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- 3D Printed scaffolds with bactericidal activity aimed for bone tissue regenerationPublication . Correia, Tiago R.; Figueira, Daniela Sofia Rodrigues; Sá, Kevin; Miguel, Sónia P.; Fradique, Ricardo Gil; Mendonça, António; Correia, I.J.Nowadays, the incidence of bone disorders has steeply ascended and it is expected to double in the next decade, especially due to the ageing of the worldwide population. Bone defects and fractures lead to reduced patient’s quality of life. Autografts, allografts and xenografts have been used to overcome different types of bone injuries, although limited availability, immune rejection or implant failure demand the development of new bone replacements. Moreover, the bacterial colonization of bone substitutes is the main cause of implant rejection. To vanquish these drawbacks, researchers from tissue engineering area are currently using computer-aided design models or medical data to produce 3D scaffolds by Rapid Prototyping (RP). Herein, Tricalcium phosphate (TCP)/Sodium Alginate (SA) scaffolds were produced using RP and subsequently functionalized with silver nanoparticles (AgNPs) through two different incorporation methods. The obtained results revealed that the composite scaffolds produced by direct incorporation of AgNPs are the most suitable for being used in bone tissue regeneration since they present appropriate mechanical properties, biocompatibility and bactericidal activity.
- Acetylcholinesterase Inhibitory Activity of Extracts from Angolan Medicinal PlantsPublication . Fernandes, Nelson; Canelo, Laura; Mendonca, Dina; Mendonça, AntónioPlants are considered important sources of new chemical entities that can be used in the development of novel therapeutic drugs for the symptomatic treatment of Alzheimer’s disease. The inhibition of acetylcholinesterase by 38 extracts from 13 medicinal plants used in Angola folk medicine are presented: Adenodolichos huillensis (roots and leaves); Boscia microphylla (leaves); Croton gratissimus (aerial part); Gymnosporia senegalensis (branches); Hymenodictyon floribundum (barks); Parinari capensis (leaves); Peucedano angolense (aerial part); Phragmanthera glaucocarpa (roots); Rhus kirkii (leaves); Solanecio mannii (branches); Solanum incanum (fruit); Tinnea antiscorbutica (aerial part) and Xylopia odoratissima (leaves). TLC bioautographic assay and Ellman’s method were used. The best results for IC50 were obtained with the toluene extract of B. microphylla leaves (0.55 ± 0.01 mg/mL) and the methanol extract of G. senegalensis branches (0.30 ± 0.00 mg/mL). The aqueous extract of the leaves of P. capensis also demonstrated acetylcholinesterase inhibitory activity in the two methods used. In conclusion, the medicinal plants P. capensis, B. microphylla and G. senegalensis represent promising sources of natural compounds with acetylcholinesterase inhibitory properties.
- Acid sulfite pretreatment in the enzymatic hydrolysis of Cytisus striatus: optimization strategyPublication . Vaz, Álvaro; Gomes, Tânia; Simões, RogérioEthanol production from lignocellulosic material includes three major steps: biomass pretreatment, which fragments the lignocellulosic matrix to facilitate the enzymes access to the substrate; hydrolysis, where the polysaccharides are converted into fermentable sugars (e.g. glucose and xylose); and finally, fermentation that produces ethanol or other biologically based chemicals (e.g. lactic acid, succinic acid). The aim of the present work was to study the effect of some operative variables of the pretreatment stage, namely sodium hydrogen sulfite and sulfuric acid loadings, temperature and time, on the release of sugars in the enzymatic hydrolysis of Cytisus striatus, performed applying a Novozymes® cocktail, with fixed charges and operating conditions. Wood branches were chipped and submitted to different reaction conditions, with a central composite experimental design 2^4+star, exploring the following variables: sulfuric acid charge (0-3%, on wood), sodium bisulfite charge (0-4 %, on wood), maximum temperature (150-190ºC) and time at maximum temperature (0-30 minutes). After pretreatment, the acid hydrolysates were recovered, the solid residues were mechanically disintegrated and thereafter subjected to enzymatic hydrolysis with an enzymatic cocktail from Novozymes®. Sugars and by-products released in the sulphite pretreatment and enzymatic treatment hydrolysates were analyzed by HPLC.
