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Abstract Background Metallic nanoparticles (NPs) are widely used as food additives for human consumption. NPs reach the bloodstream given their small size, getting in contact with all body organs and cells. NPs have adverse effects on the respiratory and intestinal tract; however, few studies have focused on the toxic consequences of orally ingested metallic NPs on the cardiovascular system. Here, the effects of two food-grade additives on the cardiovascular system were analyzed. Methods Titanium dioxide labeled as E171 and zinc oxide (ZnO) NPs were orally administered to Wistar rats using an esophageal cannula at 10 mg/kg bw every other day for 90 days. We evaluated cardiac cell morphology and death, expression of apoptotic and autophagic proteins in cardiac mitochondria, mitochondrial dysfunction, and concentration of metals on cardiac tissue. Results Heart histology showed important morphological changes such as presence of cellular infiltrates, collagen deposition and mitochondrial alterations in hearts from rats exposed to E171 and ZnO NPs. Intracellular Cyt-C levels dropped, while TUNEL positive cells increased. No significant changes in the expression of inflammatory cytokines were detected. Both NPs altered mitochondrial function indicating cardiac dysfunction, which was associated with an elevated concentration of calcium. ZnO NPs induced expression of caspases 3 and 9 and two autophagic proteins, LC3B and beclin-1, and had the strongest effect compared to E171. Conclusions E171 and ZnO NPs induce adverse cardiovascular effects in rats after 90 days of exposure, thus food intake containing these additives, should be taken into consideration, since they translocate into the bloodstream and cause cardiovascular damage.

Resumen: Introducción y objetivo: La obesidad se asocia con el hígado graso no alcohólico (HGNA) en niños. El objetivo fue explorar la asociación de factores dietéticos y sociodemográficos con el HGNA en niños y adolescentes obesos. Material y métodos: Treinta y tres pacientes obesos entre seis a 16 años fueron incluidos en este estudio transversal analítico. El diagnóstico de obesidad se realizó con puntuación z del índice de masa corporal > 2 DE. El HGNA se estimó con ultrasonido hepático, aminotransferasas séricas y elastografía. Las variables sociodemográficas se evaluaron con cuestionarios validados. La dieta se estimó mediante dos encuestas dietéticas por recordatorio de 24 horas enfocadas a la cantidad de energía, azúcares simples, ácidos grasos poliinsaturados (PUFAs) y antioxidantes. Resultados: En 13 pacientes (39.4%), se identificó esteatosis hepática por ultrasonido abdominal; 54.2% tuvieron una concentración sérica de alanina aminotransferasa por arriba de la referencia. El nivel educativo superior de ambos padres, el mayor gasto familiar mensual en alimentos y el mayor nivel socioeconómico se asociaron con HGNA. En el grupo total, el consumo de azúcares simples y grasas saturadas fue excesivo y el consumo de vitamina E y PUFAS estuvo por debajo del parámetro. Conclusiones: Se identificó HGNA en un tercio de los casos. Se demostró asociación entre HGNA y variables sociodemográficas. Ambos grupos tuvieron una ingesta aumentada de azúcares simples y disminuida de PUFAs. La ocurrencia selectiva de HGNA se podría relacionar con predisposición genética demostrada en población mexicana. Abstract: Introduction: Obesity is associated with nonalcoholic fatty liver disease (NAFLD) in children. Our aim was to analyze the association of dietary and sociodemographic factors with NAFLD in obese children and adolescents. Materials and methods: Thirty-three obese patients from 6-16 years of age were included in the present analytic cross-sectional study. Obesity was diagnosed with a body mass index z-score > 2 SD. NAFLD was estimated by liver ultrasound, serum amino transferases, and elastography. The sociodemographic variables were evaluated using validated questionnaires. Diet was estimated through two 24-hour recall dietary surveys focused on the quantity of food energy, simple sugars, polyunsaturated fatty acids (PUFAs), and antioxidants. Results: Hepatic steatosis was identified by abdominal ultrasound in 13 patients (39.4%) and the serum alanine aminotransferase level was above the upper reference value in 54.2%. A higher educational level in both parents, greater monthly food expenditure, and a higher socioeconomic level were associated with NAFLD. Overall, simple sugar and saturated fat consumption was above the recommended daily intake, whereas vitamin E and PUFA consumption was below those parameters. Conclusions: NAFLD was identified in one-third of the cases. There was an association between NAFLD and sociodemographic variables. Both groups had an increased intake of simple sugars and a reduced intake of PUFAs. The selective occurrence of NAFLD could be related to a genetic predisposition that has been demonstrated in a Mexican population.

