Xylooligosaccharides Alleviate Inflammatory Dermatoses and Related Depression-Like Behaviors in Atopic Dermatitis Mice Induced by 2,4-Dinitrofluorobenzene

Objective:To investigate the influence of xylooligosaccharides on skin inflammation,behavioral characteristics,neurotransmitters,and gut flora in a mouse model of atopic dermatitis(AD)induced by 2,4-dinitrofluorobenzene(DNFB).Methods:The AD mouse model was created by administration of DNFB for 14 consecutive days.The scoring atopic dermatitis index,enzyme-linked immunosorbent assay(ELISA),histopathology,and immunohistochemical analyses were used to assess inflammation and depression-like behaviors.Furthermore,high-throughput 16S rRNA gene sequencing was used to determine the composition of fecal microbiota.Results:Xylooligosaccharides treatment reduced the number of scratches and skin thickness,mast cell infiltration and the levels of immunoglobulin(Ig)E and T-helper cytokines compared with the AD model group.Meanwhile,xylooligosaccharides treatment reduced the immobility time of mice in the forced swimming test and increased the total movement distance and movement distance in the center area in the open-field test.Furthermore,5-hydroxytryptamine and dopamine expression in the brain was increased following xylooligosaccharides treatment.Using network pharmacology,Gene Ontology analysis showed that the targets were mainly enriched in phosphatase binding and the regulation of leukocyte differentiation,which ameliorated AD mainly through the hypoxia inducible factor-1 and phosphatidylinositide 3-kinase-protein kinase B pathways.16S rRNA gene sequencing,diversity indices,and gut microbial taxonomic composition analysis showed DNFB-induced changes in intestinal microbiota diversity in AD mice.Comparative analysis indicated that xylooligosaccharides intake improved the gut microbiome by dramatically enhancing the concentration of Lactobacillus while decreasing the concentration of Bacteroides in mice.Conclusion:Xylooligosaccharides reduce inflammatory dermatosis and related depression-like behaviors via regulating intestinal homeostasis,having medicinal value as a nutritional and functional ingredient.

Preparation of anti-canine interleukin-31 receptor alpha polyclonal antibody and evaluation of its therapeutic efect in canine atopic dermatitis

Canine atopic dermatitis(CAD)is a prevalent genetically susceptible infammatory and pruritic allergic skin condition afecting not only the health of dogs but also the quality of life of their owners.Interleukin-31(IL-31)and interleukin-31 receptor alpha(IL-31RA)are essential for the development of pruritus in primates and mice.Hence,it is expected that inhibiting IL-31RA will be an efective approach to alleviate pruritus.The purpose of the study was to produce anti-canine IL-31RA polyclonal antibodies(anti-IL-31RA pAbs)and evaluate their efcacy in inhibiting house dust mite(HDM)-evoked pruritic responses.Dogs were immunized with antigens formed by IL-31RA recombinant short peptides coupled to BSA to produce anti-IL-31RA pAbs.The CAD model was developed by using HDM allergen stimulation,and the efects of IL-31RA pAbs on the reduction of pruritus in CAD model dogs were examined.The Canine Atopic Dermatitis Extent and Severity Index(CADESI)-4 and pruritus Visual Analog Scale(pVAS)were utilized to evaluate pruritic responses,and skin tissue samples were collected from the inguinal area for pathological assessment of skin infammatory cell infltration.The results showed that anti-IL-31RA pAbs with high titers(1:128,000)and specifcity were efectively produced.In the CAD model group,the severity of skin damage,pruritus score,infammatory cell infltration and level of infammatory factors were considerably elevated.Anti-IL-31RA pAbs relieved pruritic behavior and dermatitis in dogs compared to placebo-treated dogs.In conclusion,anti-IL-31RA pAbs efectively suppressed CAD in vivo and are anticipated to be an efective novel treatment for pruritic skin disorders such as CAD.

