Using gold nanobeacons as a theranostic technique to recognize, detect, and inhibit specific nucleic acids

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Nanomedicine-based strategies to target and modulate the tumor microenvironment

Funding Information: The authors acknowledge financial support from Fundação para a Ciência e a Tecnologia / Ministério da Ciência, Tecnologia, e Ensino Superior in the framework of PhD grant 2020.06638.BD (to D.P.S.), and from the European Research Council grant agreement No 848325 (J.C. for the ERC Starting Grant). Funding Information: The authors acknowledge financial support from Funda??o para a Ci?ncia e a Tecnologia/ Minist?rio da Ci?ncia, Tecnologia, e Ensino Superior in the framework of PhD grant 2020.06638.BD (to D.P.S.), and from the European Research Council grant agreement No 848325 (J.C. for the ERC Starting Grant). None declared by authors. Publisher Copyright: © 2021 Elsevier Inc.The interest in nanomedicine for cancer theranostics has grown significantly over the past few decades. However, these nanomedicines need to overcome several physiological barriers intrinsic to the tumor microenvironment (TME) before reaching their target. Intrinsic tumor genetic/phenotypic variations, along with intratumor heterogeneity, provide different cues to each cancer type, making each patient with cancer unique. This brings additional challenges in translating nanotechnology-based systems into clinically reliable therapies. To develop efficient therapeutic strategies, it is important to understand the dynamic interactions between TME players and the complex mechanisms involved, because they constitute invaluable targets to dismantle tumor progression. In this review, we discuss the latest nanotechnology-based strategies for cancer diagnosis and therapy as well as the potential targets for the design of future anticancer nanomedicines.publishersversionpublishe

Wetspun polycaprolactone fibers for tendon regeneration

[Excerpt] Introduction Tendon and ligament injuries have a major impact on joint mobility and musculoskeletal performance. Current treatments frequently fall short of expectations, necessitating the development of artificial fibrous scaffolds that closely resemble native tissue. Wet polymeric nanofibers, particularly those based on poly(-caprolactone) (PCL), have shown promise in terms of biocompatibility, biodegradability, and mechanical strength [1].[...]The authors gratefully acknowledge the funding by Ministério da Ciência, Tecnologia e Ensino Superior, FCT, Portugal, under grants PTDC/SAU-BEB/71459/2006 and SFRH/BD/41841/2007

Machine learning for next-generation nanotechnology in healthcare

Funding: The authors acknowledge financial support from FCT Portugal in the framework of PhD grant 2020.06638.BD (to D.P.S.), and the European Research Council grant agreement 848325 (J. Conde for the ERC Starting Grant). T.R. is an Investigador Auxiliar supported by FCT Portugal (CEECIND/ 00684/2018).Nanotechnology for healthcare is coming of age, but automating the design of composite materials poses unique challenges. Although machine learning is supporting groundbreaking discoveries in materials science, new initiatives leveraging learned patterns are required to fully realize the promise of nanodelivery systems and accelerate development pipelines.publishersversionpublishe

Unsupervised algorithms to identify potential under-coding of secondary diagnoses in hospitalisations databases in Portugal

Quantifying and dealing with lack of consistency in administrative databases (namely, under-coding) requires tracking patients longitudinally without compromising anonymity, which is often a challenging task. This study aimed to (i) assess and compare different hierarchical clustering methods on the identification of individual patients in an administrative database that does not easily allow tracking of episodes from the same patient; (ii) quantify the frequency of potential under-coding; and (iii) identify factors associated with such phenomena. We analysed the Portuguese National Hospital Morbidity Dataset, an administrative database registering all hospitalisations occurring in Mainland Portugal between 2011–2015. We applied different approaches of hierarchical clustering methods (either isolated or combined with partitional clustering methods), to identify potential individual patients based on demographic variables and comorbidities. Diagnoses codes were grouped into the Charlson an Elixhauser comorbidity defined groups. The algorithm displaying the best performance was used to quantify potential under-coding. A generalised mixed model (GML) of binomial regression was applied to assess factors associated with such potential under-coding. We observed that the hierarchical cluster analysis (HCA) + k-means clustering method with comorbidities grouped according to the Charlson defined groups was the algorithm displaying the best performance (with a Rand Index of 0.99997). We identified potential under-coding in all Charlson comorbidity groups, ranging from 3.5% (overall diabetes) to 27.7% (asthma). Overall, being male, having medical admission, dying during hospitalisation or being admitted at more specific and complex hospitals were associated with increased odds of potential under-coding. We assessed several approaches to identify individual patients in an administrative database and, subsequently, by applying HCA + k-means algorithm, we tracked coding inconsistency and potentially improved data quality. We reported consistent potential under-coding in all defined groups of comorbidities and potential factors associated with such lack of completeness. Our proposed methodological framework could both enhance data quality and act as a reference for other studies relying on databases with similar problems.info:eu-repo/semantics/publishedVersio

