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1.
Nutrients ; 16(5)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38474806

RESUMO

Pregnancy is an extremely stressful period in a pregnant woman's life. Currently, women's awareness of the proper course of pregnancy and its possible complications is constantly growing. Therefore, a significant percentage of women increasingly reach for various dietary supplements during gestation. Some of the most popular substances included in multi-ingredient supplements are folic acid and choline. Those substances are associated with positive effects on fetal intrauterine development and fewer possible pregnancy-associated complications. Recently, more and more attention has been paid to the impacts of specific environmental factors, such as diet, stress, physical activity, etc., on epigenetic modifications, understood as changes occurring in gene expression without the direct alteration of DNA sequences. Substances such as folic acid and choline may participate in epigenetic modifications by acting via a one-carbon cycle, leading to the methyl-group donor formation. Those nutrients may indirectly impact genome phenotype by influencing the process of DNA methylation. This review article presents the current state of knowledge on the use of folic acid and choline supplementation during pregnancy, taking into account their impacts on the maternal-fetal unit and possible pregnancy outcomes, and determining possible mechanisms of action, with particular emphasis on their possible impacts on epigenetic modifications.


Assuntos
Metilação de DNA , Suplementos Nutricionais , Gravidez , Feminino , Humanos , Ácido Fólico/metabolismo , Epigênese Genética , Colina
2.
Sci Rep ; 14(1): 5420, 2024 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443435

RESUMO

The microalgae Haematococcus pluvialis are the main source of the natural antioxidant astaxanthin. However, the effective extraction of astaxanthin from these microalgae remains a significant challenge due to the rigid, non-hydrolyzable cell walls. Energy savings and high-efficiency cell disruption are essential steps in the recovery of the antioxidant astaxanthin from the cysts of H. pluvialis. In the present study, H. pluvialis microalgae were first cultured in Bold's Basal medium under certain conditions to reach the maximum biomass concentration, and then light shock was applied for astaxanthin accumulation. The cells were initially green and oval, with two flagella. As the induction time increases, the motile cells lose their flagellum and become red cysts with thick cell walls. Pre-treatment of aqueous two-phase systems based on deep eutectic solvents was used to decompose the cell wall. These systems included dipotassium hydrogen phosphate salt, water, and two types of deep eutectic solvents (choline chloride-urea and choline chloride-glucose). The results of pre-treatment of Haematococcus cells by the studied systems showed that intact, healthy cysts were significantly ruptured, disrupted, and facilitated the release of cytoplasmic components, thus facilitating the subsequent separation of astaxanthin by liquid-liquid extraction. The system containing the deep eutectic solvent of choline chloride-urea was the most effective system for cell wall degradation, which resulted in the highest ability to extract astaxanthin. More than 99% of astaxanthin was extracted from Haematococcus under mild conditions (35% deep eutectic solvent, 30% dipotassium hydrogen phosphate at 50 °C, pH = 7.5, followed by liquid-liquid extraction at 25 °C). The present study shows that the pre-treatment of two-phase systems based on deep eutectic solvent and, thus, liquid-liquid extraction is an efficient and environmentally friendly process to improve astaxanthin from the microalgae H. pluvialis.


Assuntos
Charadriiformes , Clorofíceas , Cistos , Microalgas , Fosfatos , Compostos de Potássio , Animais , Solventes Eutéticos Profundos , Antioxidantes , Biomassa , Água , Solventes , Colina , Ureia , Xantofilas
3.
Epigenetics ; 19(1): 2318516, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38484284

RESUMO

Epigenetic modifications, including DNA methylation, are proposed mechanisms explaining the impact of parental exposures to foetal development and lifelong health. Micronutrients including folate, choline, and vitamin B12 provide methyl groups for the one-carbon metabolism and subsequent DNA methylation processes. Placental DNA methylation changes in response to one-carbon moieties hold potential targets to improve obstetrical care. We conducted a systematic review on the associations between one-carbon metabolism and human placental DNA methylation. We included 22 studies. Findings from clinical studies with minimal ErasmusAGE quality score 5/10 (n = 15) and in vitro studies (n = 3) are summarized for different one-carbon moieties. Next, results are discussed per study approach: (1) global DNA methylation (n = 9), (2) genome-wide analyses (n = 4), and (3) gene specific (n = 14). Generally, one-carbon moieties were not associated with global methylation, although conflicting outcomes were reported specifically for choline. Using genome-wide approaches, few differentially methylated sites associated with S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), or dietary patterns. Most studies taking a gene-specific approach indicated site-specific relationships depending on studied moiety and genomic region, specifically in genes involved in growth and development including LEP, NR3C1, CRH, and PlGF; however, overlap between studies was low. Therefore, we recommend to further investigate the impact of an optimized one-carbon metabolism on DNA methylation and lifelong health.


