Types Of Lipids Research Articles

Testing quantitative magnetization transfer models with membrane lipids.

Quantitative magnetization transfer (qMT) models aim to quantify the contributions of lipids and macromolecules to the MRI signal. Hence, a model system that relates qMT parameters and their molecular sources may improve the interpretation of the qMT parameters. Here we used membrane lipid phantoms as a meaningful tool to study qMT models. By controlling the fraction and type of membrane lipids, we could test the accuracy, reliability, and interpretability of different qMT models. We formulated liposomes with various lipid types and water-to-lipids fractions and measured their signals with spoiled gradient-echo MT. We fitted three known qMT models and estimated six parameters for every model. We tested the accuracy and reproducibility of the models and compared the dependency among the qMT parameters. We compared the samples' qMT parameters with their water-to-lipid fractions and with a simple MTnorm (= MTon/MToff) calculation. We found that the three qMT models fit the membrane lipids signals well. We also found that the estimated qMT parameters are highly interdependent. Interestingly, the estimated qMT parameters are a function of the membrane lipid type and also highly related to the water-to-lipid fraction. Finally, we find that most of the lipid sample's information can be captured using the common and easy to estimate MTnorm analysis. qMT parameters are sensitive to both the water-to-lipid fraction and to the lipid type. Estimating the water-to-lipid fraction can improve the characterization of membrane lipids' contributions to qMT parameters. Similar characterizations can be obtained using the MTnorm analysis.

Lower-dose vs high-dose oral bisphenol S action of lipid metabolism in liver of male SD rat via mediating different SREBP isoforms

Bisphenol S (BPS) is commonly used for the industrial production of thermal paper, polycarbonate plastics, epoxy resins and other materials. Studies have reported that BPS can lead to triglyceride (TAG) or/and cholesterol (CHO) accumulation in the liver in zebrafish and mice, but the reasons for the different types of lipids that accumulate in the liver following BPS exposure are unclear. Here, the influences of lower-dose (10 mg/kg body weight/day) and high-dose (50 mg/kg body weight/day) BPS exposure to male SD rats on the accumulation of different lipids in the liver were explored. The results indicated that BPS treatment increased the levels of acetyl-CoA and glycogen in the liver. A lower dose of BPS upregulated the mRNA and protein expression levels of sterol regulatory element-binding protein 1 (srebp1), which is involved in the de novo synthesis of TAG in the liver, thus promoting the synthesis of glycerides (diacetylglyceride and TAG). However, a higher dose of BPS induced CHO accumulation, but inhibited the mRNA expression of genes (i.e., srebp2, hmgcr and hmgcs) involved in the de novo synthesis of CHO in the liver. Excessive accumulation of glycerides and CHO led to destruction of the physiological structure of rat liver, causing disorders in liver function. Our data provide new insight into the different mechanisms by which glyceride and CHO accumulate in the liver after BPS exposure.

Emulsion Structural Remodeling in Milk and Its Gelling Products: A Review.

The fat covered by fat globule membrane is scattered in a water phase rich in lactose and milky protein, forming the original emulsion structure of milk. In order to develop low-fat milk products with good performance or dairy products with nutritional reinforcement, the original emulsion structure of milk can be restructured. According to the type of lipid and emulsion structure in milk, the remolded emulsion structure can be divided into three types: restructured single emulsion structure, mixed emulsion structure, and double emulsion structure. The restructured single emulsion structure refers to the introduction of another kind of lipid to skim milk, and the mixed emulsion structure refers to adding another type of oil or oil-in-water (O/W) emulsion to milk containing certain levels of milk fat, whose final emulsion structure is still O/W emulsion. In contrast, the double emulsion structure of milk is a more complicated structural remodeling method, which is usually performed by introducing W/O emulsion into skim milk (W2) to obtain milk containing (water-in-oil-in-water) W1/O/W2 emulsion structure in order to encapsulate more diverse nutrients. Causal statistical analysis was used in this review, based on previous studies on remodeling the emulsion structures in milk and its gelling products. In addition, some common processing technologies (including heat treatment, high-pressure treatment, homogenization, ultrasonic treatment, micro-fluidization, freezing and membrane emulsification) may also have a certain impact on the microstructure and properties of milk and its gelling products with four different emulsion structures. These processing technologies can change the size of the dispersed phase of milk, the composition and structure of the interfacial layer, and the composition and morphology of the aqueous phase substance, so as to regulate the shelf-life, stability, and sensory properties of the final milk products. This research on the restructuring of the emulsion structure of milk is not only a cutting-edge topic in the field of food science, but also a powerful driving force in promoting the transformation and upgrading of the dairy industry to achieve high-quality and multi-functional dairy products, in order to meet the diversified needs of consumers for health and taste.

