Role of SPARC in Bone Remodeling and Cancer‐Related Bone Metastasis

There is a growing socioeconomic recognition that clinical bone diseases such as bone infections, bone tumors and osteoporotic bone loss mainly associated with ageing, are major issues in today0s society. SPARC (secreted protein, acidic and rich in cysteine), a matricellular glycoprotein, may be a promising therapeutic target for preventing or treating bone‐related diseases. In fact, SPARC is associated with tissue remodeling, repair, development, cell turnover, bone mineralization and may also participate in growth and progression of tumors, namely cancer‐related bone metastasis. Yet, the function of SPARC in such biological processes is poorly understood and controversial. The main objective of this work is to review the current knowledge related to the activity of SPARC in bone remodeling, tumorigenesis, and bone metastasis. Progress in understanding SPARC biology may provide novel strategies for bone regeneration and the development of anti‐angiogenic, anti‐proliferative, or counter‐adhesive treatments specifically against bone metastasis

Melanoma in the Eyes of Mechanobiology

Skin is the largest organ of the human body with several important functions that can be impaired by injury, genetic or chronic diseases. Among all skin diseases, melanoma is one of the most severe, which can lead to death, due to metastization. Mechanotransduction has a crucial role for motility, invasion, adhesion and metastization processes, since it deals with the response of cells to physical forces. Signaling pathways are important to understand how physical cues produced or mediated by the Extracellular Matrix (ECM), affect healthy and tumor cells. During these processes, several molecules in the nucleus and cytoplasm are activated. Melanocytes, keratinocytes, fibroblasts and the ECM, play a crucial role in melanoma formation. This manuscript will address the synergy among melanocytes, keratinocytes, fibroblasts cells and the ECM considering their mechanical contribution and relevance in this disease. Mechanical properties of melanoma cells can also be influenced by pigmentation, which can be associated with changes in stiffness. Mechanical changes can be related with the adhesion, migration, or invasiveness potential of melanoma cells promoting a high metastization capacity of this cancer. Mechanosensing, mechanotransduction, and mechanoresponse will be highlighted with respect to the motility, invasion, adhesion and metastization in melanoma cancer.The authors acknowledge to Ana Silva ([email protected]) for expert assistance with graphical design, and to Portuguese funds – FCT UID/BIM/04293/2019.info:eu-repo/semantics/publishedVersio

Behavior of prostate cancer cells in a nanohydroxyapatite/collagen bone scaffold

Prostate cancer (PCa) is the second leading cause of death among men in Europe and U.S. The metastatic dissemination pattern of PCa is unique, developing bone metastasis as the only site of progression, consequently with a prognosis very poor. The cancer cells interactions within the surrounding bone environment are critical for tumor growth and progression. Secreted protein, acidic and rich in cysteine (SPARC) is described to be involved in PCa cells migration and invasion into bone. Three-dimensional (3D) in vitro systems that are able to closely resemble the in vivo microenvironment are recently taking importance in cancer research. Original nanohydroxyapatite/collagen scaffolds were designed to resemble bone microenvironment in order to be applied as substitutes in bone defects and as potential biomaterials to mimic skeletal tumors. In fact, these 3D structures were cytocompatible and able to support osteoblast (MC3T3-E1) colonization and to promote bone ingrowth. Additionally, SPARC adsorption onto the scaffolds affected PC3 and LNCaP PCa cell lines behavior. PC3 cells were found to adapt and colonize the scaffolds, differing from LNCaP where cells underwent morphogenic changes and grew as clusters. Furthermore, for the tested SPARC concentration, SPARC plays a role in retaining LNCaP cells at the latter time points while with PC3 cells no significant differences were observed. This characterization study is required to establish a bone model to provide new insights into the poorly understood PCa mechanisms of metastasis to bone and the generation of improved therapies.info:eu-repo/semantics/publishedVersio

