Phosphatidylcholine Content Research Articles

Multi-Omics Analysis Reveals the Mechanism by Which RpACBP3 Overexpression Contributes to the Response of Robinia pseudoacacia to Pb Stress

Acyl-CoA-binding protein (ACBP) genes have been implicated in lead enrichment and translocation in plants; however, the mechanisms by which these genes contribute to the response to heavy metal stress in various taxa have not been determined. In this study, the molecular mechanisms underlying the response of Robinia pseudoacacia, an economically important deciduous tree, to Pb stress were examined using transcriptomic and metabolomic analyses. RpACBP3 overexpression increased Pb enrichment, translocation, and tolerance. After Pb stress for 3 days, 1125 differentially expressed genes (DEGs) and 485 differentially accumulated metabolites (DAMs) were identified between wild-type and RpACBP3-overexpressing R. pseudoacacia strains; after Pb stress for 45 days, 1746 DEGs and 341 DAMs were identified. Joint omics analyses showed that the DEGs and DAMs were co-enriched in α-linoleic acid metabolism and flavonoid biosynthesis pathways. In particular, DEGs and DAMs involved in α-linoleic acid metabolism and flavonoid biosynthesis were up- and down-regulated, respectively. Moreover, RpACBP3 overexpression enhanced the ability to scavenge reactive oxygen species and repair cell membranes under stress by regulating LOX gene expression and increasing the phosphatidylcholine content, thereby improving the tolerance to Pb stress. These findings lay a theoretical foundation for the future application of RpACBP3 genes in plant germplasm resource creation and phytoremediation of Pb contaminated soil in which R. pseudoacacia grow.

The metabolomic composition of the oviductal fluid is controlled by the periovulatory hormonal context in Bos indicus cows.

In cattle, oviductal function is controlled by the ovarian sex-steroids estradiol and progesterone. Here, we tested the hypothesis that the exposure to contrasting sex-steroid milieus differentially impacts the oviductal fluid composition. Estrous cycles of non-lactating, multiparous Nelore cows were pre-synchronized and then synchronized with a protocol designed two induce ovulation of large (LF group) or small (SF group) follciles. Larger preovulatory follicle (day 0) and corpora lutea (day 4) and greater estradiol (day 0) and progesterone (day 4) concentrations were observed in the LF group. Four days after induced ovulation, oviductal fluid was collected post-mortem. Quantitative mass spectrometry was used to determine the concentration of amino acids, biogenic amines, acylcarnitines, phosphatidylcholines, lysophosphatidylcholines, sphingomyelins, hexoses, prostaglandins and related compounds. Multivariate analyses (OPLS-DA) were conducted to compare the metabolomic signatures of oviductal fluids. Correlation network analysis was conducted to measure the strength and hierarchy of associations among metabolites. Of the 205 metabolites quantified, 171 were detected in at least 50% of the samples and were included in further data analysis. After OPLS-DA analysis, samples of the LF and SF were divided clearly into two non-overlapping clusters. Twenty metabolites had different or tended to have different concentrations in the oviductal fluid when comparing groups. Seven of these 20 analytes had greater concentrations in LF cows. Moreover, total sum of biogenic amines, phosphatidylcholines, and prostaglandins were higher in the SF group. The correlation network showed that the LF group metabolites' concentrations were highly intercorrelated, which was not observed in the SF group. We concluded that the periovulatory endocrine milieu regulates the composition of the oviductal fluid.

