NOX4-mediated astrocyte ferroptosis in Alzheimer’s disease

Cell & Bioscience, Journal Year: 2024, Volume and Issue: 14(1)

Published: July 2, 2024

Abstract This study investigates NADPH oxidase 4 (NOX4) involvement in iron-mediated astrocyte cell death Alzheimer’s Disease (AD) using single-cell sequencing data and transcriptomes. We analyzed AD RNA data, identified marker genes, explored biological processes astrocytes. integrated AD-related chip with ferroptosis-related highlighting NOX4. validated NOX4’s role ferroptosis vitro vivo. Astrocyte genes were enriched AD, emphasizing their role. NOX4 emerged as a crucial player astrocytic AD. Silencing mitigated ferroptosis, improved cognition, reduced Aβ p-Tau levels, alleviated mitochondrial abnormalities. promotes underscoring its significance progression.

Language: Английский

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Evodiae Fructus extract suppresses inflammatory response in HaCaT cells and improves house dust mite-induced atopic dermatitis in NC/Nga mice

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Jan. 4, 2024

Abstract This study was conducted to assess the effect of Evodiae Fructus 70% ethanol extract (EFE) on pathology atopic dermatitis using in vitro and vivo models. The major compounds EFE were identified by ultra-performance liquid chromatography with tandem mass spectrometry as rutaecarpine, evodiamine, evodol, dehydroevodiamine, limonin, synephrine, evocarpine, dihydroevocarpine, hydroxyevodiamine. significantly decreased chemokine levels tumor necrosis factor-α/interferon-γ-stimulated HaCaT cells. In house dust mite-treated NC/Nga mice, topical application score, epidermal hyperplasia thickening, mast cell infiltration, plasma histamine corticosterone. Thymic stromal lymphopoietin, CD4 + T cells, interleukin-4, intercellular adhesion molecule-1 expression lesioned skin reduced treated mice. mechanism elucidated transcriptome analysis, followed experimental validation Western blotting down-regulated activation Janus kinase (JAK)-signal transducers activators transcription (STAT) mitogen-activated protein kinases (MAPK) signaling pathways improves dermatitis-like symptoms suppressing inflammatory mediators, cytokines, chemokines regulating JAK-STAT MAPK pathways, suggesting its use a potential agent for treatment dermatitis.

Language: Английский

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Early and Sustained Improvements in Symptoms and Quality of Life with Upadacitinib in Adults and Adolescents with Moderate-to-Severe Atopic Dermatitis: 52-Week Results from Two Phase III Randomized Clinical Trials (Measure Up 1 and Measure Up 2)

American Journal of Clinical Dermatology, Journal Year: 2024, Volume and Issue: 25(3), P. 485 - 496

Published: March 25, 2024

Atopic dermatitis is a chronic inflammatory disease characterized by increased itch, skin pain, poor sleep quality, and other symptoms that negatively affect patient quality of life. Upadacitinib, an oral selective Janus kinase (JAK) inhibitor with greater inhibitory potency for JAK1 than JAK2, JAK3, or tyrosine 2, approved to treat moderate-to-severe atopic dermatitis. We aimed evaluate the effect upadacitinib on patient-reported outcomes over 52 weeks in adults adolescents Data from two phase III monotherapy trials (Measure Up 1, NCT03569293; Measure NCT03607422) were integrated. Changes pruritus, symptoms, sleep, life, mental health, impression evaluated. Patient-reported outcome assessments included Worst Pruritus Numerical Rating Scale, Patient-Oriented Eczema Measure, Dermatology Life Quality Index, Dermatitis Symptom Impact Hospital Anxiety Depression SCORing index, Patient Global Impression Severity, Change, Treatment. Minimal clinically important differences, achievement scores representing minimal burden, change baseline evaluated patients who received through week placebo 16. This analysis 1609 (upadacitinib 15 mg, N = 557; 30 567; placebo, 485). Baseline demographics characteristics generally similar across all arms. The proportion treated reporting improvements itch rapidly steadily 8, was sustained 52. Patients receiving also experienced pain which continued 16; maintained reports improved 32, quality-of-life By both groups rapid emotional state, 12, achieved meaningful anxiety depression. Improvements health 32 mg earlier those mg. Through 16, versus assessed outcomes. Adults once-daily early ClinicalTrials.gov identifiers NCT03569293 (13 August 2018) NCT03607422 (27 July 2018). dermatitis, eczema, condition causes painful itchy dry skin, burdensome has negative impact These frequently lead disruption daily activities such as school work, decreased self-confidence, social isolation, anxiety, depression, disturbance. Symptoms disturbance, can only be patients. Therefore, it consider patients' perceptions their related especially when evaluating treatment benefits. Upadacitinib orally administered drug In clinical 1 2), we investigated how (15-mg 30-mg dose) given once would life 1-year period. measured changes time skin-related activities, overall within first 1–2 treatment. increase following lasted year conclusion, led lasting well-being

Language: Английский

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Role of antioxidants supplementation in the treatment of atopic dermatitis: a critical narrative review

Frontiers in Nutrition, Journal Year: 2024, Volume and Issue: 11

Published: June 12, 2024

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by itching, epidermal barrier dysfunction, and an unbalanced reaction. AD pathophysiology involves dysregulated immune response driven T helper-2 cells. Many factors, including reactive oxygen species (ROS), are involved in pathogenesis causing cellular damage inflammation resulting dysfunction. This narrative review aims to provide comprehensive overview of the role natural molecules antioxidant compounds, highlighting their potential therapeutic value prevention management. They include vitamin D, E, pyridoxine, Vitamin C, carotenoids, melatonin. Some studies report statistically significant association between levels improvement AD, however, there conflicting results which supplementation, especially did not result AD. Therefore, clinical efficacy these dietary nutritional factors treatment needs be further evaluated trials. Meanwhile, antioxidants can incorporated into management patients personalized manner, tailored severity disease, comorbidities, individual needs.

