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In this study, poly (lactic-co-glycolic acid) (PLGA) microparticles loaded with cannabidiol (CBD) were synthesized (PLGA@CBD microparticles) and embedded up to 10 wt% in a chondroitin sulfate/polyvinyl alcohol hydrogel matrix. In vitro chemical, physical, and biological assays were carried out to validate the potential use of the modified hydrogels as biomaterials. The microparticles had spherical morphology and a narrow range of size distribution. CBD encapsulation efficiency was around 52%, loading was approximately 50%. Microparticle addition to the hydrogels caused minor changes in their morphology, FTIR and thermal analyses confirmed these changes. Swelling degree and total porosity were reduced in the presence of microparticles, but similar hydrophilic and degradation in phosphate buffer solution behaviors were observed by all hydrogels. Rupture force and maximum strain at rupture were higher in the modified hydrogels, whereas modulus of elasticity was similar across all materials. Viability of primary human dental pulp cells up to 21 days was generally not influenced by the addition of PLGA@CBD microparticles. The control hydrogel showed no antimicrobial activity against Staphylococcus aureus, whereas hydrogels with 5% and 10% PLGA@CBD microparticles showed inhibition zones. In conclusion, the PLGA@CBD microparticles were fabricated and successfully embedded in a hydrogel matrix. Despite the hydrophobic nature of CBD, the physicochemical and morphological properties were generally similar for the hydrogels with and without the CBD-loaded microparticles. The data reported in this study suggested that this original biomaterial loaded with CBD oil has characteristics that could enable it to be used as a scaffold for tissue/cellular regeneration.

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Malaria can have severe long-term effects. Even after treatment with antimalarial drugs eliminates the parasite, survivors of cerebral malaria may suffer from irreversible brain damage, leading to cognitive deficits. Angiotensin II, a natural human peptide hormone that regulates blood pressure, has been shown to be active against Plasmodium spp., the etiologic agent of malaria. Here, we tested two Ang II derivatives that do not elicit vasoconstriction in mice: VIPF, a linear tetrapeptide, which constitutes part of the hydrophobic portion of Ang II; and Ang II-SS, a disulfide-bridged derivative. The antiplasmodial potential of both peptides was evaluated with two mouse models: an experimental cerebral malaria model and a mouse model of non-cerebral malaria. The latter consisted of BALB/c mice infected with Plasmodium berghei ANKA. The peptides had no effect on mean blood pressure and significantly reduced parasitemia in both mouse models. Both peptides reduced the SHIRPA score, an assay used to assess murine health and behavior. However, only the constrained derivative (Ang II-SS), which was also resistant to proteolytic degradation, significantly increased mouse survival. Here, we show that synthetic peptides derived from Ang II are capable of conferring protection against severe manifestations of malaria in mouse models while overcoming the vasoconstrictive side effects of the parent peptide.

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Cosmetic residues have been found in water resources, especially trace elements of precursors, couplers, and pigments of hair dyes, which are indiscriminately disposed of in the sewage system. These contaminants are persistent, bioactive, and bioaccumulative, and may pose risks to living beings. Thus, the present study assessed the ecotoxicity of two types of effluents generated in beauty salons after the hair dyeing process. The toxicity of effluent derived from capillary washing with water, shampoo, and conditioner (complete effluent-CE) and effluent not associated with these products (dye effluent-DE) was evaluated by tests carried out with the aquatic organisms Artemia salina, Daphnia similis, and Danio rerio. The bioindicators were exposed to pure samples and different dilutions of both effluents. The results showed toxicity in D. similis (CE50 of 3.43% and 0.54% for CE and DE, respectively); A. salina (LC50 8.327% and 3.874% for CE and DE, respectively); and D. rerio (LC50 of 4.25-4.59% and 7.33-8.18% for CE and DE, respectively). Given these results, we can infer that hair dyes, even at low concentrations, have a high toxic potential for aquatic biota, as they induced deleterious effects in all tested bioindicators.

