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1.
Zhonghua Liu Xing Bing Xue Za Zhi ; 41(8): 1359-1364, 2020 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-32867450

RESUMO

Objectives: To analyze the epidemiological characteristics and levels of vitamin B(12) and folate as well as their relationship in women awaiting delivery, in Shaanxi province. Methods: Data were collected from healthy pregnant women who gave birth at six top hospitals in Shaanxi, from January 2014 to December 2016. Blood samples were taken prenatally to determine the levels of vitamin B(12) and folate. Quantile regression model was used to analyze the relationship between the levels of vitamin B(12) and folates in women awaiting delivery. Results: A total of 1 277 women awaiting delivery were included in this study. Among them, the median level of serum vitamin B(12) was 164.7 pg/ml, in women at late pregnancy, with the deficiency rate as 69.6%, while the median level of serum folate was 7.6 ng/ml, with the deficiency rate as 12.1%. 58.4% of these women presented simple vitamin B(12) deficiency and 0.9% with simple folate deficiency. Women living in rural areas showed lower levels of both vitamin B(12) and folate than the women from the urban areas. Both the levels of vitamin B(12) and folate increased with age but were significantly lower in women under the age of 25. Among those with or without folate deficiency, the average difference in the levels of vitamin B(12) was 37.62 pg/ml. Quantile regression models showed that the vitamin B(12) levels in women with folate deficiency were significantly lower than those without, despite the different levels of vitamin B(12). This difference appeared increasing along with the increase of the vitamin B(12) levels. Conclusions: Our data showed that both vitamin B(12) and folate were deficient in women awaiting delivery, in Shaanxi. We suggest that vitamin B(12) should also be added into the folic acid supplementation program, together with the reinforcement on health education program to improve the awareness of nutrient supplementation in rural and young women. Hopefully, these strategies could increase the levels of both vitamin B(12) and folate, in the province.


Assuntos
Deficiência de Ácido Fólico/epidemiologia , Ácido Fólico/sangue , Deficiência de Vitamina B 12/epidemiologia , Vitamina B 12/sangue , China/epidemiologia , Parto Obstétrico , Feminino , Humanos , Gravidez
2.
Int J Nanomedicine ; 15: 4899-4918, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764924

RESUMO

Purpose: The use of chemotherapeutic agents to combat cancer is accompanied by high toxicity due to their inability to discriminate between cancer and normal cells. Therefore, cancer therapy research has focused on the targeted delivery of drugs to cancer cells. Here, we report an in vitro study of folate-poly(ethylene glycol)-poly(propylene succinate) nanoparticles (FA-PPSu-PEG-NPs) as a vehicle for targeted delivery of the anticancer drug paclitaxel in breast and cervical cancer cell lines. Methods: Paclitaxel-loaded-FA-PPSu-PEG-NPs characterization was performed by in vitro drug release studies and cytotoxicity assays. The NPs cellular uptake and internalization mechanism were monitored by live-cell imaging in different cancer cell lines. Expression of folate receptor-α (FOLR1) was examined in these cell lines, and specific FOLR1-mediated entry of the FA-PPSu-PEG-NPs was investigated by free folic acid competition. Using inhibitors for other endocytic pathways, alternative, non-FOLR1 dependent routes for NPs uptake were also examined. Results: Drug release experiments of Paclitaxel-loaded PPSu-PEG-NPs indicated a prolonged release of Paclitaxel over several days. Cytotoxicity of Paclitaxel-loaded PPSu-PEG-NPs was similar to free drug, as monitored in cancer cell lines. Live imaging of cells treated with either free Paclitaxel or Paclitaxel-loaded PPSu-PEG-NPs demonstrated tubulin-specific cell cycle arrest, with similar kinetics. Folate-conjugated NPs (FA-PPSu-PEG-NPs) targeted the FOLR1 receptor, as shown by free folic acid competition of the FA-PPSu-PEG-NPs cellular uptake in some of the cell lines tested. However, due to the differential expression of FOLR1 in the cancer cell lines, as well as the intrinsic differences between the different endocytic pathways utilized by different cell types, other mechanisms of nanoparticle cellular entry were also used, revealing that dynamin-dependent endocytosis and macropinocytosis pathways mediate, at least partially, cellular entry of the FA-PPSu-PEG NPs. Conclusion: Our data provide evidence that Paclitaxel-loaded-FA-PPSu-PEG-NPs can be used for targeted delivery of the drug, FA-PPSu-PEG-NPs can be used as vehicles for other anticancer drugs and their cellular uptake is mediated through a combination of FOLR1 receptor-specific endocytosis, and macropinocytosis. The exploration of the different cellular uptake mechanisms could improve treatment efficacy or allow a decrease in dosage of anticancer drugs.


