Ultra-short laser processing of 3D bioceramic, porous scaffolds designed by freeze foaming method for orthopedic applications.

Bone substitutes are widely employed for applications in orthopedic surgery for the replacement of injured bone. Among the diverse methods that are used to design 3D bioceramic matrices, Freeze Foaming has gained attention, since it provides the ability to tune the shape of the created structures. One of the major problems related to these constructs is the lack of porosity at the outwards sides (holder) of the scaffold, thus reducing the cellular affinity and creating a rejection of the implant. In this research, we aimed to develop a bone scaffold with enhanced surface properties and improved cellular affinity. The main aim was to alter the biocompatibility characteristics of the 3D bioceramic constructs. We have produced three-dimensional, complex-shaped hollow shell structures, manufactured by Additive Manufacturing processes and as a second step, filled with a ceramic suspension by the Freeze-Foaming process. 3D constructs from HAP-derived TCP and TCP/ZrO2 were synthesized by freeze-foaming method and subsequently irradiated with a fs-laser (λ = 800 nm) spanning a range of parameters for achievement of optimal surface processing conditions. The designed scaffolds demonstrated enhanced topographical properties with improved porosity examined by SEM, EDX, and 3D profilometry after laser treatment. Wettability and computer tomography (CT) evaluation was also performed. The results from X-ray diffraction (XRD) and micro-Raman analysis did not show photochemical and surface or volume defects and changes after laser processing of the ceramic samples. Preliminary results from MG-63 osteoblast-like cell tests showed good cell affinity on the processed surfaces and no cytotoxic effect on the cells.

Osteoblasts-derived exosomes as potential novel communicators in particle-induced periprosthetic osteolysis.

The inflammatory response to wear particles derived from hip prothesis is considered a hallmark of periprosthetic osteolysis, which can ultimately lead to the need for revision surgery. Exosomes (Exos) have been associated with various bone pathologies, and there is increasing recognition in the literature that they actively transport molecules throughout the body. The role of wear particles in osteoblast-derived Exos is unknown, and the potential contribution of Exos to osteoimmune communication and periprosthetic osteolysis niche is still in its infancy. Given this, we investigate how titanium dioxide nanoparticles (TiO2 NPs), similar in size and composition to prosthetic wear particles, affect Exos biogenesis. Two osteoblastic cell models commonly used to study the response of osteoblasts to wear particles were selected as a proof of concept. The contribution of Exos to periprosthetic osteolysis was assessed by functional assays in which primary human macrophages were stimulated with bone-derived Exos. We demonstrated that TiO2 NPs enter multivesicular bodies, the nascent of Exos, altering osteoblast-derived Exos secretion and molecular cargo. No significant differences were observed in Exos morphology and size. However, functional assays reveal that Exos cargo enriched in uPA stimulates macrophages to a mixed M1 and M2 phenotype, inducing the release of pro- and anti-inflammatory signals characteristic of periprosthetic osteolysis. In addition, we demonstrated the expression of uPA in exosomes derived from the urine of patients with osteolysis. These results suggest that uPA can be a potential biomarker of osteolysis. In the future, uPa may serve as a possible non-invasive biomarker to identify patients at risk for peri-implant osteolysis.

Unveiling the Osteogenic Potential of Tetracyclines: A Comparative Study in Human Mesenchymal Stem Cells.

