Types Of Lipids Research Articles

Baking using oleogels

Baking using oleogels

Distinct DNA methylation signatures associated with blood lipids as exposures or outcomes among survivors of childhood cancer: a report from the St. Jude lifetime cohort

BackgroundDNA methylation (DNAm) plays an important role in lipid metabolism, however, no epigenome-wide association study (EWAS) of lipid levels has been conducted among childhood cancer survivors. Here, we performed EWAS analysis with longitudinally collected blood lipid data from survivors in the St. Jude lifetime cohort study.MethodsAmong 2052 childhood cancer survivors of European ancestry (EA) and 370 survivors of African ancestry (AA), four types of blood lipids, including high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol (TC), and triglycerides (TG), were measured during follow-up beyond 5-years from childhood cancer diagnosis. For the exposure EWAS (i.e., lipids measured before blood draw for DNAm), the DNAm level was an outcome variable and each of the blood lipid level was an exposure variable; vice versa for the outcome EWAS (i.e., lipids measured after blood draw for DNAm).ResultsAmong EA survivors, we identified 43 lipid-associated CpGs in the HDL (n = 7), TC (n = 3), and TG (n = 33) exposure EWAS, and 106 lipid-associated CpGs in the HDL (n = 5), LDL (n = 3), TC (n = 4), and TG (n = 94) outcome EWAS. Among AA survivors, we identified 15 lipid-associated CpGs in TG exposure (n = 6), HDL (n = 1), LDL (n = 1), TG (n = 5) and TC (n = 2) outcome EWAS with epigenome-wide significance (P < 9 × 10−8). There were no overlapping lipids-associated CpGs between exposure and outcome EWAS among EA and AA survivors, suggesting that the DNAm changes of different CpGs could be the cause or consequence of blood lipid levels. In the meta-EWAS, 12 additional CpGs reached epigenome-wide significance. Notably, 32 out of 74 lipid-associated CpGs showed substantial heterogeneity (Phet < 0.1 or I2 > 70%) between EA and AA survivors, highlighting differences in DNAm markers of blood lipids between populations with diverse genetic ancestry. Ten lipid-associated CpGs were cis-expression quantitative trait methylation with their DNAm levels associated with the expression of corresponding genes, out of which seven were negatively associated.ConclusionsWe identified distinct signatures of DNAm for blood lipids as exposures or outcomes and between EA and AA survivors, revealing additional genes involved in lipid metabolism and potential novel targets for controlling blood lipids in childhood cancer survivors.

A notable impact of lipid matrices on cholesterol bioaccessibility from phytosterols-loaded nanostructured lipid carriers during in vitro intestinal digestion

Encapsulation of phytosterols in nanostructured lipid carriers (NLCs) is an effective approach to improve their physicochemical properties, but the interaction of phytosterols in NLCs with cholesterol can be affected by lipid matrices. The objective of this study was to screen a desired phytosterols-loaded NLC (PS-NLC) formulation to reduce the absorption of intestinal cholesterol. A series of formulations were prepared using amphipathic glycerol monostearate (GMS) as the solid lipid fraction to increase lipid compatibity with phytosterols. All formulations showed a lowering effect on cholesterol bioaccessibility through in vitro intestinal digestion. And the PS-NLCs with medium chain triglycerides (MCT) as the liquid lipid showed significantly higher inhibition of cholesterol bioaccessibility (accessible fraction for intestinal absorption) than the formulations with long chain triglycerides (LCT), which could due to the solubilization of cholesterol by hydrolysis products of LCT, suggesting a notable impact of lipid type on cholesterol bioaccessibility. Furthermore, the analysis of distribution of phytosterols and cholesterol revealed a cocrystallization mechanism occurred during in vitro digestion. This study provides a certain reference for designing phytosterol-ingredient agents with a better hypocholesterolemic effect in water-dispersible functional foods.

Lyophilized Nasal Inserts of Atomoxetine HCl Solid Lipid Nanoparticles for Brain Targeting as a Treatment of Attention-Deficit/Hyperactivity Disorder (ADHD): A Pharmacokinetics Study on Rats.