Objective: The synergistic inhibitory effect of celecoxib (CXB) and dimethyl-celecoxib (DMC) plus paclitaxel (PA) or cisplatin (CP) on human cervix HeLa and SiHa cells was assessed at multiple cellular levels in order to elucidate the biochemical mechanisms triggered by the synergistic drug combinations. Methods: The effect of CXB (5 μM)/CP (2 μM) or CXB (5 μM)/PA (15 μM) and DMC (15 μM)/CP (5 μM) or DMC (15 μM)/PA (20 μM) for 24 h was assayed on cancer cell proliferation, energy metabolism, mitophagy, ROS production, glycoprotein-P activity, DNA stability and apoptosis/necrosis. Results: Drug combinations synergistically decreased HeLa and SiHa cell proliferation (>75%) and arrested cellular cycle by decreasing S and G2/M phases as well as the Ki67 content (HeLa) by 7.5–30 times. Cell viability was preserved (>90%) and no apparent effects on non-cancer cell growth were observed. Mitochondrial and glycolytic protein contents (44–95%) and ΔΨm (45–50%) in HeLa cells and oxidative phosphorylation and glycolysis fluxes (70–90%) in HeLa and SiHa cells were severely decreased, which in turn promoted a drastic fall in the ATP supply (85–88%). High levels of mitophagy proteins in HeLa cells and active mitochondrial digestion in HeLa and SiHa cells was observed. Mitochondrial fission and microtubule proteins were also affected. Intracellular ROS content (2–2.3-fold) and ROS production was stimulated (2.3–4 times), whereas content and activity of glycoprotein-P (45–85%) were diminished. DNA fragmentation was not observed and apoptosis/necrosis was not detected suggesting that cell death could be mainly associated to mitophagy induction. Conclusions: CXB or DMC combination with canonical chemotherapy may be a promising chemotherapy strategy against cervical cancer growth, because it can selectively block multiple cell processes including inhibition of energy pathways and in consequence ATP-dependent processes such as cell proliferation, glycoprotein-P activity, ROS production and mitophagy, with no apparent effects on non-cancer cells. [ABSTRACT FROM AUTHOR]

Resumo Fundamento A hipertensão arterial (HTA) representa um grande fator de risco de morbidade e mortalidade cardiovascular. Ainda não se sabe que mecanismos moleculares específicos estão associados ao desenvolvimento de hipertensão essencial. Objetivo Neste trabalho, analisamos a associação entre expressão mRNA de monócito LRP1, expressão de proteína LRP1, e espessura íntima-média de carótida (EIMC) de pacientes com hipertensão essencial. Métodos A expressão mRNA de monócito LRP1 e os níveis de proteína e EIMC foram quantificados em 200 indivíduos mexicanos, sendo 91 normotensos (NT) e 109 hipertensos (HT) A significância estatística foi definida em p < 0,05. Resultados O grupo de pacientes HT tinha EIMC maior altamente significativa em comparação com os pacientes NT (p = 0,002), e isso está relacionado ao aumento na expressão mRNA de LRP1 (6,54 versus. 2,87) (p = 0,002) e expressão de proteína LRP1 (17,83 versus 6,25), respectivamente (p = 0,001). Essas diferenças foram mantidas mesmo quando dividimos nossos grupos de estudo, levando em consideração apenas aqueles que apresentavam dislipidemia na expressão de mRNA (p = 0,041) e de proteínas (p < 0,001). Também se identificou que a indução de LRP1 mediada por LRP1 em monócitos em de maneira dependente de dose e tempo, com diferença significativa em NT versus HT (0,195 ± 0,09 versus 0,226 ± 0,12, p = 0,046). Conclusão Foi encontrado um aumento em EIMC em indivíduos com hipertensão, associada a expressões de proteína LRP1 e mRNA mais altas em monócitos, independente da presença de dislipidemia em pacientes HT. Esses resultados que a upregulation de LRP1 em monócitos de pacientes hipertensos mexicanos poderia estar envolvida na diminuição da EIMC. (Arq Bras Cardiol. 2021; 116(1):56-65)

Argentatin B has been shown to inhibit the growth of colon HCT-15, and prostate PC-3 cancer cells. However, the mechanism by which argentatin B inhibits cell proliferation is still unknown. We aimed to investigate the mechanism by which argentatin B inhibits cell proliferation. The cell cycle was studied by flow cytometry. Apoptosis was evaluated by Annexin-V-Fluos, and Hoechst 33342 dye staining. Cell senescence was evaluated by proliferation tests, and staining for SA-β-galactosidase. Senescence-related proteins (PCNA, p21, and p27) were analyzed by Western blotting. Potential toxicity of argentatin B was evaluated in CD-1 mice. Its effect on tumor growth was tested in a HCT-15 and PC-3 xenograft model. Argentatin B induced an increment of cells in sub G1, but did not produce apoptosis. Proliferation of both cell lines was inhibited by argentatin B. Forty-three percent HCT-15, and 66% PC-3 cells showed positive SA-β-galactosidase staining. The expression of PCNA was decreased, p21 expression was increased in both cell lines, but p27 expression increased only in PC-3 cells after treatment. Administration of argentatin B to healthy mice did not produce treatment-associated pathologies. However, it restricted the growth of HCT-15 and PC-3 tumors. These results indicate that treatment with argentatin B induces cell senescence.