Development of a cosmos solid emulsion

Natural products are becoming a trend in the cosmetic market, due to a growing awareness and concern with the origin of these products. The certification of natural products, especially organic ones under the COSMOS signature preserves the integrity of the constituents, in an environmentally appropriate and safe for human health, expanding the concept of "green chemistry”, guaranteeing the origin, and processing of the products, storage, manufacturing, packaging, etc. The objective of this study was to develop a moisturizing cosmetic emulsion in the solid format according to COSMOS certification, with guarantee the quality of the product in a new concept of solid cosmetic. 59 tests were carried out to optimise this emulsion, with the best possible hydration level. The different tests included variations in components and their amounts, following be evaluation of sensory aspects for each formulation. The final cosmetic emulsion formulation (Figure 1) contains components of Portuguese origin such as grape seeds oil from Douro Valley, olive oil and extract of by-products of acorn (Quercus Ilex L.) and essential oils of mandarin, geranium, coriander and cinnamon. The formulation has undergone accelerated stability tests with temperatures (40 ºC /-12 ºC). The pH, density and organoleptic characteristics were evaluate. The phenolic profile of acorn by-product (Quercus ilex L.) was performe by UHPLC-DAD-ESI-MS2. A questionnaire was applying to evaluate the acceptance after use of the moisturizing cosmetic emulsion. In stability tests, overall the formulation showed small color variations and less aroma intensity, maintaining hydration and solid state. The pH changes were from 4.68 ± 0.006 to 4.78 ± 0.05 and the density was maintaining at 0.73 kg/m3 . The polar extract of acorn by-product have as major compounds trigalloyl-HHDP-glucose, valoneic acid dilactone and gallic acid, known as antioxidants compounds. The essential oils bring beneficial properties to the skin and the aroma. In the post use of solid emulsion survey applied shown that “aroma” was the second point most valorised (47.6%), after “hydration” (90.5%). The results shown that the majority of participants (81.0%) were “very satisfied” or “satisfied” with the solid emulsion indicating the intention to use it if it is on the market (76.2%). This study highlights the research in reformulations from liquid to solid products, and the potential of using Portuguese raw materials such as acorn.Thanks to FCT (Portugal) and the ERDF under the PT2020 Program for financial support to CIMO (UIDB/00690/2020) and LAQVREQUIMTE (UIDB/50006/2020). SMC acknowledges the research contract (project AgroForWealth, CENTRO-01-0145- FEDER000001).info:eu-repo/semantics/publishedVersio

Hybrid sol-gel matrices doped with colorimetric/fluorimetric imidazole derivatives

Organic–inorganic hybrids (OIH) are materials that can be easily synthesized by the sol–gel method and combine the advantages of organic and inorganic moieties within a single polymeric matrix. Imidazole derivatives are versatile organic compounds that can change their optical properties with the variation of pH due to the protonation or deprotonation of the nitrogen atoms. This work reports the preparation of different OIHs doped with different contents of two imidazole compounds (3a,b). The obtained materials were characterized structurally by FTIR, and the dielectric properties were studied by electrochemical impedance spectroscopy. The optical properties were studied by UV-Vis absorption and fluorescence spectroscopies. The FTIR analysis showed that the presence of the imidazole does not change the structural properties of the matrices. The normalized resistance values obtained for the doped matrices ranged between 8.57 and 9.32 Ω cm2, all being higher than the undoped matrix. The σ ranged between 9.49 and 10.28 S cm−1, being all higher than the pure OIH samples. Compound 3a showed a maximum absorption peak at 390 nm, which is present in the OIH spectra, proving the presence of the compound. In the case of compound 3b, a maximum absorption wavelength at 412 nm was found, and the compound peak was not clear, which may indicate that an interaction between the compound and the matrix occurred. A synergetic effect between the intrinsic emission of the matrix and the fluorescence of 3a is found on the OIH-doped matrices.This research was funded by Fundação para a Ciência e Tecnologia (FCT) and FEDER (European Fund for Regional Development)-COMPETE-QRENEU through the Chemistry Research Centre of the University of Minho (Ref. CQ/UM (UID/QUI/00686/2019 and UID/QUI/00686/2020), project “SolSensors—Development of Advanced Fiber Optic Sensors for Monitoring the Durability of Concrete Structures”, reference POCI-01-0145-FEDER-031220, and a PhD grant to R.P.C.L. Sousa (SFRH/BD/145639/2019). The NMR spectrometer Bruker Avance III 400 is part of the National NMR Network (PTNMR) and partially supported by Infrastructure Project No 022161 (co-financed by FEDER through COMPETE 2020, POCI and PORL and FCT through PIDDAC)

New fluorescent heterocyclic materials: Synthesis, solvatochromic and fluorescence properties

Thienyl- and bithienyl-1,3-benzothiazoles 1 and 2 were synthesised by reacting various formyl thienyl and bithienyl derivatives with o-aminobenzenethiol in moderate to excellent yields. Evaluation of the solvatochromic and fluorescence properties of these compounds was carried out. Due to their strong fluorescence and also the strong push-pull character, benzothiazole derivatives 1 and 2 can be used as potential NLO materials or as fluorescent markers.Fundação para a Ciência e Tecnologia (FCT

