RESUMO
As abnormal angiogenesis is associated with exacerbation of various diseases, precise control over angiogenesis is imperative. Vascular endothelial growth factor (VEGF), the most well-known angiogenic factor, binds to VEGF receptor (VEGFR), activates various signaling pathways, and mediates angiogenesis. Therefore, blocking the VEGF-induced angiogenic response-related signaling pathways may alleviate various disease symptoms through inhibition of angiogenesis. Ulmus davidiana is a safe natural product that has been traditionally consumed, but its effects on endothelial cells (ECs) and the underlying mechanism of action are unclear. In the present study, we focused on the effect of a 60% edible ethanolic extract of U. davidiana (U60E) on angiogenesis. U60E inhibited the VEGF-mediated proliferation, tube formation, and migration ability of ECs. Mechanistically, U60E inhibited endothelial nitric oxide synthase activation and nitric oxide production by blocking the protein kinase B signaling pathway activated by VEGF and consequently inhibiting proliferation, tube formation, and migration of ECs. These results suggest that U60E could be a potential and safe therapeutic agent capable of suppressing proangiogenic diseases by inhibiting VEGF-induced angiogenesis.
Assuntos
Inibidores da Angiogênese , Células Endoteliais da Veia Umbilical Humana/metabolismo , Neovascularização Patológica/tratamento farmacológico , Extratos Vegetais , Ulmus/química , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Inibidores da Angiogênese/química , Inibidores da Angiogênese/farmacologia , Etanol/química , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Fator A de Crescimento do Endotélio Vascular/farmacologiaRESUMO
Dengue virus (DENV) is a major infectious viral pathogen that affects millions of individuals worldwide every year, causing a potentially fatal syndrome, while no commercial antiviral drugs are yet available. To develop an antiviral against dengue fever, it is necessary to understand the relationship between DENV and host cells, which could provide a basis for viral dynamics and identification of inhibitory drug targets. In this study, we designed DiD-loaded and BODIPY-ceramide-encapsulated DENV-polymersome hybrid nanovesicles (DENVSomes) prepared by an extrusion method, which trigger red fluorescence in the endosome and green in the Golgi. DENVSome monitors the dynamics of host cell-virus interaction and tracking in living cells with novel state-of-the-art imaging technologies that show images at high resolution. Also, DENVSome can be exploited to screen whether candidate antiviral drugs interact with DENVs. Consequently, we successfully demonstrated that DENVSome is an efficient tool for tracking and unraveling the mechanisms of replication and drug screening for antiviral drugs of DENV.
Assuntos
Antivirais/farmacologia , Vírus da Dengue/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos/métodos , Compostos de Boro/química , Rastreamento de Células , Dengue/virologia , Vírus da Dengue/química , Vírus da Dengue/fisiologia , Avaliação Pré-Clínica de Medicamentos/instrumentação , Corantes Fluorescentes/química , Humanos , Nanopartículas/química , Replicação Viral/efeitos dos fármacosRESUMO
Powerful adjuvants to augment vaccine efficacy with a less immunogenic vaccine system are in great demand. In this study, a novel squalene-based cationic poly(amino acid) adjuvant (CASq) that elicits both cellular (Th1) and humoral (Th2) immune responses is developed. CASq is demonstrated to promote cellular uptake of viral antigen and stimulate macrophages, leading to active production of interleukin-12. Furthermore, co-administration of inactivated pdm H1N1 vaccine with CASq significantly increases the generation of antigen-specific antibodies and T cell immune responses in mice, as well as resulting in complete prevention of disease symptoms and protection against lethal infection.
Assuntos
Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/farmacologia , Vacinas contra Influenza/imunologia , Infecções por Orthomyxoviridae/imunologia , Polímeros/química , Animais , Citocinas/metabolismo , Imunidade Celular , Imunidade Humoral , Vírus da Influenza A Subtipo H1N1/imunologia , Vacinas contra Influenza/farmacologia , Lisina/química , Camundongos , Camundongos Endogâmicos C57BL , Nanopartículas/química , Infecções por Orthomyxoviridae/prevenção & controle , Fenilalanina/química , Polímeros/farmacologia , Células RAW 264.7 , Esqualeno/química , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/farmacologiaRESUMO
Biomarker-specific photothermal nanoparticles that can efficiently sense markers that are overexpressed in distinguished adenocarcinomas have attracted much interest in an aspect of efficacy increase of cancer treatment. We demonstrated a promising prospect of a smart photothermal therapy agent employing anti-epidermal growth factor receptor aptamer (AptEGFR)-conjugated polyethylene glycol (PEG) layted gold nanorods (AptEGFR-PGNRs). The cetyltrimethylammonium bromide bilayer on GNRs was replaced with heterobifunctional PEG (COOH-PEG-SH) not only to serve as a biocompatible stabilizer and but also to conjugate AptEGFR. Subsequently, to direct photothermal therapy agent toward epithelial cancer cells, the carboxylated PEGylated GNRs (PGNRs) were further functionalized with AptEGFR using carbodiimide chemistry. Then, to assess the potential as biomarker-specific photothermal therapy agent of synthesized AptEGFR-PGNRs, the optical properties, biocompatibility, colloidal stability, binding affinity, and epicellial cancer cell killing efficacy in vitro/in vivo under near-infrared laser irradiation were investigated. As a result, AptEGFR-PGNRs exhibit excellent tumor targeting ability and feasibility of effective photothermal ablation cancer therapy.