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Antioxidants (Basel, Switzerland) Jun 2024Semaphorin 3A (SEMA3A), a nerve-repellent factor produced by keratinocytes, has an inhibitory effect on nerve extension to the epidermis. Epidermal innervation is...
Semaphorin 3A (SEMA3A), a nerve-repellent factor produced by keratinocytes, has an inhibitory effect on nerve extension to the epidermis. Epidermal innervation is involved in pruritus in inflammatory skin diseases such as atopic dermatitis (AD) and dry skin. We previously reported that tapinarof, a stilbene molecule, upregulates SEMA3A in human keratinocytes. We also showed that this mechanism is mediated via the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, and the nuclear factor erythroid 2-related factor 2 (NRF2) axis. Since some stilbenes activate AHR and NRF2, we attempted to identify other stilbenes that upregulate SEMA3A. We analyzed normal human epidermal keratinocytes (NHEKs) treated with 11 types of stilbenes and examined SEMA3A expression. We found that resveratrol and pinostilbene, antioxidant polyphenols, upregulated SEMA3A and increased nuclear AHR and NRF2 expression. In addition, AHR knockdown by small interfering RNA (siRNA) transfection abolished the NRF2 nuclear expression. Furthermore, AHR and NRF2 knockdown by siRNA transfection abrogated resveratrol- and pinostilbene-induced SEMA3A upregulation. Finally, we confirmed that resveratrol and pinostilbene increased SEMA3A promoter activity through NRF2 binding using ChIP-qPCR analysis. These results suggest that resveratrol and pinostilbene upregulate SEMA3A via the AHR-NRF2 axis in human keratinocytes.
PubMed: 38929171
DOI: 10.3390/antiox13060732 -
Diagnostics (Basel, Switzerland) Jun 2024Vernal keratoconjunctivitis is a persistent allergic ocular disease predominantly mediated by the T-helper 2 lymphocyte-associated immune response. The standard...
Vernal keratoconjunctivitis is a persistent allergic ocular disease predominantly mediated by the T-helper 2 lymphocyte-associated immune response. The standard therapeutic approaches for vernal keratoconjunctivitis include topical corticosteroids and immunosuppressive eye drops. However, managing vernal keratoconjunctivitis with only topical treatments becomes challenging during seasonally exacerbated periods. Systemic treatments such as oral corticosteroids or cyclosporine may be alternative options. Recently, dupilumab's efficacy in refractory vernal keratoconjunctivitis treatment has been documented. Here, we report a case of refractory vernal keratoconjunctivitis coexisting with atopic dermatitis that rapidly improved after upadacitinib administration. An 18-year-old Japanese woman presented with atopic dermatitis, vernal keratoconjunctivitis, and hay fever. In winter, the patient experienced widespread erythema and escalated itching, leading to significant discomfort and insomnia. Owing to the difficulty in maintaining her current regimen, upadacitinib (15 mg), a Janus kinase inhibitor was initiated. After upadacitinib administration, the treatment-resistant vernal keratoconjunctivitis and erythema improved. Upadacitinib is beneficial in severe cases of atopic dermatitis. Consequently, in our case, upadacitinib may offer therapeutic benefits for refractory vernal conjunctivitis by improving the T-helper 1/2 type immune response, autoimmunity, and oxidative stress. To our knowledge, this is the first report suggesting the potential utility of upadacitinib in managing severe vernal conjunctivitis.
PubMed: 38928687
DOI: 10.3390/diagnostics14121272 -
International Journal of Molecular... Jun 2024Antimicrobial peptides (AMPs) are crucial components of the innate immune system in various organisms, including humans. Beyond their direct antimicrobial effects, AMPs... (Review)
Review
Antimicrobial peptides (AMPs) are crucial components of the innate immune system in various organisms, including humans. Beyond their direct antimicrobial effects, AMPs play essential roles in various physiological processes. They induce angiogenesis, promote wound healing, modulate immune responses, and serve as chemoattractants for immune cells. AMPs regulate the microbiome and combat microbial infections on the skin, lungs, and gastrointestinal tract. Produced in response to microbial signals, AMPs help maintain a balanced microbial community and provide a first line of defense against infection. In preterm infants, alterations in microbiome composition have been linked to various health outcomes, including sepsis, necrotizing enterocolitis, atopic dermatitis, and respiratory infections. Dysbiosis, or an imbalance in the microbiome, can alter AMP profiles and potentially lead to inflammation-mediated diseases such as chronic lung disease and obesity. In the following review, we summarize what is known about the vital role of AMPs as multifunctional peptides in protecting newborn infants against infections and modulating the microbiome and immune response. Understanding their roles in preterm infants and high-risk populations offers the potential for innovative approaches to disease prevention and treatment.