Role of zwitterionic lipid headgroups on monolayer formation and interfacial dilatational rheology in binary mixtures of phospholipids and cholesterol: A pendant drop tensiometer study

The complex composition of biological membranes, comprising a diverse array of lipids with unique moieties, has garnered increased attention due to the recognized roles of lipids in membrane stability and biological processes. Even subtle changes in phospholipid headgroups and fatty acyl tails profoundly affect the formation and interfacial dynamics of lipid monolayers at the air-water interface. However, the molecular-level understanding of their intermolecular forces and interactions during these processes, directly relating to the lipid chemical structures, is not well-explored. To better understand these complex physicochemical phenomena, simplified model monolayers with precise control over lipid types and compositions are utilized. In this study, we employ the pendant drop tensiometer technique to investigate the formation and interfacial rheology of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE) monolayers, with varying amounts of cholesterol (CHOL) for the first time. These two phospholipids, with identical C16:0 acyl tails but different headgroups, exhibit marked differences in their interfacial interactions with CHOL and water molecules, consequently affecting monolayer formation and rheology. In the absence of CHOL, DPPE monolayers typically display a lower dilatational modulus than DPPC, attributed to increased headgroup hydration. However, introducing CHOL reverses this trend, resulting in stiffer DPPE-CHOL monolayers compared to DPPC-CHOL. With CHOL, we observe its well-known condensation effect on DPPC monolayers, yet for DPPE monolayers, both condensation and expansion effects are noted, contingent on CHOL amount. We anticipate this work will not only deepen our fundamental understanding of the structure-composition-property relationships in lipid molecules but also provide a robust foundation for comprehending more intricate biological systems.

Association between visceral adiposity index, lipid accumulation product and type 2 diabetes mellitus in US adults with hypertension: a cross-sectional analysis of NHANES from 2005 to 2018

BackgroundThe presence of hypertension significantly increases the risk of diabetes, particularly type 2 diabetes. Recently, Visceral Adiposity Index (VAI) has been introduced as a straightforward and robust alternative indicator for early detection of metabolic syndrome, cardiovascular disease, and T2DM. Visceral adiposity, more dangerous than subcutaneous fat, is associated with metabolic syndrome and cardiovascular diseases. The VAI and Lipid Accumulation Product (LAP) are indices that quantify visceral fat and lipid overaccumulation, respectively. This study aims to explore the association between VAI, LAP, and type 2 diabetes mellitus (T2DM) in US adults with hypertension using NHANES data from 2005 to 2018.MethodsWe analyzed data from 5,620 participants with hypertension in The National Health and Nutrition Examination Survey (NHANES). VAI and LAP were calculated using established formulas. The VAI is calculated based on a combination of waist circumference, body mass index (BMI), triglycerides, and high-density lipoprotein (HDL) cholesterol levels. Logistic regression models were applied to evaluate the association between these indices and T2DM, adjusting for potential confounders. Subgroup analyses by age and gender were also conducted to assess variations in risk.ResultsIn all, 5,620 participants were enrolled in our analysis, with 2,754 (49%) being female, and a mean (standard deviation, SD) age of 57 (15) years. The mean (SD) cumulative average VAI and LAP among all participants was 241 (2.71) and 75 (67), respectively. Totally, higher VAI and LAP indices were significantly associated with an increased risk of T2DM in individuals with hypertension. For VAI, the odds ratios (OR) for T2DM were higher in older adults (≥ 60 years) [95% confidence interval (CI): 1.37, 1.22–1.53, per 1 SD increase] and females [95% confidence interval (CI): 1.39, 1.27–1.52, per 1 SD increase], indicating age and gender differences in risk. Non-linear relationships were observed, suggesting thresholds beyond which the risk of T2DM escalates dramatically.ConclusionsBoth VAI and LAP are reliable markers for assessing T2DM risk in individuals with hypertension. Incorporating these indices into clinical practice could enhance the identification of high-risk individuals and facilitate early intervention strategies. Future longitudinal studies are needed to confirm these associations and explore targeted interventions.

