Search Results (135)

Atopic dermatitis (AD) is a common chronic inflammatory skin disorder characterized by immune dysregulation and skin barrier impairment. This study evaluated the anti-inflammatory and immunomodulatory effects of Camellia japonica extract in a 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model using SKH-1 hairless mice. Topical application of Camellia japonica extract for four weeks significantly alleviated AD-like symptoms by reducing epidermal thickness, mast cell infiltration, and overall skin inflammation. Hematological analysis revealed a marked decrease in total white blood cell (WBC) and neutrophil counts. Furthermore, the Camellia japonica extract significantly decreased oxidative stress, as evidenced by reduced serum reactive oxygen species (ROS) and nitric oxide (NO) levels, while enhancing the activity of antioxidant enzymes such as catalase. Importantly, allergic response markers including serum immunoglobulin E (IgE), histamine, and thymic stromal lymphopoietin (TSLP), were also downregulated. At the molecular level, Camellia japonica extract suppressed the expression of key pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and T helper 2 (Th2)-type cytokines such as IL-4 and IL-5, while slightly upregulating the anti-inflammatory cytokine IL-10. Collectively, these findings suggest that Camellia japonica extract effectively modulates immune responses, suppresses allergic responses, attenuates oxidative stress, and promotes skin barrier recovery. Therefore, application of Camellia japonica extract holds the promising effect as a natural therapeutic agent for the prevention and treatment of AD-like skin conditions. Full article

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin condition characterized by intense pruritus and a significant impact on a patient’s quality of life. Despite advancements in understanding AD pathophysiology, there remains a critical need for innovative therapeutic options to better manage this debilitating disease. This review focuses on the evolving landscape of biological therapies for AD, offering insights into their role, mechanisms of action, and potential to revolutionize patient care. In this review, we explore the underlying immunological mechanisms of AD, particularly the role of cytokines and immune pathways implicated in the disease, and how targeted biological therapies modulate these pathways. Current FDA- and EMA-approved biologics, such as Dupilumab, are also discussed in terms of their mechanisms of action, efficacy, and safety. Additionally, we compare their effectiveness, highlighting the benefits and limitations observed in clinical practice. Emerging biological therapies currently under development offer new hope, with innovative targets like IL-13, IL-31, and thymic stromal lymphopoietin (TSLP) representing promising avenues for intervention. We also delve into personalized medicine, emphasizing the importance of biomarkers for predicting treatment response and stratifying AD patients to optimize therapeutic outcomes. Moreover, the synergistic potential of combining biologics with traditional therapies is reviewed, along with a discussion of the challenges involved, including safety, long-term efficacy, and patient adherence. We address the future direction of AD treatment, including microbiome-targeting biologics and the development of next-generation immune modulators. We highlight a new era of targeted treatment possibilities for this complex condition. Full article

Asthma is defined as a chronic respiratory disease, the processes of which are mainly related to the hyperreactivity of the immune system. Airway hyperresponsiveness and remodeling are other hallmarks of asthma that are strongly involved in the progression of the disease. Moreover, asthma is associated with the occurrence of atopic dermatitis, chronic sinusitis, allergic rhinitis, and a high profile of T2-type cytokines, such as IL-4, IL-5 and IL-13. The hyperresponsiveness of the immune system is a consequence of aberrant levels of alarmins, endogenous molecules that induce pro-inflammatory responses. They are released as a result of a defect or cell death, leading to the initiation of an inflammatory reaction. High-mobility group box 1 (HMGB1), S100 proteins, interleukin-33 (IL-33), thymic stromal lymphopoietin (TSLP), and IL-25 bind to various receptors, influencing the behavior of immune cells, resulting in stimulated migration and activation of these cells. In this review, we will discuss the potential role of alarmins in the pathogenesis of asthma. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disorder marked by intricate interplay among skin barrier dysfunction, immune dysregulation, and microbial dysbiosis. While therapeutic advancements targeting T helper 2 (Th2) cytokines, such as interleukin (IL)-4 and IL-13, and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway have yielded promising outcomes, a significant proportion of patients still experience inadequate relief, particularly from persistent pruritus. Achieving minimal disease activity remains an unmet clinical priority and a cornerstone of effective AD management. This review provides an in-depth analysis of current therapeutic approaches and integrates findings from recent biologic studies, with a particular focus on innovative strategies under active investigation. These approaches include targeting components of the innate immune system, such as thymic stromal lymphopoietin (TSLP) and IL-1 family cytokines; the adaptive immune system, including OX40-OX40L interactions and Th17- and Th22-related cytokines; and mechanisms associated with pruritus, such as IL-31, histamine receptors, and neurokinin 1 receptor. Emerging insights underscore the transformative potential of personalized therapeutic regimens tailored to the distinct endotypes and severity of AD. Advances in deciphering the pathogenesis of AD are unlocking unprecedented opportunities for precision medicine, offering renewed hope for improved outcomes in this multifaceted and heterogeneous condition. Full article