Assuntos
Antineoplásicos/química , Portadores de Fármacos/química , Ácido Fólico/química , Nanopartículas/química , Poliésteres/química , Polietilenoglicóis/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Liberação Controlada de Fármacos , Endocitose/efeitos dos fármacos , Receptor 1 de Folato/metabolismo , Ácido Fólico/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Paclitaxel/química , Paclitaxel/farmacologia
3.
Beijing Da Xue Xue Bao Yi Xue Ban ; 52(4): 719-725, 2020 Aug 18.
Artigo em Chinês | MEDLINE | ID: mdl-32773809

RESUMO

OBJECTIVE: To find out the status of folic acid supplementation among women, to evaluate the prevention effects on neural tube defects (NTDs), and to explore the factors impact on folic acid supplementation compliance. METHODS: Based on the routine data of 92 121 women in prenatal health care and birth defect surveillance system in Tongzhou District of Beijing from 2013 to 2018, we described the prevalence of periconceptional folic acid supplementation, pre-pregnancy folic acid supplementation and regularly folic acid supplementation (compliance supplementation). Trend χ2 tests were used to evaluate the change of folic acid supplementation prevalence. The prevalence difference among the women with folic acid supplementation and without supplementation were tested with Fisher's exact test. Factors asso-ciated with folic acid supplementation compliance rate were analyzed with univariate and multivariate Logistic regression model. RESULTS: The prevalence of periconceptional folic acid supplementation during the six years was 90.08% and it was increased from 2013 to 2018, but the rate of pre-pregnancy and regular supplementation was only 41.5% and declined from 2013 to 2018, especially 2013 to 2015. The prevalence of NTDs among the fetuses whose mothers took folic acid during periconceptional period was 5.5/10 000, while the prevalence for the fetuses whose mothers did not take folic acid was 19.7/10 000 (P < 0.001), the rates ratio was 27.9% (χ2=23.74, P < 0.001). The difference between the prevalence of NTDs among the fetuses whose mothers took folic acid only and multiple micronutrients was not statistically significant. After controlling the confounding factors, it was found that the compliant folic acid supplementation rates in women, whose household registrations were outside Beijing and whose education levels were junior high school or below, and who were younger than 25 years old, and who were multiparas and who were pre-pregnancy underweight or obese, were lower than those of the corresponding control groups (P < 0.05). CONCLUSION: The rate of folic acid supplementation among women in Tongzhou District of Beijing was relatively high, but their compliance was poor. Women who did not take folic acid during periconception seriously affected the prevention effect of NTDs. We should focus on women who are younger than 25 years old, lower educated, pre-pregnancy underweight or obese, multiparas and nonlocal household registers, in order to improve the periconceptional folic acid supplementation compliance and improve the effects of NTDs prevention.


Assuntos
Suplementos Nutricionais , Defeitos do Tubo Neural , Adulto , Pequim , Feminino , Feto , Ácido Fólico , Humanos , Defeitos do Tubo Neural/epidemiologia , Gravidez , Prevalência
4.
Brasília; s.n; 11 ago. 2020.
Não convencional em Português | LILACS, BRISA/RedTESA, PIE | ID: biblio-1117979

RESUMO

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 14 artigos e 5 protocolos.


Assuntos
Humanos , Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Betacoronavirus/efeitos dos fármacos , Ribavirina/uso terapêutico , Avaliação da Tecnologia Biomédica , Ácido Ursodesoxicólico/uso terapêutico , Imunoglobulinas/uso terapêutico , Prednisolona/uso terapêutico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Cloroquina/uso terapêutico , Estudos Transversais , Estudos de Coortes , Interferon-alfa/uso terapêutico , Tacrolimo/uso terapêutico , Corticosteroides/uso terapêutico , Azitromicina/uso terapêutico , Ritonavir/uso terapêutico , Anticorpos Neutralizantes/uso terapêutico , Células-Tronco Mesenquimais , Lopinavir/uso terapêutico , Ácido Fólico/uso terapêutico , Meropeném/uso terapêutico , Hidroxicloroquina/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Ácido Micofenólico/uso terapêutico
5.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 49(3): 364-374, 2020 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-32762172

RESUMO

OBJECTIVE: To design and synthesize folate-modified pH-responsive chitosan-based nanomicelles and investigate the in vitro anti-tumor activity of the drug-loaded micelles. METHODS: CHI-DMA was obtained by reductive amination reaction of aldehyde-based chitosan and hydrophilic amine compounds, and CHI-DMA-LA was obtained by condensation reaction with lauric acid; FA-CHI-DMA-LA was obtained after modification with folic acid (FA). The drug-loaded nanomicelles FA-CHI-DMA-LA/DOX were assembled by solvent change method. The physicochemical properties of polymers were characterized by hydrogen nuclear magnetic resonance and transmission electron microscope. The particle size and surface potential were determined by dynamic light scattering method. Folic acid access rate, doxorubicin (DOX) loading rate and entrapped efficiency were measured by UV-vis spectrophotometer. The drug release properties of DOX-loaded micelles in vitro were monitored by fluorescence spectrophotometer at different pHs (7.4, 6.5, 5.0). The cytotoxicity against human oral cancer KB cells was detected by MTT assay. Fluorescence microscope and flow cytometry were applied to investigate the phagocytosis of DOX-loaded micelles on KB cells. RESULTS: FA-CHI-DMA-LA was synthesized. The particle sizes of FA-CHI-DMA-LA-1 and FA-CHI-DMA-LA-2 micelles which used for the subsequent experiments were (73±14) nm and (106±15) nm, zeta potential were (15.59±1.98) mV and (21.20±2.35) mV, respectively. The drug loading rates of drug-loaded micelles FA-CHI-DMA-LA-1/DOX and FA-CHI-DMA-LA-2/DOX are (4.08±1.12)%and (4.12±0.44)%, respectively. In vitro drug release is pH-responsive, with cumulative release of DOX up to 37%and 36%at pH 5.0, which is about 1.5 times higher than that of pH 7.4. For FA-CHI-DMA-LA micelles with 1.25 to 125 µg/mL concentration, the survival rate of KB cells is more than 70%after incubation for 24 hours. The cell uptake of FA-CHI-DMA-LA/DOX micelles was enhanced compared to CHI-DMA-LA/DOX, and the cell uptake was higher in incubation without FA medium than that with FA. Compared with free DOX or CHI-DMA-LA/DOX, FA-CHI-DMA-LA/DOX nanomicelles showed higher cyctoxicity to KB cells, especially the FA-CHI-DMA-LA-2/DOX nanomicelles, the cell survival rate was about 17% after incubation for 24 hours. CONCLUSIONS: FA-modified chitosan-based nanomicelle with good biocompatibility was successfully prepared, which exhibits tumor microenvironmental pH responsive drug release and tumor targeting.