- Action of Curcumin on Glioblastoma Growth: A Systematic Review with Meta-Analysis of Animal Model StudiesPublication . Luís, Ângelo; Amaral, Leonor; Domingues, F.C.; Pereira, L.; Cascalheira, JoséGliomas are aggressive brain tumors with poor prognosis even after surgical removal and radio-chemotherapy, stressing the urgency to find alternative therapies. Several preclinical studies evaluating the anticancer effect of curcumin in animal models of glioma are reported, but a systematic review with meta-analysis of these studies, considering the different experimental conditions used, has not been made up to this date. A search in different databases (Pubmed, Web of Science, Scopus, and SciELO) following the PRISMA statement was conducted during November 2023 to systematically identify articles assessing the effect of curcumin in murine xenograft models of glioma and identified 15 articles, which were subdivided into 24 studies. Tumor volume before and after treatment with curcumin or vehicle was extracted and the efficacy of curcumin was evaluated by performing a random effects meta-analysis of the data. Publication bias and the impact of different experimental conditions on curcumin efficacy were assessed. Treatment with curcumin decreased tumor volume. Comparing curcumin with control groups, the overall weighted standardized difference in means was −2.079 (95% CI: −2.816 to −1.341; p-value < 0.001). The curcumin effect was observed for different animal models, types of glioma cells, administration routes, and curcumin formulations. Publication bias was identified but does not invalidate curcumin’s effectiveness. The findings suggest the potential therapeutic efficacy of curcumin against glioma.
- Activity coefficients in the evaluation of food preservativesPublication . Mendonça, António; Vaz, Margarida I. P. M.; Mendonça, DinaFood preservatives are used in very low concentrations. However, usually they are used in aqueous high ionic strength solutions. The Pitzer model allows activity coefficient determination in these cases. Without the knowledge of activity coefficients, activity or ‘correct concentration’ cannot be known. In this work, the activity coefficients of sodium chloride, potassium chloride and calcium chloride in pure solutions were calculated by the Debye H¨uckel theory and the Pitzer theory. The calculated values were compared with experimental values. Activity coefficients of pure sodium benzoate in aqueous mixed solutions with potassium chloride or calcium chloride were evaluated using the Pitzer model. The same evaluation can be done to more complex systems once all Pitzer parameters values for the ionic species are known.
- Activity coefficients of aqueous Hydrochloric acid solutions up to a Molality of 6.0 mol kg-1 at temperatures from (5 to 45) °CPublication . Juusola, Pekka M.; Partanen, Jaakko; Vahteristo, Kari P.; Mendonça, António; Minkkinen, Pentti O.Simple three parameter activity coefficient equation originating from the DebyeHückel theory was used for the calculation of activity coefficients of aqueous hydrochloric acid at temperatures 5-45 °C up to a molality of 6 moI kg-I. N ew data from galvanic ce1ls without a liquid junction were used in the parameter estimations of this equation. These data consist of sets of measurements in the molality range 0.3-6.5 moI kg-I at temperatures 5, 15, 25, 35, and 45°C. It was observed that alI estimated parameters folIow very simple equations with respect to temperature. They are either constant or depend linearly on the temperature. The activity coefficient equation was tested with the celI potential difference data of Hamed and Ehlers (1933), ElIis (1916), Ákerlõf and Teare (1938), and Faita and Mussini (1964). It was observed that the most important data in these sets can be predicted welI by means of the activity coefficient equation. The activity coefficients obtained using the new equation were also compared to those obtained by means of the two-parameter Hückel and Pitzer equations presented by Partanen and Covington (2002) up to molality 2.0 moI kg-t, to those obtained by means of the Pitzer equations presented by Saluja et ai. (1986) and Holmes et ai. (1987), and to those obtained by means of the equation presented by Hamer and Wu (1972) for the temperature of 25°C.
- Activity coefficients of dipotassium phthalate and potassium hydrogen phthalate in water at 298.15KPublication . Mendonça, António; Juusola, Pekka M.Pitzer model parameters and modified Guggenheim equation parameters for dipotassium phthalate (K2PH) and potassium hydrogen phthalate (KHPh) were determined from cell potential difference (cpd) measurements on galvanic cells without liquid junction. Mean activity coefficients of these salts in water at 298.15 K were calculated by the Pitzer model and modified Guggenheim equations. The Pitzer parameters values obtained for K2Ph where: Beta 0(K2Ph)+steta(Cl,Ph) = 0.25 ± 0.01 mol−1 kg; Beta 1 (K2Ph)= 0.86 ± 0.08 mol−1 kg; C(K2Ph)= −0.010 ± 0.002 mol−2 kg2 and ΨK,Cl,Ph = 0.014 ± 0.005 mol−2 kg2. The Pitzer parameters values obtained for KHPh were: Beta0 (KHPh + steta(Cl,Ph)= 0.084 ± 0.013 mol−1 kg, = 0 mol−1 kg. The results were also compared to the values obtained from Pitzer parameters published in literature. The parameter values for the modified Guggenheim equations (bK,Ph = −0.041 mol−1 kg and bK,HPh = −0.020 mol−1 kg) obtained in this study were used in the mean activity coefficients calculations. The modified Guggenheim equation allows us to obtain similar mean activity coefficient values, as the Pitzer equation, up to 1.5 mol kg−1 ionic strength for K2Ph and 0.5 mol kg−1 for KHPh.
