Severe Skin Lesions Research Articles

Indigo alleviates psoriasis through the AhR/NF-κB signaling pathway: an in vitro and in vivo study.

Psoriasis is a chronic inflammatory skin disease. A strong association between the AhR/ NFκB axis and the inflammatory response in psoriasis. Indigo (IDG) has demonstrated significant anti-inflammatory properties. This study aimed to assess the anti-psoriatic efficacy of IDG while investigating the underlying mechanisms involved. In the in vitro experiments, cell viability was assessed using the CCK-8. qRT-PCR was employed to measure the mRNA levels of NF-κB, TNF-α, IL-1β, AhR, and CYP1A1. Western blotting was conducted to examine alterations in cytoplasmic and nuclear AhR protein levels. Additionally, an IDG nanoemulsion (NE) cream was prepared for the in vivo experiments. A psoriasis-like skin lesion mice model was induced using IMQ (62.5 mg/day for 7 days). The severity of psoriasis was evaluated using PASI, and skin lesions were scored while epidermal thickness was assessed via HE staining. The expression of inflammatory markers, including IL-6, IL-13, IL-17A, MCP-1, and TNF-α, was detected in skin lesions using Luminex. The levels of CYP1A1, p65, and p-p65 proteins were determined by Western blotting. LPS stimulation significantly elevated TNF-α, IL-6, and NF-κB mRNA levels, which were notably reduced by IDG treatment. Additionally, IDG significantly enhanced the expression of AhR and CYP1A1 mRNA. Further investigation revealed that IDG facilitated AhR translocation from the cytoplasm to the nucleus. In the IMQ-induced psoriasis-like mouse model, IDG NE substantially ameliorated the severity of skin lesions. Moreover, IDG NE treatment reduced the upregulation of inflammatory cytokines such as IL-6, IL-17A, MCP-1, and TNF-α in IMQ-induced skin lesions. It was also observed that IDG NE treatment increased CYP1A1 protein expression while inhibiting p65 and p-p65 protein expression. IDG emerges as a promising treatment for psoriasis, demonstrating effective therapeutic outcomes. Its mechanism of action is likely linked to the modulation of the AhR/NFκB signaling pathway.

Eosinophilic dermatosis of haematologic malignancy treated with ibrutinib: A case report

AbstractEosinophilic dermatosis of haematologic malignancy is an infrequent skin disorder characterised by severe pruritus and skin lesions resembling arthropod bites. It primarily affects individuals with underlying haematological conditions, most commonly chronic lymphocytic leukaemia (CLL). While it does not correlate with a worse prognosis for the haematological disease itself, it significantly impacts patients' quality of life due to the distressing pruritus and recurring nature. Clinical presentation typically shows erythematous papules resembling arthropod bites, with less frequent occurrences of urticarial plaques or bullous lesions. Histologically, an intense and polymorphous inflammatory infiltrate is found both in the superficial and deep dermis, marked by an abundance of eosinophils and the absence of atypical cells. Treatment of this disease remains uncertain, with corticosteroids often being the only effective therapy. Here, we present the case of an 80‐year‐old patient with a history of CLL, who experienced a widespread, itchy eruption of papules and plaques over 2 months. Despite various therapeutic attempts, the lesions only responded to high‐dose corticosteroids. Following the initiation of ibrutinib at a daily dose of 420 mg, both the skin lesions and pruritus resolved within 3 months. Ibrutinib, a tyrosine kinase inhibitor, is approved as a first‐line treatment for CLL. However, its potential as a remedy for refractory eosinophilic dermatosis has not been reported thus far.

