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1.
Food Chem ; 317: 126458, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32109656

RESUMO

A kinetic model for Maillard reaction (MR) model system of d-glucose and l-lysine was established; activation energy (Ea) of each step was calculated. Potential generation pathways of furosine and pyrraline were a combination of either 3-deoxyglucosone (3-DG) or methylglyoxal (MG) with l-lysine. Ea value for furosine generated through 3-DG pathway was 81.70 ± 14.01 kJ mol-1, which was significantly higher than that through MG pathway (52.08 ± 4.48 kJ mol-1). As for pyrraline, Ea for the 3-DG pathway (53.45 ± 4.02 kJ mol-1) was significantly lower than that through the MG pathway (110.22 ± 18.77 kJ mol-1). Results of the kinetic study indicated that furosine was preferred to be generated through the MG pathway since MG is more likely to react with each other and form a furan ring as a precursor of furosine. Pyrraline was more easily to be generated from the 3-DG pathway through cyclization of 1,4-dicarbonyl compounds to pyrrole.


Assuntos
Glucose/química , Lisina/análogos & derivados , Lisina/química , Reação de Maillard , Norleucina/análogos & derivados , Pirróis/química , Desoxiglucose/análogos & derivados , Desoxiglucose/química , Cinética , Norleucina/química , Aldeído Pirúvico/química
2.
Hell J Nucl Med ; 22(2): 103-110, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31273351

RESUMO

OBJECTIVE: Incorporation of lutetium-177 (177Lu) into suitable molecules that are implicated in cancer pathology represents a promising approach for the diagnosis and treatment of cancer. The goal of the present study was to develop a novel 177Lu labeled radiopharmaceutical agent for both radioimaging and targeted radionuclide therapy. ANIMALS AND METHODS: Given the synthetic versatility of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) ligand as a metal chelator and high demand of sugar molecules such as deoxyglucose (DG) in cancer cells, we carried out the radiosynthesis of a novel radiopharmaceutical agent, namely, 177Lu-DOTA-DG, and utilized it for imaging of cancer and also for the targeted radiation therapy of cancer tissues. RESULTS: In this study, we developed an efficient radiochemical synthesis of 177Lu-DOTA-DG and evaluated its pharmacological properties in vitro/in vivo. Our results showed DOTA-DG can be labeled with 177Lu with excellent radiochemical yield at 90oC in 30min. The resulting 177Lu-DOTA-DG exhibited high degree of stability without significant radiolysis up to 120h in human serum and phosphate buffer. Favorable pharmacokinetics profile was demonstrated by rapid blood clearance in 4T1 murine tumor mice and heterogeneous whole body biodistribution of 177Lu-DOTA-DG. Further, Comet assay experiments indicated that cancer cells treated with 177Lu-DOTA-DG showed significant higher degree of DNA damage compared to cells treated with 177Lu3+ or non-treated cells. CONCLUSION: This study showed that there is a great potential of using 177Lu-DOTA-DG as an imaging and therapeutic agent for cancer diagnosis and treatment. Furthermore, this study provides valuable information for developing novel 177Lu-labeled radiopharmaceuticals.


Assuntos
Desoxiglucose/química , Compostos Heterocíclicos com 1 Anel/química , Lutécio/uso terapêutico , Imagem Molecular/métodos , Radioisótopos/uso terapêutico , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/uso terapêutico , Animais , Transporte Biológico , Linhagem Celular Tumoral , Dano ao DNA , Estabilidade de Medicamentos , Marcação por Isótopo , Lutécio/efeitos adversos , Camundongos , Radioquímica , Radioisótopos/efeitos adversos , Compostos Radiofarmacêuticos/efeitos adversos , Compostos Radiofarmacêuticos/farmacocinética , Distribuição Tecidual
3.
J Agric Food Chem ; 67(20): 5874-5881, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31050431

