RESUMO
BACKGROUND: Atopic dermatitis (AD) is an inflammatory disease with diverse clinical features. Although AD is diagnosed mainly by clinical features, the laboratory abnormalities can be found in most patients and may be of diagnostic value. However, few studies have been performed on the clinical significance of laboratory abnormalities in adult and adolescent AD. METHODS: Adult and adolescent patients with AD were included in this study. The questionnaire and dermatological examination were completed by investigators. Laboratory tests included complete blood count, serum total IgE, and allergen-specific IgE. RESULTS: A total of 473 patients were recruited and 396 of them were diagnosed as AD. Increased serum total IgE level, peripheral eosinophils, and basophils were seen more frequently in AD patients than in non-AD patients (P < .05). Positive aeroallergens were seen more in AD patients than in non-AD patients (P < .05). Both total serum IgE level (R = .286, P < .001) and peripheral eosinophils (R = .444, P < .001) significantly correlated with EASI score. Serum total IgE level and extrinsic type AD decreased with age. Patients with elevated serum total IgE are more likely to have a personal history of atopic diseases (P = .014). AD-associated symptoms (such as flexural dermatitis, white dermographism, and anterior neck folds) are more frequently observed in AD patients with high serum IgE or eosinophilia (P < .05). CONCLUSION: The serum total IgE level, allergen-specific IgE, peripheral eosinophils, and basophils are important for the diagnosis of AD. And they are associated with the severity, age groups, and clinical manifestations.
Assuntos
Alérgenos/imunologia , Basófilos , Dermatite Atópica/etiologia , Eosinófilos , Imunoglobulina E/sangue , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Dermatite Atópica/sangue , Dermatite Atópica/diagnóstico , Dermatite Atópica/imunologia , Eosinofilia/etiologia , Feminino , Humanos , Imunoglobulina E/imunologia , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Procaspase 9 is the initiator caspase for apoptosis, but how its levels and activities are maintained remains unclear. The gigantic Inhibitor-of-Apoptosis Protein BIRC6/BRUCE/Apollon inhibits both apoptosis and autophagy by promoting ubiquitylation of proapoptotic factors and the key autophagic protein LC3, respectively. Here we show that BIRC6 forms an anti-parallel U-shaped dimer with multiple previously unannotated domains, including a ubiquitin-like domain, and the proapoptotic factor Smac/DIABLO binds BIRC6 in the central cavity. Notably, Smac outcompetes the effector caspase 3 and the pro-apoptotic protease HtrA2, but not procaspase 9, for binding BIRC6 in cells. BIRC6 also binds LC3 through its LC3-interacting region, probably following dimer disruption of this BIRC6 region. Mutation at LC3 ubiquitylation site promotes autophagy and autophagic degradation of BIRC6. Moreover, induction of autophagy promotes autophagic degradation of BIRC6 and caspase 9, but not of other effector caspases. These results are important to understand how the balance between apoptosis and autophagy is regulated under pathophysiological conditions.
Assuntos
Apoptose , Proteínas Inibidoras de Apoptose , Apoptose/genética , Proteínas Inibidoras de Apoptose/genética , Proteínas Inibidoras de Apoptose/metabolismo , Caspases/metabolismo , Autofagia/genética , Ubiquitinação , Proteínas Mitocondriais/metabolismoRESUMO
Unclear issues in protein studies include but not limited to the stability and denaturation mechanism in the presence of denaturants. Herein, we report a dynamic monitoring approach based on nanopore single-molecule biosensor, which can detect the protein's folding and unfolding transitions by recording a nanopore ionic current. When gradually increasing the concentration of denaturant guanidine hydrochloride (GdmCl), sensitive responses were observed with lysozyme unfolding. The emergence of the featured biphasic-pulse demonstrated the existence of a stable intermediate. It was the first time to experimentally confirm the dynamic equilibrium between the intermediate and the native states at single molecule level, therefore consolidating the standpoint of lysozyme denaturation process following the three-state model. Additionally, we got more insights into the conformation about the intermediate as globular-like structure, larger gyration radius, and enhanced positive charge density. We considered that the manner of denaturant toward lysozyme adopts the "direct" model based on stronger electrostatic and van der Waals forces. Nanopore biosensor exhibited excellent sensitivity with a low detection concentration of 280 pM and reproducibility in analysing the folding intermediate of lysozyme.
