Search

Background Methods Results Conclusions Chronic neuropathic pain (CNP) is a debilitating condition, often refractory to currently available drugs. Understanding biochemical alterations in peripheral tissues such as blood will be useful for understanding underlying pathophysiological processes relating to CNP.We collected blood from two independent cohorts of CNP and pain‐free controls (CNP n = 129/Controls n = 127) in the UK and Ireland to investigate the relationship between CNP‐associated molecular/biochemical alterations and a range of clinical and pain metric parameters. Multiple statistical comparisons were conducted on the data, with selected variables included in one or more of the intended inferential analyses (six models).Gene expression analysis showed that choline phosphotransferase (CHPT1) was increased (p < .001) in the CNP group compared to controls. The levels of phosphatidylcholine, a metabolite of CHPT1 in the Kennedy Pathway, were significantly (p = .008) decreased in the plasma of patients with CNP. Given the relationship between the Kennedy pathway and endocannabinoids, plasma endocannabinoids and related N‐acylethanolamines were quantified in clinical samples by HPLC‐Tandem Mass Spectrometry. Plasma levels of the endocannabinoid 2‐arachidonoylglycerol were higher in CNP samples compared to controls, and in the statistical models applied, 2‐arachidonoylglycerol significantly increased the odds of CNP (p < .001). The expression of genes related to the synthesis and catabolism of endocannabinoids also corroborated the increased plasma 2‐arachidonoylglycerol levels in patients with CNP.Endocannabinoid levels, expression of genes related to endocannabinoid metabolism, age, sex, depression and anxiety state together were strong predictors of CNP. The observed molecular changes indicate that lipid metabolism is altered in CNP and thus may represent a viable target for novel analgesics or biomarker development. [ABSTRACT FROM AUTHOR]

This work aims to characterize the serum profile of athletes after the administration of ecdysteroids, natural steroid hormones recently reported to enhance athletic performance. The combination of mass spectrometry and chemometric tools may allow to differentiate physiological effects from post‐training and intake‐driven effects. Serum samples were collected from 46 healthy male volunteers and divided into four groups: control (two capsules/day of Peak Ecdysone without training), placebo (two capsules without ecdysteroids with training), Ec1 (two capsules/day Peak Ecdysone with training), and Ec2 (eight capsules/day Peak Ecdysone with training). Metabolic profiling was measured using a SCIEX Triple Quadrupole LC‐MS/MS system coupled with the Biocrates AbsoluteIDQ p180 kit, which allows quantitation of a large panel of metabolites that were subjected to multivariate analysis. Unsupervised analysis of the data found no significant differences between the placebo and the ecdysteroid supplementation groups. By merging Ec1 and Ec2 into a single group, coded as treated, a clear discrimination between the control and placebo groups was observed. Phosphatidylcholines were among the most significant features of ecdysteroids administration, showing a dose‐dependent effect in Ec1 and Ec2 groups. As specific metabolic phenotypes can result from years of training, the discrimination of physiological effects from those caused by the administration of banned substances can be a valuable analytical strategy for the interpretation of adverse analytical findings in the anti‐doping field. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to investigate the causal relationship between phosphatidylcholine (PC) levels and dysmenorrhea using Mendelian randomization (MR) analysis. Methods: We conducted a two-sample MR analysis using GWAS data on PC levels and dysmenorrhea. Single nucleotide polymorphisms (SNPs) associated with PC levels were used as instrumental variables. MR-Egger regression and inverse variance weighting (IVW) were used to estimate the causal effect of PC levels on dysmenorrhea. Sensitivity analyses were performed to assess the robustness of the results. Results: The IVW analysis revealed a significant positive association between higher PC levels and dysmenorrhea (OR: 1.533, 95% CI: 1.039-2.262, P = 0.031). The MR-Egger regression did not detect pleiotropy. Sensitivity analyses confirmed the robustness of the results. Conclusion: This study provides evidence suggesting a causal link between increased PC levels and dysmenorrhea. Further research is needed to understand the biological mechanisms underlying this relationship and to explore potential therapeutic implications. [ABSTRACT FROM AUTHOR]

SUMMARY: Lipid remodeling plays a critical role in plant response to abiotic stress and metabolic perturbations. Key steps in this process involve modifications of phosphatidylcholine (PC) acyl chains mediated by lysophosphatidylcholine: acyl‐CoA acyltransferases (LPCATs) and phosphatidylcholine: diacylglycerol cholinephosphotransferase (ROD1). To assess their importance in lipid homeostasis, we took advantage of the trigalactosyldiacylglycerol1 (tgd1) mutant that exhibits marked increases in fatty acid synthesis and fatty acid flux through PC due to a block in inter‐organelle lipid trafficking. Here, we showed that the increased fatty acid synthesis in tgd1 is due to posttranslational activation of the plastidic acetyl‐coenzyme A carboxylase. Genetic analysis showed that knockout of LPCAT1 and 2 resulted in a lethal phenotype in tgd1. In addition, plants homozygous for lpcat2 and heterozygous for lpcat1 in the tgd1 background showed reduced levels of PC and triacylglycerols (TAG) and alterations in their fatty acid profiles. We further showed that disruption of ROD1 in tgd1 resulted in changes in fatty acid composition of PC and TAG, decreased leaf TAG content and reduced seedling growth. Together, our results reveal a critical role of LPCATs and ROD1 in maintaining cellular lipid homeostasis under conditions, in which fatty acid production largely exceeds the cellular demand for membrane lipid synthesis. Significance Statement: Characterization of tgd1 mutants reveals a critical role of PC remodeling mediated by LPCATs and ROD1 in maintaining cellular lipid homeostasis. [ABSTRACT FROM AUTHOR]

The nuclear envelope consists of an outer membrane connected to the endoplasmic reticulum, an inner membrane facing the nucleoplasm and a perinuclear space separating the two bilayers. The inner and outer nuclear membranes are physically connected at nuclear pore complexes that mediate selective communication and transfer of materials between the cytoplasm and nucleus. The spherical shape of the nuclear envelope is maintained by counterbalancing internal and external forces applied by cyto- and nucleo-skeletal networks, and the nuclear lamina and chromatin that underly the inner nuclear membrane. Despite its apparent rigidity, the nuclear envelope can invaginate to form an intranuclear membrane network termed the nucleoplasmic reticulum (NR) consisting of Type-I NR contiguous with the inner nuclear membrane and Type-II NR containing both the inner and outer nuclear membranes. The NR extends deep into the nuclear interior potentially facilitating communication and exchanges between the nuclear interior and the cytoplasm. This review details the evidence that NR intrusions that regulate cytoplasmic communication and genome maintenance are the result of a dynamic interplay between membrane biogenesis and remodelling, and physical forces exerted on the nuclear lamina derived from the cyto- and nucleo-skeletal networks. [ABSTRACT FROM AUTHOR]

Phospholipids are crucial structural components of cells. Phosphatidylcholine and phosphatidylethanolamine (both synthesized via the Kennedy pathway) and phosphatidylserine undergo interconversion. The dysregulation of this process is implicated in various diseases. This paper discusses the role of enzymes involved in the interconversion of phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine, specifically phosphatidylethanolamine N-methyltransferase (PEMT), phosphatidylserine synthases (PTDSS1 and PTDSS2), and phosphatidylserine decarboxylase (PISD), with a focus on their biochemical properties. Additionally, we describe the effects of the deregulation of these enzymes and their roles in both oncological and non-oncological diseases, including nonalcoholic fatty liver disease (NAFLD), Alzheimer's disease, obesity, insulin resistance, and type II diabetes. Current knowledge on inhibitors of these enzymes as potential therapeutic agents is also reviewed, although in most cases, inhibitors are yet to be developed. The final section of this article presents a bioinformatic analysis using the GEPIA portal to explore the significance of these enzymes in cancer processes. [ABSTRACT FROM AUTHOR]