Topics: Humans; Infant, Premature; Infant, Newborn; Microbiota; Antimicrobial Peptides; Immunity, Innate; Animals; Dysbiosis
PubMed: 38928389
DOI: 10.3390/ijms25126684 -
International Journal of Molecular... Jun 2024Atopic dermatitis (AD) is a chronic inflammatory skin condition with a high prevalence worldwide. AD pathogenesis is complex and consists of immune system dysregulation... (Review)
Review
Atopic dermatitis (AD) is a chronic inflammatory skin condition with a high prevalence worldwide. AD pathogenesis is complex and consists of immune system dysregulation and impaired skin barrier, influenced by genetic and environmental factors. The purpose of the review is to show the complex interplay between atopic dermatitis and the microbiota. Human microbiota plays an important role in AD pathogenesis and the course of the disease. Dysbiosis is an important factor contributing to the development of atopic diseases, including atopic dermatitis. The gut microbiota can influence the composition of the skin microbiota, strengthening the skin barrier and regulating the immune response via the involvement of bacterial metabolites, particularly short-chain fatty acids, in signaling pathways of the gut-skin axis. AD can be modulated by antibiotic intake, dietary adjustments, hygiene, and living conditions. One of the promising strategies for modulating the course of AD is probiotics. This review offers a summary of how the microbiota influences the development and treatment of AD, highlighting aspects that warrant additional investigation.
Topics: Dermatitis, Atopic; Humans; Dysbiosis; Gastrointestinal Microbiome; Probiotics; Microbiota; Skin; Animals
PubMed: 38928245
DOI: 10.3390/ijms25126539 -
International Journal of Molecular... Jun 2024Allergic diseases are showing increasing prevalence in Western societies. They are characterized by a heightened reactivity towards otherwise harmless environmental... (Review)
Review
Allergic diseases are showing increasing prevalence in Western societies. They are characterized by a heightened reactivity towards otherwise harmless environmental stimuli. Allergic diseases showing a wide range of severity of symptoms have a significant impact on the quality of life of affected individuals. This study aims to highlight the mechanisms that induce these reactions, how they progress, and which prenatal factors influence their development. Most frequently, the reaction is mediated by immunoglobulin E (IgE) produced by B cells, which binds to the surface of mast cells and basophils and triggers an inflammatory response. The antibody response is triggered by a shift in T-cell immune response. The symptoms often start in early childhood with eczema or atopic dermatitis and progress to allergic asthma in adolescence. An important determinant of allergic diseases seems to be parental, especially maternal history of allergy. Around 30% of children of allergic mothers develop allergic sensitization in childhood. Genes involved in the regulation of the epithelial barrier function and the T-cell response were found to affect the predisposition to developing allergic disorders. Cord blood IgE was found to be a promising predictor of allergic disease development. Fetal B cells produce IgE starting at the 20th gestation week. These fetal B cells could be sensitized together with mast cells by maternal IgE and IgE-allergen complexes crossing the placental barrier via the low-affinity IgE receptor. Various factors were found to facilitate these sensitizations, including pesticides, drugs, exposure to cigarette smoke and maternal uncontrolled asthma. Prenatal exposure to microbial infections and maternal IgG appeared to play a role in the regulation of T-cell response, indicating a protective effect against allergy development. Additional preventive factors were dietary intake of vitamin D and omega 3 fatty acids as well as decreased maternal IgE levels. The effect of exposure to food allergens during pregnancy was inconclusive, with studies having found both sensitizing and protective effects. In conclusion, prenatal factors including genetics, epigenetics and fetal environmental factors have an important role in the development of allergic disorders in later life. Children with a genetic predisposition are at risk when exposed to cigarette smoke as well as increased maternal IgE in the prenatal period. Maternal diet during pregnancy and immunization against certain allergens could help in the prevention of allergy in predisposed children.
Topics: Humans; Pregnancy; Female; Hypersensitivity; Prenatal Exposure Delayed Effects; Immunoglobulin E; B-Lymphocytes
PubMed: 38928067
DOI: 10.3390/ijms25126359 -
The Korean Journal of Physiology &... Jul 2024Atopic dermatitis (AD) is the most common inflammatory pruritic skin disease worldwide, characterized by the infiltration of multiple pathogenic T lymphocytes and...
Atopic dermatitis (AD) is the most common inflammatory pruritic skin disease worldwide, characterized by the infiltration of multiple pathogenic T lymphocytes and histological symptoms such as epidermal and dermal thickening. This study aims to investigate the effect of vinpocetine (Vinp; a phosphodiesterase 1 inhibitor) on a 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD-like model. DNCB (1%) was administered on day 1 in the AD model. Subsequently, from day 14 onward, mice in each group (Vinp-treated groups: 1 mg/kg and 2 mg/kg and dexamethasone- treated group: 2 mg/kg) were administered 100 µl of a specific drug daily, whereas 0.2% DNCB was administered every other day for 30 min over 14 days. The Vinp-treated groups showed improved Eczema Area and Severity Index scores and trans-epidermal water loss, indicating the efficacy of Vinp in improving AD and enhancing skin barrier function. Histological analysis further confirmed the reduction in hyperplasia of the epidermis and the infiltration of inflammatory cells, including macrophages, eosinophils, and mast cells, with Vinp treatment. Moreover, Vinp reduced serum concentrations of IgE, interleukin (IL)-6, IL-13, and monocyte chemotactic protein-1. The mRNA levels of IL-1β, IL-6, Thymic stromal lymphopoietin, and transforming growth factor-beta (TGF-β) were reduced by Vinp treatment. Reduction of TGF-β protein by Vinp in skin tissue was also observed. Collectively, our results underscore the effectiveness of Vinp in mitigating DNCB-induced AD by modulating the expression of various biomarkers. Consequently, Vinp is a promising therapeutic candidate for treating AD.