Acupoint catgut-embedding therapy ameliorates DNCB-induced atopic dermatitis in BALB/c mice by regulating Th2 type immune response and reducing infiltration of CD4^(+)and CD8^(+)cells

Background:This study aimed to assess how acupoint catgut-embedding therapy influences Th2-type immune response and the infiltration of CD4^(+)and CD8^(+)cells in DNCB-induced atopic dermatitis in BALB/c mice.It also conducted an initial examination of the underlying molecular mechanisms.Methods:Seventy-two mice were randomly divided into four groups:normal control,DNCB-induced atopic dermatitis model(AD),AD with acupoint catgut-embedding treatment(ADA),and AD with sham-acupoint catgut-embedding treatment.After DNCB challenge to induce AD,the ADA group received acupoint catgut-embedding therapy treatment at Zusanli(ST 36)and Quchi(LI 11)acupoints every other week from day 8.Mice in the AD with sham-acupoint catgut-embedding treatment group underwent the same procedure as the ADA group but without catgut implantation.Severity was assessed using SCORAD on treatment days 1,10,and 20.On day 18,nine mice per group were euthanized,and the remaining on day 28.Histopathological changes were observed using hematoxylin-eosin and immunohistochemistry staining.TNF-α,IL-4,IL-6,and IL-13 levels were analyzed by ELISA,and GATA3 and STAT6 protein levels by western blot.Results:After 20 days of acupoint catgut-embedding therapy treatment,mice showed reduced dermatitis scores compared to DNCB-induced AD-like mice.Significant decreases occurred in serum IL-4,IL-6,IL-13,and TNF-αlevels.Skin analysis revealed marked reductions in CD4^(+)and CD8^(+)cell infiltration,as well as GATA3 and STAT6 protein levels.Conclusion:Acupoint catgut-embedding therapy may effectively alleviate atopic dermatitis by suppressing Th2 immune responses via the STAT6-GATA3 pathway and reducing CD4^(+)and CD8^(+)T cell infiltration in skin lesions.

Blue Cap Is Effective and Safe for the Treatment of Atopic Dermatitis in Children

Background: Atopic dermatitis (AD) is the most common inflammatory skin disease in children. Treatment of AD is based on skin barrier repair and reduction of inflammation. We analyzed the efficacy and safety of activated piroctone olamine (APO)—Blue Cap—in children with AD. Materials and Methods: An open-label interventional clinical study was carried out at three clinical centers in Serbia. A total of 58 patients with AD, aged between 3 and 18 years were included and treated with Blue Cap Foam (100 ml;CATALYSIS S.L. Madrid)—Activated Piroctone Olamine—applied twice a day in the affected areas with eczema for 30 days and final assessment at 45 days from baseline. Photographic documentation, clinical evaluation, therapy effectiveness and safety questionnaires were assessed at baseline, 15, 30 and 45 days. Results: Our results demonstrated a significant reduction in signs (erythema, scaling, infiltration, excoriations, xerosis) and symptoms (pruritus) at weeks 2 and 4 of the study. At the end of the study, most patients had moderate (28.6%) to great (62.5%) disappearance of manifestations and moderate (25%) to great (71.4%) skin quality improvement. The effect and tolerability of the therapy were evaluated as very good in 66.1 % and 67.9% and good in about 14.3% and 17.9%, assessed by the investigator and patient, respectively. Three patients experienced a burning sensation at the beginning of the study, the side-effects were resolved as the patients continued applying the foam. After two weeks of cessation of the investigated foam, a significant percentage of patients experienced worsening in the final assessment done by the investigator as well as the participant. In the final assessment, a significantly high percentage (57.1%) of patients had a total reduction of manifestation, and a significant number of participants considered the applied product as treatment success, assessed by the investigator (62.5%) as well as the participants (66.4%). Conclusions: Blue Cap is effective and safe in children with AD, although further large-scale randomized controlled trials should confirm our study findings.

