Luteolin, quercetin and ursolic acid are potent inhibitors of proliferation and inducers of apoptosis in both KRAS and BRAF mutated human colorectal cancer cells

KRAS and BRAF mutations are frequent in colorectal carcinoma (CRC) and have the potential to activate proliferation and survival through MAPK/ERK and/or PI3K signalling pathways. Because diet is one of the most important determinants of CRC incidence and progression, we studied the effects of the dietary phytochemicals quercetin (Q), luteolin (L) and ursolic acid (UA) on cell proliferation and apoptosis in two human CRC derived cell lines, HCT15 and CO115, harboring KRAS and BRAF activating mutations, respectively. In KRAS mutated HCT15 cells, Q and L significantly decreased ERK phosphorylation, whereas in BRAF mutated CO115 cells the three compounds decreased Akt phosphorylation but had no effect on phospho-ERK. Our findings show that these natural compounds have antiproliferative and proapoptotic effects and simultaneously seem to act on KRAS and PI3K but not on BRAF. These results shed light on the molecular mechanisms of action of Q, L and UA and emphasize the potential of dietary choices for the control of CRC progression.This work was supported by the Foundation for Science and Technology, Portugal, by the research Grant POCI/AGR/62040/2004. CPRX and CFL were supported by the Foundation for Science and Technology, Portugal, through the Grants SFRH/BD/ 27524/2006 and SFRH/BPD/26316/2006, respectively

Integrated feature selection and classification algorithm in the prediction of work-related accidents in the retail sector: a comparative study

Assessing the different factors that contribute to accidents in the workplace is essential to ensure the safety and well-being of employees. Given the importance of risk identification in hazard prediction, this work proposes a comparative study between different feature selection techniques (χ2 test and Forward Feature Selection) combined with learning algorithms (Support Vector Machine, Random Forest, and Naive Bayes), both applied to a database of a leading company in the retail sector, in Portugal. The goal is to conclude which factors of each database have the most significant impact on the occurrence of accidents. Initial databases include accident records, ergonomic workplace analysis, hazard intervention and risk assessment, climate databases, and holiday records. Each method was evaluated based on its accuracy in the forecast of the occurrence of the accident. The results showed that the Forward Feature Selection-Random Forest pair performed better among the assessed combinations, considering the case study database. In addition, data from accident records and ergonomic workplace analysis have the largest number of features with the most significant predictive impact on accident prediction. Future studies will be carried out to evaluate factors from other databases that may have meaningful information for predicting accidents.The authors are grateful to the Foundation for Science and Technology (FCT, Portugal) for financial support through national funds FCT/MCTES (PIDDAC) to CeDRI (UIDB/05757/2020 and UIDP/05757/2020) and SusTEC (LA/P/0007/2021). This work has been supported by NORTE-01-0247-FEDER-072598 iSafety: Intelligent system for occupational safety and well-being in the retail sector. Inˆes Sena was supported by FCT PhD grant UI/BD/153348/2022.info:eu-repo/semantics/publishedVersio

Development of bacterial cellulose wound dressings with controlled delivery of vitamin D3

Book of Abstracts of CEB Annual Meeting 2017[Excerpt] Wounds, in particular traumatic (e.g. burns) and chronic ones, are a major cause of morbidity and impaired life quality. They often result in long hospitalization stays, taking up substantial health resources in developed countries. This proposal aims at developing a safe, easy-to-use and nonexpensive approach to efficiently address this problem, by attaining faster and proper wound healing. Recent studies showed that an antimicrobial peptide (AMP), LLKKK18, released from conjugates with dextrin embedded in a Carbopol hydrogel significantly improved burn wound healing. In addition to antimicrobial activity, this peptide stimulates vascularization, thus supporting a faster healing and tissue regeneration[1]. As such, one can hypothesize that a hydrogel comprising drugs that stimulate the expression of LL37 will improve wound healing while keeping the wound area infection-free. This work comprised the approach towards the development of a novel bacterial nanocellulose (BNC) dressing. BNC, already used clinically for the treatment of burn wounds due to the unique properties like high water holding capacity, high crystallinity, ultrafine fiber network, high resistance, high moldability and biocompatibility[2]. In this work BNC will be used as drug carriers for the controlled release of drugs, namely of vitamin D3, an inducer of an endogenous expression of AMP LL37, known for accelerating the wound healing process, and as a protective barrier against exogenous agents (dust, microorganism) that can impair wound healing. [...]info:eu-repo/semantics/publishedVersio

Partitioning and purification of polygalacturonases produced by Aspergillus niger URM 5162 using PEG-phosphate in an aqueous two-phase system

