The extracellular small leucine-rich proteoglycan biglycan is a key player in gastric cancer aggressiveness

Biglycan (BGN gene), an extracellular proteoglycan, has been described to be associated with cancer aggressiveness. The purpose of this study was to clarify the clinical value of biglycan as a biomarker in multiple independent GC cohorts and determine the in vitro and in vivo role of biglycan in GC malignant features. We found that BGN is commonly over-expressed in all analyzed cohorts, being associated with disease relapse and poor prognosis in patients with advanced stages of disease. In vitro and in vivo experiments demonstrated that biglycan knock-out GC cells display major phenotypic changes with a lower cell survival, migration, and angiogenic potential when compared with biglycan expressing cells. Biglycan KO GC cells present increased levels of PARP1 and caspase-3 cleavage and a decreased expression of mesenchymal markers. Importantly, biglycan deficient GC cells that were supplemented with exogenous biglycan were able to restore biological features, such as survival, clonogenic and migratory capacities. Our in vitro and in vivo findings were validated in human GC samples, where BGN expression was associated with several oncogenic gene signatures that were associated with apoptosis, cell migration, invasion, and angiogenesis. This study provided new insights on biglycan role in GC that should be taken in consideration as a key cellular regulator with major impact in tumor progression and patients’ clinical outcome.This work was funded by FEDER funds through the Operational Programme for Competitiveness Factors-COMPETE (POCI-01-0145-FEDER-016585; POCI-01-0145-FEDER-029780; POCI-01-0145-FEDER-007274; POCI-01-0145-FEDER-029780) and National Funds through the Foundation for Science and Technology (FCT), under the projects: PTDC/BBB-EBI/0567/2014 (to C.A.R.), PTDC/MED-QUI/29780/2017 (to CG), and UID/BIM/04293 supported by Norte Portugal Regional Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). F.P. was funded by FCT cofinanced by Fundo Social Europeu-FSE with a grant with reference: SFRH/BPD/115730/2016

Evidence for entanglement at high temperatures in an engineered molecular magnet

The molecular compound [Fe$_{2}$($\mu_{2}$-oxo)(C$_{3}$H$_{4}$N$_{2}$)$_{6}$(C$_{2}$O$_{4}$)$_{2}$] was designed and synthesized for the first time and its structure was determined using single-crystal X-ray diffraction. The magnetic susceptibility of this compound was measured from 2 to 300 K. The analysis of the susceptibility data using protocols developed for other spin singlet ground-state systems indicates that the quantum entanglement would remain at temperatures up to 732 K, significantly above the highest entanglement temperature reported to date. The large gap between the ground state and the first-excited state (282 K) suggests that the spin system may be somewhat immune to decohering mechanisms. Our measurements strongly suggest that molecular magnets are promising candidate platforms for quantum information processing

Impact of Truncated O-glycans in Gastric-Cancer-Associated CD44v9 Detection

CD44 variant isoforms are often upregulated in cancer and associated with increased aggressive tumor phenotypes. The CD44v9 is one of the major protein splice variant isoforms expressed in human gastrointestinal cancer cells. Immunodetection of CD44 isoforms like CD44v9 in tumor tissue is almost exclusively performed by using specific monoclonal antibodies. However, the structural variability conferred by both the alternative splicing and CD44 protein glycosylation is disregarded. In the present work, we have evaluated the role of O-glycosylation using glycoengineered gastric cancer models in the detection of CD44v9 by monoclonal antibodies. We demonstrated, using different technical approaches, that the presence of immature O-glycan structures, such as Tn and STn, enhance CD44v9 protein detection. These findings can have significant implications in clinical applications mainly at the detection and targeting of this cancer-related CD44v9 isoform and highlight the utmost importance of considering glycan structures in cancer biomarker detection and in therapy targeting.This work was funded by FEDER funds through the Operational Programme for Competitiveness Factors-COMPETE, grant numbers POCI-01-0145-FEDER-016585; POCI-01-0145-FEDER-007274; OCI-01-0145-FEDER-031028; and national funds through the Foundation for Science and Technology (FCT), grant numbers PTDC/BBB-EBI/0567/2014 (to CAR), UID/BIM/04293/2013, and PTDC/MED-QUI/29780/2017; and the project NORTE-01-0145-FEDER-000029, supported by Norte Portugal Regional Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). F. Pinto received a fellowship from FCT (SFRH/BPD/115730/2016)

Influence of the external pressure on the quantum correlations of molecular magnets

The study of quantum correlations in solid state systems is a large avenue for research and their detection and manipulation are an actual challenge to overcome. In this context, we show by using first-principles calculations on the prototype material KNaCuSi$_{4}$O$_{10}$ that the degree of quantum correlations in this spin cluster system can be managed by external hydrostatic pressure. Our results open the doors for research in detection and manipulation of quantum correlations in magnetic systems with promising applications in quantum information science

COPD : a stepwise or a hit hard approach?

