Development Of Atopic Dermatitis Research Articles

Studying the role of cortisol in the pathogenesis of atopic dermatitis during pregnancy

Introduction. Atopic dermatitis (AD) is one of the most common dermatitis, characterized by complex pathogenetic mechanisms. Psychological stress is recognized as one of the triggers of AD. Stress causes a high release of cortisol and epinephrine or norepinephrine, stimulating the immune system, primarily T helper cells type 1 (Th1 cells), to produce pro-inflammatory cytokines, leading to a cellular immune response and inflammation. In recent years, there has been an increase in incidence among pregnant women, however, the specific mechanisms of the development of AD during pregnancy still remain poorly understood. Aim. To study the role of cortisol in AD during pregnancy.Materials and methods. The study included 76 pregnant women during an exacerbation of AD, 20 non-pregnant women during an exacerbation of AD, 20 non-pregnant women without AD, 20 pregnant women without AD. The severity of AD was determined using the SCORAD index. Cortisol levels were determined in blood serum using enzyme-linked immunosorbent assay (ELISA). Anxiety level was determined using the Beck Anxiety Inventory. The level of itching was determined using a 5D itching scale.Results. Cortisol levels in pregnant women with AD (629.8 pg/ml) were significantly higher than in non-pregnant women with AD (386.15 pg/ml) (p < 0.05). Cortisol levels were correlated with the severity level (Spearman coefficient = 0.203, p = 0.018), anxiety level (Spearman coefficient = 0.411, p = 0.001), and level of itching (Spearman coefficient = 0.352, p = 0.001).Conclusions. Cortisol is important in the pathogenesis of AD during pregnancy. During pregnancy with exacerbation of AD, higher values were observed than outside pregnancy.

Early exposure to maternal stress and risk for atopic dermatitis in children: A systematic review and meta-analysis.

The incidence of atopic dermatitis (AD) in children is increasing. Early exposure to stress factors may be associated with the AD development. This study aimed to summarize studies that reported an association between stress exposure and AD development in later life. A comprehensive literature search was performed using online databases (PubMed, EMBASE, PsycINFO, and Web of Science) for articles published up to May 1, 2023. Eligible studies were screened and selected based on the inclusion criteria. We incorporated cohort or case-control studies published in English which explored the relationship between stress experienced by parents or children and AD. The pooled odds ratio (OR) was calculated according to the type of stress using a random-effects model. Twenty-two studies were included. AD was related to maternal distress (OR 1.29, 95% Confidence Interval [CI]: 1.13-1.47), maternal anxiety (OR 1.31, 95% CI: 1.18-1.46), and negative life events (OR 2.00, 95% CI: 1.46-2.76). Maternal depression during pregnancy was associated with AD (OR 1.21, 95% CI: 1.09-1.33), whereas no significant association was found for postpartum depression. Research on stress experienced by paternal or children is scare. Early maternal stress may potentially elevate the risk of AD in their offspring. Importantly, rigorously designed studies are required to corroborate the link between maternal stress and AD in children. These studies should aim to gather insights about the impact of stress during specific trimesters of pregnancy, postnatal stress, and paternal stress, and to identify potential prevention strategies.

Characteristics of the Gut Microbiota in Regard to Atopic Dermatitis and Food Allergies of Children.

The gut microbiota plays an important role in maintaining human health, as well as in the development of various pathologies, as indicated by a large amount of research. One of the manifestations of an imbalance in the gut microbiome composition is the appearance of various diseases or immune reactions, in particular, atopic dermatitis (AD) and/or food allergies (FA). In this research, using 16S NGS sequencing, it was found that the gut microbiome of children with food allergies and children with atopic dermatitis can be characterized as having higher inflammatory potential. Both groups exhibited an abundance of representatives from the Pasteurellaceae and Erysipelotrichaceae families, as well as a decrease in the relative number of representatives from the Barnesiellaceae family compared to healthy participants. In the group of participants with food allergies, there was a decrease in the relative number of Desulfovibrionaceae representatives and Bifidobacteriaceae family enrichment in relatively healthy participants. In addition, when comparing this group with patients with atopic dermatitis, it was revealed that a number of representatives of such families as Erysipelotrichaceae, Ruminococcaceae and Sutterellaceae prevailed. This information confirms that AD and FA correlate with changes in the composition of the gut microbiota. Further research is needed to determine the cause-effect connections and the effect of compounds derived from the microbiota on the AD and FA development and progression, as well as to create new probiotic drugs to prevent and modulate immune responses, including at an early age.