Pectinases, or pectinolytic enzymes, are naturally produced by plants, filamentous fungi, bacteria and yeasts. The pectinases are of great importance to clarify and reduce viscosity in fruit juices, improving and increasing tbe filtration efficiency. When used in the crushing of grapes or wine must improve juice extraction, reduce the time to clarify and enhance tbe content ofterpenes in wine. The filamentous fungi most frequently used fur industrial purposes because as much as 90% ofthe enzyme can be excreted into the culture medium. The partitioning and purification of polygalacturonases (PG) produced by Aspergillus niger URM 5162 were investigated in aqueous two-phase systems (ATPS), furmed by polyetbylene glycol and phosphate salts (PE(ijlhosphate). To evaluate the effect oftbe 4 independent variables- molar mass ofpolyetbylene glycol (PEG) (400-8000 g1nol MPEG), PEG concentration (12.5-17.5%, w/w- CPEG), phosphate concentration (15-25%, ...W, CPHOS) and pH (6.0, 8.0) - on the 3 response variables: partition coefficient (K), activity yield (Y) and purification fàctor (PF), a fuctorial design (24) was used. The endo-polygalacturonases (endo-PG) were prefurentially partitioned in tbe top phase. For endo-PG, the highest values for the response variables K, Y and PF of 1.23, 74.04% and 8.18, respectively, were obtained for a CPEG of 12.5% (...W), MPEG of8000 g1nol, and CPHOS of25% (w/w) at pH 6.0. Also, exo-polygalacturonases (exo-PG) were preferentially partitioned in the top phase. ln tbis case, the highest values ofK (2.40), Y (33.33%), and PF (1.98) were obtained with a MPEG of 8000 g1nol, CPEG of 12.5% (...W), and CPHOS of25% (...W) at pH 6.0. ln both cases, MPEG had a positive influence on K, Y and PF. The conditions ofMPEG 8000 g1nol, CPEG of 12.5% (...W), and CPHOS of25% (...W) at pH 6.0 were considered the most suitable for tbe purification of PG produced by A. niger URM 5162. Furtbermore, MPEG and CPHOS were the most important independent variables. The PEG/phosphate system is a useful cost-effective altemative for PG purification

Assessing, quantifying and valuing the ecosystem services of coastal lagoons

The natural conservation of coastal lagoons is important not only for their ecological importance, but also because of the valuable ecosystem services they provide for human welfare and wellbeing. Coastal lagoons are shallow semi-enclosed systems that support important habitats such as wetlands, mangroves, salt-marshes and seagrass meadows, as well as a rich biodiversity. Coastal lagoons are also complex social-ecological systems with ecosystem services that provide livelihoods, wellbeing and welfare to humans. This study assessed, quantified and valued the ecosystem services of 32 coastal lagoons. The main findings of the study are: (i) the definitions of ecosystem services are still not generally accepted; (ii) the quantification of ecosystem services is made in many different ways, using different units; (iii) the evaluation in monetary terms of some ecosystem service is problematic, often relying on non-monetary evaluation methods; (iv) when ecosystem services are valued in monetary terms, this may represent very different human benefits; and, (v) different aspects of climate change, including increasing temperature, sea-level rise and changes in rainfall patterns threaten the valuable ecosystem services of coastal lagoons.DEVOTES project, from the European Union's Seventh Framework Programme for research, technological development and demonstration [308392]; networks and communities of Eurolag; Future Earth Coasts; SCOR; Fundacao para a Ciencia e a Tecnologia (FCT) Investigador Programme [IF/00331/2013]; Fundacao para a Ciencia e a Tecnologia [UID/MAR/04292/2013]; CESAM by FCT/MEC national funds (PIDDAC) [UID/AMB/50017/2013 - POCI-01-0145-FEDER-007638]; FEDER; European Commission, under the 7th Framework Programme through the collaborative research project LAGOONS [283157]; FCT [SFRH/BPD/107823/2015, SFRH/BPD/91494/2012

3D printing techniques and their applications to organ-on-a-chip platforms: a systematic review

Three-dimensional (3D) in vitro models, such as organ-on-a-chip platforms, are an emerging and effective technology that allows the replication of the function of tissues and organs, bridging the gap amid the conventional models based on planar cell cultures or animals and the complex human system. Hence, they have been increasingly used for biomedical research, such as drug discovery and personalized healthcare. A promising strategy for their fabrication is 3D printing, a layer-by-layer fabrication process that allows the construction of complex 3D structures. In contrast, 3D bioprinting, an evolving biofabrication method, focuses on the accurate deposition of hydrogel bioinks loaded with cells to construct tissue-engineered structures. The purpose of the present work is to conduct a systematic review (SR) of the published literature, according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, providing a source of information on the evolution of organ-on-a-chip platforms obtained resorting to 3D printing and bioprinting techniques. In the literature search, PubMed, Scopus, and ScienceDirect databases were used, and two authors independently performed the search, study selection, and data extraction. The goal of this SR is to highlight the importance and advantages of using 3D printing techniques in obtaining organ-on-a-chip platforms, and also to identify potential gaps and future perspectives in this research field. Additionally, challenges in integrating sensors in organs-on-chip platforms are briefly investigated and discussed.The authors are grateful for the funding of FCT through the projects NORTE-01-0145- FEDER-029394, NORTE-01-0145-FEDER-030171 funded by COMPETE2020, NORTE2020, PORTUGAL2020, and FEDER. This work was also supported by Fundação para a Ciência e a Tecnologia (FCT) under the strategic grants UIDB/04077/2020, UIDB/00319/2020, UIDB/04436/2020 and UIDB/00532/2020. This work was also funded by AMED-CREST Grant Number JP20gm1310001h0002.Violeta Carvalho acknowledges the PhD scholarship UI/BD/151028/2021 attributed by FCT. Inês Gonçalves acknowledges the PhD scholarship BD/08646/2020 attributed by FCT

