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1.
Artigo em Inglês | MEDLINE | ID: mdl-39146527

RESUMO

OBJECTIVES: To investigate the effects of a Brazil nut-enriched diet on the wall thickness and the left ventricular chamber diameter of the heart, and lipid peroxidation in a CKD-induced model. METHODS: Male Wistar rats at 12 weeks of age were divided into two groups (n=16/group): the Nx group, which underwent 5/6 nephrectomy, and the Sham group, as a control. After 5 weeks, the groups were subdivided according to diet (n=8/group): the Nx and Sham groups received a control diet; the Nx5% and Sham5% groups received a diet enriched with 5 % Brazil nuts for 8 weeks. The left ventricular thickening and chamber diameter were determined. Plasma biochemical parameters were evaluated. Analysis of thiobarbituric acid reactive substances (TBARS) and antioxidant enzyme activity was performed in the plasma and the left ventricle (LV). LV mRNA expression of nuclear factor-kappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2) was evaluated by reverse transcription-polymerase chain reaction. RESULTS: The Nx5% group showed a remodeled LV wall with decreased thickness compared to the Nx group (p=0.016). Furthermore, LV TBARS concentration was reduced in the Nx5% group (p=0.0064). In addition, the Nx5% group showed an increase in plasma GPx activity (p=0.0431). No significant results were found concerning the LV mRNA expression of NF-κB and Nrf2 genes. CONCLUSIONS: A Brazil nut-enriched diet decreased LV thickness and LV TBARS concentration and increased GPx activity in a 5/6 nephrectomy experimental model, making it a promising adjuvant therapy to improve antioxidant status and cardiovascular outcomes in chronic kidney disease.

2.
Nutrition ; 125: 112482, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39024685

RESUMO

OBJECTIVE: This study investigates the effects of a Brazil nut-enriched diet on body composition and bone parameters in CKD animal model. METHODS: Male Wistar rats were assigned to the following groups: Sham (n=8), Nx (n=6), nephrectomized rats, and NxBN (n=6), nephrectomized rats and an enricheddiet with 5% Brazil nut. Body composition parameters were obtained by dual-energy X- ray absorptiometry (DXA). Bioclin kits determined plasmatic calcium. The femurs werecollected to determine absolute mass and length, bone mineral density, and biomechanical tests. RESULTS: The NxBN group exhibited a higher total body bone mineral density (BMD) value than the Nx group (0.177±0.004g/cm2vs 0,169±0.003g/cm2; p=0.0397). No significant differences were observed regarding absolute mass, length, BMD, and biomechanical parameters in the femurs of the groups. Moreover, no significant differences were found in plasmatic calcium levels among the groups. CONCLUSIONS: Brazil-nut enriched diet modulated BMD in CKD experimental model, and further studies are demanded to understand the pathways involved in this finding.


Assuntos
Bertholletia , Composição Corporal , Densidade Óssea , Dieta , Modelos Animais de Doenças , Fêmur , Ratos Wistar , Insuficiência Renal Crônica , Animais , Masculino , Insuficiência Renal Crônica/dietoterapia , Insuficiência Renal Crônica/fisiopatologia , Ratos , Dieta/métodos , Fêmur/fisiopatologia , Absorciometria de Fóton , Cálcio/sangue , Nozes
3.
Dent Traumatol ; 40(4): 453-459, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38459667

RESUMO

BACKGROUND/AIMS: The study aimed to assess the surface characteristics of sports mouthguards under mechanical stresses during cleaning, either by brushing or immersion in disinfectant solutions. MATERIAL AND METHODS: Ethylene-vinyl acetate samples, 4 mm thick, were randomly assigned to cleaning methods: control (C-no cleaning), brushing with water (B.W), brushing with neutral liquid soap (B.S), brushing with toothpaste (B.T), immersion in distilled water for 10 min (I.W), immersion in 2.25% sodium hypochlorite solution for 10 min (I.SH), and immersion in sodium bicarbonate solution for 5 min (I.SB). All cleaning methods were applied for 28 days. Surface roughness average (Ra) and wettability were measured at baseline for the control group (n = 9), and after cleaning for all the other groups. RESULTS: One-way ANOVA with Tukey tests (5% significance) indicated significant differences among groups (p < .05). The I.SB group had higher surface roughness than B.S and B.T (p < .05). B.W showed the lowest wettability, significantly lower than B.T, I.W, and I.SB (p < .05). I.SB exhibited the highest wettability, significantly different from sodium hypochlorite, neutral liquid soap, brushing with water, and control groups (p < .05). The sodium bicarbonate immersion group (I.SB) demonstrated greater statistical variation, displaying higher susceptibility to aging compared to brushing with neutral liquid soap. CONCLUSION: Cleaning mouthguards with a toothbrush, water, and neutral liquid soap emerged as the most promising method, causing minimal surface changes in the material.