Assuntos
Nanoestruturas , Antineoplásicos , Quitosana , Doxorrubicina , Portadores de Fármacos , Ácido Fólico , Humanos , Micelas , Polímeros
6.
Clin Exp Rheumatol ; 38 Suppl 125(3): 120-126, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32828144

RESUMO

OBJECTIVES: Gastrointestinal involvement and impaired nutritional status are frequent in patients with systemic sclerosis (SSc). Hereby, we hypothesised that micronutrients and/or prealbumin could be deficitary in SSc. METHODS: Patients with SSc and very early SSc (veSSc) were prospectively included. Clinical assessment, data recording and quality controls followed EUSTAR standards. The UCLA SCTCGIT 2.0 questionnaire was applied and the serum levels of zinc, selenium, prealbumin, holotranscobalamin, folic acid were measured. RESULTS: Half (52.4%) of the 176 patients with established SSc showed a deficiency in at least one of the measured nutrients. The most frequent deficit was seen in folic acid (17.9%), followed closely by selenium, prealbumin and zinc (around 15% each). Nearly a fifth (19%) of these patients had multiple deficiencies. Patients with more severe disease, including advanced skin fibrosis, positive ACR 1980 classification criteria, anemia and elevated serum inflammation markers were more likely to be nutrient deficient. Lower BMI<20kg/m2 was associated with several nutrient deficiencies. Prealbumin deficiency was associated with more frequent stomach symptoms and methotrexate therapy. A third of veSSc patients (27%, 44/74) presented a nutrient deficiency, mostly of zinc (10%). Surprisingly, micronutrient deficiencies were not associated with usual parameters of gastrointestinal involvement. CONCLUSIONS: These novel data reveal deficiencies in micronutrients and/or prealbumin are a frequent burden in patients with SSc. Moreover, these correlate with clinical aspects of the disease. Especially patients with advanced disease appear at high risk for an impaired nutrient status, suggesting that screening of micronutrients status should be performed in these patients.


Assuntos
Micronutrientes , Escleroderma Sistêmico , Ácido Fólico , Humanos , Estado Nutricional , Pré-Albumina
7.
J Assoc Physicians India ; 68(9): 36-42, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32798344

RESUMO

Objectives: Ideally, the upper reference limit of plasma or serum homocysteine (Hcy) is to be defined from the studies done on individuals with normal cobalamin and folate status. It is difficult to separate the truly healthy (Cobalamin/Folate Replete) individuals from the randomly selected, apparently healthy individuals who are sub-clinically deficient of cobalamin/folate. The present study was aimed at defining the reference values for the serum homocysteine from individuals with normalized cobalamin and folate status. Methods: In our study, 215 patients with cobalamin, folic acid deficiency were treated accordingly till complete restoration of clinical and laboratory abnormalities. The post-therapy serum Hcy values were used as reference values. Results: Post-therapy serum Hcy values 12.56 µmol/L (95th percentile), 11.4 µmol/L (85th percentile), 9.8 µmol/L (67th percentile) were seen. The hyperhomocysteinemia was more visible (17.3% gain in prevalence) in the same patient group if interpreted using the post-therapy Hcy value (11.4 µmol/L) as the cut-off. There was no difference between the genders and age groups in the pre or post-therapy Hcy values. Conclusions: The benefit of the gain in prevalence of disease or the increase in the sensitivity of the test, though small, gets magnified in common diseases and in populous countries. Selection of the individuals is as important as the method or the reagent used in the method when a particular parameter is studied. Repleting the vitamin stores in the confirmed vitamin-deficient patients is more appropriate and easily feasible, since anyway they require treatment, than doing the same on the apparently healthy people. The data thus obtained can be better used as the reference value, for a more meaningful interpretation. The reference range can in turn be used to identify the sub-clinically deficient but asymptomatic people and managed accordingly.


Assuntos
Deficiência de Ácido Fólico , Ácido Fólico/uso terapêutico , Deficiência de Vitamina B 12 , Vitamina B 12/uso terapêutico , Feminino , Deficiência de Ácido Fólico/tratamento farmacológico , Homocisteína , Humanos , Masculino , Valores de Referência , Deficiência de Vitamina B 12/tratamento farmacológico
8.
Wei Sheng Yan Jiu ; 49(3): 386-396, 2020 May.
Artigo em Chinês | MEDLINE | ID: mdl-32693904

