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1.
Int J Food Microbiol ; 306: 108272, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31376617

RESUMO

In this study, zein coatings containing Lauroyl-l-arginine ethyl ester monohydrochloride (LAE) were developed to be applied on polypropylene films and manufacture an active food packaging. The concentration of LAE and the addition of a suitable plasticizer (glycerol or oleic acid (OA)) were the main variables considered. Active plasticized zein films, with glycerol or oleic acid were characterized in terms of release kinetics, mechanical, barrier, optical, and antimicrobial properties. Results showed that active agent concentration, (5 and 10%), had no-significant effect on mechanical and WVP properties of the plasticized films. Films plasticized with OA presented greater water resistance, UV-light opacity, and water barrier properties than glycerol-plasticized films. On the contrary, the latter had better antimicrobial properties. The analysis of LAE release kinetics from films to different food simulants revealed different behaviours, depending on both film formulation and food simulant. Despite the lower water resistance of coatings containing glycerol, bags based on polypropylene/glycerol plasticized zein containing 10% of LAE presented a great antimicrobial activity in tests with chicken soup (real food system) contaminated with pathogen bacteria, concretely, the films showed 3.21 Log reduction against Listeria monocytogenes and 3.07 log reductions against Escherichia coli. These results suggest a promising strategy on the use of LAE-containing zein in active food packaging to control foodborne pathogens.


Assuntos
Antibacterianos/farmacologia , Arginina/análogos & derivados , Escherichia coli/crescimento & desenvolvimento , Embalagem de Alimentos/métodos , Listeria monocytogenes/crescimento & desenvolvimento , Zeína/farmacologia , Animais , Arginina/farmacologia , Galinhas , Escherichia coli/efeitos dos fármacos , Listeria monocytogenes/efeitos dos fármacos , Água
2.
Phys Chem Chem Phys ; 21(32): 17893-17900, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31380529

RESUMO

The dispersion interaction was reported to play a critical role in the stabilization of model dipeptide Z-Arg-OH, even greater than the conventional hydrogen bond (HB), which is opposite to the traditional opinion. Here the conformation of Z-Arg-OH has been systematically searched by the effective fragment based step-by-step strategy. All the newly-found low-energy conformers determined at the advanced DSD-PBEP86-D3(BJ)/aug-cc-pVTZ level are clearly in the stretched form with strong conventional HBs, rather than the reported folded structures with emphasis on the dispersion interactions. The simulated IR spectra of the stretched conformers fit better than those of the folded ones compared with the previous experimental observations. Near-edge X-ray absorption fine-structure (NEXAFS) spectra and X-ray photoelectron spectra (XPS) at C, N and O K-edges have also been simulated to unambiguously identify different isomers. This work thus provides valuable insight into the competitions between the conventional HB and the dispersion interactions and demonstrates that the conventional hydrogen bonding is still more important for such small peptides.


Assuntos
Arginina/análogos & derivados , Arginina/química , Dipeptídeos/química , Modelos Moleculares , Ligações de Hidrogênio , Isomerismo , Fenômenos Físicos , Conformação Proteica , Estabilidade Proteica , Solventes/química , Termodinâmica
3.
Nat Commun ; 10(1): 2917, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31266949

RESUMO

Novel antibacterial agents are needed to address the emergence of global antibiotic resistance. MraY is a promising candidate for antibiotic development because it is the target of five classes of naturally occurring nucleoside inhibitors with potent antibacterial activity. Although these natural products share a common uridine moiety, their core structures vary substantially and they exhibit different activity profiles. An incomplete understanding of the structural and mechanistic basis of MraY inhibition has hindered the translation of these compounds to the clinic. Here we present crystal structures of MraY in complex with representative members of the liposidomycin/caprazamycin, capuramycin, and mureidomycin classes of nucleoside inhibitors. Our structures reveal cryptic druggable hot spots in the shallow inhibitor binding site of MraY that were not previously appreciated. Structural analyses of nucleoside inhibitor binding provide insights into the chemical logic of MraY inhibition, which can guide novel approaches to MraY-targeted antibiotic design.


Assuntos
Antibacterianos/química , Bactérias/enzimologia , Proteínas de Bactérias/química , Produtos Biológicos/química , Inibidores Enzimáticos/química , Nucleosídeos/antagonistas & inibidores , Transferases/química , Aminoglicosídeos/química , Arginina/análogos & derivados , Arginina/química , Bactérias/química , Bactérias/genética , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Sítios de Ligação , Cristalografia por Raios X , Transferases/antagonistas & inibidores , Transferases/genética , Transferases/metabolismo
4.
Chem Commun (Camb) ; 55(52): 7482-7485, 2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31184653

RESUMO

Protein arginine (Arg) phosphorylation regulates stress responses and virulence in bacteria. With fluorescent activity probes, we show that McsB, a protein Arg kinase, can dephosphorylate phosphoarginine (pArg) residues to produce ATP from ADP, implicating the dynamic control of protein pArg levels by the kinase even without a phosphatase.