RESUMO

Dicarbonyl compounds such as methylglyoxal (MGO) and 3-deoxyglucosone (3-DG) are formed via caramelization and the Maillard reaction in food during heating or in vivo as byproducts of glycolysis. Recently, it was shown that creatine, an amino compound linked to the energy metabolism in vertebrate muscle, reacts rapidly with methylglyoxal under physiological conditions to form N-(4-methyl-5-oxo-1-imidazolin-2-yl)sarcosine (MG-HCr), a methylglyoxal-derived hydroimidazolone of creatine. Based on the observation that heated meat contains only small amounts of MGO and 3-DG when compared to many other foodstuffs, the aim of this study was to investigate a possible reaction of creatine with 3-DG and MGO in meat. From incubation mixtures consisting of 3-DG and creatine, a new hydroimidazolone of creatine, namely N-(4-butyl-1,2,3-triol-5-oxo-1-imidazolin-2-yl)sarcosine (3-DG-HCr), was isolated and characterized via spectroscopic means. To quantitate 3-DG-HCr and MG-HCr, meat and fish products were analyzed via HPLC-MS/MS using isotopically labeled standard material. Whereas samples of raw fish and meat contained only trace amounts of the hydroimidazolones (below 5 µg/kg), up to 28.3 mg/kg MG-HCr and up to 15.3 mg/kg 3-DG-HCr were found in meat and fish products. The concentrations were dependent on the heat treatment and presumably on the smoking process. In comparison to the lysine and arginine derivatives CEL, pyrraline, and MG-H1, the derivatization rate of creatine as MG-HCr and 3-DG-HCr was higher than of lysine and arginine, which clearly demonstrates the 1,2-dicarbonyl scavenging properties of creatine in meat.


Assuntos
Creatina/química , Desoxiglucose/análogos & derivados , Imidazóis/química , Carne/análise , Aldeído Pirúvico/química , Animais , Arginina/química , Bovinos , Galinhas , Cromatografia Líquida de Alta Pressão , Culinária , Desoxiglucose/química , Temperatura Alta , Lisina/química , Reação de Maillard , Suínos , Espectrometria de Massas em Tandem
4.
Food Chem ; 290: 187-195, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31000036

RESUMO

3-Deoxyglucosone (3-DG) is a metabolite from sugar degradation obtained by the Maillard reaction. It is an important precursor compound in Strecker reactionism that directly leads to known beer aging indicators and can influence the final sensory beer quality. However, the conditions of 3-DG formation in the malting process have not yet been described. To investigate the reaction pathways of 3-DG formation, we varied the composition of reactants (sugars, amino acids) by using different malting modification levels (germination time 5-7 d; steeping degree 42-45%; germination temperature 12-14 °C); final kilning temperature (60 °C to 100 °C). After its derivatization with ortho-phenylenediamine, we analyzed 3-DG with HPLC-UV. 3-DG concentration was between 5 and 120 µmol/100 g dry weight. The formation of 3-DG increased for high malt modification levels and high final kilning temperature. The abundant formation of 3-DG in the malting process is already comparable to the occurred brewing process concentration.


Assuntos
Desoxiglucose/análogos & derivados , Manipulação de Alimentos/métodos , Aminoácidos/análise , Cerveja/análise , Cromatografia Líquida de Alta Pressão , Desoxiglucose/química , Reação de Maillard , Monossacarídeos/análise , Fenilenodiaminas/análise , Espectrofotometria Ultravioleta , Temperatura
5.
J Agric Food Chem ; 67(18): 5197-5203, 2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31017427

RESUMO

Melanoidins are formed in foods during processing through the Maillard reaction between carbohydrates and amino compounds. The aim of this study was to draw conclusions about the formation mechanism and the structure of melanoidins formed at low water contents and low temperatures. In the Maillard reaction of d-glucose and γ-aminobutyric acid at low water contents 3-deoxyglucosone is the most important intermediate. Therefore, we used the reaction of 3-deoxyglucosone with γ-aminobutyric acid or ß-alanine as a simplified model system. The degradation of 3-deoxyglucosone and the color formation of the formed melanoidins were determined. In addition, the reaction mixture was analyzed with high-resolution mass spectrometry and a Kendrick analysis was applied. Oligomers consisting of up to four molecules of 3-deoxyglucosone and three amino acids and their respective dehydration products with furanoidic structure were detected. The melanoidin structure of C-C linked monomeric units postulated by Kroh et al. could be confirmed.


