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The self‐assembly of amphiphilic molecules produces structures of diverse dimensions, encompassing micelles, tubules, lamellae, and vesicles. This study focuses on elucidating the controllability of amphiphilic lipid molecule self‐assembly in size and uniformity to facilitate our understanding of the molecular characteristics that correlate with the functions and attributes of the assembled structures. Electrospray deposition allows micropatterning of lipid molecules in conjunction with a conductive–nonconductive patterned substrate. The solvent in the sprayed mist undergoes evaporation during flight, leading to the deposition of dry lipids exclusively on the conductive regions of the substrate. This process enables homogeneous lipid micropatterning, effectively circumventing the coffee‐ring effect. Subsequent hydration of the lipid pattern triggers the spontaneous formation of a size‐controlled, unilamellar vesicle array on the substrate, spanning an area of a few square millimeters. The vesicles exhibits monodispersity, with a coefficient of variation below 8% for sizes ranging from 5 to 20 μm. The size‐controlled self‐assembly process is adaptable to various lipid compositions, thereby demonstrating that the molecular characteristics manifest in the morphological features appear as phase separation, budding, and curvature of vesicle membranes. The approach further validates its suitability for conducting time‐resolved analyses of molecular transport and ligand binding on the monodispersed vesicle array. [ABSTRACT FROM AUTHOR]

Aging coincides with the progressive loss of muscle mass and strength, increased adiposity, and diminished physical function. Accordingly, interventions aimed at improving muscle, metabolic, and/or physical health are of interest to mitigate the adverse effects of aging. In this study, we tested a stem cell secretome product, which contains extracellular vesicles and growth, cytoskeletal remodeling, and immunomodulatory factors. We examined the effects of 4 weeks of 2×/week unilateral intramuscular secretome injections (quadriceps) in ambulatory aged male C57BL/6 mice (22–24 months) compared to saline‐injected aged‐matched controls. Secretome delivery substantially increased whole‐body lean mass and decreased fat mass, corresponding to higher myofiber cross‐sectional area and smaller adipocyte size, respectively. Secretome‐treated mice also had greater whole‐body physical function (grip strength and rotarod performance) and had higher energy expenditure and physical activity levels compared to control mice. Furthermore, secretome‐treated mice had greater skeletal muscle Pax7+ cell abundance, capillary density, collagen IV turnover, reduced intramuscular lipids, and greater Akt and hormone sensitive lipase phosphorylation in adipose tissue. Finally, secretome treatment in vitro directly enhanced muscle cell growth and IL‐6 production, and in adipocytes, it reduced lipid content and improved insulin sensitivity. Moreover, indirect treatment with secretome‐treated myotube culture media also enhanced muscle cell growth and adipocyte size reduction. Together, these data suggest that intramuscular treatment with a stem cell secretome improves whole‐body metabolism, physical function, and remodels skeletal muscle and adipose tissue in aged mice. [ABSTRACT FROM AUTHOR]

New advancements in nanocarrier technologies are revolutionizing the delivery of drugs through the skin, allowing for precise treatment with better absorption, stability, and bioavailability. This review investigates lipid and inorganic nanocarriers like liposomes, ethosomes, and inorganic nanoparticles and assesses their potential for delivering drugs through the skin. It emphasizes the mechanisms that enable controlled release and deeper skin penetration, which are crucial for ensuring effectiveness in clinical applications. The review synthesizes existing research, acknowledging that only few nanocarriers are successfully deployed in clinical settings. By offering a comprehensive overview, it sheds light on the progress and future obstacles to using nanocarriers for drug delivery through the skin. [ABSTRACT FROM AUTHOR]

A physiological and metabolic database for various species of Amazonian plants is crucial to the species selection and sustainable utilization of their diversity. We hypothesized that understanding the mobilization of Carapa seed reserves and water uptake during germination could provide insights into the physiological behavior and propagation to differentiate species of the same genus. Given this, the mobilization mechanisms of primary reserves, water uptake, and enzymatic activities in seeds of two species of Carapa (Carapa guianensis and Carapa vasquezii) were investigated. The lipid content was high in both species, with a value of 63.7 ± 4.7% for C. guianensis and 55 ± 1.5% for C. vasquezii. Carapa guianensis showed higher values for the other evaluated reserves. The protein profile highlights a band between 15 and 25 kDa in C. guianensis. As for the enzymatic activities investigated (lipase, amylase, protease, amd acid phosphatase), C. guianensis showed greater activity for most of them, except for acid phosphatase. Overall, the species showed different metabolic strategies and dynamics regarding the water uptake and use of reserves. Our findings indicate that distinct metabolic pathways are employed during the germination and initial seedling growth stages of two Carapa species. This trait can potentially guide the use and conservation of these species. [ABSTRACT FROM AUTHOR]

High-density lipoprotein (HDL) transports excess cholesterol from peripheral tissues back to the liver, and plasma HDL levels are inversely related to cardiovascular disease incidence. ATP-binding cassette A1 (ABCA1) is a member of the ABC protein superfamily, and generates nascent HDL, which consists of several hundreds of phospholipids and cholesterol wrapped by apolipoprotein A-I (apoA-I). However, it remains unclear whether cholesterol is a transport substrate of ABCA1. Since ATP hydrolysis of ABC proteins is typically increased by their transport substrates, we characterized the effects of cholesterol on the ATPase activity of purified ABCA1 using liposomes of various lipid compositions. ABCA1 showed substantial ATPase activity (20–30 nmol |$\cdot$| min−1 |$\cdot$| mg−1) only in liposomes containing anionic lipids, including phosphatidylserine. Cholesterol increased the ATPase activity by 1.6- to 3-fold in the presence of anionic lipids. Moreover, phosphatidylserine addition to BHK/ABCA1 cells increased phosphatidylcholine and cholesterol efflux to apoA-I. Next, we investigated the sterol specificity of ABCA1. The ATPase activity of ABCA1 was strongly enhanced by desmosterol and zymosterol, similar to cholesterol. In contrast, 7-dehydrocholesterol and lathosterol weakly increased the ATPase activity, and no increase was observed with stigmasterol or brassicasterol. These findings suggest that ABCA1 transports cholesterol and prefers cholesterol over plant sterols as a transport substrate. [ABSTRACT FROM AUTHOR]

Mutations in RAS, a family of proteins found in all human cells, drive a third of cancers, including many pancreatic, colorectal, and lung cancers. However, there is a lack of clinical therapies that can effectively prevent RAS from causing tumor growth. Recently, a protease was engineered that specifically degrades active RAS, offering a promising new tool for treating these cancers. However, like many other intracellularly acting protein-based therapies, this protease requires a delivery vector to reach its site of action within the cell. In this study, we explored the incorporation of cationic lipids into ionizable lipid nanoparticles (LNPs) to develop a RAS protease delivery platform capable of inhibiting cancer cell proliferation in vitro and in vivo. A library of 13 LNPs encapsulating RAS protease was designed, and each formulation was evaluated for in vitro delivery efficiency and toxicity. A subset of four top-performing LNP formulations was identified and further evaluated for their impact on cancer cell proliferation in human colorectal cancer cells with mutated KRAS in vitro and in vivo , as well as their in vivo biodistribution and toxicity. In vivo , both the concentration of cationic lipid and type of cargo influenced LNP and cargo distribution. All lead candidate LNPs showed RAS protease functionality in vitro , and the top-performing formulation achieved effective intracellular RAS protease delivery in vivo , decreasing cancer cell proliferation in an in vivo xenograft model and significantly reducing tumor growth and size. Overall, this work demonstrates the use of LNPs as an effective delivery platform for RAS proteases, which could potentially be utilized for cancer therapies. [Display omitted] [ABSTRACT FROM AUTHOR]

The success of mRNA vaccines against COVID-19 has enhanced the potential of lipid nanoparticles (LNPs) as a system for the delivery of mRNA. In this review, we describe our progress using a lipid library to engineer ionizable lipids and promote LNP technology from the viewpoints of safety, controlled biodistribution, and mRNA vaccines. These advancements in LNP technology are applied to cancer immunology, and a potential nano-DDS is constructed to evaluate immune status that is associated with a cancer-immunity cycle that includes the sub-cycles in tumor microenvironments. We also discuss the importance of the delivery of antigens and adjuvants in enhancing the cancer-immunity cycle. Recent progress in NK cell targeting in cancer immunotherapy is also introduced. Finally, the impact of next-generation DDS technology is explained using the MITO-Porter membrane fusion-based delivery system for the organelle targeting of the mitochondria. We introduce a successful example of the MITO-Porter used in a cell therapeutic strategy to treat cardiomyopathy. [Display omitted] • The efficiency of lipid nanoparticles is discussed from the viewpoint of a 3-dimensinal structure of ionizable lipids. • A potential nano-DDS is designed based on a cancer immunity cycle that includes sub-cycles in a tumor microenvironment. • MITO-Porter was introduced as an organelle-targeting DDS that was successfully applied to cell transplantation therapy. [ABSTRACT FROM AUTHOR]