Psychosocial and Socioeconomic Barriers to Treatment Adherence in Pediatric Atopic Dermatitis

Research Background: Atopic dermatitis (AD) is a chronic inflammatory skin condition in children that significantly impacts physical health and quality of life. Adherence to treatment regimens is crucial for effective disease management but is often hindered by various psychosocial and socioeconomic barriers. Parental mental health issues, family dynamics, financial constraints, and limited access to specialized care contribute to inconsistent treatment adherence, exacerbating the condition. Purpose/Aim: The aim of this study is to explore the multifaceted barriers to treatment adherence in children with AD and evaluate the effectiveness of current interventions targeting these challenges. The study seeks to identify strategies that can improve adherence and health outcomes by addressing psychosocial and socioeconomic factors. Method: The method involves a comprehensive review of existing literature on the impact of psychosocial and socioeconomic factors on treatment adherence in children with AD. The study also examines various interventions designed to address these barriers, including community support programs, family-centered interventions, financial aid, integrated care models, and telehealth solutions. Results: Results indicate that psychosocial barriers, such as parental anxiety and depression, significantly hinder effective disease management. Family dynamics, including poor communication and single-parent households, complicate adherence efforts. Socioeconomic factors, such as financial constraints and limited healthcare access, further impede adherence. Interventions that address these barriers show promise in improving treatment adherence and health outcomes. Community support programs and family-centered interventions enhance parental mental health and family communication. Financial aid programs and integrated care models help mitigate economic and logistical challenges. Telehealth solutions improve access to specialized care, particularly in underserved areas. Conclusion: The study concludes that a holistic approach integrating medical treatment with psychosocial and socioeconomic support is essential for managing pediatric AD effectively. Policy recommendations include increased funding for community support programs, expanded telehealth services, and the integration of social services with medical care. Addressing these barriers comprehensively can enhance treatment adherence and improve the quality of life for children with AD. Further research should focus on long-term outcomes and diverse populations to refine these interventions and ensure they meet the needs of all affected children.

Correlation Analysis Between Children with Atopic Dermatitis and Asthma and Factors Affecting Intestinal Flora

Objective:In order to reveal the potential association between intestinal flora and atopic dermatitis with asthma,the study compares the changes in intestinal flora before and after treatment with antibiotics in children and explores the risk factors for the disease development in children.The differences between asthma-controlled children and healthy children were also analyzed to investigate whether there was a correlation between the level of control and intestinal flora in asthmatic children.Methods:367 children with atopic dermatitis and asthma were selected,and the control group was healthy children who did not have other skin diseases.Fecal samples were collected from healthy children and children with asthma,and the intestinal flora was tested at Beijing Nebula Medical Testing Laboratory Co.At the same time,50 children were selected according to the inclusion and exclusion criteria to take amide antibiotics during hospitalization,and stool samples were collected before and after taking antibiotics.Results:The proportion of Gram-positive cocci increased and the proportion of Gram-positive bacilli decreased after the administration of antibiotics in children with atopic dermatitis and asthma(P<0.05),and no significant difference was shown in the gender and age of the children(P>0.05).The proportion of family history of atopic dermatitis with asthma was higher in the experimental group(P<0.05).Conclusion:The use of antibiotics in children with atopic dermatitis with asthma showed a positive correlation with changes in intestinal flora.The use of antibiotics may lead to changes in intestinal flora and increase the risk of atopic dermatitis with asthma.Antibiotic use in infancy and childhood is also recognized as a risk factor for atopic dermatitis with asthma.Therefore,the use of antibiotics should be minimized in preventing and treating atopic dermatitis with asthma.

Advancements in the application of natural extracts for atopic dermatitis treatment

Atopic dermatitis,a common chronic inflammatory skin disease,has an unclear etiology and may involve multiple factors such as genetic predisposition,immune abnormalities,and impaired skin barrier function.Currently,there is no specific medication available for the complete cure of atopic dermatitis.The current treatment approaches mainly focus on symptom relief and control rather than curative treatment.Some commonly used medications for atopic dermatitis,such as topical corticosteroids and immunosuppressants,may have certain adverse reactions and side effects.This review summarizes the research progress on natural extracts in the treatment of atopic dermatitis,aiming to provide a foundation for the development of safe and side-effectfree medications.

Successful treatment of lichen amyloidosis coexisting with atopic dermatitis by dupilumab:Four case reports

BACKGROUND Lichen amyloidosis(LA)is a chronic,severely pruritic skin disease,which is the most common form of primary cutaneous amyloidosis.The treatment of LA has been considered to be difficult.LA may be associated with atopic dermatitis(AD),and in this setting,the treatment options may be more limited.Herein,we report four cases of LA associated with AD successfully treated by dupilumab.CASE SUMMARY In this article,we describe four cases of patients who presented with recurrent skin rash accompanied by severe generalized intractable pruritus,diagnosed with refractory LA coexisting with chronic AD.Previous treatments had not produced any apparent improvement.Thus,we administered dupilumab injection subcutaneously at a dose of 600 mg for the first time and 300 mg every 2 wk thereafter.Their lesions all markedly improved.CONCLUSION Dupilumab may be a new useful treatment for LA coexisting with AD.