Melt-extruded formulations of fenofibrate with various grades of hydrogenated phospholipid exhibit promising in-vitro biopharmaceutical behavior

In the current study, it was demonstrated that three commercially available grades of hydrogenated phospholipids (HPL) differing in their content of phosphatidylcholine may be used as components for hot melt-extruded binary (HPL as sole excipient) or ternary (in combination with copovidone) solid dispersions of fenofibrate (FEN) at mass fractions between 0.5 and 20% (ternary) or 80% (binary). X-ray powder diffraction indicated complete conversion of crystalline fenofibrate into the amorphous state by hot melt extrusion for all ternary blends. In contrast, both the binary blends (HPL- and copovidone-based) contained minor remaining crystallites. Irrespectively, all solid dispersions induced during dissolution studies a supersaturated state of FEN, where the ternary ASDs showed enhanced and more complete release of FEN as compared to the binary blends and, even more pronounced, in comparison to the marketed micronized and nano-milled formulations. In terms of the cumulated amount permeated, there were marginal differences between the various formulations when combined dissolution/permeation was done using FeSSIF as donor medium; with FaSSIF as donor medium, the binary HPL-ASD containing the grade with the highest phosphatidylcholine fraction performed best in terms of permeation, even significantly better than the marketed nano-crystal formulation. Otherwise, no significant differences were seen between the various grades of HPL when FEN dissolution and permeation were analyzed for ternary solid dispersions. In conclusion, the in-vitro biopharmaceutical behaviour of hydrogenated phospholipid-containing blends manufactured by hot melt extrusion appears promising. They can be a viable formulation option for poorly water-soluble and lipophilic drug compounds like FEN.

A coumarin derivative C7 exhibits antiviral activity against WSSV by reducing phosphatidylcholine content in shrimp

The white spot syndrome virus (WSSV) causes white spot disease (WSD), a severe condition in crustacean aquaculture, leading to significant economic losses. Our previous study demonstrated that C7 is an effective therapeutic agent against WSSV infection in aquaculture. It specifically blocked viral horizontal transmission and reduced shrimp mortality in a dose- and time-dependent manner. Here, we report the potential antiviral mechanism of C7 in shrimp. C7 regulated abnormal glycerophospholipid metabolism caused by WSSV and inhibited phosphatidylcholine (PC) synthesis by more than twofold, potentially enhancing shrimp resistance to viral infection. As the primary phospholipid in the cell membrane, PC is one of the main reactants in lipid peroxidation. Our results indicated that C7 significantly reduced the levels of lipid peroxidation products 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA) induced by WSSV, whereas PC had the opposite effect. Accumulation of lipid peroxidation products inhibits stimulator of interferon genes (STING) signaling. Further evidence showed that C7 promoted STING transport from the endoplasmic reticulum to the Golgi apparatus, significantly activating the expression of the shrimp interferon analogue Vago4 gene. In contrast, PC suppressed Vago4 expression. Our results demonstrated that C7 inhibited PC synthesis, reduced the degree of lipid peroxidation, promoted STING translocation, activated Vago4 expression, and ultimately exerted antiviral effects. Therefore, C7 exhibits immunoregulatory activity as a preventative agent for enhancing the innate immunity of shrimp, making it potentially useful for future immunomodulatory approaches.

Unlocking choline's potential in Alzheimer's disease: A narrative review exploring the neuroprotective and neurotrophic role of phosphatidylcholine and assessing its impact on memory and learning

