Significance of glycolytic metabolism-related protein expression in colorectal cancer, lymph node and hepatic metastasis

Background: Colorectal cancer (CRC) is one of the most common malignancies and a leading cause of cancer death worldwide. Most cancer cells display high rates of glycolysis with production of lactic acid, which is then exported to the microenvironment by monocarboxylate transporters (MCTs). The main aim of this study was to evaluate the significance of MCT expression in a comprehensive series of primary CRC cases, lymph node and hepatic metastasis. Methods: Expressions of MCT1, MCT4, CD147 and GLUT1 were studied in human samples of CRC, lymph node and hepatic metastasis, by immunohistochemistry. Results: All proteins were overexpressed in primary CRC, lymph node and hepatic metastasis, when compared with non-neoplastic tissue, with exception of MCT1 in lymph node and hepatic metastasis. MCT1 and MCT4 expressions were associated with CD147 and GLUT1 in primary CRC. These markers were associated with clinical pathological features, reflecting the putative role of these metabolism-related proteins in the CRC setting. Conclusion: These findings provide additional evidence for the pivotal role of MCTs in CRC maintenance and progression, and support the use of MCTs as biomarkers and potential therapeutic targets in primary and metastatic CRC.This work was supported by the Fundação para a Ciência e a Tecnologia (FCT) grant ref. PTDC/SAU-FCF/104347/2008, under the scope of ‘Programa Operacional Temático Factores de Competitividade’ (COMPETE) of ‘Quadro Comunitário de Apoio III’ and co-financed by the Fundo Europeu De Desenvolvimento Regional (FEDER). Ricardo Amorim was recipient of the fellowship SFRH/BD/98002/2013, from Fundação para a Ciência e a Tecnologia (FCT Portugal).info:eu-repo/semantics/publishedVersio

SARS-CoV-2 introductions and early dynamics of the epidemic in Portugal

Genomic surveillance of SARS-CoV-2 in Portugal was rapidly implemented by the National Institute of Health in the early stages of the COVID-19 epidemic, in collaboration with more than 50 laboratories distributed nationwide. Methods By applying recent phylodynamic models that allow integration of individual-based travel history, we reconstructed and characterized the spatio-temporal dynamics of SARSCoV-2 introductions and early dissemination in Portugal. Results We detected at least 277 independent SARS-CoV-2 introductions, mostly from European countries (namely the United Kingdom, Spain, France, Italy, and Switzerland), which were consistent with the countries with the highest connectivity with Portugal. Although most introductions were estimated to have occurred during early March 2020, it is likely that SARS-CoV-2 was silently circulating in Portugal throughout February, before the first cases were confirmed. Conclusions Here we conclude that the earlier implementation of measures could have minimized the number of introductions and subsequent virus expansion in Portugal. This study lays the foundation for genomic epidemiology of SARS-CoV-2 in Portugal, and highlights the need for systematic and geographically-representative genomic surveillance.We gratefully acknowledge to Sara Hill and Nuno Faria (University of Oxford) and Joshua Quick and Nick Loman (University of Birmingham) for kindly providing us with the initial sets of Artic Network primers for NGS; Rafael Mamede (MRamirez team, IMM, Lisbon) for developing and sharing a bioinformatics script for sequence curation (https://github.com/rfm-targa/BioinfUtils); Philippe Lemey (KU Leuven) for providing guidance on the implementation of the phylodynamic models; Joshua L. Cherry (National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health) for providing guidance with the subsampling strategies; and all authors, originating and submitting laboratories who have contributed genome data on GISAID (https://www.gisaid.org/) on which part of this research is based. The opinions expressed in this article are those of the authors and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services, or the United States government. This study is co-funded by Fundação para a Ciência e Tecnologia and Agência de Investigação Clínica e Inovação Biomédica (234_596874175) on behalf of the Research 4 COVID-19 call. Some infrastructural resources used in this study come from the GenomePT project (POCI-01-0145-FEDER-022184), supported by COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation (POCI), Lisboa Portugal Regional Operational Programme (Lisboa2020), Algarve Portugal Regional Operational Programme (CRESC Algarve2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), and by Fundação para a Ciência e a Tecnologia (FCT).info:eu-repo/semantics/publishedVersio