Machine learning and biological validation identify sphingolipids as potential mediators of paclitaxel-induced neuropathy in cancer patients

Background:Chemotherapy-induced peripheral neuropathy (CIPN) is a serious therapy-limiting side effect of commonly used anticancer drugs. Previous studies suggest that lipids may play a role in CIPN. Therefore, the present study aimed to identify the particular types of lipids that are regulated as a consequence of paclitaxel administration and may be associated with the occurrence of post-therapeutic neuropathy.Methods:High-resolution mass spectrometry lipidomics was applied to quantify d=255 different lipid mediators in the blood of n=31 patients drawn before and after paclitaxel therapy for breast cancer treatment. A variety of supervised statistical and machine-learning methods was applied to identify lipids that were regulated during paclitaxel therapy or differed among patients with and without post-therapeutic neuropathy.Results:Twenty-seven lipids were identified that carried relevant information to train machine learning algorithms to identify, in new cases, whether a blood sample was drawn before or after paclitaxel therapy with a median balanced accuracy of up to 90%. One of the top hits, sphinganine-1-phosphate (SA1P), was found to induce calcium transients in sensory neurons via the transient receptor potential vanilloid 1 (TRPV1) channel and sphingosine-1-phosphate receptors.SA1P also showed different blood concentrations between patients with and without neuropathy.Conclusions:Present findings suggest a role for sphinganine-1-phosphate in paclitaxel-induced biological changes associated with neuropathic side effects. The identified SA1P, through its receptors, may provide a potential drug target for co-therapy with paclitaxel to reduce one of its major and therapy-limiting side effects.Funding:This work was supported by the Deutsche Forschungsgemeinschaft (German Research Foundation, DFG, Grants SFB1039 A09 and Z01) and by the Fraunhofer Foundation Project: Neuropathic Pain as well as the Fraunhofer Cluster of Excellence for Immune-Mediated Diseases (CIMD). This work was also supported by the Leistungszentrum Innovative Therapeutics (TheraNova) funded by the Fraunhofer Society and the Hessian Ministry of Science and Arts. Jörn Lötsch was supported by the Deutsche Forschungsgemeinschaft (DFG LO 612/16-1).

Machine learning and biological validation identify sphingolipids as potential mediators of paclitaxel-induced neuropathy in cancer patients.

Chemotherapy-induced peripheral neuropathy (CIPN) is a serious therapy-limiting side effect of commonly used anticancer drugs. Previous studies suggest that lipids may play a role in CIPN. Therefore, the present study aimed to identify the particular types of lipids that are regulated as a consequence of paclitaxel administration and may be associated with the occurrence of post-therapeutic neuropathy. High-resolution mass spectrometry lipidomics was applied to quantify d=255 different lipid mediators in the blood of n=31 patients drawn before and after paclitaxel therapy for breast cancer treatment. A variety of supervised statistical and machine-learning methods was applied to identify lipids that were regulated during paclitaxel therapy or differed among patients with and without post-therapeutic neuropathy. Twenty-seven lipids were identified that carried relevant information to train machine learning algorithms to identify, in new cases, whether a blood sample was drawn before or after paclitaxel therapy with a median balanced accuracy of up to 90%. One of the top hits, sphinganine-1-phosphate (SA1P), was found to induce calcium transients in sensory neurons via the transient receptor potential vanilloid 1 (TRPV1) channel and sphingosine-1-phosphate receptors.SA1P also showed different blood concentrations between patients with and without neuropathy. Present findings suggest a role for sphinganine-1-phosphate in paclitaxel-induced biological changes associated with neuropathic side effects. The identified SA1P, through its receptors, may provide a potential drug target for co-therapy with paclitaxel to reduce one of its major and therapy-limiting side effects. This work was supported by the Deutsche Forschungsgemeinschaft (German Research Foundation, DFG, Grants SFB1039 A09 and Z01) and by the Fraunhofer Foundation Project: Neuropathic Pain as well as the Fraunhofer Cluster of Excellence for Immune-Mediated Diseases (CIMD). This work was also supported by the Leistungszentrum Innovative Therapeutics (TheraNova) funded by the Fraunhofer Society and the Hessian Ministry of Science and Arts. Jörn Lötsch was supported by the Deutsche Forschungsgemeinschaft (DFG LO 612/16-1).