Changes in cytokine profile as a criterion for severity prediction of skin toxicity in cancer patients receiving epidermal growth factor receptor inhibitors

BACKGROUND: Globally, colorectal cancer is the third most diagnosed cancer with an increased incidence of 1.93 million cases in 2020 according to World Health Organization. Approximately one quarter of the initial manifestations of colorectal cancer are metastatic, and 40–50% of individuals with early-stage disease eventually develop metastatic colorectal cancer (mCRC). Targeted drugs, which include epidermal growth factor receptor inhibitors (EGFRi), are a frequent choice in the therapy of metastatic colorectal cancer. Clinical observations and in vivo studies have established a significant association between the administration of EGFRi drugs and skin inflammation, particularly acute in the first 3 months. However, the role of proinflammatory cytokines in the formation of severe skin lesions has not been definitively studied. Here we present clinical evidence of the involvement of a few cytokines in the formation of the pathologic cascade of reactions during EGFR blockade on keratinocyte membranes. AIM: Evaluation of changes in cytokine profile parameters based on the MILLIPLEX Analyte MAP panel to identify predictors of the severity of unwanted skin toxicity associated with epidermal growth factor receptor inhibition. MATERIALS AND METHODS: Blood serum samples from 81 patients aged 18–80 years who were taking EGFRi for oncologic disease and had adverse dermatologic reactions of severity 2 or more were analyzed. The data were analyzed using SPSS software and R 4.3.1 programming language and tidyverse, rstatix packages. Detected changes with p 0.05 were analyzed considering subgroup analysis on the basis of selected cutaneous toxicity severity degrees based on the criteria developed by the US National Cancer Institute NCI-CTC v. 4. RESULTS: Blocking of EGF receptor inhibits the expression and release of vascular endothelial growth factor (VEGF), which is the main inducer of vascular proliferation, the consequence of which is inflammation of vascular endothelium of skin capillaries. Significant increase of IFN-γ and decrease of IFN-α2 level was found in patients with manifestations of skin toxicity of 2 and more severity degree. Also, a significant criterion of severity of the skin process was an increase in the level of TNF-α. At such dissociation there is induction of STING protein (interferon gene stimulator) and increase of TNF-β production that, in its turn, leads to increase of concentration of proinflammatory cytokines G-CSF, GM-CSF, IFN-α2, IFN-γ, IL-15, IL-17A, IL-1β, IL-3, IL-6, IL-8, IP-10, TNF-α, TGF-α, IL-9. This contributes not only to the maintenance of tissue inflammation, but also to the formation of a vicious circle leading to an increase in the severity of class-mediated inflammatory response against the background of further EGFRi administration. CONCLUSION: Determination of predictors of severity of adverse dermatologic reactions is extremely important for predicting the development of severity and further personalized tactics for correction of adverse events.

Human infection with IsrRAPXV, a novel zoonotic bat-derived poxvirus.

Bats are recognized as the natural reservoir of several zoonotic viruses that pose a threat to public health worldwide. In our recent reports we describe the identification of a novel poxvirus, IsrRAPXV, in Egyptian fruit bats. This poxvirus is associated with high morbidity and mortality in bats. Herein, we describe the identification of poxvirus in a female patient hospitalized with systemic symptoms and severe painful skin lesions on her hands. We performed qPCR, whole genome sequencing and phylogenetic analysis to identify and characterize this poxvirus as the etiologic agent. The patient interacted with wounded and sick bats as a volunteer in a bat shelter run by the Israel bat sanctuary organization. Samples collected from the patient's skin lesions were positive for the presence of IsrRAPXV by PCR. Additionally, phylogenetic analysis showed that this virus is identical to IsrRAPXV originally described by us as the causative agent of skin lesions in fruit bats. Our finding suggest that IsrRAPXV is zoonotic and therefore veterinarians and volunteers working in bats shelter should meticulously follow the guidelines of working with bats and use required personal protective equipment.

Predicting psoriasis severity using machine learning: A systematic review.

In dermatology, the applications of machine learning (ML), an artificial intelligence (AI) subset that enables machines to learn from experience, have progressed past the diagnosis and classification of skin lesions. A lack of systematic reviews exists to explore the role of ML in predicting the severity of psoriasis. This systematic review aims to identify and summarize the existing literature on predicting psoriasis severity using ML algorithms and identify gaps in current clinical applications of these tools. OVID Embase, OVID MEDLINE, ACM Digital Library, Scopus, and IEEE Xplore were searched from inception to August, 2024. A total of 30 articles met our inclusion criteria and were included in this review. One article used serum biomarkers, while the remaining 29 used image-based models. The most common severity assessment score employed by these ML models was the Psoriasis Area Severity Index score, followed by Body Surface Area, with fifteen and five articles, respectively. The small size and heterogeneity of the existing literature are the primary limitations of this review. Progress in assessing skin lesion severity through ML in dermatology has advanced, but prospective clinical applications remain limited. ML and AI promise to improve psoriasis management, especially in non-image-based applications requiring further exploration. Large-scale prospective trials using diverse image datasets are necessary to evaluate and predict the clinical value of these predictive AI models.