Effect of essential oils on the planktonic of S. aureus and E. coli cells

The essential oils of aromatic plants and their components have a wide range of applications in ethno-medicine, preservation, food flavoring and fragrances and in the perfume industries. Some essential oils derived from plants have revealed promising antimicrobial activity against a wide range of bacteria, including antibiotic resistant species. The aim of this study was to examine the antimicrobial effect of essential oils of Cinnamomum zeylanicum and Cymbopogon martini against planktonic Staphylococcus aureus and Escherichia coli growth. The antimicrobial activity of the essential oils was checked by bacterial growth, at 37 ºC and 120 rpm, in the presence of increasing concentrations of each essential oil for 24 h. Essential oils were dissolved in DMSO (2.0 %) and saline water (0.85 %) with tween 80 (0.5 %) in order to obtain final concentrations of 0.06 %, 0.09 % and 0.12%, for E. coli, and 0.09 %, 0, 12 %, 0.36 % and 0.48 %, for S. aureus. Bacterial planktonic growth over time was followed by the quantification of the number of viable through cultivation of aliquots in TSA. Data showed that E. coli was more sensitive to the action of both essential oils, since complete planktonic growth inhibition was attained with a concentration of 0.09 % of the essential oil of C. zeylanicum oil and 0.06 % of the essential oil of C. Martini. Conversely, S. aureus was less sensitive to the antimicrobial action of the essential oils. C. zeylanicum essential oil inhibited S. aureus growth only at concentrations of 0.36 % and 0.48 %, after 4 and 2 hours of growth. However, unexpectedly after 24 hours those S. aureus cells recovered gradually their planktonic growth. The data pointed out that it is crucial to check the bacterial behavior in the presence of antimicrobial products in different concentrations and over time due to the possible development of bacterial tolerance towards the mechanisms of action of those products. In fact, antimicrobials may have a positive effect in the early hours of application, as demonstrated by some results of this experiment. However, for longer times, the inhibitory effect of antimicrobials can be reverted by bacteria making ineffective their use as disinfectants in food industries. Addiotionally, the continuous exposure of bacteria to antimicrobials can influence the process of microbial resistance de development and increase. These preliminary results demonstrated the possibility of using essential oils of C. zeylanicum and C. martini against two bacteria that are responsible for foodborne illnesses at low concentrations but only for slightly prolonged periods of exposure

In vivo biodistribution of carboxymethylchitosan/poly(amidoamine) dendrimer nanoparticles in rats

Carboxymethylchitosan/poly(amidoamine) dendrimer nanoparticles (CMCht/PAMAM) have recently been proposed for intracellular drug delivery purposes. These are constituted by a PAMAM dendrimer core grafted with chains of CMCht. Previous reports have shown that these nanoparticles disclosed an improved cytotoxic profile when compared to traditional dendrimers. Following on these results the present study aims to assess, for the first time, the short-term in vivo biodistribution of CMCht/PAMAM dendrimer nanoparticles upon intravenous injections in Wistar Han rats. The rats were injected in the tail vein with 1 and 10 µg/g, respectively, of fluorescein isothiocyanate (FITC) labeled CMCht/PAMAM dendrimer nanoparticles. Brain, liver, kidney and lung were collected at 24, 48 and 72 hours after injection and further stained with phalloidin-TRITC (red) and DAPI (blue) to trace the nanoparticles within the tissues. Liver, kidney and lung were also stained for haematoxylin and eosin in order to assess possible alterations in the morphology of these organs. CMCht/PAMAM dendrimer nanoparticles were observed within the vascular space and parenchyma of liver, kidney and lung, and in the choroid plexus, after 24, 48 and 72 hours upon intravenous injection of nanoparticles. No particles were observed in the brain parenchyma, nor any apparent deleterious histological changes, were observed within these organs. The present report revealed that CMCht/PAMAM dendrimer nanoparticles were stable in circulation for periods up to 72 hours, targeting the main organs/systems through internalization by the cells present in their parenchyma. These results provide positive indicators to their potential use in the future as intracellular drug delivery systems.Funds attributed by Fundação Calouste de Gulbenkian to A.J. Salgado under the scope of the The Gulbenkian Programme to Support Research in Life Sciences; Portuguese Foundation for Science and Technology (Science 2007 Program – A.J. Salgado, pre- and postdoctoral fellowships to J.M. Oliveira – SFRH/BPD/63175/2009, A.M. Frias – SFRH/BPD/45206/2008, F. Marques – SFRH/BPD/33379/2008, A.M. Falcão – SFRH/BD/44485/2008, S. Roque – SFRH/BD/24539/2005; S.R. Cerqueira – SFRH/BD/SFRH/BD/48406: 2008)

Individual and mixture toxicity evaluation of three pharmaceuticals to the germination and growth of Lactuca sativa seeds

This work aims to assess, individually and in mixtures, possible phytotoxic effects of three pharmaceuticals (paracetamol, ibuprofen and amoxicillin) on germination and early growth of Lactuca sativa seeds. Pharmaceuticals are an important group of emerging contaminants, whose presence has been described in several environmental compartments, including soils. However, knowledge on their possible impact in terrestrial organisms is still sparse and even more when mixtures are considered. Germination tests are important to evaluate the quality of soil and the toxic effects that contaminants can pose to plants. The acute effects of individual pharmaceuticals as well as binary and ternary mixtures were assessed using different endpoints, namely: percentage of seed germination, root elongation, shoot and leaf length, after an exposure time of five days. Overall, in the exposure of L. sativa seeds to individual pharmaceuticals there are indications of acute toxicity in the early plant growth. However, this inhibitory effect tends to be cancelled in the acute exposure to mixtures. This study shows the importance of evaluating the toxicity of mixtures of pharmaceuticals, since they might have distinct toxic effects when compared to the single compounds, and also because, probably, it is the closest scenario to the reality that can be found in the environment.This work received financial support from the European Regional Development Fund (ERDF) through COMPETE – Operational Competitiveness Programme and national funds provided by FCT – Foundation for Science and Technology under the projects UID/QUI/50006/2013.info:eu-repo/semantics/publishedVersio