Evolving cognition of the JAK-STAT signaling pathway: autoimmune disorders and cancer

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 19, 2023

Abstract The Janus kinase (JAK) signal transducer and activator of transcription (JAK-STAT) pathway is an evolutionarily conserved mechanism transmembrane transduction that enables cells to communicate with the exterior environment. Various cytokines, interferons, growth factors, other specific molecules activate JAK-STAT signaling drive a series physiological pathological processes, including proliferation, metabolism, immune response, inflammation, malignancy. Dysregulated related genetic mutations are strongly associated activation cancer progression. Insights into structures functions have led development approval diverse drugs for clinical treatment diseases. Currently, been developed mainly target commonly divided three subtypes: cytokine or receptor antibodies, JAK inhibitors, STAT inhibitors. And novel agents also continue be tested in preclinical studies. effectiveness safety each kind drug warrant further scientific trials before put being applications. Here, we review current understanding fundamental composition function pathway. We discuss advancements JAK-STAT–related pathogenic mechanisms; targeted therapies various diseases, especially disorders, cancers; newly inhibitors; challenges directions field.

Language: Английский

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Bioadhesive Nanoparticles in Topical Drug Delivery: Advances, Applications, and Potential for Skin Disorder Treatments

Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(2), P. 229 - 229

Published: Feb. 10, 2025

Skin disorders are the fourth most common cause of all diseases, which affect nearly one-third world’s population. Topical drug delivery can be effective in treating a range skin disorders, including microbial infections, cancer, dermatitis, burn injury, wounds, and psoriasis. Bioadhesive nanoparticles (BNPs) serve as an efficient topical system they dual purposes bioadhesives nanocarriers, mediate targeted delivery, prolong retention time, deepen penetration through layers. There is increasing demand for BNP-based applications medicine because their various advantages, biodegradability, flexibility, biocompatibility, enhanced adhesive strength. A number BNPs have already been developed evaluated potential systems. In addition, studies carried out to evaluate treatment atopic irritant contact psoriasis, severe injuries. This review article timely unique, it provides extensive unique summary recent advances wide-ranging disorders. Moreover, this also useful discussion on bioadhesion mechanism biopolymers that used prepare BNPs.

Language: Английский

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Blockage of the IL-31 Pathway as a Potential Target Therapy for Atopic Dermatitis

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(2), P. 577 - 577

Published: Feb. 8, 2023

Atopic dermatitis (AD), a pruritic, inflammatory chronic disease with multifactorial pathogenesis, has been therapeutic challenge. Novel target treatments aim to reduce not only the immunologic dysfunction and microbiome dysbiosis but also recovery of damaged skin barrier. The current review focuses on interleukin 31 (IL-31) pathway AD offers an overview clinical studies monoclonal antibodies blocking this cascade. Pruritus, key symptom AD, substantial participation IL-31 complex activation relevant signaling pathways. Epidermal keratinocytes, cells, cutaneous peripheral nerves express interleukin-31 receptor α-chain (IL-31RA), upregulated by Staphylococcus aureus toxins or Th2 cytokines involved in AD. Nemolizumab is humanized antibody that antagonizes IL-31RA, inhibiting cascade therefore contributing reducing pruritus inflammation recovering barrier patients. Phases 2 3 trials nemolizumab show suitable safety profile, fast, efficient, sustained reduction severity scores, especially when associated topical treatment. Deciphering full interplay may expand potential as targeted therapy for other pruritic conditions.

Language: Английский

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Adipokines in atopic dermatitis: the link between obesity and atopic dermatitis

Lipids in Health and Disease, Journal Year: 2024, Volume and Issue: 23(1)

Published: Jan. 23, 2024

Abstract Atopic dermatitis (AD) is a chronic skin condition with intense pruritus, eczema, and dry skin. The recurrent pruritus numerous complications in patients AD can profoundly affect their quality of life. Obesity one its comorbidities that has been confirmed to be the hazard factor also worsen severity. Nevertheless, specific mechanisms explain connection between obesity remain incompletely recognized. Recent studies have built hopes on various adipokines this connection. Adipokines, which are disturbed by an obese state, may lead immune system imbalances people promote development disease. This review focuses abnormal expression patterns potential regulatory molecular associated AD. elucidated through involvement adipokines. conduces in-depth exploration pathogenesis provides new perspective develop therapeutic targets.

Language: Английский

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Antioxidant defense of children and adolescents with atopic dermatitis: Association with disease severity

Allergologia et Immunopathologia, Journal Year: 2024, Volume and Issue: 52(1), P. 65 - 70

Published: Jan. 1, 2024

Atopic dermatitis (AD) is a relapsing, chronic cutaneous inflammatory disease with onset, in general, early childhood. Chronic skin inflammation associated overproduction of reactive oxygen species (ROS) such as superoxide and hydrogen peroxide. Oxidative stress, an imbalance between the production free radicals antioxidant defense, results tissue due to upregulation genes that encode cytokines. This condition plays important role pathogenesis AD.