Evaluation of comfort gloves made of semipermeable and textile materials in patients with hand dermatoses: Results of a controlled multicenter intervention study (ProTection II).

Comfort gloves are used in the management of hand dermatoses. To compare the acceptance and tolerability of comfort gloves made of different materials in patients with hand dermatoses and their effects on skin lesions. In a prospective multicenter study, 284 patients with hand dermatoses were invited to wear either a cotton glove (COT) or a semipermeable Sympatex glove underneath a cotton glove (SYM/COT) for two subsequent phases of 19 consecutive nights each. A total of 88 controls were asked not to wear any comfort gloves overnight. The severity of skin lesions over time was examined. Questionnaires were used to assess health-related quality of life (HRQoL) and acceptance and tolerability of the gloves. The hand dermatoses improved in all groups. No substantial intergroup differences regarding severity and HRQoL were observed. SYM/COT received better ratings regarding climate conditions and tactility while COT showed superiority in fit, wearing comfort, and practicality. We confirmed that SYM/COT and COT are well tolerated and accepted suggesting that SYM/COT is a good alternative for COT as comfort gloves in patients with hand dermatoses. Individual requirements, needs, and preferences may direct the material choice.

Effects of Herd Establishment Time and Structure on Group-on-Individual Aggression Intensity in Farm Pigs.

Aggression in farm animals affects welfare. Although one-on-one aggression was studied, group-on-individual aggression remains unresolved. This study aimed to examine how herd establishment times and structures influence aggression intensity (AI) of herds towards unfamiliar pigs. Six groups of pigs were established, with a new pig added every three days. AI was measured by skin lesion severity on the new pigs. A parabolic model based on the Levenberg-Marquardt algorithm and conjoint analysis identified factors influencing AI. Results show AI was not significantly affected by herd size but was significantly influenced by the number of pens (p < 0.01). AI showed a significant association with elevated time (T) since the establishment of the herd in six pig herds (Kendall's tau-τ = 0.976, p < 0.001). The effect of T on the AI became stronger as T increased, which was consistently validated in six pig herds. Furthermore, the interaction effect indicates a significant difference in AI between herds formed with two pens and those with more than two pens when T ≤ 12 (p < 0.05). However, as T increased beyond 12, the number of pens used to form the herd did not significantly affect AI. These findings highlight the complex interactions between herd establishment time and structural composition in shaping aggression intensity towards unfamiliar pigs.

Targeting dendritic cell activation: the therapeutic impact of paeoniflorin in cortosteroid-dependent dermatitis management.

This study investigates the mechanism through which paeoniflorin inhibits TSLP expression to regulate dendritic cell activation in corticosteroid-dependent dermatitis treatment. Utilizing databases like TCMSP, we identified paeoniflorin's components, targets, and constructed networks. Molecular docking and gene enrichment analysis helped pinpoint key targets and pathways affected by paeoniflorin. In vitro and in vivo models were used to study CD80, CD86, cytokines, T-cell activation, skin lesions, histopathological changes, TSLP, CD80, and CD86 expression. Our study revealed paeoniflorin's active constituent targeting IL-6 in corticosteroid-dependent dermatitis. In vitro experiments demonstrated reduced TSLP expression, CD80, CD86, and cytokine secretion post-paeoniflorin treatment. In vivo, paeoniflorin significantly decreased skin lesion severity, cytokine levels, TSLP, CD80, and CD86 expression. The study highlights paeoniflorin's efficacy in inhibiting TSLP expression and suppressing dendritic cell activation in corticosteroid-dependent dermatitis, suggesting its potential as a therapeutic intervention. Additionally, it offers insights into the complex molecular mechanisms underlying paeoniflorin's anti-inflammatory properties in treating corticosteroid-dependent dermatitis.

