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1.
AAPS PharmSciTech ; 25(4): 72, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575745

RESUMO

Atopic dermatitis is a skin condition characterized by lichenification (thickening and increased skin marking), eczematous lesions, dry skin, itching, and pruritus. Eugenol is an aromatic polyphenolic compound that has attracted the attention of researchers due to its anti-inflammatory, anti-oxidant, and anti-cancer properties. The primary goal of the present study was to develop and evaluate eugenol-loaded transethosomes for the treatment of AD. Eugenol-loaded transethosomes were formulated using the ethanol injection method and subsequently subjected to particle size analysis, zeta potential, entrapment efficiency, deformability index, and HRTEM analysis. Transethosomal gel was prepared by direct-dispersion method by using Carbopol 940®. Results showed transethosomes to be lipid bilayer structures with acceptable size, and high entrapment efficiency. Transethosomal formulation showed shear-thinning behavior. Eugenol-loaded transethosomal gel was significantly able to enhance the retention of the drug in the skin. Transethosomal gel was significantly able to reduce Ear thickness, DLC, TLC, and IL-6 levels in mice model of AD. These results indicate that the eugenol-loaded transethosomal gel could be a promising carrier for the topical administration of eugenol for the treatment of AD.


Assuntos
Dermatite Atópica , Eugenol , Animais , Camundongos , Eugenol/farmacologia , Absorção Cutânea , Administração Cutânea , Dermatite Atópica/tratamento farmacológico , Portadores de Fármacos/química , Pele/metabolismo , Antioxidantes/metabolismo
2.
J Dermatolog Treat ; 35(1): 2336118, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38565207

RESUMO

In this report, we describe the case of a 28-year-old female with bilateral breast cancer in the setting of a BRCA1 mutation, who presented to dermatology with an eczematous reaction, ultimately diagnosed as a cutaneous immune-related adverse event (cirAE) secondary to an immune checkpoint inhibitor (ICI), pembrolizumab. Our case report highlights a novel therapeutic option for an eczematous cirAE: the topical JAK 1/2 inhibitor, ruxolitinib. CirAEs can occur in up to 55% of patients on ICIs, a class of medications seeing rapidly increasing use in cancer therapy, and prior research has demonstrated that ICI-induced dermatitis may involve different pathways than traditionally observed in their spontaneous counterparts. Specifically, marked Th1 skewing is noted in ICI-induced dermatitis, as opposed to a predominant Th2 response which typically characterizes spontaneous atopic dermatitis. To our knowledge, this is the first case report in the literature discussing use of a topical JAK inhibitor, ruxolitinib, in the treatment of topical steroid-refractory cirAEs. Furthermore, as topical JAK inhibitors are thought to not carry the risks of systemic JAK inhibitors, including malignancy, ruxolitinib cream is a promising therapeutic option for this challenging patient population.


Assuntos
Dermatite Atópica , Inibidores de Janus Quinases , Nitrilas , Pirimidinas , Feminino , Humanos , Adulto , Inibidores de Janus Quinases/uso terapêutico , Inibidores de Checkpoint Imunológico/uso terapêutico , Pirazóis/efeitos adversos , Dermatite Atópica/tratamento farmacológico
4.
Chin Med Sci J ; 39(1): 74-78, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38623049

RESUMO

Atopic dermatitis is usually associated with various ocular complications. We report a 21-year-old Chinese male who presented to our ophthalmology clinic with bilateral retinal detachment and cataracts. The patient had a clear medical history of atopic dermatitis, which had been diagnosed eight years earlier and had been treated with loratadine and pimecrolimus. Cataract surgery was performed for both eyes, combined with scleral buckling for the right eye and pars plana vitrectomy for the left eye. During postoperative follow-up, fundus fluorescein angiography showed retinal vasculitis in both eyes and macular edema in the left eye, which coincided with an exacerbation of atopic dermatitis. Macular edema improved after four months of regular dupilumab treatment in the dermatology department. The ocular condition remained stable three years postoperatively.


