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Objective: Isoflurane, a widely used common inhalational anesthetic agent, can induce brain toxicity. The challenge lies in protecting neurologically compromised patients from neurotoxic anesthetics. Choline alfoscerate (L-α-Glycerophosphorylcholine, α-GPC) is recognized for its neuroprotective properties against oxidative stress and inflammation, but its optimal therapeutic window and indications are still under investigation. This study explores the impact of α-GPC on human astrocytes, the most abundant cells in the brain that protect against oxidative stress, under isoflurane exposure. Methods: This study was designed to examine changes in factors related to isoflurane-induced toxicity following α-GPC administration. Primary human astrocytes were pretreated with varying doses of α-GPC (ranging from 0.1 to 10.0 μM) for 24 hours prior to 2.5% isoflurane exposure. In vitro analysis of cell morphology, water-soluble tetrazolium salt-1 assay, quantitative real-time polymerase chain reaction, proteome profiler array, and transcriptome sequencing were conducted. Results: A significant morphological damage to human astrocytes was observed in the group that had been pretreated with 10.0 mM of α-GPC and exposed to 2.5% isoflurane. A decrease in cell viability was identified in the group pretreated with 10.0 μM of α-GPC and exposed to 2.5% isoflurane compared to the group exposed only to 2.5% isoflurane. Quantitative real-time polymerase chain reaction revealed that mRNA expression of heme-oxygenase 1 and hypoxia-inducible factor-1α, which were reduced by isoflurane, was further suppressed by 10.0 μM α-GPC pretreatment. The proteome profiler array demonstrated that α-GPC pretreatment influenced a variety of factors associated with apoptosis induced by oxidative stress. Additionally, transcriptome sequencing identified pathways significantly related to changes in isoflurane-induced toxicity caused by α-GPC pretreatment. Conclusion: The findings suggest that α-GPC pretreatment could potentially enhance the vulnerability of primary human astrocytes to isoflurane-induced toxicity by diminishing the expression of antioxidant factors, potentially leading to amplified cell damage. [ABSTRACT FROM AUTHOR]

To evaluate the safety of alpha-glycerylphosphorylcholine (α-GPC) as a novel food, the study of acute oral toxicity, subchronic toxicity, teratogenic toxicity and genotoxicity were conducted. In acute oral toxicity, no toxic effects were observed in rats of both genders administrated 10.0 g/kg BW α-GPC. In 90-day oral toxicity, female high-dose group (2,000 mg/kg) had lower body weight, body weight gain, empty stomach body weight, total protein (TP), albumin (ALB), and higher alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) in contrast to control group. In teratogenic toxicity, the body weights of pregnant rats on the 9th day (d9), the 12th day (d12), the 15th day (d15), and the 20th day (d20), body weight gains, and net body weight gains in high-dose group (2,000 mg/kg) decreased, the other parameters had no difference compared to control group. In genotoxicity tests (Mammalian erythrocyte micronucleus, Chromosome aberration and Ames test), all dose groups didn't display significant change compared with negative control group. Based on above results, α-GPC is actually low hazard novel food, has a NOAEL of 1,000 mg/kg BW for female rats and 2,000 mg/kg BW for male rats following 13-week oral exposure, has a NOAEL of 1,000 mg/kg BW for pregnant rats and 2,000 mg/kg BW for fetal rats in teratogenic toxicity, has no genotoxicity in vitro or in vivo. [ABSTRACT FROM AUTHOR]

Glycerylphosphorylcholine (GPC) was prepared by transesterification using supported sodium methoxide as catalyst and natural lecithin as raw material. Sodium methoxide has been proved to be an effective catalyst for the preparation of GPC, which is easy to recover and reuse. After six repeated uses, its stability is satisfactory. The effects of agitation speed, catalyst dosage, and reaction temperature on the reaction were investigated, respectively, and the optimum conditions for preparing GPC catalyzed by supported sodium methoxide were found: the concentration of phosphorylcholine was 0.1 mol·L−1, the stirring speed was 600 rpm, the amount of catalyst was 7.5 g·L−1, the reaction temperature was 45°C, and the reaction time was 4 h; then, the conversion rate of phosphatidylcholine could reach 99%. At the same time, the reaction kinetic model was established based on the mechanism of the transesterification, and the experimental data were compared with the calculated values; it was found that the experimental data fitted the model well. Finally, the reaction activation energy obtained by the Arrhenius equation is 41.6 kJ·mol−1, which indicates that the supported sodium methoxide has good catalytic performance in this reaction system.