Lipid-based drug formulations are promising systems for improving delivery of drugs to ocular tissues, such as retina. To develop lipid-based systems further, an improved understanding of their pharmacokinetics is required, but high-quality in vivo experiments require a large number of animals, raising ethical and economic questions. In order to expedite in vivo kinetic testing of lipid-based systems, we propose a barcode approach that is based on barcoding liposomes with non-endogenous lipids. We developed and evaluated a liquid-chromatography-mass spectrometry method to quantify many liposomes simultaneously in aqueous humor, vitreous, and neural retina at higher than ±20% precision and accuracy. Furthermore, we showed in vivo suitability of the method in pharmacokinetic evaluation of six different liposomes after their simultaneous injection into the rat vitreal cavity. We calculated pharmacokinetic parameters in vitreous and aqueous humor, quantified liposome concentrations in the retina, and quantitated retinal distribution of the liposomes in the rats. Compared to individual injections of the liposome formulations, the barcode-based study design enabled reduction of animal numbers from 72 to 12. We believe that the proposed approach is reliable and will reduce and refine ocular pharmacokinetic experiments with liposomes and other lipid-based systems. [Display omitted] • A method to quantify many liposome formulations and study their ocular pharmacokinetics within the same animal was developed. • The ocular pharmacokinetics of six barcoded liposomes were successfully evaluated within the same animal. • The barcode lipid method reduced the number of animals required for a pharmacokinetic study from 72 to 12. [ABSTRACT FROM AUTHOR]

The advent of lipid nanoparticles (LNPs) containing ionizable cationic lipids has enabled the encapsulation, stabilization, and intracellular delivery of nucleic acid payloads, leading to FDA-approved siRNA-based therapy and mRNA-based vaccines. Other nucleic acid-based therapeutic modalities, including protein replacement and CRISPR-mediated gene knockout and editing, are being tested in clinical trials, in many cases, for the treatment of liver-related diseases. However, to fully exploit these therapies beyond the liver, improvements in their delivery to extrahepatic targets are needed. Towards this end, both active targeting strategies based on targeting ligands grafted onto LNPs and passive targeting relying on physicochemical LNP parameters such as surface composition, charge, and size are being evaluated. Often, the latter strategy depends on the interaction of LNPs with blood components, forming what is known as the biomolecular corona. Here, I discuss potential challenges related to current LNP-based targeting strategies and the studies of the biomolecular corona on LNPs. I propose potential solutions to overcome some of these obstacles and present approaches currently being tested in preclinical and clinical studies, which face fewer biological barriers than traditional organ-targeting approaches. [Display omitted] • Presents an overview of LNP-based strategies for extrahepatic RNA delivery. • Highlights potential challenges with the LNP strategies and approaches to overcome some of them. • Stresses inherent challenges associated with biomolecular corona studies of LNPs. • Highlights that LNPs are a minor subpopulation of nanoparticles in human plasma. • Advocates innovative approaches to drive progress in the LNP field. [ABSTRACT FROM AUTHOR]

There are no FDA-approved lipid inhibitors for cancer treatment despite promising preclinical data to suggest their utility. Only fatty acid synthase (FASN) inhibitors have reached clinical-stage testing. New results suggest central nervous system (CNS)-resident tumors are primed for FASN and stearoyl-CoA desaturase 1 (SCD1) inhibitors due the paucity of microenvironmental lipids. SCD1 is an emerging therapeutic target due to the central role that monounsaturated fatty acids play in preventing cell death. Cluster of differentiation 36 (CD36) inhibitory antibodies are poised for a clinical breakthrough based on their seemingly unanimous pro-tumorigenic function in the tumor microenvironment (TME), and CD36 inhibition may enhance the activity of immune checkpoint inhibitors. Alterations in dietary lipids through prescribed diets have shown exciting activity in preclinical testing, although more optimization of diet composition and molecular targets is required. Cancer cells perturb lipid metabolic pathways for a variety of pro-tumorigenic functions, and deregulated cellular metabolism is a hallmark of cancer cells. Although alterations in lipid metabolism in cancer cells have been appreciated for over 20 years, there are no FDA-approved cancer treatments that target lipid-related pathways. Recent advances pertaining to cancer cell fatty acid synthesis (FAS), desaturation, and uptake, microenvironmental and dietary lipids, and lipid metabolism of tumor-infiltrating immune cells have illuminated promising clinical applications for targeting lipid metabolism. This review highlights emerging pathways and targets for tumor lipid metabolism that may soon impact clinical treatment. [ABSTRACT FROM AUTHOR]

Introduction: Recently, the incidence of hypertriglyceridemia-associated pancreatitis (HTG-AP) has been increasing. The pathogenesis of lipogenic pancreatitis is not fully understood. This study aimed to retrospectively analyze the laboratory data, clinical manifestations, and prognosis of patients with lipid-derived pancreatitis who received lipid purification, to explore whether lipid purification is a better treatment for acute hyperlipidemic pancreatitis. Methods: In this study, we enrolled five subjects diagnosed with HTG-AP at the Second Xiangya Hospital of Central South University between 2021 and 2022. We collected demographic data, medical histories, clinical manifestations, and laboratory data. All patients received routine therapy. Blood lipid purification was conducted using the double filtration plasmapheresis (DFPP) method. Plasma was separated from blood cells and purified to remove cholesterol, triglycerides, and low-density lipoprotein (LDL). SPSS was used for statistical analyses. Results: Following a single lipoprotein apheresis (LA) treatment, significant improvements in serum lipid levels were observed. Three patients achieved triglyceride levels below 5.65 mmol/L within 24 h, while the remaining 2 patients experienced reductions of 82% and 78%, respectively. The average triglyceride level decreased from 36.82 to 7.27 mmol/L, representing an 80% reduction from baseline. Total cholesterol decreased by 59% on average, and LDL levels decreased by 69%. Statistically significant differences were observed in triglyceride and cholesterol levels before and after treatment. Four patients exhibited increased HDL levels posttreatment, while 1 patient showed a decrease. The average HDL/TC level was 21% higher after treatment. Conclusion: LA in HTG-AP effectively improves clinical symptoms, rapidly lowers lipid levels, and achieves good therapeutic outcomes. Plain Language Summary: Hypertriglyceridemia-associated pancreatitis is a condition where high levels of fats in the blood can lead to pancreas inflammation. The treatment goal is to quickly lower these fat levels. Lipid purification, a method to remove fats from the blood, has shown promise but lacks clear guidelines for its use. This study aimed to analyze the data of patients with this type of pancreatitis who underwent lipid purification to determine its effectiveness. Five patients diagnosed with acute lipogenic pancreatitis were included in the study. They received routine therapies and underwent lipid purification using a technique called DFPP. After a single treatment, significant improvements were observed in the patients' lipid levels. Triglyceride levels decreased by 80% on average, and total cholesterol decreased by 59%. Lipid purification effectively improved symptoms, reduced lipid levels. [ABSTRACT FROM AUTHOR]

The B‐cell lymphoma 2 (BCL2) family members, BCL2‐associated protein X (BAX) and BCL2 homologous antagonist killer (BAK), are required for programmed cell death via the mitochondrial pathway. When cells are stressed, damaged or redundant, the balance of power between the BCL2 family of proteins shifts towards BAX and BAK, allowing their transition from an inactive, monomeric state to a membrane‐active oligomeric form that releases cytochrome c from the mitochondrial intermembrane space. That oligomeric state has an essential intermediate, a symmetric homodimer of BAX or BAK. Here we describe crystal structures of dimers of the core domain of BAX, comprising its helices α2–α5. These structures provide an atomic resolution description of the interactions that drive BAX homo‐dimerisation and insights into potential interaction between core domain dimers and membrane lipids. The previously identified BAK lipid‐interacting sites are not conserved with BAX and are likely to determine the differences between them in their interactions with lipids. We also describe structures of heterodimers of BAK/BAX core domains, yielding further insight into the differences in lipid binding between BAX and BAK. [ABSTRACT FROM AUTHOR]

Background: Alterations in the secretion and composition of skin surface lipids (SSL) are closely associated with the development of acne. Lipidomics is a useful tool to analyse the SSL of different types of acne. Our previous study found that phosphatidylserine and triacylglycerols dominate SSL changes in male acne and infantile acne, respectively. However, skin surface lipids as well as specific lipids in female acne patients remain to be investigated. Objectives: To analyse and compare the SSL profile of acne women and healthy women and to discuss the involvement of differential lipids in acne development. Methods: Systematic lipidomics approach (high‐throughput UPLC‐QTOF‐MS technology in combination with multivariate data analysis methods) was used to analyse the variations of SSL between acne and healthy groups. Results: Analysis revealed significant differences in lipid content and composition between the two groups. Further analysis showed that levels of 13 individual lipids were significantly different and followed the same trend as the main class and subclasses. The largest individual contributor to the subgroup was triglycerides (TG) and phosphatidylinositol (PI). In addition, female acne patients exhibited reduced ceramide chain length (CCL) and increased levels of unsaturated fatty acids (UFAs), The changes of CCL in female acne are identical to male acne. Conclusions: There was a significantly higher level of TG and PI in the SSL of female acne patients. A reduction in CCL and an increase in UFAs content might contribute to the reduced skin barrier function in acne patients. The results suggest that female acne may have different pathogenesis than male acne. [ABSTRACT FROM AUTHOR]