Active regulatory T-cells contribute to broadened T-cell repertoire diversity in ivIg-treated SLE patients

Octapharma

Characterization of Lifestyle inSpinocerebellar Ataxia Type 3 andAssociation with Disease Severity

Background: Lifestyle could influence the course of hereditary ataxias, but representative data are missing. Objective: The objective of this study was to characterize lifestyle in spinocerebellar ataxia type 3 (SCA3) and investigate possible associations with disease parameters. Methods: In a prospective cohort study, data on smoking, alcohol consumption, physical activity, physiotherapy, and body mass index (BMI) were collected from 243 patients with SCA3 and 119 controls and tested for associations with age of onset, disease severity, and progression. Results: Compared with controls, patients with SCA3 were less active and consumed less alcohol. Less physical activity and alcohol abstinence were associated with more severe disease, but not with progression rates or age of onset. Smoking, BMI, or physiotherapy did not correlate with disease parameters. Conclusion: Differences in lifestyle factors of patients with SCA3 and controls as well as associations of lifestyle factors with disease severity are likely driven by the influence of symptoms on behavior. No association between lifestyle and disease progression was detected. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder SocietyFunding agencies: This publication is an outcome of the European Spinocerebellar ataxia type 3/Machado-Joseph disease initiative (ESMI), an EU Joint Programme–Neurodegenerative Disease Research (JPND) project (see www.jpnd.eu). The project is supported through the following funding organizations under the aegis of JPND: Germany, Federal Ministry of Education and Research (funding codes 01ED1602A/B); The Netherlands, The Netherlands Organisation for Health Research and Development; Portugal, Foundation for Science and Technology (FCT); United Kingdom, Medical Research Council. This project has received funding from the European Union’s Horizon 2020 research and innovation program under Grant 643417. At the US sites, this work was in part supported by the National Ataxia Foundation and the National Institute of Neurological Disorders and Stroke Grant R01 NS080816. P.G. is supported by the National Institute for Health Research University College London Hospitals (UCLH) Biomedical Research Centre. P.G. receives also support from the North Thames Clinical Research Network (CRN). P.G. and H.G.M. work at University College London Hospitals/University College London, which receives a proportion of funding from the Department of Health’s National Institute for Health Research Biomedical Research Centres funding scheme. P.G. received funding from CureSCA3 in support of H.G.M.’s work. This work was moreover supported, in part, by the Deutsche Forschungsgemeinschaft (German Research Foundation) No. 441409627, as part of the Progression chart of Spastic ataxias (PROSPAX) consortium under the frame of the European Joint Programme on Rare Diseases (EJP RD), under the EJP RD COFUND-EJP N 825575 (to M.S., B.v.W,) and Grant 779257 “Solve-RD” from the Horizon 2020 research and innovation program to M.S

Lower Richness of Small Wild Mammal Species and Chagas Disease Risk

A new epidemiological scenario involving the oral transmission of Chagas disease, mainly in the Amazon basin, requires innovative control measures. Geospatial analyses of the Trypanosoma cruzi transmission cycle in the wild mammals have been scarce. We applied interpolation and map algebra methods to evaluate mammalian fauna variables related to small wild mammals and the T. cruzi infection pattern in dogs to identify hotspot areas of transmission. We also evaluated the use of dogs as sentinels of epidemiological risk of Chagas disease. Dogs (n = 649) were examined by two parasitological and three distinct serological assays. kDNA amplification was performed in patent infections, although the infection was mainly sub-patent in dogs. The distribution of T. cruzi infection in dogs was not homogeneous, ranging from 11–89% in different localities. The interpolation method and map algebra were employed to test the associations between the lower richness in mammal species and the risk of exposure of dogs to T. cruzi infection. Geospatial analysis indicated that the reduction of the mammal fauna (richness and abundance) was associated with higher parasitemia in small wild mammals and higher exposure of dogs to infection. A Generalized Linear Model (GLM) demonstrated that species richness and positive hemocultures in wild mammals were associated with T. cruzi infection in dogs. Domestic canine infection rates differed significantly between areas with and without Chagas disease outbreaks (Chi-squared test). Geospatial analysis by interpolation and map algebra methods proved to be a powerful tool in the evaluation of areas of T. cruzi transmission. Dog infection was shown to not only be an efficient indicator of reduction of wild mammalian fauna richness but to also act as a signal for the presence of small wild mammals with high parasitemia. The lower richness of small mammal species is discussed as a risk factor for the re-emergence of Chagas disease