4,4-Diallyl curcumin bis(2,2-hydroxymethyl)propanoate ameliorates nonalcoholic steatohepatitis in methionine-choline-deficient diet and Western diet mouse models.

Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) that causes severe liver damage, fibrosis, and scarring. Despite its potential to progress to cirrhosis or hepatic failure, approved drugs or treatments are currently unavailable. We developed 4,4-diallyl curcumin bis(2,2-hydroxymethyl)propanoate, also known as 35e, which induces upregulation of mitochondrial proteins including carnitine palmitoyltransferase I (CPT-I), carnitine palmitoyltransferase II, heat shock protein 60, and translocase of the outer mitochondrial membrane 20. Among these proteins, the upregulated expression of CPT-I was most prominent. CPT-I plays a crucial role in transporting carnitine across the mitochondrial inner membrane, thereby initiating mitochondrial ß-oxidation of fatty acids. Given recent research showing that CPT-I activation could be a viable pathway for NASH treatment, we hypothesized that 35e could serve as a potential agent for treating NASH. The efficacy of 35e in treating NASH was evaluated in methionine- and choline-deficient (MCD) diet- and Western diet (WD)-induced models that mimic human NASH. In the MCD diet-induced model, both short-term (2 weeks) and long-term (7 weeks) treatment with 35e effectively regulated elevated serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) concentrations and histological inflammation. However, the antisteatotic effect of 35e was obtained only in the short-term treatment group. As a comparative compound in the MCD diet-induced model, curcumin treatment did not produce significant regulatory effects on the liver triglyceride/total cholesterol, serum ALT/AST, or hepatic steatosis. In the WD-induced model, 35e ameliorated hepatic steatosis and hepatic inflammation, while increasing serum AST and hepatic lipid content. A decrease in epididymal adipose tissue weight and serum free fatty acid concentration suggested that 35e may promote lipid metabolism or impede lipid accumulation. Overall, 35e displayed significant antilipid accumulation and antifibrotic effects in the two complementary mice models. The development of new curcumin derivatives with the ability to induce CPT-I upregulation could further underscore their efficacy as anti-NASH agents.

Choline Metabolites Reverse Differentially the Habituation Deficit and Elevated Memory of Tau Null Drosophila.

Impaired neuronal plasticity and cognitive decline are cardinal features of Alzheimer's disease and related Tauopathies. Aberrantly modified Tau protein and neurotransmitter imbalance, predominantly involving acetylcholine, have been linked to these symptoms. In Drosophila, we have shown that dTau loss specifically enhances associative long-term olfactory memory, impairs foot shock habituation, and deregulates proteins involved in the regulation of neurotransmitter levels, particularly acetylcholine. Interestingly, upon choline treatment, the habituation and memory performance of mutants are restored to that of control flies. Based on these surprising results, we decided to use our well-established genetic model to understand how habituation deficits and memory performance correlate with different aspects of choline physiology as an essential component of the neurotransmitter acetylcholine, the lipid phosphatidylcholine, and the osmoregulator betaine. The results revealed that the two observed phenotypes are reversed by different choline metabolites, implying that they are governed by different underlying mechanisms. This work can contribute to a broader knowledge about the physiologic function of Tau, which may be translated into understanding the mechanisms of Tauopathies.

Dietary choline intake and health outcomes in U.S. adults: exploring the impact on cardiovascular disease, cancer prevalence, and all-cause mortality.