Assuntos
Dermatite Atópica , Edema Macular , Descolamento Retiniano , Vasculite Retiniana , Masculino , Humanos , Adulto Jovem , Adulto , Descolamento Retiniano/etiologia , Descolamento Retiniano/cirurgia , Descolamento Retiniano/diagnóstico , Dermatite Atópica/complicações , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/cirurgia , Vasculite Retiniana/tratamento farmacológico , Vasculite Retiniana/complicações , Vasculite Retiniana/cirurgia , Edema Macular/etiologia , Edema Macular/complicações , Recurvamento da Esclera/efeitos adversos , Estudos Retrospectivos
5.
Int Immunopharmacol ; 133: 112038, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38621336

RESUMO

Available online Atopic dermatitis (AD) is a chronic, persistent inflammatory skin disease characterized by eczema-like lesions and itching. Although topical steroids have been reported for treating AD, they are associated with adverse effects. Thus, safer medications are needed for those who cannot tolerate these agents for long periods. Mangiferin (MAN) is a flavonoid widely found in many herbs, with significant anti-inflammatory and immunomodulatory activities. However, the potential modulatory effects and mechanisms of MAN in treating Th2 inflammation in AD are unknown. In the present study, we reported that MAN could reduce inflammatory cell infiltration and scratching at the lesion site by decreasing MC903-induced levels of Th2-type cytokines, Histamine, thymic stromal lymphopoietin, Leukotriene B4, and immunoglobulin E. The mechanism may be related to reductions in MAPK and NF-κB-associated protein phosphorylation by macrophages. The results suggested that MAN may be a promising therapeutic agent for AD.


Assuntos
Citocinas , Dermatite Atópica , Macrófagos , NF-kappa B , Células Th2 , Xantonas , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/imunologia , Xantonas/farmacologia , Xantonas/uso terapêutico , Animais , NF-kappa B/metabolismo , Células Th2/imunologia , Células Th2/efeitos dos fármacos , Citocinas/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Camundongos Endogâmicos BALB C , Transdução de Sinais/efeitos dos fármacos , Humanos , Masculino , Linfopoietina do Estroma do Timo , Imunoglobulina E/metabolismo , Pele/efeitos dos fármacos , Pele/patologia , Pele/imunologia , Pele/metabolismo
6.
J Med Chem ; 67(6): 4855-4869, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38489246

RESUMO

Atopic dermatitis is a chronic relapsing skin disease characterized by recurrent, pruritic, localized eczema, while PDE4 inhibitors have been reported to be effective as antiatopic dermatitis agents. 3',4-O-dimethylcedrusin (DCN) is a natural dihydrobenzofuran neolignan isolated from Magnolia biondii with moderate potency against PDE4 (IC50 = 3.26 ± 0.28 µM) and a binding mode similar to that of apremilast, an approved PDE4 inhibitor for the treatment of psoriasis. The structure-based optimization of DCN led to the identification of 7b-1 that showed high inhibitory potency on PDE4 (IC50 = 0.17 ± 0.02 µM), good anti-TNF-α activity (EC50 = 0.19 ± 0.10 µM), remarkable selectivity profile, and good skin permeability. The topical treatment of 7b-1 resulted in the significant benefits of pharmacological intervention in a DNCB-induced atopic dermatitis-like mice model, demonstrating its potential for the development of novel antiatopic dermatitis agents.


Assuntos
Dermatite Atópica , Lignanas , Inibidores da Fosfodiesterase 4 , Camundongos , Animais , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/tratamento farmacológico , Inibidores da Fosfodiesterase 4/farmacologia , Inibidores da Fosfodiesterase 4/uso terapêutico , Dinitroclorobenzeno/farmacologia , Dinitroclorobenzeno/uso terapêutico , Lignanas/farmacologia , Lignanas/uso terapêutico , Inibidores do Fator de Necrose Tumoral/farmacologia , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Citocinas/farmacologia , Pele
7.
Int J Mol Sci ; 25(5)2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38473936