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The purpose of this study was two-fold: (i) to investigate whether the thermal treatment of direct dental resin composites (RCs) using microwave or autoclave heating cycles would modify the materials' strength as compared to the protocol without heating (control); and (ii) to compare the mechanical performance of direct and indirect RCs. Three RCs (from 3M ESPE) were tested: one indirect (Sinfony); and two direct materials (microhybrid - Filtek Z250; and nanofilled - Filtek Z350). Specimens from the direct RCs were prepared and randomly allocated into three groups according to the thermal treatment (n = 10): Control - no thermal treatment was performed; Microwave - the wet heating was performed using a microwave oven; and Autoclave - the wet heating was performed in an autoclave oven. The indirect RC was prepared following the instructions of the manufacturer. All materials were tested using flexural strength, elastic modulus, work of fracture (Wf), microhardness, and scanning electron microscopy (SEM) analyses. Data were analyzed with ANOVA and Tukey as well as Weibull analysis (α = 0.05). The thermal treatments tended to produce slight changes in the topography of direct RCs, especially by the autoclave' wet heating. Overall, the physico-mechanical properties changed after thermal treatment, although this effect was dependent on the type of RC and on the heating protocol. Sinfony showed the lowest modulus and hardness of the study, although it was the most compliant system (higher work of fracture). The load-deflection ability was also greater for the indirect RC. Reliability of the tested materials was similar among each other (p > 0.05). In conclusion, the alternative thermal treatments suggested here may significantly influence some aspects of the mechanical behavior of dental resin composites, with negative effects relying on both the chemical composition of the restorative material as well as on the wet heating protocol used. Clinicians should be aware of the possible effects that additional wet heating of direct resin composites using microwave or autoclave thermal protocols as performed here could have on the overall fracture and mechanical responses during loading circumstances.

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Novel poly(vinyl alcohol)/chondroitin sulfate (PVA/CS) composite hydrogels containing hydroxyapatite (HA) or Sr-doped HA (HASr) particles were synthesized by a freeze/thaw method and characterized aiming towards biomedical applications. HA and HASr were synthesized by a wet-precipitation method and added to the composite hydrogels in fractions up to 15 wt%. Physical-chemical characterizations of particles and hydrogels included scanning electron microscopy, energy-dispersive spectroscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, thermogravimetry, porosity, compressive strength/elastic modulus, swelling degree, and cell viability. Particles were irregular in shape and appeared to have narrow size variation. The thermal behavior of composite hydrogels was altered compared to the control (bare) hydrogel. All hydrogels exhibited high porosity. HA/HASr particles reduced total porosity without reducing pore size. The mechanical strength was improved as the fraction of HA or HASr was increased. HASr particles led to a faster water uptake but did not interfere with the total hydrogel swelling capacity. In cell viability essay, increased cell growth (above 120%) was observed in all groups including the control hydrogel, suggesting a bioactive effect. In conclusion, PVA/CS hydrogels containing HA or HASr particles were successfully synthesized and showed promising morphological, mechanical, and swelling properties, which are particularly required for scaffolding.

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Despite all the advances in adhesive dentistry, dental bonds are still fragile due to degradation events that start during application of adhesive agents and the inherent hydrolysis of resin-dentin bonds. Here, we combined two outstanding processing methods (electrospinning and cryomilling) to obtain bioactive (antimicrobial and anti-metalloproteinase) fiber-based fillers containing a potent matrix metalloproteinase (MMP) inhibitor (doxycycline, DOX). Poly(ε)caprolactone solutions containing different DOX amounts (0, 5, 25, and 50 wt%) were processed via electrospinning, resulting in non-toxic submicron fibers with antimicrobial activity against Streptococcus mutans and Lactobacillus. The fibers were embedded in a resin blend, light-cured, and cryomilled for the preparation of fiber-containing fillers, which were investigated with antibacterial and in situ gelatin zymography analyzes. The fillers containing 0, 25, and 50 wt% DOX-releasing fibers were added to aliquots of a two-step, etch-and-rinse dental adhesive system. Mechanical strength, hardness, degree of conversion (DC), water sorption and solubility, bond strength to dentin, and nanoleakage analyses were performed to characterize the physico-mechanical, biological, and bonding properties of the modified adhesives. Statistical analyses (ANOVA; Kruskal-Wallis) were used when appropriate to analyze the data (α = 0.05). DOX-releasing fibers were successfully obtained, showing proper morphological architecture, cytocompatibility, drug release ability, slow degradation profile, and antibacterial activity. Reduced metalloproteinases (MMP-2 and MMP-9) activity was observed only for the DOX-containing fillers, which have also demonstrated antibacterial properties against tested bacteria. Adhesive resins modified with DOX-containing fillers demonstrated greater DC and similar mechanical properties as compared to the fiber-free adhesive (unfilled control). Concerning bonding performance to dentin, the experimental adhesives showed similar immediate bond strengths to the control. After 12 months of water storage, the fiber-modified adhesives (except the group consisting of 50 wt% DOX-loaded fillers) demonstrated stable bonds to dentin. Nanoleakage was similar among all groups investigated. DOX-releasing fibers showed promising application in developing novel dentin adhesives with potential therapeutic properties and MMP inhibition ability; antibacterial activity against relevant oral pathogens, without jeopardizing the physico-mechanical characteristics; and bonding performance of the adhesive.

