Towards the development of an epitope-focused vaccine for SARS-CoV-2.

The rapid spread of COVID-19 on all continents and the mortality induced by SARS-CoV-2 virus, the cause of the pandemic coronavirus disease 2019 (COVID-19) has motivated an unprecedented effort for vaccine development. Inactivated viruses as well as vaccines focused on the partial or total sequence of the Spike protein using different novel platforms such us RNA, DNA, proteins, and non-replicating viral vectors have been developed. The high global need for vaccines, now and in the future, and the emergence of new variants of concern still requires development of accessible vaccines that can be adapted according to the most prevalent variants in the respective regions. Here, we describe the immunogenic properties of a group of theoretically predicted RBD peptides to be used as the first step towards the development of an effective, safe and low-cost epitope-focused vaccine. One of the tested peptides named P5, proved to be safe and immunogenic. Subcutaneous administration of the peptide, formulated with alumina, induced high levels of specific IgG antibodies in mice and hamsters, as well as an increase of IFN-γ expression by CD8+ T cells in C57 and BALB/c mice upon in vitro stimulation with P5. Neutralizing titers of anti-P5 antibodies, however, were disappointingly low, a deficiency that we will attempt to resolve by the inclusion of additional immunogenic epitopes to P5. The safety and immunogenicity data reported in this study support the use of this peptide as a starting point for the design of an epitope restricted vaccine.

Melatonin Decreases Circulating Levels of Galectin-3 and Cytokines, Motor Activity, and Anxiety Following Acute Global Cerebral Ischemia in Male Rats.

BACKGROUND: Global cerebral ischemia (GCI) elicits damages to cerebral structures, learning dysfunction, memory impairments, hyperactivity, and anxiety. Circulating levels of galectin-3 (Gal-3) are associated with patient severity and outcome. AIM: To report circulating levels of Gal-3, and cytokines (TNF-α, IL-6, IL-10) in the initial hours (acute) following GCI in a four-vessel occlusion (4-VO) rat model and the effect of melatonin treatment. METHODS: 4-VO model was used to produce GCI using male Sprague-Dawley rats. Groups were: Sham-Veh, Sham-Mel, Isch-Veh and Isch-Mel. Melatonin was administered 30 min after carotid clamp removal. Gal-3 and cytokines levels were measured at 0, 30 min, 6 h and 24 h after the end of cerebral flow interruption using ELISA kits. Motor activity and anxiety were measured using open-field test. RESULTS: Acute GCI (AGCI) followed by reperfusion decreased serum concentrations of TNF-α and increased IL-6 levels 24 h after ischemia, whereas melatonin reduced significantly the concentrations of these cytokines. In all groups IL-10 was higher 30 min and negligible at other times. Circulating levels of Gal-3 were reduced 30 min after ischemia/reperfusion. In the Isch-Mel group the neuroprotective effect generated a reduction in circulating Gal-3 at 6 and 24 h after AGCI, compared with all the groups. Motor activity was increased due to ischemic reperfusion, but acute melatonin treatment reduced locomotion, similar to the control group. Anxiety was reduced in the melatonin group. CONCLUSIONS: Melatonin treatment following AGCI reduces pro-inflammatory factors, Gal-3, motility, and anxiety, therefore it should be considered as supplementary treatment following ischemic stroke.

Anticancer Effects of Extracts from Three Different Chokeberry Species.

Colon cancer risk appears to be lowered by consumption of a diet rich in fruits and vegetables. Chokeberries are rich in phytochemicals that may act as potent anticancer agents. Phytochemicals that are particularly abundant in chokeberries include anthocyanins and phenolic acids. In this study, we compared the growth inhibitory activity of three chokeberry extracts in HT-29 human colon cancer cells. The three extracts tested were derived from Aronia arbutifolia (red), Aronia prunifolia (purple), and Aronia melanocarpa (black). Cells were incubated with either red, purple, or black chokeberry extracts and cell viability was quantified using the thiazolyl blue tetrazolium bromide (MTT) assay. The black chokeberry extract had the greatest effect in reducing cell proliferation. The extracts were also characterized for total phenols (Folin-Ciocalteu assay), total antioxidant activity (oxygen radical absorbance capacity assay), and levels of bioactive phenolic acids (high-performance liquid chromatography). The growth inhibitory activities of the extracts correlated well with total phenolic content, antioxidant activity, and levels of caffeic and chlorogenic acids. The black chokeberry extract had the greatest level of total phenols, antioxidant activity, and individual phenolic acids. This research suggests that the phenolic profile of foods such as chokeberries can help determine their cancer cell growth inhibitory activity.

The Impact of the Roast Levels of Coffee Extracts on their Potential Anticancer Activities.

