Search Results (3,495)

Phospholipid transfer protein (PLTP) is a lipid transfer protein classically studied in the context of plasma lipoprotein metabolism, high-density lipoprotein (HDL) remodeling, and cardiovascular disease risk. PLTP facilitates phospholipid transfer between lipoproteins and regulates HDL particle size and composition through interactions with apolipoprotein A-I and apolipoprotein A-II. While its systemic roles in cholesterol handling, reverse cholesterol transport, and inflammatory signaling are well established, the cell-autonomous functions of PLTP within cardiomyocytes remain poorly defined, particularly in human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). Extensive experimental and clinical studies demonstrate that PLTP enhances ABCA1-dependent cholesterol efflux primarily by stabilizing ABCA1 at the plasma membrane and by promoting the generation of lipid-poor apolipoprotein A-I and pre-β HDL particles, which serve as efficient cholesterol acceptors; the magnitude of these effects depends on cellular context, PLTP expression levels, and the availability of lipid acceptors. PLTP expression is metabolically regulated and widely distributed across tissues, including macrophages and other non-hepatic cells, supporting roles beyond circulating lipoprotein remodeling. Altered PLTP activity has been linked to atherosclerosis, cardiovascular disease, and inflammatory pathways, underscoring its relevance to cardiac pathophysiology. Emerging evidence further suggests that intracellular cholesterol distribution, rather than total cholesterol content alone, critically influences mitochondrial membrane composition, bioenergetics, and stress signaling in cardiomyocytes. These observations raise the possibility that PLTP-regulated lipid flux may indirectly shape mitochondrial function by modulating cellular cholesterol homeostasis. This review synthesizes current knowledge of PLTP biology, cholesterol metabolism, and lipoprotein remodeling, and integrates these concepts with emerging frameworks in cardiomyocyte lipid metabolism and mitochondrial physiology. We highlight human iPSC-derived cardiomyocytes as a strategic and translationally relevant platform to investigate PLTP’s non-canonical, cell-intrinsic roles, identify critical knowledge gaps, and propose future directions for elucidating how PLTP may influence mitochondrial function in human cardiac cells. Full article

Background/Objectives: Peritoneal micrometastases (micromets) remain a major barrier to durable cytoreduction in ovarian and other intra-abdominal cancers because lesions are difficult to visualize and are often resistant to systemic therapy. Liposomal doxorubicin (Dox) improves pharmacokinetics but can be limited by slow intratumoral release. Porphyrin-phospholipid (PoP) liposomes enable near-infrared light–triggered release of Dox (chemophototherapy (CPT)), creating an opportunity for intraoperative fluorescence-guided treatment planning and monitoring. Here, we evaluate a laparoscopic fluorescence imaging platform for quantifying light-triggered drug delivery. Methods: LC-Dox-PoP was applied to SCC2095sc and SKOV-3 cultures in 2D monolayers and 3D spheroid clusters. Dox fluorescence was quantified using a laparoscopic fluorescence imaging system over 1–9 μg/mL concentrations and compared with standard well-plate reader measurements. Porphyrin fluorescence was monitored to assess spheroid localization and photobleaching after activation light exposure. Results: For both cell lines, Dox fluorescence exhibited an approximate 4-fold increase at the maximum administered LC-Dox-PoP concentration, following a linear trend in both SCC2095sc and SKOV-3 cultures (R² = 0.97, 0.98 for 2D and R² = 0.98, 0.98 for spheroids). Laparoscope-derived fluorescence measurements agreed with well-plate reader measurements (R² = 0.89–0.96). Porphyrin fluorescence provided stronger complementary contrast for localizing spheroid constructs and decreased after activation light exposure, consistent with photobleaching during triggered release. Conclusions: These results support a quantitative imaging framework for fluorescence-guided monitoring of light-triggered liposomal drug release and may enable individualized CPT dosimetry for peritoneal micrometastases. Findings in SCC2095sc additionally suggest potential relevance of fluorescence-guided CPT for head and neck/oral cancer, where localized post-resection adjuvant treatment may improve control of residual disease. Full article

