A styrylpyrone dimer isolated from Aniba heringeri causes apoptosis in MDA-MB-231 triple-negative breast cancer cells.

The styrylpyrone dehydrogoniothalamin (1) and two of its dimers (2 and 3) were isolated from the leaves of Aniba heringeri (Lauraceae). Compound 3 is new, while 1 and 2 are being reported for the first time in this species. Structures were determined by 1D- and 2D-NMR spectroscopy, mass spectrometry, and optical rotation data. Cytotoxic effects and selectivity indices were evaluated in five neoplastic cell lines-PC-3 (prostate), 786-0 (renal), HT-29 (colon), MCF-7, and MDA-MB-231 (breast)-and a non-neoplastic cell line, (NIH/3T3, murine fibroblast). Compound 1 inhibited cell growth by 50% (GI50) at concentrations in the 90.4-175.7 µM range, while 2 proved active against MCF-7 and MDA-MB-231 breast cells (GI50 = 12.24, and 34.22 µM, respectively). Compound 3 showed strong cytotoxicity (GI50 = 4.4 µM) against MDA-MB-231 (an established basal triple-negative breast carcinoma (TNBC) cell line), with a high selective index of 35. This compound was subsequently evaluated for apoptosis induction in MDA-MB-231 cells, using GI50 and 50% lethal concentrations (LC50). Flow cytometry analysis showed that at LC50 compound 3 induced cell death with phosphatidylserine externalization and caspase-3 activation. Apoptotic genes were measured by RT-qPCR, revealing an upregulation of BAX, with an increase in expression of the BAX/BCL2 ratio in treated cells. Fluorescence microscopy disclosed morphological changes related to apoptosis. Overall, these findings showed compound 3 to be a promising prototype against TNBC cells that tend to respond poorly to conventional therapies.

Compounds from Natural Products Candidates to Drug for Chikungunya Virus Infection: A Systematic Review.

INTRODUCTION: Chikungunya fever is a disease caused by infection with the Chikungunya virus, transmitted by Aedes aegypti and Aedes albopictus mosquitoes. Despite its self-limited character, more than 60% of patients have chronic recurrent arthralgia with debilitating pain that lasts for years. AIM: The objective of this review was to gather and analyze evidence from the literature on potential therapeutic strategies with molecules from natural products for the treatment of Chikungunya fever. METHODS: A search was performed for clinical trials, observational studies, in vitro or in vivo, without restriction of the year of publication or language in electronic databases (Medline/PubMed, EMBASE, Google Scholar, The Cochrane Library, LILACS (BVS), clinical trial registries (Clinical Trials.gov), digital libraries from CAPES theses and dissertations (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil) and conference abstracts. A quality assessment of the selected studies was performed using the SYRCLE, RoB2 and SciRAP tools. RESULTS: 42 studies were included, which showed molecules with potential antiviral pharmacological activity or with activity in reducing the joint complications caused by CHIKV infection. CONCLUSIONS: Among the molecules found in the survey of references, regarding the class of secondary metabolites, flavonoids stood out and for this reason, the molecules may be promising candidates for future clinical trials. Overall, evidence from in vitro studies was of acceptable quality; in vivo and intervention studies showed a high risk of bias, which is a limitation of these studies.

Oral manifestations in chikungunya patients: A systematic review.

BACKGROUND: Chikungunya fever is considered an abrupt onset arbovirus transmitted by mosquitoes, mainly Aedes aegypti and Aedes albopictus. The disease has a significant impact on the quality of life of affected persons, and many of its numerous symptoms have not yet been properly clarified, such as the manifestations that can occur in the oral cavity. The aim of this study was to identify the main oral manifestations related to chikungunya fever, as well as describe the demographic characteristics of patients, by conducting a systematic review of the literature. METHODS AND FINDINGS: Searches were performed in MEDLINE (PubMed), Embase (Elsevier), LILACS (VHL), Cochrane Library, Scopus, and CAPES electronic databases for theses and dissertations published up to January 16, 2021 without language and date restrictions. Additional manual searches of gray literature, reference list, and Google Scholar were carried out. We included 27 studies highlighting mainly oral manifestations that cause masticatory discomfort such as ulcers and oral thrush, gingival bleeding, pain and burning of the oral mucous membranes, temporomandibular joint (TMJ) arthralgia, opportunistic infections, and changes in taste. CONCLUSIONS: There seems to be a predominance of oral manifestations that cause discomfort when chewing, such as ulcerations in the acute phase of the disease, with complete remission within 3 to 10 days after the onset, apparently mostly affecting women and older persons. These oral manifestations can be compatible with basic viral infections related to inflammatory response and transitory immunosuppression.