RESUMO

Long-term oral ingestion of unheated yuzu seed oil in humans reduces lipid peroxides in the blood. Moreover, yuzu seed oil contains limonin, which can induce antioxidant and anti-inflammatory effects by activating the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). Previously, Nrf2 has been shown to reduce atopic dermatitis (AD). Therefore, we hypothesized that ingesting unheated yuzu seed oil can regulate AD through Nrf2. An AD model was established using NC/Nga mice through repeated local exposure to mite antigens. Unheated and purified yuzu seed oil (100 µL/mice) or water (control, 100 µL/mice) was administered orally once a day using a gastric cannula for rodents for 28 days. On day 28, mice in the unheated yuzu seed oil group exhibited significantly lower clinical skin severity scores and ear thickness than those in the purified yuzu seed oil and water groups. Serum histamine levels remained unaltered among the three AD-induced groups. Serum Dermatophagoides farina body (Dfb)-specific immunoglobulin E (IgE) levels were significantly lower in the unheated yuzu seed oil group. Oral ingestion of yuzu seed oil in NC/Nga AD model mice significantly suppressed dermatitis deterioration and decreased serum IgE levels. Clinical trials (n = 41) have already confirmed that unheated yuzu oil is safe for long-term intake, further suggesting its potential use in improving AD symptoms.


Assuntos
Dermatite Atópica , Humanos , Camundongos , Animais , Dermatite Atópica/tratamento farmacológico , Fator 2 Relacionado a NF-E2 , Pele/patologia , Imunoglobulina E , Dermatophagoides farinae , Ingestão de Alimentos , Óleos de Plantas/farmacologia , Modelos Animais de Doenças
8.
Int Immunopharmacol ; 130: 111706, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38382265

RESUMO

BACKGROUND: YH35324, a long-acting IgETrap-Fc fusion protein, is a novel therapeutic agent for immunoglobulin E (IgE)-mediated allergic diseases. This randomized, double-blind, placebo/active-controlled, single ascending dose Phase 1 study assessed the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of YH35324 in subjects with atopy. METHODS: Eligible subjects were healthy subjects or atopic adults with mild allergic rhinitis, atopic dermatitis, food allergy, or urticaria, and a serum total IgE level of 30-700 IU/mL (Part A) or > 700 IU/mL (Part B). In Part A, 35 subjects in 5 cohorts received YH35324 (0.3, 1, 3, 6, and 9 mg/kg), 8 received omalizumab (300 mg), and 9 received placebo. In Part B, 8 subjects received YH35324 and 8 received omalizumab. RESULTS: Twenty subjects (38.5 %) in Part A (YH35324: 37.1 %, omalizumab: 50.0 %, placebo: 33.3 %) and 10 subjects (62.5 %) in Part B (YH35324: 100 %; omalizumab: 25.0 %) experienced treatment-emergent adverse events (TEAEs). TEAEs were mostly grade 1/2; no serious AEs, AE-related treatment discontinuation, or anaphylaxis were reported. YH35324 exhibited dose-proportional increase in Cmax and AUClast over the dose range of 0.3-9 mg/kg. YH35324 rapidly suppressed serum-free IgE levels to a significant extent (< 25 and < 82.8 ng/mL, both P < 0.05) and with longer duration than omalizumab. CONCLUSION: This study showed that YH35324 has a favorable safety profile and is effective in reducing serum-free IgE levels in subjects with atopic conditions.


Assuntos
Anafilaxia , Dermatite Atópica , Adulto , Humanos , Omalizumab/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Anafilaxia/induzido quimicamente , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/induzido quimicamente , Imunoglobulina E , Método Duplo-Cego , Ligante de CD40
10.
Environ Toxicol ; 39(5): 3188-3197, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38356236

RESUMO

Yin chai hu (Radix Stellariae) is a root medicine that is frequently used in Chinese traditional medicine to treat fever and malnutrition. In modern medicine, it has been discovered to have anti-inflammatory, anti-allergic, and anticancer properties. In a previous study, we were able to extract lipids from Stellariae Radix using supercritical CO2 extraction (SRE), and these sterol lipids accounted for up to 88.29% of the extract. However, the impact of SRE on the development of atopic dermatitis (AD) has not yet been investigated. This study investigates the inhibitory effects of SRE on AD development using a 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model. Treatment with SRE significantly reduced the dermatitis score and histopathological changes compared with the DNCB group. The study found that treatment with SRE resulted in a decrease of pro-inflammatory cytokines TNF-α, CXC-10, IL-12, and IL-1ß in skin lesions. Additionally, immunohistochemical analysis revealed that SRE effectively suppressed M1 macrophage infiltration into the AD lesion. Furthermore, the anti-inflammatory effect of SRE was evaluated in LPS + INF-γ induced bone marrow-derived macrophages (BMDMs) M1 polarization, SRE inhibited the production of TNF-α, CXC-10, IL-12, and IL-1ß and decreased the expression of NLRP3. Additionally, SRE was found to increase p-AMPKT172, but had no effect on total AMPK expression, after administration of the AMPK inhibitor Compound C, the inhibitory effect of SRE on M1 macrophages was partially reversed. The results indicate that SRE has an inhibitory effect on AD, making it a potential therapeutic agent for this atopic disorder.