Dupilumab for treatment of severe atopic dermatitis accompanied by lichenoid amyloidosis in adults:Two case reports

BACKGROUND Lichenoid amyloidosis(LA)is a subtype of primary cutaneous amyloidosis characterized by persistent multiple groups of hyperkeratotic papules,usually on the lower leg,back,forearm,or thigh.LA may be associated with several skin diseases,including atopic dermatitis(AD).The treatment of LA is considered to be difficult.However,as there is some overlap in the etiopathogenesis of LA and AD,AD treatment may also be effective for LA.CASE SUMMARY Case 1:A 70-year-old man was diagnosed with severe AD with LA based on large dark erythema and papules on the trunk and buttocks and dense hemispherical millet-shaped papules with pruritus on the extensor side of the lower limbs.He had a long history of the disease(8 years),with repeated and polymorphic skin lesions.Given the poor efficacy of traditional treatments,this patient was recommended to receive dupilumab treatment.At the initial stage,300 mg was injected subcutaneously every 2 wk.After 28 wk,the drug interval was extended to 1 mo due to the pandemic.Follow-up observations revealed that the patient reached an Eczema Area Severity Index of 90(skin lesions improved by 90%compared with the baseline)by the end of the study.Moreover,Investigator's Global Assessment score was 1,and scoring atopic dermatitis index and numeric rating scale improved by 97.7%and 87.5%compared with the baseline,respectively,with LA skin lesions having largely subsided.Case 2:A 30-year-old woman was diagnosed with severe AD with LA,due to dense and substantial papules on the dorsal hands similar to changes in cutaneous amyloidosis,and erythema and papules scattered on limbs and trunk with pruritus,present for 25 years.After 16 wk of dupilumab treatment,she stopped,and skin lesions completely subsided,without recurrence since the last follow-up.CONCLUSION Dupilumab shows rational efficacy and safety in the treatment of severe AD with LA,in addition to benefits in the quality of life of the patients.

Anti-inflammatory effects of amarogentin on 2,4-dinitrochlorobenzene-induced atopic dermatitis-like mice and in HaCat cells

Background:Amarogentin(AMA)is a secoiridoid glycoside extracted from Swertia and Gentiana roots and exhibits many biological effects such as antioxidative,antiinflammatory,and antitumor activities.Atopic dermatitis(AD)is a chronic inflammatory skin disease caused by disorders in the regulation of multiple inflammatory cytokines.No effective cure has been found for AD now.Methods:We constructed the HaCat and splenocyte model and tested the inhibitory effect of AMA on IL-4,IL-6,and IL-13 secretions using enzyme-linked immunosorbent assay(ELISA).The AD mouse model was constructed and treated with AMA,the severity of skin lesions was observed,epidermal tissue was collected,and epidermal thickness and mast cell infiltration were observed using hematoxylin and eosin and toluidine blue staining,respectively.The expression of kallikrein-related peptidase 7(KLK7)and filaggrin(FLG)was detected using immunostaining and Western blot analysis.The mRNA expression of KLK7 and FLG was detected using quantitative polymerase chain reaction(qPCR).Blood immunoglobulin E(IgE)secretion was detected.Results:AMA inhibited IL-6 secreted by tumor necrosis factor(TNF)-α-induced HaCaT cells and reduced IL-4 and IL-13 secreted by phytohemagglutinin(PHA)-induced primary cells in the mice spleen.It was found that the treatment of AMA with 2,4-din itrochlorobenzene-induced AD-like mice could promote the recovery of dermatitis,reduce the score of dermatitis severity and the scratching frequency,treat the skin lesions,reduce the epidermal thickness,decrease the infiltration of mast cells,reduce the IgE level in serum,decrease the expression levels of AD-related cytokines,increase protein and mRNA expression of FLG,and reduce the protein and mRNA expression of KLK7 in the skin tissues of AD-like mice.Conclusion:In conclusion,AMA inhibits inflammatory response at the cellular level,and AMA reduces the validation response of specific dermatitis mice,relieves pruritus,and repairs the damaged skin barrier.