Assuntos
Desoxiglucose/análogos & derivados , Ácido gama-Aminobutírico/química , Aminoácidos/química , Desoxiglucose/química , Glucose/química , Cinética , Reação de Maillard , Estrutura Molecular , Polímeros/química
6.
Molecules ; 24(6)2019 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-30893851

RESUMO

Folic acid has been widely introduced into nano-drug delivery systems to give nanoparticle-targeted characteristics. However, the poor water solubility of folic acid may hinder the exploitation of its ability to load antineoplastic drugs. In the present study, we designed a new folate derivative (FA-2-DG) synthesized from folic acid and 2-Deoxyglucose (2-DG). The aim of this study was to evaluate the self-assembly characteristics of FA-2-DG, and its ability of loading cisplatin. The critical micelle concentration was 7.94 × 10-6 mol L-1. Fourier transform infrared spectroscopy indicated that hydrogen bonding interaction is a main driving force for the self⁻assembly of FA-2-DG. The particle was stable in pure water or 0.5% bovine serum albumin dispersions. By forming a coordination bond, the particles assembled from FA-2-DG can load cisplatin. The loading efficiency was maximal when the molar ratio of FA-2-DG to cisplatin was 2:1.


Assuntos
Cisplatino/química , Desoxiglucose/química , Ácido Fólico/química , Micelas , Nanopartículas/química , Sistemas de Liberação de Medicamentos , Difusão Dinâmica da Luz , Ligação de Hidrogênio , Solubilidade
7.
Carbohydr Res ; 475: 48-55, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30825721

RESUMO

Six different types of O-benzyl protected proline derivatives have been synthesized from D-glycals and 2C-formyl-glycals. One of the di-O-benzyl protected proline derivatives has been utilized for the synthesis of polysubstituted pyrrolizidines via [3 + 2] cycloaddition in a stereoselective manner. Further, we also report on the stereoselective synthesis of biologically active 1C-aryl/alkyl pyrrolidines i.e. 4-epi-radicamine B, 4-epi-radicamine A, 1C-butyl and 1C-methyl pyrrolidines through double reductive amination of a variety of D-glucal derived diketones with p-methoxybenzylamine.


Assuntos
Desoxiglucose/análogos & derivados , Prolina/síntese química , Pirróis/síntese química , Desoxiglucose/química , Estrutura Molecular , Prolina/química , Pirróis/química
8.
Int J Mol Sci ; 20(3)2019 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-30736291

RESUMO

The glucose analog, 2-deoxyglucose (2-DG), specifically inhibits glycolysis of cancer cells and interferes with the growth of cancer cells. However, the excellent water solubility of 2-DG makes it difficult to be concentrated in tumor cells. In this study, a targeted nano-pharmacosome was developed with folic acid-modified 2-DG (FA-2-DG) by using amino ethanol as a cleavable linker. FA-2-DG was able to self-assemble, forming nano-particles with diameters of 10⁻30 nm. The biological effects were evaluated with cell viability assays and flow cytometry analysis. Compared with a physical mixture of folic acid and 2-DG, FA-2-DG clearly reduced cell viability and resulted in cell cycle arrest. A computational study involving docking simulation suggested that FA-2-DG can dock into the same receptor as folic acid, thus confirming that the structural modification did not affect the targeting performance. The results indicated that the nano-pharmacosome consisting of FA-2-DG can be used for targeting in a nano-drug delivery system.


Assuntos
Desoxiglucose , Ácido Fólico , Nanopartículas , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Química Sintética , Desoxiglucose/química , Ácido Fólico/química , Humanos , Modelos Moleculares , Conformação Molecular , Nanopartículas/química , Nanopartículas/ultraestrutura , Relação Estrutura-Atividade
9.
Bioorg Med Chem ; 26(22): 5922-5933, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30420329

RESUMO

Boron neutron capture therapy (BNCT) is one of the radiotherapies that involves the use of boron-containing compounds for the treatment of cancer. Boron-10 (10B) containing compounds that can accumulate in tumor tissue are expected to be suitable agents for BNCT. We report herein on the design and synthesis of some new BNCT agents based on a d-glucose scaffold, since glycoconjugation has been recognized as a useful strategy for the specific targeting of tumors. To introduce a boryl group into a d-glucose scaffold, we focused on the hydroboration of d-glucal derivatives, which have a double bond between the C1 and C2 positions. It was hypothesized that a C-B bond could be introduced at the C2 position of d-glucose by the hydroboration of d-glucal derivatives and that the products could be stabilized by conversion to the corresponding boronic acid ester. To test this hypothesis, we prepared some 2-boryl-1,2-dideoxy-d-glucose derivatives as boron carriers and evaluated their cytotoxicity and cellular uptake activity to cancer cells, especially under hypoxic conditions.