Assuntos
Protetores Bucais , Propriedades de Superfície , Escovação Dentária , Desinfetantes , Hipoclorito de Sódio/farmacologia , Humanos , Bicarbonato de Sódio , Sabões , Cremes Dentais , Molhabilidade , Fatores de Tempo , Polivinil
4.
Polymers (Basel) ; 16(2)2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38276697

RESUMO

The present work evaluates the influence of different properties of composite materials from natural sources. Films were prepared using the evaporative casting technique from corn starch reinforced with a waste material such as garlic husk (GH), using glycerin as a plasticizer. The results of the syntheses carried out demonstrated the synergy between these materials. In the morphological analysis, the compatibility and adequate dispersion of the reinforcer in the matrix were confirmed. Using Fourier transform infrared spectroscopy (FTIR), the interaction and formation of bonds between the matrix and the reinforcer were confirmed by the presence of some signals such as S-S and C-S. Similarly, thermogravimetric analysis (TGA) revealed that even at low concentrations, GH can slightly increase the decomposition temperature. Finally, from the results of dynamic mechanical analysis (DMA), it was possible to identify that the storage modulus increases significantly, up to 115%, compared to pure starch, especially at low concentrations of the reinforcer.

5.
J Am Nutr Assoc ; 43(2): 201-212, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37611162

RESUMO

Introduction: Chronic kidney disease (CKD) promotes gut dysbiosis, and enteric glial reactivity, a feature of intestinal inflammation. Brazil nut modulated enteric glial profile in healthy animals and could modulate these cells in 5/6 nephrectomized rats.Methods: A 5/6 nephrectomy-induced CKD and Sham-operated rats were divided as follows: CKD and Sham received a standard diet and CKD-BN and Sham-BN received a 5% Brazil nut enriched-diet. The protein content of glial fibrillary acid protein (GFAP), enteric glial marker, and GPx protein content and activity were assessed in the colon. The major phyla of gut microbiota were assessed.Results: CKD-BN group presented a decrease in GFAP content (p = 0.0001). The CKD-BN group modulated the abundance of Firmicutes, increasing its proportion compared to the CKD group. The CKD-BN group showed increased GPx activity in the colon (p = 0.0192), despite no significant difference in protein content.Conclusion: Brazil nut-enriched diet consumption decreased enteric glial reactivity and modulated gut microbiota in the CKD experimental model.


Assuntos
Bertholletia , Microbioma Gastrointestinal , Insuficiência Renal Crônica , Ratos , Animais , Dieta , Neuroglia/metabolismo , Insuficiência Renal Crônica/metabolismo
6.
São José dos Campos; s.n; 2024. 59 p. ilus, tab.
Tese em Português | BBO - Odontologia | ID: biblio-1572593

RESUMO

As zircônias odontológicas são notadamente conhecidas por suas propriedades biomecânicas, e evoluíram de um material branco e opaco para um material com gradiente de translucidez e múltiplas indicações clínicas. Dentre a última geração destes materiais, estão as zircônias multicamadas gradadas, que possuem um gradiente microestrutural com gradação de ítria. A zona de transição, ou interfase, entre essas camadas ainda é pouco descrita pela literatura. O presente estudo se dá diante da hipótese de que a interfase seja uma zona frágil das zircônias multicamadas, e investiga a energia necessária para separá-las, ou seja, a tenacidade à fratura da interfase. Espécimes do tipo Brazil-nut foram confeccionados para o cálculo da energia necessária para a fratura interfásica em diferentes angulações da zircônia multicamadas, verificando modalidades de falhas mistas, por tração ou por cisalhamento em testes de compressão, utilizando 3Y-TZP e 5Y-PSZ puras como controle. Os grupos foram divididos de acordo com a zircônia testada, o ângulo de teste e o envelhecimento hidrotérmico; a tenacidade à fratura da interfase se deu em N/m. Os espécimes fraturados foram submetidos à uma análise fractográfica detalhada, com classificação dos tipos de falha, caracterização em MEV e EDS. Os resultados dos testes da multicamadas foram submetidos ao teste ANOVA de 2 fatores, indicando diferença estatística entre os ângulos, mas não quanto ao envelhecimento. O teste post-hoc de Tukey revelou que a energia para fratura interfásica em 25º, predominantemente por força de cisalhamento, é significativamente maior do que os demais grupos [baseline: 964,74 (± 202,43); envelhecido: 1389,12 (± 978,47) N/m], exceto quando comparado a 15º [baseline: 1006,09 (± 373,13); envelhecido: 798,43 (± 108,67) N/m], que não difere estatisticamente de nenhum dos outros grupos. Os valores da energia interfásica para fratura de uma zircônia multicamadas se mostraram intermediários entre a 5Y-PSZ e a 3Y-TZP, sem diferença significante da multicamadas com a 3Y-TZP e ambas com diferença significativa para a 5Y-PSZ. A tenacidade à fratura da interfase de uma zircônia multicamadas, uma importante propriedade para o bom desempenho clínico do material, não foi afetada pelo envelhecimento hidrotérmico e é menor sob tensões de tração do que de cisalhamento. Os padrões de fratura variaram mas não houve diferenças em comparação aos grupos controle.(AU)


