Propolis: A complex natural product with a plethora of biological activities that can be explored for drug development

The health industry has always used natural products as a rich, promising, and alternative source of drugs that are used in the health system. Propolis, a natural resinous product known for centuries, is a complex product obtained by honey bees from substances collected from parts of different plants, buds, and exudates in different geographic areas. Propolis has been attracting scientific attention since it has many biological and pharmacological properties, which are related to its chemical composition. Several in vitro and in vivo studies have been performed to characterize and understand the diverse bioactivities of propolis and its isolated compounds, as well as to evaluate and validate its potential. Yet, there is a lack of information concerning clinical effectiveness. The goal of this review is to discuss the potential of propolis for the development of new drugs by presenting published data concerning the chemical composition and the biological properties of this natural compound from different geographic origins.

A continuous solvent- and oil-free method to prepare injectable PEGylated fibrinogen cell-laden microparticles

Injectable biomaterials with in situ cross-linking reactions have been suggested to minimize the invasiveness associated with most implantation procedures. However, problems related with the rapid liquid-to-gel transition reaction can arise because it is difficult to predict the reliability of the reaction and its end products, as well as to mitigate cytotoxicity to the surrounding tissues. An alternative minimally invasive approach to deliver solid implants in vivo is based on injectable microparticles, which can be processed in vitro with high fidelity and reliability, while showing low cytotoxicity. Their delivery to the defect can be performed by injection through a small diameter syringe needle. We present a new methodology for the continuous, solvent- and oil-free production of photopolymerizable microparticles containing encapsulated human dermal fibroblasts. A precursor solution of cells in photo-reactive PEG-fibrinogen (PF) polymer was transported through a transparent injector exposed to light-irradiation before being atomized in a jet-in-air nozzle. Shear rheometry data provided the cross-linking kinetics of each PF/cell solution, which was then used to determine the amount of irradiation required to partially polymerize the mixture prior to atomization. The partially polymerized drops fell into a gelation bath for further polymerization. The system was capable of producing cell-laden microparticles with high cellular viability, with an average diameter of between 88.1 µm to 347.1 µm and a dispersity of between 1.1 and 2.4, depending on the parameters chosen.

Stromal vascular fraction cell sheets angiogenic potential for tissue engineering and regenerative medicine applications

One of the biggest concerns in the Tissue Engineering field is the correct vascularization of engineered constructs. Strategies involving the use of endothelial cells are promising but adequate cell sourcing and neo-vessels stability are enduring challenges. In this work, we propose the hypoxic pre-conditioning of the stromal vascular fraction (SVF) of human adipose tissue to obtain highly angiogenic cell sheets (CS). For that, SVF was isolated after enzymatic dissociation of adipose tissue and cultured until CS formation in normoxic (pO2=21%) and hypoxic (pO2=5%) conditions for 5 and 8 days, in basal medium. Immunocytochemistry against CD31 and CD146 revealed the presence of highly branched capillary-like structures, which were far more complex for hypoxia. ELISA quantification showed increased VEGF and TIMP-1 secretion in hypoxia for 8 days of culture. In a Matrigel assay, the formation of capillary-like structures by endothelial cells was more prominent when cultured in conditioned medium recovered from the cultures in hypoxia. The same conditioned medium increased the migration of adipose stromal cells in a scratch assay, when compared with the medium from normoxia. Histological analysis after implantation of 8 days normoxic- and hypoxic-conditioned SVF CS in a hindlimb ischemia murine model showed improved formation of neo-blood vessels. Furthermore, Laser Doppler results demonstrated that the blood perfusion of the injured limb after 30 days was enhanced for the hypoxic CS group. Overall, these results suggest that SVF CS created under hypoxia can be used as functional vascularization units for tissue engineering and regenerative medicine.

In vitro chondrogenic commitment of human Wharton's jelly stem cells by co-culture with human articular chondrocytes.

