Self-Criticism, Neediness, and Distress Among Women Undergoing Treatment for Breast Cancer: A Preliminary Test of the Moderating Role of Adjustment to Illness

A diagnosis of cancer can be extremely stressful, and for that reason, cancer patients’ adjustment has been widely studied. Little is known, however, about how patients’ personality vulnerabilities affect their adjustment to cancer. The present study examined the moderating role of several psychological strategies of adjustment to cancer in the associations between the personality predispositions of self-criticism and neediness and distress among women diagnosed with breast cancer. Portuguese women who had been diagnosed with breast cancer for the first time (n _ 50) completed the Depressive Experiences Questionnaire, the Hospital Anxiety and Depression Scale, and the Mini-Mental Adjustment to Cancer Scale questionnaires. Both self-criticism and neediness were found to be associated with increased levels of distress, with a stronger association observed for neediness. Hierarchical regressions indicated that more adaptive adjustment to cancer (i.e., low levels of helplessness/hopelessness, low levels of anxious preoccupation, high levels of fatalism, and high levels of fighting spirit) moderates the association between neediness and distress. There was no evidence that any of the adjustment variables had any mediating effect on the relationship between the personality variables (self-criticism and neediness) and distress. Results are discussed in the context of personality vulnerability and maladaptive psychological response to the disease as a stressful life event. Implications for treatment are discussed. Though promising, the results are preliminary and more research on larger samples is warranted

Phosphorous nanofertilizers for Precise application in rice cultivation as an adaptation to climate change

Rice is the staple food of more than half of the world’s population, which is still growing. The great dependence that agriculture, and rice specially, has on fertilizers alongside extreme events that result from climatic change creates an urge for adaptation. Fertilizers are expensive, finite and a potential environmental problem. Their precise application, by the use of slow-release nanofertilizers, thus avoiding losses and consequently reducing the pressure on water resources, is one step forward in this adaptation. It can reduce costs and protect the environment while ensuring food production. Phosphorous is very important for rice, since it is involved in its flowering and root development, and its low availability to the plants constitutes a serious problem. The delivery of phosphorous through the crop cycle in the form of slow-release phosphorus nanofertilizer (Pnf) instead of the conventional annual bulk application reduces the amount of nutrients applied and increases the absorption by the crop. Combining the fertilizing effect with the use of natural stimulant compounds such as chitosan can protect the crop from diseases and increase its resilience to stress. The use of Pnf reduces the pressure on water resources and avoids imbalances in soil nutrients, thus responding to climatic change challenges and abiotic stresses.info:eu-repo/semantics/publishedVersio

Protein microspheres as suitable devices for piroxicam release

Bovine serum albumin-piroxicam (BSA-piroxicam) and human serum albumin-piroxicam (HSA-piroxicam) microspheres were sonochemically prepared and characterized. The use of polyvinyl alcohol (PVA) lead to an improvement of formulation characteristics, including smaller size, lower polydispersity index (PDl), higher entrapment efficiency and higher stability. The release kinetics of these proteinaceous microspheres was determined in presence of protease, indicating an anomalous drug transport mechanism (diffusion and polymer degradation). In presence of higher protease concentration, BSA microspheres exhibit Case II transport, leading to zero order release (protein degradation). These proteinaceous devices did not show cytotoxicity against human skin fibroblasts in vitro, for range concentrations below to 300 mg L−1, greatly supporting their potential application in the treatment of inflammatory diseases.We would like to acknowledge the financial support of European project Lidwine (contract no. NMP2-CT-2006-026741), and to POPH/FSE for co-financing and FCT for fellowship SFRH/BPD/38939/2007

Argonaute-2 protects the neurovascular unit from damage caused by systemic inflammation