BACKGROUND: Choline, an indispensable nutrient, plays a pivotal role in various physiological processes. The available evidence regarding the nexus between dietary choline intake and health outcomes, encompassing cardiovascular disease (CVD), cancer, and all-cause mortality, is limited and inconclusive. This study aimed to comprehensively explore the relationship between dietary choline intake and the aforementioned health outcomes in adults aged > 20 years in the U.S. METHODS: This study utilized data from the National Health and Nutrition Examination Survey between 2011 and 2018. Dietary choline intake was evaluated using two 24-h dietary recall interviews. CVD and cancer status were determined through a combination of standardized medical status questionnaires and self-reported physician diagnoses. Mortality data were gathered from publicly available longitudinal Medicare and mortality records. The study utilized survey-weighted logistic and Cox regression analyses to explore the associations between choline consumption and health outcomes. Restricted cubic spline (RCS) analysis was used for dose‒response estimation and for testing for nonlinear associations. RESULTS: In our study of 14,289 participants (mean age 48.08 years, 47.71% male), compared with those in the lowest quintile (Q1), the adjusted odds ratios (ORs) of CVD risk in the fourth (Q4) and fifth (Q5) quintiles of choline intake were 0.70 (95% CI 0.52, 0.95) and 0.65 (95% CI 0.47, 0.90), respectively (p for trend = 0.017). Each 100 mg increase in choline intake was associated with a 9% reduced risk of CVD. RCS analysis revealed a linear correlation between choline intake and CVD risk. Moderate choline intake (Q3) was associated with a reduced risk of mortality, with an HR of 0.75 (95% CI 0.60-0.94) compared with Q1. RCS analysis demonstrated a significant nonlinear association between choline intake and all-cause mortality (P for nonlinearity = 0.025). The overall cancer prevalence association was nonsignificant, except for colon cancer, where each 100 mg increase in choline intake indicated a 23% reduced risk. CONCLUSION: Elevated choline intake demonstrates an inverse association with CVD and colon cancer, while moderate consumption exhibits a correlated reduction in mortality. Additional comprehensive investigations are warranted to elucidate the broader health implications of choline.

The diagnostic challenge of lack of choline level elevation on 1H-MR spectroscopy in grade II-III gliomas.

The accurate diagnosis of brain tumour is very important in modern neuro-oncology medicine. Magnetic resonance spectroscopy (MRS) is supposed to be a promising tool for detecting cancerous lesions. However, the interpretation of MRS data is complicated by the fact that not all cancerous lesions exhibit elevated choline (Cho) levels. The main goal of our study was to investigate the lack of Cho lesion /Cho ref elevation in the population of grade II-III gliomas. 89 cases of gliomas grade II and III were used for the retrospective analysis - glioma (astrocytoma or oligodendroglioma) grade II (74 out of 89 cases [83%]) and III (15 out of 89 cases [17%]) underwent conventional MRI extended by MRS before treatment. Histopathological diagnosis was obtained either by biopsy or surgical resection. Gliomas were classified to the group of no-choline elevation when the ratio of choline measured within the tumour (Cho lesion ) to choline from NABT (Cho ref ) were equal to or lower than 1. Significant differences were observed between ratios of Cho lesion /Cr lesion calculated for no-choline elevation and glial tumour groups as well as in the NAA lesion /Cr lesion ratio between the no-choline elevation group and glial tumour group. With consistent data concerning choline level elevation and slightly lower NAA value, the Cho lesion /NAA lesion ratio is significantly higher in the WHO II glial tumour group compared to the no-choline elevation cases ( p < 0.000). In the current study the results demonstrated possibility of lack of choline elevation in patients with grade II-III gliomas, so it is important to remember that the lack of elevated choline levels does not exclude neoplastic lesion.

Activities of proteases in deep eutectic solvents and removal of protein from chitin by subtilisin A in betaine/glycerol.

This research intended to remove residual protein from chitin with proteases in deep eutectic solvents (DESs). The activities of some proteases in several DESs, including choline chloride/p-toluenesulfonic acid, betaine/glycerol (Bet/G), choline chloride/malic acid, choline chloride/lactic acid, and choline chloride/urea, which are capable of dissolving chitin, were tested, and only in Bet/G some proteases were found to be active, with subtilisin A, ficin, and bromelain showing higher activity than other proteases. However, the latter two proteases caused degradation of chitin molecules. Further investigation revealed that subtilisin A in Bet/G did not exhibit "pH memory", which is a universal characteristic displayed by enzymes dispersed in organic phases, and the catalytic characteristics of subtilisin A in Bet/G differed significantly from those in aqueous phase. The conditions for protein removal from chitin by subtilisin A in Bet/G were determined: Chitin dissolved in Bet/G with 0.5 % subtilisin A (442.0 U/mg, based on the mass of chitin) was hydrolyzed at 45 °C for 30 min. The residual protein content in chitin decreased from 5.75 % ± 0.10 % to 1.01 % ± 0.12 %, improving protein removal by 57.20 % compared with protein removal obtained by Bet/G alone. The crystallinity and deacetylation degrees of chitin remained unchanged after the treatment.

