Involvement of GPR43 Receptor in Effect of Lacticaseibacillus rhamnosus on Murine Steroid Resistant Chronic Obstructive Pulmonary Disease: Relevance to Pro-Inflammatory Mediators and Oxidative Stress in Human Macrophages.

BACKGROUND: Cytokine storm and oxidative stress are present in chronic obstructive pulmonary disease (COPD). Individuals with COPD present high levels of NF-κB-associated cytokines and pro-oxidant agents as well as low levels of Nrf2-associated antioxidants. This condition creates a steroid-resistant inflammatory microenvironment. Lacticaseibacillus rhamnosus (Lr) is a known anti-cytokine in lung diseases; however, the effect of Lr on lung inflammation and oxidative stress in steroid-resistant COPD mice remains unknown. OBJECTIVE: Thus, we investigated the Lr effect on lung inflammation and oxidative stress in mice and macrophages exposed to cigarette smoke extract (CSE) and unresponsive to steroids. METHODS: Mice and macrophages received dexamethasone or GLPG-094 (a GPR43 inhibitor), and only the macrophages received butyrate (but), all treatments being given before CSE. Lung inflammation was evaluated from the leukocyte population, airway remodeling, cytokines, and NF-κB. Oxidative stress disturbance was measured from ROS, 8-isoprostane, NADPH oxidase, TBARS, SOD, catalase, HO-1, and Nrf2. RESULTS: Lr attenuated cellularity, mucus, collagen, cytokines, ROS, 8-isoprostane, NADPH oxidase, and TBARS. Otherwise, SOD, catalase, HO-1, and Nrf2 were upregulated in Lr-treated COPD mice. Anti-cytokine and antioxidant effects of butyrate also occurred in CSE-exposed macrophages. GLPG-094 rendered Lr and butyrate less effective. CONCLUSIONS: Lr attenuates lung inflammation and oxidative stress in COPD mice, suggesting the presence of a GPR43 receptor-dependent mechanism also found in macrophages.

Expression of HOXA10 and HOXA11 in the endometrium of infertile patients with chronic endometritis.

OBJECTIVE: The study aimed to evaluate the impact of CE on the expression of HOXA10 and HOXA11 during the late proliferative phase in the endometrium of infertile women. METHODS: A prospective, translational cohort study was conducted in partnership with the Hospital Universitário Antônio Pedro in Niterói and the Clínica Ginendo in Rio de Janeiro after approval by the Ethics Committee. The patients were selected to participate in the study after showing an indication for hysteroscopy. All participants were divided into three groups: infertile women with endometritis (n=10), infertile women without endometritis (n=17) and fertile women without endometritis (n=10). At hysteroscopy, two endometrial samples were obtaneid, with one sent for histopathological examination per the gynecologist's request and the other used for immunohistochemistry procedures to evaluate the expression of CD138, HOXA10 and HOXA11. CD138 was used to confirm the diagnosis of CE. The analysis of HOXA10 and HOXA11 was performed using the HScoring method for immunohistochemistry with polyclonal antibodies. RESULTS: Women with and without endometritis had lower HOXA10 and HOXA11 expression values than women in the control group (fertile women without endometritis). CONCLUSIONS: The expression of HOXA10 and HOXA11 during the proliferative phase is not significantly different between infertile women with endometritis and infertile women without endometritis. Translational studies with a larger number of patients should be performed.

Vitamin D loaded into lipid nanoparticles shows insulinotropic effect in INS-1E cells.