Sensitivity of endorectal ecography in the staging of rectal chancre: correlation with pathological staging

Objectivo: Avaliar a sensibilidade da ecografia endorectal, em nossa experiência, no estadiamento do cancro do recto comparando com o resultado anatomopatológico. Material e métodos: Estudo retrospectivo, realizado entre Janeiro de 2005 e Agosto de 2009. Calculou-se a sensibilidade, a especificidade, o valor preditivo positivo e negativo para cada estadio T e N. Por meio da ela-boração de curvas ROC avaliou-se a precisão do estadiamento ecoendoscópico e por meio do teste de McNemar comparou-se com o resultado anatomopatológico. Resultados: Dos 112 doentes, 76 cumpriram os critérios de inclusão. Obtivemos uma eficácia de 75 a 97% para uT e de 75% para uN. Verificou-se sensibilidade, especificidade, valor preditivo positivo e negativo, respectivamente, de 63;98;92 e 89% para uT1; 71;76;54 e 88% para uT2; 67;81;73 e 76% para uT3; 100;97;60 e 100% para uT4; e 39;91;62 e 78% para uN. As curvas ROC indicaram que a ecografia endorectal é um bom teste para o estadiamento do T e razoável para o N. O teste de Mc-Nemar revelou que não há diferenças significativas entre o estadiamento ecoendoscópico e anatomopatológico (p>0,05). Conclusões: Conclui-se que a ecografia endorectal é uma importante ferramenta no estadiamento do cancro do recto, apresentando boa correlação com o resultado anatomopatológico.(undefined

Monocarboxylate transporters: new molecular targets for colorectal carcinoma

[Excerpt] Colorectal carcinoma (CRC) is the second leading cause of cancer-related death in industrialized countries1. 5-Fluorouracil (5-FU) is one of the most efficient chemotherapeutic agents in the treatment of CRC although resistance to 5-FU treatment has been reported2. CRC relies mostly on glycolysis to meet their energetic demands and, as a consequence, CRC cells produce large amounts of lactate that must be extruded to the tumour microenvironment by lactate transporters, namely monocarboxylate transporters (MCTs). (...

Atividade proteolítica em bactérias isoladas do solo do bioma Caatinga

As proteases compõem um grupo variado de enzimas catalíticas que desempenham importante papel nos processos fisiológicos e aplicação em processos industriais. É crescente o interesse por enzimas provenientes de microrganismos devido à sua diversidade, complexidade e seu elevado potencial biotecnológico. A Caatinga é um bioma exclusivamente  brasileiro, com ambientes ricos em espécies que apresentam adaptações únicas. Porém, a microbiota do solo da caatinga e seu potencial biotecnológico ainda são pouco explorados. O objetivo do presente trabalho foi quantificar e isolar bactérias produtoras de proteases a partir de amostras de solo da caatinga. Dentre os isolados bacterianos produtores de proteases extracelulares, dois se destacaram por apresentarem eficiência enzimática em diferentes condições de temperatura e pH. As bactérias isoladas do solo da caatinga mostraram-se resistentes às condições extremas do bioma e apresentaram ótima atividade enzimática nas amplas variações de temperatura e pH testadas, indicando potencial para uso biotecnológico

Efficacy of light-emitting diode (LED) photobiomodulation in pain management, facial edema, trismus, and quality of life after extraction of retained lower third molars : A randomized, double-blind, placebo-controlled clinical trial