Assuntos
Terapia por Captura de Nêutron de Boro , Boro/farmacologia , Desoxiglucose/análogos & derivados , Desenho de Fármacos , Monossacarídeos/farmacologia , Células A549 , Boro/química , Sobrevivência Celular/efeitos dos fármacos , Desoxiglucose/química , Desoxiglucose/farmacologia , Relação Dose-Resposta a Droga , Células HeLa , Humanos , Estrutura Molecular , Monossacarídeos/síntese química , Monossacarídeos/química , Relação Estrutura-Atividade
10.
J Agric Food Chem ; 66(44): 11806-11811, 2018 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-30336014

RESUMO

In this study, α-dicarbonyl compounds consisting of a backbone with six carbon atoms resulting from the Maillard reaction of d-fructose with γ-aminobutyric acid were determined. The reaction was carried out under mild reaction conditions at 50 °C and water contents between 0 and 90%. A thus far unknown α-dicarbonyl compound was found as the main product in the first 24 h at water contents below 50%. After isolation of its stable quinoxaline derivative, it was possible to identify the compound as 2-deoxy-d- glycero-hexo-3,4-diulose (2-deoxyglucosone). For the first time, the four C6-α-dicarbonyl compounds, 1-deoxyglucosone, 2-deoxyglucosone, 3-deoxyglucosone, and 4-deoxyglucosone, could be identified in the Maillard reaction of a hexose at the same time. This indicates the formation of a 2,3-eneaminol from the Schiff base of d-fructose and the formation of 2-amino-2-deoxy-3-ketose as an alternative to the Heyns product.


Assuntos
Desoxiglucose/química , Frutose/química , Ácido gama-Aminobutírico/química , Cinética , Reação de Maillard , Estrutura Molecular
11.
J Pharm Biomed Anal ; 158: 38-46, 2018 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-29860177

RESUMO

α-Dicarbonyl compounds (α-DCs) are very clinically important as they are considered as advanced glycation end products (AGEs) precursors and biomarkers for many chronic diseases such as diabetes and vascular diseases, in addition to their major role in progression of complications of such diseases. Aromatic aldehydes and ammonium acetate were productively used as a one-pot co-reagents for fluorogenic derivatization of α-DCs yielding fluorescent imidazole derivatives. Among the tried aromatic aldehydes, 4-carbomethoxybenzaldehyde yielded the products with best fluorescent characters. This approach for fluorogenic derivatization of α-DCs overcome the selectivity problem of the most commonly used derivatization reagent for α-DCs, α-diamino compounds, that can react unselectively with α-DCs and aldehydes. Separation of the formed imidazole derivatives of five α-DCs including glucosone, 3-deoxyglucosone, glyoxal, methyl glyoxal and dimethyl glyoxal together with ethylmethylglyoxal as an internal standard was carried out on an octyl column using a mobile phase consisted of methanol-water (15:85, v/v%) containing 0.2% formic acid with time programed flow, followed by fluorescence detection at excitation/emission wavelengths of 310/410 nm. The method showed excellent sensitivity for the targeted α-DCs with limits of detections ranging from 0.4 to 5.0 nM in human serum. Simple protein precipitation procedure was used for human serum treatment yielding very good recovery (91-105%) for the targeted α-DCs. The developed method was fully validated, then applied to the analysis of the five above mentioned clinically important α-DCs in serum samples of healthy, diabetic, rheumatic and cardiac disorders human volunteers. Due to the excellent analytical features of the developed method, including high selectivity and sensitivity, it was able to detect the pattern of the targeted α-DCs serum levels under the investigated different clinical conditions.


Assuntos
Diabetes Mellitus/sangue , Produtos Finais de Glicação Avançada/sangue , Cardiopatias/sangue , Doenças Reumáticas/sangue , Acetatos/química , Aldeídos/sangue , Aldeídos/química , Aldeídos/metabolismo , Biomarcadores/análise , Biomarcadores/metabolismo , Cromatografia Líquida de Alta Pressão/instrumentação , Cromatografia Líquida de Alta Pressão/métodos , Desoxiglucose/análogos & derivados , Desoxiglucose/análise , Desoxiglucose/química , Desoxiglucose/metabolismo , Diabetes Mellitus/metabolismo , Fluorescência , Produtos Finais de Glicação Avançada/química , Produtos Finais de Glicação Avançada/metabolismo , Voluntários Saudáveis , Cardiopatias/metabolismo , Humanos , Imidazóis/química , Imidazóis/metabolismo , Cetoses/análise , Cetoses/química , Cetoses/metabolismo , Limite de Detecção , Estresse Oxidativo , Doenças Reumáticas/metabolismo , Sensibilidade e Especificidade
12.
Food Funct ; 9(5): 2809-2819, 2018 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-29693091