Assuntos
Metilação de DNA , Placenta , Feminino , Humanos , Gravidez , Placenta/metabolismo , Estudo de Associação Genômica Ampla , Ácido Fólico , S-Adenosilmetionina/metabolismo , Colina/metabolismo , Carbono/metabolismo
4.
Waste Manag ; 178: 351-361, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38430749

RESUMO

The traditional hydrometallurgy technology has been widely used to recover precious metals from electronic waste. However, such aqueous recycling systems often employ toxic/harsh chemicals, which may cause serious environmental problems. Herein, an efficient and environment-friendly method using a deep eutectic solvent (DES) mixed system of choline chloride-ethylene glycol-CuCl2·2H2O is developed for gold (Au) recovery from flexible printed circuit boards (FPCBs). The Au leaching and precipitation efficiency can reach approximately 100 % and 95.3 %, respectively, under optimized conditions. Kinetic results show that the Au leaching process follows a nucleation model, which is controlled by chemical surface reactions with an apparent activation energy of 80.29 kJ/mol. The present recycling system has a much higher selectivity for Au than for other base metals; the two-step recovery rate of Au can reach over 95 %, whereas those of copper and nickel are < 2 %. Hydrogen nuclear magnetic resonance spectroscopy (HNMR) and density functional theory (DFT) analyses confirm the formation of intermolecular hydrogen bonds in the DES mixed system, which increase the system melting and boiling points and facilitate the Au leaching process. The Au leaching system can be reused for several times, with the leaching efficiency remaining > 97 % after five cycles. Moreover, ethylene glycol (EG) and choline chloride (ChCl) act as aprotic solvents as well as coordinate with metals, decreasing the redox potential to shift the equilibrium to the leaching side. Overall, this research provides a theoretical and a practical basis for the recovery of metals from FPCBs.


Assuntos
Resíduo Eletrônico , Ouro , Ouro/química , Colina , Cobre/química , Reciclagem/métodos , Resíduo Eletrônico/análise , Etilenoglicóis
5.
Biosens Bioelectron ; 253: 116141, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38428072

RESUMO

Rapid and precise detection of hydrogen peroxide (H2O2) holds great significance since it is linked to numerous physiological and inorganic catalytic processes. We herein developed a label-free and washing-free strategy to detect H2O2 by employing a hand-held personal glucose meter (PGM) as a signal readout device. By focusing on the fact that the reduced redox mediator ([Fe(CN)6]4-) itself is responsible for the final PGM signal, we developed a new PGM-based strategy to detect H2O2 by utilizing the target H2O2-mediated oxidation of [Fe(CN)6]4- to [Fe(CN)6]3- in the presence of horseradish peroxidase (HRP) and monitoring the reduced PGM signal in response to the target amount. Based on this straightforward and facile design principle, H2O2 was successfully determined down to 3.63 µM with high specificity against various non-target molecules. We further demonstrated that this strategy could be expanded to identify another model target choline by detecting H2O2 produced through its oxidation promoted by choline oxidase. Moreover, we verified its practical applicability by reliably determining extracellular H2O2 released from the breast cancer cell line, MDA-MB-231. This work could evolve into versatile PGM-based platform technology to identify various non-glucose target molecules by employing their corresponding oxidase enzymes, greatly advancing the portable biosensing technologies.


Assuntos
Técnicas Biossensoriais , Peróxido de Hidrogênio , Catálise , Colina , Glucose
6.
BMC Genomics ; 25(1): 301, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38515015

RESUMO

BACKGROUND: Iron deficiency (ID) during the fetal-neonatal period results in long-term neurodevelopmental impairments associated with pervasive hippocampal gene dysregulation. Prenatal choline supplementation partially normalizes these effects, suggesting an interaction between iron and choline in hippocampal transcriptome regulation. To understand the regulatory mechanisms, we investigated epigenetic marks of genes with altered chromatin accessibility (ATAC-seq) or poised to be repressed (H3K9me3 ChIP-seq) in iron-repleted adult rats having experienced fetal-neonatal ID exposure with or without prenatal choline supplementation. RESULTS: Fetal-neonatal ID was induced by limiting maternal iron intake from gestational day (G) 2 through postnatal day (P) 7. Half of the pregnant dams were given supplemental choline (5.0 g/kg) from G11-18. This resulted in 4 groups at P65 (Iron-sufficient [IS], Formerly Iron-deficient [FID], IS with choline [ISch], and FID with choline [FIDch]). Hippocampi were collected from P65 iron-repleted male offspring and analyzed for chromatin accessibility and H3K9me3 enrichment. 22% and 24% of differentially transcribed genes in FID- and FIDch-groups, respectively, exhibited significant differences in chromatin accessibility, whereas 1.7% and 13% exhibited significant differences in H3K9me3 enrichment. These changes mapped onto gene networks regulating synaptic plasticity, neuroinflammation, and reward circuits. Motif analysis of differentially modified genomic sites revealed significantly stronger choline effects than early-life ID and identified multiple epigenetically modified transcription factor binding sites. CONCLUSIONS: This study reveals genome-wide, stable epigenetic changes and epigenetically modifiable gene networks associated with specific chromatin marks in the hippocampus, and lays a foundation to further elucidate iron-dependent epigenetic mechanisms that underlie the long-term effects of fetal-neonatal ID, choline, and their interactions.