Assuntos
Arginina Quinase/metabolismo , Corantes Fluorescentes/química , Difosfato de Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Sequência de Aminoácidos , Arginina/análogos & derivados , Arginina/análise , Arginina/química , Arginina/metabolismo , Cromatografia Líquida de Alta Pressão , Compostos Organofosforados/análise , Fosforilação
5.
BMC Complement Altern Med ; 19(1): 127, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31196042

RESUMO

BACKGROUND: Xin-Ji-Er-Kang (XJEK) is a Chinese herbal formula, which has been reported to exert effective protection against cardiovascular diseases, including hypertension and myocarditis. METHODS: Cultured human umbilical vascular endothelial cells (HUVECs) were treated with angiotensin II (Ang II) and different concentrations of aqueous layer extracts (AqE). Subsequently nitric oxide (NO) and endothelial nitric oxide synthase (eNOS) expression levels were detected. In addition, fifty Kunming mice were randomized into control, Nω-nitro-L-arginine methyl ester (L-NAME), L-NAME+AqE, L-NAME+XJEK and L-NAME+fosinopril treatment groups. Following 8 weeks of treatment, the cardiac hemodynamic index was measured, relaxation of the aorta was examined and pathological changes were observed. Colorimetric analysis and enzyme linked immunosorbent assay (ELISA) were applied to determine the relevant indicators in plasma and cardiac tissues. RESULTS: The in vitro study results demonstrated that AqE could preserve endothelial function (NO, 21.05 ± 2.03 vs. 8.64 ± 0.59; eNOS, 1.08 ± 0.17 vs.0.73 ± 0.06). In addition, the in vivo results demonstrated that compared with the control group, treatment with AqE could enhance a high hemodynamic state (left ventricular systolic pressure, 116.76 ± 9.96 vs.114.5 ± 15.16), improve endothelial function (NO, 7.98 ± 9.64 vs. 1.66 ± 3.11; eNOS, 19.78 ± 3.18 vs.19.38 ± 3.85), suppress oxidative stress (OS) (superoxide dismutase, 178.17 ± 13.78 vs. 159.38 ± 18.86; malondialdehyde, 0.77 ± 0.13 vs.1.25 ± 0.36) and reverse cardiovascular remodeling. CONCLUSION: Polysaccharide from XJEK exerts protective effects against Ang II-induced injury in HUVECs and L-NAME-induced hypertension in mice and the underlying mechanism may be attributed to improving endothelial dysfunction, OS and the inflammation status in mice.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Células Endoteliais/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Remodelação Vascular/efeitos dos fármacos , Angiotensina II , Animais , Aorta/efeitos dos fármacos , Arginina/análogos & derivados , Arginina/sangue , Pressão Sanguínea/efeitos dos fármacos , Citocinas/metabolismo , Avaliação Pré-Clínica de Medicamentos , Medicamentos de Ervas Chinesas/farmacologia , Células Endoteliais/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Hipertensão/induzido quimicamente , Inflamação/tratamento farmacológico , Masculino , Malondialdeído/sangue , Camundongos , Miocárdio/metabolismo , NG-Nitroarginina Metil Éster , Óxido Nítrico/sangue , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Superóxido Dismutase/sangue
6.
Carbohydr Polym ; 216: 129-139, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31047049

RESUMO

A novel biotin and arginine modified hydroxypropyl-ß-cyclodextrin (biotin-Arg(pbf)-HP-ß-CD) was successfully synthesized. The hydroxyl groups of HP-ß-CD on the primary faces were coupled with carboxyl groups of biotin using arginine as the functional spacer. Using biotin-Arg(pbf)-HP-ß-CD as the carrier, paclitaxel (PTX)-loaded nanoparticles were developed by modified emulsion solvent evaporation method. The optimized PTX-loaded biotin-Arg(pbf)-HP-ß-CD nanoparticles had a mean diameter of 121.9 nm and zeta potential of -57.7 mV. Transmission electron microscopy (TEM) observation revealed that the nanoparticles were spherical in shape. XRD spectra confirmed the successful encapsulation of PTX. Moreover, in vitro and in vivo evaluations were performed to demonstrate the superior antitumor activity of the PTX-loaded nanoparticles. The cellular uptake study demonstrated the biotin receptor-mediated endocytosis of biotin-Arg(pbf)-HP-ß-CD nanoparticles and the increase of cellular uptake by introduction of biotin and arginine. It can be concluded that the biotin-Arg(pbf)-HP-ß-CD nanoparticles are efficient tumor-targeting drug delivery systems for PTX.