BACKGROUND: Lack of n‐3 polyunsaturated fatty acids during the period of maternity drastically lowers the docosahexaenoic acid (DHA) level in the brain of offspring and studies have demonstrated that different molecular forms of DHA are beneficial to brain development. The aim of this study was to investigate the effect of short‐term supplementation with DHA‐enriched phosphatidylserine (PS) and phosphatidylcholine (PC) on DHA levels in the liver and brain of congenital n‐3‐deficient mice. RESULTS: Dietary supplementation with DHA significantly changed the fatty acid composition of various phospholipid molecules in the cerebral cortex and liver while DHA‐enriched phospholipid was more effective than DHA triglyceride (TG) in increasing brain and liver DHA. Both DHA‐PS and DHA‐PC could effectively increase the DHA levels, but DHA in the PS form was superior to PC in the contribution of DHA content in the brain ether‐linked PC (ePC) and liver lyso‐phosphatidylcholine molecular species. DHA‐PC showed more significant effects on the increase of DHA in liver TG, PC, ePC, phosphatidylethanolamine (PE) and PE plasmalogen (pPE) molecular species and decreasing the arachidonic acid level in liver PC plasmalogen, ePC, PE and pPE molecular species compared with DHA‐PS. CONCLUSION: The effect of dietary interventions with different molecular forms of DHA for brain and liver lipid profiles is different, which may provide theoretical guidance for dietary supplementation of DHA for people. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Several studies have indicated a potential causal relationship between plasma standard lipids, such as high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), triglycerides (TG), and total cholesterol (TC), and psoriasis. However, few studies have offered causal evidence of lipid species beyond these standard lipids. We conducted an analysis using a genome-wide association study (GWAS) dataset comprising 179 lipid species, including 13 types across four major categories, to identify instrumental variables (IVs) associated with plasma lipids. We utilized two GWAS datasets from the IEU and Finngen for psoriasis vulgaris as the outcome. A two-sample Mendelian randomization (MR) analysis was used to explore the causal relationship between 179 lipid species and psoriasis vulgaris in two datasets. Lipid species showing causal association in both psoriasis datasets were compared for overlap. Our study identified potential causal relationships between six lipid species and psoriasis vulgaris: phosphatidylcholine (16:1_18:2), phosphatidylcholine (18:0_18:2), phosphatidylcholine (18:1_20:4), phosphatidylethanolamine (16:0_18:2), phosphatidylinositol (18:0_20:3), and triacylglycerol (50:1). In summary, elevated plasma levels of phosphatidylcholine (16:1_18:2), phosphatidylcholine (18:0_18:2), phosphatidylethanolamine (16:0_18:2), phosphatidylinositol (18:0_20:3), and triacylglycerol (50:1) may increase the risk of psoriasis vulgaris. Conversely, plasma phosphatidylcholine (18:1_20:4) may play a protective role against psoriasis vulgaris. [ABSTRACT FROM AUTHOR]

This study aimed to optimize a liposomal formulation to enhance the stability of a phenolic-rich extract from green walnut husk. Liposomes were prepared using varying concentrations of phosphatidylcholine (0.15–2% w/v), extract (0–1.3% v/v), and sodium laurate (0–0.2% w/v) via ethanol injection and sonication. Characterization included visual appearance, particle size, polydispersity index, surface charge, encapsulation efficiency, and morphology. Stable liposomes were achieved at 0.15% and 0.3% w/v phosphatidylcholine, although with low encapsulation efficiency (<40%). The addition of 0.2% (w/v) sodium laurate improved the stability, especially at higher phosphatidylcholine concentrations, enhancing the electrostatic repulsion. Optimal concentrations of 2% w/v phosphatidylcholine, 0.2% w/v sodium laurate, and 0.6% v/v extract were determined. The liposomes exhibited a spherical unilamellar morphology with a size of 97.5 ± 0.9 nm and a negative surface charge of –39.8 ± 0.9 mV. These nanoliposomes showed 79.7 ± 0.7% encapsulation efficiency and remained stable under pH, temperature, ionic strength, and storage time variations. Overall, the liposomes proved effective in preserving the natural phenolics of walnut husks under challenging environmental conditions. [ABSTRACT FROM AUTHOR]

Intestinal mucus serves as the first line barrier within the mucosa to protect against microbiota attack due to its water-repellent properties, which are the result of the high abundance of phosphatidylcholine bound to mucins. A deficiency of mucus phosphatidylcholine predisposes it to mucosal inflammation by the attack of commensal microbiota, as it is intrinsically low in ulcerative colitis. However, for precipitation of an acute inflammatory episode, mucus phosphatidylcholine has to fall below the critical level required for mucosal protection. Bacterial ectophospholipase could be a candidate for further thinning of the mucus phosphatidylcholine shield as shown, for example, with the ectophospholipase containing Helicobacter pylori bacterium. Despite supporting evidence for this mechanism in the intestine, the responsible ectophospholipase-carrying bacteria species are still to be defined. Applying phosphatidylcholine to the lumen can serve to fill up empty mucin-binding sites in ulcerative colitis as well as provide a substrate for the ectophospholipase-carrying bacteria preventing their attacks on the mucus phosphatidylcholine layer. Evidence supporting this concept comes from clinical trials in humans with ulcerative colitis as well as from colitis mouse models where phosphatidylcholine was substituted in the lumen. An alternative strategy could involve adding non-absorbable phospholipase inhibitors to the intestinal lumen, which has been shown to be effective in a mouse model of ulcerative colitis. Bacterial phospholipase should be considered a pathogenetic factor of the intestinal microbiota and therapeutic strategies should be developed to prevent their hyperactivity for clinical improvement of intestinal inflammation.

Abstract Objectives The Ishikawa cell line is the most widely used model system for investigating implantation and endometrial cancer. Understanding the biology of this cell line is essential for developing effective interventional strategies. To gain a deeper understanding of its cellular protein profile, we extracted cellular proteins from Ishikawa cells and analyzed the peptides using mass spectrometry. Our goal was to create a proteomic resource specifically tailored for Ishikawa cells. This data set is of particular significance in the realm of targeted drug delivery. Liposomes are synthetic spherical vesicles composed of hydrophobic bilayer phospholipids and have received immense recognition as highly effective carriers for the delivery of pharmaceutical drugs and essential nutrients to the endometrium. Phosphatidylcholine and phosphatidylethanolamine are often combined to create functional liposomal systems. To discern any potential interfering effects originating from the liposome backbone, our investigation involved direct effects of phospholipid liposomes on endometrial epithelial cells. Data description The data set includes peptide spectra derived from the intracellular proteomes of Ishikawa endometrial cancer cell isolates and their phospholipid-treated counterparts. Representing a proteome-wide profile, this dataset aims to contribute to a broader understanding of the physiology of endometrial epithelial cells. Proteomic analysis identified key proteins involved in the intricate regulation of cellular metabolism, cell cycle progression, and signaling. Between-group analysis revealed no differentially expressed proteins after adjusting for multiple testing using the applied thresholds (p-value 1). Data are available via ProteomeXchange with identifier PXD050871.

Objective: To evaluate the causal relationship between lipids and ulcerative colitis (UC) through Mendelian Randomization (MR), and to further investigate the involvement of immune cells in mediating this process. Methods: Utilizing summary statistics from genome-wide association studies (GWAS) of individuals with European ancestry, we analyzed the causal link between 179 lipid types and UC (2,569 UC cases and 453,779 controls) through Two-sample Mendelian randomization (2SMR) and Bayesian-weighted MR (BWMR). Based on this, a mediation screening of 731 immune cell phenotypes was conducted to identify exposure and mediator factors. Lastly, the role and proportion of immune cells in mediating the causal effects of lipids on UC were assessed via reverse MR (RMR) and two-step MR. Results: The results of MR showed that there was a causal relationship between the six genetically predicted lipid types and UC (P <0.05), and the four immune cell phenotypes were identified as mediators of the association between lipids and UC. Notably, Phosphatidylcholine (PC) (16:0_0:0) served as the exposure factor, and myeloid cells CD11b on CD33+ HLA DR+ CD14dim acted as the mediator. Mediation analysis showed that CD11b on CD33+ HLA DR+ CD14dim had a mediation effect of -0.0205 between PC (16:0_0:0) and UC, with the mediation effect ratio at 15.38%. Conclusion: Our findings elucidate the causal effect of lipids on UC and identify the significant mediating role of myeloid cells CD11b on CD33+ HLA DR+ CD14dim in regulating UC through PC (16:0_0:0), offering new pathways and strategies for UC clinical treatment. [ABSTRACT FROM AUTHOR]

Purpose: The COVID-19 pandemic has led to millions of confirmed cases worldwide, resulting in numerous deaths and hospitalizations. Long-term symptoms after infection or vaccination, known as Post-acute COVID-19 Syndrome (PACS) or Post-acute COVID-19 Vaccination Syndrome (PACVS), present a challenge for the healthcare system. Among the various neurological symptoms, cognitive impairments are frequently observed in PACS/PACVS patients. This study aimed to understand cognitive deficits in PACS/PACVS patients and evaluated potential treatment options, including phosphatidylcholine and computer-assisted cognitive training (CCT). Methods: The Neuro-COVID Outpatient Clinic at Evangelic Hospital Vienna evaluated n = 29 PACS/PACVS patients from May 2023 to October 2023. Enrolled patients were divided into three therapy schemes: Group A received phosphatidylcholine, B received phosphatidylcholine plus access to a computerassisted cognitive training program, and C (divided into two subgroups) served as a control group. Cognitive impairments were evaluated in multiple assessments (initial and during therapy) using the COGBAT test. Simultaneously, an assessment of the quality of life was conducted using the WHOQOL-BREF. Results: Primary cognitive impairments, especially attentional deficits were notably evident compared to the general population. While all treatment groups showed cognitive improvement (significant or with a positive trend, but without reaching the level of statistical significance) after therapy, no significant interaction was found between assessment time points and treatment schemes for overall cognitive performance, attention, memory, and executive functions, suggesting consistency across the groups. The WHOQOL-BREF primarily demonstrated deficits in the domains of physical health and psychological wellbeing. Conclusion: This study examined the impact of PACS/PACVS on cognitive performance and evaluated phosphatidylcholine and CCT as potential treatment options. Patients with PACS/PACVS showed notable cognitive deficits, especially in the domain attention. While the effectiveness of phosphatidylcholine and CCT in treating cognitive deficits was inconclusive, the study indicated the possibility of spontaneous remission of cognitive deficits in PACS/PACVS. [ABSTRACT FROM AUTHOR]

