Journal of Dermatological Treatment, Год журнала: 2025, Номер 36(1)
Опубликована: Янв. 6, 2025
Purpose/aim of the study There is limited real-world evidence regarding effectiveness and safety dupilumab in Gulf countries. The aimed to evaluate atopic dermatitis (AD) disease control adult adolescent patients (≥12 years) treated with
Язык: Английский
American Journal of Clinical Dermatology, Год журнала: 2025, Номер unknown
Опубликована: Янв. 6, 2025
Ruxolitinib cream has demonstrated anti-inflammatory and antipruritic activity was well tolerated in a phase 3 study patients aged 2–11 years with mild to moderate atopic dermatitis (AD). This examined the safety, tolerability, pharmacokinetics, efficacy, quality of life (QoL) ruxolitinib under maximum-use conditions longer-term use. Eligible were severe AD [Investigator's Global Assessment (IGA) score 3–4], ≥ 35% affected body surface area (BSA). Patients applied 1.5% twice daily all baseline-identified lesions during 4-week period, then active only up week 52 (patients ≤ 20% BSA from 8). Safety assessed by frequency severity adverse events. Pharmacokinetic parameters as secondary endpoints, efficacy QoL exploratory endpoints. Overall, 29 (median age 5 years) enrolled. Treatment-emergent events reported 9/29 (31.0%); there no special interest (i.e., serious infections, malignancies, major cardiovascular events, or thromboses) period. Mean steady-state plasma concentration period below known half-maximal inhibitory Janus kinase–mediated myelosuppression adults. Reductions IGA observed at 4 sustained as-needed use through weeks. Improvements patient-reported outcomes measures consistent results. These results support safety children (2–11 AD, including those extensive disease, are previous findings. NCT05034822, first registered 30 August 2021. is approved USA for 12 treatment (AD) involving body, recent studies supporting younger AD. Maximum-use trials look treatments more areas skin, assessing potential side effects. trial absorption, effectiveness when weeks body. needed weeks, disease control assessed. During 31% Only one patient experienced treatment-related effects application site. As-needed did not cause any other concern. The average blood level low. As expected low levels, associated oral drugs same class (e.g., levels white cells, cancers, clots) seen. decreased size relief itching treatment, amount thereafter. Disease maintained cream. findings help confirm children.
Язык: Английский
Процитировано
1
Cells, Год журнала: 2025, Номер 14(2), С. 83 - 83
Опубликована: Янв. 9, 2025
Cannabinoid compounds have potential as treatments for a variety of conditions, with cannabigerol (CBG) being known its anti-inflammatory properties. In this study, we investigated the effects CBG in cellular model 1-chloro-2,4-dinitrobenzene (DNCB)-induced atopic dermatitis (AD). model, confirmed cytotoxicity and downregulated expression inflammatory markers CCL26, IL1B, IL6, TNF (p < 0.001). mouse clinical, histological, immunological changes were analyzed. The results showed that improved severity score, epidermal thickness, mast cell count reduced cytokines (Tslp, Il1b, Il4, Il6, Il13, Il17, Il18, Il22, Il33) by qRT-PCR Western blot modulated JAK1, JAK2, TYK2, STAT1, STAT2, STAT3, p-STAT3, STAT6, p-STAT6 0.05). Subsequently, p-IκBα, NF-κB, p-NF-κB signaling factors also 0.05), corresponding skin barrier factors. study indicate effectively alleviates AD-like symptoms suggest therapeutic agent.
Язык: Английский
Процитировано
1
Dermatology and Therapy, Год журнала: 2025, Номер unknown
Опубликована: Янв. 15, 2025
Results from randomized controlled trials of upadacitinib, a Janus kinase (JAK) inhibitor, have led to its approval for the treatment moderate-to-severe atopic dermatitis (AD) in patients aged ≥ 12 years. The aim this study was report effectiveness and safety upadacitinib real-world settings over period 96 weeks. This retrospective included all treated with at our centre between April 2022 September 2024. Clinical patient-reported outcomes were recorded assessed each follow-up visit eczema area severity index (EASI), investigator global assessment (IGA), scoring (SCORAD), dermatology life quality (DLQI) worst pruritus numerical scale score (WP-NRS). All drug-related adverse events (AEs) documented. In total, 36 (44.4% female) retrospectively included. After 4 weeks treatment, mean EASI reduced 29.97 3.72 83.3/52.8/19.4% achieving EASI75/90/100 respectively. Similar reductions observed DLQI, which 20.78 2.92, WP-NRS, 7.78 1.31. Further improvements week 16, 0.75 96.4% EASI75 EASI90. At 48 achieved by 100/93.8/81.3% along DLQI NRS 0.81. nine that reached 72- 96-week timepoints had clear skin no pruritus. Six (16.7%) experienced AEs four them discontinuing medication; patient discontinued because inefficacy. long-term AD receiving demonstrated success (EASI75/90/100) can be high proportion 16 maintained up substantial life.