Background: In dentistry, one of the most common surgical procedures is the removal of retained third molars. This surgery generates great morbidity to the participants for causing pain, edema, and trismus due to surgical trauma. The objective of the present study is to evaluate the efficacy of photobiomodulation with light emitting diode (LED) in the control of pain, facial edema, trismus, and quality of life resulting from the extraction of retained lower third molars. Methods:A randomized, double-blind, placebo-controlled clinical trial involving 38 adult participants, who meet the criteria of eligibility and agree to participate in the study. Before the surgeries are performed, the facial and mouth opening measures of all the participants will be taken. Immediately after the surgeries, participants will be randomized into 2 groups. In the LED group, participants will receive LED applications (intra oral with 660 nm, 12J and extraoral with 850 nm, 108J) in the immediate postoperative, first and second days after the surgical procedure. In the control group, the participants will be attended in the same way as in the LED group, however, the person in charge of the application will simulate the irradiation. Pain (EVA and NRS-101), postoperative edema, trismus, temperature, dysphagia, and hematoma will be evaluated after 1, 2, 5, and 7 days. The oral health impact profile (OHIP-14 Questionnaire) and anxiety analysis (Beck anxiety inventory -BAI) questionnaires will be applied preoperatively and 7 days after treatment. The appropriate statistical tests will be applied for each specific analysis in a significance level of 5%. Discussion: Although the use of low-power laser in the postoperative has shown good results in the control of postoperative sequelae, this is the first study on the efficacy of the use of LED in this situation. Abbreviations: BAI = Beck anxiety inventory, LED = light emitting diode, NRS-101 = numerical rating scale 101, OHIP-14 = oral health impact profile, PBM = pohotobiomodulation, VAS = visual analog scale

Matrix Metalloproteinases on Severe COVID-19 Lung Disease Pathogenesis: Cooperative Actions of MMP-8/MMP-2 Axis on Immune Response through HLA-G Shedding and Oxidative Stress

Patients with COVID-19 predominantly have a respiratory tract infection and acute lung failure is the most severe complication. While the molecular basis of SARS-CoV-2 immunopathology is still unknown, it is well established that lung infection is associated with hyper-inflammation and tissue damage. Matrix metalloproteinases (MMPs) contribute to tissue destruction in many pathological situations, and the activity of MMPs in the lung leads to the release of bioactive mediators with inflammatory properties. We sought to characterize a scenario in which MMPs could influence the lung pathogenesis of COVID-19. Although we observed high diversity of MMPs in lung tissue from COVID-19 patients by proteomics, we specified the expression and enzyme activity of MMP-2 in tracheal-aspirate fluid (TAF) samples from intubated COVID-19 and non-COVID-19 patients. Moreover, the expression of MMP-8 was positively correlated with MMP-2 levels and possible shedding of the immunosuppression mediator sHLA-G and sTREM-1. Together, overexpression of the MMP-2/MMP-8 axis, in addition to neutrophil infiltration and products, such as reactive oxygen species (ROS), increased lipid peroxidation that could promote intensive destruction of lung tissue in severe COVID-19. Thus, the inhibition of MMPs can be a novel target and promising treatment strategy in severe COVID-19

Determinants of HIV late presentation among men who have sex with men in Portugal (2014–2019): who’s being left behind?

IntroductionHIV late presentation (LP) remains excessive in Europe. We aimed to analyze the factors associated with late presentation in the MSM population newly diagnosed with HIV in Portugal between 2014 and 2019.MethodsWe included 391 newly HIV-1 diagnosed Men who have Sex with Men (MSM), from the BESTHOPE project, in 17 countrywide Portuguese hospitals. The data included clinical and socio-behavioral questionnaires and the viral genomic sequence obtained in the drug resistance test before starting antiretrovirals (ARVs). HIV-1 subtypes and epidemiological surveillance mutations were determined using different bioinformatics tools. Logistic regression was used to estimate the association between predictor variables and late presentation (LP).ResultsThe median age was 31 years, 51% had a current income between 501–1,000 euros, 28% were migrants. 21% had never been tested for HIV before diagnosis, with 42.3% of MSM presenting LP. 60% were infected with subtype B strains. In the multivariate regression, increased age at diagnosis, higher income, lower frequency of screening, STI ever diagnosed and higher viral load were associated with LP.ConclusionOur study suggests that specific subgroups of the MSM population, such older MSM, with higher income and lower HIV testing frequency, are not being targeted by community and clinical screening services. Overall, targeted public health measures should be strengthened toward these subgroups, through strengthened primary care testing, expanded access to PrEP, information and promotion of HIV self-testing and more inclusive and accessible health services