Phosphatidylcholine (PC) is critical for the nitrogen-fixing symbiosis between rhizobia and legumes. We characterized three PC biosynthesis pathways in Rhizobium leguminosarum and evaluated their impact on nitrogen fixation in clover nodules. In the presence of choline, a PC synthase catalyzes the condensation of cytidine diphosphate-diacylglycerol with choline to produce PC. In the presence of lyso-PC, acyltransferases acylate this mono-acylated phospholipid to PC. The third pathway relies on phospholipid N-methyltransferases (Pmts), which sequentially methylate phosphatidylethanolamine (PE) through three rounds of methylation, yielding PC via the intermediates monomethyl-PE and dimethyl-PE. In R. leguminosarum, at least three Pmts participate in this methylation cascade. To elucidate the functions of these enzymes, we recombinantly produced and biochemically characterized them. We moved on to determine the phospholipid profiles of R. leguminosarum mutant strains harboring single and combinatorial deletions of PC biosynthesis genes. The cumulative results show that PC production occurs through the combined action of multiple enzymes, each with distinct substrate and product specificities. The methylation pathway emerges as the dominant PC biosynthesis route, and we pinpoint PmtS2, which catalyzes all three methylation steps, as the enzyme responsible for providing adequate PC amounts for a functional nitrogen-fixing symbiosis with clover. [ABSTRACT FROM AUTHOR]

Cholesterol homeostasis is pivotal for cellular function. Acyl-coenzyme A:cholesterol acyltransferase 1 (ACAT1), also abbreviated as SOAT1, is an enzyme responsible for catalyzing the storage of excess cholesterol to cholesteryl esters. ACAT1 is an emerging target to treat diverse diseases including atherosclerosis, cancer, and neurodegenerative diseases. F12511 is a high-affinity ACAT1 inhibitor. Previously, we developed a stealth liposome-based nanoparticle to encapsulate F12511 to enhance its delivery to the brain and showed its efficacy in treating a mouse model for Alzheimer's disease (AD). In this study, we introduce F26, a close derivative of F12511 metabolite in rats. F26 was encapsulated in the same DSPE-PEG2000/phosphatidylcholine (PC) liposome-based nanoparticle system. We employed various in vitro and in vivo methodologies to assess F26's efficacy and toxicity compared to F12511. The results demonstrate that F26 is more effective and durable than F12511 in inhibiting ACAT1, in both mouse embryonic fibroblasts (MEFs), and in multiple mouse tissues including the brain tissues, without exhibiting any overt systemic or neurotoxic effects. This study demonstrates the superior pharmacokinetic and safety profile of F26 in wild-type mice, and suggests its therapeutic potential against various neurodegenerative diseases including AD. [ABSTRACT FROM AUTHOR]

Objectives: The Ishikawa cell line is the most widely used model system for investigating implantation and endometrial cancer. Understanding the biology of this cell line is essential for developing effective interventional strategies. To gain a deeper understanding of its cellular protein profile, we extracted cellular proteins from Ishikawa cells and analyzed the peptides using mass spectrometry. Our goal was to create a proteomic resource specifically tailored for Ishikawa cells. This data set is of particular significance in the realm of targeted drug delivery. Liposomes are synthetic spherical vesicles composed of hydrophobic bilayer phospholipids and have received immense recognition as highly effective carriers for the delivery of pharmaceutical drugs and essential nutrients to the endometrium. Phosphatidylcholine and phosphatidylethanolamine are often combined to create functional liposomal systems. To discern any potential interfering effects originating from the liposome backbone, our investigation involved direct effects of phospholipid liposomes on endometrial epithelial cells. Data description: The data set includes peptide spectra derived from the intracellular proteomes of Ishikawa endometrial cancer cell isolates and their phospholipid-treated counterparts. Representing a proteome-wide profile, this dataset aims to contribute to a broader understanding of the physiology of endometrial epithelial cells. Proteomic analysis identified key proteins involved in the intricate regulation of cellular metabolism, cell cycle progression, and signaling. Between-group analysis revealed no differentially expressed proteins after adjusting for multiple testing using the applied thresholds (p-value < 0.05 and |logFC| > 1). Data are available via ProteomeXchange with identifier PXD050871. [ABSTRACT FROM AUTHOR]

Intestinal mucus serves as the first line barrier within the mucosa to protect against microbiota attack due to its water-repellent properties, which are the result of the high abundance of phosphatidylcholine bound to mucins. A deficiency of mucus phosphatidylcholine predisposes it to mucosal inflammation by the attack of commensal microbiota, as it is intrinsically low in ulcerative colitis. However, for precipitation of an acute inflammatory episode, mucus phosphatidylcholine has to fall below the critical level required for mucosal protection. Bacterial ectophospholipase could be a candidate for further thinning of the mucus phosphatidylcholine shield as shown, for example, with the ectophospholipase containing Helicobacter pylori bacterium. Despite supporting evidence for this mechanism in the intestine, the responsible ectophospholipase-carrying bacteria species are still to be defined. Applying phosphatidylcholine to the lumen can serve to fill up empty mucin-binding sites in ulcerative colitis as well as provide a substrate for the ectophospholipase-carrying bacteria preventing their attacks on the mucus phosphatidylcholine layer. Evidence supporting this concept comes from clinical trials in humans with ulcerative colitis as well as from colitis mouse models where phosphatidylcholine was substituted in the lumen. An alternative strategy could involve adding non-absorbable phospholipase inhibitors to the intestinal lumen, which has been shown to be effective in a mouse model of ulcerative colitis. Bacterial phospholipase should be considered a pathogenetic factor of the intestinal microbiota and therapeutic strategies should be developed to prevent their hyperactivity for clinical improvement of intestinal inflammation. [ABSTRACT FROM AUTHOR]

Phosphatidylserine (PS) is an important anionic phospholipid that is synthesized within the endoplasmic reticulum (ER). While PS shows the highest enrichment and serves important functional roles in the plasma membrane (PM) but its role in the nucleus is poorly explored. Using three orthogonal approaches, we found that PS is also uniquely enriched in the inner nuclear membrane (INM) and the nuclear reticulum (NR). Nuclear PS is critical for supporting the translocation of CCTα and Lipin1α, two key enzymes important for phosphatidylcholine (PC) biosynthesis, from the nuclear matrix to the INM and NR in response to oleic acid treatment. We identified the PS-interacting regions within the M-domain of CCTα and M-Lip domain of Lipin1α, and show that lipid droplet formation is altered by manipulations of nuclear PS availability. Our studies reveal an unrecognized regulatory role of nuclear PS levels in the regulation of key PC synthesizing enzymes within the nucleus. Synopsis: Phosphatidylserine (PS) is a phospholipid mainly enriched in the inner leaflet of the plasma membrane; however, its role in the nucleus remains unclear. This study describes the presence of PS in the inner nuclear membrane and nuclear reticulum, where it promotes nuclear membrane association of two key enzymes of phosphatidylcholine (PC) biosynthesis in response to oleic acid treatment. PS biosensors show its enrichment in the inner nuclear membrane (INM) and the nuclear reticulum (NR). PS in the inner nuclear membrane is synthesized at the endoplasmic reticulum. Nuclear PS interacts with two PC biosynthetic enzymes, CCTα and Lipin1α, promoting their translocation to the inner nuclear membrane. Nuclear PS biases PC biosynthesis toward membrane expansion rather than lipid droplet formation. Phosphatidylserine supports inner nuclear membrane enrichment of phosphatidylcholine biosynthetic enzymes, CCTα and Lipin1α, for nuclear membrane expansion. [ABSTRACT FROM AUTHOR]