Increasing evidence suggests a beneficial role of vitamin D (VitD) supplementation in addressing the widespread VitD deficiency, but currently used VitD3 formulations present low bioavailability and toxicity constrains. Hence, poly(L-lactide-co-glycolide) (PLGA) nanoparticles (NPs), solid-lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) were investigated to circumvent these issues. PLGA NPs prepared by emulsification or nanoprecipitation presented 74 or 200 nm, and association efficiency (AE) of 68 % and 17 %, respectively, and a rapid burst release of VitD3. Both SLN and NLCs presented higher polydispersity and larger NPs size, around 500 nm, which could be reduced to around 200 nm by use of hot high-pressure homogenization in the case of NLCs. VitD3 was efficiently loaded in both SLNs and NLCs with an AE of 82 and 99 %, respectively. While SLNs showed burst release, NLCs allowed a sustained release of VitD3 for nearly one month. Furthermore, NLCs showed high stability with maintenance of VitD3 loading for up to one month at 4 °C and no cytotoxic effects on INS-1E cells up to 72 h. A trending increase (around 30 %) on glucose-dependent insulin secretion was observed by INS-1E cells pre-treated with VitD3. This effect was consistently observed in the free form and after loading on NLCs. Overall, this work contributed to further elucidation on a suitable delivery system for VitD3 and on the effects of this metabolite on ß cell function.

Energy efficiency in winemaking industry: Challenges and opportunities.

The United Nations has issued a warning over the limited time for climate disaster prevention. In the last two decades, several countries have set targets to reduce fossil fuel usage and greenhouse gas emissions. These goals are tracked through the adoption of energy systems that prioritise efficiency and low-carbon alternatives, in alignment with the Sustainable Development Goals outlined by the United Nations. In the winemaking sector, the wine produced in the European Union comprised 65 % of the worldwide total from 2014 to 2018, with vineyards making up 4.7 % of its farms in 2020. Electricity is the primary source of energy used in vineries, accounting for around 90 % of the total energy consumption. The energy consumption associated with winemaking is mostly attributed to two key processes: fermentation, which accounts for 45 % to 90 % of the entire energy consumption, and bottling and storage, which contribute around 18 % of the overall energy consumption. The aim of this article is to provide an integrated review of energy efficiency in wineries through examining 144 academic publications. The selected publications cover various aspects, including sustainable energy utilisation in the wine industry, thermal performance analysis of buildings, energy efficiency assessment of systems and technologies, and the integration of renewable energy sources. A link has been established between the geographic distribution of academic publications and wine-producing countries. In relation to European publications, it is observed that research funding is associated with the energy directives of the European Union. It can also be concluded that wine customers are pushing for environmentally friendly practices. However, not everyone in the winemaking sector is moving in the same direction or at the same pace. To identify areas for improvement, winemakers must have supporting tools to manage energy use. Systems optimisation, monitoring, and accounting can be used to decrease energy consumption in winemaking processes or equipment. Progresses on sustainable energy use through greater energy efficiency and share of renewable energies in the wineries can contribute to the reduction of greenhouse gas emissions, and consequently, brings the wine industry closer to climate neutrality.

Antifungal Susceptibility Assessment of Innovative and Non-Conventional Lime Mortars Incorporating Almond-Shell Powder Bio-Waste Subjected to Particle-Dispersion Technique.

A favorable environment for fungi colonization in building materials' surfaces can emerge when certain hygrothermal conditions occur. Thus, reducing fungal growth susceptibility is of major interest. Furthermore, if the integration of bio-wastes is performed in parallel with the development of innovative materials for this purpose, a more sustainable and environmentally friendly material can be obtained. In this study, the fungal susceptibility of lime mortars incorporating almond-shell powder (ASP) microparticles (2 and 4%, wt.-wt. in relation to the binder content) was evaluated. The particle-dispersion technique was employed to prepare the bio-waste introduced in the mixtures. The fungal susceptibility of ASP samples was compared with nanotitania (n-TiO2) with recognized antifungal properties. Mechanical strength, water absorption, and wettability tests were also performed for a better characterization of the composites. Although the addition of 2% ASP led to mechanical properties reduction, an increase in the compressive and flexural strength resulted for 4% of the ASP content. Difficulties in fungal growth were observed for the samples incorporating ASP. No fungal development was detected in the mortar with 2% of ASP, which may be correlated with an increase in the surface hydrophobic behavior. Furthermore, mortars with ASP revealed a reduction in water absorption by capillarity ability, especially with 4% content, suggesting changes in the microstructure and pore characteristics. The results also demonstrated that an improvement in the physical and mechanical properties of the lime mortars can be achieved when ASP microparticles are previously subjected to dispersion techniques.