The study aims to investigate the ability of lyophilized nasal inserts of nanosized atomoxetine HCl solid lipid nanoparticles (ATM-SLNs) to transport atomoxetine (ATM) directly to the brain and overcome the first-pass metabolism. In this case, 16 formulae of (ATM-SLNs) were prepared using hot melt emulsification, stirring and ultrasonication method technique. A full factorial design was established with 24 trials by optimization of four variables; lipid type (Compritol 888 ATO or stearic acid) (X1), lipid to drug ratio [(1:2) or (2:1)] (X2), span 60: Pluronic f127 ratio [(1:3) or (3:1)] (X3) and probe sonication time (five or ten minutes) (X4). The prepared SLNs were characterized for entrapment efficiency (EE%), in-vitro drug release after 30 min (Q30min), particle size (PS), zeta potential (ZP) and polydispersity index (PDI). Design Expert® software was used to select the optimum two formulae. The morphological examination for the optimum two formulae was carried out using a transmission electron microscope (TEM). Furthermore, eight lyophilized nasal inserts were prepared by using a 23 full factorial design by optimization of three variables: type of (ATM-SLNs) formula (X1), type of polymer (NOVEON AA1 or HPMC K100m) (X2) and concentration of polymer (X3). They were evaluated for nasal inserts' physicochemical properties. The two optimum inserts were selected by Design Expert® software. The two optimum insets with the highest desirability values were (S4 and S8). They were subjected to DSC thermal stability study and in-vivo study on rats. They were compared with atomoxetine oral solution, atomoxetine (3 mg/kg, intraperitoneal injection) and the pure atomoxetine solution loaded in lyophilized insert. (ATM-SLNs) showed EE% range of (41.14 mg ± 1.8% to 90.6 mg ± 2.8%), (Q30min%) of (27.11 ± 5.9% to 91.08 ± 0.15%), ZP of (-8.52 ± 0.75 to -28.4 ± 0.212% mV), PS of (320.9 ± 110.81% nm to 936.7 ± 229.6% nm) and PDI of (0.222 ± 0.132% to 0.658 ± 0.03%). Additionally, the two optimum (ATM-SLNs) formulae chosen, i.e., F7 and F9 showed spherical morphology. Nasal inserts had assay of drug content of (82.5 ± 2.5% to 103.94 ± 3.94%), Q15min% of (89.9 ± 6.4% to 100%) and Muco-adhesion strength of (3510.5 ± 140.21 to 9319.5 ± 39.425). DSC results of S4 and S8 showed compatibility of (ATM) with the other excipients. S8 and S4 also showed higher trans-nasal permeation to the brain with brain targeting efficiency of (211.3% and 177.42%, respectively) and drug transport percentages of (52.7% and 43.64%, respectively). To conclude, lyophilized nasal inserts of (ATM-SLNs) enhanced (ATM) trans-nasal drug targeting permeation and brain targeting efficiency.

Extraction, Physico-Chemical Analysis and Microbial Activities Evaluation of the Body Lipid of Tripletail (&amp;lt;i&amp;gt;Lobotes surinamensis&amp;lt;/i&amp;gt;) of the Bay of Bengal

Due to the discernible variation in the marine fish lipids compositions, the direct and indirect outcomes of it on human health physiology and nutrition have emphasized heightened focus. For this, the inquisition was reported with the extraction of the body lipid of Tripletail (<i>Lobotes surinamensis</i>) of the Bay of Bengal by Bligh and Dyer extraction method and different analytical parameters were rummaged and assimilate with those of typical fish lipids. The presence of several fatty acids namely myristic acid (C14:0), palmitic acid (C16:0), stearic acid (C18:0), palmitoleic acid (C16:1), oleic acid (C18:1), vaccenic acid (C18:1), linoleic acid (C18:2), linolenic acid (C18:3), arachidonic acid (C20:4), eicosadienoic acid (C20:2), eicosapentaenoic acid (C20:5), docosapentaenoic acid (C22:5) and docosahexaenoic acid (C22:6) etc was confirmed by Gas-Liquid Chromatography (GLC). It revealed that Saturated Fatty Acids (SFA%) were higher than Unsaturated Fatty Acids (UFA%). Moreover total Monounsaturated Fatty Acids (MUFA%) were higher than Polyunsaturated Fatty Acids (PUFA%) i.e. [25.5777% > 12.6850%] and ω-3 Polyunsaturated Fatty Acids (ω-3 PUFA) were higher than ω-6 Polyunsaturated Fatty Acids (ω-6 PUFA) i.e. [8.1113% > 4.5737%] along with higher ω-3/ω-6 ratio (1.77). The muscle of the target specimen was assessed to quantify the minerals content (N, P, K and Ca). Several metals (Fe, Pb, Ni, Co, Cd, Cu, Zn, Mn, Cr, As, Mg) were estimated with the help of Atomic Absorption Spectrophotometric (AAS) method. Additionally, using established techniques, the isolated lipid sample was evaluated for microbial (bacterial and fungal) activity. Thus from the findings, it is resolved with a variety of significant facts relating to nutritional and medicinal aspects.