Assuntos
Nanoporos , Dobramento de Proteína , Desnaturação Proteica , Muramidase/química , Reprodutibilidade dos Testes , Guanidina/química , Cinética , Termodinâmica , Conformação ProteicaRESUMO
Graft-versus-host disease (GVHD) is a major life-threatening complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Inflammatory signaling pathways promote T-cell activation and are involved in the pathogenesis of GVHD. Suppressor of cytokine signaling 1 (SOCS1) is a critical negative regulator for several inflammatory cytokines. However, its regulatory role in T-cell activation and GVHD has not been elucidated. Multiomics analysis of the transcriptome and chromatin structure of granulocyte-colony-stimulating-factor (G-CSF)-administered hyporesponsive T cells from healthy donors reveal that G-CSF upregulates SOCS1 by reorganizing the chromatin structure around the SOCS1 locus. Parallel in vitro and in vivo analyses demonstrate that SOCS1 is critical for restraining T cell activation. Loss of Socs1 in T cells exacerbates GVHD pathogenesis and diminishes the protective role of G-CSF in GVHD mouse models. Further analysis shows that SOCS1 inhibits T cell activation not only by inhibiting the colony-stimulating-factor 3 receptor (CSF3R)/Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway, but also by restraining activation of the inflammasome signaling pathway. Moreover, high expression of SOCS1 in T cells from patients correlates with low acute GVHD occurrence after HSCT. Overall, these findings identify that SOCS1 is critical for inhibiting T cell activation and represents a potential target for the attenuation of GVHD.
Assuntos
Doença Enxerto-Hospedeiro , Proteína 1 Supressora da Sinalização de Citocina , Linfócitos T , Animais , Cromatina , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/genética , Fator Estimulador de Colônias de Granulócitos/farmacologia , Camundongos , Proteína 1 Supressora da Sinalização de Citocina/genética , Biologia de Sistemas/métodos , Linfócitos T/metabolismo , Transplante Homólogo/efeitos adversosRESUMO
BACKGROUND: Urticaria is a common skin disease characterized by episodes of wheals, and it has a negative effect on patients' quality of life. Large-scale population-based epidemiological studies of urticaria are scarce in China. The aim of this survey was to determine the prevalence, clinical forms, and risk factors of urticaria in the Chinese population. METHODS: This survey was conducted in 35 cities from 31 provinces, autonomous regions, and municipalities of China. Two to three communities in each city were selected in this investigation. Participants completed questionnaires and received dermatological examinations. We analyzed the prevalence, clinical forms, and risk factors of urticaria. RESULTS: In total, 44,875 questionnaires were distributed and 41,041 valid questionnaires were collected (17,563 male and 23,478 female participants). The lifetime prevalence of urticaria was 7.30%, with 8.26% in female and 6.34% in male individuals ( P â<â0.05). The point prevalence of urticaria was 0.75%, with 0.79% in female and 0.71% in male individuals ( P â<â0.05). Concomitant angioedema was found in 6.16% of patients. Adults had a higher prevalence of urticaria than adolescents and children. Living in urban areas, exposure to pollutants, an anxious or depressed psychological status, a personal and family history of allergy, thyroid diseases, and Helicobacter pylori infection were associated with a higher prevalence of urticaria. Smoking was correlated with a reduced risk of urticaria. CONCLUSION: This study demonstrated that the lifetime prevalence of urticaria was 7.30% and the point prevalence was 0.75% in the Chinese population; women had a higher prevalence of urticaria than men. Various factors were correlated with urticaria.