Atopic Dermatitis (AD) is a common inflammatory skin disease characterized primarily by its chronic and recurrent nature. This has a significant impact on productivity and human longevity. Dysbiosis of gut flora has been demonstrated to be significantly associated with the progression of AD. In our previous research, it was shown that Lactobacillus rhamnosus RL5-H3-005 (RL) and Pediococcus acidilactici RP-H3-006 (RP) have the ability to reduce the risk of disease in AD mice through the gut–mammary axis. Based on our previous work, this study aims to further investigate the effects of kynurenine (KYN), a metabolite of RL and RP, on AD mice induced by 2, 4-dinitrofluorobenzene (DNFB). In this study, we found that supplementing KYN in AD mice effectively alleviates the pathological symptoms of atopic dermatitis and further improves the levels of SCFAs in their intestines. Further research indicates that KYN’s therapeutic effects on AD are primarily manifested in the reduction of secretory immunoglobulin A (sIgA), immunoglobulin E (IgE), interleukin-4 (IL-4), IL-5, IL-13, and thymic stromal lymphopoietin (TSLP) levels in mice, while also repairing the intestinal barrier function of AD mice. Overall, the metabolites KYN of probiotics RL and RP can regulate the levels of SCFAs of mice, potentially improving the symptoms of AD mice through the gut–skin axis. Full article

Wild soybean (Glycine soja, GS) is a traditional medicine used to treat inflammation. In this study, the anti-atopic properties of GS leaf and stem extract on skin inflammation were evaluated in the Dermatophagoides farinae-extract-induced mouse model and keratinocytes. Oral administration of the GS extract reduced scratching, dermatitis score, transepidermal water loss, thickness of epidermis, inflammatory cell accumulation, and serum concentrations of thymic stromal lymphopoietin and immunoglobulin E. GS downregulated the expression of inflammatory gene markers of atopic dermatitis (AD), including interleukin (IL)-6; regulated on activation, normal T cell expressed and secreted (RANTES); thymus- and activation-regulated chemokine (TARC); and macrophage-derived chemokine (MDC) and upregulated the expression of filaggrin, a keratinocyte differentiation marker, in skin tissue. GS downregulated Janus kinase 1, signal transducer and activation of transcription (STAT) 1, and STAT3 pathways. Using ultra-performance liquid chromatography, we identified seven flavonoids in GS extract, including apigenin, epicatechin, genistein, genistin, daidzin, daidzein, and soyasaponin Bb. GS, apigenin, and genistein reduced the expression of IL-6, MDC, TARC, and RANTES and increased filaggrin via the downregulation of STAT3 phosphorylation in interferon-γ/tumor necrosis factor-α-stimulated keratinocytes. Our results suggest that GS leaf and stem extract ameliorates AD-like skin inflammation by regulating the immune response and restoring skin barrier function. Full article