Amyloid formation by islet amyloid polypeptide (IAPP) contributes to β-cell dysfunction in type 2 diabetes. Perturbation of the β-cell membrane may contribute to IAPP-induced toxicity. We examine the effects of lipid composition, salt, and buffer on IAPP amyloid formation and on the ability of IAPP to induce leakage of model membranes. Even low levels of anionic lipids promote amyloid formation and membrane permeabilization. Increasing the percentage of the anionic lipids, 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-l-serine (POPS) or 1,2-dioleoyl-sn-glycero-3-phospho(1'-rac-glycerol), enhances the rate of amyloid formation and increases the level of membrane permeabilization. The choice of zwitterionic lipid has no noticeable effect on membrane-catalyzed amyloid formation but in most cases affects leakage, which tends to decrease in the following order: 1,2-dioleoyl-sn-glycero-3-phosphocholine > 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine > sphingomyelin. Uncharged lipids that increase the level of membrane order weaken the ability of IAPP to induce leakage. Leakage is due predominately to pore formation rather than complete disruption of the vesicles under the conditions used in these studies. Cholesterol at or below physiological levels significantly reduces the rate of vesicle-catalyzed IAPP amyloid formation and decreases the susceptibility to IAPP-induced leakage. The effects of cholesterol on amyloid formation are masked by 25 mol % POPS. Overall, there is a strong inverse correlation between the time to form amyloid and the extent of vesicle leakage. NaCl reduces the rate of membrane-catalyzed amyloid formation by anionic vesicles, but accelerates amyloid formation in solution. The implications for IAPP membrane interactions are discussed, as is the possibility that the loss of phosphatidylserine asymmetry enhances IAPP amyloid formation and membrane damage in vivo via a positive feedback loop.

A two-stage enzymatic hydrolysis method, in which phospholipase A1 (PLA1) was added after phospholipase A2 (PLA2) was added for a certain time, was successfully carried out to prepare glycerylphosphorylcholine (GPC) from soybean concentrated phospholipid. Effects of reaction variables on hydrolysis reaction were optimized using response surface methodology, and the optimal conditions were as follows: PLA2 load of 1.25%, PLA1 load of 0.70%, substrate concentration of 13%, reaction temperature of 41°C, and stirring rate of 680 rpm. Under the optimal conditions, the GPC yield reached 83.07%, which is close to the predicted value by the fitted model. This paper not only provides an efficient and low-cost method to prepare GPC, but also improves the high-value utilization of soybean concentrated phospholipid. [ABSTRACT FROM AUTHOR]

Histone deacetylase (HDAC) inhibitors have emerged as effective antineoplastic agents in the clinic. Studies from our lab and others have reported that magnetic resonance spectroscopy (MRS)-detectable phosphocholine (PC) is elevated following SAHA treatment, providing a potential noninvasive biomarker of response. Typically, elevated PC is associated with cancer while a decrease in PC accompanies response to antineoplastic treatment. The goal of this study was therefore to elucidate the underlying biochemical mechanism by which HDAC inhibition leads to elevated PC. We investigated the effect of SAHA on MCF-7 breast cancer cells using (13)C MRS to monitor [1,2-(13)C] choline uptake and phosphorylation to PC. We found that PC synthesis was significantly higher in treated cells, representing 154±19% of control. This was within standard deviation of the increase in total PC levels detected by (31)P MRS (129±7% of control). Furthermore, cellular choline kinase activity was elevated (177±31%), while cytidylyltransferase activity was unchanged. Expression of the intermediate-affinity choline transporter SLC44A1 and choline kinase α increased (144% and 161%, respectively) relative to control, as determined by mRNA microarray analysis with protein-level confirmation by Western blotting. Taken together, our findings indicate that the increase in PC levels following SAHA treatment results from its elevated synthesis. Additionally, the concentration of glycerophosphocholine (GPC) increased significantly with treatment to 210±45%. This is likely due to the upregulated expression of several phospholipase A2 (PLA2) isoforms, resulting in increased PLA2 activity (162±18%) in SAHA-treated cells. Importantly, the levels of total choline (tCho)-containing metabolites, comprised of choline, PC and GPC, are readily detectable clinically using (1)H MRS. Our findings thus provide an important step in validating clinically translatable non-invasive imaging methods for follow-up diagnostics of HDAC inhibitor treatment.