Circulating low density neutrophils of breast cancer patients are associated with their worse prognosis due to the impairment of T cell responses

Funding: This work was supported by Liga Portuguesa Contra o Cancro; Fundação para a Ciência e Tecnologia (PD/BD/114023/2015, SFRH/BD/148422/2019 and 2021.08031.BD); and iNOVA4Health (UIDB/04462/2020 and DAI/2019/46).Neutrophils are prominent immune components of tumors, having either anti-tumor (N1) or pro-tumor activity (N2). Circulating neutrophils, divided into high density neutrophils (HDN) and low density neutrophils (LDN), functionally mirror those N1 and N2 cells, respectively. LDN are rare in non-pathological conditions, but frequent in cancer, exhibiting a pro-tumor phenotype. These findings have been mainly demonstrated in animal models, thus proper validation in humans is still imperative. Here, we observed that LDN were increased in the blood of breast cancer (BC) patients, particularly with metastatic disease. Within the population of non-metastatic patients, LDN were more prevalent in patients with poor response to neoadjuvant chemotherapy than patients with a good response. The higher incidence of LDN in BC patients with severe disease or resistance to treatment can be explained by their pro-tumor/immunosuppressive characteristics. Moreover, the percentage of LDN in BC patients' blood was negatively correlated with activated cytotoxic T lymphocytes and positively correlated with immunosuppressive regulatory T cells. The ability of LDN to spoil anti-tumor immune responses was further demonstrated ex vivo. Hence, this study reveals the potential of LDN as a biomarker of BC response to treatment and opens new avenues for developing new immunotherapies.publishersversionpublishe

Conversion of Cn-unsaturated into Cn-2-saturated LCFA can occur uncoupled from methanogenesis in anaerobic bioreactors

Fat, oils, and grease present in complex wastewater can be readily converted to methane, but the energy potential of these compounds is not always recyclable, due to incomplete degradation of long chain fatty acids (LCFA) released during lipids hydrolysis. Oleate (C18:1) is generally the dominant LCFA in lipid-containing wastewater, and its conversion in anaerobic bioreactors results in palmitate (C16:0) accumulation. The reason why oleate is continuously converted to palmitate without further degradation via β-oxidation is still unknown. In this work, the influence of methanogenic activity in the initial conversion steps of unsaturated LCFA was studied in 10 bioreactors continuously operated with saturated or unsaturated C16- and C18-LCFA, in the presence or absence of the methanogenic inhibitor bromoethanesulfonate (BrES). Saturated Cn-2-LCFA accumulated both in the presence and absence of BrES during the degradation of unsaturated Cn-LCFA, and represented more than 50\% of total LCFA. In the presence of BrES further conversion of saturated intermediates did not proceed, not even when prolonged batch incubation was applied. As the initial steps of unsaturated LCFA degradation proceed uncoupled from methanogenesis, accumulation of saturated LCFA can be expected. Analysis of the active microbial communities suggests a role for facultative anaerobic bacteria in the initial steps of unsaturated LCFA biodegradation. Understanding this role is now imperative to optimize methane production from LCFA.European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement No 323009, and the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit and COMPETE 2020 (POCI-01-0145-FEDER-006684), and Project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462). We also thank the Gravitation grant (project 024.002.002) of the Netherlands Ministry of Education, Culture and Science and the Netherlands Science Foundation (NWO