Open Access funded by Sociedade Portuguesa de Pneumologia Under a Creative Commons license. © 2016 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Current guidelines differ slightly on the recommendations for treatment of Chronic Obstructive Pulmonary Disease (COPD) patients, and although there are some undisputed recommendations, there is still debate regarding the management of COPD. One of the hindrances to deciding which therapeutic approach to choose is late diagnosis or misdiagnosis of COPD. After a proper diagnosis is achieved and severity assessed, the choice between a stepwise or "hit hard" approach has to be made. For GOLD A patients the stepwise approach is recommended, whilst for B, C and D patients this remains debatable. Moreover, in patients for whom inhaled corticosteroids (ICS) are recommended, a step-up or "hit hard" approach with triple therapy will depend on the patient's characteristics and, for patients who are being over-treated with ICS, ICS withdrawal should be performed, in order to optimize therapy and reduce excessive medications. This paper discusses and proposes stepwise, "hit hard", step-up and ICS withdrawal therapeutic approaches for COPD patients based on their GOLD group. We conclude that all approaches have benefits, and only a careful patient selection will determine which approach is better, and which patients will benefit the most from each approach.Funding for this paper was provided by Novartis Portugal. Funding was used to access all necessary scientific bibliography and cover meeting expenses. Novartis Portugal had no role in the collection, analysis and interpretation of data, in the writing of the paper and in the decision to submit the paper for publication.info:eu-repo/semantics/publishedVersio

Finite size analysis of a two-dimensional Ising model within a nonextensive approach

In this work we present a thorough analysis of the phase transitions that occur in a ferromagnetic 2D Ising model, with only nearest-neighbors interactions, in the framework of the Tsallis nonextensive statistics. We performed Monte Carlo simulations on square lattices with linear sizes L ranging from 32 up to 512. The statistical weight of the Metropolis algorithm was changed according to the nonextensive statistics. Discontinuities in the m(T) curve are observed for $q\leq 0.5$. However, we have verified only one peak on the energy histograms at the critical temperatures, indicating the occurrence of continuous phase transitions. For the $0.5<q\leq 1.0$ regime, we have found continuous phase transitions between the ordered and the disordered phases, and determined the critical exponents via finite-size scaling. We verified that the critical exponents $\alpha$, $\beta$ and $\gamma$ depend on the entropic index $q$ in the range $0.5<q\leq 1.0$ in the form $\alpha (q)=(10 q^{2}-33 q+23)/20$, $\beta (q)=(2 q-1)/8$ and $\gamma (q)=(q^{2}-q+7)/4$. On the other hand, the critical exponent $\nu$ does not depend on $q$. This suggests a violation of the scaling relations $2 \beta +\gamma =d \nu$ and $\alpha +2 \beta +\gamma =2$ and a nonuniversality of the critical exponents along the ferro-paramagnetic frontier.Comment: accepted for publication in Phys. Rev.

Subcritical carbon dioxide foaming of polycaprolactone for bone tissue regeneration

Accepted manuscriptThe preparation of three-dimensional polycaprolactone scaffolds using dense CO2 as foaming agent, without supercritical conditions, was evaluated in this study towards future applications in bone repair. Herein, 3D foams were obtained at 5.0 MPa and 45 °C. To induce bioactivity, β-tricalcium phosphate (β-TCP, 10 wt%) and dexamethasone (5 and 10 wt%) were dispersed in the scaffolds. Foams revealed a pore size range of 164–882 μm, 73–99% porosity and 79–99% interconnectivity, assessed by micro-computed tomography, and a Young modulus of 1.76–2.92 MPa. Dexamethasone did not impair morphology of the matrices in comparison with PCL+β-TCP, which presented a water uptake of nearly 100% after 14 days. A sustained release of dexamethasone was achieved over 35 days in physiologic solution. This study reports the feasibility of using dense CO2 to produce in one-step a porous matrix loaded with active agents opening new possibilities towards injectable systems for in situ foamingEuropean Union Seventh Framework Programme (FP7/2007-2013) under grant agreement number REGPOT-CT2012-316331-POLARIS. It was also funded by the project “Novel smart and biomimetic materials for innovative regenerative medicine approaches” (RL1-ABMR-NORTE-01-0124-FEDER-000016) co-financed by North Portugal Regional Operational Programme (ON.2 – O Novo Norte), under the National Strategic Reference Framework (NSRF), through the European Regional Development Fund (ERDF) and the project NORTE‐01‐0145‐FEDER‐000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement. The authors would like to acknowledge the funding of the project Associate Laboratory ICVS/3B’s, under grant agreement number POCI-01-0145-FEDER-007038 supported by FEDER, through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT)info:eu-repo/semantics/publishedVersio

