Search Results (464)

Background/Objectives: An elevated level of lipoprotein(a) [Lp(a)] is a genetically determined risk factor for cardiovascular disease. The atherogenic properties of Lp(a) include attribution to its role as a carrier of oxidized phospholipids (OxPL). Despite genetic control, Lp(a) levels increase with dietary saturated fat (SFA) reduction. However, little is known about the impact of dietary factors on Lp(a) risk properties. Methods: We assessed total Lp(a)-OxPL concentration, Lp(a)-OxPL subspecies abundance, and Lp(a) lipidomics in response to SFA reduction in two multicenter, randomized, controlled, crossover feeding trials, DELTA (Dietary Effects on Lipoproteins and Thrombogenic Activity) 1 (96 healthy individuals) and 2 (79 metabolically challenged individuals). In both trials, significant increases in Lp(a) levels were reported previously. Results: While no between-diet differences in the concentrations of total Lp(a)-OxPL and four major OxPL subspecies (ALDOPC, POVPC, PAzPC, and PGPC) were observed in DELTA 1, ALDOPC decreased significantly in DELTA 2 when SFA was replaced with carbohydrates (p = 0.014). Of 440 individual lipid species annotated in an untargeted analysis of the Lp(a) lipidome, 87 lipids differed significantly (p < 0.05 adjusted for multiplicity) between diets, with triacylglycerol species showing the most pronounced changes in both trials. For all intervention diets, triacylglycerol species with a higher average number of carbon atoms and double bonds increased the most in abundance with SFA reduction. Conclusions: In parallel with an increase in plasma Lp(a) levels, significant changes in Lp(a) lipid composition occurred. The findings demonstrate the dynamic nature of intraindividual Lp(a) lipid composition in response to diet interventions. Full article

Tenbrio molitor (T. molitor) is a widely utilized feed ingredient, though it is deficient in long-chain omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). To address this, dietary supplements containing EPA and DHA in ethyl ester and triglyceride forms were administered to investigate the lipid metabolism and bioenhancement potential of T. molitor. The larvae exhibited normal growth across all treatment groups. EPA/DHA levels were significantly elevated in T. molitor-enriched diets, with newly identified phospholipid species including phosphatidylcholine 18:1_20:5 (PC 18:1_20:5) and phosphatidylethanolamine 18:0_20:5 (PE 18:0_20:5). KEGG pathway analysis revealed that glycerol phospholipid metabolism (ko00564), endogenous cannabinoid signaling (ko04723), and cell division (ko04148) were the core pathways that promoted phospholipid synthesis and oxidative lipid conversion (such as peroxide value-phosphatidylcholine, POV-PC). T. molitor activates glycerophospholipid metabolism, converting EPA/DHA into more bioavailable medium- and short-chain phospholipids, thereby enhancing its nutritional value and providing a new strategy for the development of functional foods/feeds. Full article

Background: Glaucoma is a progressive optic neuropathy marked by retinal ganglion cells (RGCs), apoptosis, vascular insufficiency, oxidative stress, mitochondrial dysfunction, excitotoxicity, and neuroinflammation. While intraocular pressure (IOP) reduction remains the primary intervention, many patients continue to lose vision despite adequate pressure control. Emerging neuroprotective agents—citicoline, coenzyme Q10 (CoQ10), pyruvate, nicotinamide, pyrroloquinoline quinone (PQQ), homotaurine, berberine, and gamma-aminobutyric acid (GABA)—target complementary pathogenic pathways in experimental and clinical settings. Methods: This literature review synthesizes current evidence on glaucoma neuroprotection, specifically drawing on the most relevant and recent studies identified via PubMed. Results: Citicoline enhances phospholipid synthesis, stabilizes mitochondrial membranes, modulates neurotransmitters, and improves electrophysiological and visual field outcomes. CoQ10 preserves mitochondrial bioenergetics, scavenges reactive oxygen species, and mitigates glutamate-induced excitotoxicity. Pyruvate supports energy metabolism, scavenges reactive oxygen species, and restores metabolic transporter expression. Nicotinamide and its precursor nicotinamide riboside boost NAD⁺ levels, protect against early mitochondrial dysfunction, and enhance photopic negative response amplitudes. PQQ reduces systemic inflammation and enhances mitochondrial metabolites, while homotaurine modulates GABAergic signaling and inhibits β-amyloid aggregation. Berberine attenuates excitotoxicity, inflammation, and apoptosis via the P2X7 and GABA-PKC-α pathways. Preclinical models demonstrate synergy when agents are combined to address multiple targets. Clinical trials of fixed-dose combinations—such as citicoline + CoQ10 ± vitamin B3, citicoline + homotaurine ± vitamin E or PQQ, and nicotinamide + pyruvate—show additive improvements in RGCs’ electrophysiology, visual function, contrast sensitivity, and quality of life without altering IOP. Conclusions: A multi-targeted approach is suitable for glaucoma’s complex neurobiology and may slow progression more effectively than monotherapies. Ongoing randomized controlled trials are essential to establish optimal compound ratios, dosages, long-term safety, and structural outcomes. However, current evidence remains limited by small sample sizes, heterogeneous study designs, and a lack of long-term real-world data. Integrating combination neuroprotection into standard care holds promise for preserving vision and reducing the global burden of irreversible glaucoma-related blindness. Full article