Lipid oxidation has an impact on the quality and properties of fat‐containing products that are commonly produced by cosmetics or coatings industries. In this study, a water‐in‐oil‐in‐water emulsion (48% w/w of pre‐polymerized linseed oil stabilized with alkylpolyglucoside) was subjected to oxidation under accelerated aging conditions at 50°C over 15 days. After fat extraction from emulsion, peroxide, and p‐anisidine values were measured using standardized methods. The application of near infrared spectroscopy (NIRS) in conjunction with chemometrics was investigated to assess the quality parameters of emulsions under accelerated aging within closed flasks. Significant variations were observed across the following spectral regions: 7541–5948, 5739–3657, and 3645–3637 cm−1. Partial least squares regression discriminant analysis, possibly combined with multiplicative scattering correction preprocessing, proved to be a powerful method to classify the emulsions according to two oxidation levels defined by periods A and B. The performances of the prediction model were characterized by a precision of 85%, a predictive value of period A of 98%, a sensitivity of 99%, a specificity of 81%, and an accuracy of 90%. Thus, we demonstrate that NIRS is a suitable analytical method to discriminate emulsions according to their aging behavior. Practical Applications: The PLS‐DA method coupled to near infrared spectroscopy analyses is adapted to assess the chemical degradations of vegetable oil–based emulsions due to lipid oxidation. This tool is interesting for at‐line or off‐line monitoring of emulsions during their storage. As it is a fast and nondestructive method, the quality control of a formulation stored in a closed glass container is facilitated. This method could also be used to determine the effectiveness of an antioxidant or a drier in emulsions, respectively, prepared for cosmetics and coatings. [ABSTRACT FROM AUTHOR]

Lipid oxidation deteriorates the sensory and nutritional quality of food emulsions containing polyunsaturated fatty acids. Classically, different extraction solvents are used as a first step to measure lipid oxidation in emulsions. However, it is unclear how the applied extraction method influences the measured lipid oxidation values. In this work, we systematically examined the performance of common solvent mixtures such as chloroform, methanol, and hexane (or isooctane)–isopropanol on lipid extraction from emulsions stabilized with different emulsifiers (Tween 20 (T20), whey proteins, and pea proteins) and oxidation levels, and how this, in turn, affected the measured hydroperoxide concentrations. Chloroform–methanol was the most effective solvent (lipid yield >93 wt.%). When using hexane–isopropanol, extraction yields were consistently high for T20‐ and pea protein‐based emulsions (>60 wt.%), but in whey protein‐based emulsions, values as low as 26 wt.% were measured. In case of incomplete extraction, hydroperoxide concentrations measured by colorimetric methods need to be corrected for this effect. When using 1H NMR to assess lipid oxidation, the actual amount of extracted lipids is intrinsically taken into account. This highlights not only the importance of the extraction method in determining lipid oxidation in emulsions but also that of the actual analysis method. Practical application: This study highlights that the lipid extraction yield can vary depending not only on the emulsion composition (e.g., type of emulsifier) but also on the oxidative state of the emulsion and the extraction solvent used. If this is overlooked, errors can be made in the hydroperoxide determination. Although these effects can be corrected for, this is not standard procedure, which implies that awareness on this matter should be increased. It is also important to point out that depending on the solvent used, the different lipid classes (including various lipid oxidation products) may be extracted at different levels. Chloroform–methanol should be preferred for extraction of all lipid and lipid oxidation‐derived molecules, including aldehydes. [ABSTRACT FROM AUTHOR]

Solid Lipid Nanoparticles (SLN), the first type of lipid-based solid carrier systems in the nanometer range, were introduced as a replacement for liposomes. SLN are aqueous colloidal dispersions with solid biodegradable lipids as their matrix. SLN is produced using processes like solvent diffusion method and high-pressure homogenization, among others. Major benefits include regulated release, increased bioavailability, preservation of peptides and chemically labile compounds like retinol against degradation, cost-effective excipients, better drug integration, and a broad range of applications. Solid lipid nanoparticles can be administered via different routes, such as oral, parenteral, pulmonary, etc. SLN can be prepared by using high shear mixing as well as low shear mixing. The next generation of solid lipids, nanostructured lipid carriers (NLC), can reduce some of the drawbacks of SLN, such as its restricted capacity for drug loading and drug expulsion during storage. NLC are controlled nanostructured lipid particles that enhance drug loading. This review covers a brief introduction of solid lipid nanoparticles, manufacturing techniques, benefits, limitations, and their characterization tests. [ABSTRACT FROM AUTHOR]

Purpose: Dairy foods are often a major contributor to dietary saturated fatty acids (SFA) intake. However, different SFA-rich foods may not have the same effects on cardiovascular risk factors. We compared full-fat yogurt with low-fat yogurt and butter for their effects on cardiometabolic risk factors in healthy individuals. Methods: Randomized, two-period crossover trial conducted from October 2022 to April 2023 among 30 healthy men and women (15 to receive full-fat yogurt first, and 15 to receive low-fat yogurt and butter first). Participants consumed a diet with 1.5-2 servings of full-fat (4%) yogurt or low-fat (< 1.5) yogurt and 10–15 g of butter per day for 4 weeks, with 4 weeks wash-out when they consumed 1.5-2 servings of low-fat milk. At baseline, and the end of each 4 weeks, fasting blood samples were drawn and plasma lipids, glycemic and inflammatory markers as well as expression of some genes in the blood buffy coats fraction were determined. Results: All 30 participants completed the two periods of the study. Apolipoprotein B was higher for the low-fat yogurt and butter [changes from baseline, + 10.06 (95%CI 4.64 to 15.47)] compared with the full-fat yogurt [–4.27 (95%CI, -11.78 to 3.23)] and the difference between two treatment periods was statistically significant (p = 0.004). Non-high-density lipoprotein increased for the low-fat yogurt and butter [change, + 5.06 (95%CI (-1.56 to 11.69) compared with the full-fat yogurt [change, − 4.90 (95%CI, -11.61 to 1.81), with no significant difference between two periods (p = 0.056). There were no between-period differences in other plasma lipid, insulin, and inflammatory biomarkers or leukocyte gene expression of ATP-binding cassette transporter 1 and CD36. Conclusion: This study suggests that short-term intake of SFAs from full-fat yogurt compared to intake from butter and low-fat yogurt has fewer adverse effects on plasma lipid profile. ClinicalTrials.gov: NCT05589350, 10/15/2022. [ABSTRACT FROM AUTHOR]

Background: Artichoke (Cynara scolymus L.) has the potential to treat diabetes, dyslipidemia, hypertension, and obesity. However, the evidence from previous studies is not consistent. Objectives: This meta-analysis evaluated the efficacy of products derived from artichokes on blood glucose, lipid level, blood pressure, and anthropometric parameters. Methodology: The literature was reviewed via international databases (PubMed, ScienceDirect, and Scopus). A total of 21 RCTs with high quality, assessed by the Cochrane risk-of-bias tool, were included. Results: Artichoke was linked to a significant reduction in fasting blood sugar (FBS) (WMD: −3.76 mg/dL: 95%CI −7.31, −0.22), insulin level (WMD: −1.35 mIU/L: 95%CI −2.29, −0.41), and HOMA-IR (WMD: −1.00: 95%CI −1.95, −0.06). Similar results were observed for LDL-c (WMD: −12.94 mg/dL: 95%CI −18.02, −7.87), total cholesterol (TC) (WMD: −19.64 mg/dL: 95%CI −23.94, −15.35), and triglyceride (TG) (WMD: −13.36 mg/dL: 95%CI −19.06, −7.66). Moreover, participants who administered artichoke experienced a significant reduction in SBP (WMD: −1.59 mmHg: 95%CI −3.02, −0.16), body weight (BW) (WMD: −1.17 kg: 95%CI −1.75, −0.60), and BMI (WMD: −0.30 kg/m2: 95%CI −3.02, −0.16). Conclusion: Artichoke may improve blood glucose, lipid profile, blood pressure, and anthropometric parameters. A large, well-designed RCT and head-to-head comparison using a standardized preparation of artichoke will provide definitive data on specific participants. [ABSTRACT FROM AUTHOR]

Porphyromonas gingivalis produces five classes of serine/glycine lipids that are recovered in lipid extracts from periodontitis‐afflicted teeth and diseased gingival tissues, particularly at sites of periodontitis. Because these lipids are recovered in diseased gingival tissues, the purpose of the present study was to evaluate the capacity of cultured human gingival fibroblasts (HGF), keratinocytes, and macrophages to hydrolyze these lipids. We hypothesize that one or more of these cell types will hydrolyze the serine/glycine lipids. The primary aim was to treat these cell types for increasing time in culture with individual highly enriched serine/glycine lipid preparations. At specified times, cells and culture media samples were harvested and extracted for hydrolysis products. The serine/glycine lipids and hydrolysis products were quantified using liquid chromatography–mass spectrometry (LC–MS) and free fatty acids were quantified using gas chromatograph–mass spectrometer. LC–MS analysis used two different mass spectrometric methods. This study revealed that treatment of HGF or macrophage (THP1) cells with lipid (L) 654 resulted in breakdown to L342 and subsequent release into culture medium. However, L654 was converted only to L567 in gingival keratinocytes. By contrast, L1256 was converted to L654 by fibroblasts and macrophages but no further hydrolysis or release into medium was observed. Gingival keratinocytes showed no hydrolysis of L1256 to smaller lipid products but because L1256 was not recovered in these cells, it is not clear what hydrolysis products are produced from L1256. Although primary cultures of gingival fibroblasts and macrophages are capable of hydrolyzing specific serine/glycine lipids, prior analysis of lipid extracts from diseased gingival tissues revealed significantly elevated levels of L1256 in diseased tissues. These results suggest that the hydrolysis of bacterial lipids in gingival tissues may reduce the levels of specific lipids, but the hydrolysis of L1256 is not sufficiently rapid to prevent significant accumulation at periodontal disease sites. [ABSTRACT FROM AUTHOR]