Profiling and optimized extraction of bioactive polyphenolic compounds from young, red-fleshed apple using eco-friendly deep eutectic solvents.

Red-fleshed apple cultivars with an enhanced content of polyphenolic compounds have attracted increasing interest due to their promising health benefits. Here, we have analysed the polyphenolic content of young, red-fleshed apples (RFA) and optimised extraction conditions of phenolics by utilising natural deep eutectic solvents (NDES). We also compare the antioxidant, neuroprotective and antimicrobial activities of NDES- and methanol-extracted phenolics from young RFA. High-performance liquid chromatography coupled to high-resolution mass spectrometry (HPLC-HRMS) was used for phenolics identification and quantification. Besides young RFA, ripe red-fleshed, young and ripe white-fleshed apples were analysed, revealing that young RFA possess the highest phenolic content (2078.4 ± 4.0 mg gallic acid equivalent/100 g), and that ripe white-fleshed apples contain the least amount of phenolics (545.0 ± 32.0 mg gallic acid equivalent/100 g). The NDES choline chloride-glycerol containing 40 % w/w H2O gave similar yields at 40 °C as methanol. In addition, the polyphenolics profile, and bioactivities of the NDES extract from young RFA were comparable that of methanol extracts. Altogether, our data show that NDES extracts of young RFA are a promising source of bioactive polyphenolics with potential applications in diverse sectors, e.g., for functional food production, smart material engineering and natural therapies.

Plasma trimethylamine N-oxide (TMAO): associations with cognition, neuroimaging, and dementia.

BACKGROUND: The gut-derived metabolite Trimethylamine N-oxide (TMAO) and its precursors - betaine, carnitine, choline, and deoxycarnitine - have been associated with an increased risk of cardiovascular disease, but their relation to cognition, neuroimaging markers, and dementia remains uncertain. METHODS: In the population-based Rotterdam Study, we used multivariable regression models to study the associations between plasma TMAO, its precursors, and cognition in 3,143 participants. Subsequently, we examined their link to structural brain MRI markers in 2,047 participants, with a partial validation in the Leiden Longevity Study (n = 318). Among 2,517 participants, we assessed the risk of incident dementia using multivariable Cox proportional hazard models. Following this, we stratified the longitudinal associations by medication use and sex, after which we conducted a sensitivity analysis for individuals with impaired renal function. RESULTS: Overall, plasma TMAO was not associated with cognition, neuroimaging markers or incident dementia. Instead, higher plasma choline was significantly associated with poor cognition (adjusted mean difference: -0.170 [95% confidence interval (CI) -0.297;-0.043]), brain atrophy and more markers of cerebral small vessel disease, such as white matter hyperintensity volume (0.237 [95% CI: 0.076;0.397]). By contrast, higher carnitine concurred with lower white matter hyperintensity volume (-0.177 [95% CI: -0.343;-0.010]). Only among individuals with impaired renal function, TMAO appeared to increase risk of dementia (hazard ratio (HR): 1.73 [95% CI: 1.16;2.60]). No notable differences were observed in stratified analyses. CONCLUSIONS: Plasma choline, as opposed to TMAO, was found to be associated with cognitive decline, brain atrophy, and markers of cerebral small vessel disease. These findings illustrate the complexity of relationships between TMAO and its precursors, and emphasize the need for concurrent study to elucidate gut-brain mechanisms.

Phosphatidylcholine levels regulate hyphal elongation and differentiation in the filamentous fungus Aspergillus oryzae.