Assuntos
Deficiências de Ferro , Ferro , Gravidez , Feminino , Animais , Ratos , Masculino , Ferro/metabolismo , Cromatina/genética , Cromatina/metabolismo , Animais Recém-Nascidos , Ratos Sprague-Dawley , Epigênese Genética , Colina/farmacologia , Colina/metabolismo , Hipocampo
7.
J Cancer Res Clin Oncol ; 150(3): 142, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38503944

RESUMO

PURPOSE: Trimethylamine N-oxide (TMAO), a gut microbiome-derived metabolite, and its precursors (carnitine, choline, betaine) have not been fully examined in relation to thyroid cancer (TC) risk. The aim of this study was to assess the value of TMAO and its precursors in diagnosis of benign and malignant thyroid nodules. METHODS: In this study, high-performance liquid chromatography-tandem mass spectrometry was utilized to measure the levels of plasma TMAO and its precursors (choline, carnitine, and betaine) in 215 TC patients, 63 benign thyroid nodules (BTN) patients and 148 healthy controls (HC). The distribution of levels of TMAO and its precursors among the three groups were compared by the Kruskal-Wallis test. Receiver operating characteristic curve (ROC) analysis was performed to evaluate the sensitivity, specificity, and the predictive accuracy of single and combined biomarkers. RESULTS: In comparison to HC, TC showed higher levels of TMAO and lower levels of its precursors (carnitine, choline, and betaine) (all P < 0.001). Plasma choline (P < 0.01) and betaine (P < 0.05) were declined in BTN than HC. The levels of carnitine (P < 0.001) and choline (P < 0.05) were significantly higher in BTN than that in TC group. Plasma TMAO showed lower levels in TC with lymph node metastasis (101.5 (73.1-144.5) ng/ml) than those without lymph node metastasis (131 (84.8-201) ng/ml, P < 0.05). Combinations of these four metabolites achieved good performance in the differential diagnosis, with the area under the ROC curve of 0.703, 0.741, 0.793 when discriminating between TC and BTN, BTN and HC, TC and HC, respectively. CONCLUSION: Plasma TMAO, along with its precursors could serve as new biomarkers for the diagnosis of benign and malignant thyroid nodules.


Assuntos
Betaína , Metilaminas , Nódulo da Glândula Tireoide , Humanos , Betaína/metabolismo , Colina/metabolismo , Carnitina/metabolismo , Nódulo da Glândula Tireoide/diagnóstico , Metástase Linfática , Biomarcadores
8.
Ital J Pediatr ; 50(1): 52, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38486257

RESUMO

BACKGROUND: Orthostatic intolerance, which includes vasovagal syncope and postural orthostatic tachycardia syndrome, is common in children and adolescents. Elevated plasma homocysteine levels might participate in the pathogenesis of orthostatic intolerance. This study was designed to analyze the plasma metabolomic profile in orthostatic intolerance children with high levels of plasma homocysteine. METHODS: Plasma samples from 34 orthostatic intolerance children with a plasma homocysteine concentration > 9 µmol/L and 10 healthy children were subjected to ultra-high-pressure liquid chromatography and quadrupole-time-of-flight mass spectrometry analysis. RESULTS: A total of 875 metabolites were identified, 105 of which were significantly differential metabolites. Choline, 1-stearoyl-2-linoleoyl-sn-glycero-3-phosphocholine, 1-(1Z-octadecenyl)-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine, histidine, isocitric acid, and DL-glutamic acid and its downstream metabolites were upregulated, whereas 1-palmitoyl-sn-glycero-3-phosphocholine, 1-stearoyl-sn-glycerol 3-phosphocholine, sphingomyelin (d18:1/18:0), betaine aldehyde, hydroxyproline, and gamma-aminobutyric acid were downregulated in the orthostatic intolerance group compared with the control group. All these metabolites were related to choline and glutamate. Heatmap analysis demonstrated a common metabolic pattern of higher choline, 1-stearoyl-2-linoleoyl-sn-glycero-3-phosphocholine, and DL-glutamic acid, and lower sphingomyelin (d18:1/18:0), 1-stearoyl-sn-glycerol 3-phosphocholine, and 1-palmitoyl-sn-glycero-3-phosphocholine in patients with certain notable metabolic changes (the special group) than in the other patients (the common group). The maximum upright heart rate, the change in heart rate from the supine to the upright position, and the rate of change in heart rate from the supine to the upright position of vasovagal syncope patients were significantly higher in the special group than in the common group (P < 0.05). Choline, 1-stearoyl-2-linoleoyl-sn-glycero-3-phosphocholine, and DL-glutamic acid were positively correlated with the rate of change in heart rate from the supine to the upright position in vasovagal syncope patients (P < 0.05). CONCLUSIONS: The levels of choline-related metabolites and glutamate-related metabolites changed significantly in orthostatic intolerance children with high levels of plasma homocysteine, and these changes were associated with the severity of illness. These results provided new light on the pathogenesis of orthostatic intolerance.