Assuntos
2-Hidroxipropil-beta-Ciclodextrina/química , Antineoplásicos/uso terapêutico , Portadores de Fármacos/química , Nanopartículas/química , Paclitaxel/uso terapêutico , 2-Hidroxipropil-beta-Ciclodextrina/síntese química , 2-Hidroxipropil-beta-Ciclodextrina/toxicidade , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Arginina/análogos & derivados , Arginina/síntese química , Arginina/toxicidade , Biotina/análogos & derivados , Biotina/síntese química , Biotina/toxicidade , Carcinoma/tratamento farmacológico , Portadores de Fármacos/síntese química , Portadores de Fármacos/toxicidade , Feminino , Humanos , Células MCF-7 , Camundongos , Nanopartículas/toxicidade , Paclitaxel/química , Paclitaxel/farmacologia , Tamanho da Partícula , Neoplasias do Colo do Útero/tratamento farmacológico , Ensaios Antitumorais Modelo de Xenoenxerto
7.
J Agric Food Chem ; 67(20): 5754-5763, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31045365

RESUMO

Recently, although ginseng ( Panax ginseng C. A. Meyer) and its main component saponins (ginsenosides) have been reported to exert protective effects on cisplatin (CDDP)-induced acute kidney injury (AKI), the beneficial activities of non-saponin on CDDP-induced AKI is little known. This research was designed to explore the protective effect and underlying mechanism of arginyl-fructosyl-glucose (AFG), a major and representative non-saponin component generated during the process of red ginseng, on CDDP-caused AKI. AFG at doses of 40 and 80 mg/kg remarkably reversed CDDP-induced renal dysfunction, accompanied by the decreased levels of serum creatinine and blood urea nitrogen. Interestingly, all of oxidative stress indices were ameliorated after pretreatment with AFG continuously for 10 days. Importantly, AFG relieved CDDP-induced inflammation and apoptosis in part by mitigating the cascade initiation steps of nuclear factor κB signals and regulating the participation of the phosphatidylinositol 3-kinase/protein kinase B signal pathway. In conclusion, these results clearly provide strong rationale for the development of AFG to prevent CDDP-induced AKI.


Assuntos
Lesão Renal Aguda/tratamento farmacológico , Arginina/análogos & derivados , Cisplatino/efeitos adversos , Medicamentos de Ervas Chinesas/administração & dosagem , Glucose/administração & dosagem , Glicina/análogos & derivados , NF-kappa B/metabolismo , Panax/química , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/metabolismo , Lesão Renal Aguda/fisiopatologia , Animais , Apoptose/efeitos dos fármacos , Arginina/administração & dosagem , Arginina/química , Creatinina/metabolismo , Medicamentos de Ervas Chinesas/química , Glucose/química , Glicina/administração & dosagem , Glicina/química , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Reação de Maillard , Masculino , Camundongos Endogâmicos ICR , NF-kappa B/genética , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinase/genética , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/efeitos dos fármacos
8.
Chin J Integr Med ; 25(5): 327-333, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31065970

RESUMO

OBJECTIVE: To examine the prognostic value of serum levels of asymmetric dimethylarginine (ADMA) in patients with stable coronary heart disease (CHD) thus explore a potential biomarker of "toxin syndrome" in CHD. METHODS: In this prospective nested case-control study, 36 of 1,503 Chinese patients with stable CHD experienced at least 1 recurrent cardiovascular event (RCE) during 1-year follow-up. Serum levels of ADMA at the start of follow-up were compared between these 36 cases and 36 controls which matched to cases in terms of gender, age, history of hypertension, and myocardial infarction. RESULTS: Based on the crude model, subjects in the 2 highest ADMA quartiles showed significantly higher risk of developing RCE than those in the lowest ADMA quartile [odds ratio (OR) 4.09, 95% confidence interval (CI) 1.01 to 16.58; OR 6.76, 95% CI 1.57 to 29.07]. This association was also observed in the case-mix model (OR 5.51, 95% CI 1.23 to 24.61; OR 7.83, 95% CI 1.68 to 36.41) and multivariable model (OR 6.64, 95% CI 1.40 to 31.49: OR 13.14, 95% CI 2.28 to 75.71) after adjusting for confounders. The multivariable model which combined ADMA and high-sensitivity C-reactive protein (hsCRP) showed better predictive power with areas under the receiver operator characteristic curves (0.779) than the model of either ADMA (0.694) or hsCRP (0.636). CONCLUSION: Serum ADMA level may be a potential biomarker of "toxin syndrome" in CHD which shows favorable prognostic value in predicting 1-year RCE in patients with stable CHD. [The registration number is ChiCTR-PRNRC-07000012].