Mask decontamination methods (model N95) for respiratory protection: a rapid review.

BACKGROUND: N95 respiratory protection masks are used by healthcare professionals to prevent contamination from infectious microorganisms transmitted by droplets or aerosols. METHODS: We conducted a rapid review of the literature analyzing the effectiveness of decontamination methods for mask reuse. The database searches were carried out up to September 2020. The systematic review was conducted in a way which simplified the stages of a complete systematic review, due to the worldwide necessity for reliable fast evidences on this matter. RESULTS: A total of 563 articles were retrieved of which 48 laboratory-based studies were selected. Fifteen decontamination methods were included in the studies. A total of 19 laboratory studies used hydrogen peroxide, 21 studies used ultraviolet germicidal irradiation, 4 studies used ethylene oxide, 11 studies used dry heat, 9 studies used moist heat, 5 studies used ethanol, two studies used isopropanol solution, 11 studies used microwave oven, 10 studies used sodium hypochlorite, 7 studies used autoclave, 3 studies used an electric rice cooker, 1 study used cleaning wipes, 1 study used bar soap, 1 study used water, 1 study used multi-purpose high-level disinfection cabinet, and another 1 study used chlorine dioxide. Five methods that are promising are as follows: hydrogen peroxide vapor, ultraviolet irradiation, dry heat, wet heat/pasteurization, and microwave ovens. CONCLUSIONS: We have presented the best available evidence on mask decontamination; nevertheless, its applicability is limited due to few studies on the topic and the lack of studies on real environments.

Trypanosoma cruzi adjuvants potentiate T cell-mediated immunity induced by a NY-ESO-1 based antitumor vaccine.

Immunological adjuvants that induce T cell-mediate immunity (TCMI) with the least side effects are needed for the development of human vaccines. Glycoinositolphospholipids (GIPL) and CpGs oligodeoxynucleotides (CpG ODNs) derived from the protozoa parasite Trypanosoma cruzi induce potent pro-inflammatory reaction through activation of Toll-Like Receptor (TLR)4 and TLR9, respectively. Here, using mouse models, we tested the T. cruzi derived TLR agonists as immunological adjuvants in an antitumor vaccine. For comparison, we used well-established TLR agonists, such as the bacterial derived monophosphoryl lipid A (MPL), lipopeptide (Pam3Cys), and CpG ODN. All tested TLR agonists were comparable to induce antibody responses, whereas significant differences were noticed in their ability to elicit CD4(+) T and CD8(+) T cell responses. In particular, both GIPLs (GTH, and GY) and CpG ODNs (B344, B297 and B128) derived from T. cruzi elicited interferon-gamma (IFN-γ) production by CD4(+) T cells. On the other hand, the parasite derived CpG ODNs, but not GIPLs, elicited a potent IFN-γ response by CD8(+) T lymphocytes. The side effects were also evaluated by local pain (hypernociception). The intensity of hypernociception induced by vaccination was alleviated by administration of an analgesic drug without affecting protective immunity. Finally, the level of protective immunity against the NY-ESO-1 expressing melanoma was associated with the magnitude of both CD4(+) T and CD8(+) T cell responses elicited by a specific immunological adjuvant.

Investigação da atividade Farmacológica de espécies de Piper que ocorrem no Cerrado