Tetracyclines (TCs) are a class of broad-spectrum antibiotics with diverse pharmacotherapeutic properties due to their various functional groups being attached to a common core structure. Beyond their antibacterial activity, TCs trigger pleiotropic effects on eukaryotic cells, including anti-inflammatory and potentially osteogenic capabilities. Consequently, TCs hold promise for repurposing in various clinical applications, including bone-related conditions. This study presents the first comprehensive comparison of the in vitro osteogenic potential of four TCs-tetracycline, doxycycline, minocycline, and sarecycline, within human mesenchymal stem cells. Cultures were characterized for metabolic activity, cell morphology and cytoskeleton organization, osteogenic gene expression, alkaline phosphatase (ALP) activity, and the activation of relevant signaling pathways. TCs stimulated actin remodeling processes, inducing morphological shifts consistent with osteogenic differentiation. Osteogenic gene expression and ALP activity supported the osteoinduction by TCs, demonstrating significant increases in ALP levels and the upregulation of RUNX2, SP7, and SPARC genes. Minocycline and sarecycline exhibited the most potent osteogenic induction, comparable to conventional osteogenic inducers. Signaling pathway analysis revealed that tetracycline and doxycycline activate the Wnt pathway, while minocycline and sarecycline upregulated Hedgehog signaling. Overall, the present findings suggest that TCs promote osteogenic differentiation through distinct pathways, making them promising candidates for targeted therapy in specific bone-related disorders.

Effect of the surface finish on the mechanical properties and cellular adhesion in (Ce,Y)-TZP/Al2O3 ceramic composites for denture implants.

Ceramic composites based on (Ce, Y)-TZP/Al2O3 system have great potential for applications as dental implants due to their unusually great balance between good mechanical properties and resistance to hydrothermal degradation. Surface roughness plays an important role in controlling these properties, but few studies have investigated the relationship between cytocompatibility and surface roughness, at levels considered moderate and low, comparable to titanium implants. In this work, bending strength, hydrothermal degradation and biological evaluation of a ceramic composite based on (Ce,Y)-TZP/Al2O3 system were investigated as a function of surface roughness. Compacted samples were sintered at 1500 °C - 2h and then submitted to different surface treatments: Group 1 composed of samples with smooth surfaces, Group 2 and Group 3 composed of rough surfaces (grinded with 15 µm or 45 µm diamond sandpaper, respectively. Samples were characterized by X-ray diffraction, scanning electron microscopy, contact angle and optical profilometry and then subjected to hydrothermal degradation tests in autoclave (134 °C - 2 bar) using artificial saliva. The Piston-on-three-balls (P-3B) testing was used to determine flexural strength. To assess indirect cytotoxicity, samples were immersed in the culture medium for NIH-3T3 cells for 72 h. Furthermore, cell adhesion and proliferation were investigated using MG63 cells (human osteosarcoma) after 3, 7, 14, and 21 days of culture. Cytotoxicity, adhesion, and cell proliferation were examined by the Methyl Tetrazolium salt (MTS) and Alizarin Red, using a confocal laser microscope. The results indicated that the materials have high resistance to degradation. Furthermore, the (Ce,Y)-TZP/Al2O3 composites are not cytotoxic. The flexural strength of the composites was 913 ± 103 MPa in samples presenting original (smooth) surface, however, a reduction in the order of 17% was observed in samples containing rough surfaces. The rougher samples show the best cellular adhesion and proliferation, leading to the formation of a mineralized matrix after 21 days. These results clearly suggest that the new (Ce,Y)-TZP/Al2O3 brand is strong and highly biocompatible and warrants further study.

Bone Cell Exosomes and Emerging Strategies in Bone Engineering.

Bone tissue remodeling is a highly regulated process balancing bone formation and resorption through complex cellular crosstalk between resident bone and microenvironment cells. This cellular communication is mediated by direct cell and cell-matrix contact, autocrine, endocrine, and paracrine receptor mediated mechanisms such as local soluble signaling molecules and extracellular vesicles including nanometer sized exosomes. An impairment in this balanced process leads to development of pathological conditions. Bone tissue engineering is an emerging interdisciplinary field with potential to address bone defects and disorders by synthesizing three-dimensional bone substitutes embedded with cells for clinical implantation. However, current cell-based therapeutic approaches have faced hurdles due to safety and ethical concerns, challenging their clinical translation. Recent studies on exosome-regulated bone homeostasis and regeneration have gained interest as prospective cell free therapy in conjugation with tissue engineered bone grafts. However, exosome research is still in its nascent stages of bone tissue engineering. In this review, we specifically describe the role of exosomes secreted by cells within bone microenvironment such as osteoblasts, osteocytes, osteoclasts, mesenchymal stem cell cells, immune cells, endothelial cells, and even tumor cells during bone homeostasis and crosstalk. We also review exosome-based osteoinductive functionalization strategies for various bone-based biomaterials such as ceramics, polymers, and metals in bone tissue engineering. We further highlight biomaterials as carrier agents for exosome delivery to bone defect sites and, finally, the influence of various biomaterials in modulation of cell exosome secretome.