Wharton's jelly stem cells (WJSCs) are a potential source of transplantable stem cells in cartilage-regenerative strategies, due to their highly proliferative and multilineage differentiation capacity. We hypothesized that a non-direct co-culture system with human articular chondrocytes (hACs) could enhance the potential chondrogenic phenotype of hWJSCs during the expansion phase compared to those expanded in monoculture conditions. Primary hWJSCs were cultured in the bottom of a multiwell plate separated by a porous transwell membrane insert seeded with hACs. No statistically significant differences in hWJSCs duplication number were observed under either of the culture conditions during the expansion phase. hWJSCs under co-culture conditions show upregulations of collagen type I and II, COMP, TGFβ1 and aggrecan, as well as of the main cartilage transcription factor, SOX9, when compared to those cultured in the absence of chondrocytes. Chondrogenic differentiation of hWJSCs, previously expanded in co-culture and monoculture conditions, was evaluated for each cellular passage using the micromass culture model. Cells expanded in co-culture showed higher accumulation of glycosaminoglycans (GAGs) compared to cells in monoculture, and immunohistochemistry for localization of collagen type I revealed a strong detection signal when hWJSCs were expanded under monoculture conditions. In contrast, type II collagen was detected when cells were expanded under co-culture conditions, where numerous round-shaped cell clusters were observed. Using a micromass differentiation model, hWJSCs, previously exposed to soluble factors secreted by hACs, were able to express higher levels of chondrogenic genes with deposition of cartilage extracellular matrix components, suggesting their use as an alternative cell source for treating degenerated cartilage.

Recycled asphalt mixtures with foamed bitumen: an alternative to build ecofriendly road pavements

Nowadays, recycling has become a very important objective for the society in the scope of a closed loop product life cycle. In recent years, new recycling techniques have been developed in the area of road pavements that allow the incorporation of high percentages of reclaimed asphalt (RA) materials in recycled asphalt mixtures. The use of foamed bitumen for production of recycled asphalt mixtures is one of those techniques, which also allows the reduction of the mixing temperatures (warm mix technology). However, it is important to evaluate if this solution can maintain or improve the performance of the resulting mixtures. Thus, the main aim of the present study is to assess the performance of warm recycled asphalt mixtures incorporating foamed bitumen as the new binder and 50% RA, in comparison with a control mixture using conventional bitumen. Four mixtures have been produced with 50% RA, one of them at typical high mixing temperatures with a conventional bitumen (control mixture) and the other three with foamed bitumen at different production temperatures. These four mixtures were tested to evaluate their compactability and water sensitivity. The laboratory test results showed that the production of recycled mixtures with foamed bitumen can be reduced by 40ºC without changing the performance of the resulting mixtures.

Foamed Bitumen: an alternative way of producing asphalt mixtures

With the constant need to improve and make the production of asphalt mixtures more sustainable, new production techniques have been developed, the implementation of which implies the correct knowledge of their performance. One of the most promising asphalt production techniques is the use of foamed bitumen. However, it is essential to understand how this binder will behave when subject to the expansion process. The loss of volume of the foamed bitumen could be translated by a decay curve, which allows to determine the ideal temperature and water content added to the bitumen in order to assure adequate conditions to the mix the bitumen with the aggregates. On the present study, a conventional 160/220 pen grade bitumen was tested by using different temperatures and water contents, and it was concluded that the optimum temperature for the production of foamed bitumen (with the studied bitumen) is 150 ºC, which corresponds to a viscosity of 0.1 Pa.s. The water content mostly influence the half-life of the bitumen foam, resulting in quicker volume reductions for higher water contents.

Predicting plateau pressure in intensive medicine for ventilated patients

Barotrauma is identified as one of the leading diseases in Ventilated Patients. This type of problem is most common in the Intensive Care Units. In order to prevent this problem the use of Data Mining (DM) can be useful for predicting their occurrence. The main goal is to predict the occurence of Barotrauma in order to support the health professionals taking necessary precautions. In a first step intensivists identified the Plateau Pressure values as a possible cause of Barotrauma. Through this study DM models (classification) where induced for predicting the Plateau Pressure class (>=30 cm

Connecting free volume with shape memory properties in noncytotoxic gamma-irradiated polycyclooctene

The free volume holes of a shape memory polymer have been analysed considering that the empty space between molecules is necessary for the molecular motion, and the shape memory response is based on polymer segments acting as molecular switches through variable flexibility with temperature or other stimuli. Therefore, thermomechanical analysis (TMA) and positron annihilation lifetime spectroscopy (PALS) have been applied to analyse shape recovery and free volume hole sizes in gamma irradiated polycyclooctene (PCO) samples, as a non-cytotoxic alternative to more conventional PCO crosslinked via peroxide for future applications in medicine. Thus, a first approach relating structure, free volume holes and shape memory properties in gamma irradiated PCO is presented. The results suggest that free volume holes caused by gamma irradiation in PCO samples facilitate the recovery process by improving movement of polymer chains and open t possibilities for the design and control of the macroscopic response.