Assuntos
Dermatite Atópica , Animais , Camundongos , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/metabolismo , Dinitroclorobenzeno/toxicidade , Dinitroclorobenzeno/uso terapêutico , Proteínas Quinases Ativadas por AMP , Dióxido de Carbono/toxicidade , Dióxido de Carbono/uso terapêutico , Fator de Necrose Tumoral alfa , Citocinas/metabolismo , Macrófagos/metabolismo , Anti-Inflamatórios/uso terapêutico , Interleucina-12/toxicidade , Interleucina-12/uso terapêutico , Lipídeos , Camundongos Endogâmicos BALB C , Pele
11.
Dermatitis ; 35(S1): S62-S69, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38394048

RESUMO

Background: Preliminary studies support the use of topical coconut and sunflower seed oil for atopic dermatitis (AD). However, standardized topical formulations of fatty acids from these sources have not been studied. Objective: This study investigates whether coconut oil- and sunflower seed oil-derived isosorbide diesters can be used in conjunction with colloidal oatmeal to improve itch, AD severity, and the need for topical steroids in adults. Methods: This was a single-center, 4-week, randomized, double-blind, and vehicle-controlled study conducted between 2021 and 2022. Thirty-two male and female adults with mild-to-moderate AD were enrolled and completed the study. Participants were randomized to receive either 0.1% colloidal oatmeal (vehicle) or isosorbide diesters (IDEAS, 4% isosorbide dicaprylate and 4% isosorbide disunflowerseedate) along with 0.1% colloidal oatmeal. The main outcomes of the study were changes in the visual analogue rating of itch and 75% improvement in the Eczema Area and Severity Index score (EASI 75) at 4 weeks. Other measures included the use of topical steroids and the relative abundance of skin Staphylococcus aureus. Results: Participants in the IDEAS group had a 65.6% improvement in itch compared with 43.8% in the vehicle group (P = 0.013). In total, 56.5% and 25% of the those in the IDEAS and vehicle groups, respectively, achieved EASI 75 at 4 weeks (P = 0.07). There was no difference in skin hydration or transepidermal water loss. The relative abundance of S. aureus was decreased in the IDEAS group at week 4 compared with no change in the vehicle group (P = 0.044). Topical corticosteroid use increased in the vehicle group compared with a decrease in the IDEAS group at week 1 (292.5% vs 24.8%; P value = 0.039) and week 2 (220% vs 46%; P value = 0.08). Conclusions: Topical application of emollients containing coconut oil- and sunflower seed oil-derived fatty esters may improve itch, reduce topical steroid use, and reduce the relative abundance of S. aureus in mild-to-moderate AD. CTR number: NCT04831892.


Assuntos
Dermatite Atópica , Adulto , Humanos , Masculino , Feminino , Dermatite Atópica/tratamento farmacológico , Óleo de Girassol , Óleo de Coco , Staphylococcus aureus , Cocos , Estudos Prospectivos , Resultado do Tratamento , Prurido/tratamento farmacológico , Emolientes , Método Duplo-Cego , Índice de Gravidade de Doença , Esteroides
12.
Biomed Pharmacother ; 172: 116279, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38368838