Phosphatidylcholine (PC) is an essential lipid for liver health and lipoprotein metabolism, but its circulating levels have rarely been studied in patients with cirrhosis. Chronic hepatitis C virus (HCV) infection causes lipid abnormalities and is a major cause of cirrhosis. Effective HCV elimination with direct-acting antivirals (DAAs) is associated with the normalization of serum low-density lipoprotein cholesterol levels. Since PC is abundant in all lipoprotein particles, this study analyzed the association between serum PC species levels and liver cirrhosis before and after HCV eradication. Therefore, 27 PC species were measured by Fourier Transform Mass Spectrometry in the serum of 178 patients with chronic HCV infection at baseline and in 176 of these patients at the end of therapy. The PC species did not correlate with viral load, and the levels of 13 PC species were reduced in patients infected with genotype 3a compared to those affected with genotype 1. Four PC species were slightly elevated 12 weeks after DAA initiation, and genotype-related changes were largely normalized. Patients with HCV and cirrhosis had higher serum levels of PC 30:0 and 32:0 before and at the end of therapy. PC species containing polyunsaturated fatty acids were mostly decreased in cirrhosis. The levels of polyunsaturated, but not saturated, PC species were inversely correlated with the model of the end-stage liver disease score. A receiver operating characteristic curve analysis showed area under the curve values of 0.814 and 0.826 for PC 32:0 and 0.917 and 0.914 for % PC 32:0 (relative to the total PC levels) for the classification of cirrhosis at baseline and at the end of therapy, respectively. In conclusion, the specific upregulation of PC 32:0 in cirrhosis before and after therapy may be of diagnostic value in HCV-related cirrhosis. [ABSTRACT FROM AUTHOR]

Our recent findings revealed that human adipose tissues (AT)-derived extracellular vesicles (adiposomes) vary in cargo among obese and lean individuals. The main objective of this study was to investigate the adiposomal lipid profiles and their correlation with cardiometabolic risk factors. AT samples were collected from obese subjects and lean controls and analyzed for their characteristics and lipid content. In addition, we measured the correlation between adiposomal lipid profiles and body composition, glucose and lipid metabolic profiles, brachial artery vasoreactivity, AT arteriolar flow-induced dilation, and circulating markers such as IL-6, C-reactive protein, and nitric oxide (NO). Compared to lean controls, adiposomes isolated from obese subjects were higher in number after normalization to AT volume. The two major lipid classes differentially expressed were lysophosphatidylcholine/phosphatidylcholine (LPC/PC) and ceramides (Cer). All lipids in the LPC/PC class were several-fold lower in adiposomes from obese subjects compared to lean controls, on top of which were PC 18:2, PC 18:1, and PC 36:3. Most ceramides were markedly upregulated in the obese group, especially Cer d37:0, Cer d18:0, and Cer d39:0. Regression analyses revealed associations between adiposomal lipid profiles and several cardiometabolic risk factors such as body mass index (BMI), fat percentage, insulin resistance, arteriolar and brachial artery vasoreactivity, NO bioavailability, and high-density lipoproteins (HDL-C). We conclude that the ability of adiposomes from obese subjects to disrupt cardiometabolic function could be partly attributed to the dysregulated lipid cargo. [ABSTRACT FROM AUTHOR]

Liposomes have been widely used to improve drug accumulation in cancer therapy, enhancing anticancer efficacy and reducing side effects. The lipid components of the bilayer membrane define the fluidity of liposomes, which affects drug effectiveness. The present study evaluated the effectiveness of liposomes of differing rigidity in delivering doxorubicin (DOX). In this study, a phospholipid with a high Tm, hydrogenated soy phosphatidylcholine (HSPC), was totally or partially substituted with1-palmitoyl-2-oleoyl-sn-glycero-3- phosphocholine (POPC) or1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). The liposomes loaded DOX were composed of phosphatidylcholine (HSPC, POPC), both combined and not combined with DOPE, at a molar ratio of total phospholipids: cholesterol and DSPE-mPEG2000 were 57:38:5, respectively, and produced using a thin-layer hydration method. The in vitro cytotoxicity and in vivo antitumor activity of these liposomes was subsequently evaluated. The in vitro cytotoxicity assay used murine Lewis lung cancer (LLC) cells and Colon Carcinoma (C26) cells. For in vivo evaluation, the sample was intravenously injected into mice's tail veins at a dose of 5 mg DOX per kg of body weight. The results showed that substituting HSPC with POPC resulted in cytotoxicity profiles similar to those of DOX solution on C26 colon cancer and LLC cells. The addition of DOPE to DOX liposomes reduced antitumor activity. It can be concluded that the HSPC substituted with POPC or DOPE reduced liposome rigidity while also lowering in vivo antitumor activity. [ABSTRACT FROM AUTHOR]

The elucidation of the interaction mechanism between phospholipids and milk proteins within emulsions is pivotal for comprehending the properties of infant formula fat globules. In this study, multispectral methods and molecular docking were employed to explore the relationship between phosphatidylcholine (PC) and whey protein isolate (WPI). Observations indicate that the binding constant, alongside thermodynamic parameters, diminishes as temperature ascends, hinting at a predominantly static quenching mechanism. Predominantly, van der Waals forces and hydrogen bonds constitute the core interactions between WPI and PC. This assertion is further substantiated by Fourier transform infrared spectroscopy, which verifies PC's influence on WPI's secondary structure. A detailed assessment of thermodynamic parameters coupled with molecular docking reveals that PC predominantly adheres to specific sites within α‐lactalbumin, β‐lactoglobulin, and bovine serum albumin, propelled by a synergy of hydrophobic interactions, hydrogen bonding, and van der Waals forces, with binding energies noted at −5.59, −6.71, and −7.85 kcal/mol, respectively. An increment in PC concentration is observed to amplify the emulsification properties of WPI whilst concurrently diminishing the zeta potential. This study establishes a theoretical foundation for applying the PC–WPI interaction mechanism in food. [ABSTRACT FROM AUTHOR]

Liquid formula is a research hotspot of infant formula milk, but how to increase the physicochemical stability while maintaining the activity of nutritional components is a key bottleneck in product development. Phosphatidylcholine (PC) and whey protein isolate (WPI) are important components of infant formula, the effect of PC on the properties of WPI stable emulsion remains to be clarified. When the concentration of PC is 0.3 %, a solid intermolecular network is established, which enhances the elasticity and viscosity of the emulsion and has the best oxidation stability and storage stability. 0.3 % PC reduced the flocculation during digestion, and increased the digestibility of protein and fat (27.64 % and 82.45 %). In this study, compound emulsifier (WPI-PC) was used to establish a stable emulsion system, which provided reference for the development and utilization of functional dairy products. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Does abnormal serotonin homeostasis contribute to impaired endometrial decidualization in patients with recurrent implantation failure (RIF)? SUMMARY ANSWER Abnormal serotonin homeostasis in patients with RIF, which is accompanied by decreased monoamine oxidase (MAO) expression, affects the decidualization of endometrial stromal cells and leads to embryo implantation failure. WHAT IS KNOWN ALREADY Previous studies have indicated that the expression of MAO, which metabolizes serotonin, is reduced in the endometrium of patients with RIF, and serotonin can induce disruption of implantation in rats. However, whether abnormal serotonin homeostasis leads to impaired decidualization in patients with RIF and, if so, the mechanism involved, remains unclear. STUDY DESIGN, SIZE, DURATION Endometrial samples from 25 patients with RIF and 25 fertile patients were used to investigate the expression levels of monoamine oxidase A (MAOA), monoamine oxidase B (MAOB), and serotonin. We isolated human endometrial stromal cells to investigate the role of MAOA, MAOB, and serotonin in inducing decidualization in vitro and further explored the underlying mechanism using RNA-sequencing (RNA-seq) and liquid chromatography-mass spectrometry (LC/MS) analyses. PARTICIPANTS/MATERIALS, SETTING, METHODS The levels of serotonin in the endometrium of patients with RIF were detected by ELISA and immunohistofluorescence, and the key genes involved in abnormal serotonin metabolism were analyzed via combination with single-cell sequencing data. The effects of MAOA or MAOB on the decidualization of stromal cells were investigated using an in vitro human endometrial stromal cell-induced decidualization model and a mouse artificially induced decidualization model. The potential mechanisms by which MAOA and MAOB regulate decidualization were explored by RNA-seq and LC/MS analysis. MAIN RESULTS AND THE ROLE OF CHANCE We found that women with RIF have abnormal serotonin metabolism in the endometrium and attenuated MAO in endometrial stromal cells. Endometrial decidualization was accompanied by increased MAO in vivo and in vitro. However attenuated MAO caused an increased local serotonin content in the endometrium, impairing stromal cell decidualization. RNA-seq and LC/MS analyses showed that abnormal lipid metabolism, especially phosphatidylcholine metabolism, was involved in the defective decidualization caused by MAO deficiency. Furthermore, decidualization defects were rescued by phosphatidylcholine supplementation. LARGE SCALE DATA RNA-seq information and raw data can be found at NCBI Bioproject number PRJNA892255. LIMITATIONS, REASONS FOR CAUTION This study revealed that impaired serotonin metabolic homeostasis and abnormally reduced MAO expression were among the reasons for RIF. However, the source and other potential functions of serotonin in the endometrium remain to be further explored. WIDER IMPLICATIONS OF THE FINDINGS This study provides new insights into the mechanisms of serotonin homeostasis in human endometrial decidualization and new biomarkers or targets for the treatment of patients with RIF. STUDY FUNDING/COMPETING INTEREST(S) X. Sheng is supported by grants from the National Natural Science Foundation of China (82001629), the Wenzhou Basic Public Welfare Research Project (Y20240030), the Youth Program of Natural Science Foundation of Jiangsu Province (BK20200116), and Jiangsu Province Postdoctoral Research Funding (2021K277B). H.S. is supported by grants from the National Natural Science Foundation of China (82030040). G.Y. is supported by grants from the National Natural Science Foundation of China (82171653). The authors declare no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women of reproductive age, marked by hormonal imbalances and disruptions in glucose and lipid metabolism. Emerging research has indicated a correlation between lipids and PCOS, yet the specific lipid profiles or associated genes identified in various studies vary, and observational data alone cannot establish causation. Therefore, our study seeks to establish a causal association between lipidome and PCOS.Methods Data from genome-wide association studies, liposomes, metabolites, and PCOS-related information were collected. Four rounds of double-sample bidirectional intermediate Mendelian Randomization analyses including liposomes to disease, liposomes to metabolites, metabolites to disease, and reverse Mendelian Randomization analysis of lipids, total effect values and intermediary effect values were calculated. The proportion mediated by the intermediary effect was determined by dividing the intermediary effect value by the total effect value.Results The analyses revealed that three liposomes and nine metabolites were causally associated with PCOS. Specifically, phosphatidylcholine and 1-Stearoyl-2-Oleoyl-Glycosylphosphatidylinositol were identified as independent risk factors for PCOS through further Mendelian Randomization analysis. The risk of developing PCOS increased by 32% for every one standard deviation increase in phosphatidylcholine and by 17% for every one standard deviation increase in 1-Stearoyl-2-Oleoyl-Glycosylphosphatidylinositol. Furthermore, the study revealed that phosphatidylcholine can influence the development of PCOS with 1-Stearoyl-2-Oleoyl-Glycosylphosphatidylinositol acting as a mediator, explaining 4.97% of the effect.Conclusions This study confirmed a causal relationship between phosphatidylcholine and 1-Stearoyl-2-Oleoyl-Glycosylphosphatidylinositol with PCOS, where phosphatidylcholine can influence the occurrence of PCOS with 1-Stearoyl-2-Oleoyl-Glycosylphosphatidylinositol as a mediator.

