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1.
Anticancer Res ; 42(5): 2665-2673, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35489774

RESUMO

BACKGROUND: The purpose of this study was to evaluate the association of specific threshold values for changes in metabolic metrics measured from 1H magnetic resonance spectroscopic imaging (MRSI) to survival of patients with high-grade glioma treated with multimodality therapy. PATIENTS AND METHODS: Forty-four patients with newly diagnosed high-grade glioma were prospectively enrolled. Serial MRI and MRSI scans provided measures of tumor choline, creatine, and N-acetylaspartate (NAA). Cox regression analyses adjusted for patient age, KPS, and delivery of concurrent chemotherapy were used to assess the association of changes in metabolic metrics with survival. RESULTS: Median follow-up time for patients at risk was 13.4 years. Overall survival (OS) was longer in patients with ≤20% increase (vs. >20%) in normalized choline (p=0.024) or choline/NAA (p=0.024) from baseline to week 4 of RT. During this period, progression-free survival (PFS) was longer in patients with ≤40% increase (vs. >40%) in normalized choline (p=0.013). Changes in normalized creatine, choline/creatine, and NAA/creatine from baseline to mid-RT were not associated with OS. From baseline to post-RT, changes in metabolic metrics were not associated with OS or PFS. CONCLUSION: Threshold values for serial changes in choline metrics on mid-RT MRSI associated with OS and PFS were identified. Metabolic metrics at post-RT did not predict for these survival endpoints. These findings suggest a potential clinical role for MRSI to provide an early assessment of treatment response and could enable risk-adapted therapy in clinical trial development and clinical practice.


Assuntos
Neoplasias Encefálicas , Glioma , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/terapia , Colina/metabolismo , Creatina/metabolismo , Glioma/diagnóstico por imagem , Glioma/metabolismo , Glioma/terapia , Humanos , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética/métodos
2.
JAMA Netw Open ; 5(5): e2213242, 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35594043

RESUMO

Importance: Little is known about the association of trimethylamine N-oxide (TMAO), a novel plasma metabolite derived from L-carnitine and phosphatidylcholine, and related metabolites (ie, choline, betaine, carnitine, and butyrobetaine) with risk of death among older adults in the general population. Objective: To investigate the associations of serial measures of plasma TMAO and related metabolites with risk of total and cause-specific death (ie, deaths from cardiovascular diseases [CVDs] and non-CVDs) among older adults in the US. Design, Setting, and Participants: This prospective cohort study involved 5333 participants from the Cardiovascular Health Study-a community-based longitudinal cohort of adults aged 65 years or older-who were followed up from June 1, 1989, to December 31, 2015. Participants were from 4 communities in the US (Forsyth County, North Carolina; Sacramento County, California; Washington County, Maryland; and Allegheny County, Pennsylvania). Data were analyzed from March 17 to June 23, 2021. Exposures: Plasma TMAO, choline, betaine, carnitine, and butyrobetaine levels were measured using stored samples from baseline (June 1, 1989, to May 31, 1990, or November 1, 1992, to June 31, 1993) and follow-up examination (June 1, 1996, to May 31, 1997). Measurements were performed through stable-isotope dilution liquid chromatography with tandem mass spectrometry using high-performance liquid chromatography with online electrospray ionization tandem mass spectrometry. Main Outcomes and Measures: Deaths (total and cause specific) were adjudicated by a centralized Cardiovascular Health Study events committee based on information from medical records, laboratory and diagnostic reports, death certificates, and/or interviews with next of kin. The associations of each metabolite with mortality were assessed using Cox proportional hazards regression models. Results: Among 5333 participants in the analytic sample, the mean (SD) age was 73 (6) years; 2149 participants (40.3%) were male, 3184 (59.7%) were female, 848 (15.9%) were African American, 4450 (83.4%) were White, and 35 (0.01%) were of other races (12 were American Indian or Alaska Native, 4 were Asian or Pacific Islander, and 19 were of other races or ethnicities). During a median follow-up of 13.2 years (range, 0-26.9 years), 4791 deaths occurred. After adjustment for potential confounders, the hazard ratios for death from any cause (ie, total mortality) comparing extreme quintiles (fifth vs first) of plasma concentrations were 1.30 (95% CI, 1.17-1.44) for TMAO, 1.19 (95% CI, 1.08-1.32) for choline, 1.26 (95% CI, 1.15-1.40) for carnitine, and 1.26 (95% CI, 1.13-1.40) for butyrobetaine. Plasma betaine was not associated with risk of death. The extent of risk estimates was similar for CVD and non-CVD mortality. Conclusions and Relevance: In this cohort study, plasma concentrations of TMAO and related metabolites were positively associated with risk of death. These findings suggest that circulating TMAO is an important novel risk factor associated with death among older adults.