Funding PPBI—Portuguese Platform of BioImaging, POCI-01-0145-FEDER-022122; FCT—Fundação para a Ciência e Tecnologia, UID/Multi/00709/2013, SFRH/ BD/137440/2018 (MMP), IF/00178/2015/CP1300/CT0001 (RF); FCT—L’Oréal— UNESCO Portugal for Women in Science (RF).Background: The brain vasculature plays a pivotal role in the inflammatory process by modulating the interaction between blood cells and the neurovascular unit. Argonaute-2 (Ago2) has been suggested as essential for endothelial survival but its role in the brain vasculature or in the endothelial–glial crosstalk has not been addressed. Thus, our aim was to clarify the significance of Ago2 in the inflammatory responses elicited by these cell types. Methods: Mouse primary cultures of brain endothelial cells, astrocytes and microglia were used to evaluate cellular responses to the modulation of Ago2. Exposure of microglia to endothelial cell-conditioned media was used to assess the potential for in vivo studies. Adult mice were injected intraperitoneally with lipopolysaccharide (LPS) (2 mg/kg) followed by three daily intraperitoneal injections of Ago2 (0.4 nM) to assess markers of endothelial disruption, glial reactivity and neuronal function. Results: Herein, we demonstrated that LPS activation disturbed the integrity of adherens junctions and downregulated Ago2 in primary brain endothelial cells. Exogenous treatment recovered intracellular Ago2 above control levels and recuperated vascular endothelial-cadherin expression, while downregulating LPS-induced nitric oxide release. Primary astrocytes did not show a significant change in Ago2 levels or response to the modulation of the Ago2 system, although endogenous Ago2 was shown to be critical in the maintenance of tumor necrosis factor-α basal levels. LPS-activated primary microglia overexpressed Ago2, and Ago2 silencing contained the inflammatory response to some extent, preventing interleukin-6 and nitric oxide release. Moreover, the secretome of Ago2-modulated brain endothelial cells had a protective effect over microglia. The intraperitoneal injection of LPS impaired blood–brain barrier and neuronal function, while triggering inflammation, and the subsequent systemic administration of Ago2 reduced or normalized endothelial, glial and neuronal markers of LPS damage. This outcome likely resulted from the direct action of Ago2 over the brain endothelium, which reestablished glial and neuronal function. Conclusions: Ago2 could be regarded as a putative therapeutic agent, or target, in the recuperation of the neurovascular unit in inflammatory conditions.publishersversionpublishe

Caracterização química e microbiológica de pêras secadas em estufa solar.

A secagem solar é umas das técnicas mais antigas de conservação de frutos, particularmente os de pequena dimensão. Durante este processo ocorrem também modificações das características químicas e sensoriais dos frutos, que os podem tornar mais apelativos para o consumidor. Neste contexto, a pêra secada da variedade de S. Bartolomeu – pêra passa de Viseu surge como um produto que perde a sua acentuada adstringência com a secagem, reunindo características ímpares como a forma, a cor, o paladar, o cheiro e a capacidade de conservação (Ferreira et al., 2002). No entanto, o decréscimo da sua produção tem conduzido ao aparecimento e secagem de outras variedades regionais, também de pequenas dimensões para a produção da pêra passa. O objectivo deste trabalho consistiu na avaliação das propriedades nutricionais em fresco e após a secagem, efectuada em estufa solar, de quatro variedades regionais de pêras: S. Bartolomeu, Carapinheira Branca, Amêndoa e Amorim provenientes de Coimbra. Nas pêras secadas foram também efectuadas análises microbiológicas com vista à determinação dos mesófilos, dos bolores, das leveduras e dos coliformes totais presentes. Dos resultados obtidos concluiu-se que a polpa em fresco de todas as variedades de pêras estudadas é pobre em proteína e rica em açúcares totais, tal como acontece para a generalidade dos frutos. No entanto, os valores de fibra dietética total para as quatro variedades estão compreendidos entre cerca de 12% a 15% em massa seca, sendo superiores aos obtidos para a generalidade dos frutos e alguns cereais que, no geral, são considerados a melhor fonte de fibra dietética. Os resultados indicam que a secagem em estufa solar não afectou as características nutricionais avaliadas das quatro variedades secadas com excepção dos açúcares totais. A gama de valores de actividade da água e dos níveis populacionais de microorganismos encontrados nas diferentes variedades de pêras permite inferir que este tipo de alimentos será potencialmente seguro do ponto de vista microbiológico. Este comportamento permite-nos sugerir que as variedades Carapinheira Branca, Amêndoa e Amorim são uma potencial alternativa à variedade de S. Bartolomeu para a produção de pêra passa