Alterations in gut microbiome associated with severity of atopic dermatitis in infants.

Atopic dermatitis (AD) often arises in infancy, and gut microbial dysbiosis is associated with the development of AD. However, less is known about specific changes in early-life gut microbiome associated with AD and AD severity. This study aims to reveal the gut microbial composition and function profiles associated with the severity of AD in infants. Sixty-two infants (mean [SD] age, 4.7[1.9] months) with different severities of AD were enrolled and divided into three groups (mild, moderate and severe) according to the Scoring Atopic Dermatitis (SCORAD) index. The profiles of gut microbial composition and function were analysed by sequencing 16S ribosomal RNA amplicons. Quality of life on children and the family was evaluated using published questionnaires. Decreased levels of Clostridium sensu stricto, Collinsella and increased level of Parabacteroides presented in the severe AD group compared with the mild AD group after adjusting potential confounders (p < 0.05). There were strong positive correlations between the Scoring Atopic Dermatitis (SCORAD) index and the relative abundance (RA) of Bacteroides and functional pathways for metabolism of sphingolipids and glycosphingolipids (p < 0.05). The SCORAD index was negatively correlated with the RA of Clostridium sensu stricto (p < 0.05), and was also positively correlated with the index of quality of life on children and the family (p < 0.05). Discrepancies in gut microbial composition and functional pathways were observed in infants with mild-to-severe AD. Alterations in butyrate-producing bacteria (Clostridium sensu stricto), sphingolipid-producing bacteria (Parabacteroides, Bacteroides), and related functional pathways were associated with the severity of AD infants.

Association between CCL5, CCL11, and CCL17 polymorphisms and atopic dermatitis risk: A systematic review and meta-analysis.

Atopic dermatitis (AD) is a common and recurrent inflammatory disease with strong genetic susceptibility. The abnormal production of chemokines plays an important role in the occurrence and development of AD. A comprehensive online literature search was performed in databases of China National Knowledge Infrastructure, Wanfang, VIP China Science and Technology Journal Database, China Biomedical Literature Database, PubMed, Embase and Cochrane Library to retrieve relevant articles published from January 2000 to October 2022. The odds ratio (OR) with its 95% confidence interval (CI) was employed to calculate this relationship. A total of 7 studies were finally screened out, including 1316 AD patients and 1099 controls. There were 3 studies for CC chemokine ligand 5 (CCL5) polymorphisms, 2 for CCL11 polymorphisms, and 2 for CCL17 polymorphisms, respectively. The meta-analysis revealed a significant association between the CCL5 - 403G/A polymorphism and AD under the allelic model (A vs G: OR = 1.25, 95% CI = 1.02-1.52, P = .03), heterozygous model (AG vs GG: OR = 1.40, 95% CI = 1.08-1.80, P = .01) and dominant model (AA + AG vs GG: OR = 1.38, 95% CI = 1.08-1.76, P = .01) in a fixed-effect model. The allelic model (G vs C: OR = 1.46, 95% CI = 1.07-1.98, P < .01) and dominant model (GG + GC vs CC: OR = 1.74, 95% CI = 1.23-2.47, P < .001) of the CCL5 - 28C/G polymorphism were also associated with an increased risk of AD. However, this significant association was not found in other alleles and genotypes (P > .05). Our results show that the A allele, AG and AA + AG genotypes of the CCL5 - 403G/A polymorphism, the G allele and GG + GC genotype of the CCL5 - 28C/G polymorphism are risk factors for AD. Future studies with large population are still needed to further explore those correlations.

Recent Advancements in the Atopic Dermatitis Mechanism.