Ocular manifestations of children with atopic dermatitis in Saudi Arabia

AIM:To examine the incidence of ocular abnormalities in children with atopic dermatitis(AD)in Saudi Arabia and its association with the severity of AD.METHODS:This is a cross-sectional study on 50 children with AD who were between 5 and 16 years of age.The severity of AD was evaluated using the SCORing Atopic Dermatitis(SCORAD)index.All the children underwent slit lamp exams,visual acuity assessment,intraocular pressure measurement,and corneal topography.The children were considered to have an ophthalmic abnormality if one or more of the following signs were present:glaucoma,keratoconus suspicion,in addition to lid,conjunctival,corneal,lenticular,or retinal abnormalities.RESULTS:Based on the SCORAD severity index,14%of children had mild AD(7/50),38%had moderate AD(19/50),and nearly half had severe AD.More than half the children exhibited facial involvement,and half had peri-orbital signs.The mean SCORAD index was 35.75.The mean age was 10.48±3.6y,and the cohort showed a slight male predominance(54%males).Both eyes of the 50 children in the cohort were studied.Based on the ocular examinations,92%of the patients showed ocular abnormalities:lid abnormalities(27/50)followed by keratitis(22/50).Four patients had moderate risk for keratoconus in one eye and eight patients were suspected to have keratoconus.However,SCORAD severity index was not associated with age,sex,or the number or presence of ophthalmic abnormalities.CONCLUSION:This is the first study in Saudi Arabia to evaluate the prevalence of ocular manifestations in children with AD.The results indicate that the majority of children with AD have ocular abnormalities that mainly include lid abnormalities.Based on these findings,larger scale studies are needed to affirm whether regular screening for ophthalmic abnormalities would be beneficial for children with AD in terms of early intervention and prevention of sight-threatening complications.

Investigation of possible relationship between atopic dermatitis and salivary biomarkers,stress,and sleep disorders

Atopic dermatitis(AD)is a chronic,relapsing,multifactorial inflammatory disease with genetic,environmental,and immunological characteristics.The quality of life and sleep of patients and their families are affected by AD,which triggers stress,described as one of the factors that worsens AD.Salivary biomarkers such as cortisol,alpha-amylase,chromogranin A,and melatonin have been associated with stress and sleep disturbances.Therefore,the evaluation of stress and sleep disorders using salivary biomarkers in AD patients is important.This review aims to describe the possible relationship between atopic dermatitis and stress,sleep disorders,and salivary biomarkers,seeking to contribute to better understanding and clinical management of AD.This descriptive study is characterized as a narrative literature review.A literature search was conducted of studies published in English and Portuguese between January 2012 and October 2022 that are available in electronic media from various databases,such as Scientific Electronic Library Online,Latin American and Caribbean Literature on Health Sciences,and PubMed.AD is associated with different degrees of impact on the lives of individuals who present with the disease.Psychological stress may induce changes in saliva composition and worsen AD;at the same time,the severity of the disease may be associated with emotional impact.Further studies are needed to assess and correlate AD severity,stress,and sleep disturbances with salivary biomarkers in order to better understand this association.

Topical Application of Cudrania tricuspidata Stem Extract Inhibits Atopic Dermatitis-Like Skin Lesions in an NC/Nga Mouse Model: An Experimental Animal Study