Bacterial infections cause serious problems associated with wound treatment and serious complications, leading to serious threats to the global public. Bacterial resistance was mainly attributed to the formation of biofilms and their protective properties. Hydrogels suitable for irregular surfaces with effective antibacterial activity have attracted extensive attention as potential materials. In this study, a succinoglycan-riclin-zinc-phthalocyanine-based composite (RL-Zc) hydrogel was synthesized through an amine reaction within an hour. The hydrogel was characterized via FT-IR, SEM, and rheology analysis, exhibiting an elastic solid gel state stably. The hydrogel showed large inhibition circles on E. coli as well as S. aureus under near-infrared irradiation (NIR). RL-Zc hydrogel exhibited positively charged surfaces and possessed a superior penetrability toward bacterial biofilm. Furthermore, RL-Zc hydrogel generated abundant single oxygen and mild heat rapidly, resulting in disrupted bacterial biofilm as well as amplified antibacterial effectiveness. A metabolomics analysis confirmed that RL-Zc hydrogel induced a metabolic disorder in bacteria, which resulted from phospholipid metabolism and oxidative stress metabolism related to biofilm disruption. Hence, this study provided a potential phototherapy for biofilm-induced bacterial resistance. Full article

This study presents a novel environmentally-friendly process for the selective extraction and enrichment of DHA/EPA-containing phospholipids (PL-DHA/EPA) from krill oil. The methodology leverages differential crystallization behavior between phospholipids and triacylglycerols in ethanolic solutions, exploiting their distinct freezing point thresholds to achieve precise fractionation. Response surface methodology optimization identified optimal extraction parameters: liquid-to-material ratio of 6:1 (v/w), freezing temperature of −20 °C, freezing duration of 25 h, and rotary evaporation temperature of 45 °C, yielding a final product with 39.40% PL-DHA/EPA content. Principal component analysis revealed substantial overlap in confidence ellipses among extraction methodologies, indicating effective preservation of core phospholipid signatures from the parent krill oil while maintaining critical structural characteristics and molecular species distribution. Comprehensive analysis of phospholipid fractions and heatmap analysis revealed distinctive molecular profiles compared to conventional organic solvent extraction, with selective enrichment of EPA-containing phospholipids, particularly PC-EPA and PI-EPA species. The green extraction method demonstrated comparable oxidative stability to conventional approaches, with superior protection against secondary oxidation as evidenced by significantly lower anisidine values. This sustainable approach achieves effective phospholipid enrichment while substantially reducing environmental impact through elimination of halogenated solvents, addressing the critical need for environmentally conscious technologies in marine lipid processing with potential applications in nutraceutical and functional food industries. Full article

