Topical Anti-Inflammatory Effects of Quercetin Glycosides on Atopic Dermatitis-Like Lesions: Influence of the Glycone Type on Efficacy and Skin Absorption

Inflammation, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 14, 2025

Atopic dermatitis (AD) is a multifaceted inflammatory skin condition characterized by the involvement of various cell types, such as keratinocytes, macrophages, neutrophils, and mast cells. Research indicates that flavonoids possess anti-inflammatory properties may be beneficial in management AD. However, investigation glycoside forms for anti-AD therapy limited. We aimed to assess ability quercetin-3-O-glycosides treating AD-like lesions through silico-, cell-, animal-based platforms. The glycosylated flavonols quercitrin, isoquercitrin, rutin were used this study. also tried understand influence glycone type on bioactivity delivery glycosides. glycosides effectively reduced overexpression proinflammatory effectors interleukin (IL)-6, chemokine (C-X-C motif) ligand (CXCL)1, CXCL8, regulated upon activation normal T expressed secreted (RANTES), thymus activation-regulated (TARC) activated keratinocytes. This reduction could due inhibition extracellular signal-regulated kinase (ERK) p38 phosphorylation. Isoquercitrin (but not quercitrin rutin) arrest upregulated IL-6 CCL5 macrophage model. significantly prevented histamine release from RBL-2H3 absorption examination showed greater permeation isoquercitrin than with dual sugar moieties smaller molecular volume higher lipophilicity. deposition was enhanced about 11-fold stripped delipidized skins, which mimicked AD lesions. vivo dinitrochlorobenzene (DNCB)-induced mouse model demonstrated less erosion, scaling, epidermal hyperplasia after topical treatment. concentration cytokines/chemokines lesion decreased isoquercitrin. These effects similar those tacrolimus ointment. immunohistochemistry (IHC) displayed hyperproliferation immune infiltration results indicated quercetin provide an efficient safe way treat inflammation.

Language: Английский

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Epigenetic control of inflammation in Atopic Dermatitis

Seminars in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 154, P. 199 - 207

Published: April 27, 2023

Atopic dermatitis (AD), also known as atopic eczema, is a common but complex chronic, itchy skin condition with underlying inflammation of the skin. This ailment prevalent worldwide and affects people all ages, particularly children below five years age. The itching resulting rashes in AD patients are often result inflammatory signals, thus necessitating closer look at inflammation-regulating mechanisms for putative relief, care therapy. Several chemical- well genetically-induced animal models have established importance targeting pro-inflammatory microenvironment. Epigenetic gaining attention towards better understanding onset progression inflammation. physiological processes implications pathophysiology AD, such as, barrier dysfunction either due to reduced filaggrin / human β‐defensins or altered microbiome, reprograming Fc receptors overexpression high affinity IgE receptors, elevated eosinophil numbers IL-22 production by CD4 + T cells epigenetic that include differential promoter methylation and/or regulation non-coding RNAs. Reversing these changes has been verified reduce burden through secretion cytokines IL-6, IL-4, IL-13, IL-17, etc, benefit against experimental models. A thorough remodeling potential opening avenues novel diagnostic, prognostic therapeutic options.

Language: Английский

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Partially hydrolyzed guar gum ingestion suppresses atopic dermatitis-like symptoms through prebiotic effect in mice

Journal of Clinical Biochemistry and Nutrition, Journal Year: 2025, Volume and Issue: 76(3), P. 280 - 288

Published: Jan. 1, 2025

Growing knowledge reveals the association between gut microbiome and skin, rendering an appealing potential therapeutic target for atopic dermatitis (AD). In this study, we assessed effect of partially hydrolyzed guar gum (PHGG) on AD-like symptoms induced by topical 1-Chloro-2,4-dinitrobenzene (DNCB) in BALB/c mice. Four weeks PHGG feeding prevented loss epidermal barrier integrity epithelial hyperplasia AD lesion (p<0.05, size >0.80), indicating a reduction symptoms. According to postulated mechanism, ingestion modulates resulting enhanced butyrate production (p<0.05). Butyrate suppresses Th2 function immunity, which is believed have significance systemic immune regulation. The lowering blood cytokines (IL-4 IL-10, p<0.05) PHGG-fed group confirmed existence such pathway, can possibly be considered indirect involvement suppression response lesions. These findings encourage support skin through system, implying that daily may beneficial suppressing across gut-immune-skin axis.

