Biological activities and physicochemical characterization of alkaline lignins obtained from branches and leaves of Buchenavia viridiflora with potential pharmaceutical and biomedical applications

Funding Information: The study was funded by Foundation for the State of Pernambuco (Process - FACE-04.03/19 ), AP Researcher Research Grant - FACEPE (Process BFP-0038-0 ) and National Council for Scientific and Technological Development grant - CNPq (Process 306865/2020-3 ). This research was also funded by the Foundation for Science and Technology (FCT) through the GHTM ( UID/04413/2020 ). Thanks to MR4, who provided us with the Plasmodium falciparum strains that we used in the assays. We also thank the Laboratory of Magnetic Resonance of the Institute of Chemistry and Biotechnology (Federal University of Alagoas- UFAL) for the analysis of NMR. In addition to these, we would also like to thank Mil Madeiras Preciosas, a subsidiary of the Swiss group Precious Woods ( http://preciouswoods.com.br/ ) for providing samples of branches and leaves of Buchenavia viridiflora. Publisher Copyright: © 2022In this work, we investigated in vitro different biological activities of alkaline lignins extracted from the species Buchenavia viridiflora, a tree from the Amazon rainforest used as a wood product. The chemical composition results for the twig and leaves were, respectively (%): cellulose (30.88 and 24. 28), hemicellulose (21.62 and 23.03), lignin (29.93 and 25.46), extractives (13.06 and 20.52), and ash (4.51 and 6.72). The yield was higher for the lignin of the branches (67.9 %) when compared to the leaves (60.2 %). Lignins are of the GSH type, low molecular weight and thermally stable. They promoted moderate to low antioxidant activity, highlighting the lignin of the branches, which presented an IC50 of 884.56 μg/mL for the DPPH assay and an IC50 of 14.08 μg/mL for ABTS. In the cytotoxicity assays, they showed low toxicity against macrophage cells (IC50 28.47 and 22.58 μg/mL). In addition, they were not cytotoxic against splenocytes and erythrocytes at concentrations ranging from 100 to 6.25 μg/mL. These were able to promote splenocyte proliferation and induce the production of anti-inflammatory cytokines. And inhibit the growth of tumor cells with IC50 ranging from 12.63 to values >100 μg/mL and microbial at a concentration of 512 μg/mL. Finally, they showed antiparasitic activity by inhibiting the growth of chloroquine-sensitive and resistant Plasmodium falciparum strains. These findings reinforce that the lignins in this study are promising for potential pharmaceutical and biomedical applications.publishersversionpublishe

Critical role for CCR2 and HMGB1 in induction of experimental endotoxic shock

AbstractOur aim was to investigate CCR2 and HMGB1 involvement in a murine model of endotoxic shock. We used C57BL/6 CCR2 knockout (KO) mice and wild-type (WT) littermates to establish an optimal dose of LPS. CCR2 KO mice survived more frequently than WT mice after 80, 40 and 20mg/kg of LPS i.p. Inflammation and redox markers were high in WT mice than in CCR2 KO mice. HMGB1 expression was reduced in CCR2 KO mice in parallel to ERK 1/2 activation. Therefore, we used glycyrrhizic acid (50mg/kg), an HMGB1 inhibitor in WT mice injected with LPS, and mortality was fully abolished. Thus, drugs targeting CCR2 and HMGB1 could represent future resources for sepsis treatment

Morfofisiologia e componentes de produção de mini-melancia sob níveis de reposição hídrica e adubação nitrogenada

No semiárido do Nordeste do Brasil, a irregularidade de chuvas e elevada evapotranspiração proporcionam déficit hídrico nas plantas na maior parte dos meses do ano, destacando-se como fator limitante para produção de olerícolas. Assim, a identificação de estratégias capazes de amenizar os efeitos do déficit hídrico nas plantas é essencial para produção sob condições irrigadas. Nesse contexto, objetivou-se avaliar o efeito da adubação nitrogenada na morfofisiologia e nos componentes de produção de mini-melancia 'Sugar Baby'. O experimento foi conduzido na Fazenda Experimental ‘Rolando Rivas Castellón’, São Domingos, Paraíba, sob condições de casa de vegetação, utilizando-se o delineamento de blocos casualizados em esquema fatorial 4 × 4, correspondendo a quatro níveis de reposição hídrica (50, 75, 100 - controle e 125% da evapotranspiração real da cultura - ETr) e quatro doses de nitrogênio - DN (50, 75, 100 e 125% da dose recomendada), com 3 repetições, totalizando 48 plantas. Foram avaliadas as variáveis de trocas gasosas, os teores de pigmentos fotossintéticos, o conteúdo relativo de água e o extravasamento de eletrólitos, o crescimento e a produção de fitomassa, os componentes de produção e a qualidade pós-colheita dos frutos de mini-melancia. A irrigação deficitária com 50% da evapotranspiração real inibiu as trocas gasosas, a síntese de pigmentos fotossintéticos, o crescimento, e a qualidade dos frutos da mini-melancieira ‘Sugar Baby’, independente da dose de nitrogênio. A lâmina de água com 125% da evapotranspiração real combinada à adubação de 100% da recomendação de nitrogênio proporcionou maiores teores de clorofilas totais, número de folhas e de fitomassa seca das raízes, caule, total, parte aérea e pH dos frutos de mini-melancieira ‘Sugar Baby’

249 TP53 mutation has high prevalence and is correlated with larger and poorly differentiated HCC in Brazilian patients

<p>Abstract</p> <p>Background</p> <p>Ser-249 TP53 mutation (249^Ser) is a molecular evidence for aflatoxin-related carcinogenesis in Hepatocellular Carcinoma (HCC) and it is frequent in some African and Asian regions, but it is unusual in Western countries. HBV has been claimed to add a synergic effect on genesis of this particular mutation with aflatoxin. The aim of this study was to investigate the frequency of 249^Sermutation in HCC from patients in Brazil.</p> <p>Methods</p> <p>We studied 74 HCC formalin fixed paraffin blocks samples of patients whom underwent surgical resection in Brazil. 249^Sermutation was analyzed by RFLP and DNA sequencing. HBV DNA presence was determined by Real-Time PCR.</p> <p>Results</p> <p>249^Sermutation was found in 21/74 (28%) samples while HBV DNA was detected in 13/74 (16%). 249^Sermutation was detected in 21/74 samples by RFLP assay, of which 14 were confirmed by 249^Sermutant-specific PCR, and 12 by nucleic acid sequencing. All HCC cases with p53-249ser mutation displayed also wild-type p53 sequences. Poorly differentiated HCC was more likely to have 249^Sermutation (OR = 2.415, 95% CI = 1.001 – 5.824, p = 0.05). The mean size of 249^SerHCC tumor was 9.4 cm versus 5.5 cm on wild type HCC (p = 0.012). HBV DNA detection was not related to 249^Sermutation.</p> <p>Conclusion</p> <p>Our results indicate that 249^Sermutation is a HCC important factor of carcinogenesis in Brazil and it is associated to large and poorly differentiated tumors.</p

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field