L-α-glyceryl phosphorylcholine, also referred to as choline ethanol phosphate and phosphocholine glycerophosphate, is a naturally occurring metabolite of water-soluble phospholipids in animals. This molecular property is important for informing the crystallization and purification of drugs. The solubility of L-α-glyceryl phosphorylcholine was determined in ten pure solvents and three mixed solvents under atmospheric pressure. The experimental results indicate that L-α-glyceryl phosphorylcholine is most soluble in methanol and least soluble in acetone. Additionally, the solubility of L-α-glyceryl phosphorylcholine was found to increase with temperature within the experimental range. Furthermore, the solubility of L-α-glyceryl phosphorylcholine in binary solvents is dependent on the proportion of positive solvent and temperature. The solubility of L-α-glyceryl phosphorylcholine increases with the proportion of positive solvent. XRD and DSC results indicate that the crystal form of L-α-glyceryl phosphorylcholine remains unchanged before and after dissolution in the reagent, and its melting point temperature is 413.15 K. Various models, including the modified Apelblat model, λh model, Jouyban-Acree model, SUN model, and CNIBS/R-K model, were used to fit the solubility data of L-α-glyceryl phosphorylcholine in different solvents. The study found that the modified Apelblat model and CNIBS/R-K model were the most appropriate for fitting the data. The KAT-LSER model was used to analyze the molecular interactions between solvents and solutes, revealing that the solvent step method with non-specific polarity/polarization interaction had the greatest impact on solubility., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Certain odors have been shown not only to cause health problems and stress but also to affect skin barrier function. Therefore, it is important to understand olfactory masking to develop effective fragrances to mask malodors. However, olfaction and olfactory masking mechanisms are not yet fully understood. To understand the mechanism of the masking effect that has been studied, the responses of several target substance (TS) molecules-1,2-dioleoyl- sn -glycero-3-phosphocholine (DOPC) mixed molecular layers to odorant (OD) molecules were examined as a simple experimental model of epithelial cellular membranes injured by TS molecules. Here, we examined trans -2-nonenal, 1-nonanal, trans -2-decenal, and 1-decanal as TS molecules to clarify the effects of double bonds and hydrocarbon chain lengths on the phospholipid molecular layer. In addition, benzaldehyde and cyclohexanecarboxaldehyde were utilized as OD molecules to clarify the masking effect of the aromatic ring. Surface pressure ( Π )-area ( A ) isotherms were measured to clarify the adsorption or desorption of TS and OD molecules on the DOPC molecular layer. In addition, Fourier transform infrared spectroscopy was performed to clarify the interactions among DOPC, TS, and OD molecules. We found that TS molecules with and without double bonds had different effects on the DOPC molecular layer and that molecules with shorter chain lengths had greater effects on the DOPC molecular layer. Furthermore, OD molecules with aromatic rings counteracted the effects of the TS molecules. On the basis of this research, not only a detailed mechanism by which odor molecules affect lipid membranes without mediating olfactory receptors is elucidated but also more effective OD molecules with masking effects are proposed.

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., (© 2024. The Author(s).)