Biochemical and physical surface functionalization of polycaprolactone as a key mediator of osteogenic differentiation and vascularized tissue morphogenesis

Tese de Doutoramento em Engenharia de Tecidos, Medicina Regenerativa e Células Estaminais.

An alternative educational indicator for classifying secondary schools in Portugal

The purpose of this paper aims at carrying out a study in the area of Statistics for classifying Portuguese Secondary Schools (both mainland and islands: “Azores” and “Madeira”), taking into account the results achieved by their students in both national examinations and internal assessment. The main according consists of identifying groups of schools with different performance levels by considering the sub-national public and private education systems’ as well as their respective geographic location. For this, we developed an alternative educational indicator for the so-called Secondary Education indicator rankings released since 2001 by the Portuguese media.

Cheese whey: a cost-effective alternative for hyaluronic acid production by Streptococcus zooepidemicus

This study focuses on the optimization of cheese whey formulated media for the production of hyaluronic acid HA by Streptococcus zooepidemicus. Culture media containing whey (W; 2.1 g/L) or whey hydrolysate (WH; 2.4 g/L) gave the highest HA productions. Both W and WH produced high yields on protein consumed, suggesting cheese whey is a good nitrogen source for S. zooepidemicus production of HA. Polysaccharide concentrations of 4.0 g/L and 3.2 g/L were produced in W and WH in a further scale-up to 5 L bioreactors, confirming the suitability of the low-cost nitrogen source. Cheese whey culture media provided high molecular weight (> 3000 kDa) HA products. This study revealed replacing the commercial peptone by the low-cost alternative could reduce HA production costs by up to a 70%compared to synthetic media.

Bioactive ceramics for tissue engineering and regenerative medicine derived from marine sponges

Publicado em "Journal of tissue engineering and regenerative medicine". Vol. 8, suppl. s1 (2014)

Micro/nano-structured superhydrophobic surfaces in the biomedical field: part I: basic concepts and biomimetic approaches.

Inspired by natural structures, great attention has been devoted to the study and development of surfaces with extreme wettable properties. The meticulous study of natural systems revealed that the micro/nano-topography of the surface is critical to obtaining unique wettability features, including superhydrophobicity. However, the surface chemistry also has an important role in such surface characteristics. As the interaction of biomaterials with the biological milieu occurs at the surface of the materials, it is expected that synthetic substrates with extreme and controllable wettability ranging from superhydrophilic to superhydrophobic regimes could bring about the possibility of new investigations of cellâ material interactions on nonconventional surfaces and the development of alternative devices with biomedical utility. This first part of the review will describe in detail how proteins and cells interact with micro/nano-structured surfaces exhibiting extreme wettabilities.

Zebrafish embryos as in vivo model for toxicity evaluation: screening of nanoparticle formulations DODAB:MO and DODAC:MO

Dissertação de mestrado em Molecular Genetics

Real-Time decision support using data mining to predict blood pressure critical events in intensive medicine patients

Patient blood pressure is an important vital signal to the physicians take a decision and to better understand the patient condition. In Intensive Care Units is possible monitoring the blood pressure due the fact of the patient being in continuous monitoring through bedside monitors and the use of sensors. The intensivist only have access to vital signs values when they look to the monitor or consult the values hourly collected. Most important is the sequence of the values collected, i.e., a set of highest or lowest values can signify a critical event and bring future complications to a patient as is Hypotension or Hypertension. This complications can leverage a set of dangerous diseases and side-effects. The main goal of this work is to predict the probability of a patient has a blood pressure critical event in the next hours by combining a set of patient data collected in real-time and using Data Mining classification techniques. As output the models indicate the probability (%) of a patient has a Blood Pressure Critical Event in the next hour. The achieved results showed to be very promising, presenting sensitivity around of 95%.