Язык: Английский
Процитировано
1
Infectious Agents and Cancer, Год журнала: 2025, Номер 20(1)
Опубликована: Фев. 7, 2025
Colorectal cancer (CRC) ranks among the frequently occurring malignant neoplasms affecting gastrointestinal tract. This study aimed to explore JAK-STAT signaling pathway related genes in CRC and establish a new prognostic model. The data set used this is from public database. JAK-STAT-differentially expressed (DEGs) were identified through differential expression analysis weighted gene co-expression network (WGCNA). Prognostic selected JAK-STAT-DEGs Mendelian randomization (MR), univariate Cox regression, least absolute shrinkage selection operator (LASSO) analyses. expressions of verified by RT-qPCR. Then, risk model was built validated GSE39582. Independent factors screened underlying scores different clinical indicators, resulting construction nomogram. Additionally, immune infiltration, checkpoint inhibitors analyses enrichment (GSEA) carried out. 3,668 obtained intersection 5826 CRC-DEGs 9766 key module genes. Five (ANK3, F5, FAM50B, KLHL35, MPP2), their significantly between control groups. A constructed according In addition, nomogram exhibited superior predictive accuracy for CRC. Furthermore, results indicated notable positive correlation score (R = 0.486), stromal 0.309), ESTIMATE 0.422). Immune inhibitor ADORA2A (Cor 0.483263) strongest with score. And MPP2 most potent activating influence on cell cycle pathway, whereas ANK3 demonstrated significant inhibitory effect within apoptosis pathway. validated, which possessed an potential patients' prognosis could potentially enhance tailored guidance immunotherapy.
Язык: Английский
Процитировано
1
Journal of the European Academy of Dermatology and Venereology, Год журнала: 2023, Номер 37(12), С. 2537 - 2542
Опубликована: Июль 21, 2023
Abrocitinib is a JAK-1 selective inhibitor registered for the treatment of moderate-to-severe atopic dermatitis (AD). Although efficacy and safety have been shown in phase 3 clinical trials, data on real-world patients with history advanced systemics are scarce.The objective study was to evaluate effectiveness abrocitinib difficult-to-treat AD daily practice.In this prospective observational single-centre study, all who started context standard care between April 2021 December 2022 were included. Effectiveness assessed using clinician- patient-reported outcome measures. Adverse events evaluated.Forty-one The majority (n = 30; 73.2%) had failed (ineffectiveness) other targeted therapies, including JAK inhibitors 14, 34%) biologics 16, 39%). resulted significant decrease disease severity during median follow-up period 25 weeks (IQR 16-34). Median EASI score at baseline decreased from 14.7 10.4-25.4) 4.0 1.6-11.4) last review (p < 0.001). NRS itch 7.0 5-8) 3.0 1-2) most frequently reported AEs included gastrointestinal symptoms (27.6%), acne (20.7%) respiratory tract infections (17.2%). 16 (39%) discontinued due ineffectiveness, or both (41.2%, 41.2% 11.8%, respectively).Abrocitinib can be an effective practice, non-responders therapies.
Язык: Английский
Процитировано
17
Frontiers in Immunology, Год журнала: 2023, Номер 14
Опубликована: Ноя. 23, 2023
Pruritus is the most common symptom of dermatological disorders, and prurigo nodularis (PN) notorious for intractable severe itching. Conventional treatments often yield disappointing outcomes, significantly affecting patients’ quality life psychological well-being. The pathogenesis PN associated with a self-sustained “itch-scratch” vicious cycle. Recent investigations PN-related itch have partially revealed intricate interactions within cutaneous neuroimmune network; however, underlying mechanism remains undetermined. Itch mediators play key role in pruritus amplification understanding their action will undoubtedly lead to development novel targeted antipruritic agents. In this review, we describe series pruritogens receptors involved mediating itching PN, including cytokines, neuropeptides, extracellular matrix proteins, vasculogenic substances, ion channels, intracellular signaling pathways. Moreover, provide prospective outlook on potential therapies based existing findings.