Dental zirconias are well known for their biomechanical properties, and have evolved from a white, opaque material to one with a gradient of translucency and multiple clinical indications. Among the latest generation of these materials are graded multilayer zirconias, which have a microstructural gradient with yttria gradation. The transition zone, or interphase, between these layers is still poorly described in the literature. This study is based on the hypothesis that the interphase is a fragile zone in multilayer zirconias, and investigates the energy required to separate them, i.e. the fracture toughness of the interphase. Brazil-nut specimens were made to calculate the energy required for interphase fracture at different angles of the multilayer zirconia, checking for mixed, tensile or shear failure modes in compression tests, using pure 3Y-TZP and 5Y-PSZ as a control. The groups were divided according to the zirconia tested, the test angle and hydrothermal ageing; the fracture toughness of the interphase was measured in N/m. The fractured specimens were subjected to detailed fractographic analysis, with classification of failure types, SEM and EDS characterization. The results of the multilayer tests were submitted to the 2-way ANOVA test, indicating a statistical difference between the angles, but not in terms of aging. Tukey's post-hoc test revealed that the energy for interphase fracture at 25º, predominantly by shear force, is significantly higher than the other groups [baseline: 964.74 (± 202.43); aged: 1389.12 (± 978.47) N/m], except when compared to 15º [baseline: 1006.09 (± 373.13); aged: 798.43 (± 108.67) N/m], which does not differ statistically from any of the other groups. The interphase energy values for fracture of a multilayer zirconia were intermediate between 5Y-PSZ and 3Y-TZP, with no significant difference between the multilayer and 3Y-TZP and both with a significant difference for 5Y-PSZ. The fracture toughness of the interphase of a multilayer zirconia, an important property for the good clinical performance of the material, was not affected by hydrothermal ageing and is lower under tensile than shear stresses. Fracture patterns varied but there were no differences compared to the control groups (AU)


Assuntos
Materiais Dentários , Porcelana Dentária , Interfase
7.
Int. j. cardiovasc. sci. (Impr.) ; 37: e20230113, 2024. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1550292

RESUMO

Abstract Background: Trimethylamine N-oxide (TMAO), a gut microbiota metabolite, is associated with cardiovascular disease (CVD) development. TMAO can trigger an inflammatory response by inducing the nuclear factor-kappa B (NF-κB) signaling cascade and increasing the expression of pro-inflammatory cytokines, contributing to the worsening of CVD. This study aimed to evaluate the association between TMAO plasma levels and inflammation in patients with coronary artery disease (CAD). Methods: A cross-sectional study was carried out including 29 patients with CAD. Peripheral blood mononuclear cells (PBMC) were isolated from fasting blood samples, and NF-κB and vascular cell adhesion protein 1 (VCAM1) mRNA expression were estimated using real-time quantitative PCR. We determined TMAO plasma levels by LC-MS/MS and TNF-α by ELISA. Routine biochemical parameters were evaluated using an automatic biochemical analyzer. Correlations were estimated by Spearman or Pearson test. Statistical significance was set at the level of p < 0.05. Results: All patients presented TMAO levels within the normal range according to EUTox (normal range: 2.83 ± 1.53 mg/L; CAD patients: 0.2 [0.1 to 0.2] ng/μL). TMAO plasma levels were positively correlated with NF-κB mRNA expression (0.555; p = 0.002). Conclusion: TMAO plasma levels may be associated with NF-κB mRNA expression in patients with CAD and may contribute to the pathogenesis of this disease.