Assuntos
Betaína , Doenças Cardiovasculares , Idoso , Doenças Cardiovasculares/epidemiologia , Carnitina , Colina , Estudos de Coortes , Feminino , Humanos , Masculino , Metilaminas , Estudos Prospectivos
3.
J Chem Phys ; 156(19): 194506, 2022 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-35597634

RESUMO

Glyceline, a green solvent considered for various electrochemical applications, represents a multi-component glass former. Viewed from this perspective, the choline cation and the hydrogen bond donor glycerol, the two major constituents forming this deep eutectic solvent, were studied using nuclear magnetic resonance in a selective manner by means of suitably deuteron-labeled isotopologues. Carried out from far above to far below the glass transition temperature, measurements and analyses of the spin-lattice and spin-spin relaxation times reveal that the reorientational dynamics of the components, i.e., of glycerol as well as of chain deuterated choline chloride are slightly different. Possible implications of this finding regarding the hydrogen-bonding pattern in glyceline are discussed. Furthermore, the deuterated methyl groups in choline chloride are exploited as sensitive probes of glyceline's supercooled and glassy states. Apart from spin relaxometry, a detailed line shape analysis of the CD3 spectra yields valuable insights into the broad intermolecular and intramolecular energy barrier distributions present in this binary mixture.


Assuntos
Colina , Glicerol , Colina/química , Deutério , Glicerol/química , Espectroscopia de Ressonância Magnética , Solventes/química
4.
Clin Nucl Med ; 47(6): e457-e465, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35507438

RESUMO

ABSTRACT: Gliomas are characterized by an inherent diffuse and irregular morphology that prevents defining a boundary between tumor and healthy tissue, both in imaging assessment and surgical field. The effective identification of the extent of the disease in diffuse and multiple gliomas is crucial for their management but doing so by radiological means can be challenging. We present a broad spectrum of diffuse and multiple gliomas using 18F-fluorocholine PET/CT, demonstrating the potential of metabolic imaging in the evaluation of these gliomas, with implications in patient clinical management and outcome.


Assuntos
Glioma , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Colina/análogos & derivados , Glioma/diagnóstico por imagem , Glioma/patologia , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Compostos Radiofarmacêuticos
5.
Acta Crystallogr D Struct Biol ; 78(Pt 5): 669-682, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35503214

RESUMO

Choline-O-sulfatase (COSe; EC 3.1.6.6) is a member of the alkaline phosphatase (AP) superfamily, and its natural function is to hydrolyze choline-O-sulfate into choline and sulfate. Despite its natural function, the major interest in this enzyme resides in the landmark catalytic/substrate promiscuity of sulfatases, which has led to attention in the biotechnological field due to their potential in protein engineering. In this work, an in-depth structural analysis of wild-type Sinorhizobium (Ensifer) meliloti COSe (SmeCOSe) and its C54S active-site mutant is reported. The binding mode of this AP superfamily member to both products of the reaction (sulfate and choline) and to a substrate-like compound are shown for the first time. The structures further confirm the importance of the C-terminal extension of the enzyme in becoming part of the active site and participating in enzyme activity through dynamic intra-subunit and inter-subunit hydrogen bonds (Asn146A-Asp500B-Asn498B). These residues act as the `gatekeeper' responsible for the open/closed conformations of the enzyme, in addition to assisting in ligand binding through the rearrangement of Leu499 (with a movement of approximately 5 Å). Trp129 and His145 clamp the quaternary ammonium moiety of choline and also connect the catalytic cleft to the C-terminus of an adjacent protomer. The structural information reported here contrasts with the proposed role of conformational dynamics in promoting the enzymatic catalytic proficiency of an enzyme.