In response to the growing global demand for food, intensive genetic selection programs have been implemented to improve livestock efficiency and productivity. Understanding how such selection alters metabolism across nutritional stages is essential for optimizing feeding strategies. In this study, we examined the impact of long-term genetic selection for growth rate (GR) on the plasma metabolome of reproductive female rabbits using an untargeted metabolomics approach. Two vitrified–rederived populations from the same paternal line but separated by 18 generations of GR selection (R19V and R37V) were compared under identical environmental and nutritional conditions. We analyzed 48 plasma samples, showing that GR selection significantly influenced the metabolomic profile. Notably, R37V does exhibited a 76% increase in phospholipid LysoPE (0:0/20:4) concentrations (p < 0.0001) than R19V. GR selection affected key metabolites related to lipid metabolism and energy balance, reflecting potential changes in nutrient utilization efficiency. These findings highlight the interplay between genetics and nutrient efficiency in shaping the metabolome, offering insights that may support nutritional management in genetically improved livestock. Full article

Oxidative stress generates oxidized phospholipids (OxPLs) that alter membrane structure and inflammatory lipid signaling, yet the underlying biophysical mechanisms remain poorly understood. Here, we examine how two structurally distinct truncated oxidized phosphatidylcholines (OxPCs), 1-palmitoyl-2-(5′-oxo-valeroyl)-sn-glycero-3-phosphocholine (POVPC) and 1-palmitoyl-2-glutaryl-sn-glycero-3-phosphocholine (PGPC), remodel membrane lateral organization and regulate secretory phospholipase A₂ (sPLA₂) activity. Large unilamellar vesicles composed of sphingomyelin, cholesterol, and either monounsaturated 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) or polyunsaturated 1-palmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine (PDPC) were used to reconstitute the liquid-ordered/liquid-disordered (L_o/L_d) phase coexistence characteristic of eukaryotic plasma membranes. Fluorescence spectroscopy revealed that OxPLs modulate lipid packing and nanodomain organization in a structure- and composition-dependent manner. POVPC promoted pronounced membrane ordering and L_o domain stabilization compared with PGPC, particularly in monounsaturated membranes with low cholesterol content. In contrast, PDPC-containing membranes, especially at elevated cholesterol, exhibited enhanced structural resilience to OxPL-induced perturbations. These biophysical changes were associated with distinct functional outcomes. Notably, the relationship between membrane structural parameters and sPLA₂ activity was not linear, indicating a decoupling between bulk membrane properties and enzymatic response. sPLA₂ activity was linked to membrane lateral organization: the size of L_o domains modulate hydrolysis by influencing the physicochemical properties of L_o/L_d interfaces, which may represent preferential sites for enzyme activation. Consistent with this, POVPC reduced sPLA₂ activity through stabilization of ordered domains at both low and high cholesterol, while PGPC enhanced hydrolysis at high cholesterol. Importantly, PDPC-containing membranes attenuated sPLA₂ activity and exhibited a protective effect against OxPC-induced enzymatic activation. Together, these findings identify membrane lateral organization as a key regulator of sPLA₂ function and provide mechanistic insight into how oxidative stress can differentially modulate inflammatory lipid signaling depending on membrane composition. This work highlights membrane organization as an active determinant of enzyme activity and a potential target in pathologies associated with oxidative stress, including atherosclerosis, neuroinflammation, and metabolic disease. Full article

Dictyophora rubrovolvata is highly regarded and increasingly cultivated in China for its nutritional value, unique taste, and medicinal properties. However, the chemical composition of fresh D. rubrovolvata is unclear. This study applied a comprehensive metabolomic analysis of D. rubrovolvata to characterize and compare the metabolite profiles and identify significantly differential metabolites from three geographical origins in China. Ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS) combined with chemometrics was employed to conduct untargeted metabolomics analysis of fresh D. rubrovolvata samples collected from the Sichuan, Fujian, and Guizhou provinces in China. Among the 383 identified metabolites, lipids and organic acids were the predominant classes. There were notable variations in metabolite composition across the three geographical areas. The Sichuan (SC) group showed a high concentration of phospholipids, the Guizhou (GZ) group was characterized by specific oxidized lipids and bioactive benzenoids, and the Fujian (FJ) group showed elevated levels of the antioxidant ergothioneine. We identified 17 unique metabolites, including tryptophol, 12-oxophytodienoic acid, and various fatty acid derivatives, which may act as significantly differential metabolites for different origins. Analysis of KEGG enrichment indicated that the main metabolic pathways involved were tryptophan metabolism, glycerophospholipid metabolism, and phenylpropanoid biosynthesis. Full article