Lipidomic Analysis of Hand Skin Surface Lipids Reveals Smoking-Related Skin Changes

Smoking contributes to the formation of skin wrinkles and reduces skin function, but the mechanism is not yet fully proven. This study aims to compare and analyze the effects of smoking on skin lipids and to further investigate the harmful effects of smoking on the skin. A total of 40 subjects (20 male smokers and 20 healthy control males) were recruited for this study. Measurement of hand skin-surface lipids (SSLs) in smoking and healthy control groups was undertaken using ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Multivariate data analysis was used to investigate the differences in SSLs between the two groups. There were 1230 lipids detected in the two groups and significant differences in SSLs' composition were observed between them. Under selected conditions, 26 types of lipid with significant differences were observed between the two groups (p < 0.05). Sphingolipids (SP) and glycerolipids (GL) were significantly increased, and sterol lipids (ST) were significantly reduced. Smoking causes changes in skin lipids that disrupt skin homeostasis, making the skin more fragile and more susceptible to skin aging and diseases.

Dynamic density functional theory of multicomponent cellular membranes

We present a continuum model trained on molecular dynamics (MD) simulations for cellular membranes composed of an arbitrary number of lipid types. The model is constructed within the formalism of dynamic density functional theory and can be extended to include features such as the presence of proteins and membrane deformations. This framework represents a paradigm shift by enabling simulations that can access length scales on the order of microns and time scales on the order of seconds, all while maintaining near fidelity to the underlying MD models. These length and time scales are significant for accessing biological processes associated with signaling pathways within cells. Membrane interactions with RAS, a protein implicated in roughly 30% of human cancers, are considered as an application. Simulation results are presented and verified with MD simulations, and implications of this new capability are discussed.

Complex, convoluted, yet consistent: Protein-induced membrane remodeling around GPCRs.

Proteins embedded in cell membranes are the targets for ∼70% of all FDA-approved drugs. A single family of membrane proteins, called ‘GPCRs’ account for almost one third of all drug targets. These cell membranes are highly complicated environments, made up of many different types of constituent lipid molecules. Experimentally, the use of different types of lipids in the membrane that surrounds the protein is known to modulate the protein behavior. However, when designing or testing novel therapeutics, the influence of the membrane is often ignored; 50% of the environment is overlooked. Thus, studies carried out to optimize therapeutics can potentially be misleading - it is possible for the protein to respond differently depending on the properties of the membrane. Using novel multiscale simulations, and a sophisticated membrane model, we demonstrate just how complex and intricate the protein-lipid interaction are. Indeed, the property-altering interactions between the proteins and lipids are reciprocal. While lipids can induce changes in protein behavior, the protein can also drive either changes in lipid properties or reorganization of the lipids. The systems acclimatize and adjust to external stimuli to provide a more consistent, reliable environment for the protein to complete its function. The fine-tuning adaptation of the system further highlights the symbiotic nature of the membrane and the protein such that they should not be considered separate elements but treated as a single multicomponent drug target. This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344 and was supported by the LLNL-LDRD Program under Project No. 21-ERD-047. LLNL-ABS-840667.

Packing and elasticity in membrane mechanical properties.

