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1.
J Colloid Interface Sci ; 592: 156-166, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33652169

RESUMO

The antiretroviral (ARV) cocktailrevolved the treatment of the human immunodeficiency virus (HIV) infection. Drug combinations have been also tested to treat other infectious diseases, including the recentcoronavirus disease 2019 (COVID-19) outbreak. To simplify administration fixed-dose combinationshave been introduced, however, oral anti-HIV therapy still struggles with low oral bioavailability of many ARVs.This work investigated the co-encapsulation of two clinically relevant ARV combinations,tipranavir (TPV):efavirenz (EFV) anddarunavir (DRV):efavirenz (EFV):ritonavir (RTV),within the core of ß-casein (bCN) micelles. Encapsulation efficiency in both systems was ~100%. Cryo-transmission electron microscopy and dynamic light scattering of the ARV-loaded colloidaldispersions indicatefull preservation of the spherical morphology, and x-ray diffraction confirm that the encapsulated drugs are amorphous. To prolong the physicochemical stabilitythe formulations were freeze-driedwithout cryo/lyoprotectant, and successfully redispersed, with minor changes in morphology.Then, theARV-loaded micelles were encapsulated within microparticles of Eudragit® L100, which prevented enzymatic degradation and minimized drug release under gastric-like pH conditionsin vitro. At intestinal pH, the coating polymer dissolved and released the nanocarriers and content. Overall, our results confirm the promise of this flexible and modular technology platform for oral delivery of fixed dose combinations.


Assuntos
Antirretrovirais , Caseínas , Infecções por HIV/tratamento farmacológico , HIV-1 , Micelas , Antirretrovirais/química , Antirretrovirais/farmacocinética , Antirretrovirais/farmacologia , Caseínas/química , Caseínas/farmacocinética , Caseínas/farmacologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Combinação de Medicamentos , Humanos
2.
BMC Oral Health ; 21(1): 136, 2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33740976

RESUMO

BACKGROUND: Streptococcus mutans is a common cariogenic bacterium in the oral cavity involved in plaque formation. Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) has been introduced into tooth mousse to encourage remineralization of dental enamel. The aim of this research was to study the effect of tooth mousse containing CPP-ACP (GC Tooth Mousse®) or CPP-ACP with 0.2% fluoride (CPP-ACPF; GC Tooth Mousse Plus®; GCP) on S. mutans planktonic growth and biofilm formation. METHODS: S. mutans was cultivated in the presence of different dilutions of the tooth mousse containing CPP-ACP or CPP-ACPF, and the planktonic growth was determined by ATP viability assay and counting colony-forming units (CFUs). The resulting biofilms were examined by crystal violet staining, MTT metabolic assay, confocal laser scanning microscopy (CLSM), and scanning electron microscope (SEM). RESULTS: The CPP-ACP tooth mousse (GC) at a dilution of 5-50 mg/ml (0.5-5%) did not inhibit planktonic growth, and even increased the ATP content and the number of viable bacteria after a 24 h incubation. The same was observed for the CPP-ACPF tooth mousse (GCP), except for the higher concentrations (25 and 50 mg/ml) that led to a drop in the bacterial count. Importantly, both compounds significantly decreased S. mutans biofilm formation at dilutions as low as 1.5-3 mg/ml. 12.5 mg/ml GC and 6.25 mg/ml GCP inhibited biofilm formation by 90% after 4 h. After 24 h, the MBIC90 was 6.25 mg/ml for both. CLSM images confirmed the strong inhibitory effect GC and GCP had on biofilm formation when using 5 mg/ml tooth mousse. SEM images of those bacteria that managed to form biofilm in the presence of 5 mg/ml tooth mousse, showed alterations in the bacterial morphology, where the streptococci appear 25-30% shorter on the average than the control bacteria. CONCLUSION: Our data show that the tooth mousse containing CPP-ACP reduces biofilm formation of the cariogenic bacterium S. mutans without killing the bacteria. The use of natural substances which inhibit biofilm development without killing the bacteria, has therapeutic benefits, especially in orthodontic pediatric patients.


Assuntos
Caseínas , Streptococcus mutans , Biofilmes , Fosfatos de Cálcio , Caseínas/farmacologia , Criança , Humanos , Fosfopeptídeos , Remineralização Dentária
3.
Food Chem ; 350: 129302, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33618089

RESUMO

Caseinate was glycated with oligochitosan via transglutaminase (TGase) action and then hydrolyzed by trypsin to generate glycated caseinate hydrolysate (GCNH) that was investigated for in vivo immune-promoting activity. Caseinate hydrolysate (CNH) containing glucosamine of 5.7 g/kg had amino acid compositions similar to GCNH. In normal BALB/c mice, GCNH at 100-400 mg/(kg d) showed higher immune-promoting activity than CNH via increasing serum IgM, IgA, and IgG by 1.5-24.5%, enhancing spleen and thymus indices by 9.7-26.2%, or increasing splenocyte lymphocyte proliferation and natural killer (NK) cell activity by 1.2-11.5%. GCNH also exerted higher activity than CNH in the suppressed BALB/c mice through increasing serum IgM, IgA, and IgG by 2.6-10.5%, enhancing spleen and thymus indices by 0.4-50.1%, or increasing splenocyte lymphocyte proliferation and NK cell activity by 3.4-18.9%. The results highlight that this TGase-type oligochitosan-glycation is potential to generate functional protein ingredients that possess improved immune-promoting activity once hydrolyzed by trypsin.