The Development of Smoked Mackerel with Reduced Sodium Content.

The World Health Organization recommends reducing salt (sodium chloride, NaCl) intake by 30% by 2025. Since smoked fish can deliver up to 4 g NaCl/100 g, the aim of this study was to develop safe, healthy and attractive smoked chub mackerel (Scomber japonicus) with a reduced NaCl content. Two brines (5% and 10%) were used with different ratios of NaCl and potassium chloride (KCl). In each brine, 0%, 25%, 50% and 75% of NaCl was replaced by KCl, resulting in 1.3, 1.1, 0.9 and 0.6 g NaCl (5% brine), and 2.6, 2.0, 1.2 and 0.8 g NaCl (10% brine) per 100 g, respectively. Similar yield, nutritional, safety, texture and colour properties were found in most formulations. The most desirable taste attributes (negligible bitterness and adequate saltiness) were obtained with a 5% brine prepared with 75% NaCl + 25% KCl. Such conditions seemed to allow for obtaining an attractive product for conscious consumers.

Pharmacogenetic and pharmacokinetic assays from saliva samples can guarantee personalized drug prescription

Abstract Saliva is widely used for clinical and laboratory analysis. This study proposed to use DNA extracted from saliva for genotyping and pharmacokinetics of piroxicam. A fast and efficient genotyping method was used to determine relevant allelic variants of CYP2C9 (*2 and *3), since genetic factors can influence in non-steroidal anti-inflammatory drugs (NSAIDs) metabolization. DNA Extract All Reagents Kit® was used for DNA extraction and genotyping was performed using TaqMan® GTXpress™ Master Mix, SNP genotyping assays and a Viia7 Real-Time PCR system. Volunteers performed sequential collections of saliva samples before and after taking a single dose of piroxicam (0.25 to 72 h) which were used for pharmacokinetics assays. Piroxicam concentrations were analyzed using LC-MS/MS. Sixty-six percent of volunteers were ancestral homozygous (CYP2C9*1/*1), and 34% showed one or both polymorphisms. Of these 34%, 22 individuals showed CYP2C9*2 polymorphism, 8 CYP2C9*3, and 4 CYP2C9*2/*3. Piroxicam pharmacokinetics were performed in 5 subjects. Areas under the curve (AUC0-t(h*ng/mL)) for CYP2C9*1/*1, *1/*2 and *1/*3 were, respectively, 194.33±70.93, 166 and 303. Maximum concentrations (Cmax(ng/mL)) for these genotypes were respectively 6.46±2.56, 4.3 and 10.2. Saliva sampling was a very effective matrix for both pharmacogenetic and pharmacokinetic tests, ensuring the speed of the procedure and the well-being and agreement of the participants. Once having the knowledge about the slow and fast metabolizers, it is possible to make an adequate prescription in order to avoid the adverse effects of the medication and to guarantee greater analgesic comfort to the patients respectively.