Assuntos
Glicerol/análogos & derivados , Intolerância Ortostática , Fosforilcolina/análogos & derivados , Síncope Vasovagal , Adolescente , Criança , Humanos , Ácido Glutâmico , Glicerilfosforilcolina , Esfingomielinas , Colina , Homocisteína
9.
PLoS One ; 19(3): e0295488, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38502648

RESUMO

This study was carried out to compare the impact of choline supplementation (available from two sources synthetic and natural) on various dosages in broilers. The mode of choline supplementation, via diet and additional sources, synthetic and natural, and the data of performance, carcass quality, blood parameters, and hepatic steatosis were compared. A total of 1050 day-old male Cobb 500 broiler chicks were randomly assigned to 10 treatments, using a completely randomized design model in a factorial scheme, with 6 replicates per treatment and 25 birds per replicate. Choline was supplemented using three sources: synthetic choline chloride 60% (CC), and two sources of natural choline A (NCA), and B (NCB). The Control treatment did not receive any choline supplementation. The diets were supplemented with low, intermediate and high doses of choline sources (400g/t, 800g/t, and 1200g/t of CC; 100g/t, 200g/t, and 300g/t of both NCA and NCB). Data analysis was performed using a factorial model to investigate the effects of choline supplementation (CC, NCA, NCB) and doses on the measured variables. Overall, the results indicated that the the performance of NCA was better than CC & NCB, specifically the dose of 100g/t of NCA outperformed MAR at 100g/t & CC at 400g/t, leading to a significant increase in body weight gain (85.66g & 168.84g respectively), and a noteworthy (9- & 12-point respectively) improvement in feed conversion ratio. Furthermore, NCA contributed to a reduction in steatosis when contrasted with various NCB & CC doses, likely due to the presence of curcumins and catechins in the natural choline source. These findings demonstrated that NCA supplementation yielded superior results compared to CC and NCB across both performance and liver health aspects in broilers aged 1 to 42 days. In conclusion, NCA can be used to replace the CC 60% without compromise on the zootechnical performance in broilers.


Assuntos
Galinhas , Dieta , Animais , Masculino , Dieta/veterinária , Suplementos Nutricionais , Aumento de Peso , Colina/farmacologia , Ração Animal/análise
10.
Cereb Cortex ; 34(3)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38430105

RESUMO

Human brain development is ongoing throughout childhood, with for example, myelination of nerve fibers and refinement of synaptic connections continuing until early adulthood. 1H-Magnetic Resonance Spectroscopy (1H-MRS) can be used to quantify the concentrations of endogenous metabolites (e.g. glutamate and γ -aminobutyric acid (GABA)) in the human brain in vivo and so can provide valuable, tractable insight into the biochemical processes that support postnatal neurodevelopment. This can feasibly provide new insight into and aid the management of neurodevelopmental disorders by providing chemical markers of atypical development. This study aims to characterize the normative developmental trajectory of various brain metabolites, as measured by 1H-MRS from a midline posterior parietal voxel. We find significant non-linear trajectories for GABA+ (GABA plus macromolecules), Glx (glutamate + glutamine), total choline (tCho) and total creatine (tCr) concentrations. Glx and GABA+ concentrations steeply decrease across childhood, with more stable trajectories across early adulthood. tCr and tCho concentrations increase from childhood to early adulthood. Total N-acetyl aspartate (tNAA) and Myo-Inositol (mI) concentrations are relatively stable across development. Trajectories likely reflect fundamental neurodevelopmental processes (including local circuit refinement) which occur from childhood to early adulthood and can be associated with cognitive development; we find GABA+ concentrations significantly positively correlate with recognition memory scores.


Assuntos
Ácido Glutâmico , Glutamina , Criança , Humanos , Adolescente , Adulto Jovem , Glutamina/metabolismo , Espectroscopia de Ressonância Magnética/métodos , Ácido Glutâmico/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Colina/metabolismo , Creatina/metabolismo , Inositol/metabolismo , Ácido gama-Aminobutírico/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismo , Ácido Aspártico/metabolismo
11.
Thromb Res ; 235: 68-74, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38306775

RESUMO

INTRODUCTION: The gut microbiome plays a crucial role in various diseases, and its regulation is a potential treatment option for these conditions. However, the relationship between the gut microbiome and venous thromboembolism (VTE) remains poorly explored. METHODS: In this study, we collected feces and serum samples from 8 VTE patients and 7 healthy controls. The gut microbiota and serum metabolites were analyzed using 16S rRNA gene sequencing and liquid chromatography-mass spectrometry, respectively. Additionally, a combined analysis of microbiota and metabolome was performed. RESULTS: The alpha and beta diversity between the VTE and control groups were significantly different. Patients with VTE exhibited an overgrowth of Blautia, Roseburia, Coprococcus, and Ruminococcus. Moreover, serum metabolomics analysis revealed altered levels of choline and lithocholic acid. Pathway enrichment analysis indicated a significant upregulation of bile secretion pathways. In addition, a positive correlation was observed between the levels of serum choline and lithocholic acid and the abundance of gut flora enriched in the VTE group. CONCLUSION: This study provided novel insights into the disordered gut microbiota and serum metabolome associated with VTE, suggesting potential common pathological mechanisms between VTE and arterial thrombosis. Targeted modulation of the gut microbiome may hold promise as a preventive and therapeutic approach for VTE.