Postbiotics derived from Bacillus species are recognized as promising natural antimicrobial agents. This study aimed to systematically evaluate the inhibitory activity of postbiotics derived from B. velezensis 906 against L. monocytogenes, elucidate the underlying antibacterial mechanisms using agar diffusion assays, broth microdilution, growth kinetics, flow cytometry, phospholipid competition assays, whole-genome mining, and non-targeted metabolomics, and characterize the bioactive metabolites responsible for their antibacterial effects. The postbiotics exhibited significant antagonistic activity against Gram-positive bacteria, Gram-negative bacteria, and fungi. They also inhibited pathogens such as Salmonella and Enterobacter sakazakii. Against L. monocytogenes, the minimum inhibitory concentration was 0.0083 mg/mL. At 1 × MIC, the OD600 after 24 h remained at approximately 0.8, compared with 1.3–1.4 in the untreated control, whereas treatment at 4 × MIC almost completely inhibited bacterial growth. Mechanistic analyses suggested that the postbiotics interact with membrane phospholipids, resulting in membrane disruption, increased intracellular reactive oxygen species accumulation, and enhanced membrane permeability. Integrated genome mining and non-targeted metabolomics indicated that the antibacterial activity was associated with a coordinated antimicrobial network involving lipopeptides, polyketides, bacteriocin-related compounds, and siderophore-associated metabolites. These findings provide insight into the antibacterial basis of B. velezensis 906 postbiotics and support their potential application in food safety control. Full article

Blood metabolism in dairy cows is crucial for milk quality, functioning primarily through the “blood–milk” metabolic axis. Allium mongolicum Regel (AMR), a functional Allium herb, has been shown to regulate on ruminant lipid metabolism. This study investigated the impact of AMR ethanol extract (AME) on lactation performance, blood lipid parameters, and blood–milk metabolomes. Twelve mid-lactation Holsteins (606 ± 11 kg; milk yield 33.14 ± 2.08 kg/d) of parity 2–3 were assigned to either a basal diet (CON) or a diet supplemented with 54 g/d of AME (AEE). Results indicated that AME significantly decreased plasma triglycerides (TG), C15:0, C16:1, C18:1 n-9 c, C18:3 n-6, monounsaturated fatty acids (p < 0.05) and significantly increased C18:2 n-6 c, polyunsaturated fatty acids (p < 0.05). Lactation performance, including the average daily dry matter intake, daily yields of milk fat, protein and lactose, remained unaffected by the AME addition (p > 0.05). Metabolomic profiling revealed that AME significantly enriched the glycerophospholipid metabolism pathway in plasma, upregulating key phospholipid precursors such as L-serine and Sphinganine. Concurrently, milk metabolomics showed an upregulation of short-chain Acylcarnitines. Plasma TG correlated negatively with both plasma L-serine and milk Acylcarnitines, whereas low-density lipoprotein correlated positively with these energy-driven milk metabolites. These findings suggest that AME may contribute to remodeling the plasma lipid metabolic profile in a manner that could facilitate plasma-to-milk lipid flux. This appears to occur through enhanced hepatic lipid processing and increased mammary lipid utilization, offering preliminary insights into potential nutritional strategies for supporting lipid metabolism in dairy cows. Full article