Background: Asthma is a chronic inflammatory disorder in millions of individuals across the globe with high morbidity, mortality, and health care costs. Despite advances in asthma treatment, long-term remission is a challenging target to achieve. Objectives: This review will address the path to remission in asthma with focus on the role of biologic agents in severe asthma management and on the question as to whether long-term disease control and remission are a reality. Methods: A systematic literature review from 1971 to 2025 was conducted through databases such as PubMed, MEDLINE, Scopus, and Web of Science. Clinical trials, meta-analyses, and real-world evidence concerning biologic therapies, such as monoclonal antibodies targeting interleukin -5 (IL-5), IL-4/IL-13, immunoglobulin E, and thymic stromal lymphopoietin, were considered. Symptom control, exacerbation frequency, lung function, and oral corticosteroid (OCS) use were some of the outcomes considered. Results: Biologic treatments have yielded significant gains in asthma control and reduction of exacerbation. Complete remission—long-term resolution of symptoms, inflammation, and drug dependence—is still difficult to achieve. Early intervention with biologics may prevent irreversible airway remodeling, but long-term remission is not in sight. These drugs reduce OCS dependency, but sustainability of remission remains to be investigated. Conclusions: Biologic therapies have advanced asthma treatment, particularly in severe cases, by improving symptoms and reducing exacerbations. However, complete remission remains a distant goal. The development of standardized remission criteria, better patient stratification, and long-term clinical studies are necessary to help achieve sustained asthma control and remission. Full article

Pediatric gastroenterology is entering a pivotal phase marked by significant challenges and emerging opportunities in treating conditions like celiac disease (CeD), eosinophilic esophagitis (EoE), inflammatory bowel disease (IBD), and autoimmune hepatitis (AIH) pose significant clinical hurdles, but new therapeutic avenues are emerging. Advances in precision medicine, particularly proteomics, are reshaping care by tailoring treatments to individual patient characteristics. For CeD, therapies like gluten-degrading enzymes (latiglutenase, Kuma030) and zonulin inhibitors (larazotide acetate) show promise, though clinical outcomes are inconsistent. Immunotherapy and microbiota modulation, including probiotics and fecal microbiota transplantation (FMT), are also under exploration, with potential benefits in symptom management. Transglutaminase 2 inhibitors like ZED-1227 could help prevent gluten-induced damage. Monoclonal antibodies targeting immune pathways, such as AMG 714 and larazotide acetate, require further validation in pediatric populations. In EoE, biologics like dupilumab, cendakimab, dectrekumab (IL-13 inhibitors), and mepolizumab, reslizumab, and benralizumab (IL-5/IL-5R inhibitors) show varying efficacy, while thymic stromal lymphopoietin (TSLP) inhibitors like tezepelumab are also being investigated. These therapies require more pediatric-specific research to optimize their use. For IBD, biologics like vedolizumab, ustekinumab, and risankizumab, as well as small molecules like tofacitinib, etrasimod, and upadacitinib, are emerging treatments. New medications for individuals with refractory or steroid-dependent AIH have been explored. Personalized therapy, integrating precision medicine, therapeutic drug monitoring, and lifestyle changes, is increasingly guiding pediatric IBD management. This narrative review explores recent breakthroughs in treating CeD, EoE, IBD, and AIH, with a focus on pediatric studies when available, and discusses the growing role of proteomics in advancing personalized gastroenterological care. Full article