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Background: Macroalgae are sources of bioactive compounds due to the large number of secondary metabolites they synthesize. The Antarctica region is characterized by extreme weather conditions and abundant aggregations of macroalgae. However, current knowledge on their biodiversity and their potential for bio-prospecting is still fledging. This study evaluates the antimicrobial and cytotoxic activity of different extracts of four macroalgae (Cystosphaera jacquinotii, Iridaea cordata, Himantothallus grandifolius, and Pyropia endiviifolia) from the Antarctic region against cancer and non-cancer cell lines. Methods: The antimicrobial activity of macroalgae was evaluated by the broth microdilution method. Extracts were assessed against Staphylococcus aureus ATCC 19095, Enterococcus faecalis ATCC 4083, Escherichia coli ATCC29214, Pseudomonas aeruginosa ATCC 9027, Candida albicans ATCC 62342, and the clinical isolates from the human oral cavity, namely, C. albicans (3), C. parapsilosis, C. glabrata, C. lipolytica, and C. famata. Cytotoxicity against human epidermoid carcinoma (A-431) and mouse embryonic fibroblast (NIH/3T3) cell lines was evaluated with MTT colorimetric assay. Results: An ethyl acetate extract of H. grandifolius showed noticeable antifungal activity against all fungal strains tested, including fluconazole-resistant samples. Cytotoxicity investigation with a cancer cell line revealed that the ethyl acetate extract of I. cordata was highly cytotoxic against A-431 cancer cell line, increasing the inhibitory ratio to 91.1 and 95.6% after 24 and 48 h exposure, respectively, for a concentration of 500 µg mL-1. Most of the algal extracts tested showed little or no cytotoxicity against fibroblasts. Conclusion: Data suggest that macroalgae extracts from Antarctica may represent a source of therapeutic agents. HIGHLIGHTS Different macroalgae samples from Antarctica were collected and the lyophilized biomass of each macroalgae was extracted sequentially with different solventsThe antimicrobial and anticancer potential of macroalgae extracts were evaluatedEthyl acetate extract of H. grandifolius showed noticeable antifungal activity against all the fungal strains tested, including fluconazole-resistant samplesEthyl acetate extract of I. cordata was highly cytotoxic against the A-431 cancer cell lineMost of the algal extracts tested showed little or no cytotoxicity against normal cell lines.

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To systematically review the literature to analyze the current trends and future perspectives of dental pulp capping materials through an analysis of scientific and technological data. This study is reported in accordance with the PRISMA Statement. Nine databases were screened: PubMed (MedLine), Lilacs, IBECS, BBO, Web of Science, Scopus, SciELO, Google Scholar, and The Cochrane Library. Additionally, the following patent applications were searched online in Questel Orbit (Paris, France), USPTO, EPO, JPO, INPI, and Patentscope databases. A total of 716 papers and 83 patents were included. Calcium hydroxide was the main type of material studied, especially for direct pulp capping, followed by MTA. Patents related to adhesives or resins increased from 1998 e 2008, while in the last years, a major increase was observed in bioactive materials (containing bioactive proteins), materials derived from MTA (calcium silicate, calcium phosphate and calcium aluminate-based cements) and MTA. It was possible to obtain a scientific and technological overview of pulp capping materials. MTA has shown favorable results in vital pulp therapy that seem to surpass the disadvantages of calcium hydroxide. Recent advances in bioactive materials and those derived from MTA have shown promising results that could improve biomaterials used in vital pulp treatments. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1358-1368, 2018.

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The aim of this study was to evaluate the morphological bone response in animal experiments by applying hydroxyapatite grafts in critical and non-critical size bone defects. Current report followed the guidelines established by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Animal experiments were selected by assessing repair of bone defects with hydroxyapatite as bone graft and with blood clot only as control. Eight articles were identified in specialized literature and included in the meta-analysis. Statistical analysis was carried out with a random-effect model (p = 0.05). Subgroup analyses were further performed to investigate bone repair in critical and non-critical bone defects. Comprehensive analysis of bone repair outcome showed a statistically significant difference between hydroxyapatite and blood clot control (p < 0.05). Subgroup analyses showed statistically significant difference for critical bone defects (p < 0.05). No statistically significant difference was reported in non-critical bone defects (p > 0.05). Although animal studies revealed a high risk of bias and results should be interpreted with caution, the literature suggests that non-critical bone defects may heal spontaneously and without the need of a bone graft. Conversely, when critical-size defects are present, the use of hydroxyapatite bone graft improves the bone repair process.

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This article reports the in vitro antiplasmodial activity of two endoperoxides of the class 1,2-dioxetanes against Plasmodium falciparum: bis(adamantyl)-1,2-dioxetane and 3,3,4,4-tetramethyl-1,2-dioxetane. The results reveal that bis(adamantyl)-1,2-dioxetane displays substantial antiplasmodial activity, at least two orders of magnitude higher than that of artemisinin, while 3,3,4,4-tetramethyl-1,2-dioxetane is less active.

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