Atopic dermatitis (AD) is a recurrent, chronic, inflammatory, itchy skin disorder that affects up to 20% of the pediatric population and 10% of the adult population worldwide. Onset typically occurs early in life, and although cardinal disease features are similar across all ages, different age groups and ethnicities present distinct clinical characteristics. The disease imposes a significant burden in all health-related quality of life domains, both in children and adults, and a substantial economic cost both at individual and national levels. The pathophysiology of AD includes a complex and multifaceted interplay between the impaired dysfunctional epidermal barrier, genetic predisposition, and environmental contributors, such as chemical and/or biological pollutants and allergens, in the context of dysregulated TH2 and TH17 skewed immune response. Regarding the genetic component, the loss of function mutations encoding structural proteins such as filaggrin, a fundamental epidermal protein, and the more recently identified variations in the epidermal differentiation complex are well-established determinants resulting in an impaired skin barrier in AD. More recently, epigenetic factors have facilitated AD development, including the dysbiotic skin microbiome and the effect of the external exposome, combined with dietary disorders. Notably, the interleukin (IL)-31 network, comprising several cell types, including macrophages, basophils, and the generated cytokines involved in the pathogenesis of itch in AD, has recently been explored. Unraveling the specific AD endotypes, highlighting the implicated molecular pathogenetic mechanisms of clinically relevant AD phenotypes, has emerged as a crucial step toward targeted therapies for personalized treatment in AD patients. This review aims to present state-of-the-art knowledge regarding the multifactorial and interactive pathophysiological mechanisms in AD.

Supercritical CO2 fluid extract from Stellariae Radix ameliorates 2,4-dinitrochlorobenzene-induced atopic dermatitis by inhibit M1 macrophages polarization via AMPK activation.

Yin chai hu (Radix Stellariae) is a root medicine that is frequently used in Chinese traditional medicine to treat fever and malnutrition. In modern medicine, it has been discovered to have anti-inflammatory, anti-allergic, and anticancer properties. In a previous study, we were able to extract lipids from Stellariae Radix using supercritical CO2 extraction (SRE), and these sterol lipids accounted for up to 88.29% of the extract. However, the impact of SRE on the development of atopic dermatitis (AD) has not yet been investigated. This study investigates the inhibitory effects of SRE on AD development using a 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model. Treatment with SRE significantly reduced the dermatitis score and histopathological changes compared with the DNCB group. The study found that treatment with SRE resulted in a decrease of pro-inflammatory cytokines TNF-α, CXC-10, IL-12, and IL-1β in skin lesions. Additionally, immunohistochemical analysis revealed that SRE effectively suppressed M1 macrophage infiltration into the AD lesion. Furthermore, the anti-inflammatory effect of SRE was evaluated in LPS + INF-γ induced bone marrow-derived macrophages (BMDMs) M1 polarization, SRE inhibited the production of TNF-α, CXC-10, IL-12, and IL-1β and decreased the expression of NLRP3. Additionally, SRE was found to increase p-AMPKT172, but had no effect on total AMPK expression, after administration of the AMPK inhibitor Compound C, the inhibitory effect of SRE on M1 macrophages was partially reversed. The results indicate that SRE has an inhibitory effect on AD, making it a potential therapeutic agent for this atopic disorder.

Systemic lupus erythematosus and Atopic dermatitis: A two sample Mendelian randomization study.

