RESUMO
We are amid the historic coronavirus infectious disease 2019 (COVID-19) pandemic. Imbalances in the accessibility of vaccines, medicines, and diagnostics among countries, regions, and populations, and those in war crises, have been problematic. Nanobodies are small, stable, customizable, and inexpensive to produce. Herein, we present a panel of nanobodies that can detect the spike proteins of five SARS-CoV-2 variants of concern (VOCs) including Omicron. Here we show via ELISA, lateral flow, kinetic, flow cytometric, microscopy, and Western blotting assays that our nanobodies can quantify the spike variants. This panel of nanobodies broadly neutralizes viral infection caused by pseudotyped and authentic SARS-CoV-2 VOCs. Structural analyses show that the P86 clone targets epitopes that are conserved yet unclassified on the receptor-binding domain (RBD) and contacts the N-terminal domain (NTD). Human antibodies rarely access both regions; consequently, the clone buries hidden crevasses of SARS-CoV-2 spike proteins that go undetected by conventional antibodies.
Assuntos
COVID-19 , Anticorpos de Domínio Único , Anticorpos Antivirais , Humanos , Glicoproteínas de Membrana/metabolismo , Testes de Neutralização , SARS-CoV-2/genética , Anticorpos de Domínio Único/genética , Glicoproteína da Espícula de Coronavírus/genética , Proteínas do Envelope Viral/metabolismoRESUMO
IgG4-related disease (IgG4-RD) can affect various organs, and the pancreas and salivary gland are representative examples. We report a rare case of IgG4-RD of the paratestis. A 74-year-old man presented with left scrotal swelling. Scrotopuncture drainage and cytology confirmed a clear, yellow retention liquid (130 mL) with many small, similar lymphocytes and a few plasmacytes. Many lymphoid cells were immunopositive for CD3 on a cell block section, indicating that a predominant type of lymphoid cells was T cell. There were also some CD20 immunopositive cells and a few IgG4 immunopositive cells. Two months later the left scrotal swelling had returned, and he underwent radical inguinal orchiectomy. Microscopically, there was considerable lymphoplasmacytic inflammatory infiltration, fibrosis and abundant IgG4 immunopositive cells in the paratesticular region. The histopathologic and immunohistochemistry findings were consistent with IgG4-RD. However, the abundant T cells in the scrotal fluid complicated the cytological diagnosis in our case.
Assuntos
Doenças Autoimunes/patologia , Doença Relacionada a Imunoglobulina G4/patologia , Imunoglobulina G/imunologia , Plasmócitos/patologia , Idoso , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/imunologia , Biópsia/métodos , Humanos , Doença Relacionada a Imunoglobulina G4/diagnóstico , Doença Relacionada a Imunoglobulina G4/imunologia , Imuno-Histoquímica/métodos , Masculino , Glândulas Salivares/patologiaRESUMO
Anti-Leishmania in vitro and in vivo activities of various rhodacyanine derivatives have been examined. Among them, the fluorinatied variant SJL-01 (8) showed IC(50) of 0.011 microM against Leishmania donovani strain MHOM/ET/67/L82 (selective index of >15000) and 95-97% inhibition against L. donovani strain MHOM/ET/67/HU in female BALB/c mice by 1.3-12.5 mg/kg x 5 iv administrations. Negative results on chromosomal aberration test and in vitro micronucleus test suggest that compound 8 is a hopeful candidate for visceral leishmaniasis (VL).