[Display omitted] Lipid nanoparticles containing a cationic lipid are increasingly used in drug and gene delivery as they can display improved cellular uptake, enhanced loading for anionic cargo such as siRNA and mRNA or exhibit additional functionality such as cytotoxicity against cancer cells. This research study tests the hypothesis that the molecular structure of the cationic lipid influences the structure of the lipid nanoparticle, the cellular uptake, and the resultant cytotoxicity. Three potentially cytotoxic cationic lipids, with systematic variations to the hydrophobic moiety, were designed and synthesised. All the three cationic lipids synthesised contain pharmacophores such as the bicyclic coumarin group (CCA12), the tricyclic etodolac moiety (ETD12), or the large pentacyclic triterpenoid "ursolic" group (U12) conjugated to a quaternary ammonium cationic lipid containing twin C12 chains. The cationic lipids were doped into monoolein cubosomes at a range of concentrations from 0.1 mol% to 5 mol% and the effect of the lipid molecular architecture on the cubosome phase behaviour was assessed using a combination of Small Angle X-Ray Scattering (SAXS), Dynamic Light Scattering (DLS), zeta-potential and cryo-Transmission Electron Microscopy (Cryo-TEM). The resulting cytotoxicity of these particles against a range of cancerous and non-cancerous cell-lines was assessed, along with their cellular uptake. The molecular architecture of the cationic lipid was linked to the internal nanostructure of the resulting cationic cubosomes with a transition to more curved cubic and hexagonal phases generally observed. Cubosomes formed from the cationic lipid CCA12 were found to have improved cellular uptake and significantly higher cytotoxicity than the cationic lipids ETD12 and U12 against the gastric cancer cell-line (AGS) at lipid concentrations ≥ 75 µg/mL. CCA12 cationic cubosomes also displayed reasonable cytotoxicity against the prostate cancer PC-3 cell-line at lipid concentrations ≥ 100 µg/mL. In contrast, 2.5 mol% ETD12 and 2.5 mol% U12 cubosomes were generally non-toxic against both cancerous and non-cancerous cell lines over the entire concentration range tested. The molecular architecture of the cationic lipid was found to influence the cubosome phase behaviour, the cellular uptake and the toxicity although further studies are necessary to determine the exact relationship between structure and cellular uptake across a range of cell lines. [ABSTRACT FROM AUTHOR]

This article explores the recruitment of arbuscular mycorrhizal (AM) conserved genes for ectomycorrhizal (ECM) symbiosis. ECM symbiosis, which is a more recent form of symbiosis than AM symbiosis, involves the formation of a mantle around the root and an intercellular Hartig net. The study found that ECM host species from the Fagales order maintained the majority of AM-conserved genes, unlike other non-AM hosts. Transcriptome analysis revealed that several of these maintained genes were induced in ECM symbiosis, suggesting that ECM formation recruits AM-derived mechanisms. The study focuses on ECM-only hosts, which are plant species that exclusively engage in ECM symbiosis and have lost the ability to form AM symbiosis. The researchers discovered that ECM-only hosts maintain 64% of the AM-conserved orthologous groups (OGs), highlighting the importance of these genes in ECM symbiosis. They also identified specific genes, such as RAM2, involved in lipid biosynthesis and arbuscule formation in ECM roots. The study suggests that the preservation of AM-conserved genes in ECM-only hosts supports their role in ECM symbiosis. [Extracted from the article]

This study aimed to determine whether concentrations of testosterone and its main precursor after menopause, dehydroepiandrosterone (DHEA), are associated with lipoproteins and other lipids in community-dwelling older women. The Sex Hormones in Older Women (SHOW) study was an observational study of 6358 Australian women, aged at least 70 years, with no prior major adverse cardiovascular event who had sex hormones measured by liquid chromatography–tandem mass spectrometry. Associations between hormones and lipids were examined using multilinear regression adjusted for potential confounders. The cross-sectional analyses included 3231 participants, median age 74.0 (interquartile range 71.7–77.9) years. Compared with concentrations in the lowest quartile (Q1), testosterone concentrations in the highest quartiles (Q3 and Q4) were positively associated with high-density lipoprotein cholesterol (HDL-C) (p = 0.002 and p < 0.001, respectively) while Q4 testosterone concentrations were positively associated with total cholesterol (p = 0.038). Q2, Q3 and Q4 testosterone concentrations were significantly inversely associated with triglycerides (TG) (p = 0.024, p = 0.003 and p < 0.001, respectively). For DHEA, Q4 concentrations was positively associated with non-HDL-C (p = 0.024). In older women, higher endogenous testosterone concentrations are significantly associated with higher HDL-C and lower TG, indicating a less atherogenic profile. These findings suggest a neutral, or potentially protective, cardiovascular disease effect of testosterone in older women. [ABSTRACT FROM AUTHOR]

A commercial lipase from Rhizopus japonicus was activated and utilized for triglyceride (TG) modification for producing structured lipids via acidolysis of TGs and fatty acids. To activate the lipase, lipase powder was mixed with glass beads (GBs) in 1-dodecanol and then a buffer solution were added dropwise to form hydrated lipase aggregates. After removal of liquid phase in the mixuture, the residue consisting of hydrated lipases and GBs was lyophilized and then the hydration – aggregation-pretreated lipase loaded onto GBs was recovered. The acidolytic activity of the lipase was significantly enhanced after hydration – aggregation pretreatment, whereas untreated lipase exhibited little activity. The effects of the surface hydrophobicity, diameter, and amount of lipase loading on GBs on the acidolytic activity of the lipase were investigated. The optimal GBs and lipase loadings were 0.428 mm in diameter with a hydrophobic surface and 89.2 U/g-GB, respectively. Under these conditions, the lipase exhibited an 8-fold higher catalytic activity than that of the hydration – aggregation-pretreated lipase without GBs. Furthermore, continuous modification of olive oil with palmitic acid via acidolysis using the hydration – aggregation-pretreated lipase packed in a column reactor was achieved for 116 h. The half-life of the packed-bed reactor was 149 h. [Display omitted] ● Lyophilizing lipase aggregates with glass beads enhanced acidolytic activity. ● Activated lipase can modify olive oil with palmitic acid via acidolysis. ● A packed bed reactor was developed using the activated lipases. ● Water content affected activity and stability of lipase during continuous run. [ABSTRACT FROM AUTHOR]

Objective: Statin treatment compliance and achieving target levels differ between populations. This study aimed to determine the status of achieving the lipid targets and evaluate patients' compliance to statin treatment in type 2 diabetic patients with dyslipidemia. Method: This cross-sectional study included type 2 diabetes mellitus (T2DM) patients with dyslipidemia who applied for treatment at our polyclinics. Statin compliance was evaluated using the Modified Morisky Adherence Scale (MMAS-8) through a face-to-face interview. Cardiovascular (CV) risk was calculated according to the 2019 ESC (European Society of Cardiology) criteria by evaluating the patients' individual risk factors. LDL targets were determined according to risk categories with the same criteria. Results: A total of 504 patients (F/M: 274/230) were included. The serum LDL levels were 102.6 ± 39.2 mg/dL. Of the patients, 56.1% were under statin treatment. CV risk was very high in 73.6% of patients. LDL levels were significantly lower in users than in non-users (91.2 ± 26.0, 117.3 ± 38.4, p < 0.0001). The rate of reaching the LDL target was 14.8% in statin users. Treatment compliance was low for 40.6% of statin users. Discontinuation of statin treatment due to side effects was 15.7% (n = 14). N = 49 patients willingly discontinued statin treatment. They reported that 40.8% considered the treatment unnecessary. Conclusion: It was observed that 56.1% of type 2 diabetic patients were on statin therapy. A small percentage of them 14.8% (n = 42) reached the LDL target. Statin non-compliance and a lack of awareness of the statin treatment are the main reasons for high LDL levels in type 2 diabetic patients. [ABSTRACT FROM AUTHOR]

Background: This study examined the effects of a single all-out bout of 30-s sprint-cycle performed daily for 5 consecutive days per week for 6 weeks, on aerobic fitness, muscle strength and metabolic-health markers in physically active young males and females. Methods: Healthy, physically active 20–28 year olds, were randomly assigned to either experimental (EXP, N = 11) or non-training control (CON, N = 8) group. With supervision, the EXP group performed one bout of 30-s sprint-cycle daily, Mondays to Fridays over 6 weeks, while CON group continued with their usual lifestyle. The followings were measured at pre- and post-intervention: maximal aerobic power, peak torque of knee extensors and flexors at velocities 30° s−1 and 300° s−1, resting heart rate, resting blood pressure, body fat percentage, fasting lipid profile, fasting blood glucose, and fasting insulin levels. Results: There were no significant improvements in the EXP group for all the measured variables (all P > 0.05); except for significant interaction effects in peak torque of knee extensors at 30° s−1 (P = 0.044) and low-density lipoprotein-cholesterol (P = 0.046). Post hoc test indicate that CON group showed decline in their low-density lipo-proteins levels (P = 0.024). Conclusion: Six weeks of one all-out bout of 30-s sprint-cycle per day, for 5 consecutive days per week, was ineffective in improving cardiovascular fitness, maximal strength, and most health markers in physically active young adults. The present results when combined with the previous literature suggest that there is a possibility of a minimum threshold for a number of sprint-cycle bouts needed to be performed before any form of cardio-metabolic-health benefit is accrued. [ABSTRACT FROM AUTHOR]