Here we address how membrane properties involving head group size, acyl chain unsaturation, and lipid packing affect their structure and dynamics. Strong out-of-plane proteolipid couplings considered by the flexible surface model (FSM) affect protein function through elastic forces described by the spontaneous curvature and the bending rigidity. We hypothesized that the mechanical properties and the molecular packing resulting from different lipid types are captured by introducing a perdeuterated POPC-d31 probe lipid. Di-monounsaturated phosphatidylcholine and phosphatidylethanolamine (DOPC, DOPE), and different ratios of DOPC/DOPE mixtures were studied using MD simulations combined with experimental solid-state 2H NMR spectroscopy. Residual quadrupolar couplings obtained from de-Paked powder-type spectra yielded order parameter (SCD) profiles for the individual acyl segments giving insights into average membrane structural properties such as area per lipid and bilayer thickness [1]. The corresponding spin-lattice relaxation rates (R1Z) for the resolved peaks followed a theoretical square-law dependence on SCD providing the bending rigidity [2]. Furthermore, MD simulations for the lipid systems were carried out and order parameters were calculated and compared against the NMR-observed SCD values. Utilization of the probe lipid POPC-d31 (1−10 mol%)affected the lamellar to hexagonal phase transition temperature of DOPE lipid systems but did not affect the quadrupolar splittings of DOPE and DOPC systems. Higher bending rigidity was observed for DOPE membranes versus DOPC supporting the idea that the membrane bending rigidity is primarily governed by increased lipid packing and is related to the area-compressibility modulus. Use of a probe lipid to capture membrane mechanical properties of complex lipid systems allow investigation of the relationship of membrane mechanics in vital biological functions.

Cardiomyocyte sarcolemma modelling and lipid-protein interactions.

The cardiomyocyte sarcolemma is a crucial cellular organelle in heart function. The vital components of the sarcolemma are membrane proteins that generate and control the cardiac action potential, responsible for cardiomyocyte contractibility and heart rhythm. Their malfunction can be caused by congenital mutations and side effects of antiarrhythmic therapies and can lead to life-threatening conditions related to heart failure. Other main components are represented by several lipid types, which not only provide the matrix for membrane proteins but also play active roles in regulating protein function. Shifts in membrane physiology through changes in the lipidomic profile or lipid-protein interactions can also cause cardiac disorders. Our goal is to characterize specific lipid-protein interactions in the sarcolemma by studying lipid redistribution around proteins and identifying lipid binding sites that can potentially regulate protein function. We combined lipidomic, cryo-electron microscopy and X-ray crystallography studies to build computational models of the cardiomyocyte sarcolemma. The membrane models consist of 16 lipid species, which differ in headgroup type, levels of acyl tail unsaturation and length. We embedded a selected membrane protein (cardiac ion channel, transporter or receptor) in a lipid bilayer and performed molecular dynamics simulations with the Martini coarse-grained models. We simulated each system with a corresponding membrane protein for 120 μs and analyzed lipid-protein interactions in terms of lipid redistribution around the proteins via computing lipid depletion-enrichment index, lipid density, and predicting lipid binding sites.Our results reproduce experimental findings of the interactions between lipids and the Kir2.2 potassium channel. We propose potential lipid binding sites for other proteins, highlighting similarities and differences in lipid redistribution and interaction with the cardiomyocyte proteins. Such findings unveil new possible lipid-protein interactions in the cardiomyocyte sarcolemma and provide an understanding of their relevance in heart function.

Role of lipid composition on human plasma membrane interactions with the Ebola virus matrix protein VP40.

The Ebola virus is a very dangerous zoonotic virus and its infection can cause hemorrhagic fever with high fatality rates. The Ebola virus matrix protein VP40 is the major protein responsible for the formation of the viral matrix by localizing and assembling it at the inner leaflet of the human plasma membrane (PM). This assembly leads to the formation of virus-like-particles (VLP) and eventual budding. Anionic lipids PI(4,5)P2 (PIP2) and Phosphatidylserine (PS) have been shown to facilitate VP40-membrane binding through electrostatic interactions with cationic VP40 residues. It has been determined that Phosphatidic Acid (PA), resulting from the enzyme Phospholipase-D (PLD), may also play an active role in this process. We performed coarse-grained molecular dynamics (CGMD) simulations to investigate the effects various lipids have on VP40-lipid interactions. We used a triple-dimer structure of VP40 and a PM composed of various lipid types. Contact analyses show interactions with specific cationic VP40 residues that facilitate most of the lipid interactions. Interaction strengths between VP40 residues and lipid headgroups are found to vary when PA was included in the PM compared to when it was not. The radial distribution functions also show differences in local lipid clustering between the two systems. These simulations provide new insights on VP40 interactions with the human PM and how different lipids may influence the overall membrane association and assembly of the VP40 dimers.