Background and aimsGrowing evidence suggests nutritional intervention may influence the development and progression of Alzheimer‘s Disease (AD). Choline, an essential dietary nutrient plays a critical role in neurological development and brain function, however, its effects on AD in humans is unclear. The research aims to investigate mechanistic links between dietary choline intake and cognitive functioning, focusing on the role of phosphatidylcholine (PC) in neuroplasticity and its interaction with amyloid beta (Aβ) peptides in neuron membranes. Additionally, human evidence on potential benefits of PC interventions on AD, cognition and proposed mechanisms are evaluated. MethodsA reproducible systematic literature search was performed using a three-tranche strategy, consisting of a review, mechanism and intervention search. Using PubMed as the main database, 1254 titles and abstracts were screened, 149 papers were read in full and 65 peer-reviewed papers were accepted, critically appraised and analysed in a narrative review. ResultsPredominantly preclinical evidence demonstrated that PC enhances neuroplasticity, a key biological substrate for cognition, by activating intracellular neuronal signalling pathways or through neuron membrane function.Molecular dynamic simulation methods provided mechanistic understanding of the interconnection between neuronal PC content and the potential behaviour and trajectory of Aβ peptide aggregation. The results indicate that the neuronal membrane composition of PC is critical to inhibiting Aβ aggregation and neuronal damage, protecting the neuron from Aβ toxicity. This might provide a foundation for optimising cellular PC which may prove beneficial in the treatment or prevention of neurodegenerative disease.Altered PC metabolism in AD was evidenced in observational studies; however, whether this relationship represents a cause or consequence of AD remains to be determined. Human intervention studies did not produce conclusive evidence supporting its effectiveness in enhancing cognitive function. This lack of consistency primarily stems from methodological constraints within the conducted studies. Human observational research provided the most compelling evidence linking a higher dietary PC intake to reduced risk of dementia and significant improvements in cognitive testing. ConclusionDespite the lack of randomised control trials (RCTs) assessing the efficacy of lecithin/PC to improve cognition in AD patients, there exists promising evidence supporting its neuroprotective and neurotrophic role.This review establishes an evidence-based framework through chains of mechanistic evidence, that may provide potential strategies for enhanced neuroprotection and reduced neurodegeneration caused by AD. Considering the escalating global burden of AD and the current shortcomings in effective treatments, this review together with the limitations and gaps identified in the existing research present valuable insights that emphasise the urgency of more comprehensive research into the relationship between PC and AD.

The role of oleosins and phosphatidylcholines on the membrane mechanics of oleosomes

HypothesisOilseeds use triacylglycerides as main energy source, and pack them into highly stable droplets (oleosomes) to facilitate the triacylglycerides’ long-term storage in the aqueous cytosol. To prevent the coalescence of oleosomes, they are stabilized by a phospholipid monolayer and unique surfactant-shaped proteins, called oleosins. In this study, we use state-of-the-art interfacial techniques to reveal the function of each component at the oleosome interface. ExperimentsWe created model oil–water interfaces with pure oleosins, phosphatidylcholines, or mixtures of both components (ratios of 3:1, 1:1, 1:3), and applied large oscillatory dilatational deformations (LAOD). The obtained rheological response was analyzed with general stress decomposition (GSD) to get insights into the role of phospholipids and oleosins on the mechanics of the interface. FindingsOleosins formed viscoelastic solid interfacial films due to network formation via in-plane interactions. Between adsorbed phosphatidylcholines, weak interactions were observed, suggesting the surface stress response upon dilatational deformations was dominated by density changes. In mixtures with 3:1 and 1:1 oleosin-to-phosphatidylcholine ratios, oleosins dominated the interfacial mechanics and formed a network, while phosphatidylcholines contributed to interfacial tension reduction. At higher phosphatidylcholine concentrations (1:3 oleosin-to-phosphatidylcholine), phosphatidylcholine dominated the interface, and no network formation occurred. Our findings improve the understanding of both components’ role for oleosomes.

127 Effects of maternal pre- and post-partum supplementation of a Bacillus-based DFM on plasma metabolome profile of Bos indicus-influenced heifers and their offspring