Background: Orthostatic intolerance, which includes vasovagal syncope and postural orthostatic tachycardia syndrome, is common in children and adolescents. Elevated plasma homocysteine levels might participate in the pathogenesis of orthostatic intolerance. This study was designed to analyze the plasma metabolomic profile in orthostatic intolerance children with high levels of plasma homocysteine., Methods: Plasma samples from 34 orthostatic intolerance children with a plasma homocysteine concentration > 9 µmol/L and 10 healthy children were subjected to ultra-high-pressure liquid chromatography and quadrupole-time-of-flight mass spectrometry analysis., Results: A total of 875 metabolites were identified, 105 of which were significantly differential metabolites. Choline, 1-stearoyl-2-linoleoyl-sn-glycero-3-phosphocholine, 1-(1Z-octadecenyl)-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine, histidine, isocitric acid, and DL-glutamic acid and its downstream metabolites were upregulated, whereas 1-palmitoyl-sn-glycero-3-phosphocholine, 1-stearoyl-sn-glycerol 3-phosphocholine, sphingomyelin (d18:1/18:0), betaine aldehyde, hydroxyproline, and gamma-aminobutyric acid were downregulated in the orthostatic intolerance group compared with the control group. All these metabolites were related to choline and glutamate. Heatmap analysis demonstrated a common metabolic pattern of higher choline, 1-stearoyl-2-linoleoyl-sn-glycero-3-phosphocholine, and DL-glutamic acid, and lower sphingomyelin (d18:1/18:0), 1-stearoyl-sn-glycerol 3-phosphocholine, and 1-palmitoyl-sn-glycero-3-phosphocholine in patients with certain notable metabolic changes (the special group) than in the other patients (the common group). The maximum upright heart rate, the change in heart rate from the supine to the upright position, and the rate of change in heart rate from the supine to the upright position of vasovagal syncope patients were significantly higher in the special group than in the common group (P < 0.05). Choline, 1-stearoyl-2-linoleoyl-sn-glycero-3-phosphocholine, and DL-glutamic acid were positively correlated with the rate of change in heart rate from the supine to the upright position in vasovagal syncope patients (P < 0.05)., Conclusions: The levels of choline-related metabolites and glutamate-related metabolites changed significantly in orthostatic intolerance children with high levels of plasma homocysteine, and these changes were associated with the severity of illness. These results provided new light on the pathogenesis of orthostatic intolerance., (© 2024. The Author(s).)

This study aimed to characterize the composition of lipids in the red blood cells (RBCs) of adolescent swimmers and correlate this lipidome with the aerobic performance of the athletes. Five experimental assessments were performed by 37 adolescent swimmers. During the first session, the athletes went to the laboratory facility for venous blood sampling. The critical velocity protocol was conducted over the 4 subsequent days to measure aerobic performance (CV), comprising maximal efforts over distances of 100, 200, 400, and 800 m in a swimming pool. RBCs were obtained and extracted for analysis using the liquid chromatography-high resolution mass spectrometry untargeted approach. A total of 2146 ions were detected in the RBCs, of which 119 were identified. The enrichment pathway analysis indicated intermediary lipids in the glycerophospholipid, glycerolipid, sphingolipid, linoleic acid, and alpha-linolenic metabolisms, as well as pentose and glucuronate interconversions. A significant impact of the intermediary lipids was observed for the glycerophospholipid metabolism, including phosphatidylethanolamine (PE), phosphatidylcholine (PC), 1-acyl-sn-glycero-3-phosphocholine, sn-glycerol 3-phosphate, and phosphatidic acid. Inverse and significant associations were observed for PE 18:2/18:3 (r = -0.39; p = 0.015), PC 18:3/20:0 (r = -0.33; p = 0.041), and phosphatidic acid 18:0/0:0 (r = -0.47; p = 0.003) with aerobic performance. Swimmers who exhibited higher levels of aerobic performance also had the lowest abundance of PE, PC, and phosphatidic acid.