Assuntos
Caseínas/química , Caseínas/farmacologia , Quitina/análogos & derivados , Fatores Imunológicos/química , Fatores Imunológicos/farmacologia , Transglutaminases/metabolismo , Animais , Apoptose/efeitos dos fármacos , Caseínas/metabolismo , Quitina/química , Glicosilação , Hidrólise , Fatores Imunológicos/metabolismo , Células Matadoras Naturais/citologia , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Relação Estrutura-Atividade
4.
Int J Food Microbiol ; 341: 109074, 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33508583

RESUMO

Campylobacter jejuni (C. jejuni) is one of the most common foodborne pathogens that cause human sickness mostly through the poultry food chain. Cinnamon essential oil (CEO) has excellent antibacterial ability against C. jejuni growth. This study investigated the antibacterial mechanism of CEO against C. jejuni primarily through metabolism, energy metabolism of essential enzymes (AKPase, ß-galactosidase, and ATPase), and respiration metabolism. Results showed that the hexose monophosphate pathway (HMP) was inhibited, and that the enzyme activity of G6DPH substantially decreased upon treatment with CEO. Analysis of the effect of CEO on the expression of toxic genes was performed by the real-time PCR (RT-PCR). The expression levels of the toxic genes cadF, ciaB, fliA, and racR under CEO treatment were determined. Casein/CEO nanospheres were further prepared for the effective inhibition of C. jejuni and characterized by particle-size distribution, zeta-potential distribution, fluorescence, TEM, and GC-MS methods. Finally, the efficiency of CEO and casein/CEO nanospheres in terms of antibacterial activity against C. jejuni was verified. The casein/CEO nanospheres displayed high antibacterial activity on duck samples. The population of the test group decreased from 4.30 logCFU/g to 0.86 logCFU/g and 4.30 logCFU/g to 2.46 logCFU/g at 4 °C and at 25 °C for C. jejuni, respectively. Sensory evaluation and texture analysis were also conducted on various duck samples.


Assuntos
Antibacterianos/farmacologia , Infecções por Campylobacter/veterinária , Campylobacter jejuni/efeitos dos fármacos , Caseínas/farmacologia , Cinnamomum zeylanicum/química , Óleos Voláteis/farmacologia , Animais , Infecções por Campylobacter/tratamento farmacológico , Galinhas/microbiologia , Preparações de Ação Retardada/farmacologia , Patos/microbiologia , Metabolismo Energético/efeitos dos fármacos , Doenças Transmitidas por Alimentos/microbiologia , Doenças Transmitidas por Alimentos/prevenção & controle , Expressão Gênica/efeitos dos fármacos , Glucosefosfato Desidrogenase/antagonistas & inibidores , Humanos , Nanosferas , Via de Pentose Fosfato/efeitos dos fármacos , Aves Domésticas/microbiologia
5.
Arch Oral Biol ; 122: 105001, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33316658

RESUMO

OBJECTIVE: To evaluate the effects of combination of treatments with fluoridated toothpastes supplemented with sodium trimetaphosphate (TMP) and casein phosphopeptide-amorphous calcium phosphate (MI Paste Plus®), on the remineralization of dental enamel. DESIGN: Enamel blocks with artificial caries were randomly allocated into six groups (n = 12), according to the toothpastes: 1) without F-TMP-MI Paste Plus® (Placebo); 2) 1100 ppm F (1100 F), 3) MI Paste Plus®, 4) 1100 F + MI Paste Plus® (1100 F-MI Paste Plus®), 5) 1100 F + 3% TMP (1100 F-TMP) and 6) 1100 F-TMP + MI Paste Plus® (1100 F-TMP-MI Paste Plus®). Blocks were treated 2×/day with slurries of toothpastes (1 min). Furthermore, groups 4 and 6 received the application of MI Paste Plus® for 3 min. After pH cycling, the percentage of surface hardness recovery (%SHR); integrated loss of subsurface hardness (ΔKHN); profile analysis and lesion depth subsurface through polarized light microscopy (PLM), confocal laser scanning microscopy (LSCM), scanning electron microscopy (SEM), fluoride (F), calcium (Ca), phosphorus (P) concentrations in the enamel were determined. The data were analyzed by ANOVA (1-criterion) and Student-Newman-Keuls test (p < 0.001). RESULTS: 1100 F-TMP-MI Paste Plus® group showed the best results of %SHR, ΔKHN and PLM (p < 0.001). F concentration was similar between the 1100 F, 1100 F-MI Paste Plus®, and 1100 F-TMP-MI Paste Plus® groups (p > 0.001). 1100 F-TMP-MI Paste Plus® group showed the highest concentration of Ca and P in the enamel (p < 0.001). CONCLUSION: The association of 1100 F-TMP and MI Paste Plus® led to a significant increase in the remineralization of initial carious lesions.