Assuntos
Arginina/análogos & derivados , Doença das Coronárias/sangue , Arginina/sangue , Biomarcadores/sangue , Humanos , Razão de Chances , Curva ROC , Recidiva , Fatores de Risco , Síndrome
9.
J Food Sci ; 84(6): 1631-1637, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31059127

RESUMO

The effects of Gynura bicolor aqueous extract (GAE) upon glycemic control, coagulation disorder, lipid accumulation, and glycative, oxidative, and inflammatory stresses in diabetic mice were investigated. Mice were treated with streptozotocin to induce type 1 diabetes. Diabetic mice were divided into four groups, consumed GAE at 0%, 0.25%, 0.5%, or 1%. Normal group consumed standard mouse basal diet. After 8-week treatments, mice were sacrificed after overnight fasting. Results showed that GAE supplement at 0.5% and 1% decreased plasma glucose level and increased plasma insulin level. Diabetes lowered plasma level of protein C and anti-thrombin III; and raised plasminogen activator inhibitor-1 activity and fibrinogen level in plasma. GAE supplement at 0.5% and 1% reversed these alterations. Histological data, assayed by Oil Red O stain, indicated that GAE supplement decreased lipid accumulation in liver. GAE supplement at 0.5% and 1% reduced aldose reductase activity in heart and kidney; and lowered the levels of carboxymethyllysine and pentosidine in plasma and two organs. Diabetes decreased glutathione content, and increased reactive oxygen species, interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α production in heart and kidney. GAE supplement at three test doses reversed these changes. Diabetes upregulated the mRNA expression of p38 and nuclear factor kappa (NF-κ)B in heart and kidney. GAE supplement suppressed the mRNA expression of both p38 and NF-κB. These novel findings suggest that Gynura bicolor is a potent functional food for diabetic prevention or alleviation.


Assuntos
Antidiuréticos/administração & dosagem , Asteraceae/química , Diabetes Mellitus Experimental/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Animais , Arginina/análogos & derivados , Arginina/metabolismo , Glicemia/metabolismo , Diabetes Mellitus Experimental/metabolismo , Glutationa/metabolismo , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Lisina/análogos & derivados , Lisina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Espécies Reativas de Oxigênio/metabolismo
10.
Biomed Res Int ; 2019: 2941861, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30931324

RESUMO

Objective: The purpose of the meta-analysis was to evaluate the relationship between serum asymmetric dimethylarginine (ADMA) level and microvascular complications in diabetes mellitus (DM) including diabetic retinopathy (DR), diabetic neuropathy (DN), and diabetic nephropathy. Methods: Studies were comprehensively identified by searching Web of Science, Embase, and PubMed databases up to August 30, 2018. The meta-analysis was carried out to compare the difference of serum ADMA concentrations of DR, DN, and diabetic nephropathy patients with healthy controls. The Newcastle-Ottawa Scale and the Agency for Healthcare Research and Quality were applied to assess the methodological quality. Chi-squared Q test and I2 statistics were applied to evaluate statistical heterogeneity. Subgroup analyses were conducted and publication bias was assessed by Egger's test. Result: Ten studies were finally entered in the meta-analysis. Statistically significant heterogeneity was observed across these studies (I 2 = 77.0%, p < 0.001). Compared with DM without microvascular complications, circulating level of ADMA was significantly higher in DM with microvascular complications (all p < 0.05). Sensitivity analysis suggested that the results of this meta-analysis were shown to be stable. There was no significant publication bias (P=0.823). Conclusion: Elevated ADMA levels correlate with diabetic microangiopathies such as DR and diabetic nephropathy. ADMA may play an important role in the pathobiology of microvascular complications of diabetes.