Filamentous fungi are eukaryotic microorganisms that differentiate into diverse cellular forms. Recent research demonstrated that phospholipid homeostasis is crucial for the morphogenesis of filamentous fungi. However, phospholipids involved in the morphological regulation are yet to be systematically analyzed. In this study, we artificially controlled the amount of phosphatidylcholine (PC), a primary membrane lipid in many eukaryotes, in a filamentous fungus Aspergillus oryzae, by deleting the genes involved in PC synthesis or by repressing their expression. Under the condition where only a small amount of PC was synthesized, A. oryzae hardly formed aerial hyphae, the basic structures for asexual development. In contrast, hyphae were formed on the surface or in the interior of agar media (we collectively called substrate hyphae) under the same conditions. Furthermore, we demonstrated that supplying sufficient choline to the media led to the formation of aerial hyphae from the substrate hyphae. We suggested that acyl chains in PC were shorter in the substrate hyphae than in the aerial hyphae by utilizing the strain in which intracellular PC levels were controlled. Our findings suggested that the PC levels regulate hyphal elongation and differentiation processes in A. oryzae and that phospholipid composition varied depending on the hyphal types.

Sustainable combination of ionic liquid and deep eutectic solvent for protecting and preserving of the protein structure: The synergistic interaction of enzymes and eco-friendly hybrid ionic fluids.

Hybrid ionic fluids (HIFs) are one of the emerging and fascinating sustainable solvent media, a novel environment-friendly solvent for biomolecules. The HIFs have been synthesized by combining a deep eutectic solvent (DES), an ionic liquid (IL) having a common ion. The stability and activity of hen's egg white lysozyme (Lyz) in the presence of a recently designed new class of biocompatible solvents, HIFs have been explored by UV-visible, steady-state fluorescence, circular dichroism (CD), Fourier transform infrared spectroscopy (FT-IR) along with dynamic light scattering (DLS) measurements. This work emphasizes the effect of DES synthesized by using 1:2 choline chloride and glycerol [Glyn], ILs (1-butly-3-methylimidazolium chloride [BMIM]Cl and choline acetate [Chn][Ac]) and their corresponding HIFs on the structure and functionality of Lyz. Moving forward, we also studied the secondary structure, thermal stability and enzymatic activity and thermodynamic profile of Lyz at pH = 7 in the presence of varying concentrations (0.1 to 0.5) M of [BMIM]Cl, [Chn][Ac] ILs, [Glyn] DES and [Glyn][BMIM]Cl (hybrid ionic fluid1) as well as [Glyn][Chn][Ac] (hybrid ionic fluid2). Spectroscopic results elucidate that ILs affect the activity and structural stability of Lyz, whereas the stability and activity are increased by DES and are maintained by HIFs at all the studied concentrations. Overall, the experimental results studied elucidate expressly that the properties of Lyz are maintained in the presence of hybrid ionic fluid1 while these properties are intensified in hybrid ionic fluid2. This work has elucidated expressly biocompatible green solvents in protein stability and functionality due to the alluring properties of DES, which can counteract the negative effect of ILs in HIFs.

Roles and Mechanisms of Choline Metabolism in Nonalcoholic Fatty Liver Disease and Cancers.

Choline participates in three major metabolic pathways: oxidation, phosphorylation, and acetylation. Through oxidation, choline is converted to betaine and contributes to methyl metabolism and epigenetic regulation. Through phosphorylation, choline participates in phospholipid metabolism, and serves as the precursor of phosphocholine, phosphatidylcholine, glycerophosphocholine, and other essential compounds, thereby modulating lipid metabolism and transport. Through acetylation, choline is transformed into acetylcholine in cholinergic neurons, playing a vital role in neurotransmission. Moreover, gut microbiota can metabolize choline into trimethylamine-N-oxide, and be involved in the pathogenesis of various diseases such as nonalcoholic fatty liver disease (NAFLD), cancer, cardiovascular disease, etc. Since choline metabolism is implicated in the development of NAFLD and diverse cancers, including liver cancer, it may serve as a therapeutic target for these diseases in the future. Currently, there are numerous therapeutic agents targeting choline metabolism to treat NAFLD and cancers, but most of them are ineffective and some even have adverse effects that lead to a series of complications. Therefore, further research and clinical validation are required to obtain safe and efficacious drugs. This review comprehensively summarizes the choline metabolic pathway and its regulatory mechanisms, elucidates the roles and mechanisms of choline metabolism in the aforementioned diseases, and provides a discussion of the current advances and immense potential of this field.