Multiple behavioral risk factors for non-communicable diseases among the adolescent population in Brazil: the analysis derived from the Brazilian national survey of school health 2019.

BACKGROUND: Health risk behaviors often emerge or intensify during adolescence and tend to co-occur, exposing individuals to an even greater risk for the development of non-communicable diseases (NCDs). The likelihood of exhibiting multiple health risk factors also increases throughout life and is associated with sociodemographic characteristics contributing to their escalation and severity. In this context, the objective of this study was to analyze the association between sociodemographic characteristics and multiple behavioral risk factors for non-communicable diseases among the adolescent population in Brazil. METHODS: This cross-sectional study utilized data from the Brazilian National Survey of School Health 2019. The sample comprised 121,580 adolescents aged 13 to 17. The analyzed variables included irregular intake of fruits and vegetables, regular consumption of soft drinks and treats, insufficient physical activity, sedentary lifestyle, cigarette smoking, and alcohol consumption. To analyze MBRFs, a classification ranging from zero to five was created, and associations were estimated using Odds Ratio (OR) with the respective 95% confidence interval (CI). The Backward method was employed for the multivariate regression model, utilizing ordinal logistic regression. RESULTS: Adolescents without behavioral risk factors for NCDs constituted only 3.9% (95% CI 3.7-4.1). The most prevalent categories were two and three MBRFs, accounting for 28.3% (95% CI: 27.7-28.8) and 27.0% (95% CI: 26.5-27.5), respectively. Adolescents aged 16 and 17 (ORadj: 1.39; 95% CI: 1.32-1.48), residing in the Brazilian Southeast (ORadj: 1.66; 95% CI: 1.52-1.81), and those reporting poor or very poor self-rated health (ORadj: 2.05; 95% CI: 1.87-2.25) were more likely to exhibit multiple behavioral risk factors. Conversely, male adolescents (adjusted OR: 0.65; 95% CI: 0.62-0.69), those of mixed race (adjusted OR: 0.92; 95% CI: 0.87-0.97), and residents of rural areas (adjusted OR: 0.76; 95% CI: 0.70-0.84) were less likely to manifest MBRFs for NCDs. CONCLUSION: The majority of adolescents displayed MBRFs for NCDs, positively associated with age, region, and perceived health status. This underscores the necessity for healthcare promotional interventions throughout the life cycle, as these behaviors may persist into adulthood.

Beyond the Modernist Project: A Decolonial Turn in the History of Psychology.

In this article, the authors argue for a decolonial history of psychology that will assist in the creation of psychologies (and their histories) that are true to place and time. We briefly place contemporary history of psychology as being of service to hegemonic psychology, which has continued to enforce a coloniality of being, knowing, and doing. We outline some of its limitations in regard to individualism, neoliberalism, and the ideologies of the market. In contrast, we articulate a way to begin to reconceptualize a psychology and its history that may serve to honor and respect multiple ways of knowing and being. We offer examples of emergent approaches that are being created that are non-dualistic, non-WEIRD, and focused on lived experiences in particular places and settings. The authors are mindful of the limitations of offering superabundant examples of each point due to the length constraints that accompanied the invitation to submit this manuscript. We encourage interested readers to explore the references for additional nuances and examples of the main points.

Listeriosis in Pregnancy: A Rare but High-Risk Infection.

Listeriosis is a rare infection among the general population, with an estimated incidence in Europe of 0.49 cases per 100,000 habitants in 2021. During pregnancy, the incidence rises around ten times, peaking in the third trimester. While maternal consequences are usually mild, the potential for severe fetal and neonatal outcomes exists, leading to fetal loss, prematurity, neonatal sepsis, meningitis, and mortality. In the newborn, the clinical presentation and outcomes are associated with both gestational timing of infection and birth gestational age. We report a case of a pregnant woman with fever and nonspecific symptoms during the second trimester, leading to the diagnosis of Listeria bacteremia. We describe the steps for diagnostics, evolution, and complications and the importance of the differential diagnosis when evaluating pregnant patients.