Assuntos
Fosfatos de Cálcio/farmacologia , Cariostáticos/farmacologia , Esmalte Dentário/efeitos dos fármacos , Fluoretos/farmacologia , Polifosfatos/farmacologia , Remineralização Dentária , Caseínas/farmacologia , Cárie Dentária/tratamento farmacológico , Humanos , Técnicas In Vitro , Fosfopeptídeos/farmacologia , Distribuição Aleatória , Cremes Dentais/farmacologia
6.
Clin Interv Aging ; 15: 743-754, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32546992

RESUMO

Background: Preventative measures have recently been taken to reduce the incidence of Alzheimer's disease worldwide. We previously showed that Met-Lys-Pro (MKP), a casein-derived angiotensin-converting enzyme inhibitory peptide with the potential to cross the blood-brain barrier, attenuated cognitive decline in a mouse model of Alzheimer's disease. However, the effect of MKP on cognitive function improvement in humans remains unknown. This exploratory study sought to investigate whether MKP intake could improve cognitive function in adults without dementia. Methods: A total of 268 community-dwelling adults without dementia participated in this 24-week randomized controlled trial. Participants were randomly allocated to the MKP (n = 134) or placebo (n = 134) group. The MKP group received four tablets daily, each containing 50 µg MKP, while the placebo group received four dextrin tablets containing no detectable MKP for 24 weeks. Scores on the Japanese version of the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog) were used as the primary outcome to compare cognitive function between the MKP and placebo groups. The study products were also evaluated for safety. Results: The intention-to-treat analysis showed that there was no significant difference between the groups in terms of the ADAS-cog total score. Orientation, as measured by the respective ADAS-cog subscale, was significantly improved compared to placebo at 24 weeks post-MKP administration (P = 0.022). No serious adverse events due to MKP intake were observed. Conclusion: To the best of our knowledge, this is the first study to report the effects of MKP on human cognition. These preliminary results suggested the safety of daily MKP intake and its potential to improve orientation in adults without dementia. Further clinical studies are needed to confirm the present findings and the benefits of MKP on cognitive function.


Assuntos
Caseínas/farmacologia , Cognição/efeitos dos fármacos , Disfunção Cognitiva , Oligopeptídeos/administração & dosagem , Administração Oral , Idoso , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/prevenção & controle , Método Duplo-Cego , Feminino , Humanos , Vida Independente , Masculino , Testes Neuropsicológicos , Nootrópicos/administração & dosagem , Comprimidos , Resultado do Tratamento
7.
BMC Oral Health ; 20(1): 169, 2020 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-32532263

RESUMO

BACKGROUND: Recent preventive strategies for dental caries focus on targeting the mechanisms underlying biofilm formation, including the inhibition of bacterial adhesion. A promising approach to prevent bacterial adhesion is to modify the composition of acquired salivary pellicle. This in vitro study investigated the effect and possible underlying mechanism of pellicle modification by casein phosphopeptide (CPP) on Streptococcus mutans (S. mutans) initial adhesion, and the impact of fluoride on the efficacy of CPP. METHODS: The salivary pellicle-coated hydroxyapatite (s-HA) discs were treated with phosphate buffered saline (negative control), heat-inactivated 2.5% CPP (heat-inactivated CPP), 2.5% CPP (CPP) or 2.5% CPP supplemented with 900 ppm fluoride (CPP + F). After cultivation of S. mutans for 30 min and 2 h, the adherent bacteria were visualized by scanning electron microscopy (SEM) and quantitatively evaluated using the plate count method. Confocal laser scanning microscopy (CLSM) was used to evaluate the proportions of total and dead S. mutans. The concentrations of total, free, and bound calcium and fluoride in the CPP and fluoride-doped CPP solutions were determined. The water contact angle and zeta potential of s-HA with and without modification were measured. The data were statistically analyzed using one-way ANOVA followed by a Turkey post hoc multiple comparison test. RESULTS: Compared to the negative control group, the amount of adherent S. mutans significantly reduced in the CPP and CPP + F groups, and was lowest in the CPP + F group. CLSM analysis showed that there was no statistically significant difference in the proportion of dead S. mutans between the four groups. Water contact angle and zeta potential of s-HA surface significantly decreased in the CPP and CPP + F groups as compared to the negative control group, and both were lowest in the CPP + F group. CONCLUSIONS: Pellicle modification by CPP inhibited S. mutans initial adhesion to s-HA, possibly by reducing hydrophobicity and negative charge of the s-HA surface, and incorporating fluoride into CPP further enhanced the anti-adhesion effect.


Assuntos
Aderência Bacteriana/efeitos dos fármacos , Caseínas/farmacologia , Cárie Dentária/prevenção & controle , Durapatita/química , Fluoretos/farmacologia , Fosfopeptídeos/farmacologia , Saliva/química , Streptococcus mutans/efeitos dos fármacos , Biofilmes , Materiais Revestidos Biocompatíveis/química , Suscetibilidade à Cárie Dentária , Humanos , Saliva/microbiologia , Proteínas e Peptídeos Salivares/metabolismo , Streptococcus mutans/isolamento & purificação , Streptococcus mutans/fisiologia , Turquia
8.
J Dairy Sci ; 103(6): 4907-4918, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32253041