Choline metabolism reprogramming mediates an immunosuppressive microenvironment in non-small cell lung cancer (NSCLC) by promoting tumor-associated macrophage functional polarization and endothelial cell proliferation.

INTRODUCTION: Lung cancer is a prevalent malignancy globally, and immunotherapy has revolutionized its treatment. However, resistance to immunotherapy remains a challenge. Abnormal cholinesterase (ChE) activity and choline metabolism are associated with tumor oncogenesis, progression, and poor prognosis in multiple cancers. Yet, the precise mechanism underlying the relationship between ChE, choline metabolism and tumor immune microenvironment in lung cancer, and the response and resistance of immunotherapy still unclear. METHODS: Firstly, 277 advanced non-small cell lung cancer (NSCLC) patients receiving first-line immunotherapy in Sun Yat-sen University Cancer Center were enrolled in the study. Pretreatment and the alteration of ChE after 2 courses of immunotherapy and survival outcomes were collected. Kaplan-Meier survival and cox regression analysis were performed, and nomogram was conducted to identify the prognostic and predicted values. Secondly, choline metabolism-related genes were screened using Cox regression, and a prognostic model was constructed. Functional enrichment analysis and immune microenvironment analysis were also conducted. Lastly, to gain further insights into potential mechanisms, single-cell analysis was performed. RESULTS: Firstly, baseline high level ChE and the elevation of ChE after immunotherapy were significantly associated with better survival outcomes for advanced NSCLC. Constructed nomogram based on the significant variables from the multivariate Cox analysis performed well in discrimination and calibration. Secondly, 4 choline metabolism-related genes (MTHFD1, PDGFB, PIK3R3, CHKB) were screened and developed a risk signature that was found to be related to a poorer prognosis. Further analysis revealed that the choline metabolism-related genes signature was associated with immunosuppressive tumor microenvironment, immune escape and metabolic reprogramming. scRNA-seq showed that MTHFD1 was specifically distributed in tumor-associated macrophages (TAMs), mediating the differentiation and immunosuppressive functions of macrophages, which may potentially impact endothelial cell proliferation and tumor angiogenesis. CONCLUSION: Our study highlights the discovery of ChE as a prognostic marker in advanced NSCLC, suggesting its potential for identifying patients who may benefit from immunotherapy. Additionally, we developed a prognostic signature based on choline metabolism-related genes, revealing the correlation with the immunosuppressive microenvironment and uncovering the role of MTHFD1 in macrophage differentiation and endothelial cell proliferation, providing insights into the intricate workings of choline metabolism in NSCLC pathogenesis.

Prenatal Choline Supplementation Improves Glucose Tolerance and Reduces Liver Fat Accumulation in Mouse Offspring Exposed to Ethanol during the Prenatal and Postnatal Periods.

Prenatal alcohol exposure (AE) affects cognitive development. However, it is unclear whether prenatal AE influences the metabolic health of offspring and whether postnatal AE exacerbates metabolic deterioration resulting from prenatal AE. Choline is a semi-essential nutrient that has been demonstrated to mitigate the cognitive impairment of prenatal AE. This study investigated how maternal choline supplementation (CS) may modify the metabolic health of offspring with prenatal and postnatal AE (AE/AE). C57BL/6J female mice were fed either a Lieber-DeCarli diet with 1.4% ethanol between embryonic day (E) 9.5 and E17.5 or a control diet. Choline was supplemented with 4 × concentrations versus the control throughout pregnancy. At postnatal week 7, offspring mice were exposed to 1.4% ethanol for females and 3.9% ethanol for males for 4 weeks. AE/AE increased hepatic triglyceride accumulation in male offspring only, which was normalized by prenatal CS. Prenatal CS also improved glucose tolerance compared to AE/AE animals. AE/AE suppressed hepatic gene expression of peroxisome proliferator activated receptor alpha (Ppara) and low-density lipoprotein receptor (Ldlr), which regulate fatty acid catabolism and cholesterol reuptake, respectively, in male offspring. However, these changes were not rectified by prenatal CS. In conclusion, AE/AE led to an increased risk of steatosis and was partially prevented by prenatal CS in male mice.