Background: This study aimed to assess the response patterns of circulating lipids to exercise and diet interventions in nonalcoholic fatty liver disease (NAFLD). Methods: The 8.6-month four-arm randomized controlled study comprised 115 NAFLD patients with prediabetes who were assigned to aerobic exercise (AEx; n = 29), low-carbohydrate diet (Diet; n = 28), AEx plus low-carbohydrate diet (AED; n = 29), and nonintervention (NI, n = 29) groups. Hepatic fat content (HFC) was quantified by proton magnetic resonance spectroscopy. Serum lipidomic analytes were measured using liquid chromatography-mass spectrometry. Results: After intervention, the total level of phosphatidylcholine (PC) increased significantly in the AEx group (P = 0.043), whereas phosphatidylethanolamine (PE) and triacylglycerol decreased significantly in the AED group (P = 0.046 and P = 0.036, respectively), and phosphatidylserine decreased in the NI group (P = 0.002). Changes of 21 lipid metabolites were significantly associated with changes of HFC, among which half belonged to PC. Most of the molecules related to insulin sensitivity belonged to sphingomyelin (40 of 79). Controlling for the change of visceral fat, the significant associations between lipid metabolites and HFC remained. In addition, baseline serum lipids could predict the response of HFC to exercise and/or diet interventions (PE15:0/18:0 for AED, area under the curve (AUC) = 0.97; PE22:6(4Z,7Z,10Z,13Z,16Z,19Z)/0:0 for AEx, AUC = 0.90; and PC14:1(9Z)/19:1(9Z) for Diet, AUC = 0.92). Conclusions: Changes of lipidome after exercise and/or diet interventions were associated with HFC reductions, which are independent of visceral fat reduction, particularly in metabolites belonging to PC. Importantly, baseline PE could predict the HFC response to exercise, and PC predicted the response to diet. These results indicate that a circulating metabolomics panel can be used to facilitate clinical implementation of lifestyle interventions for NAFLD management. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the effects of salinity on the proximate composition and fatty acid profile of the Nile tilapia fillet when reared in a biofloc system. Juveniles (200 ± 10 g) were reared at salinities of 2, 8, 15 and 22 PSU for 56 days. At the end of the experiment, the proximate composition and the fatty acid profile were evaluated in the fillets. No significant differences were observed for crude protein, ether extract, dry matter and ash levels. However, saturated (SFA) and monounsaturated (MUFA) fatty acids were higher in tilapia reared at 2 PSU compared to other salinities (8, 15, and 22 PSU). The polyunsaturated fatty acids (PUFA) contents did not vary among fish reared at salinities of 2, 8, and 15 PSU but were significantly lowest in tilapia reared at 22 PSU. The overall results suggest that the different salinities do not significantly affect the proximate composition of the Nile tilapia file reared in a biofloc system. On the other hand, the fatty acid composition was influenced by salinity, as a reduction in PUFA content was observed at the highest tested salinity (22 PSU) and an increase in SFA and MUFA contents were recorded at the lowest tested salinity (2 PSU). [ABSTRACT FROM AUTHOR]

Aims: To assess the effects of COVID‐19 pandemic on clinical variables as part of the routine clinical monitoring of patients with chronic diseases in primary care. Design: A prospective longitudinal study was conducted in primary care centres of the Andalusian Health Service. Methods: Data were recorded before the pandemic (T1), during the declaration of the state of emergency (T2) and in the transition phase (T3). The Barthel index and the Short Portable Mental Status Questionnaire (SPMSQ) were used to analyse functional and cognitive changes at the three time points. HbA1c, systolic and diastolic blood pressure, heart rate, BMI and lipid levels were assessed as clinical variables. Descriptive statistics and non‐parametric chi‐square test were used for analysis. STROBE checklist was used for the preparation of this paper. Results: A total fo148 patients with chronic conditions were included in the analysis. Data analysis revealed in T2 only significant reductions in BMI, total levels of cholesterol and HDL during the onset of the pandemic. Barthel Index, SPMSQ, blood pressure and triglycerides and LDL levels worsened in T2, and the negative effects were maintained in T3. Compared to pre‐pandemic values, HbA1c levels improved in T3, but HDL levels worsened. Conclusions: COVID‐19 has drastically disrupted several functional, cognitive and biological variables. These results may be useful in identifying clinical parameters that deserve closer attention in the case of a new health crisis. Further studies are needed to assess the potential impacts of each specific chronic condition. Impact: Cognitive and functional status, blood pressure and triglycerides and LDL levels worsen in short term, maintaining the negative effects in medium‐term. [ABSTRACT FROM AUTHOR]

Algal bioprospecting in ecosystems leads to exploring native microalgae and the competency evaluation of economically producing lipids as biofuel or nutritional applications. In this study, ten microalgae species were screened from the saline water lake. Chlorella vulgaris, Chlorella sorokiniana, Chlamydomonas raudensis, Chlamydomonas hedleyi, Dunaliella salina, Picochlorum bazangan sp. nov., Tetraselmis bazangan sp. nov., Haematococcus lacustris, Nannochloropsis oceanic, and Scenedesmus rubescens were isolated and identified using 18SrDNA and tufA markers. Biodiesel potentials were assayed by the determination of biomass productivity, biochemical components, fatty acid profile, and biodiesel properties. The results showed that the maximum biomass yield (1.22 g/L) belonged to C. vulgaris. The highest protein, carbohydrate, chlorophyll, and carotenoid content were recorded in C. vulgaris, C. raudensis, C. sorokiniana, and D. salina, respectively. N. oceanica accumulated high lipid content and omega-3 fractions (31.09%). However, C. hedleyi had the highest lipid productivity (11.64 g/L/day) compared to other microalgae. The best species for biodiesel production was C. vulgaris, with a specific growth rate of 0.36 day−1, lipid productivity of 7.45 g/L/day, and C16-C18 fatty acid profile of 78.3%. The microalgae C. vulgaris had appropriate biodiesel properties of low viscosity (4.49), high cetane number (55.38), and relatively low cloud point (4.98). Another choice was N. oceanic, with high lipid productivity, cetane number (59.79), oxidative stability (56.43), and low iodine value (47.11). Microalgae T. bazangan sp. nov. had a cetane number (55.24), low cloud point (4.71), and C16-C18 fatty acid profile of 82.34%. Accordingly, C. vulgaris, T. bazangan sp. nov., and N. oceanic can be considered potential species for biodiesel. [ABSTRACT FROM AUTHOR]

Microalgae are lipid-rich microscopic eukaryotic algae that can be used aiming for more sustainable biodiesel production by employing environmentally sound processes. The present work evaluates biodiesel production using a biocatalyst and two microalgae species as oil feedstock (Chlorella vulgaris and Aurantiochytrium sp.). Lipid extraction was performed using different techniques, namely, Soxhlet extractions (8 h — both species) with different solvents (hexane; hexane:ethanol (1:1 v/v); and chloroform) and room temperature hexane extraction (72 h — Aurantiochytrium sp.). Transesterification occurred for 24 h (150 rpm), using 30 % lipase loading. The results showed that high extraction temperatures cause microalgae oil degradation, focused on unsaturated fatty acids, leading to a lower biodiesel conversion yield. Using Aurantiochytrium sp. oil, it was possible to obtain around 55 %wt. of biodiesel conversion yield using oil extracted at room temperature (6:1 methanol:oil molar ratio), whereas for the oil extracted in the Soxhlet apparatus, the biodiesel conversion yield was around 30 %wt.. The low lipid content (1.0 %wt.) and biodiesel conversion yield (up to 25 %wt.) obtained using C. vulgaris show that the biomass used in the current study has low potential for biodiesel production. However, enzymatic biodiesel production from microalgae represents a promising avenue for sustainable energy generation, offering a renewable and environmentally responsible solution to the world's energy needs. For that purpose, further studies, such as the optimisation of the extraction and transesterification of Aurantiochytrium sp. oil, should be carried out. [ABSTRACT FROM AUTHOR]

Background Down syndrome (DS) is the most prevalent chromosomal disorder, being the leading cause of intellectual disability. The increased life expectancy of individuals with DS has led to a shift in the incidence of non-communicable chronic diseases, resulting in new concerns, particularly cardiovascular disease (CVD) and Alzheimer's disease. This study aimed to analyse the blood lipid profile of a large DS cohort to establish a baseline for evaluating health risk parameters. Methods A comprehensive literature search was conducted on PubMed and Virtual Health Library databases to identify original articles published before July 2022. Selected studies were included in the meta-analysis. Results Fifteen studies reporting serum lipid levels in individuals with DS were incorporated into the analysis. The meta-analysis used the means and standard deviations extracted from the selected studies. The analysis encompassed 671 participants in the DS group and 898 euploid controls. The results indicated significant differences in total cholesterol [C] (mean difference [MD]: −3.34; CI: 95%: −4.94 to −1.73; P < 0.0001), HDL-C (MD: −3.39; CI: 95%: −6.72 to −0.06; P = 0.05) and triglycerides (MD: 21.48; CI: 95%: 9.32 to 33.65; P = 0.0005) levels between individuals with DS and their control counterparts. Conclusions Individuals with DS have less favourable blood lipid concentrations than their controls, particularly HDL-C, triglycerides, and total-C, even when grouped by age. These findings underscore the importance of closer monitoring of lipid profiles in people with DS and the necessity for specific cut-offs for this population, considering the risk for ischemic heart and Alzheimer's diseases. [ABSTRACT FROM AUTHOR]