As espécies de Piper há muitos anos vem sendo estudadas por suas utilidades descobertas pelos nativos das regiões onde se encontra, sendo que pesquisas sobre essas espécies estão se intensificando pela necessidade de encontrar novos princípios ativos para o controle e tratamento de diversas patologias. Neste sentido, o presente trabalho objetivou avaliar a atividade analgésica, anti-inflamatória e de prospecção fitoquímica dos extratos brutos etanólicos de folhas de espécies de Piper. Os extratos foram preparados pelo método de maceração estática em etanol, filtrados e secos por rotaevaporação, obtendo-se os extratos brutos etanólicos de folhas de Piper arboreum Aubl. var. arboreum (EBEF1), Piper hemmendorffii C. DC (EBEF2) e Piper hispidum Sw (EBEF3). Os estudos farmacológicos demonstraram que o EBEF1 apresentou redução da resposta hipernociceptiva evidenciada em dois modelos, no teste de formalina e no teste de pressão crescente na pata, porém neste último, tal redução foi evidenciada somente quando foi administrada uma dose de reforço do extrato. Para avaliar a atividade anti-inflamatória foi utilizado o método da mieloperoxidase. Os resultados demonstram a efetividade do EBEF1 em reduzir a migração neutrofílica para o tecido plantar. Já a análise fitoquímica, que nos dá uma relação qualitativa de compostos como fenóis, taninos, antocianidinas, antocianinas, flavonóides, leucociantocianicinas, catequinas, flavononas, xantonas e outros. No EBF1, observou-se o aparecimento da cor amarela indicando presença de flavononas, flavonóis e xantonas nas três espécies devido a intensificação da cor pardo-amarelado, indicando a presença de catequinas, assim como, o EBEF1 apresentou maior potência em sua ação anti-inflamatória quando comparado a atividade analgésica.

Zika: abordagem clínica na atenção básica (Curso completo)

Livro elaborado com o caráter autoinstrucional para capacitação dos profissionais de saúde no que tange o conhecimento sobre a temática do Zika vírus para poderem utilizar dentro de suas possibilidades e disseminar os conhecimentos para a população, além de construir parcerias com todos os equipamentos sociais para atuarem no sentido de proteger a saúde de todos. O livro é um compendio do curso Zika: Abordagem clínica na atenção básica de iniciativa da UNA-SUS, Fiocruz Mato Grosso do Sul, Secretaria de Gestão do Trabalho e da Saúde (SGTES), Secretaria de Atenção à Saúde (SAS), Secretaria de Vigilância em Saúde (SVS) e Universidade Federal de Mato Grosso do Sul (UFMS). Está dividido em quatro unidades sendo a primeira voltada para os aspectos epidemiológicos, promoção à saúde e prevenção de infecção pelo vírus Zika no que preconiza a distribuição da doença no mundo e no país; características do vírus, tropismo do vírus; modo de transmissão, período de incubação, fisiopatologia, tipo de imunidade; população de risco; conceitos básicos sobre notificação e investigação epidemiológica; meios de proteção individual e coletiva; combate ao mosquito (uso de repelentes, telas, vestimentas, eliminação de criadouros, outros); estratégias de comunicação e mobilização comunitária; educação permanente da equipe. A unidade dois trata sobre o quadro clínico e abordagem a pessoas infectadas com vírus Zika, diagnósticos diferenciais (Dengue, Chikungunya, Zika); exames laboratoriais; apoio telessaúde; tratamento da população geral com suspeita ou confirmação de infecção pelo vírus Zika; planejamento reprodutivo (população-alvo: mulheres e homens adultos e adolescentes); diagnóstico precoce de gravidez e captação para acompanhamento pré-natal; busca ativa de gestantes faltantes ao pré-natal; protocolo de rotina para seguimento da gestante na atenção básica com suporte de equipe multiprofissional. A unidade três preconiza os cuidados com as gestantes com suspeita ou confirmação de infecção pelo vírus Zika e do recém-nascido com microcefalia, seguimento da gestante com exantema na gestação (sorologia para TORCHS - toxoplasmose, rubéola, citomegalovírus, herpes vírus e sífilis), sorologia para dengue e chikungunya, PCR realizado até o 5º dia (ZIKA); diagnóstico de microcefalia no recém-nascido (aferição de perímetro cefálico, investigação laboratorial e de imagem); apoio ao aleitamento materno nos casos de suspeita ou confirmação de infecção pelo vírus Zika; apoio psicossocial à puérpera e seus pares com recém-nascido com microcefalia; comunicação de notícias difíceis; avaliação neurológica da criança; triagem neonatal (teste do pezinho, orelhinha e olhinho); indicações para estimulação precoce; acompanhamento de recém-nascidos e crianças com microcefalia (puericultura, registros na caderneta de saúde da criança, vacinação, entre outros). Na unidade quatro é abordada a questão da vigilância da infecção pelo vírus Zika e suas complicações, a notificação compulsória; os instrumentos específicos de notificação de suspeita e confirmação; vigilância de complicações decorrentes da infecção pelo vírus Zika e a atuação do profissional sentinela na identificação dessas complicações.