Hybrid polymer/lipid vesicles: Insights on phase separation and dynamics from time-resolved fluorescence and microscopy.

Recently, hybrid polymer/lipid vesicles were introduced e.g. for drug delivery comprising bimolecular recognition, and the aim is to blend into a single entity the advantages of both different and well established systems, liposomes and polymersomes (vesicles of pure polymer), allowing a fine tuning of stability, bifunctionality and permeability. A comprehensive study of phase separation and domain formation in Giant Hybrid Unilamellar Vesicles (GHUV) was carried out, using several types of polymers and lipids, considering both architecture (grafted, triblock) and molar mass variations. The micro-domains were directly visualized by confocal imaging using suitable labeled polymers and lipids, and FRET-FLIM was used for the detection of nano-domains below microscopy resolution. The sizes, stability and morphology of the observed phase separation are as predictable, dependent on the lipid/molar fraction, but other factors such as the line tension at the domain boundaries, which is fine tuned by the molar mass and polymer architecture, are ruling factors. The lateral diffusion of lipid within polymer chains was determined by FRAP, and it was concluded that no progressive (intermediate) effect is induced by the lipid, the presence of lipid domains playing a clear role.

Effects of interdigitation on the biophysical properties of lipid bilayers: A molecular dynamics study of chain asymmetric lipids.

Plasma membranes (PMs) are composed of hundreds of different lipids varying in structure and chemical properties. A major challenge in membrane biophysics is to determine how different classes of lipids contribute to the physical properties of the PM. One particularly interesting type of lipid is characterized by a different number of carbons in its two hydrocarbon chains. These chain asymmetric lipids are thought to have a higher propensity for interdigitation with lipids in the opposing leaflet and thus, to have a unique effect on interleaflet coupling. We have used molecular dynamics (MD) simulations to systematically examine fluid-phase bilayers composed of fully saturated PC lipids, each with a total of 32 acyl chain carbons, but increasing asymmetry ranging from zero to four carbons difference between the two chains. We quantified interdigitation in these bilayers using three novel methods and compared the results to standard approaches; we found general agreement in the trends, namely that increasing chain asymmetry results in increased interdigitation. We hypothesized that a greater extent of interdigitation should result in stiffer bilayers and thus, higher values of the bending modulus. To test this hypothesis, we measured various structural and mechanical properties of the simulated bilayers including thickness, lipid packing, and bending and compressibility moduli. Surprisingly, we found that the bilayers with the greatest extent of interdigitation are also the softest at a common temperature of 50°C. These results provide new insights into the structural and mechanical effects of lipid chain asymmetry and open up further questions about the nature of the coupling between lipid chain interdigitation and membrane biophysical properties.

Molecular dynamics study of the influence of cholesterol on the rigidity of an asymmetric membrane of red blood cells.

Analysis of the mechanical properties of the plasma membrane of red blood cell (RBC) is useful for the future exploration of cell-targeted methods for treatment of Alzheimer's disease. This preliminary study aimed to observe the effects cholesterol and lipid concentration/asymmetry have on the membrane rigidity and bilayer thickness. We focused on the structure-property relationship in the plasma membranes via the analysis of bending rigidity as a function of the molar concentration of the cholesterol and lipids in the plasma membrane. The plasma membrane of RBC consists mainly of cholesterol, phosphatidylcholine (PC), sphingomyelin (SM), and proteins. Cholesterol plays a key role in the plasma membrane by maintaining its viscoelasticity and structure via modulating the fluidity and rigidity of the membrane. To analyze these properties, the coarse-grained (CG) molecular dynamics (MD) simulations were performed. The membrane building included cholesterol molar concentration ranging from 10% to 30%. To replicate the asymmetry of the cell SM and PC, the molar concentrations of lipids were varied in the range of 10%-20% and 50%-80%, respectively. The initial membrane configuration was generated using CHARMM-GUI (online graphical user interface tool). The MD simulations were performed with the Gromacs (molecular dynamic simulation program) software using all-atom and coarse-grained approaches. The aggregation of cholesterol at various molar concentrations was observed along with the fluctuation of rigidity, which could be tentatively attributed to the lipid types used in the study, the ratio of cholesterol and lipids, and the use of water as a solvent for both the inner and outer leaflet. In the future we will focus on the all-atom study of the tail interactions between cholesterol and lipids in order to identify the leading factors contributing to the bending rigidity.