Assuntos
Arginina/análogos & derivados , Diabetes Mellitus/sangue , Angiopatias Diabéticas/sangue , Nefropatias Diabéticas/sangue , Arginina/sangue , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/patologia , Angiopatias Diabéticas/epidemiologia , Angiopatias Diabéticas/patologia , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/patologia , Neuropatias Diabéticas/sangue , Neuropatias Diabéticas/epidemiologia , Neuropatias Diabéticas/patologia , Retinopatia Diabética/sangue , Retinopatia Diabética/epidemiologia , Retinopatia Diabética/patologia , Feminino , Humanos , Masculino , Fatores de Risco
11.
PLoS Negl Trop Dis ; 13(4): e0007304, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31017889

RESUMO

The intracellular protozoan parasite Leishmania donovani causes human visceral leishmaniasis. Intracellular L. donovani that proliferate inside macrophage phagolysosomes compete with the host for arginine, creating a situation that endangers parasite survival. Parasites have a sensor that upon arginine deficiency activates an Arginine Deprivation Response (ADR). L. donovani transport arginine via a high-affinity transporter (LdAAP3) that is rapidly up-regulated by ADR in intracellular amastigotes. To date, the sensor and its ligand have not been identified. Here, we show that the conserved amidino group at the distal cap of the arginine side chain is the ligand that activates ADR, in both promastigotes and intracellular amastigotes, and that arginine sensing and transport binding sites are distinct in L. donovani. Finally, upon addition of arginine and analogues to deprived cells, the amidino ligand activates rapid degradation of LdAAP3. This study provides the first identification of an intra-molecular ligand of a sensor that acts during infection.


Assuntos
Sistemas de Transporte de Aminoácidos Básicos/metabolismo , Arginina/metabolismo , Leishmania donovani/metabolismo , Proteínas de Protozoários/metabolismo , Sistemas de Transporte de Aminoácidos Básicos/genética , Arginina/análogos & derivados , Sítios de Ligação , Transporte Biológico , Regulação da Expressão Gênica , Humanos , Leishmania donovani/genética , Macrófagos/parasitologia , Fagossomos/parasitologia , Proteínas de Protozoários/genética , Células THP-1
12.
Artigo em Inglês | MEDLINE | ID: mdl-30990116

RESUMO

4-pyridone-3-carboxamide-1-ß-D-ribonucleoside (4PYR) is a new nicotinamide derivative, which is potentially toxic to the endothelium. Dysfunction of the endothelium promotes cancer cell proliferation, invasiveness, and inflammatory signaling. The aim of this study was to analyze 4PYR concentration in the plasma of lung cancer patients and its relationship to other known biochemical parameters associated with the endothelium function. The concentration of 4PYR, nicotinamide, 1-methylnicotinamide (MNA), amino acids, and their derivatives were measured in samples obtained from patients with primary squamous cell carcinoma (n = 48) and control group (n = 100). The concentration of 4PYR and 4PYR/MNA ratio were significantly higher in lung cancer patients as compared to controls (0.099 ± 0.009 vs. 0.066 ± 0.006 µmol/L and 1.10 ± 0.08 vs. 1.97 ± 0.15, respectively). The plasma arginine/asymmetric dimethylarginine (Arg/ADMA) ratio was considerably lower in lung cancer patients (253 ± 17 vs. 369 ± 19) as well as plasma MNA (0.057 ± 0.004 vs. 0.069 ± 0.003 µmol/L). There was no difference in the plasma concentrations of nicotinamide and nicotinamide riboside in both groups (0.116 ± 0.019 vs. 0.131 ± 0.014 and 0.102 ± 0.006 vs. 0.113 ± 0.011, respectively). In this study, a higher 4PYR concentration was observed for the first time in patients with squamous cell carcinoma. This change may be related to the endothelial dysfunction that promote cancer progression since 4PYR and its derivatives are known to disrupt glycolytic pathway.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/sangue , Neoplasias Pulmonares/sangue , Nucleosídeos/sangue , Piridonas/sangue , Idoso , Arginina/análogos & derivados , Arginina/sangue , Carcinoma de Células Escamosas/patologia , Células Endoteliais/metabolismo , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Niacinamida/análogos & derivados , Niacinamida/sangue , Espectrometria de Massas em Tandem/métodos
13.
J Agric Food Chem ; 67(12): 3412-3422, 2019 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-30827106

RESUMO

The formation conditions of the Amadori compound (ARP) N-(1-deoxy-d-xylulos-1-yl)-alanine were determined in an aqueous Maillard reaction between l-alanine and d-xylose under a two-step temperature rising process with (-)-epigallocatechin gallate (EGCG) as an indicator followed by browning intensity detection of the final Maillard reaction products (MRPs). To clarify the mechanism of EGCG indication on the ARP formation, the change in the concentration of some key products generated during the Maillard reaction with EGCG addition was investigated. Results showed an inhibition effect of EGCG on the browning precursor formation through the generation of ARP-EGCG adducts and deoxyosone-EGCG adducts, which was proposed as an important pathway to inhibit browning during the Maillard reaction and to indicate ARP formation.