Assuntos
Microbioma Gastrointestinal , Tromboembolia Venosa , Humanos , Microbioma Gastrointestinal/genética , RNA Ribossômico 16S/genética , Metaboloma , Colina , Ácido Litocólico
12.
Clin Nucl Med ; 49(4): e141-e148, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38350065

RESUMO

PURPOSE: The aim of this study was to evaluate the diagnostic potential of 68 Ga-pentixafor PET/CT for in vivo CXCR4 receptors imaging in glioma and its possible role in response assessment to radiochemotherapy (R-CT). METHODS: Nineteen (12 men, 7 women) patients with glioblastoma multiforme (GBM) underwent 68 Ga-pentixafor PET/CT, contrast-enhanced MR, and MR spectroscopy. Patients were divided in to 2 groups, that is, group I was the presurgical (n = 9) group in which the scanning was done before surgery, and PET findings were correlated with CXCR4 receptors' density. The group II was the postsurgical (n = 10) group in which the scanning was done before and after R-CT and used for treatment response evaluation. The quantitative analysis of 68 Ga-pentixafor PET/CT evaluated the mean SUV max , SUV mean , SUV peak , and T/B values. MR spectroscopy data evaluated the ratios of tumor metabolites (choline, NAA, creatine). RESULTS: 68 Ga-Pentixafor uptake was noted in all (n = 19) the patients. In the group I, the mean SUV max , SUV mean , SUV peak , and T/B values were found to be 4.5 ± 1.6, 0.60 ± 0.26, 1.95 ± 0.8, and 6.9 ± 4.6, respectively. A significant correlation ( P < 0.005) was found between SUV mean and choline/NAA ratio. Immunohistochemistry performed in 7/9 showed CXCR4 receptors' positivity (intensity 3 + ; stained cells >50.0%). In the group II, the mean SUV max at baseline was 4.6 ± 2.1 and did not differ (4.4 ± 1.6) significantly from the value noted at post-R-CT follow-up PET/CT imaging. At 6 months' clinical follow-up, 4 patients showed stable disease. SUV max and T/B ratios at follow-up imaging were lower (3.70 ± 0.90, 2.64 ± 1.35) than the corresponding values (4.40 ± 2.8; 2.91 ± 0.93) noted at baseline. Six (6/10) patients showed disease progression, and the mean SUV max , and T/B ratio in these patients were significantly ( P < 0.05) higher than the corresponding values at baseline and also higher than that noted in the stable patients. CONCLUSIONS: 68 Ga-Pentixafor PET/CT can be used for in vivo mapping of CXCR4 receptors in GBM. The technique after validation in a large cohort of patients may have added diagnostic value for the early detection of GBM recurrence and for treatment response evaluation.


Assuntos
Complexos de Coordenação , Radioisótopos de Gálio , Glioblastoma , Glioma , Peptídeos Cíclicos , Masculino , Humanos , Feminino , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Receptores CXCR4 , Glioma/diagnóstico por imagem , Glioma/terapia , Colina
13.
Biophys Chem ; 307: 107192, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38335806

RESUMO

Tuning the self-assembly of collagen has broad applications in the biomedical field owing to their desired biological performance as collagenous materials with tunable functionalities can further determine cellular responses. In this work, an attempt has been made to tune the self-assembly of collagen using ionic liquids, viz., imidazolium chloride (IC) and choline dihydrogen phosphate (CDHP) at its physiological pH, followed by probing assembled systems using various characterization methods. Turbidity measurements of fibrillar networks were performed to ascertain the rate of fibril formation in addition of imidazolium chloride and choline dihydrogen phosphate to collagen at physiological pH. Morphological changes were examined using Scanning Electron Microscope (SEM), binding affinities were measured by Microscale Thermophoresis (MST), in addition to, changes in the shear viscosity, mechanical strength of collagen fibrils when interacted with imidazolium and choline based ILs were carried out using rotational rheometer and Quartz Crystal Microbalance (QCM) measurements. Experimental result depicts that CDHP imparts better crosslinking as well as mechanical strength compare to IC, which is already known for destabilizing the triple helix structure is inhibiting the fibril formation. This self-assembled, ionic-liquid treated collagen-fibrillar system would accelerate various force modulated fibrillar network study, for mimicking the ECM and tissue engineering application.