Abstract This study evaluated the effects of maternal supplementation during pre- and postpartum of a Bacillus-based direct-fed microbial (DFM) on plasma metabolome of Bos indicus-influenced cow-calf pairs. On d 0, 72 pregnant Brangus crossbred beef heifers (20 to 22 mo of age) were stratified by their initial body weight (BW; 431 ± 31 kg) and body condition score (BCS; 6.0 ± 0.36), and randomly allocated into 1 of 12 bahiagrass pastures (1 ha and 6 heifers/pasture). Treatments were randomly assigned to pastures (6 pastures/treatment) and consisted of heifers supplemented with 1 kg/d of soybean hulls dry matter added (BAC) or not (CON) with a Bacillus-based DFM mixture (Bovacillus; Chr. Hansen A/S, Hørsholm, Denmark) from d 0 to 242 (139 ± 4 d prepartum to 104 ± 4 d postpartum). Calves were weaned on d 242 (96 ± 30 d of age) and then allocated into 1 of 12 drylot pens and limit-fed the same concentrate at 3.25% of BW until day 319. On d 271 and 287, calves were vaccinated against pathogens associated with bovine respiratory disease and Clostridium. Blood samples were collected from all heifers on d 0 and 63 and from all calves on d 271, 274, and 287 to determine the plasma concentration of metabolites using liquid chromatography. The PLS-DA revealed a clear separation of plasma metabolome profile of BAC and CON heifers and offspring. For the heifer metabolome, 66.5% of the treatment separation on d 63 was explained using 3 components (R2 = 0.96), and BAC heifers had increased (P ≤ 0.05) plasma concentration of 17 metabolites, including phosphatidylcholines and amino acids related classes, but decreased (P ≤ 0.05) plasma concentration of 4 metabolites from triglycerides class compared with CON heifers. For the calf metabolome, 45.6 (R2 = 0.95), 56.7 (R2 = 0.95), and 61.3% (R2 = 0.99) of the treatment separation on d 271, 274, and 287, respectively, were explained using 3 components. Plasma concentrations of 9, 10, and 28 metabolites associated with protein and fatty acid metabolism increased (P ≤ 0.05) in BAC vs. CON calves on d 271, 274, and 287, respectively. Compared with CON, BAC calves had increased (P ≤ 0.05) concentration of metabolites from phosphatidylcholines class all days, from amino acids related class on d 274 and 287, and from triglycerides class on d 287. Plasma concentrations of 3 and 6 metabolites from triglycerides class decreased (P ≤ 0.05) in BAC vs. CON calves on d 271 and 274, respectively. Thus, maternal supplementation of Bacillus-based DFM altered the plasma metabolome of heifers and their calves, leading to increased plasma concentrations of phosphatidylcholine and amino acids related classes in heifers and calves, but fluctuating effects on triglycerides class concentrations in calves.

Deep Plasma Proteome Profiling by Modulating Single Nanoparticle Protein Corona with Small Molecules.

The protein corona, a dynamic biomolecular layer that forms on nanoparticle (NP) surfaces upon exposure to biological fluids is emerging as a valuable diagnostic tool for improving plasma proteome coverage analyzed by liquid chromatography-mass spectrometry (LC-MS/MS). Here, we show that spiking small molecules, including metabolites, lipids, vitamins, and nutrients (namely, glucose, triglyceride, diglycerol, phosphatidylcholine, phosphatidylethanolamine, L-α-phosphatidylinositol, inosine 5'-monophosphate, and B complex), into plasma can induce diverse protein corona patterns on otherwise identical NPs, significantly enhancing the depth of plasma proteome profiling. The protein coronas on polystyrene NPs when exposed to plasma treated with an array of small molecules (n=10) allowed for detection of 1793 proteins marking an 8.25-fold increase in the number of quantified proteins compared to plasma alone (218 proteins) and a 2.63-fold increase relative to the untreated protein corona (681 proteins). Furthermore, we discovered that adding 1000 µg/ml phosphatidylcholine could singularly enable the detection of 897 proteins. At this specific concentration, phosphatidylcholine selectively depleted the four most abundant plasma proteins, including albumin, thus reducing the dynamic range of plasma proteome and enabling the detection of proteins with lower abundance. By employing an optimized data-independent acquisition (DIA) approach, the inclusion of phosphatidylcholine led to the detection of 1436 proteins in a single plasma sample. Our molecular dynamic results revealed that phosphatidylcholine interacts with albumin via hydrophobic interactions, h-bonds, and water-bridges. Addition of phosphatidylcholine also enabled the detection of 337 additional proteoforms compared to untreated protein corona using a top-down proteomics approach. These significant achievements are made utilizing only a single NP type and one small molecule to analyze a single plasma sample, setting a new standard in plasma proteome profiling. Given the critical role of plasma proteomics in biomarker discovery and disease monitoring, we anticipate widespread adoption of this methodology for identification and clinical translation of proteomic biomarkers into FDA approved diagnostics.