RESUMO

Atopic dermatitis (AD) is a chronic inflammatory skin condition primarily driven by T helper 2 (Th2) cytokines, resulting in skin barrier defects, angiogenesis, and inflammatory responses. The marine natural product excavatolide B (EXCB), isolated from the Formosan Gorgonian coral Briareum stechei, exhibits anti-inflammatory and analgesic properties. To enhance solubility, EXCB is chemically modified into the derivatives EXCB-61 salt and EXCB-79. The study aims to investigate the therapeutic effects of these compounds on dinitrochlorbenzene (DNCB)-induced skin damage and to elucidate the underlying anti-inflammatory and anti-angiogenesis mechanism. In vitro, using lipopolysaccharide (LPS)-induced RAW 264.7 cells, all compounds at 10 µM significantly inhibited expression of inflammatory proteins (inducible nitric oxide synthase and cyclooxygenase-2), vascular endothelial growth factor (VEGF), and cytokines (interleukin (IL)-1ß, IL-6, and IL-17A). In vivo, topical application of these compounds on DNCB-induced AD mice alleviated skin symptoms, reduced serum levels of IgE, IL-4, IL-13, IL-17, and interferon-γ, and moderated histological phenomena such as hyperplasia, inflammatory cell infiltration, and angiogenesis. The three compounds restored the expression of skin barrier-related proteins (loricrin, filaggrin, and claudin-1) and reduced the expression of angiogenesis-related proteins (VEGF and platelet endothelial cell adhesion molecule-CD31) in the tissues. This is the first study to indicate that EXCB, EXCB-61 salt, and EXCB-79 can treat AD disease by reducing inflammation and angiogenesis. Hence, they may be considered potential candidates for the development of new drugs for AD.


Assuntos
Dermatite Atópica , Diterpenos , Animais , Camundongos , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/tratamento farmacológico , Inibidores da Angiogênese , Fator A de Crescimento do Endotélio Vascular , Dinitroclorobenzeno , Citocinas , Proteínas Angiogênicas , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico
13.
J Microbiol Biotechnol ; 34(4): 940-948, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38314445

RESUMO

Codium fragile has been traditionally used in oriental medicine to treat enterobiasis, dropsy, and dysuria, and it has been shown to possess many biological properties. Atopic dermatitis (AD) is one of the types of skin inflammation and barrier disruption, which leads to chronic inflammatory skin diseases. In the current investigation, the protective effects of C. fragile extract (CFE) on anti-inflammation and skin barrier improvement were investigated. In LPS-stimulated RAW 264.7 cells, nitric oxide generation and the expression levels of interleukin (IL)-1ß, IL-4, IL-6, iNOS, COX-2, and tumor necrosis factor-alpha (TNF)-α were reduced by CFE. CFE also inhibited the phosphorylation of NF-κB-p65, ERK, p-38, and JNK. Additionally, CFE showed inhibitory activity on TSLP and IL-4 expression in HaCaT cells stimulated with TNF-α/interferon-gamma (IFN-γ). Enhanced expression of factors related to skin barrier function, FLG, IVL, and LOR, was confirmed. These findings implied that CFE may be used as a therapeutic agent against AD due to its skin barrier-strengthening and anti-inflammatory activities, which are derived from natural marine products.


Assuntos
Anti-Inflamatórios , Citocinas , Dermatite Atópica , Proteínas Filagrinas , Queratinócitos , Macrófagos , Óxido Nítrico , Dermatite Atópica/tratamento farmacológico , Humanos , Camundongos , Animais , Anti-Inflamatórios/farmacologia , Queratinócitos/efeitos dos fármacos , Células RAW 264.7 , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Citocinas/metabolismo , Óxido Nítrico/metabolismo , Pele/efeitos dos fármacos , Células HaCaT , Extratos Vegetais/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Lipopolissacarídeos/farmacologia , Linhagem Celular , NF-kappa B/metabolismo , Ciclo-Oxigenase 2/metabolismo , Ciclo-Oxigenase 2/genética
14.
Nutrients ; 16(3)2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38337735