Glioblastoma (GBM) is the most lethal and aggressive primary brain tumor in adults. Despite a standard-of-care regimen involving surgical resection, radiotherapy and temozolomide (TMZ), median overall survival typically hovers between 12 and 15 months. This poor prognosis is driven by profound intratumoral heterogeneity, glioma stem cell populations, and an immunosuppressive microenvironment that collectively fuel resistance to traditional apoptosis-centric therapies. Ferroptosis—a form of regulated cell death driven by iron-dependent phospholipid peroxidation and the collapse of antioxidant defenses—has emerged as a compelling alternative for eliminating therapy-refractory GBM cells. This review examines the molecular machinery of ferroptosis in glioma and explores how an additional regulatory layer, noncoding RNAs (ncRNAs), modulates this process. We highlight key experimentally validated axes where microRNAs, long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) orchestrate iron handling and antioxidant thresholds. These include sensitizers like miR-147a and circLRFN5, which promote iron overload, and resistors like circCDK14 and TMEM161B-AS1, which act as “ferroptosis brakes”. Furthermore, we discuss how integrative analyses of TCGA and CGGA cohorts have yielded ferroptosis-related lncRNA signatures that robustly predict patient survival. Finally, we outline the clinical potential of these ncRNAs as biomarkers and therapeutic targets while addressing the delivery challenges, such as the blood–brain barrier, that must be overcome to achieve precision, ferroptosis-oriented GBM therapy. Full article

Background: H007 is a novel selective AMP-activated protein kinase (AMPK) activator with demonstrated efficacy against hyperlipidemia; however, its oral bioavailability is limited by poor solubility and low intestinal permeability. This study aimed to develop a self-microemulsifying drug delivery system (SMEDDS) incorporating a H007–phospholipid complex (H007-PC) to improve both solubility and intestinal permeability. Methods: H007-PC-SME was prepared by integrating phospholipid complexes into an SMEDDS formulation. The formulation was optimized on the basis of emulsification efficiency, droplet size, and zeta potential, and was then evaluated for stability, in vitro drug release, and cellular uptake. Different H007 formulations were orally administered to golden hamsters to assess bioavailability, and a chylomicron flow blockade hamster model was used to evaluate lymphatic transport. Results: The optimized H007-PC-SME showed good stability, rapid self-emulsification, and improved drug solubility. Relative to ordinary H007 tablets, the relative bioavailability of H007-SME and H007-PC-SME was 376.65% and 464.62%, respectively, when calculated from M1 exposure, and 314.01% and 463.55%, respectively, when calculated from MP exposure. When evaluated in a cycloheximide model, H007-SME and H007-PC-SME increased the lymphatic transport fraction of M1 from approximately 0% to 22% and 54%, and that of MP from approximately 1% to 28% and 52% compared with ordinary H007 tablets. Conclusion: H007-PC-SME combines stable phospholipid complex formation with strong self-emulsification performance and effective drug dissolution. By overcoming the intrinsic limitations of the H007 active pharmaceutical ingredient and ordinary H007 tablets, this formulation improves membrane permeability and lymphatic transport, thereby enhancing oral bioavailability and therapeutic potential. The formulation shows good stability and acceptable in vitro biocompatibility under the tested conditions. The preparation process is straightforward, reproducible, and suitable for further pharmaceutical development. Full article