RESUMO

OBJECTIVE: To study the effect of pregnant serum folate concentrations on the birth weight. METHODS: This study was a prospective cohort study. Pregnant women aged 18-45 who were examined and delivered in a county in Hebei Province from June 2016 to August 2018 and their newborns were included in the study. A total of 490 women were recruited and collected venous blood before the 20 th week of pregnancy. Basic information of women as well as their use of folic acid supplements was collected at the same time. Newborns' basic information, such as sex and birth weight, had been collected after delivery. The chemiluminescence method was used to determine the serum folate concentrations. Folate concentrations quartile were used as the cut-off point to divide subjects into four groups. The general linear model and multivariate unconditional Logistic regression analysis were used to study the effect of different serum folate concentrations on the infant birthweight. RESULTS: The age of 490 pregnant women was(27. 9±4. 1) years. The serum folate value P50(P25, P75) was 12. 3(9. 0, 14. 5) ng/mL and its' detection time was(13. 7±2. 6) weeks. 49. 3%(242/490) newborns were male. The average gestational age of the newborns was(39. 1±1. 0) weeks and the average birth weight was(3403±425) g. The birth weight of four groups' newborns were(3408±456) g, (3405±450) g, (3427±418) g and(3374±378) g, respectively. General linear model analysis showed that there was no significant difference in the effect of serum folate levels before the 20 th week of gestation on the birth weight(serum folate concentration<9. 0 ng/mL(ß=32. 24, P=0. 55), serum folate concentration 9. 0-12. 2(ß=18. 01, P=0. 74), serum folate concentration 12. 3-14. 4(ß=42. 27, P=0. 43)]. Multivariate unconditional Logistic regression analysis showed that the group with folate concentration above 14. 5 ng/mL can reduce the risk of small for gestational age(SGA) [(P=0. 02, OR=0. 08(95% CI 0. 01-0. 61)]. Comparing with ghe pregnant women whose serum folate concentration was in 9. 0-12. 4 ng/mL. Hovever, there was no significant difference between the pregnant serum folate levels and large for gestational age(LGA). CONCLUSION: There was no significant correlation between serum folate concentrations and the birth weight. But higher folate level may reduce the risk of SGA.


Assuntos
Ácido Fólico , Gestantes , Adolescente , Adulto , Peso ao Nascer , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Gravidez , Estudos Prospectivos , Adulto Jovem
9.
Chem Biol Interact ; 327: 109187, 2020 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-32610055

RESUMO

Hepatic ischemia-reperfusion injury (IRI) is not only one of the pathophysiological process involving the liver, but also a complex systemic process affecting multiple tissues and organs. IRI after liver transplant occurs due to in major resections and occlusion of vessels, or during the perioperative period, leads to acute liver failure which shows the dynamic process that involves two interrelated phases of local ischemic insult and inflammation-mediated reperfusion injury and has an impact on morbidity and mortality. The renin-angiotensin-aldosterone system (RAAS) is activated locally in the injured cells by the occurrence of I/R, which plays an essential role in the fate of the damaged tissue. However, a preclinical study explores the protective role of RAAS inhibitor in acute liver injury in a model of inflammation caused by ischemia and reperfusion. In-addition to RAAS blockers in monotherapy does not effectively block the complete pathway. Thus, the present study is designed to explore the effect of combined folic acid with RAAS blockers in combination, produce a synergistic effect. Moreover, in this review, we will describe the understanding of the possible incidence of downregulatory molecular mechanisms associated with renin-angiotensin-aldosterone system and the significance & outcome of the combination of folic acid and RAAS blockers in liver injury due to ischemia/reperfusion.


Assuntos
Ácido Fólico/uso terapêutico , Hepatopatias/tratamento farmacológico , Sistema Renina-Angiotensina/efeitos dos fármacos , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Sinergismo Farmacológico , Homocisteína/metabolismo , Humanos , Hepatopatias/fisiopatologia , Traumatismo por Reperfusão/fisiopatologia , Ácido Úrico/metabolismo
10.
Proc Natl Acad Sci U S A ; 117(28): 16527-16536, 2020 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-32601218

RESUMO

Folate deprivation drives the instability of a group of rare fragile sites (RFSs) characterized by CGG trinucleotide repeat (TNR) sequences. Pathological expansion of the TNR within the FRAXA locus perturbs DNA replication and is the major causative factor for fragile X syndrome, a sex-linked disorder associated with cognitive impairment. Although folate-sensitive RFSs share many features with common fragile sites (CFSs; which are found in all individuals), they are induced by different stresses and share no sequence similarity. It is known that a pathway (termed MiDAS) is employed to complete the replication of CFSs in early mitosis. This process requires RAD52 and is implicated in generating translocations and copy number changes at CFSs in cancers. However, it is unclear whether RFSs also utilize MiDAS and to what extent the fragility of CFSs and RFSs arises by shared or distinct mechanisms. Here, we demonstrate that MiDAS does occur at FRAXA following folate deprivation but proceeds via a pathway that shows some mechanistic differences from that at CFSs, being dependent on RAD51, SLX1, and POLD3. A failure to complete MiDAS at FRAXA leads to severe locus instability and missegregation in mitosis. We propose that break-induced DNA replication is required for the replication of FRAXA under folate stress and define a cellular function for human SLX1. These findings provide insights into how folate deprivation drives instability in the human genome.