The spiro compound, 5,5′-dimethoxy-1,3-bis(3-(trifluoromethyl)phenyl)-3,3a-dihydro-1H-spiro[cyclopenta[a]indene-2,2′-indene]-1′,8(3′H,8aH)-dione (4), was synthesized and identified by NMR spectroscopy, mass spectrometry, and X-ray crystallography. Compound 4, C₃₆H₂₆F₆O₄, was crystallized in the triclinic space group P-1with the cell parameters a = 8.8669(5) Å, b = 10.5298(8) Å, c = 17.0135(11) Å, α = 91.396(2)°, β = 90.490(2)°, γ = 109.235°, V = 1499.14(17) ų, Z = 2. In an asymmetric unit, two molecules are packed by short contacts to form an inversion dimer. The molecules are linked into chains along the a- and b-axis directions by additional short contacts in the crystal. Compound 4 was synthesized by the dimerization of (E)-5-methoxy-2-(3-(trifluoromethyl)benzylidene)-2,3-dihydro-1H-inden-1-one (3). (E)-5-Methoxy-2-(3-methoxybenzylidene)-2,3-dihydro-1H-inden-1-one (5), one of the analogs of compound 3, was compared with compound 4 based on in vitro experiments, DFT calculations, and an in silico docking study. The HOMO/LUMO energy difference and binding energy difference between the two compounds are consistent with the results obtained from an in vitro assay where 4 showed a better effect than 5. To evaluate the biological activity of 4, we examined its inhibitory effects on Early Growth Respone-1 (EGR-1)-regulated gene expression in HaCaT keratinocytes. Treatment of cells with 4 reduced interleukin-4 (IL-4)-induced thymic stromal lymphopoietin (TSLP) mRNA levels, as revealed by reverse transcription-polymerase chain reaction and quantitative real-time PCR. Furthermore, the electrophoretic mobility shift assay demonstrated that 4 inhibited IL-4-induced DNA binding of EGR-1 to the promoter region of the TSLP gene. Full article

Biologic therapies have revolutionized the treatment of severe allergic diseases, including asthma, atopic dermatitis (AD), chronic spontaneous urticaria (CSU), chronic rhinosinusitis with nasal polyps (CRSwNP), eosinophilic gastrointestinal diseases (EGIDs), and allergic rhinitis (AR). These molecularly targeted agents provide significant benefits for patients unresponsive to conventional treatments by addressing underlying immune mechanisms, particularly type 2 inflammation driven by cytokines such as IL-4, IL-5, and IL-13. Recent advancements include biologics targeting alarmins like thymic stromal lymphopoietin (TSLP) and IL-33, which may address both type 2 and non-type 2 inflammation, broadening their therapeutic scope. Despite their effectiveness, biologics remain expensive, posing socioeconomic challenges, and there are concerns regarding long-term safety and inter-individual variability in responses. Promising innovations such as bispecific antibodies and ultra-long-acting agents are under investigation, alongside digital health tools like remote biomarker monitoring and AI-driven decision support systems, which aim to enhance personalized care. However, disparities in access, particularly for underserved populations, underscore the need for policy reforms and affordable biosimilars. This review synthesizes recent findings and emerging trends, highlighting the evolving role of biologics in transforming allergic disease management and offering insights into future research directions. Full article

Atopic dermatitis (AD) is a common inflammatory skin disease characterized by recurrent eczema and chronic itching, affecting a significant portion of the global population. This study investigated the effects of Corydalis Tuber 70% ethanol extract (CTE) on tumor necrosis factor-α- and interferon-γ (TI)-stimulated human keratinocytes (HaCaT) and a house dust mite-induced AD mouse model, elucidating its mechanism via transcriptome analysis. A total of 13 compounds, including columbamine, corydaline, dehydrocorydaline, and glaucine, were identified in CTE using ultra performance liquid chromatography-tandem mass spectrometry. CTE downregulated pathways related to cytokine signaling and chemokine receptors in TI-stimulated HaCaT cells. It significantly inhibited C-C motif chemokine ligand (CCL)5, CCL17, and CCL22 levels by blocking the Janus kinase-signal transducers and activators of transcription and nuclear factor kappa-light-chain-enhancer of activated B cells pathways. In the AD mouse model, topical CTE significantly decreased dermatitis scores, epidermal thickening, and inflammatory cell infiltration. Plasma levels of histamine, immunoglobulin E, CCL17, CCL22, corticosterone, and cortisol were reduced. Lesions showed decreased thymic stromal lymphopoietin, CD4⁺ T cells, interleukin-4, and intercellular adhesion molecule-1 expression. The findings demonstrate that CTE alleviates AD by modulating inflammatory mediators, cytokines, and chemokines, reducing inflammatory cell infiltration, and alleviating stress-related factors. Full article