Assuntos
Sinorhizobium meliloti , Sulfatases , Fosfatase Alcalina/química , Fosfatase Alcalina/metabolismo , Sítios de Ligação , Colina , Ligantes , Especificidade por Substrato , Sulfatases/química , Sulfatases/metabolismo , Sulfatos
7.
Clin Nucl Med ; 47(6): 480-487, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35426853

RESUMO

OBJECTIVE: The aim of this study was to assess the prognostic performance of postoperative 18F-fluorocholine PET/CT in patients with high-grade glioma (HGG). METHODS: Patients with HGG who underwent preoperative and postoperative 18F-fluorocholine PET/CT were prospectively enrolled in the study. Postoperative MRI was classified as complete versus incomplete resection. Postoperative 18F-fluorocholine PET/CT was classified as negative (complete) or positive for metabolic residual tumor (incomplete resection) using a 5-point score system. The correlation of positive locations on PET/CT with the sites of subsequent tumor recurrence was evaluated. The concordance of postoperative imaging techniques (Cohen κ) and their relation with progression-free survival and overall survival were assessed using Kaplan-Meier method and Cox regression analysis. RESULTS: Fifty-one studies, belonging to 47 patients, were assessed. Four patients underwent 2 postoperative 18F-fluorocholine PET/CT scans as they needed a second tumor resection for recurrence. In the follow-up, 42 patients progressed, and 37 died. Concordance between postoperative PET/CT and MRI assessment was poor. Resection grade on MRI did not show any significant association with prognosis. In multivariate analysis, only age and postoperative PET/CT showed significant association with progression-free survival (hazard ratio [HR], 1.03 [1.01-1.06, P = 0.006] and 1.88 [0.96-3.71, P = 0.067], respectively) and overall survival (HR, 1.04 [1.01-1.07, P = 0.004] and 2.63 [1.22-5.68, P = 0.014], respectively). Postoperative positive 18F-fluorocholine PET/CT locations correlated with the sites of subsequent tumor recurrence in 81.82% of cases. CONCLUSION: Postoperative 18F-fluorocholine PET/CT seems superior to postoperative MRI in the outcome prediction of patients with HGG, outperforming it in the identification of the most probable location of tumor recurrence.


Assuntos
Glioma , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Colina/análogos & derivados , Glioma/diagnóstico por imagem , Glioma/metabolismo , Glioma/cirurgia , Humanos , Recidiva Local de Neoplasia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Prognóstico
8.
Int J Mol Sci ; 23(8)2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35457022

RESUMO

The mitochondrial unfolded protein response (UPRmt) is known as a conservative mechanism in response to mitochondrial dysfunction. Thus, based on UPRmt, this study was conducted to determine the mechanism of a high-fat diet (HFD) inducing mitochondrial dysfunction and its role in stimulating hepatic lipid dysregulation. The choline-activated alleviating effect was also evaluated. In vivo, yellow catfish were fed three diets (control, HFD, and HFD + choline diet) for 10 weeks. In vitro, hepatocytes isolated from yellow catfish and the HepG2 cell line were cultured and incubated with fatty acid (FA) for 48 h. (1) HFD-induced mitochondrial dysfunction via SIRT3/mtHSP70-mediated UPRmt. HFD inhibited the subcellular localization of SIRT3 into the mitochondrion, resulting in the up-regulating of mtHSP70 acetylation via lysine residues 493 and 507. The mtHSP70 acetylation promoted the stability of mtHSP70, which then led to the UPRmt and further mitochondrial dysfunction. (2) SIRT3/mtHSP70-mediated UPRmt regulated HFD/FA-induced hepatic lipid dysregulation. SIRT3/mtHSP70-mediated UPRmt reduced FA ß-oxidation via mitochondrial dysfunction and then led to lipid dysregulation. Additionally, the mtHSP70-ACOX1 interaction was confirmed. (3) Choline alleviated HFD-induced UPRmt via up-regulating the localization of SIRT3 into the mitochondrion, which in turn led to the subsequent ameliorating effect on HFD-induced hepatic lipid dysregulation. Through SIRT3-mediated mtHSP70 deacetylation, dietary choline alleviates HFD-induced hepatic lipid dysregulation via UPRmt. This provides the first proof of acetylation regulating UPRmt and the crosstalk between UPRmt and FA ß-oxidation.