The Role of One-Carbon Metabolism and Methyl Donors in Medically Assisted Reproduction: A Narrative Review of the Literature.

One-carbon (1-C) metabolic deficiency impairs homeostasis, driving disease development, including infertility. It is of importance to summarize the current evidence regarding the clinical utility of 1-C metabolism-related biomolecules and methyl donors, namely, folate, betaine, choline, vitamin B12, homocysteine (Hcy), and zinc, as potential biomarkers, dietary supplements, and culture media supplements in the context of medically assisted reproduction (MAR). A narrative review of the literature was conducted in the PubMed/Medline database. Diet, ageing, and the endocrine milieu of individuals affect both 1-C metabolism and fertility status. In vitro fertilization (IVF) techniques, and culture conditions in particular, have a direct impact on 1-C metabolic activity in gametes and embryos. Critical analysis indicated that zinc supplementation in cryopreservation media may be a promising approach to reducing oxidative damage, while female serum homocysteine levels may be employed as a possible biomarker for predicting IVF outcomes. Nonetheless, the level of evidence is low, and future studies are needed to verify these data. One-carbon metabolism-related processes, including redox defense and epigenetic regulation, may be compromised in IVF-derived embryos. The study of 1-C metabolism may lead the way towards improving MAR efficiency and safety and ensuring the lifelong health of MAR infants.

An eminent approach towards next generation solvents for sustainable packaging and stability of enzymes: a comprehensive study of ionic liquid and deep eutectic solvent mixtures.

Hybrid ionic fluids (HIFs) are newly emerging and fascinating sustainable solvent media, which are attracting a great deal of scientific interest in protecting the native structure of proteins. For a few decades, there has been a demand to consider ionic liquids (ILs) and deep eutectic solvents (DESs) as biocompatible solvent media for enzymes; however, in some cases, these solvent media also show limitations. Therefore, this work focuses on synthesising novel HIFs to intensify the properties of existing ILs and DESs by mixing them. Herein, HIFs have been synthesised by the amalgamation of a deep eutectic solvent (DES) and an ionic liquid (IL) with a common cation or anion. Later on, the stability and activity of hen's egg white lysozyme (Lyz) in the presence of biocompatible solvent media and HIFs were studied by various techniques such as UV-vis, steady-state fluorescence, circular dichroism (CD), Fourier transform infrared spectroscopy (FT-IR) and dynamic light scattering (DLS) measurements. This work emphasises the effect of a DES (synthesised using 1 : 2 choline chloride and malonic acid) [Maline], ILs (1-butyl-3-methylimidazolium chloride [BMIM]Cl or choline acetate [Chn][Ac]) and their corresponding HIFs on the structure and functionality of Lyz. Moreover, we also studied the secondary structure, thermal stability, enzymatic activity and thermodynamic profile of Lyz at pH = 7 in the presence of varying concentrations (0.1 to 0.5 M) of [BMIM]Cl and [Chn][Ac] ILs, Maline as a DES, and Maline [BMIM]Cl (HIF1) and Maline [Chn][Ac] (HIF2). Spectroscopic results elucidate that ILs affect the activity and structural stability of Lyz. In contrast, the stability and activity are inhibited by DES and are enhanced by HIFs at all the studied concentrations. Overall, the experimental results studied explicitly elucidate that the structure and stability of Lyz are maintained in the presence of HIF1 while these properties are intensified in HIF2. This study shows various applications in biocompatible green solvents, particularly in the stability and functionality of proteins, due to their unique combination where the properties counteract the negative effect of either DESs or ILs in HIFs.

