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1.
Dermatologie (Heidelb) ; 75(7): 562-565, 2024 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-38517520

RESUMO

Approximately 2% of the German population suffer from psoriasis. HybridVITA has developed a mobile application (app) that enables psoriasis patients to independently document the progression of the disease and the current psychological stress at home. The HybridVITA app was created in close collaboration with user groups to ensure optimal adaptation to their needs. Two interactive workshops were held with the user groups and the technical developers of the app as a core element of the developmental process. The workshops identified the needs and suggestions for improvement of the various user groups and formulated user stories for the further development of the app using the Scrum method. The participatory approach of the workshop enabled the project team to gather valuable practical knowledge at an early stage of development. The team's awareness of potential obstacles during the early stages of the project enabled them to proactively identify and address these issues prior to implementing the app in dermatological care. We are confident that a patient-centered and participatory approach to health app development can provide valuable insights for developers.


Assuntos
Aplicativos Móveis , Participação do Paciente , Psoríase , Humanos , Participação do Paciente/métodos , Participação do Paciente/psicologia , Psoríase/terapia , Alemanha , Dermatologia
2.
Nat Commun ; 14(1): 473, 2023 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-36709213

RESUMO

Membranous nephropathy (MN) is an antibody-mediated autoimmune disease characterized by glomerular immune complexes containing complement components. However, both the initiation pathways and the pathogenic significance of complement activation in MN are poorly understood. Here, we show that components from all three complement pathways (alternative, classical and lectin) are found in renal biopsies from patients with MN. Proximity ligation assays to directly visualize complement assembly in the tissue reveal dominant activation via the classical pathway, with a close correlation to the degree of glomerular C1q-binding IgG subclasses. In an antigen-specific autoimmune mouse model of MN, glomerular damage and proteinuria are reduced in complement-deficient mice compared with wild-type littermates. Severe disease with progressive ascites, accompanied by extensive loss of the integral podocyte slit diaphragm proteins, nephrin and neph1, only occur in wild-type animals. Finally, targeted silencing of C3 using RNA interference after the onset of proteinuria significantly attenuates disease. Our study shows that, in MN, complement is primarily activated via the classical pathway and targeting complement components such as C3 may represent a promising therapeutic strategy.


Assuntos
Glomerulonefrite Membranosa , Nefropatias , Camundongos , Animais , Glomerulonefrite Membranosa/genética , Ativação do Complemento , Glomérulos Renais/patologia , Proteínas do Sistema Complemento/metabolismo , Imunoglobulina G , Nefropatias/patologia , Proteinúria/metabolismo
3.
Int J Mol Sci ; 23(7)2022 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-35408876

RESUMO

A novel resemblance-ranking peptide library with 160,000 10-meric peptides was designed to search for selective binders to antibodies. The resemblance-ranking principle enabled the selection of sequences that are most similar to the human peptidome. The library was synthesized with ultra-high-density peptide arrays. As proof of principle, screens for selective binders were performed for the therapeutic anti-CD20 antibody rituximab. Several features in the amino acid composition of antibody-binding peptides were identified. The selective affinity of rituximab increased with an increase in the number of hydrophobic amino acids in a peptide, mainly tryptophan and phenylalanine, while a total charge of the peptide remained relatively small. Peptides with a higher affinity exhibited a lower sum helix propensity. For the 30 strongest peptide binders, a substitutional analysis was performed to determine dissociation constants and the invariant amino acids for binding to rituximab. The strongest selective peptides had a dissociation constant in the hundreds of the nano-molar range. The substitutional analysis revealed a specific hydrophobic epitope for rituximab. To show that conformational binders can, in principle, be detected in array format, cyclic peptide substitutions that are similar to the target of rituximab were investigated. Since the specific binders selected via the resemblance-ranking peptide library were based on the hydrophobic interactions that are widespread in the world of biomolecules, the library can be used to screen for potential linear epitopes that may provide information about the cross-reactivity of antibodies.


Assuntos
Anticorpos , Biblioteca de Peptídeos , Aminoácidos , Epitopos , Humanos , Peptídeos/química , Rituximab
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