RESUMO

In this study, we investigated the effect of goat milk casein hydrolysates on glucose consumption rate, intracellular glycogen concentration, and mRNA expression of gluconeogenesis-related genes, including phosphoenolpyruvate carboxykinase 1 (PCK1) and glucose-6-phosphatase catalytic subunit (G6PC), in insulin-resistant HepG2 cells. From the obtained hydrolysates, we also purified and characterized novel peptides that ameliorated high-glucose-induced insulin resistance in HepG2 cells. The 3-h hydrolysate caused the highest glucose consumption rate in insulin-resistant HepG2 cells. It also showed positive effects on promoting intracellular glycogenesis and reducing mRNA expression of PCK1 and G6PC. We separated the obtained hydrolysates into 3 fractions (F1, F2, and F3) by gel filtration chromatography; we further purified F1 using reversed-phase HPLC and identified peptides using liquid chromatography-tandem mass spectrometry. The bioactive peptides identified were SDIPNPIGSE (αS1-casein, f195-204), NPWDQVKR (αS2-casein, f123-130), SLSSSEESITH (ß-casein, f30-40), and QEPVLGPVRGPFP (ß-casein, f207-219). Our findings indicated that specific bioactive peptides from goat milk casein hydrolysates ameliorated insulin resistance in HepG2 cells that had been treated with high glucose. This is a first step toward determining whether goat milk casein hydrolysates can be used as food ingredients to ameliorate insulin resistance.


Assuntos
Caseínas/química , Cabras , Resistência à Insulina , Peptídeos/farmacologia , Animais , Caseínas/metabolismo , Caseínas/farmacologia , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Gluconeogênese/genética , Glucose/metabolismo , Glicogênio/metabolismo , Cabras/metabolismo , Células Hep G2 , Humanos , Leite/química , Peptídeos/metabolismo
9.
Cytotherapy ; 22(5): 291-300, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32220549

RESUMO

BACKGROUND: This study examined the freezing responses of peripheral blood mononuclear cells (PBMCs) and specific white blood cell subsets contained therein when cryopreserved in three combinations of osmolytes composed of sugars, sugar alcohols and amino acids. METHODS: A differential evolution algorithm with multiple objectives was used to optimize cryoprotectant composition and thus the post-thaw recoveries for both helper and cytotoxicity T cells simultaneously. RESULTS: The screening of various formulations using a differential evolution algorithm showed post-thaw recoveries greater than 80% for the two subsets of T cells. The phenotypes and viabilities of PBMC subsets were characterized using flow cytometry. Significant differences between the post-thaw recovery for helper T cells and cytotoxic T cells were observed. Statistical models were used to analyze the importance of individual osmolytes and interactions between post-thaw recoveries of three subsets of T cell including helper T cells, cytotoxic T cells and natural killer T cells. The statistical model indicated that the preferred concentration levels of osmolytes and interaction modes were distinct between the three subsets studied. PBMCs were cultured for 72 h post-thaw to determine the stability of the cells. Because post-thaw apoptosis is a significant concern for lymphocytes, apoptosis of helper T cell and cytotoxic T cells frozen in a DMSO-free cryoprotectant was analyzed immediately post-thaw and 24 h post-thaw. Both cell types showed a decrease in cell viability 24 h post-thaw compared with immediately post-thaw. Helper T cell viability dropped 17%, and cytotoxic T cells had a 10% drop in viability. Immediately post-thaw, both cell types had >30% of cells in early apoptosis, but after 24 h the number of cells in early apoptosis decreased to below 20%. CONCLUSION: This study helped us identify the freezing responses of different human PBMC subsets using combinations of osmolytes.


Assuntos
Carboidratos/farmacologia , Caseínas/farmacologia , Criopreservação/métodos , Crioprotetores/farmacologia , Dimetil Sulfóxido/farmacologia , Lipídeos/farmacologia , Células T Matadoras Naturais , Proteínas de Vegetais Comestíveis/farmacologia , Linfócitos T Citotóxicos , Linfócitos T Auxiliares-Indutores , Adulto , Idoso , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Citometria de Fluxo , Voluntários Saudáveis , Humanos , Células Jurkat , Masculino , Pessoa de Meia-Idade
10.
Sci Rep ; 10(1): 2754, 2020 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-32066788

RESUMO

The number of colon cancer cases is increasing worldwide, and type II diabetes patients have an increased risk of developing colon cancer. Diet-borne advanced glycation end-products (AGEs) may promote neoplastic transformation; however, the mechanisms involved remain elusive. The present study helped to define the relationship between dietary AGEs and cancer progression. C2BBe1 adenocarcinoma enterocytes were exposed to 200 µg/mL glycated casein (AGEs-Csn) for up to 24 h. AGEs-Csn exposure resulted in increased cell proliferation, maladaptative changes in SOD and CAT activity and moderate levels of hydrogen peroxide (H2O2) intracellular accumulation. AGEs-Csn activated pro-survival and proliferation signalling, such as the phosphorylation of mTOR (Ser2448) and Akt (Ser473). GSK-3ß phosphorylation also increased, potentially inducing extracellular matrix remodelling and thus enabling metastasis. Moreover, AGEs-Csn induced MMP-1, -3, -7, -9 and -10 expression and activated MMP-2 and MMP-9, which are regulators of the extracellular matrix and cytokine functions. AGEs-Csn induced inflammatory responses that included extracellular IL-1ß at 6 h; time-dependent increases in IL-8; RAGE and NF-κB p65 upregulation; and IκB inhibition. Co-treatment with anti-RAGE or anti-TNF-α blocking antibodies and AGEs-Csn partially counteracted these changes; however, IL-8, MMP-1 and -10 expression and MMP-9 activation were difficult to prevent. AGEs-Csn perpetuated signalling that led to cell proliferation and matrix remodelling, strengthening the link between AGEs and colorectal cancer aggressiveness.