Assuntos
Sirtuína 3 , Colina/metabolismo , Colina/farmacologia , Dieta Hiperlipídica/efeitos adversos , Ácidos Graxos/metabolismo , Fígado/metabolismo , Sirtuína 3/genética , Sirtuína 3/metabolismo
9.
J Agric Food Chem ; 70(16): 5228-5236, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35411770

RESUMO

Choline is an important factor for regulating human health and is widely present in various foods. In this work, a sensor strategy based on a choline oxidase-integrated copper(II) metal-organic framework with peroxidase-like activity is constructed for one-step cascade detection of choline. The one-step cascade strategy can avoid intermediate product transferring in general multi-step reactions, and the multi-enzyme activities can be well exerted under one condition, thus exhibiting excellent catalytic activity and enhanced stability. In the integrated system, choline is catalyzed by ChOx to produce betaine and H2O2, which eventually got converted to hydroxyl radicals by the peroxidase nanozyme, oxidized the chromogenic substrate ABTS, and produced an observable absorption peak at 420 nm. A new choline detection method was thus established and showed a satisfactory linear relationship at 6-300 µM, which has been used for the choline analysis in milk.


Assuntos
Técnicas Biossensoriais , Estruturas Metalorgânicas , Oxirredutases do Álcool , Técnicas Biossensoriais/métodos , Colina , Colorimetria/métodos , Cobre , Humanos , Peróxido de Hidrogênio , Peroxidases
10.
Artigo em Russo | MEDLINE | ID: mdl-35394724

RESUMO

OBJECTIVE: Analysis of the role of blood pressure (BP) variability in the formation of neuroplasticity in patients with type 2 diabetes mellitus (DM). MATERIAL AND METHODS: 100 patients with type 2 DM were examined, which were divided into groups depending on the presence of cognitive impairment (CI), the control group consisted of 25 people. All examined patients underwent a clinical examination, a standard set of biochemical blood tests, plasma osteopontin levels, 24-hour blood pressure monitoring (ABPM) for 24-26 h MRI of the brain (dynamic contrast and arterial spin marks, proton spectroscopy, tractography). RESULTS: Patients with type 2 diabetes and CI had higher body mass index, blood levels of glycated hemoglobin, glucose, alanine aminotransferase, low-density lipoprotein, triglycerides, total cholesterol, osteopontin, and lower levels of high-density lipoprotein (p≤0.05). The level of osteopontin was higher in patients with overweight, hyperglycemia, dyslipidemia, and in patients with CI in patients with BP variability. When assessing 24-hour blood pressure monitoring (ABPM), a significant difference was found in all standard indicators, while patients with type 2 diabetes were referred to as «non-dipper¼, in the presence of CI they noted significantly higher values of the index of time and area of stay in the suprathreshold state. BP and variability in SBP and DBP at night, as well as the risk of occult hypertension. A decrease in cerebral blood flow was revealed according to the data of contrast and non-contrast assessment of perfusion in cortical (especially in the frontal lobe) and subcortical (mainly in the putamen) structures, associated with changes in ABPM parameters. Mean SBP and DBP day and night, as well as the index of BP variability, also affect the integrity of the corticospinal, uncinate, lower longitudinal tracts, and arcuate fasciculus. The same parameters change the metabolism of the hippocampus in terms of choline (Cho), creatine (Cr), creatine phosphate (Cr2), as well as the ratio of N-acetylaspartate (NAA)/Cho, NAA/Cr, Cho/Cr. CONCLUSION: In patients with type 2 diabetes, BP variability contributes to the formation of CI through a pro-inflammatory mechanism (osteopontin), leading to impaired brain vascularization in general, white matter structure, and hippocampal metabolism.