Resumo Saliva é amplamente utilizada para análises clínicas e laboratoriais. Este estudo propôs o uso de DNA extraído da saliva para genotipagem e farmacocinética do piroxicam. Um método de genotipagem rápido e eficiente foi usado para determinar as variantes alélicas clinicamente relevantes de CYP2C9 (* 2 e * 3), uma vez que fatores genéticos podem influenciar nas respostas metabólicas individuais a medicamentos como anti-inflamatórios não esteroides (AINEs). DNA Extract All Reagents Kit® foi usado para extração de DNA e a genotipagem foi realizada usando TaqMan® GTXpress ™ Master Mix, ensaios de genotipagem SNP e um sistema Viia7 Real-Time PCR. Os voluntários realizaram coletas sequenciais de amostras de saliva antes e após a ingestão de uma única dose de piroxicam (0,25 a 72 h) que foram utilizadas para ensaios farmacocinéticos. As concentrações de piroxicam foram analisadas usando LC - MS / MS. Sessenta e seis por cento dos voluntários eram homozigotos ancestrais (CYP2C9 * 1 / * 1) e 34% apresentaram um ou ambos os polimorfismos. Destes 34%, 22 indivíduos apresentaram polimorfismo CYP2C9 * 2, 8 CYP2C9 * 3 e 4 CYP2C9 * 2 / * 3. A farmacocinética do piroxicam foi realizada em 5 indivíduos. As áreas sob a curva (AUC0-t (h * ng / mL)) para CYP2C9 * 1 / * 1, * 1 / * 2 e * 1 / * 3 foram, respectivamente, 194,33±70,93, 166 e 303. Concentrações máximas (Cmax (ng / mL)) para esses genótipos foram, respectivamente, 6,46±2,56, 4,3 e 10,2. A amostra de saliva foi uma matriz muito eficaz tanto para os testes farmacogenéticos quanto para os farmacocinéticos, garantindo a agilidade do procedimento e o bem-estar e concordância dos participantes. Com o conhecimento dos metabolizadores lentos e rápidos, é possível fazer uma prescrição adequada para evitar os efeitos adversos da medicação e garantir maior conforto analgésico aos pacientes respectivamente.

Effects of 660-nm and 780-nm Laser Therapy on ST88-14 Schwann Cells.

The aim of the present study was to evaluate the comparative effects of red (660-nm) and near-infrared (780-nm) low-level laser therapy (LLLT) on viability, mitochondrial activity, morphology and gene expression of growth factors on Schwann cells (SC). ST88-14 cells were grown in RPMI 1640 with 10 mM of HEPES, 2 mM of glutamine, 10% fetal bovine serum and 1% antibiotic-antimycotic solution at 37°C in humidified atmosphere of 5% CO2 . Cells were detached with trypsin and centrifugated at 231 g for 5 min at 10°C, and the pellet (8 × 104  cells/tube) was irradiated at the bottom of 50 ml polypropylene tube with a Twin-Laser system (660 and 780 nm, 40 mW, 1 mW cm-2 , 3.2 and 6.4 J, 80 and 160 J cm-2 with 80 and 160 s). After 1, 3 and 7 days, the analysis was performed. After irradiation, the SC increase mitochondrial activity, gene expression of the neural growth factors NGF and BDNF, and cell migration and increase the G2/M cells. SC showed neuronal morphology, normal F-actin cytoskeleton organization and positive labeling for S100. PBM increased metabolic activity, mitosis and gene expression when irradiated with red and infrared LLLT. An increase in cell migration was obtained when irradiated with infrared LLLT.

Genotoxicity of root canal sealers: a literature review.