RESUMO

Ginnalin A (also known as acertannin) is one of the most important phenolic compounds of several beverage Acer plants. In this study, it is reported for the first time that ginnalin A is an activator of the Nrf2 signaling pathway in human colon cancer cells. Ginnalin A, isolated from the leaves of Acer tataricum subsp. ginnala, exhibited promising preventive activity against colon cancer cells (HCT116, SW480 and SW620) with IC50 values of 24.8 µM, 22.0 µM and 39.7 µM, respectively. In addition, it significantly reduced the colony formation of these cells. Flow cytometry analysis indicated that ginnalin A suppressed cancer proliferation via the induction of cell cycle arrest at the S-phase. Real time PCR analysis demonstrated that ginnalin A can upregulate the mRNA expression levels of Nrf2-related antioxidant genes Nrf2, HO-1 and NQO1. Western blotting analysis revealed that ginnalin A promoted the Nrf2 nuclear translocation and upregulated the proteins Nrf2, HO-1 and NQO1. Moreover, the upregulation of p62 and the inhibition of Keap1 were also found by Western blotting analysis. Therefore, the activation of the Nrf2 signaling pathway was probably induced through the upregulation of p62 and the inhibition of Keap1.


Assuntos
Acer/química , Neoplasias Colorretais/metabolismo , Desoxiglucose/análogos & derivados , Ácido Gálico/análogos & derivados , Heme Oxigenase-1/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Extratos Vegetais/farmacologia , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Quimioprevenção , Neoplasias Colorretais/genética , Neoplasias Colorretais/fisiopatologia , Neoplasias Colorretais/prevenção & controle , Desoxiglucose/química , Desoxiglucose/farmacologia , Ácido Gálico/química , Ácido Gálico/farmacologia , Heme Oxigenase-1/genética , Humanos , Fator 2 Relacionado a NF-E2/genética , Extratos Vegetais/química , Transdução de Sinais/efeitos dos fármacos
13.
Phytochemistry ; 150: 12-22, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29529525

RESUMO

Gymnema sylvestre (Retz.) R.Br. ex Sm. (Asclepiadaceae) is a well-known Ayurvedic anti-sweet plant for the treatment of type 2 diabetes mellitus. Although it was previously proposed that G. sylvestre exhibits chemical variation based on geography, most research on G. sylvestre has used material originating from India. Morphological and anatomical descriptions, ITS1-5.8S-ITS2 DNA sequencing, and acid hydrolysis analyses showed that G. sylvestre samples from Vietnam are distinguishable from those of Indian origin and thus suggest a dissimilarity among G. sylvestre samples with different geographic distributions. An LC-MS-guided strategy targeting 3ß-glucuronide oleane-triterpenes in the Vietnamese G. sylvestre variety led to the isolation of four known compounds and nine previously undescribed compounds, named gymnemosides ND1-ND9. None of the isolated compounds were reported in the Indian sample, further supporting the geo-diversity of G. sylvestre. Three compounds, gymnemosides ND7-9, exerted significant stimulatory effects on the uptake of 2-NBDG in 3T3-L1 adipocyte cells and thus have potential as lead molecules for anti-diabetes agents.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Gymnema sylvestre/genética , 4-Cloro-7-nitrobenzofurazano/análogos & derivados , 4-Cloro-7-nitrobenzofurazano/química , Desoxiglucose/análogos & derivados , Desoxiglucose/química , Hipoglicemiantes , Índia , Ácido Oleanólico/química , Extratos Vegetais/química , Folhas de Planta/química , Saponinas/química , Vietnã
14.
Nucl Med Rev Cent East Eur ; 21(1): 32-36, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29319137

