatment of inflammatory skin diseases. We now report the pharmacological anti-inflammatory profile of DRM02, a novel pyrazolylbenzothiazole derivative with selective in vitro inhibitory activity toward PDE4 isoforms A, B and D. DRM02 treatment of cultured primary human and mouse epidermal keratinocytes interfered with pro-inflammatory cytokine production elicited by interleukin-1α and tumor necrosis factor-α. Similarly, DRM02 inhibited the production of pro-inflammatory cytokines by human peripheral blood mononuclear cells ex vivo and cultured THP-1 monocyte-like cells, with IC50 values of 0.6–14 µM. These anti-inflammatory properties of DRM02 were associated with dose-dependent repression of nuclear factor-κB (NF-κB) transcriptional activity. In skin inflammation in vivo mouse models, topically applied DRM02 inhibited the acute response to phorbol ester and induced Th2-type contact hypersensitivity reactivity. Further, DRM02 also decreased cutaneous clinical changes and expression of Th17 immune pathway cytokines in a mouse model of psoriasis evoked by repeated topical imiquimod application. Thus, the overall pharmacological profiling of the PDE4 inhibitor DRM02 has revealed its potential as a topical therapy for inflammatory skin disorders and restoration of skin homeostasis. [ABSTRACT FROM AUTHOR]

Psoriasis is an inflammatory, immune-mediated disease. Plexins are transmembrane proteins that are involved in immune system regulation and inflammation. This work aimed to investigate the immunohistochemical expression of Plexin-B2 in plaque psoriasis in both lesional and perilesional skin. This case‐control study included 30 patients with psoriasis vulgaris in comparison with 20 age- and sex‐matched apparently healthy persons. We used the Psoriasis Area and Severity Index (PASI) score to evaluate psoriasis severity. Biopsies from 30 lesional, 30 perilesional, and 20 control-skin patients were subjected to histopathological and immunohistochemical evaluations of Plexin-B2. There was significant stepwise overexpression of Plexin-B2 in proliferating keratinocytes from controls (66 ± 31.02) to perilesional (116 ± 41.95) and lesional (159.7 ± 63.05) skin (P <.001). Also, Plexin-B2 showed significant overexpression in dermal inflammatory cells of lesional psoriatic skin (153.67 ± 72.71) when compared to controls skin (25.71 ± 11.34) (P <.001). There was a significant positive correlation between Plexin-B2 expression and psoriasis severity (r = 0.557; P <.001). Plexin-B2 could promote skin inflammation, as well as keratinocyte proliferation in psoriasis vulgaris; therefore, it may be used as a targeted therapy for psoriasis treatment. [ABSTRACT FROM AUTHOR]

The current application was aimed to evaluate the therapeutic potential of selenium and ketoconazole nanoparticles loaded hyaluronic acid gel against seborrhoeic dermatitis (SD). Amalgamation of ketoconazole (antifungal medication) and selenium (pro-oxidant) in an optimized formulation setting may help in the treatment of SD. In this study, selenium and ketoconazole nanoparticles loaded hyaluronic acid (HA) hydrogel was prepared by mechanical mixing followed by sonication. Results of the optimized batch showed a mean particle size of 121 ± 12 nm for ketoconazole and 51 ± 7 nm for selenium. SEM and TEM study revealed the prepared nanoparticles are of nanoscale dimension, with smooth spherical outline. Finally, the optimized nanoparticles were incorporated into HA hydrogel. Hydrogel exhibits desirable physical, mechanical and rheological characteristics appropriate for topical application. Optimized gel formulation exhibited an enhanced permeability with better antifungal, and anti-inflammatory activities, compared with the plain drug suspension. The optimized hydrogel with ketoconazole and selenium in nanotemplate could offer a potential strategy for the treatment of SD. [ABSTRACT FROM AUTHOR]

A new coordination polymer of [Zn(bdc)(bimb)](DMF)(H2O)2 (1, H2bdc = 1,4-dicarboxybenzene, bimb = 6,6'-bis(1H-benzo[d]imidazol-2-yl)-2,2'-bipyridine) has been successfully synthesized by reaction of Zn(NO3)2·6H2O, H2bdc and bimb in a mixed solvent of DMF and water at 80 °C for three days. Furthermore, an ultrasound synthesis technique has been implemented to reduce the particle size of the complex 1 to generate nanoscale 1 (denoted as nano 1). We constructed the dermatitis mice model with DNFB-induction. The scoring index of the AD lesion in mice was evaluated after nano 1 treatment and the ELISA was used to measure the level of inflammatory medium after nano 1 exposure. [ABSTRACT FROM AUTHOR]

Eugenol is a phytochemical present in aromatic plants has generated considerable interest in the pharmaceutical industries mainly in cosmetics. A series of eugenol esters (ST1-ST7) and chloro eugenol (ST8) have been synthesized. The structures of newly synthesized compounds were confirmed by ¹H and 13C NMR and mass spectrometry. In an effort to evaluate the pharmacological activity of eugenol derivatives, we explored its anti-inflammatory potential against skin inflammation using in-vitro and in-vivo bioassay. Synthesized derivatives significantly inhibited the production of pro-inflammatory cytokines against LPS-induced inflammation in macrophages. Among all derivatives, ST8 [Chloroeugenol (6-chloro, 2-methoxy-4-(prop-2-en-1-yl)-phenol)] exhibited most potent anti-inflammatory activity without any cytotoxic effect. We have further evaluated the efficacy and safety in in-vivo condition. ST8 exhibited significant anti-inflammatory activity against TPA-induced skin inflammation without any skin irritation effect on experimental animals. These findings suggested that ST8 may be a useful therapeutic candidate for the treatment of skin inflammation. [ABSTRACT FROM AUTHOR]