RESUMEN
On March 11, 2020, the World Health Organization (WHO) officially declared the outbreak caused by the new coronavirus (SARS-CoV-2) a pandemic. The rapid spread of the disease surprised the scientific and medical community. Based on the latest reports, news, and scientific articles published, there is no doubt that the coronavirus has overloaded health systems globally. Practical actions against the recent emergence and rapid expansion of the SARS-CoV-2 require the development and use of tools for discovering new molecular anti-SARS-CoV-2 targets. Thus, this review presents bioinformatics and molecular modeling strategies that aim to assist in the discovery of potential anti-SARS-CoV-2 agents. Besides, we reviewed the relationship between SARS-CoV-2 and innate immunity, since understanding the structures involved in this infection can contribute to the development of new therapeutic targets. Bioinformatics is a technology that assists researchers in coping with diseases by investigating genetic sequencing and seeking structural models of potential molecular targets present in SARS-CoV2. The details provided in this review provide future points of consideration in the field of virology and medical sciences that will contribute to clarifying potential therapeutic targets for anti-SARS-CoV-2 and for understanding the molecular mechanisms responsible for the pathogenesis and virulence of SARS-CoV-2.
Asunto(s)
Antivirales/uso terapéutico , Betacoronavirus/efectos de los fármacos , Betacoronavirus/inmunología , Biología Computacional , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/inmunología , Descubrimiento de Drogas , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/inmunología , Animales , Betacoronavirus/patogenicidad , COVID-19 , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/transmisión , Humanos , Inmunidad Innata , Pandemias , Neumonía Viral/diagnóstico , Neumonía Viral/transmisión , SARS-CoV-2RESUMEN
BACKGROUND: The immunopathogenesis of severe asthma has been associated with an inefficient regulatory response. There are a few studies about the CD4 T cells profile among individuals with severe asthma refractory to treatment. OBJECTIVE: To evaluate the CD4 T lymphocyte profile from individuals with severe asthma according to their response to treatment, relating to their atopy status and age of asthma onset. METHODS: We evaluated nineteen individuals with severe asthma refractory to treatment (SAR), 21 with well-controlled or partly controlled severe asthma (CSA) and 23 with mild-to-moderate asthma (MMA). Lymphocytes were obtained from PBMC, and the frequency of expression of different molecules in this population was assessed using the flow cytometry. RESULTS: We observed the frequency of CD4+ IFN-γ+ T cells was higher in atopic individuals with SAR than with CSA. In addition, among the atopic and early-onset asthma (EOA), the frequency of CD4+ CTLA-4+ T cells was lower in the SAR group than the CSA group. In relation to non-atopic and late-onset asthma (LOA) phenotypes, we noted the frequency of CD4+ FoxP3+ T cells was lower in individuals with SAR than with CSA. We also observed among the LOA patients, the frequency of CD4+ TGF-ß+ T cells was decreased in SAR group than the in CSA group. CONCLUSION AND CLINICAL RELEVANCE: Our data suggest that refractoriness to treatment in asthma is associated with a lower expression of distinct regulatory molecules by CD4 T cells between those who are atopic and have EOA and those who are non-atopic and have LOA. Thus, these results may contribute to the identification of new regulatory strategies to treat asthma according to their phenotypes.
Asunto(s)
Asma/inmunología , Asma/metabolismo , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Inmunomodulación , Adulto , Edad de Inicio , Asma/diagnóstico , Biomarcadores , Antígeno CTLA-4/metabolismo , Citocinas/metabolismo , Femenino , Citometría de Flujo , Humanos , Hipersensibilidad Inmediata/inmunología , Hipersensibilidad Inmediata/metabolismo , Hipersensibilidad Inmediata/patología , Inmunoglobulina E/inmunología , Inmunofenotipificación , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Masculino , Persona de Mediana Edad , Pruebas de Función Respiratoria , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Vitamina D/metabolismoRESUMEN
Malondialdehyde (MDA), an end product of lipid peroxidation and biomarker for oxidative stress, and its soluble receptor (sRAGE) were evaluated in 42 patients with type 1 diabetes mellitus, but without chronic complications, during the early years after diagnosis (0-10 years) and through the further progression of the disease (10-20 and > 20 years after diagnosis). Clinical and biochemical parameters of the cohort of diabetic patients were compared with those determined in 24 healthy individuals. The median levels of MDA in plasma were similar in type 1 diabetes patients and in healthy subjects. In contrast, statistically significant increases were detected in the median values of sRAGE in patients with type 1 diabetes compared with healthy subjects (2423.75 versus 1472.75 pg/ml; p=0.001, Mann-Whitney test). However, no significant between-group differences (p>0.05) were observed in levels of sRAGE when diabetic patients were grouped according to time elapsed after diagnosis. It is concluded that increased plasma levels of sRAGE in type 1 diabetes may provide protection against cell damage and may be sufficient to eliminate excessive circulating MDA during early years after disease onset.