Arachidonic acid (AA) is a polyunsaturated fatty acid, an essential component of the brain membrane phospholipids. It is released into the bloodstream in response to various pathological conditions. Its potential as a biomarker for oxidative membrane damage determines the importance of its reliable quantification. Therefore, the aim of the current study was to develop a simple and robust LC-MS method that is easy to implement for routine testing of free arachidonic acid (AA) in human serum. The method included a simple two-step sample preparation procedure based on liquid–liquid extraction and protein precipitation, followed by AA analysis by UPLC coupled with PDA and QDa detectors. The ICH M10 guideline was followed for validation studies. The method demonstrated high selectivity and linearity with R² = 0.9952 for solvent-based and R² = 0.9979 for matrix-matched calibration. The LODs and LOQs were 0.046 µg/mL and 0.133 µg/mL, respectively. The accuracy and precision were between 6 and 14% RSD. No carry-over and matrix interferences were observed. The method was successfully applied to real serum samples, where AA concentrations ranged from 0.82 to 2.69 µg/mL, consistent with data of other studies. This method provides a reliable, reproducible, and rapid alternative for AA quantification in research and routine practice. Full article

Status epilepticus occurs when a seizure lasts more than five minutes or when multiple seizures occur with incomplete return to baseline. SE induces a myriad of pathological changes involving synaptic and extra-synaptic factors. The transition from a self-limiting seizure to a self-sustaining one is established by maladaptive receptor trafficking, whereby GABA_A receptors are progressively endocytosed while glutamatergic receptors (NMDA and AMPA) are transported to the synaptic membrane, causing excitotoxicity and alteration in glutamate-dependent downstream signaling. The subsequent influx of Ca²⁺ exposes neurons to increased levels of [Ca²⁺]i, which overwhelms mitochondrial buffering, resulting in irreversible mitochondrial membrane depolarization and mitochondrial injury. Oxidative stress resulting from mitochondrial leakage and increased production of reactive oxygen species activates the inflammasome and induces a damage-associated molecular pattern. Neuroinflammation perpetuates oxidative stress and exacerbates mitochondrial injury, thereby jeopardizing mitochondrial energy supply in a state of accelerated ATP consumption. Additionally, Ca²⁺ overload can directly damage neurons by activating enzymes involved in the breakdown of proteins, phospholipids, and nucleic acids. The cumulative effect of these effector pathways is neuronal injury and neuronal death. Surviving neurons undergo long-term alterations that serve as a substrate for epileptogenesis. This review highlights the multifaceted mechanisms underlying SE self-sustainability, pharmacoresistance, and subsequent epileptogenesis. Full article

Urban expansion fragments once-contiguous forest patches, generating pronounced edge gradients that modulate soil physicochemical properties and biodiversity. We quantified how fragmentation reshaped the soil microbiome continuum and its implications for soil carbon storage in a temperate urban mixed deciduous forest. A total of 18 plots were considered in this study, with six plots for each fragment type. Intact interior forest (F), internal forest path fragment (IF), and external forest path fragment (EF) soils were sampled at 0–15, 15–30, and 30–45 cm depths and profiled through phospholipid-derived fatty acid (PLFA) chemotyping and amino sugar proxies for living microbiome and microbial-derived necromass assessment, respectively. Carbon fractionation was performed through the chemical oxidation method. Diversity indices (Shannon–Wiener, Pielou evenness, Margalef richness, and Simpson dominance) were calculated based on the determined fatty acids derived from the phospholipid fraction. The microbial biomass ranged from 85.1 to 214.6 nmol g⁻¹ dry soil, with the surface layers of F exhibiting the highest values (p < 0.01). Shannon diversity declined systematically from F > IF > EF. The microbial necromass varied from 11.3 to 23.2 g⋅kg⁻¹. Fragmentation intensified the stratification of carbon pools, with organic carbon decreasing by approximately 14% from F to EF. Our results show that EFs possess a declining microbiome continuum that weakens their carbon sequestration capacity in urban forests. Full article