Language: Английский

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Potential Natural Biomolecules Targeting JAK/STAT/SOCS Signaling in the Management of Atopic Dermatitis

Molecules, Journal Year: 2022, Volume and Issue: 27(14), P. 4660 - 4660

Published: July 21, 2022

Atopic dermatitis (AD) is a chronic inflammatory skin disease caused by the dysregulation of cytokines and other immune mediators. JAK/STAT classical signal transduction pathway involved in various biological processes, its contributes to key aspects AD pathogenesis. Suppressor cytokine signaling (SOCS) proteins negatively regulate immune-related responses mediated pathway. JAK/STAT-mediated production including IL-4, IL-13, IL-31, TSLP inhibits expression important barrier triggers pruritus AD. The SOCS regulates JAK-mediated facilitates maintaining disruptions seen STATs are crucial dendritic-cell-activated Th2 cell differentiation skin, releasing cytokines, indicating that Th2-mediated disorder. aid balancing Th1/Th2 cells and, moreover, onset maintenance allergic reducing activation differentiation. play pivotal role cytokine-signaling events act via Therapies relying on natural products derived biomolecules have proven beneficial when compared with synthetic regimen. In this review, we focused available literature potential natural-product-derived targeting JAK/STAT/SOCS signaling, mainly emphasizing family (SOCS1, SOCS3, SOCS5) acting as negative regulators modulating pathogenesis disorders.

Language: Английский

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Efficacy and safety of topical JAK inhibitors in the treatment of atopic dermatitis in paediatrics and adults: A systematic review

Experimental Dermatology, Journal Year: 2023, Volume and Issue: 32(5), P. 599 - 610

Published: Jan. 24, 2023

Abstract Atopic dermatitis (AD) is the most common skin inflammatory disease. Dysregulation of innate and adaptive immune systems plays a major role in pathophysiology AD. JAKi (Janus Kinase Inhibitors) reduce production pro‐inflammatory cytokines represent promising novel treatment for To assess summarize overall efficacy safety topial AD adults pediatrics, broad search was performed on Ovid Medline, Embase, Cochrane Library, Web Sciences, Scopus, CINAHL Google Scholar until 14 June 2022. After screening, 19 studies remained final review. The current systematic review conducted according to PRISMA, protocol registered PROSPERO (ID #CRD42022303321). Topical delgocitinib, tofacitinib, ruxolitinib, cerdulatinib ifidancitinib are effective treating significantly improve EASI, IGA, pruritus‐NRS score some other indexes adults. Moreover, topical delgocitinib observed have great paediatrics. All showed minimal risk mild‐to‐moderate adverse effects. Available safe modalities Nevertheless, further with longer duration head‐to‐head comparative trials necessary find best option least

Language: Английский

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A Review of Existing and New Treatments for the Management of Hand Eczema

Journal of Cutaneous Medicine and Surgery, Journal Year: 2023, Volume and Issue: 27(5), P. 493 - 503

Published: July 27, 2023

Hand eczema is a chronic condition that affects an estimated 14.5% of the general population. It has severe quality life ramifications in those struggle with it, including days missed from work or school, productivity loss and impaired functioning. For years, standard care included topical moisturizing creams, steroids more recently systemic agents. As new therapeutic targets emerge recent advances are being developed, it now possible than ever hand can be managed via underlying mechanisms. A review literature was conducted to identify current treatment options for eczema. The terms ‘hand eczema’, dermatitis’ were used search PubMed, CENTRAL Embase. To therapies still undergoing investigation, we dermatitis’, ‘atopic ‘vesicular hands and/or feet’ Clinicaltrials.gov all studies until December 2022. There 56 ongoing clinical trials identified pharmacological treatments on 2000 - 2022, 16 ongoing. These dupilumab, ruxolitinib, delgocitinib (LEO124249), gusacitinib (ASN002), AFX 5931, roflumilast (ARQ-252). Two major classes drugs emerging include IL-4/IL-13 inhibitors JAK inhibitors. With increase efficacy seen these drugs, also noting improved adverse effect profiles, making them attractive add clinician’s management toolbox patients

Language: Английский

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Ozonated Sunflower Oil (OSO) Alleviates Inflammatory Responses in Oxazolone-Induced Atopic Dermatitis (AD)-Like Mice and LPS-Treated RAW 264.7 Cells

Journal of Microbiology and Biotechnology, Journal Year: 2024, Volume and Issue: 34(4), P. 765 - 773

Published: Jan. 12, 2024

Language: Английский

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Gut microbiota and skin pathologies: Mechanism of the gut-skin axis in atopic dermatitis and psoriasis

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 141, P. 112658 - 112658

Published: Aug. 12, 2024

Language: Английский

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IL-22 in Atopic Dermatitis

Cells, Journal Year: 2024, Volume and Issue: 13(16), P. 1398 - 1398

Published: Aug. 22, 2024

Atopic dermatitis (AD) is a prevalent and chronic inflammatory skin condition characterized by multifaceted pathophysiology that gives rise to diverse clinical manifestations. The management of AD remains challenging due the suboptimal efficacy existing treatment options. Nonetheless, recent progress in elucidating underlying mechanisms disease has facilitated identification new potential therapeutic targets promising drug candidates. In this review, we summarize newest data, considering multiple connections between IL-22 AD. presence circulating been found correlate with severity identified as critical factor driving response associated condition. Elevated levels patients are correlated increased proliferation keratinocytes, alterations microbiota, impaired epidermal barrier function. Collectively, these factors contribute manifestation characteristic symptoms observed

Language: Английский

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