Prevalence and factors associated with possible cases of familial hypercholesterolemia in Brazilian adults: a cross-sectional study.

This study aimed to estimate the prevalence of possible cases of FH and analyze associated factors in the adult Brazilian population. Cross-sectional study with laboratory data from the Brazilian National Health Survey, with 8521 participants. Possible cases of FH were defined according to the Dutch Lipid Clinic Network criteria. The prevalence and 95% confidence intervals (95% CI) of possible cases of FH were estimated according to sociodemographic variables, lifestyle, diabetes, hypertension, altered tests, treatment and self-rated health. Logistic regression was used to analyze the associations. The prevalence of possible cases of FH was 0.96%, higher in women, between 45 and 59 years, white race/skin color and others, less education, people with diabetes, hypertension and total cholesterol ≥ 310 mg/dL. The presence of FH was positively associated with regular self-rated health (OR 1.96; 95% CI 0.99-3.84), poor/very poor (OR 3.02; 95% CI 1.30-7.03) and negatively with black race/skin color (OR 0.10; 95% CI 0.02-0.46) and complete elementary school, incomplete high school (OR 0.47; 95% CI 0.23-0.98) and complete high school and more (OR 0.45; 95% CI 0.21-0.95). FH affects 1:104 Brazilian adults, these findings contribute to understanding the burden of disease in Brazil. Due to the scarcity of studies on FH in low- and middle-income countries, further studies are desirable.

Corrigendum: Comparison of 3DCRT and IMRT out-of-field doses in pediatric patients using Monte Carlo simulations with treatment planning system calculations and measurements.

[This corrects the article DOI: 10.3389/fonc.2022.879167.].

Viral genetic clustering and transmission dynamics of the 2022 mpox outbreak in Portugal.

Pathogen genome sequencing during epidemics enhances our ability to identify and understand suspected clusters and investigate their relationships. Here, we combine genomic and epidemiological data of the 2022 mpox outbreak to better understand early viral spread, diversification and transmission dynamics. By sequencing 52% of the confirmed cases in Portugal, we identified the mpox virus sublineages with the highest impact on case numbers and fitted them into a global context, finding evidence that several international sublineages probably emerged or spread early in Portugal. We estimated a 62% infection reporting rate and that 1.3% of the population of men who have sex with men in Portugal were infected. We infer the critical role played by sexual networks and superspreader gatherings, such as sauna attendance, in the dissemination of mpox virus. Overall, our findings highlight genomic epidemiology as a tool for the real-time monitoring and control of mpox epidemics, and can guide future vaccine policy in a highly susceptible population.

Temporal and spatial distribution trends of polio vaccine coverage in less than one-year old children in Brazil, 2011-2021.

BACKGROUND: Low polio vaccine coverage can result in the spread of Poliovirus to areas free from viral circulation. This study analyzed the temporal trends and spatial distribution of polio vaccine coverage in one year-old children in Brazil, between 2011 and 2021. METHODS: This was an ecological, time-series study (2011 to 2021) with annual vaccine coverages against poliomyelitis, extracted from the Information System of the National Immunization Program from the 26 States and the Distrito Federal (DF). The percentage reductions in vaccination coverage in Brazil and in the Regions were calculated. Prais-Winsten regression models were used to analyze time series for the Regions and States, and spatial analysis identified the distribution of clusters (high-high; low-low; high-low and low-high) of vaccination coverages across Brazilian municipalities, using a 5% significance level. RESULTS: From 2011 to 2021, the coverage of polio vaccines decreased by 29,9%. There was a progressive increase observed in clusters resulting in low vaccination coverages (140 low-low Brazilian municipalities in 2011 vs. 403 in 2021), mostly reported in the North and Northeast regions of the country. There was a downward trend in vaccination coverages in 24 of the 26 States and DF (p ≤ 0.05). CONCLUSIONS: The reduction in polio vaccine coverage, as observed in the North and Northeast regions of Brazil, may favor the spread of Poliovirus. Therefore, vaccination strategies should be prioritized for children residing in areas with sharp and recurrent declines in vaccination coverages, including travelers, migrants, and refugees.