Assuntos
Diabetes Mellitus Tipo 2 , Hipertensão , Pressão Sanguínea , Monitorização Ambulatorial da Pressão Arterial , Colina , Creatina/metabolismo , Diabetes Mellitus Tipo 2/complicações , Humanos , Hipertensão/diagnóstico , Plasticidade Neuronal , Osteopontina
11.
Food Chem ; 384: 132498, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35413771

RESUMO

A series of new deep eutectic solvents based on choline levulinate and various hydrogen bond donors were prepared and characterized by1H NMR, FT-IR, TG, and DSC. In particular, their physicochemical properties (density, viscosity, conductivity, and thermal stability) were determined and their usability as an enhancing additive to the enzymatic reaction mixture, for the enzyme was checked. It has been shown, that prepared DES, exhibits low viscosity (at 40 °C within the range 0.1-0.8 Pa·s), high thermal stability (in almost all cases above 150 °C), and density within the range 1.1-1.17 g cm-3. Also, it has been shown, that obtained mixtures can stabilize the enzymes, and positively influence on its activity. The addition of up to 15% (v/v) of DES mixture composed of choline levulinate: ethylene glycol, enhanced more than threefold lactose hydrolysis yield by ß-galactosidase. The present study shows the relevance of the newly designed DES series for improving enzymes properties with the potential to apply in the effective conversion of food processing origin substrates.


Assuntos
Lactose , Aceleração , Colina/química , Hidrólise , Solventes/química , Espectroscopia de Infravermelho com Transformada de Fourier , beta-Galactosidase
12.
Cardiol Clin ; 40(2): 161-169, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35465890

RESUMO

A novel pathophysiological model of interest is the association between heart failure (HF) and the gastrointestinal system, the 'gut hypothesis'. The choline and carnitine metabolic by-product, Trimethylamine N-oxide (TMAO) is one of the more prominent molecules associated with the link between HF and the gut. Indeed, TMAO levels are increased in HF populations and higher TMAO levels are associated with poor prognosis, whereas low TMAO levels either at baseline/follow up confer better prognosis. Considering that TMAO levels seem not to be affected by guideline-HF treatment, this model could represent a novel and independent therapeutic target for HF.


Assuntos
Microbioma Gastrointestinal , Insuficiência Cardíaca , Colina/metabolismo , Colina/uso terapêutico , Microbioma Gastrointestinal/fisiologia , Humanos , Metilaminas/metabolismo , Metilaminas/uso terapêutico
13.
J Colloid Interface Sci ; 620: 293-312, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35429708

RESUMO

The development of green corrosion inhibitors is a challenging task as it has to comply with strict environmental regulations. Ionic liquids (ILs) have recently been proposed as promising corrosion inhibitors. The present paper reports on two ILs designed to act as green and efficient high-temperature corrosion inhibitors. The prepared ILs, namely, choline formate (ChF) and choline acetate (ChA), are composed of biologically active ions. To elucidate their structure and corrosion inhibition effect on mild steel in 5% HCl the ILs were subjected to characterization tests like proton nuclear magnetic resonance (1H NMR), carbon nuclear magnetic resonance (13C NMR) and Fourier Transform infra-red (FT-IR) spectroscopy and corrosion tests like weight loss measurements, potentiodynamic polarization measurements (PDP), and electrochemical impedance spectroscopy (EIS). The effectiveness of the inhibition (%IE) increased with increasing concentrations and temperature up to 50 °C. ChF and ChA exhibited the highest inhibition efficacies of 96.9% and 99.5%, respectively at a temperature of 50 °C and concentration of 2 × 10-3 M. Above 50 °C their inhibition performance diminished, displaying an efficacy of 77.6% for ChF and 79.3% for ChA at 80 °C. The results of polarization measurements suggested mixed type behavior of inhibitors, and adsorption followed Langmuir adsorption isotherm. Furthermore, surface studies like scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS) revealed protecting capability of the investigated inhibitors. FT-IR, and Raman spectroscopic studies revealed the adsorption of ILs on the Fe surface, and an ultra-violet visible (UV-vis.) spectroscopy study confirms the formation of Fe2+- ILs complex. X-ray Photoelectron Spectroscopy (XPS) was conducted to study the formation of corrosion products and protective film over the mild steel surface. Density functional theory (DFT) calculations and molecular dynamics (MD) simulations were also done to understand the inhibition mechanism of ILs.