A two-center randomized controlled trial of a repairing mask as an adjunctive treatment for mild to moderate rosacea.

To investigate the efficacy and safety of a repairing mask as an adjunctive treatment for skin barrier maintenance of mild to moderate rosacea. Patients with rosacea were recruited in this dual center randomized controlled trial from November 2019 to December 2021. A total of 64 patients were included and randomized into two groups at a ratio of 3:1 into a mask group (n = 47) and a control group (n = 17). Patients in the mask group received treatment with Dr. Yu Centella asiatica repairing facial mask three times weekly for a duration of 6 weeks. All participants were instructed to continue their regimen of 50 mg oral minocycline twice daily and to apply Dr. Yu Intensive Hydrating Soft Cream twice daily. The primary endpoint of this study was the Investigator Global Assessment (IGA) score. A total of 54 patients completed this trial, with 41 in the mask group and 13 in the control group. After using this facial mask for 3 and 6 weeks, the IGA, facial skin dryness, facial flushing, and severity of skin lesion in the mask group showed significantly improvement (p < 0.05). Moreover, the change in the delta degree of skin flushing was significantly higher than that in the control group (p = 0.037). Throughout the study, no adverse events were reported in either group of participants. The Dr. Yu Centella asiatica repairing facial mask, as an adjunctive treatment of rosacea, appears to effectively repair and protect the skin barrier, alleviate cutaneous symptoms of rosacea, and is both efficacious and safe for patient use.

Efficacy and safety of therapies related to acupuncture for acute herpes zoster: A PRISMA systematic review and network meta-analysis.

Herpes zoster (HZ) is mainly characterized by intense pain and severe skin lesions, particularly during the acute phase, which seriously affects the patient's quality of life. Acupuncture is a widely used and effective treatment for HZ. However, there are many types of acupuncture, which have different curative efficacy. This study employed a network meta-analysis (NMA) to assess and rank the clinical efficacy of different acupuncture therapies. The database of Cochrane Library, Web of Science, PubMed, MEDLINE, Embase, China National Knowledge Infrastructure (CNKI), Chinese BioMedical Database, VIP Database, and Wanfang Database were searched from inception to December 31, 2022 to identify eligible randomized controlled trials (RCTs) of acupuncture related therapies in the treatment of acute HZ. The outcome indicators measured were visual analogue scale (VAS), date of cessation of herpes increase (DCHI), effective rate (ER), postherpetic neuralgia (PHN), and adverse events (AEs). Bayesian network meta-analyses were performed using the GeMTC package (version 1.0-1) and R software (version 4.2.3). A total of 59 RCTs with 3930 patients were included. The results of this NMA were as follows: compared with pharmacotherapy, electroacupuncture (EA) + pricking and cupping (PC) shown the best efficacy to improve VAS score and reduce DCHI. In terms of ER, EA + fire needle (FN) had the highest results of probability ranking. PC was more effective in reducing the incidence of PHN. Furthermore, this study shown that the incidence of AEs associated with acupuncture-related therapies was acceptable. This study indicated that therapies related to acupuncture were both effective and safe in treating acute HZ, and could significantly reduce patients' symptoms such as pain and skin lesions with fewer adverse events. Clinically, the selection of the appropriate therapy should be based on practical considerations. However, due to the limitations of this study, more high-quality trials are required to evaluate the efficacy and safety of acupuncture-related therapy for the treatment of acute HZ.

Effectiveness of Shel (purgation) with Tshawa-suum (herbal medicine paste) on Langshu: an observational study