Assuntos
Endodesoxirribonucleases/metabolismo , Ácido Fólico/metabolismo , Síndrome do Cromossomo X Frágil/metabolismo , Mitose , Rad51 Recombinase/metabolismo , DNA/genética , DNA/metabolismo , Reparo do DNA , Endodesoxirribonucleases/genética , Síndrome do Cromossomo X Frágil/genética , Síndrome do Cromossomo X Frágil/fisiopatologia , Humanos , Rad51 Recombinase/genética , Proteína Rad52 de Recombinação e Reparo de DNA/genética , Proteína Rad52 de Recombinação e Reparo de DNA/metabolismo , Recombinases/genética , Recombinases/metabolismo
11.
Plant Foods Hum Nutr ; 75(3): 337-343, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32638209

RESUMO

Concerns about the nutritional and sensory qualities of gluten-free (GF) products has generated interest in the evaluation of novel gluten-free ingredients. Folate content is of particular interest due to limited sources of enriched folic acid in a GF diet as well as lack of nutrient composition data in novel flours. The aim of this study was to determine the total folate content and chemical composition of GF flours commercially available in Canada. A tri-enzyme method was used to extract folate from the flour samples, and a microbiological assay was used to measure the total folate contents. The chemical compositions of the GF flours were determined according to standard Association of Official Agricultural Chemists (AOAC) International methods. Compared to all-purpose flour, 265 ± 6.9 µg/100 (dry-weight basis), chickpea flour registered the highest folate content 451 ± 10.8 µg/100 (dry-weight basis) followed by quinoa flour, 174 ± 12.4 µg/ 100 g folate (dry-weight basis). Fonio, had a total starch content of ~77% but was not a source of folate. Flaxseed, chickpea, chia and coconut flours had the highest reported protein contents (mean value: 21.3 ± 1.3%) whereas flaxseed (~42%), and chia (~35%), had the highest lipid content. These findings may inform the selection of gluten-replacement flours with acceptable nutritional properties.


Assuntos
Farinha , Ácido Fólico , Dieta Livre de Glúten , Glutens , Valor Nutritivo
12.
Beijing Da Xue Xue Bao Yi Xue Ban ; 52(3): 451-456, 2020 Jun 18.
Artigo em Chinês | MEDLINE | ID: mdl-32541977

RESUMO

OBJECTIVE: To explore the effect of subchronic combined oral exposure of titanium dioxide nanoparticles and glucose on levels of serum folate and vitamin B12 in young SD rats. METHODS: At first, the physical and chemical properties of titanium dioxide nanoparticles, such as particle size, shape, crystal form and agglomeration degree in solution system, were characterized in detail. Eighty 4-week-old young SD rats were randomly divided into 8 groups (10 rats in each group, half male and half female). The rats were exposed to titanium dioxide nanoparticles through intragastric administration at 0, 2, 10 and 50 mg/kg body weight with or without 1.8 g/kg glucose daily for 90 days. At last, the concentrations of serum folate and vitamin B12 were detected. RESULTS: Titanium dioxide nanoparticles were anatase crystals, closely spherical shape, with an average particle size of (24±5) nm. In male young rats, compared with the control group, the serum folate concentration was significantly increased when exposed to titanium dioxide nanoparticles (10 mg/kg) and glucose. The difference was statistically significant (P<0.05). However, in female and male young rats, compared with glucose (1.8 g/kg) exposure group, titanium dioxide nanoparticles (50 mg/kg) and glucose significantly reduced the serum folate concentration. The difference was statistically significant (P<0.05). Through statistical analysis of factorial design and calculation of interaction, obvious antagonistic effect was observed between titanium dioxide nanoparticles and glucose on the serum folate concentration in the young female SD rats. The combined oral exposure of titanium dioxide nanoparticles and glucose had little effect on the concentration of serum vitamin B12 in the young SD rats, with no significant interaction between the two substances. It was only found that titanium dioxide nanoparticles (2 mg/kg) and glucose significantly increased the serum vitamin B12 concentration, compared with glucose (1.8 g/kg) exposure group. The difference was statistically significant (P<0.05). CONCLUSION: Subchronic combined oral exposure of titanium dioxide nanoparticles and glucose had an obvious antagonistic effect on serum folate concentrations in young SD rats.


Assuntos
Nanopartículas Metálicas , Animais , Feminino , Ácido Fólico , Glucose , Masculino , Ratos , Ratos Sprague-Dawley , Titânio , Vitamina B 12 , Vitaminas
13.
Proc Natl Acad Sci U S A ; 117(27): 15837-15845, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32571957

RESUMO

Despite broad appreciation of their clinical utility, it has been unclear how vitamin B12 and folic acid (FA) function at the molecular level to directly prevent their hallmark symptoms of deficiency like anemia or birth defects. To this point, B12 and FA have largely been studied as cofactors for enzymes in the one-carbon (1C) cycle in facilitating the de novo generation of nucleotides and methylation of DNA and protein. Here, we report that B12 and FA function as natural antagonists of aryl hydrocarbon receptor (AhR). Our studies indicate that B12 and FA bind AhR directly as competitive antagonists, blocking AhR nuclear localization, XRE binding, and target gene induction mediated by AhR agonists like 2,3,7,8-tetrachlorodibenzodioxin (TCDD) and 6-formylindolo[3,2-b]carbazole (FICZ). In mice, TCDD treatment replicated many of the hallmark symptoms of B12/FA deficiency and cotreatment with aryl hydrocarbon portions of B12/FA rescued mice from these toxic effects. Moreover, we found that B12/FA deficiency in mice induces AhR transcriptional activity and accumulation of erythroid progenitors and that it may do so in an AhR-dependent fashion. Consistent with these results, we observed that human cancer samples with deficient B12/FA uptake demonstrated higher transcription of AhR target genes and lower transcription of pathways implicated in birth defects. In contrast, there was no significant difference observed between samples with mutated and intact 1C cycle proteins. Thus, we propose a model in which B12 and FA blunt the effect of natural AhR agonists at baseline to prevent the symptoms that arise with AhR overactivation.