Mycobacterium abscessus belongs to the largest group of mycobacteria, the rapid-growing saprophytic mycobacteria, and is one of the most difficult-to-treat opportunistic pathogen. Several features pertain to the high adaptability of M. abscessus to the host. These include the capacity to survive and persist within amoebae, to transition from a smooth to a rough morphotype that occurs during the course of the disease and to express of a wide array of virulence factors. The main objective of this narrative review consists to report major assets of M. abscessus that contribute to the virulence of these rapid-growing saprophytic mycobacteria. Strikingly, many of these determinants, whether they are from a mycobacterial origin or acquired by horizontal gene transfer, are known virulence factors found in slow-growing and strict pathogens for humans and animals. In the light of recent published work in the field we attempted to highlight major features characterizing M. abscessus pathogenicity and to explain why this led to the emergence of this mycobacterial species in patients with cystic fibrosis. M. abscessus genome plasticity, the smooth-to-rough transition, and the expression of a panel of enzymes associated with virulence in other bacteria are key players in M. abscessus virulence. In addition, the very large repertoire of lipid transporters, known as mycobacterial membrane protein large and small (MmpL and MmpS respectively), deeply influences the pathogenicity of M. abscessus , as exemplified here for some of them. All these traits largely contribute to make M. abscessus a unique mycobacterium regarding to its pathophysiological processes, ranging from the early colonization steps to the establishment of severe and chronic pulmonary diseases. [ABSTRACT FROM AUTHOR]

Human iPSC-derived airway organoids (iPSC-AOs) exhibit cellular heterogenicity resembling the human native airway. Bioinformatics analysis revealed a robust dysregulation in inflammation, lipid-metabolism pathway, and alternative splicing in SARS-CoV-2 infected airway organoids. Manipulating lipid homeostasis using cholesterol-lowering drugs (e.g. Statins) relocated the viral entry receptor angiotensin-converting enzyme-2 (ACE-2), leading to the reduction of SARS-CoV-2 entry and replication. [Display omitted] • Single-cell RNA sequencing showed that iPSC-AOs exhibition of the genetic profiles highly resembling the genotypes of human airways. • iPSC-AOs are susceptible to SARS-COV-2 infection and the expressions of S and N proteins after viral infection. • Bioinformatics analysis indicated the involvement of aberrant enrichment of lipid transport and lipid pathways in infected iPSC-AOs. • Statin preincubation relocated ACE2, reduced N protein, and limited SARS-CoV-2 infection in iPSC-AOs. • Lipid modifications consistently inhibited viral entry of various SARS-CoV-2 strains (wild-type, alpha, delta, omicron). Modifications of lipid metabolism were closely associated with the manifestations and prognosis of coronavirus disease of 2019 (COVID-19). Pre-existing metabolic conditions exacerbated the severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection while modulations of aberrant lipid metabolisms alleviated the manifestations. To elucidate the underlying mechanisms, an experimental platform that reproduces human respiratory physiology is required. Here we generated induced pluripotent stem cell-derived airway organoids (iPSC-AOs) that resemble the human native airway. Single-cell sequencing (ScRNAseq) and microscopic examination verified the cellular heterogeneity and microstructures of iPSC-AOs, respectively. We subjected iPSC-AOs to SARS-CoV-2 infection and investigated the treatment effect of lipid modifiers statin drugs on viral pathogenesis, gene expression, and the intracellular trafficking of the SARS-CoV-2 entry receptor angiotensin-converting enzyme-2 (ACE-2). In SARS-CoV-2-infected iPSC-AOs, immunofluorescence staining detected the SARS-CoV-2 spike (S) and nucleocapsid (N) proteins and bioinformatics analysis further showed the aberrant enrichment of lipid-associated pathways. In addition, SARS-CoV-2 hijacked the host RNA replication machinery and generated the new isoforms of a high-density lipoprotein constituent apolipoprotein A1 (APOA1) and the virus-scavenging protein deleted in malignant brain tumors 1 (DMBT1). Manipulating lipid homeostasis using cholesterol-lowering drugs (e.g. Statins) relocated the viral entry receptor angiotensin-converting enzyme-2 (ACE-2) and decreased N protein expression, leading to the reduction of SARS-CoV-2 entry and replication. The same lipid modifications suppressed the entry of luciferase-expressing SARS-CoV-2 pseudoviruses containing the S proteins derived from different SARS-CoV-2 variants, i.e. wild-type, alpha, delta, and omicron. Together, our data demonstrated that modifications of lipid pathways restrict SARS-CoV-2 propagation in the iPSC-AOs, which the inhibition is speculated through the translocation of ACE2 from the cell membrane to the cytosol. Considering the highly frequent mutation and generation of SARS-CoV-2 variants, targeting host metabolisms of cholesterol or other lipids may represent an alternative approach against SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Summary: Objective: To prospectively evaluate the relationship between cumulative environmental stress and cardiometabolic risk in middle childhood, and to examine whether hair cortisol, a measure of hypothalamic pituitary adrenal‐axis activity, mediates this relationship. Methods: In a cohort of children from low‐income households (n = 320; 59% Hispanic, 23% Black, body mass index (BMI) percentile >50th at enrollment), environmental stressors including family and neighbourhood factors representing disadvantage/deprivation, and cortisol concentrations from hair samples, were measured over five timepoints beginning when children were 2–4 years old. Cardiometabolic risk factors (i.e., BMI, blood pressure, lipids, blood sugar, C‐reactive protein) were measured at the final timepoint when children were 7–11 years of age. Results: In adjusted logistic regression models, greater cumulative environmental stress was associated with a higher likelihood of elevated cardiometabolic risk in middle childhood (p = 0.01). Children from minoritized racial/ethnic groups had a higher prevalence of both stressors and cardiometabolic risk factors. Cumulative environmental stress was associated with higher hair cortisol concentrations (p < 0.01). However, hair cortisol was not directly associated with cardiometabolic risk factors and did not explain the association between environmental stress and cardiometabolic risk in causal mediation analysis. Conclusions: The influence of cumulative stress on cardiometabolic health can be observed in middle childhood and may contribute to cardiometabolic health disparities, highlighting the importance of public health interventions to mitigate disadvantage. [ABSTRACT FROM AUTHOR]

The plant cuticle controls non‐stomatal water loss and can serve as a barrier against biotic agents, whereas the heteropolymer suberin and its associated waxes are deposited constitutively at specific cell wall locations. While several transcription factors controlling cuticle formation have been identified, those involved in the transcriptional regulation of suberin biosynthesis remain poorly characterized. The major goal of this study was to further analyse the function of the R2R3‐Myeloblastosis (MYB) transcription factor AtMYB41 in formation of the cuticle, suberin, and suberin‐associated waxes throughout plant development.For functional analysis, the organ‐specific expression pattern of AtMYB41 was analysed and Atmyb41ge alleles were generated using the CRISPR/Cas9 system. These were investigated for root growth and water permeability upon stress. In addition, the fatty acid, wax, cutin, and suberin monomer composition of different organs was evaluated by gas chromatography.The characterization of Atmyb41ge mutants revealed that AtMYB41 negatively regulates the production of cuticular lipids and fatty acid biosynthesis in leaves and seeds, respectively. Remarkably, biochemical analyses indicate that AtMYB41 also positively regulates the formation of cuticular waxes in stems of Arabidopsis thaliana.Overall, these results suggest that the AtMYB41 acts as a negative regulator of cuticle and fatty acid biosynthesis in leaves and seeds, respectively, but also as a positive regulator of wax production in A. thaliana stems. [ABSTRACT FROM AUTHOR]

Background and Purpose: Oat β‐glucan could ameliorate epidermal hyperplasia and accelerate epidermal barrier repair. Dectin‐1 is one of the receptors of β‐glucan and many biological functions of β‐glucan are mediated by Dectin‐1. Dectin‐1 promotes wound healing through regulating the proliferation and migration of skin cells. Thus, this study aimed to investigate the role of oat β‐glucan and Dectin‐1 in epidermal barrier repair. Experimental Approach: To investigate the role of Dectin‐1 in the epidermal barrier, indicators associated with the recovery of a damaged epidermal barrier, including histopathological changes, keratinization, proliferation, apoptosis, differentiation, cell–cell junctions and lipid content were compared between WT and Dectin‐1−/− mice. Further, the effect of oat β‐glucan on the disruption of the epidermal barrier was also compared between WT and Dectin‐1−/− mice. Key Results: Dectin‐1 deficiency resulted in delayed recovery and marked keratinization, as well as abnormal levels of keratinocyte differentiation, cell–cell junctions and lipid synthesis during the restoration of the epidermal barrier. Oat β‐glucan significantly reduces epidermal hyperplasia, promotes epidermal differentiation, increases cell–cell junction expression, promotes lipid synthesis and ultimately accelerates the recovery of damaged epidermal barriers via Dectin‐1. Oat β‐glucan could promote CaS receptor expression and activate the PPAR‐γ signalling pathway via Dectin‐1. Conclusion and Implications: Oat β‐glucan promote the recovery of damaged epidermal barriers through promoting epidermal differentiation, increasing the expression of cell–cell junctions and lipid synthesis through Dectin‐1. Dectin‐1 deficiency delay the recovery of epidermal barriers, which indicated that Dectin‐1 may be a potential target in epidermal barrier repair. [ABSTRACT FROM AUTHOR]

This study proposes a landscape-based scenario for the origin of viruses and cells, focusing on the adaptability of preexisting replicons from the RNP (ribonucleoprotein) world. The scenario postulates that life emerged in a subterranean "warm little pond" where organic matter accumulated, resulting in a prebiotic soup rich in nucleotides, amino acids, and lipids, which served as nutrients for the first self-replicating entities. Over time, the RNA world, followed by the RNP world, came into existence. Replicators/replicons, along with the nutritious soup from the pond, were washed out into the river and diluted. Lipid bubbles, enclosing organic matter, provided the last suitable environment for replicons to replicate. Two survival strategies emerged under these conditions: cell-like structures that obtained nutrients by merging with new bubbles, and virus-like entities that developed various techniques to transmit themselves to fresh bubbles. The presented hypothesis provides the possibility for the common origin of cells and viruses on rocky worlds hosting liquid water, like Earth. [ABSTRACT FROM AUTHOR]