7 Tesla magnetic resonance spectroscopic imaging predicting IDH status and glioma grading.

INTRODUCTION: With the application of high-resolution 3D 7 Tesla Magnetic Resonance Spectroscopy Imaging (MRSI) in high-grade gliomas, we previously identified intratumoral metabolic heterogeneities. In this study, we evaluated the potential of 3D 7 T-MRSI for the preoperative noninvasive classification of glioma grade and isocitrate dehydrogenase (IDH) status. We demonstrated that IDH mutation and glioma grade are detectable by ultra-high field (UHF) MRI. This technique might potentially optimize the perioperative management of glioma patients. METHODS: We prospectively included 36 patients with WHO 2021 grade 2-4 gliomas (20 IDH mutated, 16 IDH wildtype). Our 7 T 3D MRSI sequence provided high-resolution metabolic maps (e.g., choline, creatine, glutamine, and glycine) of these patients' brains. We employed multivariate random forest and support vector machine models to voxels within a tumor segmentation, for classification of glioma grade and IDH mutation status. RESULTS: Random forest analysis yielded an area under the curve (AUC) of 0.86 for multivariate IDH classification based on metabolic ratios. We distinguished high- and low-grade tumors by total choline (tCho) / total N-acetyl-aspartate (tNAA) ratio difference, yielding an AUC of 0.99. Tumor categorization based on other measured metabolic ratios provided comparable accuracy. CONCLUSIONS: We successfully classified IDH mutation status and high- versus low-grade gliomas preoperatively based on 7 T MRSI and clinical tumor segmentation. With this approach, we demonstrated imaging based tumor marker predictions at least as accurate as comparable studies, highlighting the potential application of MRSI for pre-operative tumor classifications.

An inverse association of dietary choline with atherosclerotic cardiovascular disease among US adults: a cross-sectional NHANES analysis.

BACKGROUND: The role of diet choline in atherosclerotic cardiovascular disease (ASCVD) is uncertain. Findings from animal experiments are contradictory while there is a lack of clinical investigations. This study aimed to investigate the association between choline intake and ASCVD based on individuals from the National Health and Nutrition Examination Survey (NHANES) database. METHODS: This cross-sectional study was conducted in 5525 individuals from the NHANES between 2011 and 2018. Participants were categorized into the ASCVD (n = 5015) and non-ASCVD (n = 510) groups. Univariable and multivariable-adjusted regression analyses were employed to investigate the relationship between diet choline and pertinent covariates. Logistic regression analysis and restricted cubic spline analysis were used to evaluate the association between choline intake and ASCVD. RESULTS: ASCVD participants had higher choline intake compared to those without ASCVD. In the higher tertiles of choline intake, there was a greater proportion of males, married individuals, highly educated individuals, and those with increased physical activity, but a lower proportion of smokers and drinkers. In the higher tertiles of choline intake, a lower proportion of individuals had a history of congestive heart failure and stroke. After adjusting for age, gender, race, ethnicity, and physical activity, an inverse association between choline intake and heart disease, stroke, and ASCVD was found. A restricted cubic spline analysis showed a mirrored J-shaped relationship between choline and ASCVD, stroke and congestive heart failure in males. There was no association between dietary choline and metabolic syndrome. CONCLUSION: An inverse association was observed between choline intake and ASVCD among U.S. adults. Further large longitudinal studies are needed to test the causal relationship of choline and ASVCD.

A prospective study on the early evaluation of response to androgen receptor-targeted agents with 11C-Choline, 68Ga-PSMA, and 18F-FACBC PET in metastatic castration-resistant prostate cancer: a single-center experience.