Assuntos
Arginina/análogos & derivados , Catequina/análogos & derivados , Monossacarídeos/química , Alanina/química , Arginina/química , Catequina/química , Produtos Finais de Glicação Avançada/química , Reação de Maillard , Temperatura Ambiente , Xilose/química
14.
J Pharm Biomed Anal ; 169: 82-89, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-30844626

RESUMO

Pediatric chronic kidney disease (CKD) is currently assessed using glomerular filtration rate (GFR), which is calculated from different equations based on serum creatinine concentration. However, serum creatinine is affected by several factors and is not reliable enough for the diagnosis of CKD, especially at early stages. Recent targeted and untargeted metabolomics studies found 7 new potential biomarkers that could be useful for early pediatric chronic kidney disease diagnosis. Thus, a new LC-QQQ-MS analytical method has been developed and validated aimed at routine analysis of these 7 potential biomarkers: NG,NG'-dimethyl-l-arginine di(p-hydroxyazobenzene-p'-sulfonate) (SDMA), S-adenosyl-l-methionine (SAM), n-butyryl-l-carnitine (nC4), iso-butyryl-l-carnitine (iC4), citrulline (CIT), creatinine (CNN) and d-erytro-sphingosine-1-phosphate (S1P), in addition to creatinine, the classical biomarker for CKD diagnosis. Then, this analytical method has been used for the quantification of plasma samples from a heterogeneous group of CKD pediatric patients and a control pediatric population. Data analysis of these results showed that it is possible to differentiate between CKD and control populations based on the metabolite concentration in plasma.


Assuntos
Biomarcadores/sangue , Biomarcadores/química , Plasma/química , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/diagnóstico , Arginina/análogos & derivados , Arginina/sangue , Arginina/química , Criança , Pré-Escolar , Cromatografia Líquida/métodos , Citrulina/química , Creatinina/sangue , Diagnóstico Precoce , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Masculino , Metabolômica/métodos , S-Adenosilmetionina/sangue , S-Adenosilmetionina/química , Espectrometria de Massas em Tandem/métodos
15.
Amino Acids ; 51(5): 773-782, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30830311

RESUMO

Rheumatoid arthritis (RA) patients have increased risk of cardiovascular disease (CVD) death. Elevated asymmetric dimethylarginine (ADMA) levels have been reported to be an independent predictor of CVD morbidity and mortality, however, the role of ADMA in RA remains undetermined. To derive a more accurate estimation on circulating ADMA levels in RA patients, a meta-analysis was performed. Embase, PubMed, and The Cochrane Library database (up to October 7 2018) were used to acquire published literatures. Heterogeneity test was performed by the Q statistic and quantified using I2. Publication bias was evaluated using a funnel plot and Egger's linear regression test. A total of 174 articles were identified, 16 studies with 1365 subjects (666 RA patients and 699 healthy individuals) were ultimately included. Plasma/serum ADMA levels appeared to be higher in RA patients than healthy controls (SMD = 0.84, 95% CI 0.32, 1.35). By assessing the BMI, age, disease duration and disease activity as subgroups, BMI ≥ 24 and BMI < 24 groups both showed elevated ADMA levels than controls, disease duration ≥ 8, age < 50 and disease activity ≥ 3.2 and < 5.1 group had a higher ADMA level than control groups. However, disease duration < 8, disease activity ≥ 5.1 and age ≥ 50 groups showed no difference between two groups. Circulating ADMA levels are higher in RA patients compared with healthy controls. In addition, ADMA levels are influenced by age, disease duration and disease activity.


Assuntos
Arginina/análogos & derivados , Artrite Reumatoide/sangue , Artrite Reumatoide/diagnóstico , Biomarcadores/sangue , Arginina/sangue , Estudos de Casos e Controles , Humanos , Fatores de Risco
16.
Nature ; 566(7742): 94-99, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30728519

RESUMO

Small molecules containing the N-nitroso group, such as the bacterial natural product streptozotocin, are prominent carcinogens1,2 and important cancer chemotherapeutics3,4. Despite the considerable importance of this functional group to human health, enzymes dedicated to the assembly of the N-nitroso unit have not been identified. Here we show that SznF, a metalloenzyme from the biosynthesis of streptozotocin, catalyses an oxidative rearrangement of the guanidine group of Nω-methyl-L-arginine to generate an N-nitrosourea product. Structural characterization and mutagenesis of SznF reveal two separate active sites that promote distinct steps in this transformation using different iron-containing metallocofactors. This biosynthetic reaction, which has little precedent in enzymology or organic synthesis, expands the catalytic capabilities of non-haem-iron-dependent enzymes to include N-N bond formation. We find that biosynthetic gene clusters that encode SznF homologues are widely distributed among bacteria-including environmental organisms, plant symbionts and human pathogens-which suggests an unexpectedly diverse and uncharacterized microbial reservoir of bioactive N-nitroso metabolites.