8.
Artigo em Inglês | MEDLINE | ID: mdl-37917394

RESUMO

Dairy foods have become an interest in chronic kidney disease (CKD) due to their nutritional profile, which makes them a good substrate for probiotics incorporation. This study evaluated the effect of probiotic-enriched Minas cheese with Lactobacillus acidophilus La-05 in an experimental rat model for CKD on cardiac, inflammatory, and oxidative stress parameters. Male Wistar rats were divided into 4 groups (n = 7/group): 5/6 nephrectomy + conventional Minas cheese (NxC); 5/6 nephrectomy + probiotic Minas cheese (NxPC); Sham + conventional Minas cheese (ShamC); Sham + probiotic Minas cheese (ShamPC). Offering 20 g/day of Minas cheese with Lact. acidophilus La-05 (108-109 log CFU/g) for 6 weeks. The cardiomyocyte diameter was determined. Superoxide dismutase (SOD) activity in plasma, heart, kidney, and colon tissue was performed. At the end of supplementation, no significant changes in lipid profile and renal parameters were found. The NxPC group showed a decrease in cardiomyocyte diameter compared to the NxC group (16.99 ± 0.85 vs. 19.05 ± 0.56 µm, p = 0.0162); also they showed reduced plasmatic SOD activity (502.8 ± 49.12 vs. 599.4 ± 94.69 U/mL, p < 0.0001). In summary, probiotic-enriched Minas cheese (Lact. acidophilus La-05) consumption suggests a promisor cardioprotective effect and was able to downregulate SOD activity in a rat model of CKD.

9.
Molecules ; 28(16)2023 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-37630332

RESUMO

Extracellular synthesis of functional cyclodextrins (CDs) as intermediates of starch assimilation is a convenient microbial adaptation to sequester substrates, increase the half-life of the carbon source, carry bioactive compounds, and alleviate chemical toxicity through the formation of CD-guest complexes. Bacteria encoding the four steps of the carbohydrate metabolism pathway via cyclodextrins (CM-CD) actively internalize CDs across the microbial membrane via a putative type I ATP-dependent ABC sugar importer system, MdxEFG-(X/MsmX). While the first step of the CM-CD pathway encompasses extracellular starch-active cyclomaltodextrin glucanotransferases (CGTases) to synthesize linear dextrins and CDs, it is the ABC importer system in the second step that is the critical factor in determining which molecules from the CGTase activity will be internalized by the cell. Here, structure-function relationship studies of the cyclo/maltodextrin-binding protein MdxE of the MdxEFG-MsmX importer system from Thermoanaerobacter mathranii subsp. mathranii A3 are presented. Calorimetric and fluorescence studies of recombinant MdxE using linear dextrins and CDs showed that although MdxE binds linear dextrins and CDs with high affinity, the open-to-closed conformational change is solely observed after α- and ß-CD binding, suggesting that the CM-CD pathway from Thermoanaerobacterales is exclusive for cellular internalization of these molecules. Structural analysis of MdxE coupled with docking simulations showed an overall architecture typically found in sugar-binding proteins (SBPs) that comprised two N- and C-domains linked by three small hinge regions, including the conserved aromatic triad Tyr193/Trp269/Trp378 in the C-domain and Phe87 in the N-domain involved in CD recognition and stabilization. Structural bioinformatic analysis of the entire MdxFG-MsmX importer system provided further insights into the binding, internalization, and delivery mechanisms of CDs. Hence, while the MdxE-CD complex couples to the permease subunits MdxFG to deliver the CD into the transmembrane channel, the dimerization of the cytoplasmatic promiscuous ATPase MsmX triggers active transport into the cytoplasm. This research provides the first results on a novel thermofunctional SBP and its role in the internalization of CDs in extremely thermophilic bacteria.


Assuntos
Proteínas de Transporte , Dextrinas , Proteínas de Transporte/genética , Polissacarídeos , Firmicutes , Bactérias Anaeróbias , Amido
10.
J Infect Dev Ctries ; 17(1): 86-92, 2023 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-36795931

RESUMO

INTRODUCTION: Non-typhoidal Salmonella (NTS), are frequently found in sewage and are one of the main causes of diarrhea in developed and developing countries due to poor sanitation conditions. In addition, NTS can potentially act as reservoirs and vehicles for the transmission of antimicrobial resistance (AMR), which can be facilitated by the discharge of sewage effluents into environmental matrices. This study aimed to analyze a NTS Brazilian collection, focusing on their antimicrobial susceptibility profile and the presence of clinically relevant AMR-encoding genes. METHODOLOGY: Forty-five non-clonal NTS strains from serotypes Salmonella enteritidis (n = 6), Salmonella enterica serovar 1,4,[5],12:i:- (S. 1,4,[5],12:i:-) (n = 25), Salmonella cerro (n = 7), Salmonella typhimurium (n = 3) and Salmonella braenderup (n = 4) were studied. Antimicrobial susceptibility testing was done using the Clinical and Laboratory Standards Institute guidelines (2017) and genes encoding resistance to beta-lactams, fluoroquinolones and aminoglycosides were identified by polymerase chain reaction and sequencing. RESULTS: Resistance to ß-lactams, fluoroquinolones, tetracyclines and aminoglycosides was frequent. The highest rates were observed for nalidixic acid (89.0%), followed by tetracycline (67.0%), ampicillin (67.0%), amoxicillin + clavulanic acid (64.0%); ciprofloxacin (47.0%) and streptomycin (42.0%). The AMR-encoding genes detected were qnrB, oqxAB, blaCTX-M and rmtA. CONCLUSIONS: Raw sewage has been considered a valuable tool to evaluate epidemiological population patterns and this study supports the view that NTS with pathogenic potential and resistance to antimicrobials are circulating in the studied region. This is worrisome due to the dissemination of these microorganisms throughout the environment.