Whole-body vibration (WBV), a training method based on the stimulation of muscle contraction by mechanical vibration generated in a vibrating platform, is claimed to be effective in diabetes management. This meta-analysis evaluated WBV effects against other exercises, placebo, or no intervention in type-2 diabetes. Medline, Scopus, and Web of Science databases were systematically searched through June 2023. Randomized controlled trials reported the effect of WBV on glucose (hemoglobin A1C and fasting blood glucose), and lipid profiles (total cholesterol, triglycerides, high, and low-density lipoprotein) were included. Two researchers independently extracted the characteristics of the studies, participants, WBV intervention and comparisons, and the outcomes from the included articles. The Physiotherapy Evidence Database (PEDro) scale assessed trial quality. In this review, all articles had no high risk of bias according to the PEDro scale, with studies achieving optimal, excellent, and good scores. Network meta-analysis revealed that WBV was effective for reducing hemoglobin A1C when compared with conventional (mean difference: − 1.58%, 95%CrI: − 2.51, − 0.47) and resistance exercise (mean difference: − 1.32%, 95%CrI: − 1.96, − 0.33). WBV had also a desirable but insignificant effect on hemoglobin A1C compared to stretching and balance exercises, placebo, and no intervention. The current pairwise meta-analysis did not show that WBV favors fasting blood glucose and lipids. WBV may have potential advantages for glycemic control in type-2 diabetes. However, uncertainties in the findings remain due to the limited number of studies and their heterogeneity. [ABSTRACT FROM AUTHOR]

Lipid-lowering therapies, particularly non-statin regimens, are underutilized as ~2/3 of patients with atherosclerotic cardiovascular (CV) disease (CVD) are not optimally managed, and do not attain target low-density lipoprotein cholesterol (LDL-C) concentrations, despite statin treatment. Statins have been the mainstay of hypolipidemic therapies; however, they are plagued by adverse effects, which have partly hindered their more widespread use. Ezetimibe is often the first added mode of treatment to attain LDL-C goals as it is efficacious and also allows the use of a smaller dose of statin, while the need for more expensive therapies is obviated. We herein provide a comprehensive review of the effects of ezetimibe in lipid lowering and reducing CV events and improving outcomes. Of the hypolipidemic therapies, oral ezetimibe, in contrast to newer agents, is the most convenient and/or affordable regimen to be utilized as mono- or combined therapy supported by data from CV outcomes studies attesting to its efficacy in reducing CVD risk and events. When combined with a statin, the statin dose could be lower, thus curtailing side-effects, while the hypolipidemic effect is enhanced (by ~20%) as the percentage of patients with target level LDL-C (<70 mg/dL) is higher with combined treatment versus a high-intensity statin. Ezetimibe could also serve as an alternative treatment in cases of statin intolerance. In conclusion, ezetimibe has an excellent safety/tolerability profile; it is the first added treatment to a statin that can attain LDL-C targets. In the combined therapy, the hypolipidemic effect is enhanced while the dose of statin could be lower, thus limiting the occurrence of side-effects. Ezetimibe could also serve as an alternative mode of treatment in cases of statin intolerance. [ABSTRACT FROM AUTHOR]

Diosgenin (DG), a well-known steroidal sapogenin, is abundantly found in the plants of the Dioscoreaceae family and exhibits diverse pharmacological properties. In our previous study, we demonstrated that DG supplementation protected Caenorhabditis elegans from high glucose-induced lipid deposition, oxidative damage, and lifespan reduction. Nevertheless, the precise biological mechanisms underlying the beneficial effects of DG have not yet been described. In this context, the present study aims to elucidate how DG reduces molecular and cellular declines induced by high glucose, using the powerful genetics of the C. elegans model. Treatment with DG significantly (p < 0.01) prevented fat accumulation and extended lifespan under high-glucose conditions without affecting physiological functions. DG-induced lifespan extension was found to rely on longevity genes daf-2, daf-16, skn-1, glp-1, eat-2, let-363, and pha-4. Specifically, DG regulates lipophagy, the autophagy-mediated degradation of lipid droplets, in C. elegans, thereby inhibiting fat accumulation. Furthermore, DG treatment did not alter the triglyceride levels in the fat-6 and fat-7 single mutants and fat-6;fat-7 double mutants, indicating the significant role of stearoyl-CoA desaturase genes in mediating the reduction of fat deposition by DG. Our results provide new insight into the fat-reducing mechanisms of DG, which might develop into a multitarget drug for preventing obesity and associated health complications; however, preclinical studies are required to investigate the effect of DG on higher models. [ABSTRACT FROM AUTHOR]

Calcification of aortic valve leaflets is a growing mortality threat for the 18 million human lives claimed globally each year by heart disease. Extensive research has focused on the cellular and molecular pathophysiology associated with calcification, yet the detailed composition, structure, distribution and etiological history of mineral deposition remains unknown. Here transdisciplinary geology, biology and medicine (GeoBioMed) approaches prove that leaflet calcification is driven by amorphous calcium phosphate (ACP), ACP at the threshold of transformation toward hydroxyapatite (HAP) and cholesterol biomineralization. A paragenetic sequence of events is observed that includes: (1) original formation of unaltered leaflet tissues: (2) individual and coalescing 100’s nm- to 1 μm-scale ACP spherules and cholesterol crystals biomineralizing collagen fibers and smooth muscle cell myofilaments; (3) osteopontin coatings that stabilize ACP and collagen containment of nodules preventing exposure to the solution chemistry and water content of pumping blood, which combine to slow transformation to HAP; (4) mm-scale nodule growth via ACP spherule coalescence, diagenetic incorporation of altered collagen and aggregation with other ACP nodules; and (5) leaflet diastole and systole flexure causing nodules to twist, fold their encasing collagen fibers and increase stiffness. These in vivo mechanisms combine to slow leaflet calcification and establish previously unexplored hypotheses for testing novel drug therapies and clinical interventions as viable alternatives to current reliance on surgical/percutaneous valve implants. [ABSTRACT FROM AUTHOR]

Comprehensive Summary HpnG plays a crucial role in the production of ribosylhopane, a key intermediate in the biosynthesis of bacteriohopanepolyol. Despite early extensive studies, the precise function of HpnG has remained elusive. Here, we report functional characterization of HpnG as a purine nucleoside phosphorylase, which converts adenosylhopane to phosphoribosylhopane in the presence of phosphate. HpnG demonstrates broad substrate specificity and impressive stability, making it a valuable enzymatic tool for applications in nucleoside processing and related biotechnology. [ABSTRACT FROM AUTHOR]

Nesfatin-1 (NESF-1) has been shown to modulate lipid metabolism. We have identified a nesfatin-1-like-peptide (NLP) processed from a related precursor nucleobindin 1 (NUCB1). Here we determined if NLP, like NESF-1, regulates lipid accumulation in vitro, and tested if the disruption of nucb1 gene affects hepatic lipid metabolism genes in mice. Hepatocytes (HepG2/C3A cells) express NLP and NESF-1 and both peptides significantly reduced lipogenic enzyme mRNAs and enhanced beta-oxidation enzyme mRNAs. Lipid contents in oleic acid induced HepG2/C3A cells were attenuated by NESF-1 and NLP. The inhibitory effect on cellular lipid content was blocked by compound C, an inhibitor of AMPK. The disruption of nucb1 gene affected lipid metabolism-related enzyme mRNAs, endogenous nucb2 mRNA and AMPK phosphorylation. The lipid-lowering effects identified here highlights the potential of nucleobindins and peptides processed from them to address lipid disorders, and its possible benefits in metabolic disease management. Nesfatin-1 and nesfatin-1-like peptide reduced lipid content in oleic acid-induced HepG2/C3A cells, an effect that was blocked by an AMPK inhibitor compound C. This highlights the therapeutic potential for nesfatin-1 and NLP in lipid disorders. [ABSTRACT FROM AUTHOR]

This retrospective study aimed to evaluate the effects on the clinical signs of poisoning and adverse effects of intravenous lipid emulsion treatment in 82 animals (dogs and cats) with suspected poisonings over 18 months. Physical examination parameters and state of consciousness were documented every hour after the intravenous administration of a bolus of 2 ml/kg and 0.25 ml/kg/min over 60 minutes of a 20% intravenous lipid emulsion. The modified Glasgow coma scale and laboratory findings (blood gas analysis, triglyceride, lactate) were evaluated initially and three hours after discontinuing intravenous lipid emulsion administration. A statistical evaluation of the occurrence of adverse effects and the development of laboratory values was performed. A decrease in respiratory rate in the second control (8–12 hours) after ILE was observed. Three hours after completing of the intravenous lipid emulsion, triglyceride concentration increased about 10 times (p <0.001). Venous carbon dioxide partial pressure, bicarbonate, base excess, as well as the electrolytes sodium, potassium and ionized calcium decreased significantly (p <0.001). Patients who experienced a worsening of the modified Glasgow coma scale had a higher increase in triglyceride concentrations (p = 0.041) and plasma lactate (p = 0.034) and a larger decrease in bicarbonate concentrations (p = 0.053) compared to others. About 54% (n = 44) of the patients showed adverse effects which could be attributed to the administration of intravenous lipid emulsion and may be associated with a higher triglyceride increase. All of them were completely reversible within 33 hours. Adverse effects associated with intravenous lipid emulsion therapy were observed in half of the patients and were associated with a higher increase in triglycerides. [ABSTRACT FROM AUTHOR]