Assuntos
Líquidos Iônicos , Aço , Colina , Corrosão , Líquidos Iônicos/química , Espectroscopia de Infravermelho com Transformada de Fourier , Aço/química
14.
Tomography ; 8(2): 1090-1096, 2022 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-35448723

RESUMO

We aimed to retrospectively analyze consecutive prostate cancer patients diagnosed with biochemical or clinical recurrence after local treatment with curative intent, with no evidence of distant metastases, who underwent positron emission tomography/computed tomography (PET/CT) with choline followed by salvage lymph node dissection (SLND) in three academic centers between 2013 and 2020. A total of 27 men were included in the analyses. Sensitivity, specificity, positive and negative predictive values, and accuracy of choline-PET/CT in predicting pathology-proven lymph node involvement were 75%, 43%, 79%, 38% and 67% on per-patient and 70%, 86%, 80%, 78%, and 79% on per-site analyses, respectively, with the differences in specificity and NPV between per-patient and per-site analyses being statistically significant (p = 0.03 and 0.04, respectively). The study provides further insight into the role of preoperative choline-PET/CT in patients undergoing SLND for recurrent PC.


Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata , Colina , Humanos , Excisão de Linfonodo/métodos , Masculino , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Estudos Retrospectivos
15.
Contrast Media Mol Imaging ; 2022: 5885860, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35360264

RESUMO

A total of 35 patients with aphasia after cerebral infarct were included. Among them, 15 conjunctures were sensory (Wernicke's) aphasia and 20 cases were motor (Broca) aphasia. Perfusion Weighted Imaging (PWI) and Magnetic Resonance Spectroscopy (MRS) were performed on the attached hard area to measure the local cerebral blood flow (rCBF) and sectional cerebral blood compass (rCBV), mean conveyance tense (MTT), point delay (TTP), and N-acetylaspartate (NAA), choline (Cho), creatine (Cr)), and lactic acidic (lactate, Lac) and generally a relative analysis. Results. Among the patients with contaminative aphasia, rCBF was way diminished in the contralateral mirror extent. MTT and TTP were significantly longer than the contralateral mirror range, NAA and Cho were sullenness than the contralateral side, and the Lac peak appeared. The distinction was statistically taken (P < 0.05). Compared with the contralateral mirror circumference, motor aphasia was significantly reduced in rCBF and rCBV, and MTT and TTP were way prolonged. NAA and Cho were reduced compared with the contralateral side, and the Lac peak appeared. The dispute was statistically momentous (P < 0.05). Conclusion. After cerebral infarction, the language cosine extent of patients with aphasia bestows a rank of hypoperfusion and light metabolism, suggesting that it may be the pathogeny of aphasia.


Assuntos
Afasia , Creatina , Afasia/diagnóstico por imagem , Afasia/etiologia , Colina , Creatina/metabolismo , Humanos , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética/métodos
16.
Chem Biol Interact ; 360: 109956, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35452634

RESUMO

In this work, new sulfonylhydrazone compounds with alkyl derivatives (SH1- SH4 series) were synthesized via a green chemistry method, and their inhibition effects on acetylcholinesterase and butyrylcholinesterase (AChE, BChE) were determined in vitro. This work was designed in two stages; in the first stage, using compounds that contain both sulfonamide and hydrazine groups which have important pharmacological properties, a series of sulfonyl hydrazone with alkyl derivatives (SH1- SH4) were synthesized with a method that is less time-consuming and more environmentalist that was by using different substitute groups containing aldehyde and ketone compounds. The structures of the synthesized compounds were characterized by elemental analyses, 1H NMR, 13C NMR, FT-IR methods. In the second stage, the effects of the synthesized sulfonyl hydrazones with alkyl derivatives on acetylcholinesterase and butyrylcholinesterase enzymes were examined. According to the results, all the synthesized compounds inhibited AChE and BChE enzymes. When the IC50 values were compared, SH2-3 (IC50 = 5.27 ± 0.05 µM) and SH3-3 (IC50 = 12.29 ± 1.47 µM) compounds which are containing the butyl group have the best inhibition effect on the AChE enzyme and BChE enzyme, respectively. In addition, the predictive properties of all compounds in terms of drug similarity were scanned using five Lipinski rules and ADME estimations. In silico ADME studies play an important role in improving and predicting drug compounds. In the ADME study; The absorption, distribution, metabolism, elimination, and properties of the molecules given below were theoretically calculated. Also, to evaluate the binding interactions between the sulfonylhydrazone compounds and enzymes, molecular docking studies were performed and the compounds with the best inhibition effect SH2-3 (for AChE enzyme) and SH3-3 (for BChE enzyme) were tested. Both in vitro and silico the results showed that two compounds could act as potent inhibitors of AChE, BChE.