Assuntos
Colágeno Tipo I , Líquidos Iônicos , Colágeno Tipo I/química , Líquidos Iônicos/química , Eletricidade Estática , Colágeno/química , Colina , Fosfatos
14.
Life Sci ; 341: 122498, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38340980

RESUMO

AIMS: Non-alcoholic fatty liver disease (NAFLD) has become a global epidemic. Excessive fibrogenesis, characterized by activation of hepatic stellate cells (HSCs), is a hallmark event in late stages of NAFLD. HSC activation is metabolically programmed by anaerobic glycolysis. In the present study we investigated the involvement of suppressor of variegation 3-9 homolog 1 (Suv39h1), a lysine methyltransferase, in NAFLD-associated liver fibrosis. METHODS AND MATERIALS: Liver fibrosis was induced by feeding the mice with a methionine-and-choline deficient (MCD) diet for 8 weeks. RESULTS: We report that germline deletion of Suv39h1 attenuated liver fibrosis in mice fed an MCD diet. In addition, HSC conditional deletion of Suv39h1 similarly ameliorated liver fibrosis in the NAFLD mice. Interestingly, co-culturing with hepatocytes exposed to palmitate promoted glycolysis in wild type HSCs but not in Suv39h1 deficient HSCs. Mechanistically, Suv39h1 facilitated the recruitment of hypoxia induced factor (HIF-1α) to stimulate the transcription of hexokinase 2 (HK2) in HSCs thereby enhancing glycolysis. Importantly, a positive correlation between Suv39h1, HK2, and myofibroblast markers was identified in liver specimens from NAFLD patients. SIGNIFICANCE: In conclusion, our data identify a novel pathway that contributes to the liver fibrosis and points to the possibility of targeting Suv39h1 for the intervention of liver fibrosis in NAFLD.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Animais , Humanos , Camundongos , Anaerobiose , Colina/metabolismo , Células Estreladas do Fígado/metabolismo , Fígado/metabolismo , Cirrose Hepática/patologia , Metionina , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/metabolismo
15.
Int J Mol Sci ; 25(4)2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38397122

RESUMO

Metabolic dysfunction-associated steatotic liver disease (MASLD) and its advanced subtype, metabolic dysfunction-associated steatohepatitis (MASH), have emerged as the most common chronic liver disease worldwide, yet there is no targeted pharmacotherapy presently available. This study aimed to investigate the possible in vivo function of STE20-type protein kinase MST4, which was earlier implicated in the regulation of hepatocellular lipotoxic milieu in vitro, in the control of the diet-induced impairment of systemic glucose and insulin homeostasis as well as MASLD susceptibility. Whole-body and liver-specific Mst4 knockout mice were generated by crossbreeding conditional Mst4fl/fl mice with mice expressing Cre recombinase under the Sox2 or Alb promoters, respectively. To replicate the environment in high-risk subjects, Mst4-/- mice and their wild-type littermates were fed a high-fat or a methionine-choline-deficient (MCD) diet. Different in vivo tests were conducted in obese mice to describe the whole-body metabolism. MASLD progression in the liver and lipotoxic damage to adipose tissue, kidney, and skeletal muscle were analyzed by histological and immunofluorescence analysis, biochemical assays, and protein and gene expression profiling. In parallel, intracellular fat storage and oxidative stress were assessed in primary mouse hepatocytes, where MST4 was silenced by small interfering RNA. We found that global MST4 depletion had no effect on body weight or composition, locomotor activity, whole-body glucose tolerance or insulin sensitivity in obese mice. Furthermore, we observed no alterations in lipotoxic injuries to the liver, adipose, kidney, or skeletal muscle tissue in high-fat diet-fed whole-body Mst4-/- vs. wild-type mice. Liver-specific Mst4-/- mice and wild-type littermates displayed a similar severity of MASLD when subjected to an MCD diet, as evidenced by equal levels of steatosis, inflammation, hepatic stellate cell activation, fibrosis, oxidative/ER stress, and apoptosis in the liver. In contrast, the in vitro silencing of MST4 effectively protected primary mouse hepatocytes against ectopic lipid accumulation and oxidative cell injury triggered by exposure to fatty acids. In summary, these results suggest that the genetic ablation of MST4 in mice does not mitigate the initiation or progression of MASLD and has no effect on systemic glucose or insulin homeostasis in the context of nutritional stress. The functional compensation for the genetic loss of MST4 by yet undefined mechanisms may contribute to the apparent discrepancy between in vivo and in vitro phenotypic consequences of MST4 silencing.