Assuntos
Metaloproteínas/metabolismo , Estreptozocina/biossíntese , Estreptozocina/química , Arginina/análogos & derivados , Domínio Catalítico/genética , Coenzimas/metabolismo , Cristalografia por Raios X , Guanidina/metabolismo , Ferro/metabolismo , Metaloproteínas/química , Metaloproteínas/genética , Modelos Moleculares , Família Multigênica , Compostos de Nitrosoureia/metabolismo , Streptomyces/enzimologia , Streptomyces/genética
17.
Pediatr Emerg Care ; 35(3): 226-230, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30747788

RESUMO

OBJECTIVE: Carbon monoxide poisoning (COP) is the leading cause of mortality and morbidity due to poisoning worldwide. Because children are affected more quick and severely from COP, they may require a longer treatment period, even if carboxyhemoglobin (CO-Hb) and/or lactate levels return to normal. Therefore, a new marker that predicts the duration of treatment and the final outcomes of COP is needed. METHODS: This case control study was conducted on 32 carbon monoxide-poisoned patients younger than 18 years who had been admitted to pediatric emergency department. The control group included age- and sex-matched 30 healthy children. Blood samples were obtained for analysis of arterial blood gases, CO-Hb percent, methemoglobine, lactate, and asymmetric dimethylarginine (ADMA). RESULTS: Asymmetric dimethylarginine levels were significantly increased (P < 0.05) in patients with COP on admission and after the treatment when compared with controls (1.36 [0.89-6.94], 1.69 [0.76-7.81], 1.21 [0.73-3.18] nmol/L, respectively). There was no positive correlation between CO-Hb and ADMA levels on admission and at 6 hours (P = 0.903, r = 0.218, P = 0.231, r = 0.022, respectively). Positive correlation was found between lactate and CO-Hb levels on admission (P = 0.018, r = 0.423). CONCLUSIONS: This study showed that ADMA levels were still high after 6 hours of 100% oxygen therapy in children with COP, even CO-Hb and/or lactate levels return to normal range. On the basis of these results, we consider that ADMA may be a useful biomarker in patient with COP.


Assuntos
Arginina/análogos & derivados , Biomarcadores/sangue , Intoxicação por Monóxido de Carbono/sangue , Adolescente , Arginina/sangue , Gasometria/métodos , Intoxicação por Monóxido de Carbono/terapia , Carboxihemoglobina/análise , Estudos de Casos e Controles , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Ácido Láctico/sangue , Masculino , Metemoglobina/análise
18.
Molecules ; 24(3)2019 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-30699887

RESUMO

Phe-Arg-ß-naphthylamide (PAßN) has been characterized as an efflux pump inhibitor (EPI) acting on the major multidrug resistance efflux transporters of Gram-negative bacteria, such as AcrB in Eschericha coli. In the present study, in vitro random mutagenesis was used to evolve resistance to the sensitizing activity of PAßN with the aim of elucidating its mechanism of action. A strain was obtained that was phenotypically similar to a previously reported mutant from a serial selection approach that had no efflux-associated mutations. We could confirm that acrB mutations in the new mutant were unrelated to PAßN resistance. The next-generation sequencing of the two mutants revealed loss-of-function mutations in lpxM. An engineered lpxM knockout strain showed up to 16-fold decreased PAßN activity with large lipophilic drugs, while its efflux capacity, as well as the efficacy of other EPIs, remained unchanged. LpxM is responsible for the last acylation step in lipopolysaccharide (LPS) synthesis, and lpxM deficiency has been shown to result in penta-acylated instead of hexa-acylated lipid A. Modeling the two lipid A types revealed steric conformational changes due to underacylation. The findings provide evidence of a target site of PAßN in the LPS layer, and prove membrane activity contributing to its drug-sensitizing potency.