Systemic lupus erythematosus (SLE) and atopic dermatitis (AD) are common diseases in human populations. Previous studies have suggested a potential association between SLE and AD. However, the causal relationship and direction between the two conditions remain unclear. The aim of this study is to evaluate the causal relationship between SLE and AD. In this study, we employed Mendelian randomization (MR) analysis to investigate the causal relationship between SLE and AD. MR analysis has the advantage of reducing confounding factors, determining the direction of causality, and providing quantitative effect estimates. We obtained summary data from genome-wide association studies (GWAS) on SLE and AD from publicly available databases. Five MR methods, namely MR Egger, weighted median, inverse variance weighted, simple mode, and weighted mode, were used to assess the causal relationship between SLE and AD. Several techniques, including MR-Egger intercept, MR-PRESSO, and Cochran's Q test, were utilized to evaluate heterogeneity and pleiotropy. Our study demonstrated a causal relationship between the prevalence of SLE and an increased risk of AD (MR Egger OR: 1.567, 95% CI: [1.041, 1.285], P = 0.009; IVW OR: 1.085, 95% CI: [1.005, 1.143], P = 0.035). Furthermore, sensitivity analyses did not detect heterogeneity or pleiotropy. Our research finds that SLE is a contributing factor to the development of AD, providing valuable insights into the pathogenesis and prevention of both diseases. Key Points • Currently, there is no research that clearly indicates a causal relationship between SLE and AD. This study, for the first time, identified a positive causal relationship between SLE and AD. • The results of this study contribute to our understanding of the pathogenesis and treatment strategies for SLE and AD, providing some guidance for future clinical practice.

Outlining the skin-homing and circulating CLA+NK cells in patients with severe atopic dermatitis

Atopic dermatitis (AD) is a complex, multifactorial skin disease, characterized by pruritus and predominant Th2 inflammation. Innate immune cells may play a role in AD development and are composed of granulocytes, macrophages, innate-like T cells, and innate lymphoid cells. This study investigates the phenotypic and functional profile of circulating CLA+ natural killer (NK) cells and its role in the skin-homing to NK cells infiltrated in adults’ skin with AD. We selected 44 AD patients and 27 non-AD volunteers for the study. The results showed increased frequencies of both CLA+CD56bright and CLA+CD56dim NK cell populations in the peripheral blood, mainly in severe AD patients. Upon SEB stimulation, we observed an augmented percentage of CLA+CD56dim NK cells expressing CD107a, IFN-γ, IL-10, and TNF, reinforcing the role of staphylococcal enterotoxins in AD pathogenesis. Additionally, we demonstrated increased dermal expression of both NK cell markers NCAM-1/CD56 and pan-granzyme, corroborating the skin-homing, mostly in severe AD. Further studies are necessary to elucidate the potential role of NK cells in the chronification of the inflammatory process in AD skin, as well as their possible relationship with staphylococcal enterotoxins, and as practicable therapeutic targets.

Association of Interleukin-17A and Interleukin-17F Gene Polymorphisms with Atopic Dermatitis in Chinese Children.

Background: Atopic dermatitis (AD) is a chronic, recurrent inflammatory disease associated with an unbalanced immune response in the upper layers of the skin tissue, mostly starting in childhood. As important factors in gene expression regulation, polymorphisms in interleukin (IL)-17A and IL-17F may be associated with the susceptibility and severity of AD. Methods: Blood samples and clinical information were obtained from 132 patients with AD and 100 healthy children. Using multiplex polymerase chain reaction and next-generation sequencing, five potential single-nucleotide polymorphisms (SNPs) of IL-17A and IL-17F were genotyped in all participants. The relationship between SNPs and susceptibility to or severity of AD was examined by analyzing haplotypes and genetic models. Results: The IL-17A rs3819025 polymorphism was substantially associated with higher AD risk in both the allele model (p = 0.03; odds ratio [OR] = 1.76; confidence interval [CI]: 1.05-2.95) and the dominant model (p = 0.04, OR = 1.85; CI: 1.03-3.33). There was no correlation between AD susceptibility and the IL-17A (rs2275913 and rs4711998) or IL-17F (rs763780 and rs12203736) SNPs (all p > 0.05). Additionally, the five IL-17A and IL-17F SNPs did not significantly differ across the mild-to-moderate and severe subgroups (all p > 0.05). Conclusions: The IL-17A/rs3819025 polymorphism was linked to the development of AD, whereas the IL-17F polymorphism was unrelated to the susceptibility to and severity of AD. The IL-17A polymorphism may provide valuable information to speculate on the susceptibility to AD in Chinese Han children.

Changes in oral, skin, and gut microbiota in children with atopic dermatitis: a case-control study.