Assuntos
Anti-Infecciosos , Febre Tifoide , Humanos , Brasil/epidemiologia , Esgotos , Anti-Infecciosos/farmacologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Febre Tifoide/tratamento farmacológico , Salmonella typhimurium/genética , Fluoroquinolonas , Aminoglicosídeos , beta-Lactamas , Testes de Sensibilidade Microbiana , Farmacorresistência Bacteriana
11.
Interface (Botucatu, Online) ; 27: e220098, 2023. ilus, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1448515

RESUMO

Abstract Medical schools must incorporate the teaching of professionalism into the curriculum to ensure that the next generations of physicians are prepared for a compassionate, humane, and ethical professional practice, suitable to the interests of society in a world with ever-increasing and ever-changing demands. This study's greatest contribution is to highlight the interns' poor performance in the legal and support aspects of the situations addressed. The data speak in favor of an institutionalized training policy as the first step toward getting the healthcare sector to prioritize competence in healthcare for victims of violence related to gender and non-heterosexual sexuality.(AU)


Resumen Las escuelas médicas deben incorporar la enseñanza del profesionalismo al currículo para asegurar que las próximas generaciones de médicos estén preparadas para una práctica profesional compasiva, humana y ética, adecuada a los intereses de la sociedad en un mundo con demandas cada vez mayores y en constante cambio. La mayor contribución de este estudio es mostrar el deficiente desempeño de los pasantes en los aspectos jurídicos y de soporte de las situaciones abordadas. Los datos se muestran a favor de una política de capacitación institucionalizada como un primer paso para que el sector de salud priorice la competencia en atención a la salud de las víctimas de violencia relacionada al genero y a la sexualidad no heterosexual.(AU)


Resumo As escolas médicas devem incorporar o ensino do profissionalismo ao currículo para garantir que as próximas gerações de médicos estejam preparadas para uma prática profissional compassiva, humana e ética, adequada aos interesses da sociedade em um mundo com demandas cada vez maiores e em constante mudança. A maior contribuição deste estudo é evidenciar o fraco desempenho dos estagiários nos aspectos jurídicos e de apoio nas situações abordadas. Os dados falam a favor de uma política de capacitação institucionalizada como o primeiro passo para que o setor da saúde priorize a competência em atenção à saúde das vítimas de violência relacionada a gênero e a sexualidade não heterossexual.(AU)

13.
Demetra (Rio J.) ; 18: 73690, 2023. tab
Artigo em Inglês, Português | LILACS | ID: biblio-1532674

RESUMO

Introdução: A disbiose intestinal é uma característica comum na síndrome cardiorrenal e está associada ao aumento de toxinas urêmicas, como o N-óxido de trimetilamina (TMAO), que estão envolvidas com a inflamação e mortalidade cardiovascular. A castanha-do-Brasil (semente típica brasileira) possui propriedades anti-inflamatórias e antioxidantes, mas não há evidências dos seus efeitos na modulação da microbiota intestinal e redução de toxinas urêmicas. Objetivo: Avaliar o impacto do consumo de castanha-do-Brasil nos níveis de TMAO e marcadores de inflamação em um paciente com síndrome cardiorrenal. Métodos: Um paciente com doença arterial coronariana (66 anos e IMC, 26 kg/m2), estágio 3 da DRC (TFGe 36 mL/min), recebeu uma castanha-do-Brasil por dia durante três meses. Resultados: Os níveis plasmáticos de TMAO e a expressão de mRNA de NF-κB foram reduzidos e a atividade da glutationa peroxidase (GPx) aumentou após esta intervenção. Conclusão: A prescrição de castanha-do-Brasil pode ser uma estratégia promissora para mitigar as complicações relacionadas à síndrome cardiorrenal. Este caso apoia o conceito de "alimento como remédio" visando o fenótipo urêmico na síndrome cardiorrenal.


Introduction: Gut dysbiosis is a common feature in cardiorenal syndrome, and it is linked to increased uremic toxins, like trimethylamine-n-oxide (TMAO), which are involved with inflammation and cardiovascular mortality. Brazil nut (typical Brazilian seed) has anti-inflammatory and antioxidant properties, but there is no evidence of the effects of gut microbiota modulation and reduction of uremic toxins. Objective: To assess the impact of Brazil nut consumption on TMAO levels and inflammation markers in a patient with cardiorenal syndrome. Methods: Acoronary artery disease patient(66 years and BMI, 26 kg/m2),stage-3 of CKD (eGFR 36 mL/min), receivedone Brazil nut per day for three months. Results: TMAO plasma levels and NF-κB mRNA expression were reduced, and glutathione peroxidase (GPx) activity increased after this intervention. Conclusion: Brazil nut prescription may be a promising strategy to mitigate complications related tothe cardiorenal syndrome. This case supports the concept of "Food as medicine" targeting the uremic phenotype in cardiorenal syndrome.