Язык: Английский
Процитировано
17
Frontiers in Immunology, Год журнала: 2024, Номер 14
Опубликована: Янв. 11, 2024
Background Heat shock protein 90 (HSP90) is an important chaperone supporting the function of many proinflammatory client proteins. Recent studies indicate HSP90 inhibition may be a novel mechanism action for inflammatory skin diseases; however, this has not been explored in atopic dermatitis (AD). Objectives Our study aimed to investigate as target treat AD. Methods Experimental models AD were used including primary human keratinocytes stimulated with cytokines (TNF/IFNγ or TNF/IL-4) and mouse model established by MC903 applications. Results In using RT-qPCR, inhibitor RGRN-305 strongly suppressed gene expression Th1- ( TNF , IL1B IL6 ) Th2-associated CCL17 CCL22, TSLP) chemokines related We next demonstrated that topical oral robustly MC903-induced AD-like inflammation mice reducing clinical signs (oedema erythema) immune cell infiltration into (T cells, neutrophils, mast cells). Interestingly, exhibited similar slightly inferior efficacy but less weight loss compared dexamethasone. Furthermore, RNA sequencing biopsies revealed attenuated transcriptome alterations, suppressing genes implicated AD-associated Il1b, Il4, Il6, Il13 ), which was confirmed RT-qPCR. Lastly, we discovered Western blot disrupted JAK-STAT signaling activity STAT3 STAT6 keratinocytes, consistent enrichment analyses from model. Conclusion experimental mimicking AD, proving treating
Язык: Английский
Процитировано
7
MedComm – Oncology, Год журнала: 2024, Номер 3(1)
Опубликована: Март 1, 2024
Abstract Janus Kinases (JAKs) play a crucial role as therapeutic targets for various cancers. However, the current JAK inhibitors (JAKi) available have limited benefits due to their lack of selectivity. This review focuses on structural analysis elucidate molecular determinants JAKs specificity and discovery design selective JAKi. It includes descriptions comparison different structures binding sites, comparative JAKi modes, detailed interaction fingerprints (IFPs), an extensive structure‐selectivity relationship (SSRs). Moreover, also explores challenges possibilities using computational structure‐based methods discovering designing Other approaches, such targeting pseudokinase domain, well covalent allosteric designs, are covered. Based this analysis, key corresponding rational medicinal chemistry strategies proposed facilitate development highly Overall, we aim enhance understanding explore that can lead effective in cancer therapy, thus improving prognosis patients.
Язык: Английский
Процитировано
7
Molecules, Год журнала: 2024, Номер 29(2), С. 538 - 538
Опубликована: Янв. 22, 2024
Silicosis is a complex occupational disease without recognized effective treatment. Celastrol, natural product, has shown antioxidant, anti-inflammatory, and anti-fibrotic activities, but the narrow therapeutic window high toxicity severely limit its clinical application. Through structural optimization, we have identified highly efficient low-toxicity celastrol derivative, CEL-07. In this study, systematically investigated potential underlying mechanisms of CEL-07 in silicosis fibrosis. By constructing mouse model analyzing with HE, Masson, Sirius Red, immunohistochemical staining, significantly prevented progress inflammation fibrosis, it effectively improved lung respiratory function mice. Additionally, markedly suppressed expression inflammatory factors (IL-6, IL-1α, TNF-α, TNF-β) fibrotic (α-SMA, collagen I, III), promoted apoptosis fibroblasts by increasing ROS accumulation. Moreover, bioinformatics analysis combined experimental validation revealed that inhibited pathways associated (PI3K-AKT JAK2-STAT3) apoptosis-related proteins. Overall, these results suggest may serve as candidate for treatment silicosis.
Язык: Английский
Процитировано
6
Lipids in Health and Disease, Год журнала: 2024, Номер 23(1)
Опубликована: Янв. 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.
Язык: Английский
Процитировано
6