Variations in the milk lipidomic profile of lactating dairy cows fed the diets containing alfalfa hay versus alfalfa silage

Alfalfa is primarily stored as silage or hay in livestock production. Previous research has shown that the storage method of grass significantly influences milk composition. This study aimed to investigate milk production performance and lipid composition in dairy cows fed diets consisting of alfalfa hay or alfalfa silage as roughage. Forty-two mid-lactation Holstein dairy cows were selected and randomly divided into three groups, each receiving a total mixed ration consisting of alfalfa hay (AH), 50% alfalfa silage + 50% alfalfa hay (AHAS), or alfalfa silage (AS). The results showed that milk fat content (P = 0.049) and milk fat yield (P < 0.001) were significantly higher in the AH and AHAS groups compared to the AH group. With increased supplementation of alfalfa silage in the diet, ω-3 polyunsaturated fatty acid content increased significantly (P < 0.001), while ω-6 polyunsaturated fatty acid content (P = 0.007) and the ratio of ω-6 to ω-3 polyunsaturated fatty acids decreased (P < 0.001). The contents of sphingomyelins, phosphatidylserines, phosphatidylethanolamines, and phosphatidylglycerols in the AHAS and AS samples were higher than in the AH samples, although the differences were not statistically significant. Additionally, the content of phosphatidylcholines was significantly higher in the AS group compared to the AH group (P = 0.032). In conclusion, feeding dairy cows a diet consisting of alfalfa silage can increase the major phospholipid content and polyunsaturated fatty acid composition in raw milk, which is more conducive to human health. These findings provide valuable insights into the benefits of alfalfa silage for dairy cows.

Longitudinal characterization of the muscle metabolome in dairy cows during the transition from lactation cessation to lactation resumption

Skeletal muscle is vital in maintaining metabolic homeostasis and adapting to the physiological needs of pregnancy and lactation. Despite advancements in understanding metabolic changes in dairy cows around calving and early lactation, there are still gaps in our knowledge, especially concerning muscle metabolism and the changes associated with drying off. This study aimed to characterize the skeletal muscle metabolome in the context of the dietary and metabolic changes occurring during the transition from the cessation of lactation to the resumption of lactation in dairy cows. Twelve Holstein dairy cows housed in tie stalls were dried off 6 weeks (wk) before the expected calving date. Cows were individually fed ad libitum total mixed rations composed of grass silage, corn silage, and concentrate during lactation and of corn silage, barley straw, and concentrate during the dry period. The metabolome was characterized in skeletal muscle samples (M. longissimus dorsi) collected on wk -7 (9 d before dry-off), -5 (6 d after dry-off), and wk -1, and 1 relative to calving. The targeted metabolomics approach was conducted using the MxP Quant 500 kit (Biocrates Life Sciences AG) with liquid chromatography, flow injection, and electrospray ionization triple quadrupole mass spectrometry. Statistical analysis on the muscle metabolite data was performed using MetaboAnalyst 5.0, which allowed us to conduct various multivariate analyses such as principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), informative heat map generation, and hierarchical clustering. The statistical analysis revealed a clear separation between pregnancy (wk -7, -5, and -1) and post-calving (wk 1). Starting 5 wk before calving and continuing through the first wk thereafter, the concentration of 3-methylhistidine (3-MH) in the muscle increased. This coincided with an increase in the concentrations of 11 AA (Phe, His, Tyr, Trp, Arg, Asn, Leu, Ile, Gly, Ser, and Thr) in the first wk after calving, whereas Gln decreased. l-arginine pathway metabolites (homoarginine, ornithine, citrulline, and asymmetric dimethylarginine), betaine, and sarcosine followed a similar pattern, increasing from wk -7 to -5, but decreasing from wk -1 to 1. The transition from pregnancy to lactation was associated with an increase in concentrations of the long-chain acylcarnitine species C16, C16:1, C18, and C18:1 in the muscle, whereas the concentrations of phosphatidylcholine and sphingomyelin in the muscle remained stable. The significant changes observed in the metabolome mainly concerned the AA and AA-related metabolites, indicating muscle protein breakdown in the first wk after calving. The metabolites produced by the L-Arg pathway might contribute to regulating skeletal muscle mass and function in periparturient dairy cows. The elevated concentrations of long-chain acylcarnitine species in the muscle in the first wk after calving suggest incomplete fatty acid oxidation, likely due to insufficient metabolic adaptation in response to the fatty acid load around the time of calving.