Introduction: Skin disease is one of the most common diseases treated at the National Traditional Medicine Hospital in Bhutan. Since the establishment of Inpatient Department in 2018, Shel (purgation) with Tshawa-suum paste application is used as the treatment for Langshu skin disorders. This study was conducted to assess the effectiveness of Shel with Tshawa-suum paste on Langshu. Methods: It was an observational study conducted among patients admitted with Langshu at the National Traditional Medicine Hospital, Thimphu, Bhutan. A structured questionnaire was used to collect the sociodemographic details of the patients and Eczema Area and Severity Index (EASI) score was used to assess the severity and extent of skin lesions. Patients were assessed at three time points: before the treatment, after 7 days of treatment and on day 30 when the patients reported for follow-up care. Results: The mean age of the patients (±SD) was 38.81 (±17.63) years and 57.14% were male. The majority of the patients were farmers (42.43%). At baseline, there were 6 patients with very severe Langshu lesion, 44 with severe and 20 with moderate condition. By day 30, only 3 had severe, 34 had mild and 33 had moderate condition. The study found statistically significant reduction in the mean EASI score from 30.12 on Day 0 to 17.25 on Day 7 and 8.46 on Day 30 (p &lt; 0.001). Conclusions: This study shows that the use of Shel with Tshawa-suum paste resulted in decrease in size and severity of Langshu skin lesions.

Low levels of chicken body louse (Menacanthus stramineus) infestations affect chicken welfare in a cage-free housing system

BackgroundThe chicken body louse is an obligate ectoparasite of domestic chickens. Chicken body lice feed on feathers, and infestation with this louse is linked to decreases in egg production, hen weight, and feed conversion efficiency. However, it is unknown how chicken body lice impact egg-laying chickens in cage-free environments. Welfare and behavior metrics were collected from flocks of egg-laying chickens either infested with chicken body lice or left uninfested.MethodsIn two trials, two flocks of cage-free commercial egg-laying chickens were infested with chicken body lice or maintained as uninfested controls. At three timepoints, behavior and welfare of all chickens was measured. On-animal sensors were used to quantify pecking, preening, and dustbathing behavior. Other animal-based welfare metrics included recording comb wounds and skin lesions.ResultsBirds infested with chicken body lice exhibited significantly more preening behaviors than uninfested birds, even at low louse levels. Moderate or severe skin lesions were detected on birds that were moderately infested with chicken body lice while skin lesions were never detected on uninfested birds.ConclusionsThe welfare of chickens was impacted by the chicken body louse, a chewing louse that primarily feather feeds. Evidence of skin lesions on infested birds suggests that lice may cause more damage to birds than previously thought, and further evaluation of louse economic damage is necessary.Graphical

240 Impact of structural traits on semen collection training and lesion characteristics in Duroc boars

Abstract Rising incidence of lameness in boar stud contributes to increased morbidity and mortality, affecting longevity and likely semen output. Lameness is not unique to the boar and affects the swine industry as a whole, contributing to millions of dollars in losses every year. Hypothesized contributors to lameness incidence are body, feet, and leg structure. In the boar stud lameness affects the ability of the boar to mount the dummy and can cause pain-related stress which can impact reproductive function. Lameness is also often accompanied by skin lesions or wounds which can lead to infection and further semen production. Our objectives were to evaluate the relationship between boar structural traits and semen collection training traits and determine if structural traits influence presence and severity of skin lesions. Structural traits of developing Duroc boars (n = 82; 190 ± 10.3 d of age) were assessed at arrival to the stud and 6 wk later. Structural traits assessed included front and rear leg set, foot shape, chest width, and hip width (1 = poor; 5 = ideal). An overall structure score for each boar was determined by adding all structural trait scores. Lesions were assessed on a zero to three scale (0 = no lesions; 3 = severe lesions). Based on overall structure score, boars were categorized into one of three groups (poor, intermediate, or ideal) to determine if structural traits affected the presence and severity of lesions. All boars were subjected to semen collection training 1 wk after arriving at the stud and considered trained when successful mounting and ejaculation occurred. Pearson’s correlation coefficients were determined between total structure score, lesion severity, and semen collection training characteristics. The GLIMMIX procedure of SAS was used to assess lesion presence differences between structure groups. Structure score and lesion severity were not significantly correlated (-0.017; P = 0.91) with number of attempts to train, time to mount, or time to collection of ejaculates. Upon arrival at the stud, boars in the poor structure group displayed a greater (P &amp;lt; 0.01) incidence of lesions than intermediate and Ideal structure groups but did not have greater lesion severity (P = 0.74). After 6 wk in the boar stud, there were no differences (P = 0.83) in lesion presence or severity between structure groups, suggesting the lameness issues are more likely caused by housing environment or other factors than structural traits.