Background: Dyslipidemia, which is characterized by an unfavorable lipid profile, is a key risk factor for cardiovascular disease (CVD). Understanding the relationships between epigenetic aging and lipid levels may help guide early prevention and treatment efforts for dyslipidemia. Methods: We used weighted linear regression to cross-sectionally investigate the associations between five measures of epigenetic age acceleration estimated from whole blood DNA methylation (HorvathAge Acceleration, HannumAge Acceleration, PhenoAge Acceleration, GrimAge Acceleration, and DunedinPACE) and four blood lipid measures (total cholesterol (TC), LDL-C, HDL-C, and triglycerides (TG)) in 3,813 participants (mean age = 70 years) from the Health and Retirement Study (HRS). As a sensitivity analysis, we examined the same associations in participants who fasted prior to the blood draw (n = 2,531) and in participants who did not take lipid-lowering medication (n = 1,869). Using interaction models, we also examined whether demographic factors including age, sex, and educational attainment modified the relationships between epigenetic age acceleration and blood lipids. Results: After adjusting for age, race/ethnicity, sex, fasting status, and lipid-lowering medication use, greater epigenetic age acceleration was associated with lower TC, HDL-C, and LDL-C, and higher TG (p < 0.05), although the effect sizes were relatively small (e.g., < 7 mg/dL of TC per standard deviation in epigenetic age acceleration). GrimAge acceleration and DunedinPACE associations with all lipids remained significant after further adjustment for body mass index, smoking status, and educational attainment. These associations were stronger in participants who fasted and who did not use lipid-lowering medication, particularly for LDL-C. We observed the largest number of interactions between DunedinPACE and demographic factors, where the associations with lipids were stronger in younger participants, females, and those with higher educational attainment. Conclusion: Multiple measures of epigenetic age acceleration are associated with blood lipid levels in older adults. A greater understanding of how these associations differ across demographic groups can help shed light on the relationships between aging and downstream cardiovascular diseases. The inverse associations between epigenetic age and TC and LDL-C could be due to sample limitations or non-linear relationships between age and these lipids, as both TC and LDL-C decrease faster at older ages. [ABSTRACT FROM AUTHOR]

Cancer prognosis remains a critical clinical challenge. Lipidomic analysis via mass spectrometry (MS) offers the potential for objective prognostic prediction, leveraging the distinct lipid profiles of cancer patient-derived specimens. This review aims to systematically summarize the application of MS-based lipidomic analysis in prognostic prediction for cancer patients. Our systematic review summarized 38 studies from the past decade that attempted prognostic prediction of cancer patients through lipidomics. Commonly analyzed cancers included colorectal, prostate, and breast cancers. Liquid (serum and urine) and tissue samples were equally used, with liquid chromatography–tandem MS being the most common analytical platform. The most frequently evaluated prognostic outcomes were overall survival, stage, and recurrence. Thirty-eight lipid markers (including phosphatidylcholine, ceramide, triglyceride, lysophosphatidylcholine, sphingomyelin, phosphatidylethanolamine, diacylglycerol, phosphatidic acid, phosphatidylserine, lysophosphatidylethanolamine, lysophosphatidic acid, dihydroceramide, prostaglandin, sphingosine-1-phosphate, phosphatidylinosito, fatty acid, glucosylceramide and lactosylceramide) were identified as prognostic factors, demonstrating potential for clinical application. In conclusion, the potential for developing lipidomics in cancer prognostic prediction was demonstrated. However, the field is still nascent, necessitating future studies for validating and establishing lipid markers as reliable prognostic tools in clinical practice. [ABSTRACT FROM AUTHOR]

The use of new materials in the field of biofuel production has been represented as a step in the development of remarkable catalysts. The use of lipases in the production of biodiesel is often seen as a cost-limiting step, as the operating expenses in recovering such catalysts can lead to unfeasible market expectations. In this study, hydroxyapatite (HAp) particles were evaluated as a support to immobilize commercial lipase, following application in ethyl ester synthesis. First, hydroxyapatite was synthesized through the co-precipitation method at constant pH and selected as a support to be used in enzyme immobilization. The characterization of the biocatalyst support materials produced was carried out using DRX, BET, FTIR, TGA, and SEM analysis. The lipase from Thermomyces lanuginosus was then immobilized in the matrices, and, subsequently, there was transesterification of the vegetable oil deodorization distillate (VODD). The biodiesel samples generated showed that they were within commercial standards, achieving ester conversion greater than 96.5%. Other properties such as density (0.87 g.cm−3) and viscosity (4.36 mm2.s−1) meet the specifications required by ASTM to be used as a biofuel. In the experiment planning technique, the results revealed an experimental trend and a defined behavior: a higher lipase loading in the immobilization and the use of temperatures in the range of 40–50 °C favor high conversions of ethyl esters. Thus, this confirms that the enzymatic chemical catalyst was able to form the main fatty acid esters even using a residual lipid raw material. [ABSTRACT FROM AUTHOR]

Messenger RNA (mRNA) has emerged as a promising therapeutic modality for various diseases. However, efficient delivery of mRNA into target cells remains a significant challenge. In this study, the combinatorial synthesis and characterization of a novel series of ionizable biscarbamate lipids (IBLs) for mRNA lipid nanoparticle (LNP) delivery are reported. A simplified and scalable method is developed, resulting in IBLs suitable for formulating mRNA into stable LNPs. Two generations of IBLs are synthesized and evaluated for their mRNA transfection capacity in vitro, using eGFP as a reporter protein, leading to the identification of S‐Ac7‐DOG as a lead IBL. Upon intramuscular vaccination, S‐Ac7‐DOG LNPs instigated robust antigen‐specific CD8+ T cell responses against an mRNA encoded viral oncoprotein and a tumor neo‐antigen. In comparison to MC3 LNPs, which are used as a benchmark, S‐Ac7‐DOG LNPs exhibit low reactogenicity, robust mRNA transfection, and a distinct biodistribution, with higher accumulation in draining lymph nodes and spleen. These findings highlight the potential of IBLs as a novel and promising class of ionizable lipids for mRNA delivery in vaccines and beyond. [ABSTRACT FROM AUTHOR]

Background: Metabolic syndrome (MetS) is a cluster of risk factors related to diabetes and cardiovascular disease (CVD). Given that early identification of MetS might decrease CVD risk, it is imperative to establish a simple and cost-effective method to identify individuals at risk of MetS. The purpose of this study was to explore the relationships between several atherogenic indices (including AIP, TyG index, non-HDL-C, LDL-c/HDL-c, and TC/HDL-c) and MetS, and to assess the ability of these indices to predict MetS. Methods: The present cross-sectional study was conducted using baseline data from 9809 participants of the Hoveyzeh Cohort Study (HCS). MetS was defined based on the International Diabetes Federation (IDF). To examine the discriminatory abilities of each atherogenic indices in the identification of MetS, a receiver-operating characteristic curve was conducted. Logistic regression analysis was also performed to evaluate the relationship between atherogenic indices and MetS. Results: All of the atherogenic indices including the TyG index, AIP, non-HDL-C, TC/HDL-c, and LDL-c/HDL-c were significantly higher in participants with MetS than in those without MetS. According to the ROC curve analysis, the TyG index revealed the highest area under the curve (0.79 and 0.85 in men and women, respectively), followed by the AIP (0.76 and 0.83 in men and women, respectively). The best cutoff values for the TyG index and AIP were 8.96 and 0.16 for men and 8.84 and 0.05 for women, respectively. The TyG index and AIP were also strongly associated with MetS. Conclusion: Among the 5 atherogenic indices evaluated, the TyG index and AIP were strongly related to MetS. The TyG index also demonstrated superior discriminative ability compared to other atherogenic indices in predicting MetS. [ABSTRACT FROM AUTHOR]

Introduction: Hepatitis B Virus (HBV) is widely recognized as a "metabolic virus" that disrupts hepatic metabolic homeostasis, rendering it one of the foremost risk factors for hepatocellular carcinoma (HCC). Except for antiviral therapy, the fundamental principles underlying HBV− and HBV+ HCC have remained unchanged, limiting HCC treatment options. Objectives: In this study, we aim to identify the distinctive metabolic profile of HBV-associated HCC, with the promise of identifying novel metabolic targets that confer survival advantages and ultimately impede cancer progression. Methods: We employed a comprehensive methodology to evaluate metabolic alterations systematically. Initially, we analyzed transcriptomic and proteomic data obtained from a public database, subsequently validating these findings within our test cohort at both the proteomic and transcriptomic levels. Additionally, we conducted a comprehensive analysis of tissue metabolomics profiles, lipidomics, and the activity of the MAPK and AKT signaling pathway to corroborate the abovementioned changes. Results: Our multi-omics approach revealed distinct metabolic dysfunctions associated with HBV-associated HCC. Specifically, we observed upregulated steroid hormone biosynthesis, primary bile acid metabolism, and sphingolipid metabolism in HBV-associated HCC patients' serum. Notably, metabolites involved in primary bile acid and sphingolipids can activate the MAPK/mTOR pathway. Tissue metabolomics and lipidomics analyses further validated the serum metabolic alterations, particularly alterations in lipid composition and accumulation of unsaturated fatty acids. Conclusion: Our findings emphasize the pivotal role of HBV in HCC metabolism, elucidating the activation of a unique MAPK/mTOR signaling axis by primary bile acids and sphingolipids. Moreover, the hyperactive MAPK/mTOR signaling axis transduction leads to significant reprogramming in lipid metabolism within HCC cells, further triggering the activation of the MAPK/mTOR pathway in turn, thereby establishing a self-feeding circle driven by primary bile acids and sphingolipids. [ABSTRACT FROM AUTHOR]