The role of lysophosphatidic acid acyltransferase 1 in reproductive growth of Arabidopsis thaliana.

Lysophosphatidic acid acyltransferase1 (LPAT1) catalyzes the second step of de novo glycerolipid biosynthesis in chloroplasts. However, the embryonic-lethal phenotype of the knockout mutant suggested an unknown role for LPAT1 in non-photosynthetic reproductive organs. Reciprocal genetic crossing of the lpat1-1 heterozygous line suggested a female gametophytic defect of the lpat1-1 knockout mutant. By suppressing LPAT1 specifically during seed development, we showed that LPAT1 suppression affected silique growth and seed production. Glycerolipid analysis of the LPAT1 knockdown lines revealed a pronounced decrease of phosphatidylcholine (PC) content in mature siliques along with an altered polyunsaturation level of the polar glycerolipids. In seeds, the acyl composition of triacylglycerol (TAG) was altered albeit not the content. These results indicate that plastidic LPAT1 plays an important role in reproductive growth and extraplastidic glycerolipid metabolism involving PC and TAG.

Maximizing the Use of Ivermectin Transethosomal Cream in the Treatment of Scabies.

In an effort to tackle the skin reactions frequently observed with topical application of ivermectin (IVM), a study was conducted to develop and optimize transethosomes (TESMs) loaded with IVM for scabies treatment. A three-factor, two-level (23) full factorial design was employed. Soyabean phosphatidylcholine concentration (A), ethanol concentration (B) and Span 60 amount (C) were studied as independent factors, while entrapment efficiency (EE), particle size (PS), polydispersity index (PDI), zeta potential (ZP) and drug release after 6 h (Q6h) were characterized. The skin sensitivity of the optimized formulation was evaluated by skin irritation test and histopathological examination. The EE% ranged from 88.55 ± 0.576% to 94.13 ± 0.305%, PS was from 318.033 ± 45.61 nm to 561.400 ± 45.17 nm, PDI was from 0.328 ± 0.139 to 0.671 ± 0.103, ZP was from -54.13 ± 1.09 mV to -60.50 ± 2.34 mV and Q6h was from 66.20 ± 0.30% to 93.46 ± 0.86%. The IVM-loaded transethosomal cream showed lower skin irritation and a more intact epidermal layer with intact keratinocyte, compared to the marketed cream which showed severe destruction of the keratin layer. Therefore, patient compliance can be improved by encapsulating IVM within TESMs to minimize its skin reactions.