Assuntos
Humanos , Biomarcadores/sangue , Bertholletia , Síndrome Cardiorrenal , Disbiose , Glutationa Peroxidase
14.
Front Immunol ; 13: 1021828, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36569901

RESUMO

Introduction: The anti-CD20 antibody rituximab (RTX) has substantially improved outcomes of patients with B-cell lymphomas, although more efficient therapies are needed for refractory or relapsing lymphomas. An approach to increase the clinical effectiveness of anti-tumor therapy is the use of antibody-cytokine fusion proteins (immunocytokines (ICKs)) to deliver at the tumor site the antibody effector functions and cytokines that trigger anti-tumor activities. In particular, IL-2-based ICKs have shown significant results in preclinical studies but not in clinical trials due to the toxicity profile associated to high doses IL-2 and the undesired expansion of Tregs. Methods: To improve the efficacy of RTX therapy, we fused a murine (mIgG2a) or a human (hIgG1) version of RTX to a mutated IL-2 (no-alpha mutein), which has a disrupted affinity for the high affinity IL-2 receptor (IL-2R) to prevent the stimulation of Tregs and reduce the binding to endothelial cells expressing CD25, the α chain of high affinity IL-2R. Characterization of anti-CD20-IL2no-alpha ICKs was performed by SDS-PAGE, Western-blotting and SEC-HPLC and also by several functional in vitro techniques like T-cell proliferation assays, apoptosis, CDC and ADCC assays. The in vivo activity was assessed by using murine tumor cells expressing huCD20 in C57/Bl6 mice. Results: Both ICKs exhibited similar in vitro specific activity of their IL2no-alpha mutein moieties and kept CD20-binding capacity. Anti-CD20-IL2no-alpha (hIgG1) retained antibody effector functions as complement-dependent cytotoxicity and enhanced direct apoptosis, NK cell activation and antibody-dependent cellular cytotoxicity relative to RTX. In addition, both ICKs demonstrated a higher antitumor efficacy than parental molecules or their combination in an EL4-huCD20 tumor model in immunocompetent mice. Anti-CD20-IL2no-alpha (hIgG1) strongly expanded NK and CD8+ T cells but not Tregs in tumor-bearing mice. Discussion: These findings suggest that anti-CD20-IL2no-alpha could represent an alternative treatment for B cell lymphoma patients, mainly those refractory to RTX therapy.


Assuntos
Interleucina-2 , Linfoma de Células B , Humanos , Camundongos , Animais , Células Endoteliais/patologia , Recidiva Local de Neoplasia , Rituximab/farmacologia , Rituximab/uso terapêutico , Anticorpos/uso terapêutico
15.
Microb Pathog ; 170: 105697, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35926804

RESUMO

The prevalence of multidrug-resistant (MDR) bacteria and the limited efficacy of current available antibiotics cause every year approximately 700 000 deaths per year. This study aimed to evaluate the anti-inflammatory effect and antibacterial potential of the ibuprofen derivative Methyl 2-(-4-isobutylphenyl)propanoate (MET-IBU). The molecular structure of MET-IBU was confirmed by Nuclear Magnetic Resonance (NMR) and, Attenuated Total Reflectance Fourier Transform Infrared spectroscopy (ATR-FTIR) spectroscopy. Our in vivo study using adult zebrafish model demonstrated that the ibuprofen derivative MET-IBU also possesses anti-inflammatory effect, and in vitro antibacterial activity assays showed that in the association of ampicillin, norfloxacin, and gentamicin with MET-IBU occurred reduction in the minimum inhibitory concentration (MIC) for MDR bacterial strains of Escherichia coli 06 and Staphylococcus aureus 10, indicating a potentiating in the growth inhibition of these pathogenic bacteria. Regarding the strain of Staphylococcus aureus K2068 (overexpressing mepA gene), a potentiation of ethidium bromide was found in the association with MET-IBU, indicating the action of this compound on the efflux pump mechanism present in this strains. This result corroborates the molecular docking study that indicated a high affinity of the MET-IBU with the MepA efflux pump. It was also noticed an antibiotic potentiating activity in the association MET-IBU with norfloxacin against strains of Staphylococcus aureus 1199B (overexpressing norA gene) when compared to the norfloxacin control. This enhanced antibiotic effect of MET-IBU is associated with a second resistance mechanism, which is due to the modification in the topoisomerase enzyme. These results bring attention to the ibuprofen derivative MET-IBU as possible candidate for the development of new options for the treatment of bacterial infections with protective anti-inflammatory action.