Lipid Peroxidation and Type I Interferon Coupling Fuels Pathogenic Macrophage Activation Causing Tuberculosis Susceptibility.

A quarter of human population is infected with Mycobacterium tuberculosis, but less than 10% of those infected develop pulmonary TB. We developed a genetically defined sst1-susceptible mouse model that uniquely reproduces a defining feature of human TB: the development of necrotic lung granulomas and determined that the sst1-susceptible phenotype was driven by the aberrant macrophage activation. This study demonstrates that the aberrant response of the sst1-susceptible macrophages to prolonged stimulation with TNF is primarily driven by conflicting Myc and antioxidant response pathways leading to a coordinated failure 1) to properly sequester intracellular iron and 2) to activate ferroptosis inhibitor enzymes. Consequently, iron-mediated lipid peroxidation fueled IFNβ superinduction and sustained the Type I Interferon (IFN-I) pathway hyperactivity that locked the sst1-susceptible macrophages in a state of unresolving stress and compromised their resistance to Mtb. The accumulation of the aberrantly activated, stressed, macrophages within granuloma microenvironment led to the local failure of anti-tuberculosis immunity and tissue necrosis. The upregulation of Myc pathway in peripheral blood cells of human TB patients was significantly associated with poor outcomes of TB treatment. Thus, Myc dysregulation in activated macrophages results in an aberrant macrophage activation and represents a novel target for host-directed TB therapies.

Raft-like lipid mixtures in the highly coarse-grained Cooke membrane model.

Lipid rafts are nanoscopic assemblies of sphingolipids, cholesterol, and specific membrane proteins. They are believed to underlie the experimentally observed lateral heterogeneity of eukaryotic plasma membranes and implicated in many cellular processes, such as signaling and trafficking. Ternary model membranes consisting of saturated lipids, unsaturated lipids, and cholesterol are common proxies because they exhibit phase coexistence between a liquid-ordered (lo) and liquid-disordered (ld) phase and an associated critical point. However, plasma membranes are also asymmetric in terms of lipid type, lipid abundance, leaflet tension, and corresponding cholesterol distribution, suggesting that rafts cannot be examined separately from questions about elasticity, curvature torques, and internal mechanical stresses. Unfortunately, it is challenging to capture this wide range of physical phenomenology in a single model that can access sufficiently long length- and time scales. Here we extend the highly coarse-grained Cooke model for lipids, which has been extensively characterized on the curvature-elastic front, to also represent raft-like lo/ld mixing thermodynamics. In particular, we capture the shape and tie lines of a coexistence region that narrows upon cholesterol addition, terminates at a critical point, and has coexisting phases that reflect key differences in membrane order and lipid packing. We furthermore examine elasticity and lipid diffusion for both phase separated and pure systems and how they change upon the addition of cholesterol. We anticipate that this model will enable significant insight into lo/ld phase separation and the associated question of lipid rafts for membranes that have compositionally distinct leaflets that are likely under differential stress-like the plasma membrane.