Vesicles made by several methods contain the ratio of phospholipids in the stock solution.

In this project, we measured the lipid composition of five-component vesicles produced via different methods. When making vesicles, it is typically assumed that the final lipid composition of the vesicles is identical to that of the stock solution. However, it is known that cholesterol incorporates poorly into vesicles made by emulsion phase transfer, and there is some evidence that PE lipids may not fully incorporate into vesicles made by electroformation. Here, we made a stock solution of a five-component mixture of DPPC, DOPC, DLPE, DOPG, and cholesterol. We produced vesicles from this stock solution using some of the most common methods: electroformation, gentle hydration, extrusion, and emulsion phase transfer. We then extracted the lipids from these vesicles using the Bligh and Dyer technique and used mass spectrometry to quantify the amount of each lipid type in the sample. We find that DOPC incorporates less readily into vesicles produced via emulsion phase transfer than other lipids do. For most of the methods we tested, the lipid composition of the vesicles is close to that of the stock solution, implying that results can be compared for vesicles made by these methods.

OPRLM: Orientations of proteins in realistic lipid membranes.

A new web tool and a database, OPRLM (Orientations of Proteins in Realistic Lipid Membranes), has been created based on the OPM database and the broadly used GHARMM-GUI toolset. The database provides a complete set of experimental 3D structures of integral and peripheral membrane proteins from the Protein Data Bank that are positioned in planar and curved lipid bilayers using implicit and explicit membrane representations. Membrane systems vary from single-component artificial lipid bilayers to multi-component bilayers with complex lipid composition corresponding to 18 biomembranes with either asymmetric or symmetric distribution of lipid types between two leaflets: 14 “average” eukaryotic cellular and organelle membranes (plasma membranes of mammals, plants, and fungi, endoplasmic reticulum and apparatus Golgi membranes of mammals and fungi, mammalian membranes of endosomes and lysosomes, mitochondrial outer and inner membranes, plant vacuole membranes, thylakoid membranes of plants and cyanobacteria), the outer and the inner membranes of Gram-negative bacteria (E. coli), and “average” cell membranes of Gram-positive bacteria and archaebacteria. All these membrane systems are accessible for public use in CHARMM-GUI Archive (https://www.charmm-gui.org/docs/archive/biomembrane). The web tool allows users of any level of expertise an easy setup of protein-membrane systems for atomic molecular dynamics (MD) simulations in pre-assembled realistic lipid membranes formed by mixtures of explicit lipids. OPRLM is publicly available at https://oprlm.org/.

Assessment of properties of gluten-based edible film formulated with beeswax and DATEM for hamburger bread coating.

Using edible films and coatings is one of the effective methods of improving the quality of bread. The aim of the present work was the development of gluten-based films containing lipids to be applied as bread coating, intending to improve quality and delay staleness. In this study, two types of lipids including beeswax and DATEM (diacetyl tartaric ester monoglycerides) were incorporated into gluten film at different levels. The findings showed that inserting both lipids together into gluten for film preparation, weakened the developed films in terms of mechanical and moisture barrier properties. Adding DATEM to the gluten film formulae decreased the elongation at the break and the tensile strength of the film. Using gluten-beeswax coatings for hamburger bread, compared to gluten-DATEM coatings, indicated a significant decrease in the hardness and staling feature. Moreover, applying sorbate as a preservative along with the solvents used in the film preparation prevented the growth of mold during the bread shelf life. In conclusion, the findings in this study indicated that the type and levels of lipids added to the edible gluten-based films and coatings affected the film properties and coated hamburger bread quality, significantly.