High ammonia nitrogen stress significantly compromises the survival of Litopenaeus vannamei under low-salinity conditions. However, existing studies predominantly focus on ammonia nitrogen responses under single stressors or normal seawater salinity. The molecular regulatory mechanisms, metabolic remodeling patterns, and key pathway interactions in shrimp subjected to high ammonia nitrogen stress under low-salinity environment remain unclear. In this study, we employed integrated transcriptomic and metabolomic analyses to unveil the underlying molecular responses and metabolic biomarkers in the gills of L. vannamei to ammonia stress under low-salinity conditions. First, L. vannamei underwent low-salinity acclimation from 30‰ to 5‰ salinity and was then reared for one week to acclimate to the experimental environment. Subsequently, shrimp were treated with 42.32 mg/L ammonia nitrogen for a consecutive 96 h period. Integrated transcriptomic and metabolomic analyses elucidated the stress response patterns in the gills of L. vannamei under low-salinity ammonia nitrogen exposure. Specifically, 352, 802, and 140 differentially expressed genes (DEGs) were identified at 12 h, 48 h, and 96 h post-exposure, respectively. GO and KEGG enrichment analyses revealed that the significant DEGs were primarily enriched in six major pathways: autophagy, immune-related pathway, ABC transporter, fatty acid degradation and metabolism, metabolic pathway, and PPAR signaling pathway. Metabolomic profiling identified numerous differentially accumulated metabolites (DAMs) in both positive and negative ion modes, with significantly altered DAMs mainly consisting of organic acids and their derivatives, phospholipids, and other related metabolites. Key DAMs included taurine, guanosine, 1-palmitoyl-sn-glycero-3-phosphocholine, pseudouridine, and betaine. Integrative multi-omics analysis revealed that L. vannamei mediates stress responses by modulating five core pathways under low-salinity/high-ammonia-nitrogen dual stress: fatty acid degradation and metabolism (e.g., acyl-CoA dehydrogenase short chain (Acads), acetyl-CoA acetyltransferase 2 (ACAT2)), autophagy (e.g., autophagy-related protein 101-like (atg101)), immune regulation pathway (e.g., V-type proton ATPase subunit H-like (VhaSFD), actin-5C-like (Act5C)), metabolic pathway (e.g., molybdopterin synthase catalytic subunit-like (Mocs2B), cytochrome P450 2U1-like (Cyp2b1)), and ABC transporter (e.g., ATP-binding cassette sub-family D member 3-like (ABCD3), ATP-binding cassette sub-family B member 10 (ABCB10)). Through characterization of these core pathways, this study reveals the fundamental mechanisms by which L. vannamei responds to high ammonia nitrogen stress following low-salinity acclimation, providing a theoretical foundation for estuarine shrimp farming. Full article

Estimation of the postmortem interval (PMI) remains a major challenge in forensic science. We used attenuated total reflection (ATR)–Fourier-transform infrared (FTIR) spectroscopy combined with chemometric modeling for PMI prediction using vitreous humor samples from 20 forensic cases with known PMI (24.8–97.6 h) and 10 with unknown PMI. The intensities of vibrational bands commonly associated with PMI were analyzed, and several peaks in the carbohydrate/phosphate region showed significant correlations with PMI. Principal component analysis revealed time-dependent spectral evolution, with PC1 (48.1%) associated mainly with carbohydrate/phosphate variations and PC2 (37.6%) with protein structural changes. Partial least squares regression with two latent variables achieved a cross-validated RMSE of 15.8 h (R² = 0.53) on all 20 known samples. Variable importance analysis identified glycoprotein degradation (1190 cm⁻¹) and phospholipid breakdown (736 cm⁻¹) as the dominant predictors, with traditional carbohydrate bands playing a secondary role. Predictions for unknown samples ranged from 27.1 to 80.1 h, with five of ten falling within the 90% prediction interval (±20 h) of the available estimates. This study presents a promising PMI estimation model that performed well on unseen samples, even if the sample size represents a methodological limitation that will be addressed in future investigations through larger, more diverse datasets. Full article

The cell membrane serves as the first line of defense against adverse environmental factors and is first to adapt to changing conditions. Cell membranes in both coral and its symbionts, which use different membrane adaptation strategies, have to acclimatize to various abiotic stressors. As our molecular-genetics analysis showed, colonies of Junceella fragilis were associated with dinoflagellates Cladocopium thermophilum, Gerakladium endoclionum and Breviolum minutum. We analyzed the phospholipid (PL) molecular species of the wild and cultivated Junceella fragilis and their dinoflagellates (phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylinositol (PI), ceramideaminoethylphosphonate (CAEP)), as well as thylakoid membrane lipids of dinoflagellates (glycolipids and betaine lipids). When comparing wild and cultivated J. fragilis colonies, there were no significant differences in thylakoid lipids, but there were differences in host membrane phospholipids, namely in PC, PE and PS. Thus, the profile of PL molecular species of the membrane is very sensitive to environmental factors, which probably explains the observed differences in the profiles of molecular PL species in this study. Full article