Assuntos
Ácido Fólico/metabolismo , Desnutrição/metabolismo , Receptores de Hidrocarboneto Arílico/antagonistas & inibidores , Receptores de Hidrocarboneto Arílico/metabolismo , Vitamina B 12/metabolismo , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Carbazóis/farmacologia , Anormalidades Congênitas , Feminino , Deficiência de Ácido Fólico/tratamento farmacológico , Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias , Dibenzodioxinas Policloradas/farmacologia , Receptores de Hidrocarboneto Arílico/agonistas , Receptores de Hidrocarboneto Arílico/genética , Deficiência de Vitamina B 12/tratamento farmacológico
14.
Arch. argent. pediatr ; 118(3): 160-165, jun. 2020. tab, ilus
Artigo em Inglês, Espanhol | LILACS, BINACIS | ID: biblio-1102717

RESUMO

Introducción. La fortificación y suplementación son estrategias para la prevención de carencias de micronutrientes. El objetivo fue describir la procedencia de la ingesta del hierro y ácido fólico a lo largo del ciclo vital de la población de la Ciudad Autónoma de Buenos Aires. Población y métodos. Análisis de la información de la Primera Encuesta Alimentaria y Nutricional de la Ciudad Autónoma de Buenos Aires 2011, que tomó una muestra probabilística por conglomerados. El consumo se recabó con recordatorio de 24 horas. Se calculó el aporte de hierro y ácido fólico, y se categorizó en contenido natural, harina de trigo enriquecida, leche del Plan Materno Infantil, alimentos fortificados y suplementos. Resultados. De los 5369 individuos evaluados, prácticamente, la totalidad obtenía hierro y ácido fólico de contenido natural (el 58 % y el 29 % del consumo, respectivamente). Más del 90 % consumía harina de trigo enriquecida, que aportaba el 28 % del hierro y el 54 % del ácido fólico. Los alimentos fortificados mostraron consumo y aporte muy variable. La leche del Plan Materno Infantil mostró muy baja participación, inclusive en grupos específicos. El aporte de suplementos fue bajo, excepto en < 2 años (el 30 % consumía suplementos de hierro, que aportaban el 38 % de este).Conclusión. Además del aporte natural de los alimentos, la harina de trigo enriquecida representó una importante contribución en el consumo de ácido fólico y hierro de esta población; los alimentos fortificados y los suplementos tuvieron una participación diferente según el grupo etario.


Introduction. Fortification and supplementation are two strategies for micronutrient deficiency prevention. The objective of this study was to describe the source of iron and folic acid intake throughout the life cycle in the population of the Autonomous City of Buenos Aires.Population and methods. Analysis of the information collected in the First Survey on Nutritional Food Intake of the Autonomous City of Buenos Aires (2011), which had a probability cluster sampling design. Consumption was assessed by means of a 24-hour recall. Iron and folic acid intake was estimated and categorized into natural content, enriched wheat flour, milk from the Maternal and Child Plan, fortified foods, and supplements.Results. Out of the 5369 studied individuals, practically all got iron and folic acid from natural contents (58 % and 29 % of intake, respectively). More than 90 % consumed enriched wheat flour, which provided 28 % of iron and 54 % of folic acid. Fortified food consumption and intake varied greatly. Milk intake from the Maternal and Child Plan was small, even in specific groups. Intake from supplements was low, except in children < 2 years old (30 % consumed iron supplements, which accounted for 38 % of iron).Conclusion. In addition to natural intake from foods, enriched wheat flour accounted for a major source of folic acid and iron in this population; intake from fortified foods and supplements varied by age group.


Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Alimentos Fortificados , Ácido Fólico/administração & dosagem , Ferro/administração & dosagem , Consumo de Alimentos , Epidemiologia Descritiva , Estudos Transversais , Inquéritos e Questionários , Suplementos Nutricionais , Farinha , Anemia/prevenção & controle
15.
Int J Nanomedicine ; 15: 3433-3445, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32523342

RESUMO

Background: Reconstituted lipoproteins (rLips) based on endogenous lipid nanostructures has been increasingly regarded as an excellent and promising antitumor drug delivery. However, some problems relating to the main component, apolipoprotein, for instance, rare source, unaffordable price, and low specificity of relevant receptor expression, become chief obstacles to its broad development and application. Purpose: The primary aim of this study is to develop biomimetic rLips by utilizing folic acid (FA)-modified bovine serum albumin (BSA) as a replacement for apolipoprotein and demonstrate its tumor targeting and antitumor efficacy. Methods: The amino groups of BSA were covalently conjugated with FA through the amide reaction. PTX-loaded nanostructured lipid carrier (termed as P-NLC) consisting of phospholipid, cholesteryl ester, triglyceride and cholesterol was prepared by the emulsification-evaporation method and utilized as the lipid core. FA-modified BSA (FA-BSA) was characterized for the protein substitute degree and attached with NLC by incubation-insert method to form the lipoprotein-mimic nanocomplex (termed as PFB-rLips). The morphology of nanoparticles was observed under transmission electron microscopy (TEM), and the particle size and zeta potential were determined using dynamic light scattering. In vitro release behavior of PTX from PFB-rLips was investigated with the dialysis method. Hemolysis tests were conducted to evaluate the biosecurity of PFB-rLips. Cell uptake and cytotoxicity assays were performed on human hepatocytes (LO2) and human hepatoma cells (HepG2). Tumor targeting was assessed using in vivo imaging system in H22 tumor-bearing mice model. Antitumor efficacy in vivo was investigated and compared between Taxol® (paclitaxel) formulation and PTX-incorporated nanoparticles in the same tumor model. Results: A fixed molar ratio 50:1 of FA to BSA was chosen as the optimal input ratio based on the balance between appropriate degree of protein substitution and amphiphilicity of FA-BSA. The morphology of FB-rLips exhibited as a homogeneous spherical structure featured by lipid cores surrounded with a cloudy protein shell observed under TEM. The particle size, zeta potential and encapsulation efficiency were 174.6±3.2 nm, -17.26±0.9 mV and 82.2±2.4%, respectively. In vitro release behavior of PTX from PFB-rLips was slow and sustained. The uptake of FB-rLips was much higher in HepG2 cells than in LO2 cells. Furthermore, the uptake of FB-rLips was significantly higher than that of rLips without FA involved (termed as B-rLips) and NLC in HepG2 cells. Hemolysis and cytotoxicity assays showed good biocompatibility of FB-rLips. The internalization mechanism of FB-rLips mainly depended on clathrin-mediated and caveolin-mediated endocytosis coupling with energy consumption, and FA receptors expressed on tumor cells played a critical role in cellular uptake process. CCK-8 studies demonstrated that PFB-rLips exhibited significantly better tumor killing ability than Taxol® (paclitaxel) formulation in vitro. Moreover, FB-rLips produced more excellent tumor-targeting properties than NLC through in vivo imaging assays. On the basis of this, PTX-loaded FB-rLips also performed more remarkable anticancer activity than other therapy groups in H22 tumor-bearing mice. Conclusion: FB-rLips would serve as a potential nanocarrier for improving tumor-targeting and therapeutic efficacy while reducing the side effects on normal tissues and organs.