Synthesis, molecular Docking and biological evaluation of new 1-Aryl-3-[3-(thieno[3,2-b]pyridin-7-ylthio)phenylureas as Potent Type II VEGFR-2 Tyrosine Kinase inhibitors

The vascular endothelial growth factor receptor 2 (VEGFR-2) is a tyrosine kinase receptor, expressed primarily in endothelial cells, and is activated by the specific binding of VEGF to the VEGFR-2 extracellular regulatory domain. Once activated, VEGFR-2 undergoes autophosphorylation, triggering signaling pathways leading to endothelial cell proliferation and subsequent angiogenesisY1 Small molecules may act as inhibitors by competing for the ATP-binding s'1te of the VEGFR-2 intracellular tyrosine kinase domain, thereby preventing the intracellular signa ling that leads to angiogenesis. [ZJ Here, we present the synthesis of new 1-aryl-3-[3-(thieno[3,2-b]pyridin-7-ylthio)phenyl]ureas la-c, as potent type 11 VEGFR-2 inhibitors based on molecular docking (Figure A) and biological evaluation including enzymatic assays using the VEGFR-2 tyrosine kinase domain (ICso=l0-28 nM) and studies in human umbilical vein endothelial cells (HUVECs). The latter included cell viability (MTS), proliferation (BrdU) and Western blot for total and phosphorylated VEGFR-2 (Figure B). The predicted docked poses were analyzed in detail and a plausible explanation for compounds 1 potency was obtained base9 on the simultaneous presence of a S-linker and the arylurea moiety in the meta position as a new substitution pattern for the type 11 VEGFR-2 inhibitors. These chemical features place the thieno[3,2-b]pyridine and the terminal aryl ring in close superimposition to a pyrrolo[3,2-d]pyrimidine derivative. The presence of hydrofobic substituents (F and Me) in the terminal aryl ring is also important. For these compounds a significant inhibition in HUVECs proliferation upon VEGF stimulation was observed at low concentrations (0.5-1.0 IJ.M) without affecting cell viability. Westernblot analysis demonstrated that compounds 1 significantly the inhibited VEGFR-2 phosphorylation at 1.0 jlM, thus confirming their anti-angiogenic potential

Anti-hepatocellular carcinoma activity using human HepG2 cells and hepatotoxicity of 6-substituted methyl 3-aminothieno[3,2-b]pyridine-2-carboxylate derivatives: in vitro evaluation, cell cycle analysis and QSAR studies

Hepatocellular carcinoma (HCC) is a highly complex cancer, resistant to commonly used treatments and new therapeutic agents are urgently needed. A total of thirty-two thieno[3,2-b]pyridine derivatives of two series: methyl 3-amino-6-(hetero)arylthieno[3,2-b]pyridine-2-carboxylates (1a-1t) and methyl 3-amino-6-[(hetero)arylethynyl]thieno[3,2-b]pyridine-2-carboxylates (2a-2n), previously prepared by some of us, were evaluated as new potential anti-HCC agents by studying their in vitro cell growth inhibition on human HepG2 cells and hepatotoxicity using a porcine liver primary cell culture (PLP1). The presence of amino groups linked to a benzene moiety emerges as the key element for the anti-HCC activity. The methyl 3-amino-6-[(3-aminophenyl)ethynyl]thieno[3,2-b]pyridine-2-carboxylate (2f) is the most potent compound presenting GI50 values on HepG2 cells of 1.2 μM compared to 2.9 μM of the positive control ellipticine, with no observed hepatotoxicity (PLP1 GI50>125 μM against 3.3 μM of ellipticine). Moreover this compound changes the cell cycle profile of the HepG2 cells, causing a decrease in the % of cells in the S phase and a cell cycle arrest in the G2/M phase. QSAR studies were also performed and the correlations obtained using molecular and 1D descriptors revealed the importance of the presence of amino groups and hydrogen bond donors for anti-HCC activity, and hydrogen bond acceptors for hepatotoxicity. The best correlations were obtained with 3D descriptors belonging to different subcategories for anti-HCC activity and hepatotoxicity, respectively. These results point to different molecular mechanisms of action of the compounds in anti-HCC activity and hepatotoxicity. This work presents some promising thieno[3,2-b]pyridine derivatives for potential use in the therapy of HCC. These compounds can also be used as scaffolds for further synthesis of more potent analogues.FCT, FEDER/COMPETE/QREN/E