Fundamentals of Edible Coatings and Combination with Biocontrol Agents: A Strategy to Improve Postharvest Fruit Preservation.

Challenges in global food supply chains include preserving postharvest quality and extending the shelf life of fruits and vegetables. The utilization of edible coatings (ECs) combined with biocontrol agents (BCAs) represents a promising strategy to enhance the postharvest quality and shelf life of these commodities. This review analyzes the most recent developments in EC technologies and their combination with BCAs, highlighting their synergistic effects on postharvest pathogen control and quality maintenance. Various types of ECs, including polysaccharides, proteins, and lipids, are discussed alongside coating fundamentals and the mechanisms through which BCAs contribute to pathogen suppression. The review also highlights the efficacy of these combined approaches in maintaining the physicochemical properties, sensory attributes, and nutritional value of fruits. Key challenges such as regulatory requirements, consumer acceptance, and the scalability of these technologies are addressed. Future research directions are proposed to optimize formulations, improve application techniques, and enhance the overall efficacy of these biocomposite coatings and multifunctional coatings. By synthesizing current knowledge and identifying gaps, this review provides a comprehensive understanding of the potential and limitations of using ECs and BCAs for sustainable postharvest management.

Reinterpretation of lycopane as a biomarker of archaea based on its occurrence in authigenic sulfur-bearing carbonates

The tail-to-tail linked C40 isoprenoid hydrocarbon lycopane is a biomarker found in a wide variety of environments and in some extremophilic archaea but is also a possibly degradation product of a carotenoid (bacterioruberin) as well as plants (various lycopenes) and green algae (lycopadiene). Although potential producers are known, the source of lycopane in water-column and sedimentary environments is commonly ambiguous. In this study, the occurrence of 13C-depleted lycopane (δ13C = −114 to −106 ‰) in authigenic, sulfur-bearing carbonates from Monte Palco (Sicily) is used to re-evaluate the environmental significance of lycopane. In the Monte Palco authigenic carbonates, lycopane is accompanied by other, similarly 13C-depleted apolar isoprenoids such as PMI, squalane, and sulfurized homologues, including a tail-to-tail linked C35 isoprenoid, as well as typical lipids of anaerobic methanotrophic archaea (ANME) like glycerol dibiphytanyl glycerol tetraether (GDGT)-0, −2, archaeol, and sn3-hydroxyarchaeol. The δ13C values of lycopane reveal linear correlations with values of PMI and squalane (n = 7; r2 = 0.71 and 0.82, respectively), probably reflecting a similar cellular function of the tail-to-tail linked isoprenoids in the archaeal source organisms. Lycopane is interpreted to represent a membrane intercalant, produced in response to extreme environmental conditions. The new observations resulting from the analysis of the Monte Palco authigenic carbonates – including the similarities in 13C-depletion of PMI, squalane, and lycopane but also with other archaeal membrane lipids like archaeol, sn3-hydroxyarchaeol, and GDGT-0 (measured as ether-cleaved biphytanes) – allowed us to re-interpret the potential source organism of lycopane in modern and ancient anoxic and euxinic basins (Cariaco Trench, Black Sea, late Cenomanian black shales of the Cape Verde Basin). These new data agree with unknown archaea as producers of lycopane as a response to environmental stress at chemoclines. The previous interpretation of lycopane as a biomarker of photoautotrophic bacteria in anoxic basins is challenged by our new findings. An alternative explanation for these occurrences is lycopane production by Marine Group II Euryarchaeota, archaea closely associated with primary producers. Lycopane production by archaea is probably more widespread than previously recognized. Future research should evaluate the potential of lycopane as a biomarker of archaeal adaptation to extreme environmental conditions.