Background: Previous research has demonstrated that 20 kHz probe or 37 kHz bath sonication of poloxamers comprising polypropylene glycol (PPG) and polyethylene glycol (PEG) blocks can generate degradation byproducts that are toxic to mammalian cells and organisms. Herein, an investigation of a PEGylated phospholipid micelle was undertaken to identify low-molecular-weight sonolytic degradation byproducts that could be cytotoxic. The concern here lies with the fact that sonication is a frequently employed step in drug delivery manufacturing processes, during which PEGylated phospholipids can be subjected to shear forces and other extreme oxidative and thermal conditions. Methods: Control and 20 kHz-sonicated micelles of DSPE-mPEG2000 were analyzed using dynamic light scattering (DLS) and zeta potential analyses to study colloidal properties, matrix-assisted laser desorption/ionization–time of flight (MALDI-TOF) mass spectroscopy (MS) and proton nuclear magnetic resonance (¹H-NMR) spectroscopy to study the structural integrity of DSPE-mPEG2000, and ¹H-NMR spectroscopy and high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection to quantitate the formation of low-molecular-weight degradation byproducts. Results: MALDI-TOF-MS analyses of 20 kHz-sonicated DSPE-mPEG2000 revealed the loss of ethylene glycol moieties in accordance with depolymerization of the PEG chain; ¹H-NMR spectroscopy showed the presence of formate, a known oxidative/thermal degradation product of PEG; and HPLC-UV showed that the generation of formate was dependent on 20 kHz probe sonication time between 5 and 60 min. Conclusions: It was found that 20 kHz sonication can degrade the PEG chain of DSPE-mPEG2000, altering the micelle’s PEG corona and generating formate, a known ocular toxicant. Full article

This study developed phospholipid-based liposomes loaded with extract from wild thyme (Thymus serpyllum L.) tea processing residues to enhance polyphenol stability and delivery. Liposomes were prepared with phospholipids alone or combined with 10–30 mol% cholesterol or β-sitosterol. The effect of different lipid compositions on encapsulation efficiency (EE), particle size, polydispersity index (PDI), zeta potential, stability, thermal properties, diffusion coefficient, and diffusion resistance of the liposomes was investigated. Liposomes with 10 mol% sterols (either cholesterol or β-sitosterol) exhibited the highest EE of polyphenols, while increasing sterol content to 30 mol% resulted in decreased EE. Particle size and PDI increased with sterol content, while liposomes prepared without sterols showed the smallest vesicle size. Encapsulation of the extract led to smaller liposomal diameters and slight increases in PDI values. Zeta potential measurements revealed that sterol incorporation enhanced the surface charge and stability of liposomes, with β-sitosterol showing the most pronounced effect. Stability testing demonstrated minimal changes in size, PDI, and zeta potential during storage. UV irradiation and lyophilization processes did not cause significant polyphenol leakage, although lyophilization slightly increased particle size and PDI. Differential scanning calorimetry revealed that polyphenols and sterols modified the lipid membrane transitions, indicating interactions between extract components and the liposomal bilayer. FT-IR spectra confirmed successful integration of the extract into the liposomes, while UV exposure did not significantly alter the spectral features. Thiobarbituric acid reactive substances (TBARS) assay demonstrated the extract’s efficacy in mitigating lipid peroxidation under UV-induced oxidative stress. In contrast, liposomes enriched with sterols showed enhanced peroxidation. Polyphenol diffusion studies showed that encapsulation significantly delayed release, particularly in sterol-containing liposomes. Release assays in simulated gastric and intestinal fluids confirmed controlled, pH-dependent polyphenol delivery, with slightly better retention in β-sitosterol-enriched systems. These findings support the use of β-sitosterol- and cholesterol-enriched liposomes as stable carriers for polyphenolic compounds from wild thyme extract, as bioactive antioxidants, for food and nutraceutical applications. Full article

Choline has been recognized as an essential nutrient involved in various physiological functions critical to human health. Adequate daily intake of choline has been established by the US National Academy of Medicine in 1998, considering choline requirements for different ages, sex differences and physiological states (e.g., pregnancy). By serving as a precursor for acetylcholine and phospholipids, choline is important for cholinergic transmission and the structural integrity of cell membranes. In addition, choline is involved in lipid and cholesterol transport and serves as a methyl donor after oxidation to betaine. Extracellular choline is transported across the cell membrane via various transport systems (high-affinity and low-affinity choline transporters) with distinct features and roles. An adequate dietary intake of choline during pregnancy supports proper fetal development, and throughout life supports brain, liver, and muscle functions, while choline deficiency is linked to disease states like fatty liver. Choline has important roles in neurodevelopment, cognition, liver function, lipid metabolism, and cardiovascular health. While its signaling role has been considered mostly indirect via acetylcholine and phosphatidylcholine which are synthesized from choline, emerging evidence supports a role for choline as an intracellular messenger acting on Sigma-1R, a non-opioid intracellular receptor. These new findings expand the cell signaling repertoire and increase the current understanding of the role of choline while warranting more research to uncover the molecular mechanisms and significance in the context of GPCR signaling, the relevance for physiology and disease states. Full article