Atopic dermatitis (AD) is a common clinical recurrent atopic disease in dermatology, most seen in children and adolescents. In recent years, AD has been found to be closely associated with microbial communities. To explore the synergistic effects between colonizing bacteria from different sites and AD, we comparatively analyzed the skin, oral, and gut microbiota of children with AD (50 individuals) and healthy children (50 individuals) by 16S rRNA gene sequencing. Twenty samples were also randomly selected from both groups for metabolic and macrogenomic sequencing. The results of our sequencing study showed reduced microbiota diversity in the oral, skin, and gut of children with AD (P < 0.05). Metabolomics analysis showed that serotonergic synapse, arachidonic acid metabolism, and steroid biosynthesis were downregulated at all three loci in the oral, skin, and gut of children with AD (P < 0.05). Macrogenomic sequencing analysis showed that KEGG functional pathways of the three site flora were involved in oxidative phosphorylation, ubiquitin-mediated proteolysis, mRNA surveillance pathway, ribosome biogenesis in eukaryotes, proteasome, basal transcription factors, peroxisome, MAPK signaling pathway, mitophagy, fatty acid elongation, and so on (P < 0.05). The combined microbial, metabolic, and macrogenetic analyses identified key bacteria, metabolites, and pathogenic pathways that may be associated with AD development. We provides a more comprehensive and in-depth understanding of the role of the microbiota at different sites in AD patients, pointing to new directions for future diagnosis, treatment and prognosis.

Anti-Inflammatory Herbal Extracts and Their Drug Discovery Perspective in Atopic Dermatitis.

Atopic dermatitis (AD) is an allergic disorder characterized by skin inflammation. It is well known that the activation of various inflammatory cells and the generation of inflammatory molecules are closely linked to the development of AD. There is accumulating evidence demonstrating the beneficial effects of herbal extracts (HEs) on the regulation of inflammatory response in both in vitro and in vivo studies of AD. This review summarizes the anti-atopic effects of HEs and its associated underlying mechanisms, with a brief introduction of in vitro and in vivo experiment models of AD based on previous and recent studies. Thus, this review confirms the utility of HEs for AD therapy.

Exploring causal correlations between circulating cytokines and atopic dermatitis: a bidirectional two-sample Mendelian randomization study.

Numerous observational studies have reported associations between circulating cytokines and atopic dermatitis (AD); however, the causal relationships between them remain unclear. To explore the causal correlations and direction of causal effects between AD and levels of 91 circulating cytokines. Two-sample Mendelian randomization (MR) analyses were conducted to examine the causal relationships between 91 circulating cytokines and AD using summary statistics from genome-wide association studies (GWAS). Reverse MR analyses were performed to investigate reverse causation. Pleiotropy and heterogeneity tests were conducted to assess the robustness of the findings. Additional transcriptome database and clinical peripheral blood mononuclear cells (PBMCs) samples were utilized to validate the results of MR analyses. Levels of interleukin (IL)-13, IL-18 Receptor 1, Tumor necrosis factor ligand superfamily member 14 (TNFSF14), TNF-related activation-induced cytokine (TRANCE), C-X-C motif chemokine (CXCL)11, IL-33, TNF-beta and CD5 were suggestively associated with the risk of AD (odds ratio, OR: 1.202, 95% CI: 1.018-1.422, p = 0.030; OR: 1.029, 95% CI: 1.029-1.157, p = 0.004; OR: 1.159, 95% CI: 1.018-1.320, p = 0.026; OR: 1.111, 95% CI: 1.016-1.214, p = 0.020; OR: 0.878, 95% CI: 0.783-0.984, p = 0.025; OR: 0.809, 95% CI: 0.661-0.991, p = 0.041; OR: 0.945, 95% CI: 0.896-0.997, p = 0.038; OR: 0.764, 95% CI: 0.652-0.895, p = 8.26e-04). In addition, levels of cytokines including Axin-1, CXCL5, CXCL10, Oncostatin-M (OSM), Sulfotransferase 1A1 (SULT1A1) and TNFSF14 were suggested to be consequences of AD (Beta: -0.080, p = 0.016; Beta: -0.062, p = 0.036; Beta: -0.066, p = 0.049; Beta: -0.073, p = 0.013; Beta: -0.089, p = 0.008; Beta: -0.079, p = 0.031). IL-13, IL-18R1, TNFSF14, and TRANCE were upregulated in both lesional skin biopsies and PBMCs from AD patients. The study indicates that several cytokines, including IL-13, IL-18R1, TNFSF14, TRANCE, CXCL11, IL-33, TNF-beta, and CD5, are upstream of AD development, whereas a few circulating cytokines are potentially downstream in the development of AD.