Since the membrane fluidity controls the cellular functions, it is important to identify the factors that determine the cell membrane viscosity. Cell membranes are composed of not only lipids and proteins but also polysaccharide chain-anchored molecules, such as glycolipids. To reveal the effects of grafted polymers on the membrane fluidity, in this study, we measured the membrane viscosity of polymer-grafted giant unilamellar vesicles (GUVs), which were prepared by introducing the poly (ethylene glycol) (PEG)-anchored lipids to the ternary GUVs composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), and cholesterol. The membrane viscosity was obtained from the velocity field on the GUV generated by applying a point force, based on the hydrodynamic model proposed by Henle and Levine. The velocity field was visualized by a motion of the circular liquid ordered (L o ) domains formed by a phase separation. With increasing PEG density, the membrane viscosity of PEG-grafted GUVs increased gradually in the mushroom region and significantly in the brush region. We propose a hydrodynamic model that includes the excluded volume effect of PEG chains to explain the increase in membrane viscosity in the mushroom region. This work provides a basic understanding of how grafted polymers affect the membrane fluidity., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Background: Nutrition plays a key role in training and athletic performance and dietary supplements can make a small, but potentially valuable, contribution to achieving peak athletic performance. This study is the first to investigate the effects of supplementation from the combination of BCAAs, L-citrulline, and A-GPC on exercise performance., Methods: In this randomized, double-blind, crossover study 30 male trained cyclists (age: 43.7 ± 8.5 years) completed a 20 km cycling time trial (TT) test and a high intensity endurance cycling (HIEC) test following a 7-day supplementation period with either a supplement containing 8 g BCAAs, 6 g L-citrulline, and 300 mg A-GPC or a placebo (15 g maltodextrin). For each trial, mean values for time to completion, peak and average power output, OMNI rating of perceived exertion, and visual analogue scale (VAS) responses on perceived exertion were computed for the 20 km TT test. Mean values for time to fatigue and VAS responses on perceived exertion were computed for the HIEC test. Procedures for dietary intake and exercise patterns were implemented to achieve consistency throughout the study period., Results: There was a significant increase ( p  = .003) in peak power in the 20 km TT (354.27 ± 87.88 and 321.67 ± 63.65, for supplement and placebo trials, respectively) and a significant increase ( p  = .001) in time to fatigue in the HIEC test (0:19:49 ± 0:11:13 min and 0:14:33 ± 0:09:59 min, for supplement and placebo trials, respectively) with the test supplement compared to the placebo. With the test supplement, there was an average increase in TT peak power of 11% and an average increase in time to fatigue of 36.2% in the HIEC test compared to the placebo. There was no significant improvement in time to completion, average power, OMNI rating of perceived exertion, or VAS responses on perceived exertion in the TT test and no significant improvement in VAS measures of perceived exertion in the HIEC test., Conclusions: The combination of BCAAs, L-citrulline, and A-GPC used in this study improves cycling performance and may be useful for individuals seeking to improve athletic performance, particularly in disciplines requiring lower body muscular strength and endurance.

We have studied the effect of relative composition of γ-Oryzanol (γ-Or) on the liquid expanded-liquid condensed phase coexistence region in the mixed Langmuir monolayer of γ-Or and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) molecules at air-water interface. The surface manometry studies at a fixed temperature show that the mixture of γ-Or and DPPC forms a stable monolayer at air-water interface. As the relative composition of γ-Or increases the range of area per molecule over which the coexistence of liquid expanded (LE)-liquid condensed (LC) phases exists reduces. Although the LE-LC phase coexistence corresponds to the first-order phase transition, the slope of the surface pressure-area per molecule isotherm is non-zero. Earlier studies have attributed the non-zero slope in LE-LC phase coexistence region to the influence of the strain between the ordered LC phase and disordered LE phase. The effect of strain on the coexistence of LE-LC phases can be studied in terms of molecular density-strain coupling. Our analysis of the liquid condensed-liquid expanded coexistence region in the isotherms of mixed monolayers of DPPC and γ-Or shows that with the increase in the mole fraction of sterol in the mixed monolayer the molecular lateral density-strain coupling increases. However, at 0.6 mole fraction of γ-Or in the mixed monolayer the coupling decreases. This is corroborated by the observation of minimum Gibb's free energy of the mixed monolayer at this relative composition of γ-Or indicating better packing of molecules., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study explores the hysteresis phenomenon in DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine) monolayers, considering several variables, including temperature, compression and expansion rates, residence time, and subphase content. The investigation focuses on analyzing the influence of these variables on key indicators such as the π-A isotherm curve, loop area, and compression modulus. By employing the Langmuir-Blodgett technique, the findings reveal that all the examined factors significantly affect the aforementioned parameters. Notably, the hysteresis loop, representing dissipated energy, provides valuable insights into the monolayer's viscoelasticity, molecular packing, phase transition changes, and resistance during the isocycle process. These findings contribute to a comprehensive understanding of the structural and dynamic properties of DPPC monolayers, offering insights into their behavior under varying conditions. Moreover, the knowledge gained from this study can aid in the development of precise models and strategies for controlling and manipulating monolayer properties, with potential applications in drug delivery systems, surface coatings, as well as further investigation into air penetration into alveoli and the blinking mechanism.