Assuntos
Doença de Alzheimer , Butirilcolinesterase , Acetilcolinesterase/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Butirilcolinesterase/metabolismo , Colina , Inibidores da Colinesterase/química , Esterases/metabolismo , Humanos , Hidrazonas/química , Hidrazonas/farmacologia , Simulação de Acoplamento Molecular , Espectroscopia de Infravermelho com Transformada de Fourier , Relação Estrutura-Atividade
17.
Nutr Res ; 101: 23-30, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35364359

RESUMO

Postmenopausal women are at high risk of hepatic steatosis, which may be associated one-carbon metabolism (OCM) abnormalities. We hypothesized that lower folate, choline, betaine, and glutathione (GSH) concentrations but higher total homocysteine and trimethylamine N-oxide concentrations are associated with fatty liver (FL) in postmenopausal women. We aimed to identify relationships between OCM and nonalcoholic fatty liver disease biomarkers in postmenopausal women. A total of 131 postmenopausal women participated in this study and were stratified by the incidence of FL based on the hepatic steatosis index (HSI). Food intake was evaluated using dietary records. Aspartate aminotransferase and alanine aminotransferase concentrations in serum were measured using the colorimetric method. Total homocysteine and GSH concentrations in plasma were measured using high-performance liquid chromatography. Folate and phosphatidylcholine (PC) concentrations were determined in red blood cells using an enzyme-linked immunosorbent assay. Other OCM biomarkers concentrations were measured using the isotope dilution analysis. Women with FL (HSI > 36) had lower GSH, choline, and betaine concentrations than women without FL (HSI < 36). Higher HSI level was negatively correlated with betaine and PC and positively correlated with plasma choline/betaine ratio. Lower GSH and higher carnitine concentrations in the blood are associated with an increased risk of FL. MTHFR (rs180130) T-allele carriers had lower levels of GSH than the CC homozygotes. Postmenopausal women with FL have lower GSH, choline, and betaine concentrations, which may play a role in fat accumulation in the liver. It seems important to consider the dietary intakes of these nutrients in postmenopausal women.


Assuntos
Betaína , Fígado Gorduroso , Biomarcadores , Colina , Feminino , Ácido Fólico , Glutationa , Homocisteína , Humanos , Pós-Menopausa
18.
Nutrients ; 14(8)2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35458214

RESUMO

Dietary trimethylamines, such as choline, metabolized by intestinal microbiota to trimethylamine are absorbed by the gut and oxidized to trimethylamine N-oxide (TMAO). The objective of this study was to determine the effect of choline supplementation on atherosclerosis progression in Apoe-/- mice expressing human cholesterol ester transfer protein (hCETP) using the same diets as in previously reported studies. Mice expressing hCETP, after transfection with AAV2/8-hCETP, were fed an 18% protein diet with either 0.09% (standard chow), 0.5% or 1% choline for 16 weeks. Control mice not transfected with hCETP were fed 1% choline. Dietary choline supplementation increased plasma TMAO levels at 8 and 16 weeks. When atherosclerotic lesions were measured in the thoracic aorta and aortic root, there were no differences between any of the treatment groups in the amount of plaque development at either site. Throughout the study, no significant changes in plasma lipids or major classes of lipoproteins were observed in hCETP-expressing mice. Plasma-oxidized low density lipoprotein, myeloperoxidase and high density lipoprotein inflammatory index were measured at 16 weeks, with no significant changes in any of these inflammatory markers between the four treatment groups. Despite increasing plasma TMAO levels, dietary choline supplementation in Apoe-/- mice expressing hCETP did not promote atherosclerosis.