Risk Factors of Onset Time and Persistence of Atopic Dermatitis in Children Under Age 5 Years: A Cross-Sectional Study.

Background: The prevalence of atopic dermatitis (AD) is high among children, with development of AD occurring during early childhood in most affected children and some having a chronic disease course. Risk factors for AD in this group remain undefined. Objectives: We analyzed the medical records of children with AD under 5 years of age. We summarized characteristics of the natural course of AD in these children and explored relevant risk factors of AD in infancy and early childhood. Methods: Using a self-developed questionnaire, we investigated 716 children under 5 years of age who were treated for AD at the Dermatology Department of the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China. We conducted the study from October 2021 to September 2022 using telephone and on-site interviews with the children's parents. In parental interviews, data were gathered on neonatal diseases, comorbidities, parental allergy history, maternal history of tobacco and alcohol use, and basic infant information at birth. Some children were tested for serum total immunoglobulin E (IgE) before this study. Results: Neonatal hyperbilirubinemia, neonatal respiratory distress syndrome (NRDS), neonatal infection, and infection during childhood had a significant impact on persistent symptoms and the onset of first symptoms in children with AD (P < 0.05). Allergic diseases as common comorbidities with AD, which had earlier onset of AD related to more obvious disease activity (P < 0.05). Parental history of allergy was also significant in AD (P < 0.05). Serum total iIgE levels in children with AD showed an impact on the clinical course of AD; neonatal hyperbilirubinemia and NRDS may affect IgE levels (P < 0.05). Persistent AD had a significant effect on the physical growth of children with height/length for age Z score ≤3 and weight for height/length Z score ≤3 (P < 0.05). Conclusions: Early adverse events in infants, infection before onset, and susceptibility to infection may affect the onset and clinical course of childhood AD. Serum total IgE levels affect the progression of AD. Persistent AD in childhood may have a slight impact on children's physical growth.

Nurturing Infants to Prevent Atopic Dermatitis and Food Allergies: A Longitudinal Study.

Atopic dermatitis (AD) at a young age often precedes the development of food allergies. Although AD affects millions of infants worldwide, prenatal and postnatal risk factors, and their association with the development of food allergies later on, are not fully elucidated. This study seeks to investigate AD epidemiology in infancy and its risk factors, examining early-life factors (both prenatal and postnatal) that could contribute to the later development of food allergies. Between January 2019 and December 2019, 501 infants were included in this prospective cohort study. Longitudinal data collection was performed through maternal interviews, the first one conducted within three days after the delivery and the second within 24 to 36 months after the delivery, encompassing variables such as demographics, family history of atopy, maternal smoking, antibiotic use during pregnancy, the mode of delivery, breastfeeding history, food practices, and greenness exposure within 3 days from delivery, while they were still in the hospital. Maternal smoking during pregnancy (p = 0.001) and an older sibling atopy history (p = 0.03) was significantly linked to AD incidence. Cesarean section delivery (p = 0.04) was associated with a higher risk of food allergies in infants with AD. Having a garden at home correlated with a higher likelihood of AD (p = 0.01), and food elimination without medical guidance (p = 0.02) due to AD correlated with an elevated risk of food allergies. Encouraging timely allergenic food introduction while promoting dietary diversity, rich in plant-based foods, maternal smoking cessation, and professional dietary guidance may help minimize AD and food allergy risk. Future studies should address the role of greenness in the development of AD and food allergies.