OBJECTIVES: Root canal sealers are widely used worldwide in endodontics to prevent reinfection and growth of surviving microorganisms. Considering the strong correlation between genetic damage and carcinogenesis, evaluation of genotoxicity induced by endodontic sealers is recommended for elucidating the true health risks to patients and professionals. The purpose of this article was to provide a comprehensive review of studies involving genotoxicity analysis of endodontic sealers and the used methodologies. MATERIALS AND METHODS: A literature search was made in PubMed using the following combination of words "genotoxicity," "mutagenicity," "endodontic sealers," and "root canal sealers." A total of 39 articles with genotoxicity studies were selected for the present study. RESULTS: Sealers have been ranked in decreasing order of their genotoxicity as: ZOE sealers > GIC sealers > S sealers > ER sealers > MR sealers > Novel sealers > CH sealers > CS sealers. CONCLUSIONS: All published data showed some evidence of genotoxicity for most of the commercial root canal sealers; however, contradictory results were found, mainly for AH Plus, the most studied sealer. CLINICAL RELEVANCE: The information provided would direct the endodontists to use the less genotoxic materials in endodontic treatment in a way to reduce DNA damage promoting oral healthcare.

Doxycycline restores the impaired osteogenic commitment of diabetic-derived bone marrow mesenchymal stromal cells by increasing the canonical WNT signaling.

Diabetes mellitus comprehends a group of chronic metabolic disorders, associated with damage and dysfunction of distinct tissues, including bone. At the cellular level, an impaired osteoblastogenesis has been reported, affecting the viability, proliferation and functionality of osteoblasts and precursor populations, hampering the bone metabolic activity, remodeling and healing. Tetracyclines embrace a group of broad-spectrum antibacterial compounds with potential anabolic effects on the bone tissue, through antibacterial-independent mechanisms. Accordingly, this study aims to address the modulatory capability and associated molecular signaling of a low dosage doxycycline - a semi-synthetic tetracycline, in the functional activity of osteoblastic progenitor cells (bone marrow-derived mesenchymal stromal cells), established from a translational diabetic experimental model. Bone marrow-derived mesenchymal stromal cells were isolated from streptozotocin-induced diabetic Wistar rat with proven osteopenia. Cultures were characterized, in the presence of doxycycline (1 µg ml-1) for proliferation, metabolic activity, apoptosis, collagen synthesis and relevant gene expression with the osteogenic and adipogenic program. The activation of the Wnt/ß-catenin pathway was further detailed. Doxycycline normalized the viability, proliferation and metabolic activity of the established cultures, further decreasing cell apoptosis, to levels similar to control. The addition of this drug to the culture environment further increased the osteogenic activation, upregulating the expression of osteogenic markers and collagen synthesis, at the same time that a decreased adipogenic priming was attained. These processes were found to me mediated, at least in part, by the restoration of the signaling through the Wnt/ß-catenin pathway.

Dry-Cured Meat Products According to the Smoking Regime: Process Optimization to Control Polycyclic Aromatic Hydrocarbons.

The manufacturing of dry-cured meat products usually includes a smoking step. Polycyclic aromatic hydrocarbons (PAHs) are potentially carcinogenic chemical compounds that may result from smoking. The aim of the present study was to optimize the smoking regime of traditional dry-cured meat products in order to minimize the presence of PAHs. Dry-cured sausages were submitted to different smoking regimes: (A) no smoking; (B) 20 h effective smoking; (C) 60 h effective smoking; (D) effective smoking until reaching 38%-40% weight losses. Three independent batches were produced per smoking regime, and three samples per batch were analyzed. Microbiological, physicochemical, and sensory analyses were performed. The total PAHs content was generally low and did not differ significantly in meat products submitted to the four different smoking regimes. The PAH4 and benzo(α)pyrene levels were below the established legal limits in all analyzed dry-cured sausages. Nevertheless, non-smoked sausages always showed lower PAHs values for all PAHs groups.

Molecular and Cellular Aspects of Socket Healing in the Absence and Presence of Graft Materials and Autologous Platelet Concentrates: a Focused Review.