Language: Английский

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Efficacy and Safety of 611 in Chinese Adults with Moderate-to-Severe Atopic Dermatitis: Results from a Phase II Trial

Dermatology and Therapy, Journal Year: 2025, Volume and Issue: unknown

Published: March 9, 2025

Atopic dermatitis (AD) is a chronic inflammatory skin disease. 611, humanized monoclonal antibody, selectively targets the interleukin (IL)-4 receptor alpha, thereby inhibiting signaling of both and IL-13. This phase 2 study aimed to evaluate efficacy safety 611 in Chinese adults with moderate-to-severe AD. randomized, double-blind, placebo-controlled was conducted between October 2022 September 2023. Eligible patients AD were randomly assigned 1:1:1 ratio receive at dose either 300 mg (loading 600 mg) every weeks (Group A) or 4 B), placebo for 16 weeks, followed by an 8-week follow-up period. The primary endpoint proportion achieving least 75% reduction Eczema Area Severity Index (EASI-75) score week 16. pharmacodynamics also assessed. After treatment, 60.0% Group A 48.8% B achieved EASI-75, significantly higher than group (15.6%, p < 0.01). Additionally, doses improved Investigator's Global Assessment (IGA) scores, peak pruritus numerical rating scale (NRS), other endpoints. Patients receiving demonstrated significant reductions serum thymus activation-regulated chemokine (TARC) total immunoglobulin E (IgE) levels. incidence treatment-emergent adverse events (TEAEs) similar across all dosage groups. most common 611-related TEAE upper respiratory tract infections. No new concerns identified. high favorable profile ClinicalTrials.gov, NCT05544591.

Language: Английский

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Cure for the itch: current clinical standards and therapies in allergic eczema

Frontiers in Allergy, Journal Year: 2025, Volume and Issue: 6

Published: April 3, 2025

Allergic Eczema (AE) is a chronic, relapsing skin condition that significantly affects the quality of life AE patients and their caretakers. Decades scientific clinical research has helped understand highly complex underpinnings presentation wherein multitude variables, including conspicuous variables such as environmental allergens, immunological triggers, genetic predisposition individuals, to more nuanced socio-economic status, play an important part. Given complexity disease, it imperative develop biomarkers enabling early reliable identifications help in active management thereby minimizing impact burden disease on patients. In this mini review, we provide brief overview AE, affected demographics, trigger its onset, summarize discovery various total specific serum IgE levels, Th2 cytokine filaggrin (FLG) mutations, periostin levels skin, etc. have been developed over years further improve state monitoring progression. Lastly, also interventions therapies, topical agents, phototherapy, biologics, are available manage AE-related complications. While vastly improved standard care diagnosis for patients, there still many unmet needs developing non-invasive, effective, predictors which can usher better personalized treatments demographics.

Language: Английский

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Real-World Effectiveness and Safety of Upadacitinib and Abrocitinib in Moderate-to-Severe Atopic Dermatitis: A 52-Week Retrospective Study

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(9), P. 2953 - 2953

Published: April 24, 2025

Background: Atopic dermatitis (AD) is a chronic pruritic inflammatory disease affecting children and adults. Upadacitinib abrocitinib are selective Janus kinase 1 inhibitors approved for the treatment of moderate-to-severe AD. Although their efficacy safety described in phase 3 clinical trials, real-world data limited. Objectives: We aimed to evaluate effectiveness upadacitinib real-life adult population with AD throughout an extended observation period. Methods: This retrospective observational study was conducted by analyzing from electronic records IRCCS Humanitas Research Hospital January 2023 December 2024. Patients were administered either (15 or 30 mg) (100 200 mg). Effectiveness evaluated using clinician-reported scores (Investigator Global Assessment [IGA] Eczema Area Severity Index [EASI]) patient-reported outcomes (peak pruritus numerical rating scale [PP-NRS]) at weeks 8, 16, 32 52. Statistical significance set probability value (p-value) < 0.05. Adverse events also collected. Results: In total, 129 patients included study, 84 them reached 52 weeks. At week 52, EASI 75, 90, 100 responses 88.9%, 70.8%, 54.2% upadacitinib, 100%, 91.7%, 75% abrocitinib. An IGA score equal 0 achieved 84.7% treated 100% those receiving A four-point reduction baseline PP-NRS reported 86.1% 83.3% after one year follow-up. Conclusions: Our showed comparable even higher terms compared phase-3 no new concerns, supporting

Language: Английский

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Construction and Evaluation of an Artificial Intelligence Assistant Decision-Making System Focused on the Treat-to-Target Framework and Full Process Management for Atopic Dermatitis: Study Protocol for a Randomized Controlled Trial