RESUMO

BACKGROUND: Mesoporous nanoparticles have a great potential in targeted therapy approaches due to their ideal properties for encapsulation of various drugs, proteins and also biologically active molecules. MATERIAL AND METHODS: We used mesoporous hydroxyapatite (HA) nanoparticles as a drug carrier and developed radiolabeled mesoporous HA containing of 2-deoxy-D-glucose (2DG) and Doxorubicin (DOX) with technetium-99m (99mTc) for imaging in in vitro and in vivo studies. RESULTS: 2DG and DOX in presence of mesoporous HA nanoparticles more reduced the fraction of viable cells in the MDA-MB-231, MCF-7 human and MC4-L2 Balb/c mice breast cancer cells. The radiochemical purity of the nano-2DG-DOX complex with 99mTc was calculated to 96.8%. The results of cellular uptake showed a 44.77% increase in uptake of the [99mTc]-nano-2DG-DOX compared to the complex without nanoparticles (p < 0.001). CONCLUSION: Radioisotopic imaging demonstrated a high biochemical stability for [99mTc]-nano-2DG-DOX complex. The results demonstrated that [99mTc]-nano-2DG-DOX, may be used as an attractive candidate in cancer imaging and treatment managing.


Assuntos
Neoplasias da Mama/patologia , Desoxiglucose/química , Doxorrubicina/química , Portadores de Fármacos/química , Durapatita/química , Nanopartículas/química , Tecnécio/química , Animais , Transporte Biológico , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Desoxiglucose/metabolismo , Desoxiglucose/farmacologia , Desoxiglucose/uso terapêutico , Doxorrubicina/metabolismo , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Humanos , Marcação por Isótopo , Camundongos , Porosidade , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Metabolomics ; 14(4): 39, 2018 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-30830377

RESUMO

INTRODUCTION: Metabolomics allows exploration of novel biomarkers and provides insights on metabolic pathways associated with disease. To date, metabolomics studies on CKD have been largely limited to Caucasian populations and have mostly examined surrogate end points. OBJECTIVE: In this study, we evaluated the role of metabolites in predicting a primary outcome defined as dialysis need, doubling of serum creatinine or death in Brazilian macroalbuminuric DKD patients. METHODS: Non-targeted metabolomics was performed on plasma from 56 DKD patients. Technical triplicates were done. Metabolites were identified using Agilent Fiehn GC/MS Metabolomics and NIST libraries (Agilent MassHunter Work-station Quantitative Analysis, version B.06.00). After data cleaning, 186 metabolites were left for analyses. RESULTS: During a median follow-up time of 2.5 years, the PO occurred in 17 patients (30.3%). In non-parametric testing, 13 metabolites were associated with the PO. In univariate Cox regression, only 1,5-anhydroglucitol (HR 0.10; 95% CI 0.01-0.63, p = .01), norvaline and L-aspartic acid were associated with the PO. After adjustment for baseline renal function, 1,5-anhydroglucitol (HR 0.10; 95% CI 0.02-0.63, p = .01), norvaline (HR 0.01; 95% CI 0.001-0.4, p = .01) and aspartic acid (HR 0.12; 95% CI 0.02-0.64, p = .01) remained significantly and inversely associated with the PO. CONCLUSION: Our results show that lower levels of 1,5-anhydroglucitol, norvaline and L-aspartic acid are associated with progression of macroalbuminuric DKD. While norvaline and L-aspartic acid point to interesting metabolic pathways, 1,5-anhydroglucitol is of particular interest since it has been previously shown to be associated with incident CKD. This inverse biomarker of hyperglycemia should be further explored as a new tool in DKD.


Assuntos
Albuminúria/metabolismo , Desoxiglucose/química , Nefropatias Diabéticas/metabolismo , Metabolômica , Albuminúria/sangue , Biomarcadores/sangue , Biomarcadores/metabolismo , Brasil , Creatinina/sangue , Creatinina/metabolismo , Nefropatias Diabéticas/sangue , Método Duplo-Cego , Cromatografia Gasosa-Espectrometria de Massas , Humanos
16.
Semin Cancer Biol ; 49: 1-8, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29174601