TSLP is an alarmin released upon activation of epithelia in response to various external stimuli and is involved in type 2 cytokine-mediated pathological disorders. The formation of a high-affinity heterodimeric receptor complex, comprising the thymic stromal lymphopoietin receptor (TSLPR) chain and IL-7Rα, is required for signaling. This study investigated whether TSLP and TSLPR expression in peripheral blood or nasal polyps could provide a valuable approach for the molecular phenotyping of patients with chronic rhinosinusitis with nasal polyps (CRSwNP). The study population comprised 156 unrelated Caucasian individuals, including 45 controls and 111 patients with CRSwNP. Quantitative PCR analysis of TSLP and TSLPR was performed on the population study’s peripheral blood and nasal biopsy. The data were analyzed for potential associations, and possible use as a biomarker was studied. Significant differences were observed in TSLP and TSLPR blood expression between the control group and patients. Similarly, the expression of TSLP observed in biopsy samples was statistically significantly elevated in the polyp tissue of the patient compared with healthy controls. The combination of TSLP and TSLPR expression testing with peripheral blood eosinophils represents a more specific biomarker in patients exhibiting low eosinophil values. Further investigation of TSLP/TSLPR mRNA levels in peripheral blood may yield new minimally invasive biomarkers. Full article

In recent years, a global increase in allergy incidence following chemical exposure has been observed. While the process of skin sensitization is well characterized through the adverse outcome pathway (AOP) framework, the immunological mechanisms underlying respiratory sensitization remain less well understood. Respiratory sensitizers are classified as substances of very high concern (SVHC) under the European Union (EU) regulation for the registration, evaluation, authorization and restriction of chemicals (REACH), emphasizing the importance of evaluating respiratory tract sensitization as a critical hazard. However, the existing new approach methodologies (NAMs) for the identification of skin sensitizers lack the capacity to differentiate between skin and respiratory sensitizers. Thus, it is imperative to develop physiologically relevant test systems specifically tailored to assess respiratory sensitizers. This study aimed to evaluate the efficacy of ALIsens^®, a three-dimensional (3D) in vitro alveolar model designed for the identification of respiratory sensitizers and to determine its ability to correctly identify sensitizers. In this study, we used a range of skin sensitizers and non-sensitizers to define the optimal exposure dose, identify biomarkers, and establish tentative thresholds for correct sensitizer classification. The results demonstrate that ALIsens^® is a promising in vitro complex model that could successfully discriminate respiratory sensitizers from skin sensitizers and non-sensitizers. Furthermore, the thymic stromal lymphopoietin receptor (TSLPr) cell surface marker was confirmed as a reliable biomarker for predicting respiratory sensitization hazards. Full article

The root bark of Dictamus dasycarpus Turcz. has been traditionally used for the topical treatment of skin disorders like pruritus. This study was designed to investigate the inflammatory and skin barrier protective effects of D. dasycarpus in mice with calcipotriol (MC903)-induced atopic dermatitis (AD). Topical skin lesions on male Balb/c mice (8 weeks old) were treated topically with an ethanolic extract of D. dasycarpus (EEDD), and skin water content, water holding capacity (WHC), histopathological abnormalities, and inflammatory cytokine and chemokine levels were investigated. Topical application of EEDD effectively alleviated skin lesion severity, improved skin water content and WHC, and ameliorated histopathological abnormalities, including hyperkeratosis, blood vessel numbers near the epidermis, spongiotic changes, and immune cell infiltration in skin tissues. EEDD also suppressed inflammatory cytokines and chemokines, such as tumor necrosis factor (TNF)-α, thymic stromal lymphopoietin (TSLP), interleukin (IL)-1β, IL-4, IL-8, and monocyte chemotactic protein (MCP)-1. In RAW264.7 cells, EEDD reduced nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) expression and suppressed the phosphorylations of extracellular signal-regulated kinase (ERK) and p38. These results suggest that the root bark of D. dasycarpus has therapeutic potential due to its anti-dermatitis and skin barrier protective effects in AD and that it could be used as an ingredient in skincare products. Full article