Coffee is one of the most widely consumed beverages in the world and contains numerous phytochemicals that are beneficial to consumer health. The phytochemical profile of coffee, however, can be affected by the roast level. In this study, we compared the effect of roasting level on the growth inhibitory activity of HT-29 (colon) and SCC-25 (oral) cancer cell lines. The different roasting stages selected for this study were green, cinnamon/blonde, city/medium, full city/medium-dark, and full city plus/dark. Cancer cells were treated with various concentrations of coffee extracts for 72 hr. Cell viability was quantified using the thiazolyl blue tetrazolium bromide assay. It was found that the lighter roast extracts, Cinnamon in particular, reduced cell growth more than darker roast extracts. The Cinnamon extract had the greatest amount of total phenolic content and antioxidant activity. Relative levels of gallic, caffeic, and chlorogenic acid in the extracts were also compared. The Cinnamon coffee extract had the highest levels of gallic and caffeic acids, which have both been widely-regarded as bioactive phytochemicals. In conclusion, the consumption of lighter roasted coffee, may contribute to the prevention of certain types of cancer such as oral and colon. PRACTICAL APPLICATION: Chemical compounds in coffee may reduce the risk for certain types of cancers. These compounds may be particularly abundant in lighter roasted coffee. Therefore, lighter roasted coffee could contribute to the prevention of cancer through a healthy diet.

[Tuberculosis in indigenous peoples in the Brazilian Amazon: an epidemiological study in the Upper Rio Negro region]. / Tuberculose em indígenas da Amazônia brasileira: estudo epidemiológico na região do Alto Rio Negro.

OBJECTIVE: To describe the sociodemographic, clinical, and epidemiological characteristics of reported tuberculosis cases among indigenous individuals of São Gabriel de Cachoeira, State of Amazonas, Brazil, and to identify the factors associated with mortality during treatment; and to estimate the prevalence of latent tuberculosis infection (LTBI) and associated factors and obtain information on the therapeutic course and the individual perceptions regarding acquistion of tuberculosis in the district of Iauaretê. METHODS: Firstly, a retrospective epidemiological study (1997 to 2007) was conducted using data from the Brazilian Notifiable Diseases Surveillance System (SINAN). Next, a cross-sectional study (2010) was conducted with respiratory symptomatic subjects and contacts of Iauaretê. RESULTS: Seven hundred and twenty-three new cases were reported, with incidence of 273.4/100 000 and mortality of 13.2/100 000. There was a predominance of males (57%), aged > 45 years (37.6%), people with no schooling (42.7%), and cases from rural areas (76.9%). Patients aged 0 to 20 years were at lower risk of death when compared to those aged > 45 years (OR = 0.3; IC95%: 0.1 a 0.9). In Iauaretê, with 15.3% of the reported cases, 184 people were interviewed. A prevalence of LTB of 76.1% was reported. Tuberculin skin test > 5 mm was associated with the > 15-year old age group, history of active tuberculosis, and radiological alterations. A previous history of tuberculosis was cited by 54 people (29.3%). The main explanation for the disease was "puffing/poisoning" (24.1%). The therapeutic course included industrialized drugs (42.6%), medicinal plants/roots, shamanism, and prayer (42.7%). CONCLUSIONS: The risk of tuberculosis infection and disease in this population was high. Despite the reduced incidence resulting from recent efforts, tuberculosis control requires closer surveillance of contacts and improvement in communication strategies between health teams and indigenous populations.

Tuberculose em indígenas da Amazônia brasileira: estudo epidemiológico na região do Alto Rio Negro / Tuberculosis in indigenous peoples in the Brazilian Amazon: an epidemiological study in the Upper Rio Negro region

OBJETIVO: Descrever as características sociodemográficas e clínico-epidemiológicas dos casos de tuberculose notificados na população indígena do Município de São Gabriel de Cachoeira, Estado do Amazonas, Brasil, e identificar fatores associados ao óbito durante o tratamento; e estimar a prevalência de infecção latente por tuberculose (ILTB) e fatores associados e obter informações sobre o itinerário terapêutico e a percepção acerca do adoecimento dos indígenas do Distrito de Iauaretê. MÉTODOS: Primeiramente, realizou-se um estudo epidemiológico retrospectivo (1997 a 2007) com base nos dados do Sistema de Informação de Agravos de Notificação. Posteriormente, realizou-se um estudo transversal (2010) em sintomáticos respiratórios e contatos no Distrito Indígena de Iauaretê. RESULTADOS: Registraram-se 723 casos novos, com incidência de 273,4/100 000 e mortalidade de 13,2/100 000. Houve predomínio em homens (57%), idade > 45 anos (37,6%), pessoas sem escolaridade (42,7%) e na área rural (76,9%). Doentes de 0 a 20 anos apresentaram menor chance de óbito quando comparados à idade > 45 anos (OR = 0,3; IC95%: 0,1 a 0,9). Em Iauaretê, que concentrou 15,3% das notificações, foram entrevistados 184 indígenas. Revelou-se prevalência de ILTB de 76,1%. Prova tuberculínica > 5 mm associou-se com idade > 15 anos, história de tuberculose ativa e alterações radiológicas. Tuberculose anterior foi citada por 54 indígenas (29,3%). A principal explicação para o adoecimento foi sopro/envenenamento (24,1%). O itinerário terapêutico incluiu medicamentos industrializados (42,6%), plantas medicinais/raízes, pajelança/xamanismo e reza (42,7%). CONCLUSÕES: A prevalência de infecção tuberculosa e doença ativa nessa população foi elevada. As estratégias de controle tiveram resultados positivos, com redução na incidência em tempos recentes. Entretanto, para controlar a tuberculose é necessário intensificar a vigilância dos contatos e aperfeiçoar as estratégias de comunicação das equipes com a população indígena.