Background: Docosahexaenoic acid (DHA) is important for optimal neurodevelopment and brain function during the childhood when the brain is still under development. Methods: The effects of DHA-Phosphatidylcholine (DHA-PC) and the recombination of DHA-Triglyceride with egg PC (DHA-TG + PC) or α-Glycerylphosphorylcholine (DHA-TG + α-GPC) were comparatively analyzed on DHA recovery and the DHA accumulation kinetics in tissues including cerebral cortex, erythrocyte, liver, and testis were evaluated in the weaning n-3 deficient mice. Results: The concentration of DHA in weaning n-3 deficient mice could be recovered rapidly by dietary DHA supplementation, in which DHA-PC exhibited the better efficacy than the recombination of DHA-Triglyceride with egg PC or α-GPC. Interestingly, DHA-TG + α-GPC exhibited the greater effect on DHA accumulation than DHA-TG + PC in cerebral cortex and erythrocyte (p < 0.05), which was similar to DHA-PC. Meanwhile, DHA-TG + PC showed a similar effect to DHA-PC on DHA repletion in testis, which was better than that of DHA-TG + α-GPC (p < 0.05). Conclusion: We concluded that different forms of DHA supplements could be applied targetedly based on the DHA recovery in different tissues, although the supplemental effects of the recombination of DHA-Triglyceride with egg PC or α-GPC were not completely equivalent to that of DHA-PC, which could provide some references to develop functional foods to support brain development and function. [ABSTRACT FROM AUTHOR]

Background: Recent studies have suggested that alpha glycerylphosphorylcholine (A-GPC) may be an effective ergogenic aid. The present study was designed to assess the efficacy of two doses of A-GPC in comparison to placebo and caffeine for increasing countermovement jump performance, isometric strength, and psychomotor function. Methods: Forty-eight healthy, college aged males volunteered for the present study and underwent baseline assessment of countermovement jump (CMJ), isometric mid thigh pull (IMTP), upper body isometric strength test (UBIST), and psychomotor vigilance (PVT). Following this assessment participants were randomly assigned to groups consisting of 500 mg A-GPC, 250 mg A-GPC, 200 mg Caffeine or Placebo taken daily. Blood samples were collected 1 h and 2 h post initial dose to quantify serum free choline and thyroid stimulating hormone then subjects returned after 7 days of supplementation to repeat CMJ, IMTP, UBIST and PVT. Results: No differences were noted between groups for IMTP, UBIST or PVT performance. Serum free choline was found to be elevated in the two A-GPC groups as compared to placebo (132% and 59% respectively). Serum TSH was found to be significantly depressed in the 500 mg A-GPC group compared to other treatments (p < 0.04). Group differences were noted for maximum velocity and maximum mechanical power on the CMJ (p < 0.05) with the 250 mg A-GPC group demonstrating the greatest improvements in result. Conclusions: Based upon this evidence, and previous evidence regarding A-GPC, it should be considered as an emerging ergogenic supplement. [ABSTRACT FROM AUTHOR]

Background: A lucid dream is a dream in which one is aware of the fact that one is dreaming. Various cognitive and technical methods exist to induce lucid dreaming, most of which show only little success when tested scientifically. Until now, only few studies have dealt with inducing lucid dreaming by supplements, with, however, promising results. Objective: We have continued this line of research by conducting a double-blind randomized placebo-controlled field study in order to investigate pharmacological lucid dream induction using L-alpha-glycerylphosphorylcholine (α-GPC), a prescription-free drug acting as an acetylcholine precursor. Additionally, we tested whether cholinergic activation changes dream emotions or bizarreness. Materials and methods: Following the baseline night with placebo, 23 participants with little lucid dreaming experience and 10 participants with advanced experience were administered a placebo on one night and 1200 mg of α-GPC on one night. The Lucidity and Consciousness in Dreams (LuCiD) scale was used to measure the level of dream lucidity. In addition, dream reports were collected to analyse dream content alterations. Results and conclusion: Out of 75 dreams in total, six were rated as lucid: two in the baseline condition, two in the placebo condition and two in the α-GPC condition. There was no significant alteration of dream content such as dream emotions or bizarreness. Thus, previous anecdotal findings about lucidity-promoting or dream-altering effects of α-GPC were not confirmed in our study. [ABSTRACT FROM AUTHOR]

Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) from the group of phenylacetic acid derivatives, which has analgesic, anti-inflammatory and antipyretic properties. The interaction of non-steroidal anti-inflammatory drugs with cell membranes can affect their physicochemical properties, which, in turn, can cause a number of side effects in the use of these drugs. Electron paramagnetic resonance (EPR) spectroscopy could be used to study the interaction of diclofenac with a membrane, if its spin-labeled analogs existed. This paper describes the synthesis of spin-labeled diclofenac (diclofenac-SL), which consists of a simple sequence of transformations such as iodination, esterification, Sonogashira cross-coupling, oxidation and saponification. EPR spectra showed that diclofenac-SL binds to a lipid membrane composed of palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC). 2 H electron spin echo spectroscopy (ESEEM) was used to determine the position of the diclofenac-SL relative to the membrane surface. It was established that its average depth of immersion corresponds to the 5th position of the carbon atom in the lipid chain.