As people live longer, the burden of aging-related brain diseases, especially dementia, is increasing. Brain aging increases the risk of cognitive impairment, which manifests as a progressive loss of neuron function caused by the impairment of synaptic plasticity via disrupting lipid homeostasis. Therefore, supplemental dietary lipids have the potential to prevent brain aging. This review summarizes the important roles of dietary lipids in brain function from both structure and mechanism perspectives. Epidemiological and animal studies have provided evidence of the functions of polyunsaturated fatty acids (PUFAs) in brain health. The results of interventions indicate that phospholipids—including phosphatidylcholine, phosphatidylserine, and plasmalogen—are efficient in alleviating cognitive impairment during aging, with plasmalogen exhibiting higher efficacy than phosphatidylserine. Plasmalogen is a recognized nutrient used in clinical trials due to its special vinyl ether bonds and abundance in the postsynaptic membrane of neurons. Future research should determine the dose-dependent effects of plasmalogen in alleviating brain-aging diseases and should develop extraction and storage procedures for its clinical application.

Plasma trimethylamine n-oxide (TMAO) concentration increases in responses to feeding TMAO, choline, phosphatidylcholine, L-carnitine, and betaine but it is unknown whether concentrations change following a mixed macronutrient tolerance test (MMTT) with limited amounts of TMAO precursors. In this proof-of-concept study, we provided healthy female and male adults (n = 97) ranging in age (18-65 years) and BMI (18-44 kg/m2) a MMTT (60% fat, 25% sucrose; 42% of a standard 2000 kilo calorie diet) and recorded their metabolic response at fasting and at 30 min, 3 h, and 6 h postprandially. We quantified total exposure to TMAO (AUC-TMAO) and classified individuals by the blood draw at which they experienced their maximal TMAO concentration (TMAO-response groups). We related AUC-TMAO to the 16S rRNA microbiome, to two SNPs in the exons of the FMO3 gene (rs2266782, G>A, p.Glu158Lys; and rs2266780, A>G, p.Glu308Gly), and to a priori plasma metabolites. We observed varying TMAO responses (timing and magnitude) and identified a sex by age interaction such that AUC-TMAO increased with age in females but not in males (p-value = 0.0112). Few relationships between AUC-TMAO and the fecal microbiome and FMO3 genotype were identified. We observed a strong correlation between AUC-TMAO and TNF-α that depended on TMAO-response group. These findings promote precision nutrition and have important ramifications for the eating behavior of adults who could benefit from reducing TMAO exposure, and for understanding factors that generate plasma TMAO.

Choline is an essential nutrient, with high requirements during fetal and postnatal growth. Tissue concentrations of total choline are tightly regulated, requiring an increase in its pool size proportional to growth. Phosphatidylcholine and sphingomyelin, containing a choline headgroup, are constitutive membrane phospholipids, accounting for >85% of total choline, indicating that choline requirements are particularly high during growth. Daily phosphatidylcholine secretion via bile for lipid digestion and very low-density lipoproteins for plasma transport of arachidonic and docosahexaenoic acid to other organs exceed 50% of its hepatic pool. Moreover, phosphatidylcholine is required for converting pro-apoptotic ceramides to sphingomyelin, while choline is the source of betaine as a methyl donor for creatine synthesis, DNA methylation/repair and kidney function. Interrupted choline supply, as during current total parenteral nutrition (TPN), causes a rapid drop in plasma choline concentration and accumulating deficit. The American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) defined choline as critical to all infants requiring TPN, claiming its inclusion in parenteral feeding regimes. We performed a systematic literature search in Pubmed with the terms "choline" and "parenteral nutrition", resulting in 47 relevant publications. Their results, together with cross-references, are discussed. While studies on parenteral choline administration in neonates and older children are lacking, preclinical and observational studies, as well as small randomized controlled trials in adults, suggest choline deficiency as a major contributor to acute and chronic TPN-associated liver disease, and the safety and efficacy of parenteral choline administration for its prevention. Hence, we call for choline formulations suitable to be added to TPN solutions and clinical trials to study their efficacy, particularly in growing children including preterm infants. [ABSTRACT FROM AUTHOR]

Glycerophospholipids have hydrophobic and hydrophilic moieties. Previous studies suggest that phospholipids with different moieties have different effects on rodent behavior; however, the relationship between chemical structures and behavioral effects remains unclear. To clarify the functions of phospholipid moieties, we injected male rats with phospholipids with different moieties and conducted behavioral tests. Exploratory activity was reduced by phosphatidylethanolamine (PE)(18:0/22:6) but not PE(18:0/18:0) or PE(18:0/20:4). Conversely, exploratory activity was increased by plasmanyl PE(16:0/22:6), which harbors an alkyl–ether linkage, but not by phosphatidylcholine (PC)(16:0/22:6) or plasmanyl PC(16:0/22:6). Docosahexaenoic acid (DHA)(22:6) and an alkyl–ether linkage in PE were thus postulated to be involved in exploratory activity. Anxiety-like behavior was reduced by plasmenyl PC(18:0/20:4), which harbors a vinyl–ether linkage, but not by PC(18:0/20:4) or plasmanyl PC(18:0/20:4), suggesting the anxiolytic effects of vinyl–ether linkage. The activation of social interaction was suppressed by PE(18:0/18:0), PE(18:0/22:6), PC(16:0/22:6), plasmanyl PE(16:0/22:6), and plasmanyl PC(16:0/22:6) but not by PE(18:0/20:4), plasmenyl PE(18:0/20:4), or plasmanyl PC(18:0/22:6). DHA may suppress social interaction, whereas arachidonic acid(20:4) or a combination of alkyl–ether linkage and stearic acid(18:0) may restore social deficits. Our findings indicate the characteristic effects of different phospholipid moieties on rat behavior, and may help to elucidate patterns between chemical structures and their effects. [ABSTRACT FROM AUTHOR]

Monogalactosyldiacylglycerol (MGDG) is the main lipid constituent of thylakoids and a structural component of photosystems and photosynthesis-related proteo-lipid complexes in green tissues. Previously reported changes in MGDG abundance upon stress treatments are hypothesized to reflect mobilization of MGDG-based polyunsaturated lipid intermediates to maintain extraplastidial membrane integrity. While exchange of lipid intermediates between compartmental membranes is well documented, physiological consequences of mobilizing an essential thylakoid lipid, such as MGDG, for an alternative purpose are not well understood. Arabidopsis seedlings exposed to mild (50 mM) salt treatment displayed significantly increased abundance of both MGDG and the extraplastidial lipid, phosphatidylcholine (PC). Interestingly, similar increases in MGDG and PC were observed in Arabidopsis fad3 mutant seedlings defective in endoplasmic reticulum (ER)–localized linolenic acid formation, in which compensatory plastid-to-ER-directed mobilization of linolenic acid–containing intermediates takes place. The postulated (salt) or evident (fad3) plastid–ER exchange of intermediates concurred with altered thylakoid function according to parameters of photosynthetic performance. While salt treatment of wild-type seedlings inhibited photosynthetic parameters in a dose-dependent manner, interestingly, untreated fad3 mutants did not show overall reduced photosynthetic quantum yield. By contrast, we observed a reduction specifically of non-photochemical quenching (NPQ) under high light, representing only part of observed salt effects. The decreased NPQ in the fad3 mutant was accompanied by reduced activity of the xanthophyll cycle, leading to a reduced concentration of the NPQ-effective pigment zeaxanthin. The findings suggest that altered ER-located fatty acid unsaturation and ensuing inter-organellar compensation impacts on the function of specific thylakoid enzymes, rather than globally affecting thylakoid function. [ABSTRACT FROM AUTHOR]