RESUMO

Atopic dermatitis (AD) is a persistent inflammatory skin condition resulting from an intricate interplay among genetic, immunological, and environmental factors. Erigeron annuus (EA), an annual winter plant belonging to the family Asteraceae, possesses anti-inflammatory, cytoprotective, and antioxidant activities. In this study, we hypothesized that Erigeron annuus extract (EAE) could be an effective agent for ameliorating AD-like symptoms. To confirm this hypothesis in vitro, we used H2O2-stimulated human keratinocytes (HaCaT cells) to demonstrate that pre-treatment with EAE protected against oxidative stress. HaCaT cells pretreated with EAE and stimulated with H2O2 showed decreased intracellular malondialdehyde content, increased superoxide dismutase activity, and reduced intracellular reactive oxygen species accumulation. To verify the in vivo hypothesis based on the intracellular results, an AD disease mouse model was induced with 1-chloro-2,4-dinitrobenzene (DNCB), and EAE was orally administered at a non-toxic concentration according to the toxicity evaluation results. The results showed that AD disease models in BALB/c mice exhibited reduced ear epidermal thickness, scratching behavior, and mast cell infiltration. In conclusion, our results indicate that EAE has the potential to improve AD by upregulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway.


Assuntos
Dermatite Atópica , Erigeron , Humanos , Animais , Camundongos , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/tratamento farmacológico , Pele/metabolismo , Dinitroclorobenzeno/toxicidade , Erigeron/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Dinitrobenzenos/efeitos adversos , Dinitrobenzenos/metabolismo , Heme Oxigenase-1/metabolismo , Peróxido de Hidrogênio/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Camundongos Endogâmicos BALB C , Citocinas/metabolismo
15.
Am J Clin Dermatol ; 25(2): 327-332, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38243107

RESUMO

BACKGROUND: Ruxolitinib cream is the first topical Janus kinase (JAK) inhibitor approved in the United States (US) for the treatment of mild to moderate atopic dermatitis and nonsegmental vitiligo. A postmarketing study with oral tofacitinib, approved for rheumatoid arthritis, triggered class warnings for JAK inhibitors, including risk of serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis. Because ruxolitinib cream is indicated for inflammatory conditions, it is subject to the same warnings as oral JAK inhibitors in the US. Here, nearly 14,000 patient-years of postmarketing safety data from the first year following market approval of ruxolitinib cream were reviewed. METHODS: The Incyte global safety database (21 September 2021-20 September 2022) and US FDA Adverse Event Reporting System (as of 30 September 2022) were queried for adverse event (AE) reports received for ruxolitinib cream. RESULTS: The search identified 294 postmarketing individual case safety reports containing 589 events, including four serious AEs and no fatal AEs. AEs (i.e., any unfavorable sign, symptom, or disease) representing >2% of all events included application site pain (n = 16), atopic dermatitis (n = 15), skin irritation (n = 15), scratch (n = 14), and condition aggravated (n = 13). The four serious AEs were skin cancer (n = 2), pericarditis, and thrombocytopenia (both n = 1), none of which had sufficient information to assess possible relatedness to ruxolitinib cream. Serious AEs associated with the class warnings for JAK inhibitors were not reported. CONCLUSIONS: Postmarketing safety data from the year following approval suggest ruxolitinib cream is generally well tolerated, without significant systemic AEs, and with a low incidence of application site reactions.


Assuntos
Dermatite Atópica , Inibidores de Janus Quinases , Pirazóis , Pirimidinas , Humanos , Estados Unidos , Dermatite Atópica/tratamento farmacológico , Nitrilas/uso terapêutico , Emolientes/uso terapêutico
16.
J Cutan Med Surg ; 28(1): 59-67, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38229411

RESUMO

Psoriasis, hidradenitis suppurativa (HS), atopic dermatitis (AD), and chronic spontaneous urticaria (CSU), are common, immune-mediated, chronic, inflammatory skin diseases that can affect the pediatric population. While there is adequate evidence supporting the use of biologics in pediatric patients, concerns regarding safety and efficacy amongst healthcare providers are not uncommon. However, new emerging evidence in this population highlights the safety of biologic therapy, making it crucial to review and establish a practical guide for their use. This article describes a methodological framework for initiating biologics in the management of pediatric psoriasis, HS, AD, and CSU, with a special focus on baseline work-up, monitoring, dosing, and considerations in this population.