Quercetin (QE) is a naturally occurring flavonoid found in many fruits, vegetables, and other plant-based foods. It is recognized for its diverse pharmacological activities. Among its many therapeutic potentials, its antidiabetic properties are of particular interest due to the growing worldwide prevalence of diabetes mellitus. QE improves glycemic control by enhancing insulin sensitivity, stimulating glucose uptake, and preserving pancreatic beta cell function. These effects are mediated by the modulation of key molecular pathways, including AMPK, PI3K/Akt, and Nrf2/ARE, as well as by the suppression of oxidative stress and pro-inflammatory cytokines, such as TNF-α and IL-6. Furthermore, QE mitigates the progression of diabetic complications such as nephropathy, retinopathy, and vascular dysfunction, reducing lipid peroxidation and protecting endothelial function. However, the clinical application of quercetin is limited by its low water solubility, poor bioavailability, and extensive phase II metabolism. Advances in formulation strategies, including the use of nanocarriers, co-crystals, and phospholipid complexes, have shown promise in improving its pharmacokinetics. This review elucidates the mechanistic basis of QE quercetin antidiabetic action and discusses strategies to enhance its therapeutic potential in clinical settings. Full article

Oxidized phospholipids (OxPLs) are increasingly recognized as biologically active lipids involved in various pathologies. Both exposure to pathogenic factors and the efficacy of protective mechanisms are critical to disease development. In this study, we characterized an immunoassay that quantified the total capacity of the plasma to degrade or mask OxPLs, thereby preventing their interaction with cells and soluble proteins. OxLDL-coated plates were first incubated with human blood plasma or a control vehicle, followed by an ELISA using a monoclonal antibody specific to oxidized phosphatidylethanolamine. Pretreatment with the diluted blood plasma markedly inhibited mAb binding. The masking assay was optimized by evaluating the buffer composition, the compatibility with various anticoagulants, potential interfering compounds, the kinetic parameters, pre-analytical stability, statistical robustness, and intra- and inter-individual variability. We propose that this masking assay provides a simple immunological approach to assessing protective mechanisms against lipid peroxidation products. Establishing this robust and reproducible method is essential for conducting clinical association studies that explore masking activity as a potential biomarker of the predisposition to a broad range of lipid-peroxidation-related diseases. Full article

Obesity and related metabolic disorders are closely linked to dysregulated lipid metabolism, where the metabolic balance of diacylglycerol (DAG) played a pivotal role. Although cis-palmitoleic acid (cPOA) exhibits anti-obesity effects, its efficacy varies across dietary conditions, and its molecular mechanisms remains unclear. In this study, we investigated the dose-dependent regulatory effects of cPOA on DAG metabolic shunting in db/db mice, employing lipidomics, pathway analysis, and gene/protein expression assays. Under a basal diet, low-dose cPOA (75 mg/kg) inhibited DAG-to-triglyceride (TAG) conversion, reducing hepatic lipid accumulation, while medium-to-high doses (150–300 mg/kg) redirected DAG flux toward phospholipid metabolism pathways (e.g., phosphatidylcholine [PC] and phosphatidylethanolamine [PE]), significantly lowering body weight and adiposity index. In high-fat diet (HFD)-fed mice, cPOA failed to reduce body weight but alleviated HFD-induced hepatic pathological damage by suppressing DAG-to-TAG conversion and remodeling phospholipid metabolism (e.g., inhibiting PE-to-PC conversion). Genetic and protein analyses revealed that cPOA downregulated lipogenic genes (SREBP-1c, SCD-1, FAS) and upregulated fatty acid β-oxidation enzymes (CPT1A, ACOX1), while dose-dependently modulating DGAT1, CHPT1, and PEMT expression to drive DAG metabolic shunting. Notably, DAG(36:3, 18:1–18:2) emerged as a potential biomarker for HFD-aggravated metabolic dysregulation. This study elucidated cPOA as a bidirectional regulator of lipid synthesis and oxidation, improving lipid homeostasis through dose-dependent DAG metabolic reprogramming. These findings provide novel insights and strategies for precision intervention in obesity and related metabolic diseases. Full article