Indexes of skin activity and damage in patients with systemic lupus erythematosus – CLASI and R-CLASI

Introduction. Cutaneous Lupus Disease Area and Severity Index (CLASI) and its modified version, the Revised Cutaneous Lupus Erythematosus Disease Areas and Severity Index (R-CLASI) are tools for quantifying skin and mucosal lesions in patients with both cutaneous lupus erythematosus and its systemic variant. Evaluation of the scales of activity and skin damage in systemic lupus erythematosus (SLE) is associated with the need to stratify their quantitative characteristics. The Cutaneous Lupus Disease Area and Severity Index (CLASI) and its modified version the Revised Cutaneous Lupus Erythematosus Disease Area and Severity Index (R-CLASI) are a tool for quantifying skin and mucosal lesions in patients with both cutaneous lupus erythematosus (CLE) and its system version.Objective. To validate the indexes of objective assessment of skin activity and damage CLASI and R-CLASI in the Russian cohort of patients with systemic lupus erythematosus and compare it with dermatological assessments of the quality of life.Material and methods. The study included 55 patients with SLE with various types of skin and mucosal lesions, the median age was 30.0 [26.0; 40.0] years, the duration of the disease was 7.0 [3.0; 14.0] years. To assess the active (reversible) lesion and irreversible skin damage, the CLASI and R-CLASI indexes were used, for the general assessment of activity and damage in SLE, the SLEDAI-2K and SLICC/ACR DI were used.Results. The most common variant of skin lesions in patients with SLE is acute cutaneous lupus erythematosus (ACLE) – 45%, as well as alopecia, which occurs in 62% of cases. The median activity index for CLASI was 5.0 [2.0; 11.0], and R-CLASI was 7.0 [3.0; 18.0]; the median damage index for CLASI was 5.0 [2.0; 11.0], and R-CLASI was 2.0 [0.0; 7.0]. A significant relationship was revealed between the medians of CLASI and R-CLASI scores depending on the degree of activity according to SLEDAI-2K (Systemic Lupus Erythematosus Disease Activity Index) and the damage Index (DI) in SLE (SLICC/ACR DI, Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index) when recalculating these indexes only for skin and mucous lesions. According to the ROC analysis, the CLASI and R-CLASI skin activity and damage indices showed high sensitivity (CLASI activity index – 98%, R-CLASI – 93%, CLASI and R-CLASI damage index – 91%) and specificity (CLASI activity index – 64%, R-CLASI – 71%, CLASI and R-CLASI damage index – 86%).Conclusion. To assess the severity of skin and mucosal lesions in patients with SLE in the Russian Federation, it is reasonable to use the CLASI and R-CLASI indices. The CLASI and R-CLASI indices reflect the level of activity and severity of skin lesions, with higher values of these indices indicating more severe skin lesions and a significant impact on the overall well-being of SLE patients. Patients with high values of these indices often experience feelings of embarrassment, discomfort, difficulty in performing daily tasks, and limitations in social life. To assess the severity of skin and mucous lesions in patients with SLE in the Russian Federation, it is advisable to use the CLASI and R-CLASI indexes.

Severity Assessment and IL-5 Evaluation after Immunotherapy in Atopic Dermatitis Mice

Background: The effectiveness of immunotherapy in atopic dermatitis (AD) has been debated for many years. Immunotherapy suppresses Th2 cytokines, such as IL-5, which play a crucial role in the pathogenesis of AD. This study assessed the effect of immunotherapy on severity and IL-5 expression in AD mice.Methods: Male BALB/c mice were separated into three groups. The mice were sensitized with Dermatophagoides pteronyssinus allergen for seven days, except the mice in control group. The house dust mite (HDM) immunotherapy was injected subcutaneously every 3 days for 1.5 months with increasing doses (0.1, 1, 10, 100 μg in 100 μL PBS) every 4 injections. The mice in AD model and control group received placebo injections. Following immunotherapy, the mice were exposed to HDM allergen patch two times with 2 weeks interval in between. The mice were evaluated for severity score as the clinical marker and IL-5 expression with semiquantitative method as the histological marker.Results: The evaluation of severity score from two independent researchers showed a substantial agreement (Cohen’s kappa 0.613, p &lt;0.001). The severity score of the immunotherapy group was significantly lower than the AD model group, while both immunotherapy and AD model group had significantly higher score than control group. IL-5 expression in the immunotherapy group was lower than the AD model group and slightly higher than control group. The mean difference between groups was not significant.Conclusion: The severity of skin lesion and IL-5 expression in AD mice receiving immunotherapy were lower than AD model group.Keywords: Atopic dermatitis; BALB/c mice; House dust mites; IL-5, Skin severity score; Tropical disease