PubMed: 38926838
DOI: 10.4196/kjpp.2024.28.4.303 -
Drug Discoveries & Therapeutics Jun 2024Staphylococcus aureus, a Gram-positive bacterium, causes inflammatory skin diseases, such as atopic dermatitis, and serious systemic diseases, such as sepsis. In the...
Staphylococcus aureus, a Gram-positive bacterium, causes inflammatory skin diseases, such as atopic dermatitis, and serious systemic diseases, such as sepsis. In the skin and nasal environment, peptidoglycan (PGN)-degrading enzymes, including lysozyme and lysostaphin, affects S. aureus PGN. However, the effects of PGN-degrading enzymes on the acute innate immune-inducing activity of S. aureus have not yet been investigated. In this study, we demonstrated that PGN-degrading enzymes induce acute silkworm hemolymph melanization by S. aureus. Insoluble fractions of S. aureus treated with lysozyme, lysostaphin, or both enzymes, were prepared. Melanization of the silkworm hemolymph caused by the injection of these insoluble fractions was higher than that of S. aureus without enzyme treatment. These results suggest that structural changes in S. aureus PGN caused by PGN-degrading enzymes affect the acute innate immune response in silkworms.
PubMed: 38925960
DOI: 10.5582/ddt.2024.01026 -
BMJ Open Jun 2024Children with atopic dermatitis (AD) are more at risk for the neurodevelopmental disorders attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder...
INTRODUCTION
Children with atopic dermatitis (AD) are more at risk for the neurodevelopmental disorders attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) with parallel increases in global prevalences. Children afflicted with these conditions appear to share similar problems in sensory modulation but investigational studies on the underlying aetiology are scarce. This scoping review aims to find knowledge gaps, collate hypotheses and to summarise available evidence on the shared pathophysiology of AD, ADHD and ASD in children.
METHODS AND ANALYSIS
Our study will follow the methodological manual published by the Joanna Briggs Methodology for Scoping Reviews and will be reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews. The following electronic databases will be searched for studies focused on children with AD and symptoms of ADHD and/or ASD: Medline ALL via Ovid, Embase, Web of Science Core Collection and the Cochrane Central Register of Controlled Trials via Wiley.
ETHICS AND DISSEMINATION
This review does not require ethics approval as it will not be conducted with human participants. We will only use published data. Our dissemination strategy includes peer review publication and conference reports.
Topics: Humans; Dermatitis, Atopic; Autism Spectrum Disorder; Attention Deficit Disorder with Hyperactivity; Systematic Reviews as Topic; Child; Research Design
PubMed: 38925697
DOI: 10.1136/bmjopen-2023-081280 -
JMIR Dermatology Jun 2024Online patient-oriented platforms such as PatientsLikeMe (PLM) offer a venue for individuals with various diagnoses to share experiences and build community, though they...
Online patient-oriented platforms such as PatientsLikeMe (PLM) offer a venue for individuals with various diagnoses to share experiences and build community, though they may not be representative of the larger patient population. This potentially limits generalizability and raises concerns about the spread of misinformation, emphasizing the need for informed use and health care provider engagement.
Topics: Humans; Dermatology; Internet; Self-Help Groups; Social Support
PubMed: 38924778
DOI: 10.2196/50453 -
Veterinary Sciences May 2024(1) Background: Dysbiosis is frequently observed in Canine Atopic Dermatitis (CAD). Antimicrobial treatment may be necessary to treat flare ups and the use of topical...
(1) Background: Dysbiosis is frequently observed in Canine Atopic Dermatitis (CAD). Antimicrobial treatment may be necessary to treat flare ups and the use of topical treatments is beneficial to prevent the development of bacterial resistance. Wipes are an easy way to apply antiseptic agents on the skin. The aim of this study was to evaluate the benefits of 3% chlorhexidine impregnated wipes (Pyoskin wipes, MP Labo, France) on local areas of dysbiosis in dogs with CAD. (2) Methods: A total of 20 dogs suffering from CAD presented with localised areas of dysbiosis were included in this study. Affected areas were cleansed with the daily application of chlorhexidine wipes once a day for 14 days. Follow-up visits were scheduled after one and two weeks. Clinical signs (lesions and pruritus), dysbiosis scored by cytological counts (cocci and ) and investigator and owner global appreciation were evaluated. (3) Results: A statistically significant decrease in clinical scores and cytological counts were observed as soon as D7 and until D14. Both owner and investigator appreciation were considered high (4) Conclusions: The use of chlorhexidine impregnated wipes is a useful and easy way to manage localised dysbiosis in atopic dogs and allows limiting of systemic medication to prevent bacterial resistance.
PubMed: 38921987
DOI: 10.3390/vetsci11060240