Assuntos
Infecções por Escherichia coli , Infecções Estafilocócicas , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Farmacorresistência Bacteriana Múltipla , Escherichia coli/metabolismo , Ibuprofeno/farmacologia , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Norfloxacino/química , Norfloxacino/farmacologia , Propionatos/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus , Peixe-Zebra
16.
J Food Biochem ; 46(10): e14294, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35762459

RESUMO

Oxidative stress, adipose tissue, and bone compartments can be disturbed in chronic diseases. Non-pharmacological strategies, such as Brazil nuts (BNs), can improve these parameters. This study evaluated the effects of BN supplementation at different concentrations on body composition, lipid profile, and peroxidation in healthy rats. Male Wistar rats were divided into three groups: control (CT), Brazil nut 5% (BN5), and Brazil nut 10% (BN10) groups. Body composition, brown adipose tissue (BAT), plasma lipid peroxidation, and lipid profile were evaluated in the three groups. The BN5 group showed an improvement in all bone parameters compared with that of the CT group (p  < .0001). The BN5 and BN10 groups showed reduced plasma lipid peroxidation compared with that of the CT group (p = .0009), whereas the BN10 group presented lower BAT lipid peroxidation than that of the other groups (p = .01). High-density lipoprotein-cholesterol (HDL-c) levels were higher in the BN5 group than in the CT group (p = .01). Conclusively, the use of BNs in a controlled manner promoted improvement in bone parameters, HDL-c levels, and lipid peroxidation in healthy rats. PRACTICAL APPLICATIONS: Nuts has been included in the diet because of their versatility, acceptance, and easy access. Among them, Brazil nut (BN) is considered one of the major known food sources of selenium as well as a source of fibers, unsaturated fatty acids, and phenolic compounds. Studies have shown that BN supplementation is effective in reducing oxidative stress, inflammation, lipid peroxidation, and selenium deficiency when used as a non-pharmacological strategy in experimental models of chronic diseases and in clinical trials. The present study showed that controlled administration of BN improved bone parameters, high-density lipoprotein-cholesterol levels, and lipid peroxidation in healthy rats. Therefore, BN is a promising non-pharmacological agent for the prevention of the onset of chronic non-communicable diseases.


Assuntos
Bertholletia , Selênio , Animais , Masculino , Ratos , Composição Corporal , Colesterol , Dieta , Suplementos Nutricionais , Ácidos Graxos Insaturados , Peroxidação de Lipídeos , Lipídeos , Lipoproteínas HDL , Ratos Wistar
17.
J Food Biochem ; 46(8): e14201, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35467017

RESUMO

The purposes of this study were to assess the effect of Brazil nut supplementation on trimethylamine N-oxide (TMAO) levels and glutathione peroxidase (GPx) activity in patients with coronary artery disease (CAD). Patients with CAD were randomly assigned to two groups, Brazil nut group (23 patients, 48% male, 62.7 ± 6.8 years, 29.4 ± 5.8 kg/m2 ), which received one Brazil nut per day for 3 months, and the control group (14 patients, 43% male, 63.7 ± 8.7 years, 28.4 ± 4.2 kg/m2 ) who did not receive any supplementation. After 3 months, TMAO levels and their precursors did not change in either group. Although not significant, GPx activity increased by 41% in the Brazil nut group. TMAO levels were negatively associated with total fiber intake (r = -0.385 and p = .02). A 3-month Brazil nut supplementation did not change TMAO levels and GPx activity in CAD patients. PRACTICAL APPLICATIONS: Trimethylamine N-oxide (TMAO) has been associated with oxidative stress and cardiovascular disease risk. Thus, the increase in antioxidants enzymes production could be a promising strategy to reduce TMAO-mediated oxidative stress. In this context, nutritional strategies are well-known as activators of cellular antioxidant responses. As Brazil nuts have a known role in reducing oxidative stress by increasing glutathione peroxidase (GPx) activity (a selenium-dependent antioxidant enzyme), this study hypothesized that Brazil nuts could be a strategy that, via antioxidant capacity, would reduce TMAO plasma levels. Although no changes in TMAO levels and GPx activity can be observed in this study, it is believed that other results can be obtained depending on the dosage used. Thus, this study can open new paths and direct other studies with different doses and treatment times to evaluate the effects of Brazil Nuts on TMAO levels.


