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.

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.

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.

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.

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.

A Dead Sea Water-Enriched Body Cream Improves Skin Severity Scores in Children with Atopic Dermatitis

Dead Sea (DS) mud and water are known for their unique composition of minerals, and for their therapeutic properties on inflammatory skin diseases. The objective of the study was to evaluate the efficacy of an emollient cream enriched with DS water in children with atopic dermatitis (AD). Eighty six AD children were randomized in a double-blind controlled study to receive twice-daily topical treatment with a body cream enriched with DS minerals (TP) compared to two types of control: 1) DM, DS minerals with lower DS water concentrations than TP, and 2) an emollient (E) with no DS minerals. Efficacy was assessed by a change in clinical skin severity scores: SCORing Atopic Dermatitis (SCORAD), investigator’s global assessment (IGA) and patient global assessment (PGA) as well as by objective physiological parameters: transepidermal water loss (TEWL), stratum corneum hydration (SCH), affected body surface area (BSA) and Objective Severity Assessment of Atopic Dermatitis (OSAAD). The total length of the trial was 12 weeks divided to 6 visits at weeks 0, 2, 4, 6, 8, 12. The study showed that both TP and DM creams improved OSAAD scores. Only TP improved TEWL and SCH. TP was the most effective regarding TEWL, SCH and OSAAD compared to DM and E. Treatment with E decreased more significantly IGA score compared to TP. Although within each treatment group significant improvements in SCH, BSA, SCORAD, IGA and PGA were observed, the reduction in BSA, SCORAD and PGA was not significantly different among the groups. Our results clearly show the benefits of TP as a leave on-skin emulsion enrich with DS water in terms of skin barrier function. Thus, TP can serve as an effective adjuvant treatment for AD skin as well as for its maintenance.

Recent advances of TCM treatment of childhood atopic dermatitis

Atopic dermatitis( AD) is a common and frequently encountered disease, which frequently appears in children. According to statistics, the percentage of AD patients between ages of 6 to 20 in dermatology clinics is 30%~1, and the incidence in school-age children is 2%~3%~2. AD has no corresponding nomenclature in traditional Chinese medicine(TCM). According to the initial time of attack in early childhood, it can be classified as NaiXuan and TaiXuan; according to the location of the disease(elbow fossa and popliteal fossa), it can be classified as Si Wan Feng; according to the specific cases of different characteristics of lesions, it can be classified as ShiChuang, Jin Yinchuang, XueFengChuang. In TCM, the etiology of AD is complicated. It is generally considered that the pathogenesis of AD is spleen deficiency and damp-heat^3. When children suffer from pathogenic wind, pathogenic dampness, pathogenic heat, or insufficient natural endowment, damp-heat is produced and it injures patients' skin. Also latent damp-heat can deplete the blood and succus in the body, dry the skin and lead to AD. In short, AD can be divided into 3 syndrome types in TCM: syndrome of spleen deficiency, syndrome of damp-heat, syndrome of blood deficiency. At present, the clinical study of AD treated by TCM is increasing, but the study of children's treatment is still rare. This article aims to make a summary of clinical studies of children's AD treated with TCM in recent years.

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.

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.

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.

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.

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.

Intervention of the Mahuang Lianqiao Chixiaodou decoction on immune imbalance in atopic dermatitis-like model mice

Objective:To explore the potential mechanism of intervention on the immune imbalance of atopic dermatitis(AD) by studying the effects of Mahuang Lianqiao Chixiaodou decoction(MLCD) on skin damage and inflammation factors in an AD-like mouse model.Methods:Ninety-six male BALB/c mice were divided into normal,model,positive control(mometasone furoate),and traditional Chinese medicine treatment(MLCD) groups by a random number table.2,4-dinitrofluorobenzene was used to induce AD-like mice in all groups except the normal group.The treatment or intervention was administered for seven consecutive days on days 4,18,32,and 39.The mRNA relative expressions of interleukin-4(IL-4),IL-10,interferon-γ(IFN-γ),thymic stromal lymphopoietin(TSLP),and the TSLP receptor(TSLPR) were measured using quantitative real-time polymerase chain reaction,and the serum immunoglobulin E,IL-4,IL-10,and IFN-γ levels were detected using enzyme-linked immunosorbent assay.Results:Compared with the normal group,the hematoxylin-eosin staining of the skin lesions of the mice in the model group was significantly thickened on days 11,25,and 39.Compared with the model group,the epidermal thickness of the positive control group was significantly alleviated on day 39(P <.001),and that of the MLCD group was significantly improved on days 25 and 39(P <.001).Compared with the four observation time points,MLCD had the best treatment effect on day 39 of the experiment and significantly improved the skin damage performance and relieved pathological lesions.On day 39,compared with the model group,MLCD downregulated the skin mRNA relative expressions of IL-4(P=.009),TSLP(P=.030),and TSLPR(P <.001),and reduced the mouse serum levels of IL-4(P=.003).For other serum indicators,no significant difference was observed between the model and MLCD groups.Conclusion:MLCD improved AD-like mice skin damage by regulating the Th1/Th2 immune imbalance.

