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1.
Int J Biol Macromol ; 224: 233-242, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36272566

RESUMO

Novel aerogel-like wound dressing able to sense the healing progress was developed. Anthocyanins (Ac) have been reported as a significant pH-sensory extract with various biological activities. Herein, anthocyanins were extracted from red-cabbage (Brassica oleracea L. Var. capitata). The anthocyanin probe was integrated as a water-soluble direct dye at various concentrations into carboxymethyl cellulose/polyvinyl alcohol composite in the presence of potassium aluminum sulfate mordant. The generated composites were then freeze-dried to provide the corresponding aerogel-like smart wound dressing to function as an antibacterial and biochromic bulk presenting a comfort dressing biosensor to monitor the progress of a wound healing. Reducing the pH value of a wound mimicking fluid resulted in a hypsochromic shift from 592 to 446 nm. The halochromic activity of anthocyanin showed colorimetric changes from purple to pink. The colorimetric measurements of the prepared anthocyanin-containing aerogel-like diagnostic assay were explored by CIE Lab coordinates and UV-Vis absorption spectra. The effects of the anthocyanin content on the morphology, stiffness, air-permeability, and mechanical behavior of the aerogel-like wound dress were explored by various analytical methods. Both cytotoxicity and antibacterial activity of were investigated.


Assuntos
Antocianinas , Infecção dos Ferimentos , Humanos , Antocianinas/química , Álcool de Polivinil/química , Carboximetilcelulose Sódica , Colorimetria , Bandagens , Antibacterianos/farmacologia , Extratos Vegetais
3.
Science ; 361(6404): 810-813, 2018 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-30026316

RESUMO

RIPK1 (receptor-interacting serine/threonine kinase 1) is a master regulator of signaling pathways leading to inflammation and cell death and is of medical interest as a drug target. We report four patients from three unrelated families with complete RIPK1 deficiency caused by rare homozygous mutations. The patients suffered from recurrent infections, early-onset inflammatory bowel disease, and progressive polyarthritis. They had immunodeficiency with lymphopenia and altered production of various cytokines revealed by whole-blood assays. In vitro, RIPK1-deficient cells showed impaired mitogen-activated protein kinase activation and cytokine secretion and were prone to necroptosis. Hematopoietic stem cell transplantation reversed cytokine production defects and resolved clinical symptoms in one patient. Thus, RIPK1 plays a critical role in the human immune system.


Assuntos
Artrite/genética , Doenças Inflamatórias Intestinais/genética , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Imunodeficiência Combinada Severa/genética , Alelos , Artrite/imunologia , Citocinas/metabolismo , Feminino , Fibroblastos/metabolismo , Fibroblastos/patologia , Humanos , Doenças Inflamatórias Intestinais/imunologia , Linfopenia/genética , Masculino , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Linhagem , Imunodeficiência Combinada Severa/imunologia
4.
Nat Genet ; 47(5): 523-527, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25774636

RESUMO

Human genetic factors predispose to tuberculosis (TB). We studied 7.6 million genetic variants in 5,530 people with pulmonary TB and in 5,607 healthy controls. In the combined analysis of these subjects and the follow-up cohort (15,087 TB patients and controls altogether), we found an association between TB and variants located in introns of the ASAP1 gene on chromosome 8q24 (P = 2.6 × 10(-11) for rs4733781; P = 1.0 × 10(-10) for rs10956514). Dendritic cells (DCs) showed high ASAP1 expression that was reduced after Mycobacterium tuberculosis infection, and rs10956514 was associated with the level of reduction of ASAP1 expression. The ASAP1 protein is involved in actin and membrane remodeling and has been associated with podosomes. The ASAP1-depleted DCs showed impaired matrix degradation and migration. Therefore, genetically determined excessive reduction of ASAP1 expression in M. tuberculosis-infected DCs may lead to their impaired migration, suggesting a potential mechanism of predisposition to TB.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Células Dendríticas/fisiologia , Tuberculose Pulmonar/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adulto , Estudos de Casos e Controles , Movimento Celular , Células Cultivadas , Feminino , Expressão Gênica , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Íntrons , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Transporte Proteico
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