OBJECTIVES: The present manuscript aims to critically detail the physiologic process of socket healing, in the absence or presence of grafting materials or platelet concentrates, addressing the associated molecular and cellular events that culminate in the restoration of the lost tissue architecture and functionality. MATERIAL AND METHODS: An electronic search in the National Library of Medicine database MEDLINE through its online site PubMed and Web of Science from inception until May 2019 was conducted to identify articles concerning physiologic process of socket healing, in the absence or presence of grafting materials or platelet concentrates. The search was restricted to English language articles without time restriction. Additionally, a hand search was carried out in oral surgery, periodontology and dental implants related journals. RESULTS: In total, 122 literature sources were obtained and reviewed. The detailed biological events, at the molecular and cellular level, that occur in the alveolus after tooth extraction and socket healing process modulated by grafting materials or autologous platelet concentrates were presented as two entities. CONCLUSIONS: Tooth extraction initiates a convoluted set of orderly biological events in the alveolus, aiming wound closure and socket healing. The healing process comprises a wide range of events, regulated by the interplay of cytokines, chemokines and growth factors that determine cellular recruitment, proliferation and differentiation in the healing milieu, in a space- and time-dependent choreographic interplay. Additionally, the healing process may further be modulated by the implantation of grafting materials or autologous platelet concentrates within the tooth socket, aiming to enhance the regenerative outcome.

What is the Main Processing Factor Influencing Staphylococcus Species Diversity in Different Manufacturing Units?

The microbiota of traditional dry-cured sausages and industrial environment was assessed to characterize the diversity of coagulase-negative staphylococci (CNS), and establish potential relationships with hygiene level or technological characteristics. Eight processing units from South Portugal were audited according to a checklist of requirements. Environmental and products' samples at different production stages were evaluated regarding hygiene and safety criteria. CNS were recovered, characterized, and their potential use as starters evaluated. Low genetic diversity was observed for Staphylococcus xylosus, whereas Staphylococcus equorum showed diverse genetic profiles. Staphylococcus xylosus predominated in products with a long period of cold smoking, Staphylococcus saprophyticus in products with a long period of hot smoking, Staphylococcus epidermidis in products with a short period of cold smoking, and S. equorum in nonsmoked products. Most S. xylosus were resistant to tetracycline, whereas S. equorum were susceptible. Antibioresistance restricted the selection of starters due to safety recommendations. PRACTICAL APPLICATION: The present manuscript highlighted a few staphylococci strains that could potentially be used as starter cultures in fermented meat products. These selected strains do not show resistance to antimicrobials, exhibit adequate technological features, and are well adapted to the industrial environments of meat processing industries using different processing technologies. Therefore, the selected strains ready to be used in the manufacturing of traditional fermented meat products to ensure safety, standardize product properties, and shorten ripening.

Effect of low power laser in biomodulation of cultured osteoblastic cells of Wistar rats1.

PURPOSE: To analyze aspects of the biomodulating effect of light in biological tissues, bone cells from surgical explants of the femur of rats were irradiated with low intensity laser. METHODS: Bone cells were cultured and irradiated with LASER light (GaAlAs). Growth, cell viability, mineralized matrix formation, total protein dosage, immunostimulatory properties, cytochemical analysis, gene expression of bone proteins were examined using live cell imaging and cell counting by colorimetric assay. The gene expression of: alkaline phosphatase (ALP), type 1 collagen, osteocalcin and osteopontin through the real-time polymerase chain reaction. RESULTS: At 8 days, the viability of the irradiated culture was 82.3% and 72.4% in non-irradiated cells. At 18 days, the cellular viability (with laser) was 77.42% and 47.62% without laser. At 8 days, the total protein concentration was 21.622 mg / mol in the irradiated group and 16, 604 mg / mol in the non-irradiated group and at 18 days the concentration was 37.25 mg / mol in the irradiated group and 24, 95 mg / mol in the non-irradiated group. CONCLUSION: The laser interfered in the histochemical reaction, cell viability, matrix mineralization, and maintained the cellular expression of proteins.

Photobiomodulation is associated with a decrease in cell viability and migration in oral squamous cell carcinoma.