Interleukin 33 supports squamous cell carcinoma growth via a dual effect on tumour proliferation, migration and invasion, and T cell activation

Interleukin (IL)-33 is an important cytokine in the tumour microenvironment; it is known to promote the growth and metastasis of solid cancers, such as gastric, colorectal, ovarian and breast cancer. Our group demonstrated that the IL-33/ST2 pathway enhances the development of squamous cell carcinoma (SCC). Conversely, other researchers have reported that IL-33 inhibits tumour progression. In addition, the crosstalk between IL-33, cancer cells and immune cells in SCC remains unknown. The aim of this study was to investigate the effect of IL-33 on the biology of head and neck SCC lines and to evaluate the impact of IL-33 neutralisation on the T cell response in a preclinical model of SCC. First, we identified epithelial and peritumoural cells as a major local source of IL-33 in human SCC samples. Next, in vitro experiments demonstrated that the addition of IL-33 significantly increased the proliferative index, motility and invasiveness of SCC-25 cells, and downregulated MYC gene expression in SCC cell lines. Finally, IL-33 blockade significantly delayed SCC growth and led to a marked decrease in the severity of skin lesions. Importantly, anti-IL-33 monoclonal antibody therapy increase the percentage of CD4+IFNγ+ T cells and decreased CD4+ and CD8+ T cells secreting IL-4 in tumour-draining lymph nodes. Together, these data suggest that the IL-33/ST2 pathway may be involved in the crosstalk between the tumour and immune cells by modulating the phenotype of head and neck SCC and T cell activity. IL-33 neutralisation may offer a novel therapeutic strategy for SCC.

Image-based remote evaluation of PASI scores with psoriasis by the YOLO-v4 algorithm.

As a chronic relapsing disease, psoriasis is characterized by widespread skin lesions. The Psoriasis Area and Severity Index (PASI) is the most frequently utilized tool for evaluating the severity of psoriasis in clinical practice. Nevertheless, long-term monitoring and precise evaluation pose difficulties for dermatologists and patients, which is time-consuming, subjective and prone to evaluation bias. To develop a deep learning system with high accuracy and speed to assist PASI evaluation, we collected 2657 high-quality images from 1486 psoriasis patients, and images were segmented and annotated. Then, we utilized the YOLO-v4 algorithm to establish the model via four modules, we also conducted a human-computer comparison through quadratic weighted Kappa (QWK) coefficients and intra-class correlation coefficients (ICC). The YOLO-v4 algorithm was selected for model training and optimization compared with the YOLOv3, RetinaNet, EfficientDet and Faster_rcnn. The model evaluation results of mean average precision (mAP) for various lesion features were as follows: erythema, mAP = 0.903; scale, mAP = 0.908; and induration, mAP = 0.882. In addition, the results of human-computer comparison also showed a median consistency for the skin lesion severity and an excellent consistency for the area and PASI score. Finally, an intelligent PASI app was established for remote disease assessment and course management, with a pleasurable agreement with dermatologists. Taken together, we proposed an intelligent PASI app based on the image YOLO-v4 algorithm that can assist dermatologists in long-term and objective PASI scoring, shedding light on similar clinical assessments that can be assisted by computers in a time-saving and objective manner.