Assuntos
Portadores de Fármacos/química , Ácido Fólico/uso terapêutico , Lipoproteínas/química , Nanopartículas/química , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Liberação Controlada de Fármacos , Endocitose/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Ácido Fólico/síntese química , Ácido Fólico/química , Hemólise/efeitos dos fármacos , Humanos , Camundongos , Nanopartículas/ultraestrutura , Neoplasias/patologia , Paclitaxel/química , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Tamanho da Partícula , Coelhos , Soroalbumina Bovina/química , Eletricidade Estática
16.
Nat Commun ; 11(1): 2936, 2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32522993

RESUMO

Stress response pathways are critical for cellular homeostasis, promoting survival through adaptive changes in gene expression and metabolism. They play key roles in numerous diseases and are implicated in cancer progression and chemoresistance. However, the underlying mechanisms are only poorly understood. We have employed a multi-omics approach to monitor changes to gene expression after induction of a stress response pathway, the unfolded protein response (UPR), probing in parallel the transcriptome, the proteome, and changes to translation. Stringent filtering reveals the induction of 267 genes, many of which have not previously been implicated in stress response pathways. We experimentally demonstrate that UPR-mediated translational control induces the expression of enzymes involved in a pathway that diverts intermediate metabolites from glycolysis to fuel mitochondrial one-carbon metabolism. Concomitantly, the cells become resistant to the folate-based antimetabolites Methotrexate and Pemetrexed, establishing a direct link between UPR-driven changes to gene expression and resistance to pharmacological treatment.


Assuntos
Antimetabólitos/farmacologia , Ácido Fólico/farmacologia , Regulon/genética , Resposta a Proteínas não Dobradas/efeitos dos fármacos , Resposta a Proteínas não Dobradas/genética , Animais , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Humanos , Metotrexato/farmacologia , Pemetrexede/farmacologia , Proteoma/efeitos dos fármacos , Proteoma/genética , Regulon/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos , Transcriptoma/genética
19.
Nutr Metab Cardiovasc Dis ; 30(6): 939-947, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32404292

RESUMO

BACKGROUND AND AIMS: Elevated homocysteine concentration is associated with a higher risk of cardiovascular disease. The aim of our study was to determine the environmental and genetic factors associated with serum homocysteine concentration in healthy young adults. Moreover, we aimed to determine the cutoff value of homocysteine concentration for predicting unfavorable MTHFR genotype and to investigate whether this association is modified by dietary patterns and serum folate status. METHODS AND RESULTS: A total of 744 healthy individuals, aged 18-35 years, were included in the study. Diet quality was assessed by establishing diet quality scores and adherence to the pro-Healthy Diet Index (pHDI) and non-Healthy Diet Index (nHDI). Genotyping was performed using the TaqMan method. Multivariate analysis showed that pHDI, creatinine, folate concentrations, and the T/T genotype of the C677T polymorphism in MTHFR, as well as the interaction between the T/T genotype of MTHFR (C677T polymorphism) and folate level, were most strongly related to homocysteine concentrations. The specificity of a homocysteine >13.1 µmol/l in predicting T/T homozygous status was 76% (area under the curve 0.68). CONCLUSION: Healthy dietary patterns, folate, and creatinine levels, as well as the C677T polymorphism, proved to be the strongest predictors of homocysteine concentrations. T/T genotype of MTHFR modifies the relationship between folate and homocysteine.