A549 cells are widely used as an in vitro model of alveolar type II (ATII) epithelial cells; however, their phenotype and metabolic state are highly sensitive to culture conditions, cell density, and the duration of static, non-passaged cultivation. Here, we examined how prolonged static culture affects lipid metabolism, mitochondrial bioenergetics, and viability in A549 cells. A549 cultures were maintained without passaging for up to 25 days in DMEM or Ham’s F-12 and analyzed using lipid secretion assays, targeted lipidomics, [¹⁴C]-acetate incorporation, Seahorse bioenergetic profiling, and transcriptional analysis of stress-associated markers. Several surfactant-associated readouts were highest during early culture, peaking on day 7, as evidenced by elevated expression of ABCA3 and SP-A and maximal secretion of surfactant-associated phospholipids. With prolonged cultivation and increasing culture density, cellular phosphatidylglycerol levels declined progressively and became nearly undetectable by day 25, accompanied by reduced anabolic lipid metabolism, lower oxygen consumption, and impaired glycolytic activity. These changes coincided with increased reactive oxygen species, elevated intracellular Ca²⁺ levels, and increased expression of stress-associated transcripts, including CASP1, IL1B, and C3. Later stages were also associated with reduced mitochondrial respiration and decreased viability. Collectively, our findings show that prolonged static culture is associated with metabolic remodeling and reduced bioenergetic capacity in A549 cells. Full article

The increasing prevalence of obesity and Alzheimer’s disease (AD) in the aging population underscores an urgent need to understand the common cellular and metabolic mechanisms they share. Accumulated evidence suggests that overlapping metabolic disturbances contribute to the pathogenesis of these two conditions. In this review, we highlight key underlying interconnecting metabolic pathways: (1) adipose-brain crosstalk mediated by adipokines and adipose tissue-derived extracellular vesicles that can modulate neuronal function and amyloid pathology, (2) dysregulated lipid metabolism affecting cholesterol, sphingolipids, and phospholipids and thereby promoting inflammation, amyloid precursor protein processing, and tau hyperphosphorylation, (3) impaired glycolysis and insulin resistance, which accelerate both obesity and neurodegenerative processes, (4) mitochondrial dysfunction marked by disrupted tricarboxylic acid cycle enzymes and electron transport chain complexes, leading to elevated reactive oxygen species and driving both obesity and AD pathology, and (5) gut microbiota dysbiosis, which can trigger inflammation as well as amyloid and tau aggregation. Together, these mechanisms show that metabolic alterations appear early, preceding clinical disease, and that understanding these underlying connections can provide strategies to protect metabolic health and prevent disease progression. Full article

This study focused on elucidating the effects of chitosan (Ch), hyaluronic acid (HA), and titanium dioxide nanoparticles (nano-TiO₂) on the physicochemical characteristics of a model bacterial membrane (layer) composed of the phospholipid DPPG (1,2-dipalmitoyl-sn-glycero-3-phospho-rac-(1-glycerol) sodium salt). The membrane was prepared on mica using the Langmuir–Blodgett (LB) technique from an aqueous subphase containing Ch, HA and/or TiO₂. Its surface properties were subsequently characterized by optical profilometry and surface free energy estimation. The nanoscale topography of the DPPG layer provided a biomimetic platform that reflects the organization of bacterial membranes, enabling a precise evaluation of how external agents, such as Ch, HA, and nano-TiO₂, modify the surface’s structural and energetic properties. The results showed that the LB films exhibit mildly heterogeneous topography, which can be attributed to lipid domains with distinct molecular packing densities. Depending on the type of biopolymer employed with TiO₂, distinct topographic architectures of the DPPG monolayers were obtained. Furthermore, the presence of nano-TiO₂ was clearly manifested as a topographic irregularity, while the analysis of hydrophilic–hydrophobic properties revealed a structurally perturbed lipid film. The results provide detailed insight into how these specific molecules (Ch, HA, nano-TiO₂) interact at the molecular level with model bacterial membranes, offering a comprehensive picture of cell–microenvironment interactions. Full article