Assuntos
Aterosclerose , Colina , Metilaminas , Animais , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Aterosclerose/genética , Aterosclerose/prevenção & controle , Proteínas de Transferência de Ésteres de Colesterol/genética , Colina/metabolismo , Suplementos Nutricionais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
19.
Metabolomics ; 18(5): 28, 2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35486220

RESUMO

INTRODUCTION: Closed head injury (CHI) causes neurological disability along with systemic alterations that can activate neuro-endocrine response through hypothalamic-pituitary-adrenal (HPA) axis activation. A dysregulated HPA axis function can lead to relocation of energy substrates and alteration in metabolic pathways and inflammation at the systemic level. OBJECTIVES: Assessment of time-dependent changes in serum metabolites and inflammation after both mild and moderate CHI. Along with this, serum corticosterone levels and hypothalamic microglial response were observed. METHODS: Rats underwent mild and moderate weight-drop injury and their serum and hypothalamus were assessed at acute, sub-acute and chronic timepoints. Changes in serum metabolomics were determined using high resolution NMR spectroscopy. Serum inflammatory cytokine, corticosterone levels and hypothalamic microglia were assessed at all timepoints. RESULTS: Metabolites including lactate, choline and branched chain amino acids were found as the classifiers that helped distinguish between control and injured rats during acute, sub-acute and chronic timepoints. While, increased αglucose: ßglucose and TMAO: choline ratios after acute and sub-acute timepoints of mild injury differentiated from moderate injured rats. The injured rats also showed distinct inflammatory profile where IL-1ß and TNF-α levels were upregulated in moderate injured rats while IL-10 levels were downregulated in mild injured rats. Furthermore, injury specific alterations in serum metabolic and immunologic profile were found to be associated with hyperactive HPA axis, with consistent increase in serum corticosterone concentration post injury. The hypothalamic microglia showed a characteristic activated de-ramified cellular morphology in both mild and moderate injured rats. CONCLUSION: The study suggests that HPA axis hyperactivity along with hypothalamic microglial activation led to temporal changes in the systemic metabolism and inflammation. These time dependent changes in the metabolite profile of rats can further strengthen the knowledge of diagnostic markers and help distinguish injury related outcomes after TBI.


Assuntos
Traumatismos Cranianos Fechados , Sistema Hipófise-Suprarrenal , Animais , Colina/metabolismo , Corticosterona/metabolismo , Traumatismos Cranianos Fechados/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Inflamação/metabolismo , Metabolômica , Sistema Hipófise-Suprarrenal/metabolismo , Ratos
20.
Carbohydr Polym ; 288: 119353, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35450624

RESUMO

This work demonstrates that acetylated maize starches (AMS) with varied degree of substitution (DS, 0.26-2.63) was synthesized in ionic liquids (ILs) (imidazolium chloride, imidazolium carboxylate and choline carboxylate) at 85 °C without catalyst. The DS of AMS and reaction efficiency increased with decreasing alkyl chain length of cations or anions, while decreased as the choline cation replaced the imidazolium cation and the chloride anion replaced the acetate anion. The AMS synthesized in imidazolium-based ILs exhibited much higher hydrophobicity and thermal stability than the native starch. Rheological properties of ILs and ATR-FTIR analysis of acetic anhydride/ILs mixtures indicated that a shorter alkyl side chain or the combination of an imidazolium cation and an acetate anion gave ILs lower viscosities and weaker interactions between acetic anhydride molecules, which favored the acetylation of starch. These findings provide insights into the design of green processes to modify starch and the application of acetylated starch.


Assuntos
Anidridos Acéticos/síntese química , Líquidos Iônicos , Ânions , Ácidos Carboxílicos/química , Cátions , Colina/química , Líquidos Iônicos/química , Amido , Zea mays
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