<i>Momordica charantia</i>Ameliorates Atopic Dermatitis by Inhibiting the Expression of Inducible Nitric Oxidase Synthase in NC/Nga Mice

Introduction: Momordica charantia (MC) has been reported to possess various beneficial effects. Improvement in natural aging of the skin has been observed with the use of MC. However, few studies have detailed the effects of MC on atopic dermatitis (AD). Therefore, in this study, we investigated the effects of MC on the skin symptoms of AD. Methods: Specific pathogen-free and conventional NC/Nga mice were orally administered a 50 mg/kg/day dose of MC every day for 2 weeks. Results: The expression levels of lipopolysaccharide (LPS), inducible nitric oxidase synthase (iNOS), and prostaglandin E2 (PGE2) remarkably increased in AD, but were suppressed by MC administration. As a result, the degradation of filaggrin by PGE2 was suppressed. Furthermore, in AD, iNOS induced macrophage type 1 and increased NO levels. In contrast, due to suppression of iNOS with MC administration, macrophages shifted to type 2 and an increase in L-ornithine was observed, which subsequently promoted filaggrin synthesis. Conclusions: These findings indicate that the AD-like skin symptoms were decelerated by MC via the regulation of the LPS/iNOS/PGE2/filaggrin and LPS/iNOS/Arginase 1/L-ornithine/ filaggrin signaling pathways.

Enzyme-treated date plum leave extract ameliorates atopic dermatitis-like skin lesion in hairless mice

Objective: To evaluate the effect of different extracts of Diospyros lotus leaves in atopic dermatitis Methods: Diospyros lotus leaves were extracted in ethanol and treated with or without hydrochloric acid or α-rhamnosidase to obtain three different extracts-ethanol, acid-hydrolyzed, and enzyme-hydrolyzed leaf extracts of date plum. The myricitrin content in all samples was measured using HPLC analysis. In vitro antioxidant and anti-inflammatory activities of the extracts were determined by measuring DPPH radical scavenging activities and nitric oxide production in RAW264.7 cells, respectively. Sevenweek-old male hairless mice were used to evaluate the anti-atopic dermatitis effects of three extracts in vivo. Splenocytes and mast cells were used to further determine the anti-atopic dermatitis effects of the major compound in the ethanol leaf extract.Results: Enzyme-hydrolyzed leaf extract showed significant in vitro antioxidant and anti-inflammatory activities, and attenuated atopic dermatitis-like skin symptoms and clinical signs more significantly than ethanol and acid-hydrolyzed leaf extracts in 1-fluoro-2,4-dinitrobenzene and house dust mite antigen-treated hairless mice. Enzyme-hydrolyzed leaf extract also suppressed the serum level of immunoglobulin E, interleukin(IL)-4, tumor necrosis factor(TNF)-α, interferon(IFN)-γ, thymic stromal lymphopoietin, and thymus and activation-regulated chemokine in mice with atopic dermatitis. Furthermore, histological analysis revealed that enzymehydrolyzed leaf extract suppressed the increased epidermal thickness, dermal infiltration of inflammatory cells, and infiltration and degranulation of mast cells more markedly than the other two extracts in atopic dermatitis-like skin lesions. In addition, this extract effectively inhibited the production of IFN-γ, IL-4, and thymus and activation-regulated chemokine compared with the other two extracts in concanavalin A-stimulated splenocytes. Myricitrin, a major compound of enzyme-hydrolyzed leaf extract, suppressed atopic dermatitis biomarkers in stimulated mouse splenocytes andHMC-1 human mast cells. Conclusions: These results suggest that enzyme-hydrolyzed leaf extract might be a potential candidate to treat atopic dermatitis.