Assuntos
Produtos Biológicos , Urticária Crônica , Dermatite Atópica , Dermatologia , Hidradenite Supurativa , Psoríase , Humanos , Criança , Produtos Biológicos/uso terapêutico , Pele , Dermatite Atópica/tratamento farmacológico , Hidradenite Supurativa/tratamento farmacológico , Psoríase/tratamento farmacológico
17.
Am J Clin Dermatol ; 25(3): 447-461, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38236520

RESUMO

Atopic dermatitis (AD) is a chronic, heterogeneous, inflammatory disease characterized by skin lesions, pruritus, and pain. Patients with moderate-to-severe AD experience chronic symptoms, intensified by unpredictable flares, and often have comorbidities and secondary complications, which can result in significant clinical burden that impacts the patient's overall quality of life. The complex interplay of immune dysregulation and skin barrier disruption drives AD pathogenesis, of which T-cell-dependent inflammation plays a critical role in patients with AD. Despite new targeted therapies, many patients with moderate-to-severe AD fail to achieve or sustain their individual treatment goals and/or may not be suitable for or tolerate these therapies. There remains a need for a novel, efficacious, well-tolerated therapeutic option that can deliver durable benefits across a heterogeneous AD patient population. Expression of OX40 [tumor necrosis factor receptor superfamily, member 4 (TNFRSF4)], a prominent T-cell co-stimulatory molecule, and its ligand [OX40L; tumor necrosis factor superfamily, member 4 (TNFSF4)] is increased in AD. As the OX40 pathway is critical for expansion, differentiation, and survival of effector and memory T cells, its targeting might be a promising therapeutic approach to provide sustained inhibition of pathogenic T cells and associated inflammation and broad disease control. Antibodies against OX40 [rocatinlimab (AMG 451/KHK4083) and telazorlimab (GBR 830)] or OX40L [amlitelimab (KY1005)] have shown promising results in early-phase clinical studies of moderate-to-severe AD, highlighting the importance of OX40 signaling as a new therapeutic target in AD.


Assuntos
Dermatite Atópica , Terapia de Alvo Molecular , Ligante OX40 , Receptores OX40 , Dermatite Atópica/imunologia , Dermatite Atópica/tratamento farmacológico , Humanos , Receptores OX40/antagonistas & inibidores , Receptores OX40/imunologia , Receptores OX40/metabolismo , Ligante OX40/antagonistas & inibidores , Ligante OX40/metabolismo , Índice de Gravidade de Doença , Pele/imunologia , Pele/patologia , Qualidade de Vida , Linfócitos T/imunologia , Linfócitos T/metabolismo , Transdução de Sinais/imunologia , Transdução de Sinais/efeitos dos fármacos , Resultado do Tratamento
18.
J Microbiol Biotechnol ; 34(4): 765-773, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38247218

RESUMO

Ozone, a highly reactive oxidant molecule, is widely used as a complementary therapy for various skin diseases, including wound healing, pressure ulcers, diabetic foot, and infections. However, there is limited research on the effectiveness of ozone for atopic dermatitis (AD). Ozonated sunflower oil (OSO) is an active ingredient obtained from partially ozonated sunflower oil (SO). OSO markedly reduced the LPS-induced increase in IL-1ß and nitric oxide (NO) levels in RAW 264.7 mouse macrophage cells. Oxazolone (OXZ) was applied to hairless mice to induce AD-like skin symptoms and immune response. OSO significantly alleviated the OXZ-induced increases in the number of infiltrating mast cells, epidermal thickness, AD symptoms, thymic stromal lymphopoietin (TSLP), and filaggrin, as well as the serum levels of NO, IgE, IL-1ß, and TNF-α. Furthermore, OSO inhibited the IL-4/STAT3/MAPK pathway and the expression of NF-κB. Our results suggest that OSO treatment could relieve AD-mediated skin damage through its anti-inflammatory and antioxidant activities. Therefore, it can be used as a therapeutic agent against AD-related skin diseases.