The treatment of squamous cell carcinoma (SCC) involves surgery, chemotherapy, and/or radiotherapy, which can cause mucositis (inflammation of the oral mucosa that causes considerable pain and can compromise the continuity of oncological treatment). Photobiomodulation (PBM) has been successfully used in the treatment of mucositis, but doubts arise regarding the use of laser for areas in which tumor cells may remain. In this study, the effect of PBM on the viability, mitochondrial activity, proliferation, apoptosis, and migration of cells derived from oral SCC was evaluated. SCC9 cells were irradiated with laser (660 and 780 nm, using 11 dosimetric parameters) and submitted to mitochondrial and caspase 3 activity tests after 1 and 3 days. Based on the results, cell viability (neutral red assay), proliferation (BrdU assay), and migration (scratch-wound assay) were evaluated using only the dosimetric parameters recommended for mucositis. Non-irradiated cells served as the control. The experiments were performed in triplicate. The 11 parameters diminished mitochondrial activity and induced tumor cell apoptosis. Using the parameters recommended for mucositis, irradiation with 780 nm (70 mW, 4 J/cm2) proved to be the safest and led to a reduction in cell viability, the induction of apoptosis, and a reduction in the migration capacity of the tumor cells.

Effect of low power laser in biomodulation of cultured osteoblastic cells of Wistar rats

Abstract Purpose: To analyze aspects of the biomodulating effect of light in biological tissues, bone cells from surgical explants of the femur of rats were irradiated with low intensity laser. Methods: Bone cells were cultured and irradiated with LASER light (GaAlAs). Growth, cell viability, mineralized matrix formation, total protein dosage, immunostimulatory properties, cytochemical analysis, gene expression of bone proteins were examined using live cell imaging and cell counting by colorimetric assay. The gene expression of: alkaline phosphatase (ALP), type 1 collagen, osteocalcin and osteopontin through the real-time polymerase chain reaction. Results: At 8 days, the viability of the irradiated culture was 82.3% and 72.4% in non-irradiated cells. At 18 days, the cellular viability (with laser) was 77.42% and 47.62% without laser. At 8 days, the total protein concentration was 21.622 mg / mol in the irradiated group and 16, 604 mg / mol in the non-irradiated group and at 18 days the concentration was 37.25 mg / mol in the irradiated group and 24, 95 mg / mol in the non-irradiated group. Conclusion: The laser interfered in the histochemical reaction, cell viability, matrix mineralization, and maintained the cellular expression of proteins

Modulation of human osteoclastogenesis and osteoblastogenesis by lycopene.

Lycopene is a lipid-soluble pigment that is mainly found in tomato. It is the carotenoid that presents the highest antioxidant potential, and due to that, it has been implicated in a decrease of the risk of several oxidative-stress-related disorders, such as cancer, inflammatory diseases and osteoporosis. Nevertheless, at the present, there is no detailed information about how lycopene affects bone metabolism. The aim of the present work was to characterize the cellular and molecular effects of lycopene on human osteoclast and osteoblast differentiation and function. It was observed that lycopene, at levels found in plasma after the ingestion of lycopene-containing products, decreased osteoclast differentiation but did not affect cell density/survival; calcium-phosphate resorbing ability was also decreased. On the other hand, osteoblast proliferation (via a decrease on apoptosis) and differentiation were increased in the presence of lycopene. The observed effects in both cell types appeared to be related to significant changes in MEK signaling pathway, but also in protein kinase C pathway in osteoclasts and NFkB signaling in osteoblasts. In conclusion, lycopene appears to promote an anabolic state of bone metabolism, stimulating osteoblastogenesis and inhibiting osteoclastogenesis, which may contribute to the promotion of a proper health status of bone tissue. This information might be relevant for the prevention and delay in the progression of osteolytic bone conditions.

The Anticancer Potential of Ionic Liquids.