Assuntos
Caseínas/farmacologia , Enterócitos/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Produtos Finais de Glicação Avançada/farmacologia , Adenocarcinoma/etiologia , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/metabolismo , Caseínas/química , Catalase/genética , Catalase/metabolismo , Linhagem Celular Tumoral , Neoplasias do Colo/etiologia , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Enterócitos/metabolismo , Enterócitos/patologia , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Glicosilação , Humanos , Proteínas I-kappa B/genética , Proteínas I-kappa B/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-8/genética , Interleucina-8/metabolismo , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Modelos Biológicos , NF-kappa B/genética , NF-kappa B/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo
11.
BMC Oral Health ; 20(1): 49, 2020 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-32046691

RESUMO

BACKGROUND: This study investigated the remineralisation effect of bioactive glass on artificial dentine caries. METHODS: Dentine disks with artificial caries were treated with bioactive glass (group BAG), casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) (group CPP-ACP), sodium fluoride glycerol (group F) or deionized water (group W). All disks were subjected to pH cycling for 28 days subsequently. The topography, microhardness and remineralisation depth of the dentine carious lesion were assessed by atomic force microscopy (AFM), microhardness testing and confocal laser scanning microscope (CLSM), respectively. RESULTS: AFM images indicated mineral depositions on the surface of the carious lesion in group BAG. The changes of Vickers hardness number (ΔVHN, mean ± SD) after pH cycling were 9.67 ± 3.60, 6.06 ± 3.83, 5.00 ± 2.19 and - 1.90 ± 2.09 (p < 0.001) in group BAG, group CPP-ACP, group F and group W, respectively. The remineralisation depth (mean ± SD) of the carious lesion in group BAG, group CPP-ACP, group F and group W were 165 ± 11 µm, 111 ± 11 µm, 75 ± 6 µm and 0 µm (p < 0.001), respectively. CONCLUSION: Bioactive glass possessed a promising remineralisation effect on artificial dentine caries and could be a therapeutic choice for caries management.


Assuntos
Caseínas/farmacologia , Cárie Dentária/tratamento farmacológico , Esmalte Dentário/efeitos dos fármacos , Dentina/efeitos dos fármacos , Vidro/química , Remineralização Dentária , Caseínas/uso terapêutico , Dureza , Humanos , Fluoreto de Sódio
12.
Nutrients ; 12(1)2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31952248

RESUMO

This study evaluated the effects and the underlying mechanisms of casein glycomacropeptide hydrolysate (GHP) on high-fat diet-fed and streptozotocin-induced type 2 diabetes (T2D) in C57BL/6J mice. Results showed that 8-week GHP supplementation significantly decreased fasting blood glucose levels, restored insulin production, improved glucose tolerance and insulin tolerance, and alleviated dyslipidemia in T2D mice. In addition, GHP supplementation reduced the concentration of lipopolysaccharides (LPSs) and pro-inflammatory cytokines in serum, which led to reduced systematic inflammation. Furthermore, GHP supplementation increased muscle glycogen content in diabetic mice, which was probably due to the regulation of glycogen synthase kinase 3 beta and glycogen synthase. GHP regulated the insulin receptor substrate-1/phosphatidylinositol 3-kinase/protein kinase B pathway in skeletal muscle, which promoted glucose transporter 4 (GLUT4) translocation. Moreover, GHP modulated the overall structure and diversity of gut microbiota in T2D mice. GHP increased the Bacteroidetes/Firmicutes ratio and the abundance of S24-7, Ruminiclostridium, Blautia and Allobaculum, which might contribute to its antidiabetic effect. Taken together, our findings demonstrate that the antidiabetic effect of GHP may be associated with the recovery of skeletal muscle insulin sensitivity and the regulation of gut microbiota.


Assuntos
Caseínas/farmacologia , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/tratamento farmacológico , Dieta Hiperlipídica/efeitos adversos , Fragmentos de Peptídeos/farmacologia , Animais , Caseínas/administração & dosagem , Diabetes Mellitus Experimental , Suplementos Nutricionais , Microbioma Gastrointestinal/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Transportador de Glucose Tipo 4/metabolismo , Masculino , Camundongos , Fragmentos de Peptídeos/administração & dosagem
13.
Ultrason Sonochem ; 62: 104861, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31796325

RESUMO

Emodin is a bioactive compound with strong anti-inflammatory and antioxidant properties. Micellar casein is casein concentrates close to the native state of casein micelles. The interaction of emodin and micellar casein under heat treatment in the absence and presence of ultrasound was investigated, and the properties of microencapsulated emodin in micellar casein were compared. Fluorescence experiments proved that the major interaction between emodin and micellar casein was through hydrophobic forces under heat treatment in the absence and presence of ultrasound. However, ΔH, ΔS and ΔG of emodin-casein complexation without sonication were higher than those with sonication, in contradiction to binding constants. The particle sizes of emodin-casein complexes in the presence of ultrasound were smaller than those without sonication, while the specific surface area showed an opposite trend. As to encapsulation, emodin-casein capsules under heat-sonication treatment showed higher antioxidant properties than those of heat treatment alone under similar experimental conditions. Interestingly, micellar casein-emodin encapsulation in the presence of ultrasound showed a lower release rate of emodin in gastrointestinal conditions than that without ultrasound at the emdoin concentration of 10 µmol per gram casein. Ultrasound has been shown to be a potential processing technology for customizing the release kinetics of bioactive compounds.