El notable incremento mundial en el consumo de plásticos y su l argo tiempo de residencia en el ambiente muestran la gran neces idad de productos con caracterís ticas biodegradables. En este proyecto fueron desarrollados polímeros biodegradables a base del ácido cítrico y del glicerol. La síntesis de esto s se lleva a cabo a diferentes condiciones de concentración y a temperatura constante. Se des arrollaron mediante un proceso económicamente viable. Se caracterizaron p or medio de las siguientes técnicas: Numero ácido, espectroscop ia infrarroja FTIR, índice de refracc ión, viscosidad, análisis de impacto, ensayo de tensión, dure za, calorimetría, el % de Humed ad (método de la estufa con recirculación de aire), determinación de densi dad, además de pruebas cualitativas para corroborar su biodegra dabilidad. Los polímeros elaborados fueron mezclados con una formulación de PVC grado médico, obteniendo un polímero hibrido y se pudo observar que modifica sus propiedades mecánicas.

Curcumin has protective effects against toxic agents and shows preventive properties for various diseases. Particulate material with an aerodynamic diameter of ≤10 μm (PM10) and titanium dioxide nanoparticles (TiO2-NPs) induce endothelial dysfunction and activation. We explored whether curcumin is able to attenuate different events related to endothelial activation. This includes adhesion, expression of adhesion molecules and oxidative stress induced by PM10 and TiO2-NPs. Human umbilical vein endothelial cells (HUVEC) were treated with 1, 10 and 100 μM curcumin for 1 h and then exposed to PM10 at 3 μg/cm2 or TiO2-NPs at 10 μg/cm2. Cell adhesion was evaluated by co-culture with U937 human myelomonocytic cells. Adhesion molecules expression was measured by flow cytometry after 3 or 24 h of exposure. Oxidative stress was determined by 2,7-dichlorodihydrofluorescein (H2DCF) oxidation. PM10 and TiO2-NPs induced the adhesion of U937 cells and the expression of E- and P-selectins, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and platelet-endothelial cell adhesion molecule-1 (PECAM-1). The expression of E- and P-selectins matched the adhesion of monocytes to HUVEC after 3 h. In HUVEC treated with 1 or 10 μM curcumin, the expression of adhesion molecules and monocytes adhesion was significantly diminished. Curcumin also partially reduced the H2DCF oxidation induced by PM10 and TiO2-NPs. Our results suggest an anti-inflammatory and antioxidant role by curcumin attenuating the activation caused on endothelial cells by exposure to particles. Therefore, curcumin could be useful in the treatment of diseases where an inflammatory process and endothelial activation are involved.

Titanium dioxide nanoparticles (TiO2 NPs) are widely used in industry and daily life. TiO2 NPs can penetrate into the body, translocate from the lungs into the circulation and come into contact with cardiac cells. In this work, we evaluated the toxicity of TiO2 NPs on H9c2 rat cardiomyoblasts. Internalization of TiO2 NPs and their effect on cell proliferation, viability, oxidative stress and cell death were assessed, as well as cell cycle alterations. Cellular uptake of TiO2 NPs reduced metabolic activity and cell proliferation and increased oxidative stress by 19-fold measured as H2DCFDA oxidation. TiO2 NPs disrupted the plasmatic membrane integrity and decreased the mitochondrial membrane potential. These cytotoxic effects were related with changes in the distribution of cell cycle phases resulting in necrotic death and autophagy. These findings suggest that TiO2 NPs exposure represents a potential health risk, particularly in the development of cardiovascular diseases via oxidative stress and cell death.

Eu3+-(5% mol)-doped Lu2SiO5 optical quality films were prepared using the sol–gel method and dip-coating technique from lutetium and europium salts as the lanthanide precursors and tetraethyl orthosilicate (TEOS) as the silicon source. To increase the thickness of the films, 3-Glycidyloxypropyl trimethoxysilane (Glymo) was added as the rheological agent during sol formation. Structural, morphological, and luminescent properties were investigated for Lu2SiO5, Eu3+:Lu2SiO5, and Eu3+:Lu2SiO5/Glymo in order to obtain high quality in luminescent films. X-ray diffraction (XRD) results show that the incorporation of the Eu3+ ions do not affect the A-Type and B-Type monoclinic crystalline phase typical of Lu2SiO5, even after five dipping cycles on quartz substrates and a final annealing process at 1100 °C. The morphology and topography of the films were studied by SEM and AFM. These techniques revealed films without surfactant that were uniform with low rugosity while the film with surfactant presented porous hills and valleys with uneven high values of roughness. The photoluminescence spectrum of Eu3+:Lu2SiO5 films showed 2 broad emission peaks centered at 589 nm and 612 nm. The presence of Glymo in the system promoted the formation of residual Lu2Si2O7 compounds with the highest lifetime values compared with films without surfactant. The results of the films are promising for luminescent applications. [ABSTRACT FROM AUTHOR]