Anaerobic adhesives effect on counter-torque of abutment screws on implants with external hexagon and conical connections: An in vitro study.

BACKGROUND: Abutment screw loosening is a common complication of implant supported prostheses, especially for single crowns. In engineering, anaerobic adhesives (AA) are used to provide chemical locking between screw surfaces, but their application in implantology remains unclear. PURPOSE: The purpose of this article is to evaluate, in vitro, the effect of AA on counter-torque of abutment screws for cemented prosthesis on dental implants with external hexagon connection (EHC) and conical connection (CC). MATERIALS AND METHODS: Sample was composed by 60 specimens, 30 dental implants with EHC and 30 with CC. Abutments (transmucosal 3 mm straight universal abutment) were installed without AA (control group) or with application of AA with two different adhesive strength: medium strength (LOCTITE® 242) and high strength (LOCTITE® 277). The specimens were subjected to mechanical cycling at 37°C, with a load setting of 133 N, a 1.3 Hz frequency, and 1 200 000 cycles. The abutments were removed, and the counter-torque values were registered. Screws and implants were inspected using a stereomicroscope to verify the presence of residual adhesive and damage the internal structures. The data were analyzed using descriptive statistics and comparison tests (p < 0.05). RESULTS: Comparing to the torque of installation, the medium strength AA kept the counter-torque values for CC implants and the high strength AA kept the counter-torque for EHC implants and increased for CC implants. In the intergroup comparisons, control group presented significantly lower counter-torque values than other groups, both for EHC and CC implants. High strength AA presented similar results to medium strength AA in the EHC implants, but in the CC implants presented higher counter-torque values. Damage in threads was more frequent in the groups that received high strength AA. CONCLUSION: The use of AA increased the counter-torque of abutment screws, both in implants with EHC and CC.

Downregulation of Sirtuin 1 Does Not Account for the Impaired Long-Term Potentiation in the Prefrontal Cortex of Female APPswe/PS1dE9 Mice Modelling Alzheimer's Disease.

Alzheimer's disease (AD), which predominantly affects women, involves at its onset a metabolic deregulation associated with a synaptic failure. Here, we performed a behavioral, neurophysiological and neurochemical characterization of 9-month-old female APPswe/PS1dE9 (APP/PS1) mice as a model of early AD. These animals showed learning and memory deficits in the Morris water maze, increased thigmotaxis and anxiety-like behavior and showed signs of fear generalization. Long-term potentiation (LTP) was decreased in the prefrontal cortex (PFC), but not in the CA1 hippocampus or amygdala. This was associated with a decreased density of sirtuin-1 in cerebrocortical synaptosomes and a decreased density of sirtuin-1 and sestrin-2 in total cerebrocortical extracts, without alterations of sirtuin-3 levels or of synaptic markers (syntaxin, synaptophysin, SNAP25, PSD95). However, activation of sirtuin-1 did not affect or recover PFC-LTP deficit in APP/PS1 female mice; instead, inhibition of sirtuin-1 increased PFC-LTP magnitude. It is concluded that mood and memory dysfunction in 9-month-old female APP/PS1 mice is associated with a parallel decrease in synaptic plasticity and in synaptic sirtuin-1 levels in the prefrontal cortex, although sirtiun1 activation failed to restore abnormal cortical plasticity.

Environmental heterogeneity of a tropical river-to-sea continuum and its relationship with structure and phytoplankton dynamics - Lençóis Maranhenses National Park.