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by elevated immunoglobulin E (IgE), mast cell infiltration and skin lesions including pruritus, erythema and eczema. Cudrania tricuspidata extracts have been clinically administered for a long time in the East Asia including Korean and China as a home-remedy to diminish the inflammation of gastritis and hepatitis. To examine whether it works on AD or not, an AD-like animal model was experimented in this study. AD was induced by applying Dermatophagoides farinae (D. farinae) extract to the backs of 9-week old NC/Nga mice for 21 days. Following this, an ethanol extract of C. tricuspidata stems (EECT) was applied topically for 14 days to the sensitized skin, while distilled water was used as a control (EECT0 mice). Anti-AD effects of EECT were evaluated using scores for AD-like skin lesions, serum IgE levels and mast cell counts in the skin dermal layers to assess inflammation. Topically applied ethanol extract of Cudrania tricuspidata stems (EECT 7.5, 25 and 75 mg/mL) markedly reduced AD-like skin lesions after 4 days (by 30.1%, 31.4% and 38.5%, respectively) and also after 14 days (by 63.6%, 66.1% and 49.6%, respectively), while distilled water improved AD by 17.8% and 38.7%, respectively (p D. farinae extract (p = 0.003) and EECT attenuated the mast cell overproduction, and reduced mast cell degranulation markedly. Attenuation was most obvious in the early stage of EECT treatment when the AD was most acute.

Curative effect of BCG-polysaccharide nuceic acid on atopic dermatitis in mice

Objective:To explore the effect of bacilli Galmette-Gurin(BCG)-polysaccharide nuceic acid on atopic dermatitis in mice and its mechanism.Methods:Forty NC/Nga mice were selected and randomly divided into Group A(model group),Group B(dexamethasone treatment group),Group C(BCG polysaccharide nucleic acid treatment group) and Group D(control group) with 10 mice in each group.Atopic dermatitis model were constructed by applying 2,4-dinitrochlorobenzene on the skin of the mice.Mice in Group D were treated with acetone solution(100 μ L) on the foot pad and abdomen after hair removal at the age of 7 weeks.then on ear skin at the age of 8-13 weeks.For mice in A,B and C groups,100 μL of acetone solution containing 2,4-dinitrochlorobenzene was applied to the foot pad and the abdomen at the age of 7 weeks,then on ear skins at the age of8 to 13 weeks.At the age of 7-13 weeks,mice in Group A and Group D were treated with 100 μL saline(i.p.);mice were given dexamethasone(0.1 mL/kg,i.p.) every other day for 7 weeks in Group B;mice were treated with BCG polysaccharide nucleic acid(0.5 mg/kg,i.p.) every other day for7 weeks in Group C.The ear thickness was measured every week and the scratching frequency was recorded 1 times for 10 min a week.The mice were sacrificed after the last administration of drugs,IgE,IL-4,IL-10,IL-I2 and IFN- γ in the plasma were detected using ELISA,and RT-PCR method was employed to detect the concentrations of IL-4,IL-10,IL-12 and IFN- γ proteins.After IIK staining,the lesion degree of inflammation in ear tissue was observed microscopically.Results:The ear thickness and scratching frequency of Group A were significantly higher than those in group B,C and D(P<0.05),and there was no significant difference between Group B and C(P>0.05);the concentrations of IgE,IL-4 and IL-10 in the plasma and the expression of IL-4,IL-10 mRNA in the spleen tissues of Group A,B and C were all significantly higher than those of Group D(P<0.05);the concentrations of plasma IL-12 and IFN- γ,and spleen protein expression of IL-12 and IFN- γ in Group C mice were significantly higher than those of Group A(P<0.05).Histological observation showed obvious ear tissue exudation,erythema,swelling,desquamation of skin,and scabbing in Group A.Histopathology of the skin lesion also showed hyperkeratosis,focal-parakeratosis,stratum spinosum hypertrophy,mild sponge-like edema,a large number of lymphocytes along with plasma cell infiltration in dermis,angiectasis and hyperemia in Group A,while degree of ear skin lesion in Group B and D mice was significandy lighter than that of Group A.Conclusions:BCC polysaccharide nucleic acid can significandy reduce the serum IgE concentrations,increase the expression of IL-12,IFN- γ protein,correct the imbalance of Th1/Th2 in atopic dermatitis mice,and has obvious inhibitory effect on atopic dermatitis in NC/Nga mice.