Choline alfoscerate (α-GPC) is a common choline compound and acetylcholine precursor in the brain, which has been shown to be effective in the treatment of Alzheimer’s disease and dementia. α-GPC has been shown to enhance memory and cognitive function in stroke and Alzheimer’s patients but currently remains untested in patients suffering from epilepsy. This study aimed to evaluate whether α-GPC treatment after seizure can ameliorate seizure-induced cognitive impairment and neuronal injury. The potential therapeutic effects of α-GPC on seizure-induced cognitive impairment were tested in an animal model of pilocarpine-induced seizure. Seizures were induced by intraperitoneal injection of pilocarpine (25 mg/kg) in male rats. α-GPC (250 mg/kg) was injected into the intramuscular space once daily for one or three weeks from immediately after seizure, or from 3 weeks after the seizure onset for 3 weeks. Here we found that immediate 1-week treatment of α-GPC showed no neuroprotective effects and neurogenesis. Immediate 3-week treatment of α-GPC showed neuroprotective effect but no effect on neurogenesis. To evaluate the effect of late treatment of α-GPC on cognitive impairment following seizure, rats were injected α-GPC from 3 weeks after seizure for 3 weeks and subjected to a water maze test. In the present study, we found that administration of α-GPC starting at 3 weeks after seizure improved cognitive function through reduced neuronal death and BBB disruption, and increased neurogenesis. Therefore, α-GPC injection may serve as a beneficial treatment for improvement of cognitive function in epilepsy patients. [ABSTRACT FROM AUTHOR]

Background: We hypothesized that L-alpha-glycerylphosphorylcholine (GPC), a deacylatedphosphatidylcholine derivative, can influence the mitochondrial respiratory activity and in this way, may exert tissue protective effects. Methods: Rat liver mitochondria were examined with high-resolution respirometry to analyze the effects of GPC on the electron transport chain in normoxic and anoxic conditions. Besides, Sprague-Dawley rats were subjected to sham operation or standardized liver ischemia-reperfusion (IR), with or without GPC administration. The reduced glutathione (GSH) and oxidized glutathione disulfide (GSSG), the tissue myeloperoxidase, xanthine oxidoreductase and NADPH oxidases activities were measured. Tissue malondialdehyde and nitrite/nitrate formation, together with blood superoxide and hydrogen-peroxide production were assessed. Results: GPC increased the efficacy of complex I-linked mitochondrial oxygen consumption, with significantly lower in vitro leak respiration. Mechanistically, liver IR injury was accompanied by deteriorated mitochondrial respiration and enhanced ROS production and, as a consequence, by significantly increased inflammatory enzyme activities. GPC administration decreased the inflammatory activation in line with the reduced oxidative and nitrosative stress markers. Conclusion: GPC, by preserving the mitochondrial complex I function respiration, reduced the biochemical signs of oxidative stress after an IR episode. This suggests that GPC is a mitochondria-targeted compound that indirectly suppresses the activity of major intracellular superoxide-generating enzymes. [ABSTRACT FROM AUTHOR]