Assuntos
Caseínas/química , Emodina/química , Temperatura Alta , Micelas , Ondas Ultrassônicas , Antioxidantes/farmacologia , Caseínas/farmacologia , Formas de Dosagem , Emodina/farmacologia , Interações Hidrofóbicas e Hidrofílicas , Tamanho da Partícula , Difração de Pó , Ligação Proteica , Análise Espectral/métodos , Termodinâmica
14.
J Dent ; 91: 103225, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31693918

RESUMO

OBJECTIVES: To determine if chewing gum containing casein phosphopeptide stabilised amorphous calcium phosphate (CPP-ACP) promoted an increase in the abundance of Streptococcus sanguinis and other species associated with dental health in supragingival plaque in a clinical study. MATERIALS AND METHODS: Nineteen participants were recruited for a three-leg cross-over, randomised, controlled clinical trial. Participants chewed a sugar-free gum with or without CPP-ACP six times daily for 20 min over two weeks. The study also involved no gum chewing (no gum) for the same two week period. Participants were randomly assigned to one of the test gums or no gum for each intervention period. Participants abstained from oral hygiene and had washout periods of two weeks between intervention periods. After each intervention period, supragingival plaque was collected and analysed for bacterial composition by sequencing the V4 variable region of the 16S rRNA gene. Data were analysed using a linear mixed model. RESULTS: The CPP-ACP gum intervention produced a significant (p < 0.01) increase in the proportions of S. sanguinis (112%), as well as the commensal species Rothia dentocariosa (127%), Corynebacterium durum (80%) and Streptococcus mitis (55%) when compared with the no gum intervention. All the species that were promoted by the CPP-ACP gum are known to possess one or both of the alkali-producing enzymes arginine deiminase and nitrate reductase. CONCLUSION: This clinical study demonstrated that chewing a sugar-free gum containing CPP-ACP promoted prebiosis by significantly increasing the proportion of S. sanguinis and other health-associated bacterial species in supragingival plaque. CLINICAL SIGNIFICANCE: Regular chewing of CPP-ACP sugar-free gum increases the proportions of health-associated commensal species in supragingival plaque to promote prebiosis and oral homeostasis.


Assuntos
Caseínas/farmacologia , Goma de Mascar , Esmalte Dentário/efeitos dos fármacos , Placa Dentária/metabolismo , Prebióticos , Estudos Cross-Over , Esmalte Dentário/metabolismo , Placa Dentária/tratamento farmacológico , Humanos , RNA Ribossômico 16S , Streptococcus , Streptococcus sanguis , Açúcares/efeitos adversos , Remineralização Dentária
15.
J Food Sci ; 84(11): 3083-3090, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31599975

RESUMO

Studies on the discovery and function of antioxidants are consistently being performed because oxidative stress can cause various diseases. Many compounds and natural products have antioxidant activity in vitro; however, it is often difficult to reproduce their effects in vivo. Additionally, methods to measure antioxidant activities in cells are also scarce. Here, we investigated the antioxidant activity of milk proteins by observing the formation of arsenite-induced stress granules as a tool to evaluate antioxidant activity in cells. Milk proteins not only decreased the formation of stress granules in several cell types but also scavenged 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical cations in vitro. In addition, milk proteins inhibited cellular senescence based on an SA-ß-galactosidase assay, and increased differentiation to myotubes from myoblasts isolated from the skeletal muscles of mouse pups. Taken together, our results demonstrate that milk proteins have an antiaging effect, especially prevention of skeletal muscle loss, through their antioxidant activities. PRACTICAL APPLICATION: Our results provide that antioxidant effects of milk proteins containing α-caseins, ß-caseins, and ß-lactoglobulin can mitigate aging-related damage induced by oxidative stress through showing inhibition of cellular senescence and increase of differentiation and maturation of myoblast. Therefore, we suggest that milk proteins could be potent health supplements to prevent aging-associated diseases, especially sarcopenia.


Assuntos
Antioxidantes/farmacologia , Caseínas/farmacologia , Bovinos , Lactoglobulinas/farmacologia , Leite/química , Envelhecimento/efeitos dos fármacos , Animais , Antioxidantes/análise , Arsenitos/farmacologia , Senescência Celular/efeitos dos fármacos , Feminino , Camundongos , Proteínas do Leite/farmacologia , Estresse Oxidativo/efeitos dos fármacos
16.
Comp Med ; 69(5): 384-400, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31575381