RESUMO

Reactive 1,2-dicarbonyl compounds (DCs) are generated from carbohydrates during food processing and storage and under physiological conditions. In the recent decades, much knowledge has been gained concerning the chemical formation pathways and the role of DCs in food and physiological systems. DCs are formed mainly by dehydration and redox reactions and have a strong impact on the palatability of food, because they participate in aroma and color formation. However, they are precursors of advanced glycation end products (AGEs), and cytotoxic effects of several DCs have been reported. The most abundant DCs in food are 3-deoxyglucosone, 3-deoxygalactosone, and glucosone, predominating over methylglyoxal, glyoxal, and 3,4-dideoxyglucosone-3-ene. The availability for absorption of individual DCs is influenced by the release from the food matrix during digestion and by their reactivity towards constituents of intestinal fluids. Some recent works suggest formation of DCs from dietary sugars after their absorption, and others indicate that certain food constituents may scavenge endogenously formed DCs. First works on the interplay between dietary DCs and diseases reveal an ambiguous role of the compounds. Cancer-promoting but also anticancer effects were ascribed to methylglyoxal. Further work is still needed to elucidate the reactions of DCs during intestinal digestion and pathophysiological effects of dietary DCs at doses taken up with food and in "real" food matrices in disease states such as diabetes, uremia, and cancer.


Assuntos
Carboidratos/química , Exposição Dietética/efeitos adversos , Alimentos , Estresse Oxidativo , Desoxiglucose/análogos & derivados , Desoxiglucose/química , Desoxiglucose/metabolismo , Desoxiglucose/farmacologia , Galactose/análogos & derivados , Galactose/química , Galactose/farmacologia , Glioxal/química , Glioxal/metabolismo , Glioxal/farmacologia , Humanos , Cetoses/química , Cetoses/metabolismo , Cetoses/farmacologia , Oxirredução , Estresse Oxidativo/efeitos dos fármacos
17.
Rejuvenation Res ; 21(5): 389-404, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28891383

RESUMO

The world is experiencing an epidemic of type-2-diabetes mellitus (T2DM). This has led to increased morbidity and mortality, explosive growth in health care budgets, and an even greater adverse, if indirect, impact on societies and economies of affected countries. While genetic susceptibility to T2DM is a major determinant of its prevalence, changes in lifestyles also play a role. One such change has been a transition from traditional diets characterized by low caloric and high nutrient density to calorie-rich but nutrient-poor Western diets. Given this, one solution to the epidemic of T2DM would be to abandon Western diets and revert to traditional eating patterns. However, traditional diets cannot provide enough calories for the increasing global population, so transition from traditional to Western foodstuffs appears to be irreversible. Consequently, the only practical solution to problems caused by these changes is to modify Western diets, possibly by supplementing them with functional foods containing nutrients that would compensate for these dietary deficits. I present in this study a hypothesis to explain why shifts from traditional to Western diets have been so problematic and to suggest nutrients that may counteract these adverse effects. I postulate that the components of traditional diets that may compensate for deficiencies of Westerns diets are scavengers of reactive α-dicarbonyls produced as unavoidable by-products of glucose and lipid metabolism. Most important among these scavengers are some plant secondary metabolites: polyphenols, phlorotannins, and carotenoids. They are found in alcoholic beverages and are abundant in seasonings, cocoa, coffee, tea, whole grains, pigmented vegetables, fruits, and berries.


Assuntos
Consumo de Bebidas Alcoólicas , Desoxiglucose/análogos & derivados , Diabetes Mellitus Tipo 2/prevenção & controle , Dieta , Depuradores de Radicais Livres/uso terapêutico , Radical Hidroxila/química , Polifenóis/uso terapêutico , Desoxiglucose/química , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Estilo de Vida
18.
Anal Biochem ; 537: 20-25, 2017 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-28847591

RESUMO

Epithelial brush-border membrane vesicles (BBMVs) were isolated from the intestine of common carp and studied systematically by enzyme activity, transmission electron microscopy and immunoblotting. The uptake time course and the substrate concentration effect were assessed, and then, the ability of phlorizin and cytochalasin B to inhibit uptake was analyzed. The results show that sucrase, alkaline phosphatase and Na+-K+-ATPase activities in these vesicles were enriched 7.94-, 6.74- and 0.42-fold, respectively, indicating a relatively pure preparation of apical membrane with little basolateral contamination. The vesicular structure was in complete closure, as confirmed by electron microscopy. The presence of SGLT1 on the BBMVs was confirmed by Western blot analysis. In the time course experiment, the glucose uptake by BBMVs in Na+ medium displayed an initial accumulation (overshoot) at 5 min followed by a rapid return to equilibrium values at 60 min. Over the 2-NBDG concentration range selected, the external 2-NBDG concentration in NaSCN medium graphed as a curved line. Phlorizin and cytochalasin B had an obvious inhibitory effect on 2-NBDG transport in carp BBMVs, and the detected fluorescence intensity decreased. The inhibition rate in the 1000 µM group was the strongest at 64.18% and 63.61% of phlorizin and cytochalasin B, respectively, indicating the presence of carriers other than SGLT1. This study is the first to demonstrate that 2-NBDG can be used as a convenient and sensitive probe to detect glucose uptake in fish BBMVs. This technology will provide a convenient method to discover new effects and factors in glucose metabolism.