BACKGROUND: The early identification of responsive and resistant patients to androgen receptor-targeting agents (ARTA) in metastatic castration-resistant prostate cancer (mCRPC) is not completely possible with prostate-specific antigen (PSA) assessment and conventional imaging. Considering its ability to determine metabolic activity of lesions, positron emission tomography (PET) assessment might be a promising tool. PATIENTS AND METHODS: We carried out a monocentric prospective study in patients with mCRPC treated with ARTA to evaluate the role of different PET radiotracers: 49 patients were randomized to receive 11C-Choline, Fluorine 18 fluciclovine (anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid - FACBC) (18F-FACBC), or Gallium-68-prostate-specific-membrane-antigen (68Ga-PSMA) PET, one scan before therapy and one 2 months later. The primary aim was to investigate the performance of three novel PET radiotracers for the early evaluation of response to ARTA in metastatic CRPC patients; the outcome evaluated was biochemical response (PSA reduction ≥50%). The secondary aim was to investigate the prognostic role of several semiquantitative PET parameters and their variations with the different radiotracers in terms of biochemical progression-free survival (bPFS) and overall survival (OS). The study was promoted by the Italian Department of Health (code RF-2016-02364809). RESULTS: Regarding the primary endpoint, at log-rank test a statistically significant correlation was found between metabolic tumor volume (MTV) (P = 0.018) and total lesion activity (TLA) (P = 0.025) percentage variation among the two scans with 68Ga-PSMA PET and biochemical response. As for the secondary endpoints, significant correlations with bPFS were found for 68Ga-PSMA total MTV and TLA at the first scan (P = 0.001 and P = 0.025, respectively), and MTV percentage variation (P = 0.031). For OS, statistically significant correlations were found for different 68Ga-PSMA and 18F-FACBC parameters and for major maximum standardized uptake value at the first 11C-Choline PET scan. CONCLUSIONS: Our study highlighted that 11C-Choline, 68Ga-PSMA, and 18F-FACBC semiquantitative PET parameters and their variations present a prognostic value in terms of OS and bPFS, and MTV and TLA variations with 68Ga-PSMA PET a correlation with biochemical response, which could help to assess the response to ARTA.

The effects of exposure to and timing of a choline-deficient diet during pregnancy and early postnatal life on the skeletal muscle transcriptome of the offspring.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is related to muscle loss, but the precise mechanism underlying this association remains unclear. The aim of the present study was thus to determine the influence of maternal fatty liver and dietary choline deficiency during pregnancy and/or lactation periods on the skeletal muscle gene expression profile among 24-day-old male rat offspring. METHODS: Histological examination of skeletal muscle tissue specimens obtained from offspring of dams suffering from fatty liver, provided with proper choline intake during pregnancy and lactation (NN), fed a choline-deficient diet during both periods (DD), deprived of choline only during pregnancy (DN), or only during lactation (ND), was performed. The global transcriptome pattern was assessed using a microarray approach (Affymetrix® Rat Gene 2.1 ST Array Strip). The relative expression of selected genes was validated by real-time PCR (qPCR). RESULTS: Morphological differences in fat accumulation in skeletal muscle related to choline supply were observed. The global gene expression profile was consistent with abnormal morphological changes. Mettl21c gene was overexpressed in all choline-deficient groups compared to the NN group, while two genes, Cdkn1a and S100a4, were downregulated. Processes of protein biosynthesis were upregulated, and processes related to cell proliferation and lipid metabolism were inhibited in DD, DN, and ND groups compared to the NN group. CONCLUSIONS: Prenatal and early postnatal exposure to fatty liver and dietary choline deficiency leads to changes in the transcriptome profile in skeletal muscle of 24-day old male rat offspring and is associated with muscle damage, but the mechanism of it seems to be different at different developmental stages of life. Adequate choline intake during pregnancy and lactation can prevent severe muscle disturbance in the progeny of females suffering from fatty liver.

Molecular dynamics simulations of choline chloride and ascorbic acid deep eutectic solvents: Investigation of structural and dynamics properties.

Deep eutectic solvents (DESs) composed of choline chloride (ChCl) and ascorbic acid (AA) were investigated using the molecular dynamics (MD) simulations. The analyses of the configuration, radial distribution function (RDFs), coordination number, spatial distribution function (SDFs), interaction energies, hydrogen bond number, and self-diffusion coefficient of the ChCl/AA binary systems of different concentrations showed that the stability of the hydrogen bond network and the mutual attraction between systems were the strongest at the experimental eutectic concentration (molar ratio of 2:1). In our simulated temperature range from 303.15 to 353.15 K, the hydrogen bonding network of ChCl/AA DES does not undergo considerable alterations, indicating that its stability was insensitive to temperature. In addition, the influence of the water content on the ChCl/AA DES system was further investigated. The simulated results revealed that the water molecules could disrupt the formation of the hydrogen bonding network by occupyin positions that are essential for the formation of hydrogen bonds within the DES system.