Effect of sulfate and iron (III) on LCFA degradation by a methanogenic community

[Excerpt] Under anaerobic conditions long chain fatty acids (LCFA) can be converted to methane by syntrophic bacteria and methanogenic archaea. LCFA degradation was also reported in the presence of alternative hydrogenotrophic partners, such as sulfate-reducing bacteria (SRB) and iron-reducing bacteria (IRB), which generally show higher affinity for H2 than methanogens and are more resistant to LCFA [1,2,3]. Their presence in a microbial culture degrading LCFA can be advantageous to reduce LCFA toxicity towards methanogens, although high concentrations of external electron acceptor (EEA) can lead to outcompetition of methanogens and cease methane production. In this work, we tested the effect of adding sub-stoichiometric concentrations of sulfate and iron(III) to methanogenic communities degrading LCFA. (...

p53 Function Re-Establishment and Apoptosis Induction in Cervical Cancer Cells

Funding Information: Funding: This work was supported by the Foundation for Science and Technology (FCT), through funds from the State Budget, and by the European Regional Development Fund through the “Pro-grama Operacional Regional do Centro (Centro 2020)—Sistema de Apoio à Investigação Científica e Tecnológica—Programas Integrados de IC&DT” (Project Centro-01-0145-FEDER-000019—C4—Centro de Competências em Cloud Computing) and the project ref: UIDB/00709/2020. This work was also supported by national funds from FCT—Fundação para a Ciência e a Tecnologia, I.P., in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences—UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy—i4HB. D. Gomes also acknowledges the doctoral fellowship from FCT (ref: 2020.06792.BD). This work was also supported by the Ramalingaswami Fellowship (BT/RLF/Re-entry/64/2017), Department of Biotechnology, Govt. of India (V.K.). Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.Cervical cancer is the fourth leading cause of death in women worldwide, with 99% of cases associated with a human papillomavirus (HPV) infection. Given that HPV prophylactic vaccines do not exert a therapeutic effect in individuals previously infected, have low coverage of all HPV types, and have poor accessibility in developing countries, it is unlikely that HPV-associated cancers will be eradicated in the coming years. Therefore, there is an emerging need for the development of anti-HPV drugs. Considering HPV E6’s oncogenic role, this protein has been proposed as a relevant target for cancer treatment. In the present work, we employed in silico tools to discover potential E6 inhibitors, as well as biochemical and cellular assays to understand the action of selected compounds in HPV-positive cells (Caski and HeLa) vs. HPV-negative (C33A) and non-carcinogenic (NHEK) cell lines. In fact, by molecular docking and molecular dynamics simulations, we found three phenolic compounds able to dock in the E6AP binding pocket of the E6 protein. In particular, lucidin and taxifolin were able to inhibit E6-mediated p53 degradation, selectively reduce the viability, and induce apoptosis in HPV-positive cells. Altogether, our data can be relevant for discovering promising leads for the development of specific anti-HPV drugs.publishersversionpublishe

Seaweed Secondary Metabolites with Beneficial Health Effects : An Overview of Successes in In Vivo Studies and Clinical Trials

Macroalgae are increasingly viewed as a source of secondary metabolites with great potential for the development of new drugs. In this development, in vitro studies are only the first step in a long process, while in vivo studies and clinical trials are the most revealing stages of the true potential and limitations that a given metabolite may have as a new drug. This literature review aims to give a critical overview of the secondary metabolites that reveal the most interesting results in these two steps. Phlorotannins show great pharmaceutical potential in in vivo models and, among the several examples, the anti-dyslipidemia activity of dieckol must be highlighted because it was more effective than lovastatin in an in vivo model. The IRLIIVLMPILMA tridecapeptide that exhibits an in vivo level of activity similar to the hypotensive clinical drug captopril should still be stressed, as well as griffithsin which showed such stunning results over a variety of animal models and which will probably move onto clinical trials soon. Regarding clinical trials, studies with pure algal metabolites are scarce, limited to those carried out with kahalalide F and fucoxanthin. The majority of clinical trials currently aim to ascertain the effect of algae consumption, as extracts or fractions, on obesity and diabetes.This research was funded by project MACBIOBLUE (MAC/1.1b/086), program Interreg MAC 2014–2020 co-financed by DRCT (Azores Regional Government), supporting G.P. Rosa’s grant, as well as by FCT—Fundação para a Ciência e a Tecnologia, the European Union, QREN, FEDER, and COMPETE, through funding the cE3c center (FCT UID/BIA/00329/2013, 2015–2018 and UID/BIA/00329/2019) and the QOPNA research unit (FCT UID/QUI/00062/2019)info:eu-repo/semantics/publishedVersio