Assuntos
Fígado Gorduroso , Doenças Metabólicas , Hepatopatia Gordurosa não Alcoólica , Humanos , Camundongos , Animais , Camundongos Obesos , Hepatócitos/metabolismo , Fígado Gorduroso/metabolismo , Fígado/metabolismo , Glucose/metabolismo , Dieta Hiperlipídica/efeitos adversos , Camundongos Knockout , Colina/metabolismo , Insulina/metabolismo , Doenças Metabólicas/metabolismo , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo
16.
J Proteomics ; 296: 105107, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38325729

RESUMO

To explore the effect of feeding fermented distiller's grains (FDG) diets on spleen and mesenteric lymph nodes (MLN) immune status and metabolomics in finishing cattle, eighteen Guanling crossbred cattle (18 months old, 250.0 ± 25 kg) were randomly divided into 3 groups: a basal diet (Control) group, an FDG-15% group, and an FDG-30% group (containing 0%, 15% and 30% FDG to partially replace the concentrates, respectively). After 75 days, the spleens and MLN were collected for detection of relative spleen weight, immune parameters, and metabolomic analysis. Compared with the Control group, FDG-30% group significantly increased (P<0.05) the relative spleen weight. In addition, the level of IL-17A in the spleen of the FDG-30% group was significantly higher than that of the FDG-15% group. Metabolomic analysis showed that differential metabolites (VIP>1, P<0.05) of spleen and MLN in FDG-15% and FDG-30% groups are mostly lipids and lipid molecules. KEGG analysis illustrated that choline metabolism in cancer, glycerophospholipid metabolism, biosynthesis of unsaturated fatty acids and insulin resistance were metabolic pathways in spleen shared by FDG-15% group vs.Control group and FDG-30% group vs.Control group, and choline metabolism in cancer was a metabolic pathway in MLN shared by FDG-15% group vs.Control group and FDG-30% group vs.Control group. These results suggest that feeding FDG may promote spleen development by regulating choline metabolism in cancer, glycerophospholipid metabolism, biosynthesis of unsaturated fatty acids and insulin resistance. Additionally, it may affect MLN development by regulating choline metabolism in cancer. SIGNIFICANCE: Fermented distiller's grains (FDG) is a high quality alternative to feed because it is rich in beneficial microorganisms and nutrients. The spleen and mesenteric lymph nodes (MLN) are important peripheral immune organs in animals, whose status reflects the health of the animal. However, there are few reports on the effect of feeding FDG diets on spleen and MLN immune status and metabolomics in domestic animals. In this study, we found that feeding FDG may promote spleen development by regulating choline metabolism in cancer, glycerophospholipid metabolism, biosynthesis of unsaturated fatty acids and insulin resistance metabolic pathways, and may affect MLN development by regulating choline metabolism in cancer. This study extends our understanding of the metabolomics of the spleen and MLN in FDG and helps to further understand of the immunomodulatory effects of the FDG diet.


Assuntos
Resistência à Insulina , Neoplasias , Bovinos , Animais , Baço , Fluordesoxiglucose F18 , Ração Animal/análise , Dieta/veterinária , Ácidos Graxos Insaturados , Linfonodos , Glicerofosfolipídeos , Colina
17.
PLoS One ; 19(2): e0297289, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38315685

RESUMO

Alzheimer's disease (AD) is characterized by cognitive and memory impairments and neuropathological abnormalities. AD has no cure, inadequate treatment options, and a limited understanding of possible prevention measures. Previous studies have demonstrated that AD model mice that received a diet high in the essential nutrient choline had reduced amyloidosis, cholinergic deficits, and gliosis, and increased neurogenesis. In this study, we investigated the lifelong effects of perinatal choline supplementation on behavior, cognitive function, and amyloidosis in AppNL-G-F AD model mice. Pregnant and lactating mice were given a diet containing either 1.1 g/kg (control) or 5 g/kg (supplemented) of choline chloride until weaning and subsequently, all offspring received the control diet throughout their life. At 3, 6, 9, and 12 months of age, animals were behaviorally tested in the Open Field Test, Elevated Plus Maze, Barnes Maze, and in a contextual fear conditioning paradigm. Immunohistochemical analysis of Aß42 was also conducted on the brains of these mice. AppNL-G-F mice displayed hippocampal-dependent spatial learning deficits starting at 3-months-old that persisted until 12-months-old. These spatial learning deficits were fully prevented by perinatal choline supplementation at young ages (3 and 6 months) but not in older mice (12 months). AppNL-G-F mice also had impaired fearful learning and memory at 9- and 12-months-old that were diminished by choline supplementation. Perinatal choline supplementation reduced Aß42 deposition in the amygdala, cortex, and hippocampus of AppNL-G-F mice. Together, these results demonstrate that perinatal choline supplementation is capable of preventing cognitive deficits and dampening amyloidosis in AppNL-G-F mice and suggest that ensuring adequate choline consumption during early life may be a valuable method to prevent or reduce AD dementia and neuropathology.


