RESUMO
Dengue (DENV) and Chikungunya (CHIKV) viruses can be transmitted simultaneously by Aedes mosquitoes, and there may be co-infections in humans. However, how the adaptive immune response is modified in the host has yet to be known entirely. In this study, we analyzed the cross-reactivity and neutralizing activity of IgG antibodies against DENV and CHIKV in sera of patients from the Mexican Institute of Social Security in Veracruz, Mexico, collected in 2013 and 2015 and using IgG antibodies of BALB/c mice inoculated with DENV and/or CHIKV. Mice first inoculated with DENV and then with CHIKV produced IgG antibodies that neutralized both viruses. Mice were inoculated with CHIKV, and then with DENV; they had IgG antibodies with more significant anti-CHIKV IgG antibody neutralizing activity. However, the inoculation only with CHIKV resulted in better neutralization of DENV2. In sera obtained from patients in 2013, significant cross-reactivity and low anti-CHIKV IgG antibody neutralizing activity were observed. In CHIKV-positive 2015 sera, the anti-DENV IgG antibody neutralizing activity was high. These results suggest that CHIKV stimulates DENV2-induced memory responses and vice versa. Furthermore, cross-reactivity between the two viruses generated neutralizing antibodies, but exchanging CHIKV for DENV2 generated a better anti-CHIKV neutralizing response.
Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Febre de Chikungunya , Vírus Chikungunya , Reações Cruzadas , Vírus da Dengue , Dengue , Imunoglobulina G , Camundongos Endogâmicos BALB C , Animais , Vírus Chikungunya/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Dengue/imunologia , Dengue/virologia , Vírus da Dengue/imunologia , Humanos , Febre de Chikungunya/imunologia , Febre de Chikungunya/virologia , Reações Cruzadas/imunologia , Camundongos , México , Feminino , Testes de Neutralização , Masculino , Coinfecção/imunologia , Coinfecção/virologia , AdultoRESUMO
BACKGROUND: Photodynamic therapy (PDT) is used to treat tumors through selective cytotoxic effects. PDT induces damage-associated molecular patterns (DAMPs) expression, which can cause an immunogenic death cell (IDC). In this study we identified potential immunogenic epitopes generated by PDT on triple-negative breast cancer cell line (MDA-MB-231). METHODS: MDA-MB-231 cells were exposed to PDT using ALA (160 µg/mL)/630 nm at 8 J/cm2. Membrane proteins were extracted and separated by 2D PAGE. Proteins overexpressed were identified by LC-MS/MS and analyzed in silico through a peptide-HLA docking in order to identify the epitopes with more immunogenicity and antigenicity properties, as well as lower allergenicity and toxicity activity. The selected peptides were evaluated in response to macrophage activation and cytokine release by flow cytometry. RESULTS: Differential proteins were overexpressed in the cells treated with PDT. A group of 16 peptides were identified from them, established in a rigorous selection by measuring antigenicity, immunogenicity, allergenicity, and toxicity in silico. The final selection was based on molecular dynamics, where 2 peptides showed the highest stability regarding to the RMSD value. These peptides were obtained from the proteins calreticulin and HSP90. The cytokine analysis evidenced macrophage activation by the releasing of TNF. CONCLUSION: Two peptides were identified from calreticulin and HSP90; proteins induced by PDT in MDA-MB-231 cells. Both epitopes showed immunogenic potential as a peptide-based vaccine for triple-negative breast cancer.
Assuntos
Neoplasias da Mama , Fotoquimioterapia , Neoplasias de Mama Triplo Negativas , Vacinas , Humanos , Feminino , Fármacos Fotossensibilizantes , Fotoquimioterapia/métodos , Calreticulina/metabolismo , Calreticulina/uso terapêutico , Epitopos/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Cromatografia Líquida , Espectrometria de Massas em Tandem , Vacinas/uso terapêutico , Citocinas/metabolismo , Linhagem Celular TumoralRESUMO
Cancer is one of the leading causes of deaths worldwide. The agents capable of causing damage to genetic material are known as genotoxins and, according to their mode of action, are classified into mutagens, carcinogens or teratogens. Genotoxins are involved in the pathogenesis of several chronic degenerative diseases including hepatic, neurodegenerative and cardiovascular disorders, diabetes, arthritis, cancer, chronic inflammation and ageing. In recent decades, researchers have found novel bioactive phytocompounds able to counteract the effects of physical and chemical mutagens. Several studies have shown potential antigenotoxicity in a variety of fruits. In this review (Part 1), we present an overview of research conducted on some fruits (grapefruit, cranberries, pomegranate, guava, pineapple, and mango) which are frequentl consumed by humans, as well as the analysis of some phytochemicals extracted from fruits and yeasts which have demonstrated antigenotoxic capacity in various tests, including the Ames assay, sister chromatid exchange, chromosomal aberrations, micronucleus and comet assay.