Among the many challenges that the pharmaceutical industry currently faces is the need to develop innovative and effective therapies. The investigation of alternative and effective therapies against cancer is a current goal of the pharmaceutical industry. Ionic liquids (ILs) have emerged recently as a topic of study by researchers in the pharmaceutical industry in their search for new therapeutic agents. By definition, ILs are organic salts with melting points below 100 °C that are composed only by ions. Their main advantage lies in the numerous possible combinations of cations and anions, which allow adjustments in their physicochemical properties. The combination between ILs and active pharmaceutical ingredients (APIs) may improve the properties of APIs. In addition, the antitumor properties of these compounds have been described. Several studies have reported the use of ILs in biomedical applications as therapeutic agents, namely as antitumor agents. This review describes the recent proposed applications of ILs as antitumor agents.

A anorexia e a bulimia: entre o corpo, o eu e o outro / Anorexia and bulimia: between the body, the ego and the other

O comportamento alimentar, originário e essencial desde o nascimento, remete o sujeito à complexidade da sua relação com o próprio corpo, marca indelével dos efeitos da alteridade. A clínica psicanalítica da anorexia e da bulimia, por sua vez, nos confronta de saída com a questão do corpo, assim como nos coloca diante da especificidade dos processos da adolescência. Tal especificidade evoca as vicissitudes da relação precoce com a mãe no que diz respeito ao gerenciamento pulsional e sua relação com a identificação primária e, consequentemente, com os ideais, a diferenciação, a autonomia, o tempo e a morte. Este artigo traz para a discussão algumas hipóteses, elaboradas a partir da metapsicologia, com o objetivo de contribuir para uma melhor compreensão do processo de construção da imagem corporal. Destaca que o investimento materno, através da escuta e interpretação das sensações corporais realizadas pela mãe, vai construindo para o bebê a imagem de seu corpo e assim sua identidade. Para concluir, enfatiza os possíveis desdobramentos dessa construção teórica na escuta do analista diante das particularidades do manejo transferencial desses casos(AU)

The eating behavior, originating and essential since birth, makes the individual aware of the complex relationship with his own body, an indelible mark of the effects of alterity. On the other hand, the psychoanalytical practice related to anorexia and bulimia immediately confront us with the issue of the body, as well as with the specific processes of adolescence. Such specificities evoke the vicissitudes of the early relationship with the mother regarding the management of the drives and the relationship with primary identification and consequently with ideals, differentiation, autonomy, time and death. This paper discusses some hypotheses based on metapsychology, with the aim of providing a better understanding of the process of constructing the body image. It stresses that the maternal investment, by listening and interpreting the bodily sensations, builds the baby's image of his own body and, therefore, his identity. Finally, it emphasizes the possible repercussions of that theoretical construction in the analyst's listening, given the peculiarities of the transference management in such cases(AU)

El comportamiento alimentario, originario y esencial desde el nacimiento, remite al sujeto a su relación con el propio cuerpo, marca indeleble de los efectos de la alteridad. La clínica psicoanalítica de la anorexia y de la bulimia, a su vez, nos enfrenta de inmediato a la cuestión del cuerpo y a la especificidad de los procesos de la adolescencia. Esa especificidad evoca las vicisitudes de la relación precoz con la madre en lo que dice respecto al manejo pulsional y a su relación con la identificación primaria y, en consecuencia, con los ideales, la diferenciación, la autonomía, el tiempo y la muerte. En este artículo se ponen sobre el tapete algunas hipótesis, elaboradas a partir de la metapsicología, con el objetivo de contribuir a una mejor comprensión del proceso de construcción de la imagen corporal. Se resalta que la investidura materna, por medio de la escucha e interpretación de las sensaciones corporales realizadas por la madre, va construyendo para el bebé la imagen de su cuerpo y, así, su identidad. Para concluir, se enfatizan las posibles repercusiones de dicha construcción teórica en la escucha del analista ante las particularidades del manejo transferencial de esos casos(AU)