Infectious, atopic and inflammatory diseases, childhood adversities and familial aggregation are independently associated with the risk for mental disorders: Results from a large Swiss epidemiological study

AIM To examine the associations between mental disorders and infectious, atopic, inflammatory diseases while adjusting for other risk factors.METHODS We used data from PsyC oL aus, a large Swiss Population Cohort Study(n = 3720; age range 35-66). Lifetime diagnoses of mental disorders were grouped into the following categories: Neurodevelopmental, anxiety(early and late onset), mood and substance disorders. They were regressed on infectious, atopic and other inflammatory diseases adjusting for sex, educational level, familial aggregation, childhood adversities and traumatic experiences in childhood. A multivariate logistic regression was applied to each group of disorders. In a complementary analysis interactions with sex were introduced via nested effects. RESULTS Associations with infectious, atopic and other chronic inflammatory diseases were observable together with consistent effects of childhood adversities and familial aggregation, and less consistent effects of trauma in each group of mental disorders. Streptococcal infections were associated with neurodevelopmental disorders(men), and measles/mumps/rubella-infections with early and late anxiety disorders(women). Gastric inflammatory diseases took effect in mood disorders(both sexes) and in early disorders(men). Similarly, irritable bowel syndrome was prominent in a sex-specific way in mood disorders in women, and, moreover, was associated with early and late anxiety disorders. Atopic diseases were associated with late anxiety disorders. Acne(associations with mood disorders in men) and psoriasis(associations with early anxiety disorders in men and mood disorders in women) contributed sex-specific results. Urinary tract infections were associated with mood disorders and, in addition, in a sex-specific way with late anxiety disorders(men), and neurodevelopmental and early anxiety disorders(women).CONCLUSION Infectious, atopic and inflammatory diseases areimportant risk factors for all groups of mental disorders. The sexual dimorphism of the associations is pronounced.

Modulatory effects of the fruits of Tribulus terrestris L. on the function of atopic dermatitis-related calcium channels,Orai1 and TRPV3

Objective: To examine the effects of Tribulus terrestris L.(T. terrestris) extract on the modulation of calcium channels to evaluate its use in topical agents for treatment of atopic dermatitis.Methods: The 70% methanol extract of T. terrestris was prepared. Human HEK293 T cells with over-expressed calcium release-activated calcium channel protein 1(Orai1),transient receptor potential vanilloid 1, or transient receptor potential vanilloid 3(TRPV3)were treated with T. terrestris extract. Modulation of ion channels was measured using a conventional whole-cell patch-clamp technique.Results: T. terrestris extract(100 mg/m L) significantly inhibited Orai1 activity in Orai1-stromal interaction molecule 1 co-overexpressed HEK293 T cells. In addition, T. terrestris extract significantly increased the TRPV3 activity compared with 2-Aminoethyl diphenylborinate(100 mmol/L), which induces the full activation of TRPV3.Conclusions: Our results suggest that T. terrestris extract may have a therapeutic potential for recovery of abnormal skin barrier pathologies in atopic dermatitis through modulating the activities of calcium ion channels, Orai1 and TRPV3. This is the first study to report the modulatory effect of a medicinal plant on the function of ion channels in skin barrier.

Atopic eczema treatment now and in the future:Targeting the skin barrier and key immune mechanisms in human skin

The skin facilitates a number of key roles but its functioning can be impaired by disease. Atopic eczema is a chronic inflammatory disease where the skin barrier has become leaky, and inflammation occurs. It affects up to 20% of children and 3% of adults worldwide, manifesting as red itchy patches of skin with varying severity. This review aims to investigate the leaky skin barrier and immune mechanisms from the perspective of potential novel treatments. The complexity of atopic eczema as a disease is what makes it difficult to treat. Genome-wide association studies have highlighted possible genetic variations associated with atopic eczema, however in some cases, individuals develop the disease without these genetic risk factors. Loss of function mutations in the filaggrin gene are one of these associations and this is plausible due to its key role in barrier function. The Th2 immune response is the link with regards to the immune mechanisms as atopic inflammation often occurs through increased levels of interleukin(IL)-4 and IL-13. Eczematous inflammation also creates susceptibility to colonisation and damage by bacteria such as Staphylococcus aureus. Potential novel treatments are becoming ever more specific, offering the hope of fewer side effects and better disease control. The best new treatments highlighted in this review target the immune response with human beta defensin 2, phosphodiesterase-4 inhibitors and monoclonal antibodies all showing promise.