RESUMO

Periodontitis is an important public health concern worldwide. Because rodents from the genus Rattus are resistant to spontaneous periodontitis, experimental periodontitis must be initiated by mechanical procedures and interventions. Due to their exacerbated Th1 response and imbalanced Th17 regulatory T-cell responses, Lewis rats are highly susceptible to inducible inflammatory and autoimmune diseases. We hypothesized that feeding Lewis rats a diet high in sucrose and casein (HSC) would alter the oral microenvironment and induce inflammation and the development of periodontitis lesions without mechanical intervention. A baseline group (BSL, n = 8) was euthanized at age 6 wk. Beginning at 6 wk of age, 2 groups of Lewis rats were fed standard (STD, n = 12) or HSC (n = 20) chow and euthanized at 29 wk of age. We evaluated the degree of periodontitis through histology and µCT of maxillae and mandibles. The HSC-induced inflammatory response of periodontal tissues was assessed by using immunohistochemistry. Gene expression analysis of inflammatory cytokines associated with Th1 and Th17 responses, innate immunity cytokines, and tissue damage in response to bacteria were assessed also. The potential systemic effects of HSC diet were evaluated by assessing body composition and bone densitometry endpoints; serum leptin and insulin concentrations; and gene expression of inflammatory cytokines in the liver. Placing Lewis rats on HSC diet for 24 wk induced a host Th1-immune response in periodontal tissues and mild to moderate, generalized periodontitis characterized by inflammatory cell infiltration (predominantly T cells and macrophages), osteoclast resorption of alveolar bone, and hyperplasia and migration of the gingival epithelium. HSC-fed Lewis rats developed periodontitis without mechanical intervention in the oral cavity and in the absence of any noteworthy metabolic abnormalities. Consequently, the rat model we described here may be a promising approach for modeling mild to moderate periodontitis that is similar in presentation to the human disease.


Assuntos
Modelos Animais de Doenças , Periodontite/induzido quimicamente , Ratos Endogâmicos Lew , Animais , Caseínas/farmacologia , Humanos , Ratos , Sacarose/farmacologia
17.
Biomedica ; 39(2): 291-299, 2019 06 15.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31529816

RESUMO

Introduction: Sodium caseinate (CS) and its components (alpha-casein, beta-casein, and kappa-casein) have been shown to inhibit the proliferation of the mouse hematopoietic 32D clone 3 (32Dcl3) cell line and induce its differentiation into macrophages. It is well-known that alpha-casein induces IL-1ß production and that this cytokine inhibits the proliferation via the production of tumor necrosis factor alpha (TNF-alpha), but it is not known if CS and the caseins inhibit the proliferation via TNF-alpha production. Objective: To evaluate if CS and alpha-casein, beta-casein and kappa-casein inhibit the proliferation on 32Dcl3 cell line via TNF-alpha. Materials and methods: We used different concentrations of CS, alpha-casein, betacasein and kappa-casein in 32Dcl3 cells to evaluate cell proliferation. We assessed cell viability by MTT, induction to apoptosis by flow cytometry, and TNF-alpha synthesis by ELISA. Additionally, we performed anti-TNF-alpha neutralization assays on 32Dcl3 cells treated with CS and alpha-casein and we evaluated proliferation. Results: The results showed that CS, alpha-casein, beta-casein, and kappa-casein reduced proliferation of the 32Dcl3 cell line without affecting the viability and that only CS and alpha-casein induced apoptosis and the release of TNF-alpha. The 32Dcl3 cells treated with CS and alpha-casein reestablished their proliferation by using anti-TNF-alpha antibodies. Conclusion: TNF-alpha was the main responsible for the inhibition of proliferation in 32Dcl3 cells treated with CS or alpha-casein.


Assuntos
Caseínas/farmacologia , Células Mieloides/efeitos dos fármacos , Mielopoese/efeitos dos fármacos , Fator de Necrose Tumoral alfa/fisiologia , Animais , Apoptose/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Células Clonais , Macrófagos/citologia , Camundongos , Células Mieloides/citologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/biossíntese
18.
J Dairy Sci ; 102(12): 10711-10723, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31548055

RESUMO

The objective of this work was to obtain casein hydrolysates with aspartic proteinases present in extracts from the artichoke flower (Cynara scolymus L.) and evaluate their antioxidant, antimicrobial, and angiotensin-I converting enzyme (ACE) inhibitory activity in vitro. The casein hydrolysates produced by the action of C. scolymus had elevated antihypertensive and antioxidant activity due to their high hydrophobic peptide content (93.84, 96.58, and 90.54% at 2, 4, and 16 h of hydrolysis, respectively). Hydrolysis time and molecular weight (<3 kDa) had a significant influence on the hypertensive and antioxidant activity of the hydrolysates, which were greater at hydrolysis times of 4 and 16 h and corresponding to the <3 kDa fractions. The <3 kDa fraction of the 16 h hydrolysate had an ACE inhibitory activity with a half-maximal inhibitory concentration (IC50) of 71.77 µg peptides per mL; DPPH and ABTS•+ radical scavenging activities of 6.27 µM and 6.21 mM Trolox equivalents per mg of peptides, respectively; and iron (II) chelation activity with an IC50 of 221.49 µg of peptides per mL. Antimicrobial activity against Enterococcus faecalis was also observed in the hydrolysates. From the peptide sequences identified in the hydrolysates, we detected 22 peptides (from the BIOPEP database) that were already in their bioactive form (AMKPWIQPK, AMKPWIQPKTKVIPYVRYL, ARHPHPHLSFM, DAQSAPLRVY, FFVAPFPEVFGK, GPVRGPFPII, KVLPVPQK, LLYQEPVLGPVRGPFPIIV, MAIPPKKNQDK, NLHLPLPLL, PAAVRSPAQILQ, RELEELNVPGEIVESLSSSEESITR, RPKHPIKHQ, RPKHPIKHQGLPQEVLNENLLRF, SDIPNPIGSENSEK, TPVVVPPFLQP, VENLHLPLPLL, VKEAMAPK, VLNENLLR, VYPFPGPIH, VYQHQKAMKPWIQPKTKVIPYVRY, VYQHQKAMKPWIQPKTKVIPYVRYL) and are reported to display antioxidant, antimicrobial, and ACE inhibitory activity. We also identified 12,116, 14,513, and 25,169 peptide sequences in the hydrolysates at 2, 4, and 16 h, respectively, that were contained in the primary sequence, and these are reported to display ACE inhibitory, antioxidant, dipeptidyl peptidase IV inhibition, antithrombotic, opioid, immunomodulation, antiamnesic, anticancer, chelating, and hemolytic bioactivity.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Caseínas/farmacologia , Cynara scolymus/enzimologia , Peptídeo Hidrolases/metabolismo , Hidrolisados de Proteína/farmacologia , Inibidores da Enzima Conversora de Angiotensina/química , Inibidores da Enzima Conversora de Angiotensina/isolamento & purificação , Animais , Anti-Infecciosos/isolamento & purificação , Anti-Hipertensivos/isolamento & purificação , Anti-Hipertensivos/farmacologia , Antioxidantes/química , Caseínas/isolamento & purificação , Bovinos , Peso Molecular , Hidrolisados de Proteína/química , Hidrolisados de Proteína/isolamento & purificação
19.
J Dairy Sci ; 102(11): 9598-9604, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31521365