Forsythia velutina Nakai extract: A promising therapeutic option for atopic dermatitis through multiple cell type modulation.

Atopic dermatitis (AD) is a complex condition characterized by impaired epithelial barriers and dysregulated immune cells. In this study, we demonstrated Forsythia velutina Nakai extract (FVE) simultaneously inhibits basophils, macrophages, keratinocytes, and T cells that are closely interrelated in AD development. We analyzed the effect of FVE on nitric oxide and reactive oxygen species (ROS) production in macrophages, basophil degranulation, T cell activation, and tight junctions in damaged keratinocytes. Expression of cell-type-specific inflammatory mediators was analyzed, and the underlying signaling pathways for anti-inflammatory effects of FVE were investigated. The anti-inflammatory effects of FVE were validated using a DNCB-induced mouse model of AD. Anti-inflammatory activity of compounds isolated from FVE was validated in each immune cell type. FVE downregulated the expression of inflammatory mediators and ROS production in macrophages through TLR4 and NRF2 pathways modulation. It significantly reduced basophil degranulation and expression of type 2 (T2) and pro-inflammatory cytokines by perturbing FcεRI signaling. Forsythia velutina Nakai extract also robustly inhibited the expression of T2 cytokines in activated T cells. Furthermore, FVE upregulated the expression of tight junction molecules in damaged keratinocytes and downregulated leukocyte attractants, as well as IL-33, an inducer of T2 inflammation. In the AD mouse model, FVE showed superior improvement in inflammatory cell infiltration and skin structure integrity compared to dexamethasone. Dimatairesinol, a lignan dimer, was identified as the most potent anti-inflammatory FVE compound. Forsythia velutina Nakai extract and its constituent compounds demonstrate promising efficacy as a therapeutic option for prolonged AD treatment by independently inhibiting various cell types associated with AD and disrupting the deleterious link between them.

WTAP-Mediated N6-Methyladenosine of RNAs Facilitate the Pathophysiology of Atopic Dermatitis

N6-methyladenosine (m6A) is the most abundant dynamic and reversible internal chemical modification of RNA in eukaryotic cells and is essential in multiple pathophysiological processes. However, it has not been reported in atopic dermatitis (AD). We used Arraystar m6A-mRNA epitranscriptomic microarray to screen for differentially expressed genes (DEGs) and their m6A levels, and m6A-related enzymes in patients with AD. We confirmed that the m6A RNA methyltransferase Wilms tumor 1-associated protein (WTAP) and two candidate DEGs (S100 calcium-binding protein A9 [S100A9] and serpin peptidase inhibitor, clade B (ovalbumin), member 3 [SERPINB3] were significantly upregulated in keratinocytes in public data and epidermal lesions of patients with AD. In vitro cell experiments confirmed that WTAP influenced the expression of the two candidate DEGs and promoted primary human epidermal keratinocytes (HEKs) proliferation while inhibiting HEKs differentiation. Furthermore, we showed that WTAP, S100A9, and SERPINB3 expression correlated with AD severity. Our findings revealed that WTAP-mediated m6A modification promoted the expression of S100A9 and SERPINB3 to aggravate HEK proliferation and dysdifferentiation contributing to the pathophysiological development of AD.

Lacticaseibacillus rhamnosus and breastmilk are associated with a decreased risk of atopic dermatitis in very low birth weight premature infants.

In this study, we analyse the influence of nutrition during the early neonatal period on the development and prevention of atopic dermatitis (AD) in children with a history of very low birth weight (VLBW). A retrospective cohort study was performed of VLBW preterm infants to assess the risk of their developing AD during childhood, according to nutrition with breastmilk and/or probiotic supplementation during the neonatal period. The analysis focused on nutritional and early childhood follow-up data for 437 newborns, of whom 184 received probiotics up to 36 weeks postmenstrual age. AD was present in 23.5% of the study sample. Of the children who did not develop AD, 44.9% had received probiotics from birth to 36 weeks of gestational age. Therefore, the administration of probiotics to infants at less than 36 weeks postmenstrual age is associated with a protective effect against the development of AD (odds ratio (OR) 0.57; 95% confidence interval (CI) 0.34-0.93). Moreover, a protective interaction was observed between probiotic administration and breastmilk (OR 0.46; 95% CI 0.25-0.82). The adjusted data in the regression model allow us to observe a statistically significant association with the protective effect of Lacticaseibacillus rhamnosus with the development of AD at school age (OR 0.55; 95% CI 0.30-0.99). Probiotic supplementation in VLBW newborns is associated with a decreased risk of subsequent development of AD. Breastmilk strengthens the protective effect of probiotics against the development of AD.