Assuntos
Bertholletia , Doença da Artéria Coronariana , Antioxidantes , Doença da Artéria Coronariana/tratamento farmacológico , Suplementos Nutricionais , Feminino , Glutationa Peroxidase , Humanos , Masculino , Metilaminas , Óxidos
18.
Int Urol Nephrol ; 54(10): 2645-2652, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35347555

RESUMO

BACKGROUND AND OBJECTIVES: Recent studies have shed light on the potential role of curcumin in mitigating inflammation in patients with chronic kidney disease (CKD). This study aimed to evaluate the effects of curcumin supplementation on plasma levels of markers of inflammation and oxidative stress in patients with CKD undergoing hemodialysis (HD). METHODS: These are secondary exploratory analyses from a previous double-blind, randomized controlled pilot study registered under ClinicalTrials.gov Identifier no. NCT00123456. It included 28 hemodialysis patients from a previous study divided into two groups: curcumin group (receiving juice with 2.5 g of turmeric 3×/week for 12 weeks) and a control group. The TNF-α, IL-6 and Ox-LDL plasma levels were measured by sandwich enzyme immunoassays ELISA; lipid peroxidation was measured by the reaction between malondialdehyde (MDA) and thiobarbituric acid. RESULTS: After 12 weeks of supplementation with curcumin, the TNF-α plasma levels were significantly reduced [from 15.0 (8.23-73.3) to 6.17 (1.11-55.0) pg/mL, p = 0.01]. CONCLUSION: 12 weeks of treatment with curcumin in HD patients resulted in a reduction in the biomarker of inflammation (TNF-α), confirming our previous hypothesis that curcumin has an anti-inflammatory effect.


Assuntos
Curcumina , Insuficiência Renal Crônica , Biomarcadores , Curcumina/farmacologia , Curcumina/uso terapêutico , Suplementos Nutricionais , Método Duplo-Cego , Humanos , Inflamação/complicações , Estresse Oxidativo , Diálise Renal/efeitos adversos , Insuficiência Renal Crônica/complicações , Fator de Necrose Tumoral alfa
19.
Folia Microbiol (Praha) ; 67(3): 447-457, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35112321

RESUMO

Due to the increase in fungal resistance to existing drugs, a need exists to search for new antifungals. This study aimed to evaluate the antifungal activity of α, ß, and δ-damascone and inclusion complexes with ß-cyclodextrin against different Candida spp. The inclusion complex of ß-damascone was prepared by the co-evaporation method using three molar proportions (1:1; 2:1; 3:1 (ßDA-ßCD)) and analyzed using Fourier transform infrared spectroscopy (FTIR). Standard Candida albicans (CA INCQS 40,006), Candida krusei (CK INCQS 40,095), and Candida tropicalis (CT INCQS 40,042) strains were used to evaluate antifungal activity. The substances were tested individually or in association with fluconazole (FCZ). The IC50 and cell viability curve constructions were performed using the microdilution method. The minimum fungicidal concentration (MFC) was determined by the subculture method in a solid medium. The α, ß, and δ-DA isolated or in combination with fluconazole (FCZ) showed significant antifungal activity. ß-damascone showed effective complexation in the three molar proportions assayed; however, none of the inclusion complexes was demonstrated clinically significant effects against the fungal tested. Then, all compounds have shown promising antifungal activities; however, in vivo assays are necessary to have therapeutical application in the future.


Assuntos
Antifúngicos , beta-Ciclodextrinas , Antifúngicos/química , Antifúngicos/farmacologia , Candida , Fluconazol/farmacologia , Testes de Sensibilidade Microbiana , Norisoprenoides/farmacologia , beta-Ciclodextrinas/farmacologia
20.
Molecules ; 27(2)2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35056741

RESUMO

The purpose of the present work was to prepare polypropylene (PP) matrix composited filled with chemically treated pistachio shell particles (PTx), and evaluate their effect on the composites' thermal properties. PP-PTx composites were formulated in different PTx content (from 2 to 10 phr) in a mixing chamber, using the melt-mixing process. The PTx were chemically treated using a NaOH solution and infrared spectroscopy (FTIR). According to thermogravimetric analysis (TGA), the treatment of pistachio shell particles resulted in the remotion of lignin and hemicellulose. The thermal stability was evaluated by means of TGA, where the presence of PTx in composites showed a positive effect compared with PP pristine. Thermal properties such as crystallization temperature (Tc), crystallization enthalpy (∆Hc), melting temperature (Tm) and crystallinity were determinate by means differential scanning calorimetry (DSC); these results suggest that the PTx had a nucleation effect on the PP matrix, increasing their crystallinity. Dynamic mechanical analysis (DMA) showed that stiffness of the composites increase compared with that PP pristine, as well as the storage modulus, and the best results were found at a PTx concentration of 4 phr. At higher concentrations, the positive effect decreased; however, they were better than the reference PP.


Assuntos
Materiais Biocompatíveis/química , Pistacia/química , Polipropilenos/química , Varredura Diferencial de Calorimetria , Cristalização , Lignina , Nozes/química , Espectroscopia de Infravermelho com Transformada de Fourier , Termodinâmica , Termogravimetria
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