Assuntos
Dieta Saudável , Comportamento Alimentar , Interação Gene-Ambiente , Homocisteína/sangue , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo Genético , Adolescente , Adulto , Fatores Etários , Biomarcadores/sangue , Creatinina/sangue , Feminino , Ácido Fólico/sangue , Voluntários Saudáveis , Humanos , Masculino , Adulto Jovem
20.
Cochrane Database Syst Rev ; 5: CD011033, 2020 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-32364620

RESUMO

BACKGROUND: Buerger's disease (thromboangiitis obliterans) is a non-atherosclerotic, segmental inflammatory pathology that most commonly affects the small and medium sized arteries, veins, and nerves in the upper and lower extremities. The aetiology is unknown, but involves hereditary susceptibility, tobacco exposure, immune and coagulation responses. In many cases, there is no possibility of revascularisation to improve the condition. Pharmacological treatment is an option for patients with severe complications, such as ischaemic ulcers or rest pain.This is an update of the review first published in 2016. OBJECTIVES: To assess the effectiveness of any pharmacological agent (intravenous or oral) compared with placebo or any other pharmacological agent in patients with Buerger's disease. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, AMED, the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials register to 15 October 2019. The review authors searched LILACS, ISRCTN, Australian New Zealand Clinical Trials Registry, EU Clinical Trials Register, clincialtrials.gov and the OpenGrey Database to 5 January 2020. SELECTION CRITERIA: We included randomised controlled trials (RCTs) involving pharmacological agents used in the treatment of Buerger's disease. DATA COLLECTION AND ANALYSIS: Two review authors, independently assessed the studies, extracted data and performed data analysis. MAIN RESULTS: No new studies were identified for this update. Five randomised controlled trials (total 602 participants) compared prostacyclin analogue with placebo, aspirin, or a prostaglandin analogue, and folic acid with placebo. No studies assessed other pharmacological agents such as cilostazol, clopidogrel and pentoxifylline or compared oral versus intravenous prostanoid. Compared with aspirin, intravenous prostacyclin analogue iloprost improved ulcer healing (risk ratio (RR) 2.65; 95% confidence interval (CI) 1.15 to 6.11; 98 participants; 1 study; moderate-certainty evidence), and helped to eradicate rest pain after 28 days (RR 2.28; 95% CI 1.48 to 3.52; 133 participants; 1 study; moderate-certainty evidence), although amputation rates were similar six months after treatment (RR 0.32; 95% CI 0.09 to 1.15; 95 participants; 1 study; moderate-certainty evidence). When comparing prostacyclin (iloprost and clinprost) with prostaglandin (alprostadil) analogues, ulcer healing was similar (RR 1.13; 95% CI 0.76 to 1.69; 89 participants; 2 studies; I² = 0%; very low-certainty evidence), as was the eradication of rest pain after 28 days (RR 1.57; 95% CI 0.72 to 3.44; 38 participants; 1 study; low-certainty evidence), while amputation rates were not measured. Compared with placebo, the effects of oral prostacyclin analogue iloprost were similar for: healing ischaemic ulcers (iloprost 200 mcg: RR 1.11; 95% CI 0.54 to 2.29; 133 participants; 1 study; moderate-certainty evidence, and iloprost 400 mcg: RR 0.90; 95% CI 0.42 to 1.93; 135 participants; 1 study; moderate-certainty evidence), eradication of rest pain after eight weeks (iloprost 200 mcg: RR 1.14; 95% CI 0.79 to 1.63; 207 participants; 1 study; moderate-certainty evidence, and iloprost 400 mcg: RR 1.11; 95% CI 0.77 to 1.59; 201 participants; 1 study; moderate-certainty evidence), and amputation rates after six months (iloprost 200 mcg: RR 0.54; 95% CI 0.19 to 1.56; 209 participants; 1 study, and iloprost 400 mcg: RR 0.42; 95% CI 0.13 to 1.31; 213 participants; 1 study). When comparing folic acid with placebo in patients with Buerger's disease and hyperhomocysteinaemia, pain scores were similar, there were no new cases of amputation in either group, and ulcer healing was not assessed (very low-certainty evidence). Treatment side effects such as headaches, flushing or nausea were not associated with treatment interruptions or more serious consequences. Outcomes such as amputation-free survival, walking distance or pain-free walking distance, and ankle brachial index were not assessed by any study. Overall, the certainty of the evidence was very low to moderate, with few studies, small numbers of participants, variation in severity of disease of participants between studies and missing information (for example regarding baseline tobacco exposure). AUTHORS' CONCLUSIONS: Moderate-certainty evidence suggests that intravenous iloprost (prostacyclin analogue) is more effective than aspirin for eradicating rest pain and healing ischaemic ulcers in Buerger's disease, but oral iloprost is not more effective than placebo. Very low and low-certainty evidence suggests there is no clear difference between prostacyclin (iloprost and clinprost) and the prostaglandin analogue alprostadil for healing ulcers and relieving pain respectively in severe Buerger's disease. Very low-certainty evidence suggests there is no clear difference in pain scores and amputation rates between folic acid and placebo, in people with Buerger's disease and hyperhomocysteinaemia. Further well designed RCTs assessing the effectiveness of pharmacological agents (intravenous or oral) in people with Buerger's disease are needed.


Assuntos
Inibidores da Agregação de Plaquetas/uso terapêutico , Tromboangiite Obliterante/tratamento farmacológico , Adulto , Alprostadil/uso terapêutico , Amputação/estatística & dados numéricos , Aspirina/uso terapêutico , Epoprostenol/análogos & derivados , Epoprostenol/uso terapêutico , Ácido Fólico/uso terapêutico , Hematínicos/uso terapêutico , Humanos , Iloprosta/uso terapêutico , Masculino , Pessoa de Meia-Idade , Dor/tratamento farmacológico , Placebos/uso terapêutico , Prostaglandinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Tromboangiite Obliterante/cirurgia , Úlcera/tratamento farmacológico
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