Assuntos
Arginina/análogos & derivados , Aciltransferases/genética , Aciltransferases/metabolismo , Arginina/farmacologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/metabolismo , Proteínas de Escherichia coli/antagonistas & inibidores , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Lipopolissacarídeos/farmacologia , Testes de Sensibilidade Microbiana , Proteínas Associadas à Resistência a Múltiplos Medicamentos/antagonistas & inibidores , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Mutagênese/efeitos dos fármacos , Mutação/genética
19.
Int J Mol Sci ; 20(3)2019 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-30744089

RESUMO

A relevant part of embolic strokes of undetermined source (ESUS) is assumed to be due to non-detected atrial fibrillation (AF). In this study, we aimed to investigate if markers of endothelial dysfunction and damage may indicate AF risk in embolic stroke. Eighty-eight patients with ischemic stroke confirmed by imaging were assigned to one of three groups: ESUS, AF, or micro-/macroangiopathy. ESUS patients underwent prolonged Holter electrocardiography scheduled for three days. The National Institutes of Health Stroke Scale (NIHSS), the CHA2DS2VASC score, and the carotid intima⁻media thickness (CIMT) were obtained. Markers of endothelial (dys)function (L-arginine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA)) were measured at day seven after stroke. ESUS patients were younger and had fewer cardiovascular risk factors than patients with determined stroke etiology. Compared with AF patients, ESUS patients showed significantly lower values of SDMA (p = 0.004) and higher values of L-arginine (p = 0.031), L-arginine/ADMA ratio (p = 0.006), L-arginine/SDMA ratio (p = 0.002), and ADMA/SDMA ratio (p = 0.013). Concordant differences could be observed comparing ESUS patients with those with newly diagnosed AF (p = 0.026; p = 0.03; p = 0.009; p = 0.004; and p = 0.046, respectively). CIMT was significantly larger in AF than in ESUS patients (p < 0.001), and was identified as an AF risk factor independent from CHA2DS2VASC in the regression analysis (p = 0.014). These findings may support future stratification for AF risk in patients who have suffered embolic stroke.


Assuntos
Arginina/análogos & derivados , Fibrilação Atrial/sangue , Fibrilação Atrial/etiologia , Espessura Intima-Media Carotídea , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/complicações , Idoso , Idoso de 80 Anos ou mais , Arginina/sangue , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Biomarcadores , Endotélio/metabolismo , Endotélio/patologia , Feminino , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Curva ROC , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Tromboembolia/etiologia
20.
J Vet Intern Med ; 33(2): 508-515, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30758070

RESUMO

BACKGROUND: Iatrogenic hypothyroidism might worsen the prognosis of cats with azotemic CKD after thyroidectomy. Varying thyroxine concentrations influence utility of creatinine in assessing renal function. Symmetric dimethylarginine (SDMA) has limited studies in cats with changing thyroid status. OBJECTIVES: Thyroid status is stable 6 months post-thyroidectomy. Symmetric dimethylarginine and creatinine are linearly associated without influence from total thyroxine concentration (tT4). ANIMALS: Electronic records of 2 first opinion practices were searched using the term "thyroidectomy" to include 81 client-owned cats that had undergone bilateral thyroidectomy. METHODS: Retrospective cross-sectional study assessing thyroid hormone concentrations of 68 cats within 6 months of surgery. A longitudinal study of thyroid status in 23 cats with >18 months follow-up post-thyroidectomy. A generalized estimating equation assessed the associations of bodyweight, tT4 and creatinine concentrations on SDMA concentration. RESULTS: Sixty-eight cats had follow-up within 6 months. Fifteen cats (22%) had persistent, or recurrent, hyperthyroidism and 33 cats (49%) were hypothyroid. Twenty-three of the euthyroid/hypothyroid cats had long-term follow-up (595-1955 days); 4 cats (17%) remained hypothyroid, 19 cats (83%) were euthyroid (often transiently), and 9 of 23 cats (44%) developed recurrent hyperthyroidism. Symmetric dimethylarginine and creatinine were linearly associated, but hyperthyroid cats had higher SDMA concentrations, relative to creatinine (P = .003). CONCLUSIONS AND CLINICAL IMPORTANCE: Cats have changes in thyroid function for years after bilateral thyroidectomy, with a high incidence of recurrent hyperthyroidism. Both SDMA and creatinine are affected by thyroxine concentrations, and the effect is greater in hyperthyroid cats.


Assuntos
Arginina/análogos & derivados , Azotemia/veterinária , Doenças do Gato/etiologia , Tireoidectomia/veterinária , Animais , Arginina/sangue , Azotemia/sangue , Peso Corporal , Doenças do Gato/sangue , Doenças do Gato/patologia , Gatos , Creatinina/sangue , Estudos Transversais , Hipertireoidismo/complicações , Hipertireoidismo/veterinária , Hipotireoidismo/complicações , Hipotireoidismo/veterinária , Estudos Longitudinais , Estudos Retrospectivos , Tireoidectomia/efeitos adversos , Tiroxina/sangue
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