Multifunctional graphene-based magnetic nanocarriers optimized with copolymer Pluronic F127 for biomedical applications

The limitations of current cancer therapies prompt the urgent need for a more effective therapeutic strategy [1]. Graphene-based magnetic nanoparticles (GbMNPs) due to their unique properties, such as high chemical and thermal stability, high charge carrier mobility, large surface area for functionalization and superparamagnetic properties, have the potentiality to be used as efficient multifunctional nanocarrier systems [2]. However, one of the challenges of GbMNPs in biomedical applications is their tendency for agglomeration or precipitation in electrolyte solutions, such as those of body fluids [3]. To overcome this drawback, the developed GbMNPs were grafted with copolymer Pluronic F127 (PF127), yielding the materials denoted as GbMNPs@PF127. PF127 is a water-soluble and biocompatible triblock copolymer (PEO100-PPO65-PEO100) approved by the U.S. Food and Drug Administration (FDA) for use as food additive and in pharmaceutical formulations [4]. This grafting strategy allows the incorporation of a hydrophilic corona that reduces the aggregation of nanoparticles and the adsorption of blood proteins [4, 5]. Also, increases the biocompatibility of the nanosystems and its colloidal stability, prolonging blood circulation [5]. In this study, GbMNPs@PF127 were covalently conjugated with Doxorubicin (DOX), a highly effective chemotherapeutic drug against a broad spectrum of cancers. The developed therapeutic nanosystems were characterized and investigated to be used as multifunctional nanocarriers to combine thermo-chemotherapy, revealing exceptional features, such as: (i) high loading of the chemotherapeutic drug DOX; (ii) high pH stimuli-responsive controlled release; (iii) high heating efficiency profile under AMF with thermo-responsive drug release; as well as (iv) good haem- and biocompatibility even at high concentrations. The presented strategy and findings can represent a new way to design and synthesize highly stable graphene-based materials with novel structures for synergetic thermo-chemotherapy triggered by the abnormal cell microenvironment for a more effective treatment of cancer.This work was financially supported by: Project POCI-01-0145-FEDER-006984 Associate Laboratory LSRE-LCM funded by FEDER through COMPETE2020 - Programa Operacional Competitividade e Internacionalização (POCI) - and by nationalfunds through FCT - Fundação para a Ciência e Tecnologia R.O.R. acknowledgs the PHD scholarship SFRH/BD/97658/2013 granted by FCT. A.M.T.S. acknowledges the FCT Investigator 2013 Programme (IF/01501/2013), with financing from the European Social Fund and the Human Potential Operational Programme.info:eu-repo/semantics/publishedVersio

New potential anti-hepatocellular carcinoma (HCC) agents: in vitro evaluation of anti-HCC activity and hepatotoxicity of 6-substituted methyl 3-aminothieno[3,2-b]pyridine-2-carboxylates and QSAR studies

Hepatocellular carcinoma (HCC) is a major health problem with more than 660,000 new cases per year worldwide [1]. HCC is resistant to commonly used treatments like chemotherapy and radiotherapy and new anti-HCC therapies are urgently needed. Sorafenib was the first approved small molecule against HCC and underlines the importance of identifying potential new anti-HCC drugs [2]. Thirty-two 6-substituted methyl 3-aminothieno[3,2-b]pyridine-2-carboxylates, previously prepared by some of us [3,4], were evaluated as potential new anti-HCC agents by studying their in vitro cell growth inhibition on human HepG2 cells, generally regarded as a good HCC model, and hepatotoxicity using a porcine liver primary cell culture (PLP1). The presence of amino groups linked to a benzene moiety on the substituent of the 6-position emerged as the key element for the anti-HCC activity