OBJECTIVE: To describe the sociodemographic, clinical, and epidemiological characteristics of reported tuberculosis cases among indigenous individuals of São Gabriel de Cachoeira, State of Amazonas, Brazil, and to identify the factors associated with mortality during treatment; and to estimate the prevalence of latent tuberculosis infection (LTBI) and associated factors and obtain information on the therapeutic course and the individual perceptions regarding acquistion of tuberculosis in the district of Iauaretê. METHODS: Firstly, a retrospective epidemiological study (1997 to 2007) was conducted using data from the Brazilian Notifiable Diseases Surveillance System (SINAN). Next, a cross-sectional study (2010) was conducted with respiratory symptomatic subjects and contacts of Iauaretê. RESULTS: Seven hundred and twenty-three new cases were reported, with incidence of 273.4/100 000 and mortality of 13.2/100 000. There was a predominance of males (57%), aged > 45 years (37.6%), people with no schooling (42.7%), and cases from rural areas (76.9%). Patients aged 0 to 20 years were at lower risk of death when compared to those aged > 45 years (OR = 0.3; IC95%: 0.1 a 0.9). In Iauaretê, with 15.3% of the reported cases, 184 people were interviewed. A prevalence of LTB of 76.1% was reported. Tuberculin skin test > 5 mm was associated with the > 15-year old age group, history of active tuberculosis, and radiological alterations. A previous history of tuberculosis was cited by 54 people (29.3%). The main explanation for the disease was "puffing/poisoning" (24.1%). The therapeutic course included industrialized drugs (42.6%), medicinal plants/roots, shamanism, and prayer (42.7%). CONCLUSIONS: The risk of tuberculosis infection and disease in this population was high. Despite the reduced incidence resulting from recent efforts, tuberculosis control requires closer surveillance of contacts and improvement in communication strategies between health teams and indigenous populations.

Tuberculose entre os indígenas de São Gabriel da Cachoeira, AM: estudo epidemiológico com base em casos notificados e dados provenientes do Distrito Indígena de Iauaretê / Tuberculosis among the Indians of San Gabriel da Cachoeira, AM: epidemiological study based on data from reported cases and the District of Indigenous Iauaretê

A tuberculose (TB) se mantém como um dos principais problemas de saúde para os povos indígenas no Brasil. Realizou-se um estudo que caracterizou o perfil epidemiológico dos casos de TB notificados no SINAN, em São Gabriel da Cachoeira (SGC), no período 1997-2007, e analisaram-se os dados provenientes de uma investigação de indivíduos com sintomas respiratórios realizada no Distrito Indígena de Iauaretê, em 2010. Observaram-se altas taxas de incidência (216,1 / 100.000 habitantes) e de mortalidade (8,9/100.000) por TB entre a população de SGC com uma expressiva proporção de casos (15,6 por cento) diagnosticados em Iauaretê. A análise das notificações revelou que houve concentração de casos em homens (56,9 por cento), em maiores de 45 anos (37,1 por cento), em pessoas sem escolaridade (41,6 por cento), e na zona rural (74,8 por cento). De acordo com o modelo de regressão logística, a variável faixa etária de 20-45 anos foi considerada preditora para o óbito nos pacientes que iniciaram tratamento para TB (OR: 3,0; IC95 por cento: 1,1-8,3). A análise dos dados provenientes de Iauaretê mostrou alta prevalência de infecção pelo Mycobacterium tuberculosis (...) e antecedente de TB (...) mostraram associação com respostas à prova tuberculínica (..) 5 mm. Dos 184 entrevistados em Iauaretê, 54 (29,8 por cento) referiram história anterior de TB. Esse subgrupo narrou como principal causa para o adoecimento sopro e/ou envenenamento (13/54; 24,1 por cento), e o itinerário terapêutico inicial utilizado foi uso de plantas medicinais e/ou pajelança / xamanismo, seguido do uso de medicamentos farmacêuticos (42,6 por cento e 42,7 por cento, respectivamente). Os resultados indicam que a transmissão da TB em SGC se mantém em altos patamares ao longo do tempo, fazendo com que a população esteja submetida a um permanente risco de infecção e doença. Por fim, as evidências indicam que outros problemas devem ser considerados no diagnóstico diferencial ou como fatores de risco para TB mostrando a necessidade de estabelecer protocolos específicos para o controle da TB em indígenas, sobretudo no que tange à detecção, ao diagnóstico, ao tratamento e acompanhamento dos casos identificados, e também aos problemas relacionados ao acesso aos serviços de saúde.