Language: Английский

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Biomarkers in Atopic Dermatitis

Dermatology and Therapy, Journal Year: 2024, Volume and Issue: 14(7), P. 1729 - 1738

Published: June 14, 2024

Atopic dermatitis (AD) is a chronic inflammatory skin condition. The pathogenesis involves genetic, environmental, and immunological factors as well barrier dysfunction of the epidermis. Biomarkers may play significant role in diagnosis, severity assessment, treatment monitoring AD. They are categorizable into diagnostic prognostic stratification biomarkers, offering potential for more personalized approach. Although there have been tremendous therapeutic advancements with interleukin (IL) antagonists Janus kinase (JAK) inhibitors, domain biomarkers still requires further research to clarify their place diagnosis prognosis AD unravel better scientific basis medical care patients This article reviews various relation different phenotypes endotypes.

Language: Английский

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Update on the pathogenesis of atopic dermatitis

Anais Brasileiros de Dermatologia, Journal Year: 2024, Volume and Issue: 99(6), P. 895 - 915

Published: Aug. 12, 2024

Atopic dermatitis is a chronic, recurrent, and multifactorial skin-mucosal manifestation resulting from the interaction between elements mainly associated with skin barrier deficit, homeostasis of immune response, neurological aspects, patterns reactivity to environmental antigens, which are established in genetically predisposed individuals. In addition skin, atopic diathesis involves other organs such as airways (upper lower), eyes, digestive tract, neuropsychiatric inflict additional morbidity on dermatological patient. The different phenotypes disease fundamentally depend participation each these factors, life circumstances, age groups, occupational exposure patterns, physical activity, pollution, genetic load, climatic factors. A better understanding complexity its pathogenesis allows not only therapeutic targets but also how identify preponderant that mediate activity circumstance, for selecting best treatment strategies mitigation triggering This narrative review presents an update dermatitis, especially aimed at clinical manifestations, main context available strategies.

Language: Английский

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Immunohistochemical investigation of transient receptor potential melastatin-2 and spexin immunoreactivity in atopic dermatitis and mycosis fungoides

Archives of Dermatological Research, Journal Year: 2025, Volume and Issue: 317(1)

Published: Jan. 10, 2025

Language: Английский

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Effectiveness of Tralokinumab in Different Phenotypes of Atopic Dermatitis: A Real-World Study

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

Published: Jan. 25, 2025

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritus and relapsing course, affecting approximately 25% of children 4–7% adults. This study evaluated the efficacy, safety, quality-of-life impact tralokinumab, humanized monoclonal antibody targeting interleukin-13 (IL-13), in treating moderate-to-severe AD real-world setting, with focus on different phenotypes. An observational cohort 30 adults treated tralokinumab for ≥ 16 weeks was analyzed. Clinical demographic data were collected, outcomes assessed using Eczema Area Severity Index (EASI), Dermatology Life Quality (DLQI), numeric rating scales (NRS) sleep disturbances. By week 16, 60% achieved 75% improvement EASI (EASI75) 31% reached 90% (EASI90), reflecting substantial clinical improvements. A 4-point reduction NRS observed 63% patients increasing to 70% 32. Similarly, significant improvements disturbance sustained effects through Subgroup analysis revealed superior responses early-onset atopic comorbidities. Lower total immunoglobulin E (IgE) levels at correlated better outcomes, suggesting IgE as potential biomarker. 32, had DLQI ≤ 5, indicating minimal impact. Additionally, 88% least one therapeutic target, 81% met composite endpoints combining clinician-assessed patient-reported outcomes. The safety profile consistent trials, mild conjunctivitis injection site reactions most common adverse events. These findings support an effective well-tolerated treatment, emphasizing importance phenotype-specific approaches management.

Language: Английский

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Design and characterization of κ-Carrageenan:PVA hydrogels to repurpose the topical delivery of betamethasone

International Journal of Pharmaceutics, Journal Year: 2025, Volume and Issue: 671, P. 125305 - 125305

Published: Feb. 1, 2025

Atopic dermatitis (AD) is a severe inflammatory skin disorder, affecting children and adults worldwide, despite the several existing treatments, it necessary to find new alternative topical therapies. Hydrogels may represent good tool treat AD due their high water content, making them excellent candidates for drug delivery vehicles in research. This work aimed develop characterize hybrid hydrogels composed of gel-forming polymers (k-carrageenan polyvinyl alcohol) cutaneous betamethasone (up 0.2 mg mL-1) widely used manage AD, with retention. Bergamot oil menthol essential oils were also incorporated into study effects on penetration retention corticosteroid. Rheological properties revealed pseudoplastic behavior hydrogels, favorable characteristic application. Cytocompatibility towards fibroblasts keratinocytes was determined, revealing safe usage hydrogel blends up 100 mL-1, corresponding 20 µg mL-1 betamethasone, but compromised by presence higher tested concentrations (50 mL-1). The ex vivo pig ear permeation assay showed that promote % added dose (c.a. 10 µg) even after 24 h permeation, independently use oils' composition, showing they might be strategy skin.

Language: Английский

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