ß-diversity and functional traits of phytoplankton indicators associated with environmental heterogeneity were investigated as environmental quality descriptors in coastal (CS), estuarine (ES), and limnetic (LS) sectors in a tropical river-to-sea ecosystem. Results showed that environmental heterogeneity was marked by spatial differences, contributing to biological heterogeneity. Sporadic and recurrent blooms were associated with environmental spatiotemporal variations and reflected a reduction in ES α-diversity. Salinity acted as an environmental filter that governed the structure and dynamics of the community. The spatial heterogeneity and high turnover of phytoplankton resulted in reliable bioindicators selection. Colonial, bloom-forming and harmful species were associated with highly suspended particulate matter (SPM) because these species are better adapted to these conditions. Species small in size were associated with high concentrations of silicate and chlorophyll-a in the ES because of the occurrence of diatom recurrent blooms. Most flagellates indicators genera have bloom-forming potential. Integrating morphofunctional with taxonomic approaches enabled detailed observations of environmental filters, supporting the selection of priority species and areas for introducing biodiversity monitoring programs and conservation in tropical ecosystems.

Blood count reference intervals for the Brazilian adult population: National Health Survey / Intervalos de referência de hemograma da população adulta brasileira: Pesquisa Nacional de Saúde

Objective: to estimate the reference intervals (RIs) of complete blood count parameters in the Brazilian adult population. Methods: Cross-sectional study, with data from the National Health Survey (PNS), between 2014-2015. The final sample consisted of 2,803 adults. The final sample consisted of 2,803 adults. To establish the RI, exclusion criteria were applied, outliers were removed and partitions were made by sex, age and race/skin color. The non-parametric method was adopted. Differences were assessed using the Mann Withney and Kruskal Wallis tests (p≤0.05). Results: There were statistically significant differences for the following hematological parameters based on sex, red blood cells, hemoglobin, hematocrit, MCH, MCHC, eosinophils and absolute monocytes, neutrophils and platelets (p≤0.05). When analyzed by age, the RIs were statistically different in females for hematocrit, MCV, white blood cells and RDW and in males for red blood cells, white blood cells, eosinophils, mean platelet volume, MCV, RDW and MCH(p≤0.05). For race/color there were differences in the RIs for parameters of hemoglobin, MCH, MCHC, white blood cells and mean platelet volume, neutrophils and absolute eosinophils (p ≤ 0.05). Conclusion: The differences found in the RIs of some in blood count parameters in Brazilian adults reaffirm the importance of having their own laboratory reference standards. The results can support a more accurate interpretation of tests, adequate identification and disease prevention in Brazil.

Objetivo: estimar os intervalos de referência (IR) de parâmetros de hemograma completo na população adulta brasileira. Métodos: Estudo transversal, com dados da Pesquisa Nacional de Saúde (PNS), entre 2014-2015. A amostra final constitui-se de 2.803 adultos. Para estabelecer os IR, aplicou-se critérios de exclusão, removeram-se outliers e feito particionamentos por sexo, idade e raça/cor da pele. Adotou-se o método não paramétrico.  As diferenças foram avaliadas pelos testes Mann Withney e Kruskal Wallis (p≤0,05). Resultados: houve diferenças estatisticamente significativas nos IR segundo sexo para glóbulos vermelhos, hemoglobina, hematócrito, HCM, CHCM, eosinófilos, monócitos, neutrófilos absolutos e plaquetas (p≤0,05). Quando analisados por idade,  houve diferenças nos IR de mulheres para hematócrito, VCM, glóbulos brancos e RDW e nos homens de glóbulos vermelhos, glóbulos brancos, eosinófilos, volume plaquetário médios, VCM, RDW e HCM (p≤0,05). Para raça/cor houve diferenças nos IR de hemoglobina, HCM, CHMC, glóbulos brancos e volume plaquetário médio, neutrófilos e eosinófilos absolutos (p ≤ 0,05). Conclusão: As diferenças encontradas nos IR de alguns em parâmetros de hemograma em adultos brasileiros  reafirmam a importância de se ter padrões de referência laborarias próprios. Os resultados podem subsidiar a interpretação mais precisa dos exames, identificação adequada e a prevenção de doenças no Brasil.