Intranasal delivery of sulpiride nanostructured lipid carrier to central nervous system; in vitro characterization and in vivo study

The low and erratic oral absorption of sulpiride (SUL) a dopaminergic receptor antagonist, and its P-glycoprotein efflux in the gastrointestinal tract restricted its oral route for central nervous system disorders. An intranasal formulation was formulated based on nanostructured lipid carrier to tackle these obstacles and deliver SUL directly to the brain. Sulipride-loaded nanostructured lipid carrier (SUL-NLC) was prepared using compritol®888 ATO and different types of liquid lipids and emulsifiers. SUL-NLCs were characterized for their particle size, charge, and encapsulation efficiency. Morphology and compatibility with other NLC excipients were also studied. Moreover, SUL in vitro release, nanodispersion stability, in vivo performance and SUL pharmacokinetics were investigated. Results delineates that SUL-NLC have a particle size ranging from 366.2 ± 62.1 to 640.4 ± 50.2 nm and encapsulation efficiency of 75.5 ± 1.5%. SUL showed a sustained release pattern over 24 h and maintained its physical stability for three months. Intranasal SUL-NLC showed a significantly (p < 0.01) higher SUL brain concentration than that found in plasma after oral administration of commercial SUL product with 4.47-fold increase in the relative bioavailability. SUL-NLCs as a nose to brain approach is a promising formulation for enhancing the SUL bioavailability and efficient management of neurological disorders.

Effect of lipid type on betulin-stabilized water-in-oil Pickering emulsion: emulsion properties, in vitro digestion, and betulin bioaccessibility.

The Pickering emulsion delivery technique is widely acknowledged for its efficacy in serving as a carrier that can encapsulate functional components effectively. Previous studies have shown significant differences in the stability of Pickering emulsions composed of different oil phases and in the bioaccessibility of the encapsulated functional ingredients. This study therefore investigated the effects of different carrier oils in the betulin self-stabilized water-in-oil (W/O) Pickering emulsion on the stability of the emulsion and bioaccessibility of betulin. The results showed that the oil type was one of the main factors affecting the stability of the emulsion. Palm oil and coconut oil provided better storage stability and centrifugal stability due to the high saturated fatty acid content. The bioavailability of betulin correlated significantly with the composition and characteristics of fatty acids in carrier oils. Carrier oils rich in low-saturation long-chain fatty acids tended to release more free fatty acids (FFAs), thus forming larger and more mixed micelles with stronger swelling and dissolution ability, resulting in a relatively high bioaccessibility of betulin. In contrast, the bioaccessibility of betulin in the emulsion prepared by coconut oil (with high saturated fatty acid content) was relatively low (1.17%). The results of this study indicate that selecting an appropriate carrier oil is important for the design of self-stabilized W/O Pickering emulsions to improve the bioaccessibility of betulin and other lipophilic bioactivities effectively. © 2024 Society of Chemical Industry.

Comparison of ionizable lipids for lipid nanoparticle mediated DNA delivery

Lipid nanoparticles (LNPs) are successfully used for RNA-based gene delivery. In the context of gene replacement therapies, however, delivery of DNA expression plasmids using LNPs as a non-viral vector could be a promising strategy for the induction of longer-lasting effects.Therefore, DNA expression plasmids (3 to 4 kbp) coding for fluorescent markers or luciferase were combined with LNPs. Different clinically used ionizable lipids (DLin-MC3-DMA, SM-102, and ALC-0315) were tested to compare their influence on DNA plasmid delivery.DNA-LNPs were characterized with respect to their colloidal properties (size, polydispersity, ζ-potential, morphology), in vitro performance (cellular uptake, DNA delivery, and gene expression), and in vivo characteristics (biodistribution and luciferase gene expression). At an optimized N/P ratio of 6, spherical, small and monodisperse particles with anionic ζ-potential were obtained. Efficient transgene expression was achieved with a minimum amount of 1 pg DNA per initially plated cells. Zebrafish studies allowed selection of DNA-LNPs, which demonstrated prolonged blood circulation, avoidance of macrophage clearance, and vascular extravasation.Our comparative study demonstrates a high impact of the ionizable lipid type on DNA-LNP performance. Superior transfection efficiency of DNA-LNPs containing the ionizable lipid ALC-0315 was confirmed in wildtype mice.

All-Atom Membrane Builder via Multiscale Simulation.