Regulation of <i>α</i>-Melanocyte-Stimulating Hormone by Testosterone Is Associated with the Onset of Atopic Dermatitis Symptoms during Exercise

Objective: Atopic dermatitis (AD) symptoms are altered with exercise. However, no study has investigated the association between testosterone and AD. The aim of this study was to investigate the role of testosterone by which the strength and weakness of exercise affects the skin symptoms of AD. Methods: Specific pathogen-free (SPF) and conventional NC/Nga mice were used. NC/Nga mice spontaneously developed dermal symptoms similar to AD patients. Two exercises, mild (20 m/min, 60 min) and rigorous (25 m/min, 90 min), were carried out using a treadmill four times every alternate day. Furthermore, we administered testosterone (0, 5, 50, 500, and 5000 pg/mice) to non-exercised conventional NC/Nga mice. On the final day of this experiment, we analyzed the plasma levels of immunoglobulin E (IgE), interleukin (IL)-6, IL-4, IL-13, testosterone and α-melanocyte-stimulating hormone (α-MSH) by ELISA kit. Results: Symptoms manifested by NC/Nga mice were strongly exacerbated upon severe exercise but were ameliorated during mild exercise. Between mild and severe exercised conventional mice, the plasma level of IgE was not changed. On administering an equivalent amount of testosterone, depending on the exercise, AD-like symptoms in non-exercising NC/Nga mice were ameliorated with mild exercise and exacerbated through rigorous exercise. Plasma IL-6, IL-4, and IL-13 levels remained unchanged between +50 pg (mild) and +500 pg (severe) testosterone administration. Plasma α-MSH levels were elevated with +500 pg testosterone but decreased with +50 pg testosterone administration. Conclusion: The present results suggest that exercise largely mimics AD symptoms depending on the α-MSH and testosterone levels.

Atopic Dermatitis Deteriorates Dextran Sodium Sulfate-Induced Ulcerative Colitis via Thymic Stromal Lymphopoietin in Mice

It has been reported that atopic dermatitis (AD) and ulcerative colitis are related. However, the mechanism underlying this association has not been clarified. We therefore explored how AD induces ulcerative colitis. We developed an AD mouse model (NC/Nga mice) with ulcerative colitis by administering dextran sodium sulfate (DSS) for five days. DSS-induced ulcerative colitis was deteriorated in our conventional AD mouse model compared with specific-pathogen-free (SPF) mice. The plasma levels of thymic stromal lymphopoietin (TSLP) and tumor necrosis factor-α increased the most in DSS-treated conventional mice. Furthermore, the expression of dendritic cells (DC), retinoid-related orphan receptor (ROR)γt (marker of T helper 17 cells [Th17]), interleukin (IL)-17, GATA binding protein 3 (GATA3) (marker of Th2), and IL-4 increased the most in the colon of the DSS-treated conventional mice compared with DSS-treated SPF mice. In addition, TSLP inhibitor (TSLP neutralizing antibody) did not exacerbate ulcerative colitis in DSS-treated conventional mice. These results indicate that TSLP/DC/Th2 and Th17 play major roles in the exacerbation of ulcerative colitis by AD.

Mesenchymal stem cells and cell-free preparations for treating atopic dermatitis

Atopic dermatitis(AD)is a chronic cutaneous inflammatory disease caused by an interaction between genetic,immune and epidermal barrier factors.Several treatments can be used to treat this disease but there are patients that do not respond to actual drugs.So,there is a need to develop effective therapies for AD.Mesenchymal stem cells(MSCs)are non-hematopoietic multipotent adult progenitor cells with immunomodulatory power and self-regenerating capacity to repair tissue damage,so they could be a potential effective treatment for AD.MSCs-Conditioned Medium(CM)and MSCs-exosomes are cell-free preparation with molecules secreted by stem cells that could be also beneficial for AD.This viewpoint reviews the actual development of MSCs,MSCs-CM and MSCs-exosomes for treating patients with AD.