- Activity coefficients of sodium benzoate and potassium benzoate in water at 298.15 KPublication . Mendonça, António; Cardoso, Cristina M. P.; Juusola, Pekka M.Industrial additives, like sodium benzoate and potassium benzoate, are used in low concentrations in aqueous solutions. However, in general, the ionic strength of the aqueous media is high. The Pitzer model allows the determination of activity coefficients in aqueous media. In this work, Pitzer parameters for sodium benzoate were recalculated (β(0)=0.162 mol−1 kg and β(1)=0.38 mol−1 kg) and Pitzer parameters for potassium benzoate were determined (β(0)=0.157 mol−1 kg and β(1)=0.27 mol−1 kg) from cell potential difference (cpd) measurements on galvanic cells without liquid junction. From these values, activity coefficients of potassium benzoate in water and in aqueous potassium chloride solutions were calculated by the Pitzer model. The activity coefficients were also calculated by modified Guggenheim equations with parameters obtained in this work and the results of the two models were compared.
- Adenosine inhibits human astrocyte proliferation independently of adenosine receptor activationPublication . Marcelino, Helena; Nogueira, Vanda Cristina Simões; Santos, Cecilia; Quelhas, Patricia; Carvalho, Tiago; Gomes, João Fonseca; Tomás, Joana; Diógenes, Maria José; Sebastião, Ana M; Cascalheira, JoséBrain adenosine concentrations can reach micromolar concentrations in stressful situations such as stroke, neurodegenerative diseases or hypoxic regions of brain tumours. Adenosine can act by receptor-independent mechanism by reversing the reaction catalysed by S-adenosylhomocysteine (SAH) hydrolase, leading to SAH accumulation and inhibition of S-adenosylmethionine (SAM)-dependent methyltransferases. Astrocytes are essential in maintaining brain homeostasis but their pathological activation and uncontrolled proliferation plays a role in neurodegeneration and glioma. Adenosine can affect cell proliferation, but the effect of increased adenosine concentration on proliferation of astrocytes is not clarified and was addressed in present work. Human astrocytes (HA) were treated for 3 days with test drugs. Cell proliferation/viability was assessed by the MTT assay and by cell counting. Cell death was evaluated by assessing lactate dehydrogenase (LDH) release and by western blot analysis of αII-Spectrin cleavage. 30µM-Adenosine caused a 40%±3% (p < .05, n = 5) reduction in cell proliferation/viability, an effect reversed by 2U/ml-adenosine deaminase, but unchanged in the presence of antagonists of any of the adenosine receptors. Adenosine alone did not induce cell death. 100µM-Homocysteine alone caused 16%±3% (p < .05) decrease in HA proliferation. Combined action of adenosine and homocysteine decreased HA proliferation by 76%±4%, an effect higher (p < .05) than the sum of the effect of adenosine and homocysteine alone (56%±5%). The inhibitory effect of adenosine on HA proliferation/viability was mimicked by two adenosine kinase inhibitors and attenuated in the presence of folate (100µM) or SAM (50-100µM). The results suggest that adenosine reduces HA proliferation by a receptor-independent mechanism probably involving reversal of SAH hydrolase-catalysed reaction.
- An overview of electrospun membranes loaded with bioactive molecules for improving the wound healing processPublication . Miguel, Sónia; Sequeira, Rosa; Moreira, André; Cabral, C.S.D.; Mendonça, António; Ferreira, Paula; Correia, I.J.Nowadays, despite the intensive research performed in the area of skin tissue engineering, the treatment of skin lesions remains a big challenge for healthcare professionals. In fact, none of the wound dressings currently used in the clinic is capable of re-establishing all the native features of skin. An ideal wound dressing must confer protection to the wound from external microorganisms, chemical, and physical aggressions, as well as promote the healing process by stimulating the cell adhesion, differentiation, and proliferation. In recent years different types of wound dressings (such as films, hydrocolloids, hydrogels, micro/nano fibers) have been developed. Among them, electrospun nanofibrous membranes due to their intrinsic properties like high surface area-to-volume ratio, porosity and structural similarity with the skin extracellular matrix have been regarded as highly promising for wound dressings applications. Additionally, the nanofibers available in these membranes can act as drug delivery systems, which prompted the incorporation of biomolecules within their structure to prevent skin infections as well as improve the healing process. In this review, examples of different bioactive molecules that have been loaded on polymeric nanofibers are presented, highlighting the antibacterial biomolecules (e.g. antibiotics, silver nanoparticles and natural extracts-derived products) and the molecules capable of enhancing the healing process (e.g. growth factors, vitamins, and anti-inflammatory molecules).