Mechanism of improving skin barrier function in a mouse model of atopic dermatitis using Mahuang Lianqiao Chixiaodou decoction and its disassembled formula

Objective: To reveal the mechanism of Mahuang Lianqiao Chixiaodou decoction and its disassembled formula for improving the skin barrier function in a mouse model of atopic dermatitis(AD).Methods: Sixty specific-pathogen free male BALB/c mice were randomly divided into the control group,model group, whole formula group(WF), exterior-releasing formula group(ERF), interior-clearing formula group(ICF), and positive control group(PC). A mouse model of AD was established using the semiantigen 2,4-dinitrofluorobenzene induction method. The lesion scores, transepidermal water loss and p H, and skin histopathology of mice in each group were observed. The expressions of filaggrin, loricrin,and involucrin were detected by the streptavidin peroxidase immunohistochemical method and western blotting, and their mRNA expressions were detected by quantitative polymerase chain reaction.Results: Mice in the WF, ERF, ICF, and PC groups showed reduced skin lesion performance, improved histopathology, decreased skin lesion score, transepidermal water loss and pH, and upregulated expressions of proteins including filaggrin, loricrin, and involucrin, and their mRNAs. The most obvious regulatory effect was observed in the WF group, followed by the ICF, ERF, and PC groups, accordingly.Conclusions: Mahuang Lianqiao Chixiaodou decoction and its disassembled formula can improve the skin barrier function in a mouse model of AD by upregulating filaggrin, loricrin, and involucrin, and their mRNA expressions, and the most optimal effect was noted in the WF group, followed by the ICF and ERF groups, which suggests that the effect of clearing heat and resolving dampness in improving the skin barrier function of AD is more obvious and is one of the key treatments for AD.

Efficacy and tolerance of tacrolimus and pimecrolimus for atopic dermatitis: a meta-analysis

Tacrolimus ointment and pimecrolimus cream have proved to be suitable for the treatment of atopic dermatitis. We conducted a meta-analysis of the efficacy, adverse events/withdrawal of tacrolimus versus pimecrolimus in the treatment of atopic dermatitis. According to our meta-analysis, 0.1% tacrolimus was more effective than 1% pimecrolimus in the treatment of adult patients and moderate to very severe pediatric patients, and more 0.1% mild pediatric patients treatal with pimecrolimus withdrew from the trials because of a lack of efficacy or the occurrence of adverse events, compared with mild pediatric patients treated with 0.03% tacrolimus. The combined analyses of tacrolimus with pimecrolimus showed that tacrolimus was more effective than pimecrolimus （week 3： RR=0.67, 95%CI=0.56-0.80; week 6/end of study： RR=0.65, 95%CI=0.57-0.75）, and fewer tacrolimus-treated patients withdrew because of a lack of efficacy （RR=0.32, 95CI%=0.19-0.53） or the occurrence of adverse events （RR=0.43, 95%CI=0.24-0.75）, compared with pimecrolimus-treated patients. In conclusion, tacrolimus has higher efficacy and better tolerance than pimecrolimus in the treatment of atopic dermatitis.

Ovalicin attenuates atopic dermatitis symptoms by inhibiting IL-31 signaling and intracellular calcium influx

Atopic dermatitis(AD)is a common skin disorder difficult to be treated with medication.This study investigated the potential of ovalicin extracted from Cordyceps militaris for the treatment of AD using in vitro and in vivo models.We found that,in canine macrophage cell line DH82,lipopolysaccharide(LPS)upregulated the expression of genes associated with inflammation and pruritic responses through activating calcium and interleukin-31(IL-31)signaling,and the upregulation could be suppressed by ovalicin,with an effect significantly stronger than dexamethasone.Ovalicin also reduced the expression of IL-31 downstream genes,including JAK2(Janus kinase 2),TRPV1(transient receptor potential vanilloid receptor-1),and HRH2(histamine receptor H2).Ovalicin significantly alleviated the allergic symptoms in the AD mouse model.Histologically,the number of macrophages and mast cells infiltrated in the dermis was significantly reduced by ovalicin treatment.In the skin tissue of AD mice,reduction of IL-31 receptor was observed in the ovalicin treated group compared to the group without ovalicin treatment.To our knowledge,this is the first study to elucidate the anti-atopic mechanism of ovalicin,which could be an alternative to steroidal drugs commonly used for AD treatment.