Nanotechnology applied to drug delivery – formulation, development and characterization studies

Azelaic acid shows bacteriostatical activity against many microorganism species and is commonly used in the treatment of acne. However, some technical issues and a reduced patient compliance have been associated with its topical application forms. Thus, nanotechnology may represent an innovative strategy that might help to overcome these problems. The objective of this study was to develop and to characterize PLGA nanoparticles containing azelaic acid. Nanoparticles were produced by a modified spontaneous emulsification/solvent diffusion method and then included into a gel of Carbopol 940. Several parameters were characterized such as zeta potential, particle size and encapsulation efficiency. Particle mean size was 378.63 nm (with PI around 0.09) and zeta potential was -7.82 mV. The encapsulation efficiency of azelaic acid was 76 ± 3.81%. Consequently, these PLGA nanoparticles can be considered a useful tool for azelaic acid delivery

[Retroperitoneal laparoscopic nephrectomy in children younger than nine years-old: state of the art]

Introdução e Objectivos: Em Portugal, a experiência em retroperitoneoscopia pediátrica é escassa. Os autores apresentam a primeira série portuguesa de nefrectomias realizadas por esta via, em crianças com idade inferior a nove anos, e uma revisão da literatura sobre o tema. Material e Métodos: Análise retrospectiva dos processos das crianças submetidas a nefrectomia laparoscópica retroperitoneal (NLR), de Janeiro de 2009 e Dezembro de 2009, num Departamento de Cirurgia Pediátrica. A revisão da literatura foi realizada através de uma pesquisa na base de dados Medline. Resultados: Foram realizadas oito NLR. A média de idades dos doentes operados foi 4,5 anos (mínimo = 11 meses, máximo = 8,6 anos). As indicações cirúrgicas encontradas foram: quatro rins multiquísticos, três nefropatias de refluxo, uma nefropatia obstructiva. Quatro NLR foram realizadas à esquerda. O tempo cirúrgico médio foi 99 minutos (mínimo = 50 minutos, máximo 180 minutos), notando-se um encurtamento do mesmo à medida que aumenta a experiência da equipa. Não houve nenhuma conversão para lombotomia. A média de tempo de internamento foi 1,5 dias (mínimo = 1 dia, máximo = 2 dias). Não se registaram complicações intra-operatórias nem pós-operatórias. Conclusão: A NLR é exequível em crianças de idade inferior a nove anos e deve ser considerado tratamento de eleição na idade pediátrica

Effects of positive airway pressure therapy on cardiovascular and metabolic markers in males with obstructive sleep apnea

Introduction: Obstructive sleep apnea syndrome (OSAS) is associated with cardiovascular/ metabolic complications. Some analytical parameters (homocysteine, glycemic and lipidic profiles) are recognized markers of these consequences. Limited data is available on the association of these markers and OSAS’s severity/response to positive airway pressure therapy (PAP). Material and methods: In this prospective study we analyzed polysomnographic and analytical data of male patients admitted to sleep laboratory. The aim was to evaluate metabolic/cardiovascular markers in snorers and OSAS patients, to relate with sleep parameters and PAP response. One-hundred and three patients were included, and 73 (71%) were OSAS patients. OSAS patients were similar to snorers except for higher body mass index (BMI) and dyslipidemia. Severe OSAS patients showed higher glycemia, HbA1c, insulin, and insulin resistance, and lower HDL cholesterol in comparison to mild---moderate (p < 0.05, p < 0.05, p < 0.001, p < 0.001, p < 0.05, respectively). Glycemic profile and triglycerides were slightly correlated with OSAS severity. 46 OSAS patients were submitted to 6 months of PAP, with a statistical decrease in mean values of homocysteine, glycemia, total and LDL cholesterol(p < 0.05, p < 0.05, p < 0.05, respectively), and in glycemia and LDL cholesterol in severe grouponly (p < 0.05, p < 0.05, respectively).Results: This study demonstrated an association between glucose metabolism parameters andtriglycerides with OSAS severity underlying the complexity of the process leading to cardiovas-cular/metabolic complications in this disorder. Moreover, homocysteine, glycemic and lipidicprofiles changed significantly after 6 months of PAP therapy in OSAS, supporting its cardiovas-cular and metabolic protective effect.Conclusion: Our study has reinforced the importance of analytical cardiovascular/metabolicevaluation as complementary tool of diagnosis/treatment response in OSAS.info:eu-repo/semantics/publishedVersio