Alteration of the Essential Role of Endothelial Cells for Promoting Self-Renewal and Lineage Differentiation by Glucosylceramide and 16,16-dimethyl Prostaglandin E2

Bone marrow endothelial cells (BMECs) play an essential role for supporting hematopoietic stem cell expansion, self-renewal, and lineage differentiation. It has been known that BMECs receiving chronic constitutive inflammatory signals play a significant role in promoting functional alterations in hematopoietic stem cells (HSCs). Among many types of Inflammatory agents, bioactive lipids, including glucosylceramide (GlcCer) and dimethyl-Prostaglandin (dmPGE2) has been recently shown to be the potent mediator of inflammation through their own cognate receptor, CLEC4E (Mincle) and PGE receptors, respectively. Despite their biological significance, however, it is not known if GlcCer and dmPGE2, directly induce gene expression of self-renewal and lineage differentiation factors in BMECs or any other endothelial cells in general. We attempt to model the effect of GlcCer and dmPGE2 in vitro by employing primary human vein endothelial cells (HUVECs), and modified HUVECs transduced with E4ORF1 enhancing glucose uptake pathway. We hypothesize that GlcCer and dmPGE2 treatment will trigger reduction in the expression of ANGPTL2, JAG1, and PTN, while an increase in KITLG, CCL5, M-CSF, and GM-CSF in HUVEC. The significance of this study could be identifying a major pathway that contributes to the loss of self-renewal and increased myeloid lineage differentiated mediated by endothelial cells upon exposure to GlcCer. Results showed varied expressions of self-renewal and maintenance genes by GlcCer and dmPGE2. In conclusion, HUVEC may not be a good model for in vitro study as there was no expression seen in the lineage differentiation gene M-CSF and varied GM-CSF expression. However, the results of our study could potentially be utilized for in vitro expansion of HSCs for autologous bone marrow transfer, further genetic manipulation of endothelial cells, and characterization of the signal transduction pathway.

Lipidomic Profiling of Rice Bran after Green Solid-Liquid Extractions for the Development of Circular Economy Approaches.

Rice bran is a rather underutilized by-product of the rice industry that nowadays is far from being valorized. In this study, the lipidomic profile of bran of the Italian rice variety, Roma, has been evaluated through ultra performance liquid chromatography-tandem mass spectrometry. Crude lipid extracts were obtained from rice bran treated with different green solvents (1-butanol, ethanol and methyl tert-butyl ether/methanol mixture) in combination with an ultrasonic pre-treatment, and then compared with extracts obtained with standard solvents (chloroform/methanol mixture). Lipid yield, number and type of lipids and composition of prevalent lipid classes extracted were evaluated in order to provide an exhaustive lipid profile of the rice bran and to identify the most efficient green solvent for solid-liquid extractions. Twelve different lipid classes and a maximum of 276 lipids were identified. Ethanol and methyl tert-butyl ether/methanol solvents provided higher lipid extraction yields, the former being the most effective solvent for the extraction of triglycerides and N-acylethanolamines and the latter the most effective for the extraction of diglycerides, phospholipids and ceramides at 4 °C. Moreover, extraction with ethanol at 20 °C gave similar results as at 4 °C in terms of lipid yield and for most of the classes of lipids extracted. Taken together, our results indicate ethanol and methyl tert-butyl ether/methanol as excellent solvents for lipid extraction from rice bran, with the aim to further valorize this food by-product in the perspective of a circular economy.

Advances in Physicochemical and Biochemical Characterization of Archaeosomes from Polar Lipids of Aeropyrum pernix K1 and Stability in Biological Systems.

Archaeosomes are vesicles made from archaeal lipids. They are characterized by remarkable thermostability, resistance to enzymatic degradation, long-term stability, and immunomodulatory properties. In this review the current status of physicochemical properties of archaeal lipids and their stability in biological systems is presented, focusing on total polar lipids from Aeropyrum pernix K1. The isolated total polar lipids from Aeropyrum pernix K1 consist exclusively of glycerol ether lipids with isoprenoid groups attached to glycerol via ether linkages. More specifically, the two major polar lipids extracted from the membranes are C25,25-achaetidyl(glucosyl)inositol and C25,25-achaetidylinositol. An overview of the results of the effects of temperature and pH on the stability, structural organization, fluidity, and permeability of archaeosomes composed of pure C25,25 was examined by a combination of techniques, including fluorescence emission spectroscopy, electron paramagnetic resonance, differential scanning calorimetry, and confocal microscopy. We also compared the physicochemical properties of pure vesicles composed of either archaeal lipids or conventional lipids (e.g., 1,2-dipalmitoyl-sn-glycero-3-phosphocholine) with mixed vesicles composed of both lipid types. Archaeal lipids are discussed in terms of their potential use as a targeted drug delivery system based on the results of in vivo and cytotoxicity studies.