SUMMARY: Rhizobial phosphatidylcholine (PC) is thought to be a critical phospholipid for the symbiotic relationship between rhizobia and legume host plants. A PC‐deficient mutant of Sinorhizobium meliloti overproduces succinoglycan, is unable to swim, and lacks the ability to form nodules on alfalfa (Medicago sativa) host roots. Suppressor mutants had been obtained which did not overproduce succinoglycan and regained the ability to swim. Previously, we showed that point mutations leading to altered ExoS proteins can reverse the succinoglycan and swimming phenotypes of a PC‐deficient mutant. Here, we report that other point mutations leading to altered ExoS, ChvI, FabA, or RpoH1 proteins also revert the succinoglycan and swimming phenotypes of PC‐deficient mutants. Notably, the suppressor mutants also restore the ability to form nodule organs on alfalfa roots. However, nodules generated by these suppressor mutants express only low levels of an early nodulin, do not induce leghemoglobin transcript accumulation, thus remain white, and are unable to fix nitrogen. Among these suppressor mutants, we detected a reduced function mutant of the 3‐hydoxydecanoyl‐acyl carrier protein dehydratase FabA that produces reduced amounts of unsaturated and increased amounts of shorter chain fatty acids. This alteration of fatty acid composition probably affects lipid packing thereby partially compensating for the previous loss of PC and contributing to the restoration of membrane homeostasis. Significance Statement: The membrane lipid phosphatidylcholine (PC) is crucial for the bacterium Sinorhizobium meliloti when generating nitrogen‐fixing nodules on the roots of their host plant. Although PC‐deficient mutants of S. meliloti cannot form any nodules on their host plant, suppressor mutants were isolated which partially recover the ability to trigger nodule formation. Among these suppressor mutants, we detected a reduced function mutant of FabA that produces reduced amounts of unsaturated and increased amounts of shorter chain fatty acids thereby probably affecting lipid packing. [ABSTRACT FROM AUTHOR]

Coronary heart disease, also known as ischemic heart disease, is induced by atherosclerosis, which is initiated by subendothelial retention of lipoproteins. Plasma lipoproteins, including high density lipoprotein, low density lipoprotein (LDL), very low density lipoprotein, and chylomicron, are composed of a surface monolayer containing phospholipids and cholesterol and a hydrophobic core containing triglycerides and cholesteryl esters. Phospholipids play a crucial role in the binding of apolipoproteins and enzymes to lipoprotein surfaces, thereby regulating lipoprotein metabolism. High LDL-cholesterol is a well-known risk factor for coronary heart disease, and statins reduce the risk of coronary heart disease by lowering LDL-cholesterol levels. In contrast, the relationships of phospholipids in plasma lipoproteins with coronary heart disease have not yet been established. To further clarify the physiological and pathological roles of phospholipids, we have developed the simple high-throughput assays for quantifying all major phospholipid classes, namely phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidic acid, phosphatidylinositol, phosphatidylglycerol + cardiolipin, and sphingomyelin, using combinations of specific enzymes and a fluorogenic probe. These enzymatic fluorometric assays will be helpful in elucidating the associations between phospholipid classes in plasma lipoproteins and coronary heart disease and in identifying phospholipid biomarkers. This review describes recent progress in the identification of phospholipid biomarkers of coronary heart disease. [ABSTRACT FROM AUTHOR]

Acute myocardial infarction(AMI) is one of the most common causes of sudden cardiac death, but the accurate AMI identification biomarkers are still lacking. Recently, lipidomics shed new light on the exploration of AMI biomarkers. In this study, lipid molecules were examined in rat myocardial tissue based on Liquid chromatography-tandem mass spectrometry (LC-MS/MS) lipidomics to screen for metabolic markers for the identification of AMI. Results showed that 70 lipid molecules with different expressions identified by distinguishing between the sham group and the AMI 5 min group, 275 differentially expressed lipid molecules identified by distinguishing between the sham group and the AMI 4 hour group. And 257 differentially expressed lipid molecules identified by distinguishing between the AMI 5 min group and the AMI 4 hour group. Comprehensive analysis shows that PC (18:0_18:1)+HCOO and PC (16:0_18:2)+HCOO exhibited more significant changes. Two lipid molecules were applied to build AMI-identification models, the accuracy rate reached 77.8% and R2 = 0.539. [ABSTRACT FROM AUTHOR]

Polysaccharide-based systems have very good emulsifying and stabilizing properties, and starch plays a leading role. Their modifications should add new quality features to the product to such an extent that preserves the structure-forming properties of native starch. The aim of this manuscript was to examine the physicochemical characteristics of the combinations of starch with phospholipids or lysozymes and determine the effect of starch modification (surface hydrophobization or biological additives) and preparation temperature (before and after gelatinization). Changes in electrokinetic potential (zeta), effective diameter, and size distribution as a function of time were analyzed using the dynamic light scattering and microelectrophoresis techniques. The wettability of starch-coated glass plates before and after modification was checked by the advancing and receding contact angle measurements, as well as the angle hysteresis, using the settle drop method as a complement to profilometry and FTIR. It can be generalized that starch dispersions are more stable than analogous n-alkane/starch emulsions at room and physiological temperatures. On the other hand, the contact angle hysteresis values usually decrease with temperature increase, pointing to a more homogeneous surface, and the hydrophobization effect decreases vs. the thickness of the substrate. Surface hydrophobization of starch carried out using an n-alkane film does not change its bulk properties and leads to improvement of its mechanical and functional properties. The obtained specific starch-based hybrid systems, characterized in detail by switchable wettability, give the possibility to determine the energetic state of the starch surface and understand the strength and specificity of interactions with substances of different polarities in biological processes and their applicability for multidirectional use. [ABSTRACT FROM AUTHOR]

We aimed to investigate the associations between maternal intake of folate, vitamin B12, B6, B2, methionine, choline, phosphatidylcholine and betaine during the period surrounding pregnancy and offspring weight outcomes from birth to early adulthood. These associations were examined among 2454 mother–child pairs from the Nurses' Health Study II and Growing Up Today Study. Maternal energy-adjusted nutrient intakes were derived from food frequency questionnaires. Birth weight, body size at age 5 and repeated BMI measurements were considered. Overweight/obesity was defined according to the International Obesity Task Force (<18 years) and World Health Organization guidelines (18+ years). Among other estimands, we report relative risks (RRs) for offspring ever being overweight with corresponding 95% confidence intervals across quintiles of dietary factors, with the lowest quintile as the reference. In multivariate-adjusted models, higher maternal intakes of phosphatidylcholine were associated with a higher risk of offspring ever being overweight (RRQ5vsQ1 = 1.16 [1.01–1.33] p-trend: 0.003). The association was stronger among offspring born to mothers with high red meat intake (high red meat RRQ5vsQ1 = 1.50 [1.14–1.98], p-trend: 0.001; low red meat RRQ5vsQ1 = 1.05 [0.87–1.27], p-trend: 0.46; p-interaction = 0.13). Future studies confirming the association between a higher maternal phosphatidylcholine intake during pregnancy and offspring risk of being overweight or obese are needed. [ABSTRACT FROM AUTHOR]

Purpose: Investigate the association between choline and betaine intake and all-cause mortality in a large Swedish cohort. Methods: Women (52,246) and men (50,485) attending the Västerbotten Intervention Programme 1990–2016 were included. Cox proportional hazard regression models adjusted for energy intake, age, BMI, smoking, education, and physical activity were used to estimate mortality risk according to betaine, total choline, phosphatidylcholine, glycerophosphocholine, phosphocholine, sphingomyelin, and free choline intakes [continuous (per 50 mg increase) and in quintiles]. Results: During a median follow-up of 16 years, 3088 and 4214 deaths were registered in women and men, respectively. Total choline intake was not associated with all-cause mortality in women (HR 1.01; 95% CI 0.97, 1.06; P = 0.61) or men (HR 1.01; 95% CI 0.98, 1.04; P = 0.54). Betaine intake was associated with decreased risk of all-cause mortality in women (HR 0.95; 95% CI 0.91, 0.98; P < 0.01) but not in men. Intake of free choline was negatively associated with risk of all-cause mortality in women (HR 0.98; 95% CI 0.96, 1.00; P = 0.01). No other associations were found between intake of the different choline compounds and all-cause mortality. In women aged ≥ 55 years, phosphatidylcholine intake was positively associated with all-cause mortality. In men with higher folate intake, total choline intake was positively associated with all-cause mortality. Conclusion: Overall, our results do not support that intake of total choline is associated with all-cause mortality. However, some associations were modified by age and with higher folate intake dependent on sex. Higher intake of betaine was associated with lower risk of all-cause mortality in women. [ABSTRACT FROM AUTHOR]