Assuntos
Citocinas , Dermatite Atópica , Lipopolissacarídeos , Óxido Nítrico , Oxazolona , Ozônio , Óleo de Girassol , Animais , Camundongos , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/tratamento farmacológico , Células RAW 264.7 , Citocinas/metabolismo , Oxazolona/toxicidade , Óxido Nítrico/metabolismo , Imunoglobulina E/sangue , NF-kappa B/metabolismo , Modelos Animais de Doenças , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Interleucina-1beta/metabolismo , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Fator de Transcrição STAT3/metabolismo , Pele/efeitos dos fármacos , Pele/patologia , Linfopoietina do Estroma do Timo , Inflamação/tratamento farmacológico , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Filagrinas , Interleucina-4/metabolismo , Anti-Inflamatórios/farmacologia
19.
J Ethnopharmacol ; 323: 117702, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38176665

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Qing-Re-Chu-Shi Decoction (QRCSD), a traditional Chinese herbal formula, has been employed as a complementary and alternative therapy for inflammatory skin diseases. However, its active constituents and the mechanistic basis of its action on atopic dermatitis remain in adequately understood. AIM OF THE STUDY: Atopic dermatitis (AD) is an allergic dermatitis marked by eczematous lesions and pruritus. The study aimed to elucidate the underlying effects of QRCSD on AD and to identify the components responsible for its therapeutic efficacy in a mouse model. MATERIALS AND METHODS: Network pharmacology and UPLC-mass analysis were used to anticipate the pharmacological mechanisms and to identify active components of QRCSD, respectively. A DNCB-induced AD-like model was established in NC/Nga mice. QRCSD or prednisolone (as a positive control) was administered via gavage every other day from day14 to day 21. Dermatitis severity score, scratching behavior, skin barrier function, spleen index, Th1/Th2 lymphocyte ratio, and serum IgE levels were evaluated. Protein arrays, including 40 inflammatory cytokines, were performed on skin lesions, followed by confirmation experiments of Western blotting in dorsal skin lesions. RESULTS: The construction of a QRCSD-AD-Network and topological analysis firstly proposed potential targets of QRCSD acting on AD. Animal experiments demonstrated that oral administration of QRCSD ameliorated AD-like lesions, reduced epidermal thickness and mast cell count, decreased serum IgE levels, augmented tight junction protein (Claudin 1, Occludin) levels, and regulated the Th1/Th2 balance in the spleen, as well as spleen index. Elevated levels of interleukin (IL)-4, IL-5, IL-6, IL-17, and Eotaxin were revealed in AD-like skin lesions by protein arrays. Western blotting confirmed that the phosphorylation levels of ERK, P38, JNK, STAT3 and P65 were downregulated, and IL-6 expression was also reduced following QRCSD treatment. CONCLUSIONS: The study enhances the understanding of the anti-inflammatory and immunomodulatory effects of QRCSD, showcasing its significant protective role against atopic dermatitis. Treatment with QRCSD may be considered as a viable candidate for complementary and alternative therapy in managing atopic dermatitis.


Assuntos
Dermatite Atópica , Camundongos , Animais , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/patologia , Dinitroclorobenzeno/toxicidade , Pele/patologia , Interleucina-6/metabolismo , Citocinas/metabolismo , Anti-Inflamatórios/efeitos adversos , Imunoglobulina E
20.
PLoS One ; 19(1): e0296408, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38181031

RESUMO

In atopic dermatitis (AD), nerves are abnormally stretched near the surface of the skin, making it sensitive to itching. Expression of neurotrophic factor Artemin (ARTN) involved in such nerve stretching is induced by the xenobiotic response (XRE) to air pollutants and UV radiation products. Therefore, AD can be monitored by the XRE response. Previously, we established a human keratinocyte cell line stably expressing a NanoLuc reporter gene downstream of XRE. We found that 6-formylindolo[3,2-b]carbazole (FICZ), a tryptophan metabolite and known inducer of the XRE, increased reporter and Artemin mRNA expression, indicating that FICZ-treated cells could be a model for AD. Lavender essential oil has been used in folk medicine to treat AD, but the scientific basis for its use is unclear. In the present study, we investigated the efficacy of lavender essential oil and its major components, linalyl acetate and linalool, to suppress AD and sensitize skin using the established AD model cell line, and keratinocyte and dendritic cell activation assays. Our results indicated that lavender essential oil from L. angustifolia and linalyl acetate exerted a strong AD inhibitory effect and almost no skin sensitization. Our model is useful in that it can circumvent the practice of using animal studies to evaluate AD medicines.


Assuntos
Dermatite Atópica , Lavandula , Animais , Humanos , Dermatite Atópica/tratamento farmacológico , Pele , Monoterpenos
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