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(9), P. 3015 - 3015

Published: April 27, 2025

Background/Objectives: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by recurrent rashes and itching, which seriously affects the quality of life patients brings heavy economic burden to society. The treat-to-target (T2T) strategy was proposed guide optimal use systemic therapies in with moderate severe AD, patients' adherence emphasized along combined evaluation from both health providers patients. While effective treatments for AD are available, non-adherence treatment common clinical practice due unawareness self-evaluation lack concern about specific follow-up time points clinics, leads failure repeated relapse AD. Methods: This project consists three parts. First, an artificial intelligence (AI) model diagnosis severity grading based on deep learning will be trained. Second, AI assistant decision-making system (AIADMS) form app developed. Third, we design prospective, randomized controlled trial test hypothesis that AIADMS implementation T2T could help control progression improve outcomes. Results: A total 232 participants diagnosed included allocated into group or group. In group, assisted using during process management at scheduled points, including 2 weeks, 4 8 12 6 months, months after treatment. diagnosis, treatment, carried out according current routine face-to-face basis. primary outcome overall efficiency rate treating objectives PP-NRS, EASI, SCORAD, POEM, DLQI weeks calculated as "Total number 5 objectives/total *100%". Spss20.0 software used analyze data principle intent treat. Trial Registration: protocol registered National Institutes Health Clinical Trials Registry registration NCT06362629 11 April 2024. Conclusions: study aims integrating advanced technology, patient engagement, clinician oversight through achieve goals safe long-term control.

Language: Английский

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T cell immunophenotypes and IgE responses in patients with moderate‐to‐severe atopic dermatitis receiving dupilumab

Clinical and Translational Allergy, Journal Year: 2025, Volume and Issue: 15(5)

Published: May 1, 2025

Abstract Background Targeting the interleukin‐4 receptor alpha (IL‐4Rα) subunit has proven clinical efficacy in atopic dermatitis (AD). Objective This study assessed peripheral phenotype and function of T‐cells, but also levels total sIgE its receptors AD patients receiving dupilumab. Methods were clinically ( n = 75) blood samples taken 25). Multiparametric flow cytometry was performed to characterize T‐cell subsets (before treatment 6 months later). Total specific IgE measured by ImmunoCap, soluble CD23 FcεR1 serum ELISA, eosinophils differential analysis. Results SCORing Atopic Dermatitis scores body surface area involvement decreased upon after 67% 77% from baseline. At T cell level, we observed a 0.55‐fold reduction Th2‐cells mean 27% increase regulatory T‐cells baseline, accompanied shifts towards Th1 Th17 phenotypes. Furthermore, circulating CD4 + CXCR5 TFH17 TFH17.1 positive cells (mean 40% 42%) T‐cell‐specific IL‐2 (+0.96‐fold) IL‐10 (+1.96‐fold) secretion increased, whereas IL‐4 −55%) IL‐17A −27%) reduced. Eosinophil counts −22%), −47%) House Dust Mite −40%) decreased, remained unchanged. Conclusions The cytokine profiles during anti‐IL4‐Ra suggest that targeting this pathway promotes systemic shift compartment reducing helper type 2 complementary responses. sustainability these disease‐modifying effects requires further investigation.

Language: Английский

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Human Tendon‐on‐a‐Chip for Modeling the Myofibroblast Microenvironment in Peritendinous Fibrosis

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: 14(4)

Published: Nov. 15, 2024

Understanding the myofibroblast microenvironment is critical to developing therapies for fibrotic diseases. Here development of a novel human tendon-on-a-chip (hToC) reported model this crosstalk in peritendinous adhesions, which currently lacks biological therapies. The hToC facilitates cellular and paracrine interactions between vascular component, contains endothelial cells monocytes, tissue hydrogel component that houses tendon macrophages. It found replicates some aspects vivo inflammatory phenotypes preclinical clinical samples, including activated mTOR signaling, inflammation, contraction induced by activation, cytokines secretion, transendothelial migration monocytes hydrogel. Transcriptional analysis demonstrates significant overlap enriched pathways with tenolysis activation signaling. Rapamycin suppresses inflammation phenotype hToC, provides proof-of-concept its utility as an vitro tool investigating multicellular fibrosis testing therapeutics mitigate it.

Language: Английский

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Predictive Factors of Early Response to Dupilumab in Patients with Moderate-to-Severe Atopic Dermatitis

Journal of Clinical Medicine, Journal Year: 2023, Volume and Issue: 12(20), P. 6575 - 6575

Published: Oct. 17, 2023

Efforts have been made to identify factors influencing clinical response in patients with atopic dermatitis (AD) treated dupilumab. A retrospective single-center observational study was carried out by analyzing data from 492 aged 12 years and older moderate-to-severe AD. The aimed baseline demographic that could predict the achievement of a mild level disease, i.e., an Eczema Area Severity Index (EASI) ≤ 7, within 4 weeks dupilumab initiation. Classic, generalized lichenoid inflammatory phenotypes compared nummular eczema phenotype (OR = 6.9, 95% CI 2.04-23.48 OR 4.22, 1.22-14.66, respectively) EASI 24 between 24-29, ≥ 29 3.1, 1.81-5.41 1.8, 1.05-3.07, respectively), were found be predictive early dupilumab, highlighting importance biological treatment

Language: Английский

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