This study investigated the incorporation of nervonic acid into the chemical structure of phosphatidylcholine via a lipase-catalyzed acidolysis reaction to obtain a functional phospholipid. Lipase immobilization was conducted, and Amberlite XAD7-HP was selected as a carrier to immobilize phospholipase A1 (PLA1) for subsequent experiments. The main acidolysis reaction parameters, including enzyme load, substrate ratio, temperature, and water content, were studied against the reaction time. The optimum reaction conditions obtained were enzyme load, 20%; reaction temperature, 55 °C; water content, 1%; and reaction time, 9 h. The maximum incorporation of nervonic acid into phosphatidylcholine was 48 mol%, with PC recovery at 61.6 mol%. The positional distribution of structured phosphatidylcholine shows that nervonic acid was found in the sn-1 position due to enzyme specificity and in the sn-2 position, possibly due to acyl migration. [ABSTRACT FROM AUTHOR]

In this study, the phospholipid species [i.e., phosphatidylethanolamine (PE), phosphatidylcholine (PC), and sphingomyelin (SM)] in human milk (HM) were compared according to their fatty acid (FA) composition. 34 HM samples were collected and classified into three groups (A < B < C) according to their fat content. Stearic acid (C18:0) was the main FA in PE, PC, and SM. The highest concentrations of arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosapentaenoic acid (DPA) were observed in PE, whereas docosahexaenoic acid (DHA) was predominant in SM. Although PC exhibited the highest total saturated FAs (SFAs) and PE contained the highest unsaturated FAs (UFAs), very long-chain SFAs and monounsaturated FAs (MUFAs) were preferentially distributed in SM. PC and SM had higher saturation compared to PE. Regarding the effect of the fat content of HM on the FA composition of the phospholipid species, a limited influence was observed on the composition of SFAs and MUFAs of PE, SM, and particularly PC. However, a more pronounced effect on the composition of polyunsaturated FAs (PUFAs) in phospholipids was observed, especially for linoleic acid (LA), α-linolenic acid (ALA), EPA, and DHA, indicating that the composition of FAs in the phospholipid species was probably affected by the maternal diet. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the impact of physical solid dispersions of spray-dried glibenclamide (SG) on the surface of microcrystalline cellulose (MC) and mannitol (M) surfaces, as well as their combination with phosphatidylcholine (P), on enhancing the dissolution rate of glibenclamide (G). Solid dispersions were prepared using varying proportions of 1:1, 1:4, and 1:10 for SG on the surface of MC (SGA) and M (SGM), and then combined with P, in a proportion of 1:4:0.02 using spray drying. The particle size, specific surface area, scanning electron microscopy (SEM), X-ray diffraction (XRD), and dissolution rate of SGA and SGM were characterized. SEM analysis revealed successful adhesion of SG onto the surface of the carrier surfaces. XRD showed reduced crystalline characteristic peaks for SGA, while SGM exhibited a sharp peaks pattern. Both SGA and SGM demonstrated higher dissolution rates compared to SG and G alone. Furthermore, the dissolution rates of the solid dispersions of SG, MC and P (SGAP), and SG, M, and P (SGMP) were sequentially higher than that of SGA and SGM. The study suggests that physical solid dispersions of SG on MC and M, along with their combination with P, can effectively enhance the dissolution rate of G. These findings may be valuable in developing of oral solid drug dosage forms utilizing SGA, SGM, SGAP, and SGMP. [ABSTRACT FROM AUTHOR]

X-ray diffraction was used to study oriented films formed from solutions in chloroform of egg phosphatidylcholine, the synthetic hybrid antioxidant ICHPHAN-10-C-10, and their mixtures containing 12.5 and 32 wt % of ICHPHAN. The air-dried films obtained from phosphatidylcholine and ICHPHAN were multiphase and, in addition to nonlayered lipid phases, contained the crystalline phase of ICHPHAN. With an increase in the degree of hydration of such films, the formation of a single lamellar phase consisting of lipids and ICHPHAN occurred in them. The appearance and disappearance of the crystalline phase of ICHPHAN in the films with a change in their degree of hydration was reversible. The electron density profiles of lipid membranes calculated with a resolution of ~1.2 nm showed that in the presence of ICHPHAN, the membrane thickness was reduced and the ordering of lipid hydrocarbon chains in it decreased. The results we obtained indicated the ability of ICHPHAN to integrate from the crystalline phase into lipid membranes in large quantities. [ABSTRACT FROM AUTHOR]

PurposeThe COVID-19 pandemic has led to millions of confirmed cases worldwide, resulting in numerous deaths and hospitalizations. Long-term symptoms after infection or vaccination, known as Post-acute COVID-19 Syndrome (PACS) or Post-acute COVID-19 Vaccination Syndrome (PACVS), present a challenge for the healthcare system. Among the various neurological symptoms, cognitive impairments are frequently observed in PACS/PACVS patients. This study aimed to understand cognitive deficits in PACS/PACVS patients and evaluated potential treatment options, including phosphatidylcholine and computer-assisted cognitive training (CCT).MethodsThe Neuro-COVID Outpatient Clinic at Evangelic Hospital Vienna evaluated n = 29 PACS/PACVS patients from May 2023 to October 2023. Enrolled patients were divided into three therapy schemes: Group A received phosphatidylcholine, B received phosphatidylcholine plus access to a computer-assisted cognitive training program, and C (divided into two subgroups) served as a control group. Cognitive impairments were evaluated in multiple assessments (initial and during therapy) using the COGBAT test. Simultaneously, an assessment of the quality of life was conducted using the WHOQOL-BREF.ResultsPrimary cognitive impairments, especially attentional deficits were notably evident compared to the general population. While all treatment groups showed cognitive improvement (significant or with a positive trend, but without reaching the level of statistical significance) after therapy, no significant interaction was found between assessment time points and treatment schemes for overall cognitive performance, attention, memory, and executive functions, suggesting consistency across the groups. The WHOQOL-BREF primarily demonstrated deficits in the domains of physical health and psychological well-being.ConclusionThis study examined the impact of PACS/PACVS on cognitive performance and evaluated phosphatidylcholine and CCT as potential treatment options. Patients with PACS/PACVS showed notable cognitive deficits, especially in the domain attention. While the effectiveness of phosphatidylcholine and CCT in treating cognitive deficits was inconclusive, the study indicated the possibility of spontaneous remission of cognitive deficits in PACS/PACVS.

INTRODUCTION: Although Staphylococcus aureus is the leading cause of biofilm-related infections, the lipidomic distributions within these biofilms is poorly understood. Here, lipidomic mapping of S. aureus biofilm cross-sections was performed to investigate heterogeneity between horizontal biofilm layers. METHODS: S. aureus biofilms were grown statically, embedded in a mixture of carboxymethylcellulose/gelatin, and prepared for downstream matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS). Trapped ion mobility spectrometry (TIMS) was also applied prior to mass analysis. RESULTS: Implementation of TIMS led to a ∼ threefold increase in the number of lipid species detected. Washing biofilm samples with ammonium formate (150 mM) increased signal intensity for some bacterial lipids by as much as tenfold, with minimal disruption of the biofilm structure. MALDI TIMS IMS revealed that most lipids localize primarily to a single biofilm layer, and species from the same lipid class such as cardiolipins CL(57:0) - CL(66:0) display starkly different localizations, exhibiting between 1.5 and 6.3-fold intensity differences between layers (n = 3, p

Non-alcoholic metabolic-associated steatohepatitis (MASH) is a condition characterized by increasingly high prevalence and incidence, and also represents an important unmet medical need when it comes to effective pharmacotherapy. In this work, we aimed to explore the therapeutic possibilities of the synergistic combined use of glycyrrhizinic acid (GA) and phosphatidylcholine (PC) to prevent experimental MASH. Adult C57Bl/6 mice were used to model dietary/toxic MASH and treated orally by either GA (34.3 mg/kg/d) or a GA + PC combination (34.3 + 158.1 mg/kg/d) for 3 months. Animal locomotion, behaviour, short-term memory, physical performance, neuromuscular joint function, blood biochemistry, and oxidative stress marker levels were evaluated, followed by histological examination of the liver, skeletal muscle and sciatic nerve with tissue ammonia and lipid content determination. Real-time polymerase chain reaction was used to measure the relative expression of several pathogenetic transcript markers. GA and PC showed moderate additive synergism in their anti-inflammatory, antioxidant, hypoammonaemic, hypoglycaemic, and pro-cognitive activities. Differential effects of the agents were seen in regard to anxiety- and depression-like behaviour as well as gene expression. Our results indicate partial pharmacological synergism between GA and PC and validate further research of its potential clinical applications.