RESUMO

Gastrointestinal conditions in which the transit of contents is altered may benefit from nutritional approaches to influencing health outcomes. Milk proteins modulate the transit of contents along different regions, suggesting that they have varying effects on neuromuscular function to alter gastrointestinal motility. We tested the hypothesis that bovine whey and casein milk protein hydrolysates could have direct modulatory effects on colonic motility patterns in isolated rat large intestine. Casein protein hydrolysate (CPH), whey protein concentrate (WPC), whey protein hydrolysate (WPH), and a milk protein hydrolysate (MPH; a hydrolyzed blend of 60% whey to 40% casein) were compared for their effects on spontaneous contractile waves. These contractions propagate along the length of the isolated intact large intestine (22 cm) between the proximal colon and rectum and were detected by measuring activity at 4 locations. Milk proteins were perfused through the tissue bath, and differences in contraction amplitude and frequency were quantified relative to pretreatment controls. Propagation frequency was decreased by CPH, increased by MPH, and unaffected by intact whey proteins. The reduced motility with CPH and increased motility with MPH indicate a direct action of these milk proteins on colon tissue and provide evidence for differential modulation by hydrolysate type. These findings mirror actions on lower gastrointestinal transit reported in vivo, with the exception of WPH, suggesting that other factors are required.


Assuntos
Caseínas/farmacologia , Colo/efeitos dos fármacos , Trânsito Gastrointestinal , Contração Muscular/efeitos dos fármacos , Proteínas do Soro do Leite/farmacologia , Animais , Bovinos , Intestino Grosso , Masculino , Hidrolisados de Proteína/farmacologia , Ratos , Ratos Sprague-Dawley , Reprodução
20.
J Dairy Sci ; 102(10): 8604-8613, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31378502

RESUMO

The objective of this work was to better understand the effect of differences in milk protein composition, and specifically, a change in ß-casein to total casein in a milk-based matrix, on growth performance and metabolic and inflammatory responses using a piglet model. Three formulas were optimized for piglets, with similar metabolizable energy, total protein content, and other essential nutrients. Only the protein type and ratio varied between the treatments: the protein fraction of the control diet contained only whey proteins, whereas 2 other matrices contained a whey protein to casein ratio of 60:40, and differed in the amount of ß-casein (12.5 and 17.1% of total protein). Piglets fed formula containing whey proteins and caseins, regardless of the concentration of ß-casein, showed a significantly higher average daily gain, average daily feed intake, and feed efficiency compared with piglets consuming the formula with only whey protein. Consumption of the formula containing only whey protein showed higher levels of plasma glucagon-like peptide-1 and ghrelin compared with the consumption of formula containing casein and whey protein. A positive correlation was observed between postprandial time and glucagon-like peptide-1 response. The intestinal pro-inflammatory cytokine tumor necrosis factor α increased significantly in piglets fed the whey protein/casein diet compared with those fed whey protein formula. All formula-fed piglets showed a lower level of IL-6 cytokine compared with the ad libitum sow-fed piglets, regardless of composition. No significant differences in the anti-inflammatory IL-10 concentration were observed between treatment groups. Milk protein composition contributed to the regulation of piglets' metabolic and physiological responses, with whey protein/casein formula promoting growth performance and a different immune regulatory balance compared with a formula containing only whey protein. Results indicated no differences between treatments containing different levels of ß-casein.


Assuntos
Ração Animal , Caseínas/farmacologia , Citocinas/metabolismo , Proteínas do Leite/farmacologia , Animais , Caseínas/metabolismo , Dieta/veterinária , Metabolismo Energético , Feminino , Interleucina-10/metabolismo , Masculino , Leite/metabolismo , Proteínas do Leite/química , Proteínas do Leite/metabolismo , Distribuição Aleatória , Suínos , Proteínas do Soro do Leite/análise , Proteínas do Soro do Leite/metabolismo , Proteínas do Soro do Leite/farmacologia
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