Assuntos
Doença de Alzheimer , Amiloidose , Gravidez , Feminino , Camundongos , Animais , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/prevenção & controle , Doença de Alzheimer/patologia , Camundongos Transgênicos , Lactação , Modelos Animais de Doenças , Encéfalo/metabolismo , Amiloidose/patologia , Colina/farmacologia , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/prevenção & controle , Transtornos da Memória/patologia , Aprendizagem em Labirinto , Suplementos Nutricionais , Peptídeos beta-Amiloides/metabolismo
18.
Sci Rep ; 14(1): 3242, 2024 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-38331924

RESUMO

Concussion is commonly characterized by a cascade of neurometabolic changes following injury. Magnetic Resonance Spectroscopy (MRS) can be used to quantify neurometabolites non-invasively. Longitudinal changes in neurometabolites have rarely been studied in pediatric concussion, and fewer studies consider symptoms. This study examines longitudinal changes of neurometabolites in pediatric concussion and associations between neurometabolites and symptom burden. Participants who presented with concussion or orthopedic injury (OI, comparison group) were recruited. The first timepoint for MRS data collection was at a mean of 12 days post-injury (n = 545). Participants were then randomized to 3 (n = 243) or 6 (n = 215) months for MRS follow-up. Parents completed symptom questionnaires to quantify somatic and cognitive symptoms at multiple timepoints following injury. There were no significant changes in neurometabolites over time in the concussion group and neurometabolite trajectories did not differ between asymptomatic concussion, symptomatic concussion, and OI groups. Cross-sectionally, Choline was significantly lower in those with persistent somatic symptoms compared to OI controls at 3 months post-injury. Lower Choline was also significantly associated with higher somatic symptoms. Although overall neurometabolites do not change over time, choline differences that appear at 3 months and is related to somatic symptoms.


Assuntos
Concussão Encefálica , Sintomas Inexplicáveis , Humanos , Criança , Concussão Encefálica/diagnóstico , Encéfalo/metabolismo , Espectroscopia de Ressonância Magnética/métodos , Colina/metabolismo
19.
Int J Mol Sci ; 25(4)2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38396980

RESUMO

This review summarizes our research on nicotinic acetylcholine receptors in human chromaffin cells. Limited research has been conducted in this field on human tissue, primarily due to the difficulties associated with obtaining human cells. Receptor subtypes were characterized here using molecular biology and electrophysiological patch-clamp techniques. However, the most significant aspect of this study refers to the cross-talk between the two main subtypes identified in these cells, the α7- and α3ß4* subtypes, aiming to avoid their desensitization. The article also reviews other aspects, including the regulation of their expression, function or physical interaction by choline, Ca2+, and tyrosine and serine/threonine phosphatases. Additionally, the influence of sex on their expression is also discussed.


Assuntos
Células Cromafins , Receptores Nicotínicos , Humanos , Receptores Nicotínicos/metabolismo , Colina/metabolismo , Fenômenos Eletrofisiológicos , Células Cromafins/metabolismo
20.
PLoS One ; 19(2): e0298787, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38386679

RESUMO

People living with HIV are at three times greater risk for depressive symptoms. Inflammation is a notable predictor of depression, and people with HIV exhibit chronic inflammation despite antiretroviral therapy. We hypothesised that inflammatory biomarkers may mediate the association between HIV status and depressive symptoms. Participants (N = 60, 53% girls, median [interquartile range (IQR)] age 15.5 [15.0, 16.0] years, 70% living with HIV, of whom 90.5% were virally-suppressed) completed the nine-item Patient Health Questionnaire (PHQ-9). We measured choline and myo-inositol in basal ganglia, midfrontal gray matter, and peritrigonal white matter using magnetic resonance spectroscopy, and 16 inflammatory proteins in blood serum using ELISA and Luminex™ multiplex immunoassays. Using structural equation mediation modelling, we calculated standardised indirect effect estimates with 95% confidence intervals. Median [IQR] total PHQ-9 score was 3 [0, 7]. HIV status was significantly associated with total PHQ-9 score (B = 3.32, p = 0.022). Participants with HIV showed a higher choline-to-creatine ratio in the basal ganglia than those without HIV (ß = 0.86, pFDR = 0.035). In blood serum, participants with HIV showed higher monocyte chemoattractant protein-1 (MCP-1, ß = 0.59, pFDR = 0.040), higher chitinase-3 like-1 (YKL-40, ß = 0.73, pFDR = 0.032), and lower interleukin-1beta (IL-1ß, ß = -0.67, pFDR = 0.047) than those without HIV. There were no significant associations of any biomarkers with total PHQ-9 score. None of the indirect effects were significant, mediating <13.1% of the association. Findings remained consistent when accounting for age, gender, and time between neuroimaging and PHQ-9 administration. Using a robust analytical approach in a community-based sample, we have shown that participants living with HIV reported greater depressive symptoms than those without HIV, but we did not find that neuroimaging and blood biomarkers of inflammation significantly mediated this association. Further studies with participants experiencing severe depression may help to elucidate the links between HIV, inflammation, and depression.


Assuntos
Depressão , Inflamação , Feminino , Humanos , Adolescente , Masculino , Depressão/complicações , Inflamação/complicações , Gânglios da Base , Colina , Interleucina-1beta , Biomarcadores
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