Multiomics analysis reveals the potential of LPCAT1-PC axis as a therapeutic target for human intervertebral disc degeneration

Intervertebral disc degeneration (IDD) is a highly prevalent musculoskeletal disorder that is associated with considerable morbidity. However, there is currently no drug available that has a definitive therapeutic effect on IDD. In this study, we aimed to identify the molecular features and potential therapeutic targets of IDD through a comprehensive multiomics profiling approach. By integrating transcriptomics, proteomics, and ultrastructural analyses, we discovered dysfunctions in various organelles, including mitochondria, the endoplasmic reticulum, the Golgi apparatus, and lysosomes. Metabolomics analysis revealed a reduction in total phosphatidylcholine (PC) content in IDD. Through integration of multiple omics techniques with disease phenotypes, a pivotal pathway regulated by the lysophosphatidylcholine acyltransferase 1 (LPCAT1)-PC axis was identified. LPCAT1 exhibited low expression levels and exhibited a positive correlation with PC content in IDD. Suppression of LPCAT1 resulted in inhibition of PC synthesis in nucleus pulposus cells, leading to a notable increase in nucleus pulposus cell senescence and damage to cellular organelles. Consequently, PC exhibits potential as a therapeutic agent, as it facilitates the repair of the biomembrane system and alleviates senescence in nucleus pulposus cells via reversal of downregulation of the LPCAT1-PC axis.

Study on the interaction mechanism of whey protein isolate with phosphatidylcholine: By multispectral methods and molecular docking.

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 -7.85kcal/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.

Tolnaftate-Loaded Ethosomal Gel for Topical Delivery: Formulation and In Vitro Evaluation

Abstract Objectives Tolnaftate (TOL) is used as a topical antifungal agent but has poor skin penetration. Therefore, the present study is designed to formulate an ethosomal gel of TOL to enhance drug penetration through the skin. Methods Using the cold method ethosomal formulations with different concentrations of ethanol and soy phosphatidylcholine (SPC) were formulated. The formulation of ethosomes was characterized by vesicle size, polydispersity index and zeta potential, % drug entrapment efficiency (EE), and scanning electron microscopy (SEM). The optimized ethosomal formula was incorporated in a 1% Carbopol hydrogel dosage. Evaluation of in vitro penetration of prepared gel was performed on goat skin using Franz diffusion cells and compared with conventional gel. Result The ethosomal formulation EF5 showed the highest % EE (76.82%) with a small vesicle size of 210.1 nm and was selected as the optimized formulation. The SEM result shows that the vesicles were spherical, smooth, and in the 200-nm range. In vitro, permeability study shows that steady-state flux of TOL from ethosomal and conventional gels were 6.667 and 3.685 µg/cm/h, respectively (p &lt; 0.001). It indicated that the flux of Ethosomal hydrogel (EHG) is 2.0-fold higher than conventional hydrogel (CHG); this may be due to the flexible nature of ethosomes and ethosomal core containing ethanol, which dissolves the lipid bilayer of skin and overcomes the barrier. In vitro, an antifungal study shows that the incorporation of TOL in ethosomal hydrogel retains their activity. Conclusion From the results, it was concluded that TOL topical ethosomal gel for antifungal activity will possibly be a good choice.

Glycerophospholipid metabolism changes association with ozone exposure

Exposure to ozone (O3) has been associated with cardiovascular outcomes in humans, yet the underlying mechanisms of the adverse effect remain poorly understood. We aimed to investigate the association between O3 exposure and glycerophospholipid metabolism in healthy young adults. We quantified plasma concentrations of phosphatidylcholines (PCs) and lysophosphatidylcholines (lysoPCs) using a UPLC-MS/MS system. Time-weighted personal exposures were calculated to O3 and co-pollutants over 4 time windows, and we employed orthogonal partial least squares discriminant analysis to discern differences in lipids profiles between high and low O3 exposure. Linear mixed-effects models and mediation analysis were utilized to estimate the associations between O3 exposure, lipids, and cardiovascular physiology indicators. Forty-three healthy adults were included in this study, and the mean (SD) time-weighted personal exposures to O3 was 9.08 (4.06) ppb. With shorter exposure durations, O3 increases were associated with increasing PC and lysoPC levels; whereas at longer exposure times, the opposite relationship was shown. Furthermore, two specific lipids, namely lysoPC a C26:0 and lysoPC a C17:0, showed significantly positive mediating effects on associations of long-term O3 exposure with pulse wave velocity and systolic blood pressure, respectively. Alterations in specific lipids may underlie the cardiovascular effects of O3 exposure.