Background & Aims: Changes in phosphatidylcholine levels in the liver have been associated with the development of metabolic dysfunction–associated steatotic liver disease. Here, the effects of supplementing phosphatidylcholine on the development of early signs of metabolic dysfunction–associated steatohepatitis were assessed. Methods: Male and female C57BL/6J mice were fed a liquid control or a fructose-, fat-, and/or cholesterol-rich diet for 7 or 8 weeks. The diets of female mice were fortified ± phosphatidylcholine (12.5 mg/g diet). In liver tissue and portal blood, indices of liver damage, inflammation, and bacterial endotoxemia were measured. J774A.1 cells and human monocytes preincubated with phosphatidylcholine (0.38 mmol/L) were challenged with lipopolysaccharide (50–100 ng/mL) ± the peroxisome proliferator-activated receptor γ (PPARγ) activator pioglitazone (10 μmol/L) or ± a liver receptor homolog 1 (LRH-1) antagonist 1-(3′-[1-(2-[4-morpholinyl]ethyl)-1H-pyrazol-3-yl]-3-biphenylyl)ethanon (1–10 μmol/L). Results: In fructose-, fat-, and/or cholesterol-rich diet–fed mice the development of fatty liver and the beginning of inflammation were associated with significantly lower hepatic phosphatidylcholine levels when compared with controls. Supplementing phosphatidylcholine significantly attenuated the development of fatty liver and inflammation, being associated with protection against the induction of PPARγ2, and activation of nuclear factor of κ light polypeptide gene enhancer in B-cell inhibitor α whereas Lrh1 expression was unchanged. The protective effects of phosphatidylcholine on the lipopolysaccharide-induced activation of J774A.1 cells and human monocytes were attenuated significantly by the PPARγ activator pioglitazone and the LRH-1 antagonist. Conclusions: Our data suggest that phosphatidylcholine levels in the liver are lower in early metabolic dysfunction–associated steatohepatitis in mice and that supplementation of phosphatidylcholine can diminish the development of metabolic dysfunction–associated steatotic liver disease through mechanisms involving LRH-1/PPARγ2/ nuclear factor κ-light-chain enhancer of activated B-cell signaling.

This study aimed to evaluate the effects of supplementation with a polyherbal phytogenic additive (PPA) on the productive performance, dietary energetics, blood metabolites, carcass traits, meat quality, and gene expression of finishing lambs. Thirty-six male Pelibuey lambs (23.61 ± 0.57 kg body weight (BW)) were housed in individual pens and assigned to four treatments (n = 9) with different doses of PPA: 0 (CON), 2.5 (PPAL), 5 (PPAM), and 7.5 (PPAH) g of PPA/kg of DM for 56 days. Average daily gain, dry matter intake, and observed dietary net energy for maintenance and weight gain increased linearly (p < 0.05) in lambs supplemented with PPAH. A linear reduction (p = 0.02) in FCR was detected in lambs fed PPAM and PPAH. The PPAH supplementation linearly increased (p < 0.001) Longissimus dorsi muscle area, but other carcass traits were not affected (p > 0.05) by PPA doses. The physicochemical characteristics of the meat and the hematological parameters of the lambs were not affected (p > 0.05) by the PPA doses. The glucose, uric acid, creatinine, and bilirubin serum concentrations decreased linearly (p < 0.05) in lambs supplemented with PPAM and PPAH. Gene ontology analyses showed that nine biological processes were modified (p < 0.05), including DNA replication, drug metabolism–cytochrome P450, oxidative phosphorylation, and chemical carcinogenesis–reactive oxygen species. In conclusion, high doses (7.5 g/kg DM) of PPA can improve growth performance and dietary energy utilization efficiency in finishing lambs. Likewise, gene expression analysis indicates that supplementation with high doses of PPA could improve energy production and antioxidant status in finishing lambs.

Non-alcoholic metabolic-associated steatohepatitis (MASH) is a condition characterized by increasingly high prevalence and incidence, and also represents an important unmet medical need when it comes to effective pharmacotherapy. In this work, we aimed to explore the therapeutic possibilities of the synergistic combined use of glycyrrhizinic acid (GA) and phosphatidylcholine (PC) to prevent experimental MASH. Adult C57Bl/6 mice were used to model dietary/toxic MASH and treated orally by either GA (34.3 mg/kg/d) or a GA + PC combination (34.3 + 158.1 mg/kg/d) for 3 months. Animal locomotion, behaviour, short-term memory, physical performance, neuromuscular joint function, blood biochemistry, and oxidative stress marker levels were evaluated, followed by histological examination of the liver, skeletal muscle and sciatic nerve with tissue ammonia and lipid content determination. Real-time polymerase chain reaction was used to measure the relative expression of several pathogenetic transcript markers. GA and PC showed moderate additive synergism in their anti-inflammatory, antioxidant, hypoammonaemic, hypoglycaemic, and pro-cognitive activities. Differential effects of the agents were seen in regard to anxiety- and depression-like behaviour as well as gene expression. Our results indicate partial pharmacological synergism between GA and PC and validate further research of its potential clinical applications. [ABSTRACT FROM AUTHOR]

The coming of the hyper-aged society in Taiwan prompts us to investigate the relationship between the metabolic status of sarcopenic patients and their most adverse outcome–death. We studied the association between any plasma metabolites and the risk for mortality among older Taiwanese sarcopenic patients. We applied a targeted metabolomic approach to study the plasma metabolites of adults aged ≥65 years, and identified the metabolic signature predictive of the mortality of sarcopenic patients who died within a 5.5-year follow-up period. Thirty-five sarcopenic patients who died within the follow-up period (Dead cohort) had shown a specific plasma metabolic signature, as compared with 54 patients who were alive (Alive cohort). Only 10 of 116 non-sarcopenic individuals died during the same period. After multivariable adjustment, we found that sex, hypertension, tetradecanoyl-carnitine (C14-carnitine), and docosahexaenoic acid (DHA)-containing phosphatidylcholine diacyl (PCaa) C38:6 and C40:6 were important risk factors for the mortality of sarcopenic patients. Low PCaa C38:6 levels and high C14-carnitine levels correlated with an increased mortality risk; this was even the same for those patients with hypertension (HTN). Our findings suggest that plasma PCaa C38:6 and acylcarnitine C14-carnitine, when combined, can be a better early biomarker for evaluating the mortality risk of sarcopenia patients. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) is a global public health issue characterized by excess weight, abdominal obesity, dyslipidemia, hyperglycemia, and a progressive increase in insulin resistance. Human population studies of T2D development and its effects on systemic metabolism are confounded by many factors that cannot be controlled, complicating the interpretation of results and the identification of early biomarkers. Aged, sedentary, and overweight/obese non-human primates (NHPs) are one of the best animal models to mimic spontaneous T2D development in humans. We sought to identify and distinguish a set of plasma and/or fecal metabolite biomarkers, that have earlier disease onset predictability, and that could be evaluated for their predictability in subsequent T2D studies in human cohorts. In this study, a single plasma and fecal sample was collected from each animal in a colony of 57 healthy and dysmetabolic NHPs and analyzed for metabolomics and lipidomics. The samples were comprehensively analyzed using untargeted and targeted LC/MS/MS. The changes in each animal's disease phenotype were monitored using IVGTT, HbA1c, and other clinical metrics, and correlated with their metabolic profile. The plasma and fecal lipids, as well as bile acid profiles, from Healthy, Dysmetabolic (Dys), and Diabetic (Dia) animals were compared. Following univariate and multivariate analyses, including adjustments for weight, age, and sex, several plasma lipid species were identified to be significantly different between these animal groups. Medium and long-chain plasma phosphatidylcholines (PCs) ranked highest at distinguishing Healthy from Dys animals, whereas plasma triglycerides (TG) primarily distinguished Dia from Dys animals. Random Forest (RF) analysis of fecal bile acids showed a reduction in the secondary bile acid glycoconjugate, GCDCA, in diseased animals (AUC 0.76[0.64, 0.89]). Moreover, metagenomics results revealed several bacterial species, belonging to the genera Roseburia, Ruminococcus, Clostridium, and Streptococcus, to be both significantly enriched in non-healthy animals and associated with secondary bile acid levels. In summary, our results highlight the detection of several elevated circulating plasma PCs and microbial species associated with fecal secondary bile acids in NHP dysmetabolic states. The lipids and metabolites we have identified may help researchers to differentiate individual NHPs more precisely between dysmetabolic and overtly diabetic states. This could help assign animals to study groups that are more likely to respond to potential therapies where a difference in efficacy might be anticipated between early vs. advanced disease. [ABSTRACT FROM AUTHOR]