Exosomes derived from human dermal fibroblasts (HDFn-Ex) alleviate DNCB-induced atopic dermatitis (AD) via PPARα.

Atopic dermatitis (AD) is a chronic inflammatory skin disease. Skin barrier dysfunction is the initial step in the development of AD. Recently, exosomes have been considered as potential cell-free medicine for skin defects such as aging, psoriasis and wounds. The aim of this study was to investigate the effects of human dermal fibroblast-neonatal-derived exosome (HDFn-Ex) on AD. HDFn-Ex increased the expression of peroxisome proliferator activated receptor α (PPARα) and alleviated the 1-chloro-2,4-dinitrobenzene (DNCB)-mediated downregulation of filaggrin, involucrin, loricrin, hyaluronic acid synthase 1 (HAS1) and HAS2 in human keratinocyte HaCaT cells. However, these effects were inhibited by the PPARα antagonist GW6471. In the artificial skin model, HDFn-Ex significantly inhibited DNCB-induced epidermal hyperplasia and the decrease in filaggrin and HAS1 levels via a PPARα. In the DNCB-induced AD-like mouse model, HDFn-Ex administration reduced epidermis thickening and mast cell infiltration into the dermis compared to DNCB treatment. Moreover, the decreases in PPARα, filaggrin and HAS1 expression, as well as the increases in IgE and IL4 levels induced by DNCB treatment were reversed by HDFn-Ex. These effects were blocked by pre-treatment with GW6471. Furthermore, HDFn-Ex exhibited an anti-inflammatory effect by inhibiting the DNCB-induced increases in IκBα phosphorylation and TNF-α expression. Collectively, HDFn-Ex exhibited a protective effect on AD. Notably, these effects were regulated by PPARα. Based on our results, we suggest that HDFn-Ex is a potential candidate for treating AD by recovering skin barrier dysfunction and exhibiting anti-inflammatory activity.

Trajectory of stratum corneum lipid subclasses in the first year of life and associations with atopic dermatitis: A prospective cohort study

AbstractBackgroundTrajectories of stratum corneum (SC) lipid subclasses and their associations with infant atopic dermatitis (AD) are unclear. This study aimed to quantify the trajectories of 15 SC subclasses and carbon chain lengths and their associations with AD within 12 months.MethodsIn total, 213 newborns were enrolled at birth with nonlesional skin samples collected from the inner forearm at birth, 42 days, 3, 6, and 12 months, respectively. Lesional skin samples were collected from 120 AD patients at clinic with the disease onset within the first year of life. Mass spectrometry was applied to assess relative contents of 12 ceramide (CER), three free fatty acid (FFA) subclasses, and average carbon chain length (CCL). AD incident within 1 year old was diagnosed by dermatologists according to UK criteria.ResultsSixty‐four (30.0%) cases of ADs occurred in the cohort. All SC lipid subclasses and CCLs, but EOP varied significantly during the first year. AD infants showed lower NP but higher NS, NH, AP, hydroxy FFA, and CCL of FFAs compared with nonaffected infants. After normalization by age, the differences remained and were more pronounced in lesional skin of clinical AD infants compared with non‐ADs. NS, NH, and CCL of FFAs in lesional skin of AD infants showed positive and significant correlations with the levels of transepidermal water loss at 3 month; some evidence supports a negative correlation for NP.ConclusionsWe provide an overview of developmental trajectories of 15 CER and FFA subclasses across the first year of healthy infants and a link between the imbalance of some subclasses with the development of AD.