I present an automated and flexible tool designed for constructing bilayer membranes at all-atom (AA) resolution. The builder initiates the construction and equilibration of bilayer membranes at Martini coarse-grained (CG) resolution, followed by resolution enhancement to the atomic level using the accompanying backmapping tool. Notably, this tool enables users to create bilayer membranes with user-defined lipid compositions and protein structures, while also offering the flexibility to accommodate new lipid types. To assess the simplicity and robustness of the tool, I demonstrate the construction of several membranes incorporating protein structures. The tool is freely available at github.com/ksy141/mstool.

Simulating Bacterial Membrane Models at the Atomistic Level: A Force Field Comparison.

Molecular dynamics (MD) simulations are currently an indispensable tool to understand both the dynamic and nanoscale organization of cell membrane models. A large number of quantitative parameters can be extracted from these simulations, but their reliability is determined by the quality of the employed force field and the simulation parameters. Much of the work on parametrizing and optimizing force fields for biomembrane modeling has been focused on homogeneous bilayers with a single phospholipid type. However, these may not perform effectively or could even be unsuitable for lipid mixtures commonly employed in membrane models. This work aims to fill this gap by comparing MD simulation results of several bacterial membrane models using different force fields and simulation parameters, namely, CHARMM36, Slipids, and GROMOS-CKP. Furthermore, the hydrogen isotope exchange (HIE) method, combined with GROMOS-CKP (GROMOS-H2Q), was also tested to check for the impact of this acceleration strategy on the performance of the force field. A common set of simulation parameters was employed for all of the force fields in addition to those corresponding to the original parametrization of each of them. Furthermore, new experimental order parameter values determined from NMR of several lipid mixtures are also reported to compare them with those determined from MD simulations. Our results reveal that most of the calculated physical properties of bacterial membrane models from MD simulations are substantially force field and lipid composition dependent. Some lipid mixtures exhibit nearly ideal behaviors, while the interaction of different lipid types in other mixtures is highly synergistic. None of the employed force fields seem to be clearly superior to the other three, each having its own strengths and weaknesses. Slipids are notably effective at replicating the order parameters for all acyl chains, including those in lipid mixtures, but they offer the least accurate results for headgroup parameters. Conversely, CHARMM provides almost perfect estimates for the order parameters of the headgroups but tends to overestimate those of the lipid tails. The GROMOS parametrizations deliver reasonable order parameters for entire lipid molecules, including multicomponent bilayers, although they do not reach the accuracy of Slipids for tails or CHARMM for headgroups. Importantly, GROMOS-H2Q stands out for its computational efficiency, being at least 3 times faster than GROMOS, which is already faster than both CHARMM and Slipids. In turn, GROMOS-H2Q yields much higher compressibilities compared to all other parametrizations.

Role of myeloid cells in mediating the effects of lipids on ulcerative colitis.

To evaluate the causal relationship between lipids and ulcerative colitis (UC) through Mendelian Randomization (MR), and to further investigate the involvement of immune cells in mediating this process. Utilizing summary statistics from genome-wide association studies (GWAS) of individuals with European ancestry, we analyzed the causal link between 179 lipid types and UC (2,569 UC cases and 453,779 controls) through Two-sample Mendelian randomization (2SMR) and Bayesian-weighted MR (BWMR). Based on this, a mediation screening of 731 immune cell phenotypes was conducted to identify exposure and mediator factors. Lastly, the role and proportion of immune cells in mediating the causal effects of lipids on UC were assessed via reverse MR (RMR) and two-step MR. The results of MR showed that there was a causal relationship between the six genetically predicted lipid types and UC (P <0.05), and the four immune cell phenotypes were identified as mediators of the association between lipids and UC. Notably, Phosphatidylcholine (PC) (16:0_0:0) served as the exposure factor, and myeloid cells CD11b on CD33+ HLA DR+ CD14dim acted as the mediator. Mediation analysis showed that CD11b on CD33+ HLA DR+ CD14dim had a mediation effect of -0.0205 between PC (16:0_0:0) and UC, with the mediation effect ratio at 15.38%. Our findings elucidate the causal effect of lipids on UC and identify the significant mediating role of myeloid cells CD11b on CD33+ HLA DR+ CD14dim in regulating UC through PC (16:0_0:0), offering new pathways and strategies for UC clinical treatment.