Real world insights for psoriasis: the association of severity of skin lesions with work productivity, medical consumption costs and quality of life

Background Psoriasis is a prevalent, chronic skin disease with a potential impact on work productivity, medical consumption costs, and quality of life. The influence of the extent of skin lesions on these outcomes is not well known. Objective We determined associations of self-reported skin lesions with self-reported work productivity, medical consumption costs, and health-related quality of life in respondents with psoriasis. Methods In this cross-sectional study, we included respondents with self-reported psoriasis in the Netherlands in an online questionnaire. We assessed the self-reported percentage body surface area (BSA) of psoriasis lesions. We used validated instruments to assess work productivity (WPAI-PsO), medical consumption costs (iMCQ), and health-related quality of life (EQ-5D-5L and the DLQI). We used ordinal logistic regression to associate BSA categories >1% versus 0-1% with outcomes adjusted for multiple confounders. Results We included 501 respondents with a mean age of 43 ± 12 years; 64% were men. Median BSA was 2% (interquartile range 1–5%). A higher BSA was associated with higher overall work impairment due to psoriasis (common odds ratio [cOR] 2.44, 95% confidence interval [CI] 1.40–4.29; n = 205), higher medical consumption costs (cOR 2.06, 95% CI 1.45–2.94) and lower health-related quality of life. Associations were strongest with a BSA cutoff of 0% or 1% compared to 2% or higher categories. Discussion In our study, having few to no lesions in psoriasis was associated with lower overall work impairment due to psoriasis, lower medical consumption costs, and higher health-related quality of life.

Magnolol Reduces Atopic Dermatitis-like Symptoms in BALB/c Mice.

In traditional Korean medicines, Magnolia officinalis is commonly included for the remedy of atopic dermatitis, and magnolol is a major constituent of Magnolia officinalis. Its pharmacological effects include anti-inflammatory, hepatoprotective, and antioxidant effects. Using BALB/c mice repeatedly exposed to 1-chloro-2,4-dinitrobenzene (DNCB), magnolol was evaluated in atopic dermatitis-like lesions. Administration of magnolol (10 mg/kg, intraperitoneal injection) markedly relieved the skin lesion severity including cracking, edema, erythema, and excoriation, and significantly inhibited the increase in IgE levels in the peripheral blood. A DNCB-induced increase in mast cell accumulation in atopic dermatitis skin lesions was reversed by magnolol administration, as well as a rise in expression levels of pro-inflammatory Th2/Th17/Th1 cytokines' (IL-4, IL-13, IL-17A, IFN-γ, IL-12A, TARC, IL-8, and IL-6) mRNAs in the lymph nodes and skin (n = 5 per group). In lymph nodes, magnolol reversed DNCB's increase in CD4+RORγt+ Th17 cell fraction and decrease in CD4+FoxP3+ regulatory T cell fraction. The results also showed that magnolol suppressed T cell differentiation into Th17 and Th2 cells, but not Th1 cells. Magnolol suppresses atopic dermatitis-like responses in the lymph nodes and skin, suggesting that it may be feasible to use it as a treatment for atopic dermatitis through its suppression of Th2/Th17 differentiation.

Characterisation, prevalence and severity of skin lesions caused by ophidiomycosis in a population of wild snakes

Ophidiomycosis is an emerging infectious disease affecting wild snakes in the Northern Hemisphere. Recently confirmed in Great Britain, the prevalence, severity and significance of ophidiomycosis has yet to be characterised in free-living snakes at a population level in Europe. Therefore, a population of barred grass snakes (Natrix helvetica) in eastern England was monitored for three seasons (May 2019 to October 2021), to investigate the prevalence (25.5%; 191/750 snakes) and severity of skin lesions and their aetiology. The most frequently observed skin lesion characteristics were changes in scale colour, crusting, and scale margin erosion. The majority of such lesions (96.9%; 185/191 snakes) was observed on the ventral surface along the length of the body. The severity of skin lesions was considered mild in more than half of the cases (53.1%; 98/191 snakes). Predominantly, skin lesions were observed in adult snakes (72.8%; 139/191 snakes). Combined histological examinations and qPCR tests of skin lesions from N. helvetica sloughs and/or carcasses confirmed a diagnosis of ophidiomycosis. Further targeted surveillance, supported by molecular and histological examinations to confirm skin lesion aetiology, is required to determine the extent to which our findings reflect the occurrence of ophidiomycosis in populations within wider landscapes.