Assuntos
4-Cloro-7-nitrobenzofurazano/análogos & derivados , Desoxiglucose/análogos & derivados , Glucose/metabolismo , Mucosa Intestinal/metabolismo , Vesículas Secretórias/metabolismo , Espectrometria de Fluorescência , 4-Cloro-7-nitrobenzofurazano/química , 4-Cloro-7-nitrobenzofurazano/metabolismo , Animais , Transporte Biológico/efeitos dos fármacos , Carpas , Citocalasina B/farmacologia , Desoxiglucose/química , Desoxiglucose/metabolismo , Glucose/análise , Glucose/química , Microscopia Eletrônica de Transmissão , Florizina/farmacologia , Vesículas Secretórias/química , Vesículas Secretórias/enzimologia , Transportador 1 de Glucose-Sódio/metabolismo , Tiocianatos/química
19.
PLoS One ; 12(6): e0178202, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28582426

RESUMO

Gold nanoparticles are predominantly used in diagnostics, therapeutics and biomedical applications. The present study has been designed to synthesize differently capped gold nanoparticles (AuNps) by a simple, one-step, room temperature procedure and to evaluate the potential of these AuNps for biomedical applications. The AuNps are capped with glucose, 2-deoxy-D-glucose (2DG) and citrate using different reducing agents. This is the first report of synthesis of 2DG-AuNp by the simple room temperature method. The synthesized gold nanoparticles are characterized with UV-Visible Spectroscopy, Fourier transform infrared spectroscopy (FTIR), Transmission electron microscopy (TEM) and selected area electron diffraction (SAED), Dynamic light scattering (DLS), and Energy-dispersive X-ray spectroscopy (SEM-EDS). Surface-enhanced Raman scattering (SERS) study of the synthesized AuNps shows increase in Raman signals up to 50 times using 2DG. 3-(4, 5-dimethylthiozol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay has been performed using all the three differently capped AuNps in different cell lines to assess cytotoxcity if any, of the nanoparticles. The study shows that 2DG-AuNps is a better candidate for theranostic application.


Assuntos
Desoxiglucose/química , Glucose/química , Ouro/química , Nanopartículas Metálicas/química , Nanomedicina Teranóstica/métodos , Sobrevivência Celular/efeitos dos fármacos , Ácido Cítrico/química , Ouro/farmacologia , Células HCT116 , Células HeLa , Células Hep G2 , Humanos , Nanopartículas Metálicas/ultraestrutura , Tamanho da Partícula
20.
Nat Commun ; 8: 15560, 2017 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-28504272

RESUMO

Sirt1 is an NAD+-dependent protein deacetylase that regulates many physiological functions, including stress resistance, adipogenesis, cell senescence and energy production. Sirt1 can be activated by energy deprivation, but the mechanism is poorly understood. Here, we report that Sirt1 is negatively regulated by ATP, which binds to the C-terminal domain (CTD) of Sirt1. ATP suppresses Sirt1 activity by impairing the CTD's ability to bind to the deacetylase domain as well as its ability to function as the substrate recruitment site. ATP, but not NAD+, causes a conformational shift to a less compact structure. Mutations that prevent ATP binding increase Sirt1's ability to promote stress resistance and inhibit adipogenesis under high-ATP conditions. Interestingly, the CTD can be attached to other proteins, thereby converting them into energy-regulated proteins. These discoveries provide insight into how extreme energy deprivation can impact Sirt1 activity and underscore the complex nature of Sirt1 structure and regulation.


Assuntos
Trifosfato de Adenosina/química , Sirtuína 1/metabolismo , Adipogenia , Animais , Sítios de Ligação , Desoxiglucose/química , Regulação da Expressão Gênica , Células HEK293 , Humanos , Masculino , Camundongos , Mutação , Plasmídeos , Domínios Proteicos , Sirtuína 1/genética , Fatores de Transcrição/metabolismo
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