Lipid Assessment in Diabetic Patients in Karbala Hospital: A Cross-Sectional Study

One of the most prevalent illnesses, diabetes is not transmissible from an infected individual to a healthy one because it is present in every nation on Earth, including Iraq. Hyperglycemia is characterized by problems in the metabolism of proteins, lipids, and carbohydrates in addition to persistent hyperglycemia. The glycated hemoglobin (HbA1c) level has to be 6.5% in order to satisfy the diabetes diagnostic requirements. This study examined the relationship between high lipid levels and type 2 diabetes. The investigation's goal was to look at the connection between blood lipid levels and blood sugar levels. Furthermore, therapy and early identification of lipid abnormalities in individuals may lower the chance of atherosclerotic cardiovascular disease. In hospitals located in Karbala, Iraq, this cross-sectional observational research was carried out between January and June of 2024. Four hundred patients between the ages of twenty-five and sixty-five were chosen for this reason. Blood glucose, triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and glycated hemoglobin (HbA1c) were all assessed.

Lipidome and proteome analyses provide insights into Mariana Trench Snailfish (Pseudoliparis swirei) adaptation to the hadal zone

The hadal zone environment, characterized by extreme hydrostatic pressure, low temperatures, and limited food availability, presents substantial survival challenges for deep-sea fish species. In this study, we captured five deep-sea fish species (Bathysaurus mollis, Coryphaenoides rudis, Ilyophis sp., I. brunneus and Pseudoliparis swirei) from the Mariana Trench at depths ranging from 2027 to 7125 ​m, by employing China's “Exploration I and Exploration II”. By combining lipidomic and proteomic analyses, we aimed to explore the genetic basis of adaptive evolution to the hadal zone in fish. The results indicate several key findings: (1) P. swirei (Mariana hadal snailfish, MHS) may enhance energy storage and utilization during prolonged fasting periods by significantly increasing liver tissue levels of cholesterol ester (CE), ether-linked triacylglycerol (TG-O), coenzyme Q (CoQ), and ATPase content; (2) MHS could maintain membrane fluidity under high pressure by increasing the proportion of unsaturated fatty acids while reducing levels of cholesterol and phosphatidylethanolamine (PE) content. (3) The regulation of lipid types and ratios could increase the risk of lipid peroxidation. To counter oxidative stress, MHS likely elevates monounsaturated fatty acid content and enhances antioxidants such as transferrin and heat shock proteins. Overall, this study provides new insights into the adaptive mechanisms of MHS to deep-sea conditions through the lipidome and proteome analyses, thus broadening our understanding of its resilience in the hadal zone.

Influence of phospholipid head and tail molecular structures on cell membrane mechanical response under tension.

Biological cell membranes are primarily comprised of a diverse lipid bilayer with multiple phospholipid (lipid) types, each of which is comprised of a hydrophilic headgroup and two hydrophobic hydrocarbon tails. The lipid type determines the molecular structure of head and tail groups, which can affect membrane mechanics at nanoscale and subsequently cell viability under mechanical loading. Hence, using molecular dynamics simulations, the current study investigated seven membrane phospholipids and the effect of their structural differences on physical deformation, mechanoporation damage, and mechanical failure of the membranes under tension. The inspected phospholipids showed similar yield stresses and strains, as well as pore evolution and damage, but significantly different failure strains. In general, failure occurred at a lower strain for lipids with a larger equilibrium area per lipid. The obtained results suggest that larger headgroup structure, greater degree of unsaturation, and tail-length asymmetry influenced the phospholipids' ability to pack against each other, increased the fluidity and equilibrium area per lipid of the membrane, and resulted in lower failure strain. Overall, this study provides insights on how different phospholipid structures affect membrane physical responses at the molecular level and serves as a reference for future studies of more complex membrane systems with intricate biophysical properties.