Matrix-assisted laser desorption/ionization mass spectrometry (MALDI/MS) has potential applications in the qualitative analysis of phospholipids (PLs). However, its capability for quantitative analysis is limited by the unavailability and/or high cost of isotope-labeled internal standards (interSTDs, e.g., 1-oleoyl (d7)-2-hydroxy-sn-glycero-3-phosphocholine, 1-pentadecanoyl-2-oleoyl (d7)-sn-glycero-3-phosphocholine). This study investigated and validated whether only two PL interSTDs could be used to normalize the entire PL species in a complex bio-lipid background (i.e., urinary lipid extracts). The normalized intensities of PL ionization standards (ionSTDs) were found to have better linear regressions (R 2  > 0.984 for all PL subcategories) than those of traditional methods, such as total ion current and matrix-peak normalization methods. Furthermore, the intra-day precision of all the analyte concentrations after normalizing using our ionSTD method was superior to those of traditional methods. The inter-day precision of all the negatively charged analytes also differed statistically between our ionSTD and the two traditional methods. Meanwhile, a comparison of the three normalization methods revealed that the precision of all the positive analytes using the ionSTD method was comparable. Consequently, a cost-effective, fast, simple, convenient, and reliable quantitative method, defined as "qShot MALDI analysis," was developed to analyze PLs that could potentially be applied in clinical biomarker screening, especially in a negative mode., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Fluoxetine (FLX), used in the clinic to treat depression, is a well-known cationic amphiphilic antidepressant. However, there is a lack of research on the effect of FLX on the surface behavior of lipid monolayers under different surface pressures. In this study, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine/CHOL (DPPC/POPC/CHOL) monolayers were prepared via the Langmuir method, and FLX was added to these monolayers under various surface pressures. The effect of FLX on the surface behavior of DPPC/POPC/CHOL monolayers under various surface pressures was studied using a combination of surface pressure-area isotherms, compressibility modulus-surface pressure curves, and atomic force microscope (AFM). The results showed that the effect of FLX on the lipid monolayers was different under different surface pressures. The interaction between FLX and lipid molecules was weak under low surface pressures, and FLX could easily intercalate between the lipid molecules to inhibit monolayer phase transition. The interaction between FLX and lipid molecules was enhanced and FLX tended to self-aggregate to reduce the monolayer stability when the surface pressure was high. This study lays the foundation for further studies on the interaction between FLX and lipid monolayers., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study aimed to optimize the preparation of l -α-glycerylphosphorylcholine ( l -α-GPC) via phospholipase A 1 (Lecitase Ultra)-catalyzed hydrolysis of soy phosphatidylcholine (PC). The reaction was performed in n -hexane–water biphasic media in a stirred batch reactor, and modeling and optimization were conducted using response surface methodology. Optimal conditions to completely hydrolyze PC to l -α-GPC were: temperature, 50 °C; reaction time, 30 h; water content, 69 g/100 g of PC weight; and enzyme loading, 13 g/100 g of PC weight. The optimal n -hexane-to-water ratio in the medium was 5.8:1 (v/v), and 21.3 g of PC was treated as the substrate in 100 mL of the medium. l -α-GPC with purity 99.3 g/100 g was obtained from the reaction products after diethyl ether extraction and silica column chromatography. These findings suggest that the use of n -hexane–water media increases the productivity of l -α-GPC compared to the aqueous media used in enzymatic reaction systems in other published studies. [ABSTRACT FROM AUTHOR]

Background: Ergogenic aides are widely used by fitness enthusiasts and athletes to increase performance. Alpha glycerylphosphorylcholine (A-GPC) has demonstrated some initial promise in changing explosive performance. The purpose of the present investigation was to determine if 6 days of supplementation with A-GPC would augment isometric force production compared to a placebo. Methods: Thirteen college-aged males (Means ± SD; Age: 21.9 ± 2.2 years, Height: 180.3 ± 7.7 cm, Weight: 87.6 ± 15.6 kg; VO2 max: 40.08 ± 7.23 ml O2*Kg-1*min-1, Body Fat: 17.5 ± 4.6 %) gave written informed consent to participate in the study. The study was a double blind, placebo controlled, cross-over design. The participants reported to the lab for an initial visit where they were familiarized with the isometric mid thigh pull in a custom squat cage on a force platform and upper body isometric test against a high frequency load cell, and baseline measurements were taken for both. The participant then consumed either 600 mg per day of A-GPC or placebo and at the end of 6 days performed isometric mid thigh pulls and an upper body isometric test. A one-week washout period was used before the participants' baseline was re-measured and crossed over to the other treatment. Results: The A-GPC treatment resulted in significantly greater isometric mid thigh pull peak force change from baseline (t = 1.76, p = 0.044) compared with placebo (A-GPC: 98.8. ± 236.9 N vs Placebo: -39.0 ± 170.9 N). For the upper body test the A-GPC treatment trended towards greater change from baseline force production (A-GPC: 50.9 ± 167.2 N Placebo: -14.9 ± 114.9 N) but failed to obtain statistical significance (t = 1.16, p = 0.127). Conclusions: A-GPC is effective at increasing lower body force production after 6 days of supplementation. Sport performance coaches can consider adding A-GPC to the diet of speed and power athletes to enhance muscle performance. [ABSTRACT FROM AUTHOR]