Efeito da curcumina e três análogos ­ DMAD, DMAM E RI75 ­ sobre viabilidade, diferenciação e expressão gênica em pré-osteoblastos / Effect of curcumin and three of its analogues - DMAD, DMAM and RI75 - on pre-osteoblast cells' viability, differentiation, and gene expression

A curcumina, encontrada nos rizomas da cúrcuma (Curcuma longa L.), tem sido amplamente estudada devido aos seus potenciais benefícios à saúde que, entre outros, incluem propriedades anti-inflamatórias, antioxidantes e cicatrizantes. No entanto, devido à sua baixa biodisponibilidade e farmacocinética desfavorável, compostos análogos são desenvolvidos e estudados para obter melhores características biofarmacêuticas e aumentar os efeitos biológicos. Neste trabalho, avaliamos a atividade da curcumina e três de seus análogos sintéticos (DMAD, DMAM e RI75) sobre a viabilidade e diferenciação de uma linhagem celular pré-osteoblástica (MC3T3-E1). A expressão dos genes fator de crescimento endotelial vascular (vegf), do ligante 12 da quimiocina de motivo C-X-C (cxcl12) e do fator de transcrição runt- related 2 (runx2) também foi avaliada. As células foram estimuladas com curcumina e os três análogos usando concentrações de 10, 30 ou 50 µM. A curcumina e os análogos testados apresentaram nenhuma, ligeira ou moderada citotoxicidade celular em comparação com o controle negativo, após 24, 48 e 72 horas, nas concentrações testadas. Os resultados de atividade de mineralização para a curcumina e o análogo DMAD não apresentaram diferença estatística com o grupo controle, enquanto os análogos DMAM e RI75 apresentaram menor atividade de mineralização. Nenhuma das substâncias apresentou expressão gênica diferencial de cxcl12, um ativador de células endoteliais e inflamatórias. Por outro lado, em comparação com o controle, o análogo de curcumina RI75 mostrou regulação positiva de runx2 e vegf, ambos relacionados ao reparo tecidual. Os resultados sugerem que os análogos DMAD, DMAM e RI75 apresentam citotoxicidade semelhante ou inferior à curcumina natural e maior atividade biológica, com destaque para o análogo RI75, sendo substâncias com potencial promissor para biomodificações de materiais.

Curcumin, found in the rhizomes of turmeric (Curcuma longa L.), has been widely studied due to its potential health benefits which, among others, include anti inflammatory, antioxidant and healing properties. However, due to their low bioavailability and unfavorable pharmacokinetics, analogous compounds are developed and studied to obtain better biopharmaceutical characteristics and increase biological effects. In this work, we evaluated the activity of curcumin and three of its synthetic analogues (DMAD, DMAM and RI75) on the viability and differentiation of a pre-osteoblastic cell line (MC3T3-E1). The expression of the genes vascular endothelial growth factor (vegf), C-X-C motif chemokine ligand 12 (cxcl12) and runt related transcription factor 2 (runx2) was also evaluated. Cells were stimulated with curcumin and the three analogues using concentrations of 10, 30 or 50 µM. Curcumin and the analogues tested showed no, slight or moderate cellular cytotoxicity compared to the negative control, after 24, 48 and 72 hours, at the concentrations tested. The mineralization activity results for curcumin and the DMAD analogue showed no statistical difference with the control group, while the DMAM and RI75 analogues showed lower mineralization activity. None of the substances showed differential gene expression of cxcl12, an activator of endothelial and inflammatory cells. On the other hand, compared to the control, the curcumin analogue RI75 showed upregulation of runx2 and vegf, both related to tissue repair. The results suggest that the DMAD, DMAM and RI75 analogues present similar or lower cytotoxicity compared to natural curcumin and greater biological activity, especially the RI75 analogue, being, therefore, substances with promising potential for biomodification of materials.