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1.
Comput Biol Med ; 181: 108988, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39168013

RESUMO

Rosacea is a chronic dermatological condition that currently lacks a clear treatment approach due to an uncomprehensive knowledge of its pathogenesis. The main obstacle lies in understanding its etiology and the mode of action of the different drugs used. This study aims to clarify these aspects by employing drug repositioning. Using an in silico approach, we performed a transcriptomic analysis comparing samples from individuals with diverse types of rosacea to those from healthy controls to identify genes deregulated in this disease. Subsequently, we realized molecular docking and molecular dynamics studies to assess the binding affinity of drugs currently used to treat rosacea and drugs that target proteins interacting with, and thus affecting, proteins deregulated in rosacea. Our findings revealed that the downregulation of SKAP2 and upregulation of S100A7A in rosacea, could be involved in the pathogenesis of the disease. Furthermore, considering the drugs currently used for rosacea management, we demonstrated stable interactions between isotretinoin and BFH772 with SKAP2, and permethrin and PAC-14028 with S100A7A. Similarly, considering drugs targeting SKAP2 and S100A7A interactome proteins, we found that pitavastatin and dasatinib exert stable interactions with SKAP2, and lovastatin and tirbanibulin with S100A7A. In addition, we determine that the types of bonds involved in the interactions were different in SKAP2 from S100A7A. The drug-SKAP2 interactions are hydrogen bonds, whereas the drug-S100A7A interactions are of the hydrophobic type. In conclusion, our study provides evidence for the possible contribution of SKAP2 and S100A7A to rosacea pathology. Furthermore, it provides significant information on the molecular interactions between drugs and these proteins, highlighting the importance of considering structural features and binding interactions in the design of targeted therapies for skin disorders such as rosacea.


Assuntos
Reposicionamento de Medicamentos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Rosácea , Rosácea/tratamento farmacológico , Rosácea/metabolismo , Humanos , Proteína A7 Ligante de Cálcio S100/metabolismo , Proteína A7 Ligante de Cálcio S100/genética , Proteína A7 Ligante de Cálcio S100/química , Farmacóforo
2.
Curr Rheumatol Rev ; 18(3): 272-277, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35086454

RESUMO

BACKGROUND: Notwithstanding the frequent coexistence of autoimmune thyroid disease (ATD) and primary Sjögren's Syndrome (SS), it is still unknown how often this association is studied along with its clinical impact. OBJECTIVE: This study aimed to describe real-world screening practices for ATD in patients with SS and evaluate clinical outcomes of patients with both diagnoses using validated activity and chronicity indexes. METHODS: It is a retrospective study of 223 patients with SS attending a tertiary referral center. Patients were under rheumatology surveillance and might have attended other clinics, including internal medicine and/or endocrinology. We registered glandular and extraglandular features, serology and scored the activity (ESSDAI) and the accrual damage (SSDDI) indexes. We also identified any thyroid function tests (TFT) performed, anti-thyroid antibodies, images, and histological thyroid examinations. A single endocrinologist reviewed all data. RESULTS: One hundred forty-nine patients had at least one set of TFT. Younger age was associated with a lack of screening (OR 0.98, 95 % CI 0.95-0.99, p=0.01). Sixty-nine patients had thyroid disease, with the most common diagnosis being ATD (n=24). Patients with ATD had a lower prevalence of Ro/SSA and anti-La/SSB antibodies but similar cumulative SS activity and damage scores. CONCLUSION: At least one-third of our patients were not screened for thyroid disease, with these patients being the youngest. Thyroid disorders were found in about 40 % of patients with SS, with ATD being the most common. Having SS/ATD did not confer more disease activity or damage accrual. These results highlight the importance of making treating physicians aware of screening for thyroid disease in this population.


Assuntos
Síndrome de Sjogren , Doenças da Glândula Tireoide , Anticorpos Antinucleares , Humanos , Prevalência , Estudos Retrospectivos
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