Effects of short-term supplementation with DHA-enriched phosphatidylcholine and phosphatidylserine on lipid profiles in the brain and liver of n-3 PUFA-deficient mice in early life after weaning.

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. 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. 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.

Soybean oil emulsion stabilized by phosphatidylcholine and whey protein isolate: impact on interfacial properties, physicochemical characteristics, and digestive properties

Abstract 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.

Skeletal muscle PGC-1α remodels mitochondrial phospholipidome but does not alter energy efficiency for ATP synthesis.

Exercise training is thought to improve the mitochondrial energy efficiency of skeletal muscle. Some studies suggest exercise training increases the efficiency for ATP synthesis by oxidative phosphorylation (OXPHOS), but the molecular mechanisms are unclear. We have previously shown that exercise remodels the lipid composition of mitochondrial membranes, and some of these changes could contribute to improved OXPHOS efficiency (ATP produced by O2 consumed or P/O). Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) is a transcriptional co-activator that coordinately regulates exercise-induced adaptations including mitochondria. We hypothesized that increased PGC-1α activity is sufficient to remodel mitochondrial membrane lipids and promote energy efficiency. Mice with skeletal muscle-specific overexpression of PGC-1α (MCK-PGC-1α) and their wildtype littermates were used for this study. Lipid mass spectrometry and quantitative PCR were used to assess muscle mitochondrial lipid composition and their biosynthesis pathway. The abundance of OXPHOS enzymes was determined by western blot assay. High-resolution respirometry and fluorometry analysis were used to characterize mitochondrial bioenergetics (ATP production, O2 consumption, and P/O) for permeabilized fibers and isolated mitochondria. Lipidomic analyses of skeletal muscle mitochondria from wildtype and MCK-PGC-1α mice revealed that PGC-1α increases the concentrations of cone-shaped lipids such as phosphatidylethanolamine (PE), cardiolipin (CL), and lysophospholipids, while decreases the concentrations of phosphatidylcholine (PC), phosphatidylinositol (PI) and phosphatidic acid (PA). However, while PGC-1α overexpression increased the abundance of OXPHOS enzymes in skeletal muscle and the rate of O2 consumption (JO2), P/O values were unaffected with PGC-1α in permeabilized fibers or isolated mitochondria. Collectively, overexpression of PGC-1α promotes the biosynthesis of mitochondrial PE and CL but neither PGC-1α nor the mitochondrial membrane lipid remodeling induced in MCK-PGC-1α mice is sufficient to increase the efficiency for mitochondrial ATP synthesis. These findings suggest that exercise training may increase OXPHOS efficiency by a PGC-1α-independent mechanism, and question the hypothesis that mitochondrial lipids directly affect OXPHOS enzymes to improve efficiency for ATP synthesis.

The Effect of Liposomes of Various Compositions on the Skin and Its Derivatives After II-IIIA Degree Thermal Burns.

This study examines the pathological processes and conditions arising from an experimental modeling of II-IIIA degree thermal burns in laboratory animals. These conditions are characterized by skin structure defects, diminished skin functions, especially the barrier function, and damage to skin derivatives like hair follicles and sebaceous glands. We compared the effect of liposomes composed of soybean lecithin of 90% phosphatidylcholine content and liposomes composed of lecithin of 26% phosphatidylcholine content on the epidermis, dermis and its capillaries, hair follicles, and the sebaceous glands of the laboratory animals 24 h after experimental modeling of II-IIIA degree thermal skin burns. We discuss the dependency of liposome effects on the skin and its derivatives on the fatty acid composition of the lecithin used, with particular focus on phosphatidylinositol, phosphatidic acids, as well as oleic and linoleic acids.