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Within cell plasma membranes, unsaturated lipids are asymmetrically distributed over the inner and outer leaflets, offering an attractive local structural feature. However, the mechanism to keep lipid transmembrane asymmetry and the closely related transmembrane movement (flip-flop) for unsaturated lipids remain poorly understood. Here, we applied sum frequency generation vibrational spectroscopy to investigate this lipid transmembrane asymmetry upon mimicking the cell membrane homeostatic processes. On the one hand, unsaturated lipids were found to hinder the flip-flop process and preserve lipid transmembrane asymmetry in model cell membranes, owing to the steric hindrance caused by their bent tails. On the other hand, local unsaturated lipids in the mixed unsaturated/saturated lipid bilayer were conducive to the formation of the local asymmetry. Therefore, lipid unsaturation can be recognized as an intrinsic key factor to form and maintain lipid transmembrane asymmetry in cell membranes. [ABSTRACT FROM AUTHOR]

Both sugars and lipids are important biomolecular building blocks with exceptional conformational flexibility and adaptability to their environment. Glycolipids bring together these two molecular components in the same assembly and combine the complexity of their conformational landscapes. In the present study, we have used selective double resonance vibrational spectroscopy, in combination with a computational approach, to explore the conformational preferences of two glycolipid models (3-0-acyl catechol and guaiacol α-D-glucopyranosides), either fully isolated in the gas phase or controlled interaction with a single water molecule. We could identify the preferred conformation and structures of the isolated and micro-hydrated species and evidence of the presence of a strong water pocket, which may influence the conformational flexibility of such systems, even in less controlled environments. [ABSTRACT FROM AUTHOR]

Fatty acids from cooking fumes and hypochlorous acid (HOCl) released from indoor cleaning adversely affect respiratory health, but the molecular-level mechanism remains unclear. Here, the effect of cooking oil fumes [palmitic acid (PA), oleic acid (OA), and linoleic acid (LA)] on lung model phospholipid (POPG) hydrochlorination mediated by HOCl at the air–water interface of the hanged droplets was investigated. Interfacial hydrochlorination of POPG was impeded by OA and LA, while that of POPG was facilitated by PA. The effect on POPG hydrochlorination increased with the decrease in oil fume concentration. A potential mechanism with respect to the chain length of these oil fumes, regardless of their saturation, was proposed. PA with a short carbon chain looses the POPG packing and leads to the exposure of the C=C double bonds of POPG, whereas OA and LA with a long carbon chain hinder HOCl from reaching the C=C bonds of POPG. These results for short chain and low concentration dependence suggest that the decay of oil fumes or the conversion of short-chain species by indoor interfacial chemistry might be adverse to lung health. These results provide insights into the relationship between indoor multicomponent pollutants and the respiratory system. [ABSTRACT FROM AUTHOR]

Biological lipid membranes are generally asymmetric, not only with respect to the composition of the two membrane leaflets but also with respect to the state of mechanical stress on the two sides. Computer simulations of such asymmetric membranes pose unique challenges with respect to the choice of boundary conditions and ensemble in which such simulations are to be carried out. Here, we demonstrate an alternative to the usual choice of fully periodic boundary conditions: The membrane is only periodic in one direction, with free edges running parallel to the single direction of periodicity. In order to maintain bilayer asymmetry under these conditions, nanoscale "sticky tapes" are adhered to the membrane edges in order to prevent lipid flip-flop across the otherwise open edge. In such semi-periodic simulations, the bilayer is free to choose both its area and mean curvature, allowing for minimization of the bilayer elastic free energy. We implement these principles in a highly coarse-grained model and show how even the simplest examples of such simulations can reveal useful membrane elastic properties, such as the location of the monolayer neutral surface. [ABSTRACT FROM AUTHOR]

• Lipid droplet (LD) accumulation in the brain depends upon ageing, oxidative stress and inflammation. • The Peridroplet mitochondria plays a vital role in lipid metabolism and regulates mitochondrial oxidative phosphorylation. • Abnormal astrocytic OXPHOS causes LD build up, which can cause neurodegeneration. Energy metabolism in the brain has been considered one of the critical research areas of neuroscience for ages. One of the most vital parts of brain metabolism cascades is lipid metabolism, and fatty acid plays a crucial role in this process. The fatty acid breakdown process in mitochondria undergoes through a conserved pathway known as β-oxidation where acetyl-CoA and shorter fatty acid chains are produced along with a significant amount of energy molecule. Further, the complete breakdown of fatty acids occurs when they enter the mitochondrial oxidative phosphorylation. Cells store energy as neutral lipids in organelles known as Lipid Droplets (LDs) to prepare for variations in the availability of nutrients. Fatty acids are liberated by lipid droplets and are transported to various cellular compartments for membrane biogenesis or as an energy source. Current research shows that LDs are important in inflammation, metabolic illness, and cellular communication. Lipid droplet biology in peripheral organs like the liver and heart has been well investigated, while the brain's LDs have received less attention. Recently, there has been increased awareness of the existence and role of these dynamic organelles in the central nervous system, mainly connected to neurodegeneration. In this review, we discussed the role of beta-oxidation and lipid droplet formation in the oxidative phosphorylation process, which directly affects neurodegeneration through various pathways. [ABSTRACT FROM AUTHOR]

As a dynamic organelle, lipid droplets (LDs) are intricately involved in lipid storage, metabolism and various life processes. Their aberrant behaviour commonly signifies cellular dysfunction, which may contribute to the occurrence of a variety of diseases, particularly non-alcoholic fatty liver disease (NAFLD). Thus, it holds immense medical significance to develop specific probes targeting LDs to monitor the changes in the development of NAFLD. To this end, a D–π–A structural probe TSB was synthesized by Knoevenagel reaction based on triphenylamine and β-diketone boron difluoride. Optical studies revealed that probe TSB exhibited a strong solvation effect and a large Stokes shift (up to 299 nm in acetonitrile solution). Moreover, wash-free and co-localization experiments demonstrated the probe's precise targeting of LD sites within cells through a washing-free procedure with extreme specificity. Importantly, TSB has been validated for distinguishing between fatty liver and normal liver at the organ level, thereby holding potential for early diagnosis of NAFLD. These experimental findings will lay a theoretical foundation for the design and synthesis of more superior fluorescent probes specifically targeting LDs. [ABSTRACT FROM AUTHOR]

Purpose: Some diseases require that patients receive parenteral nutrition (PN) over a prolonged time period. Long-term administration of PN can further complicate an already complex therapy, posing additional risk of potential complications. This article is based on presentations and discussions held at the International Safety and Quality of PN Summit, providing insights into aspects of home PN (HPN) and examples of good HPN practice. Summary: One critical step in the HPN process is when patients transition from a hospital to a home setting, and vice versa. Generally, electronic PN ordering is not feasible in an HPN setting, leading to potential difficulties in communication and coordination. HPN requires that patients (or their home caregivers) administer PN, and thus their education and competency are crucial. Likewise, the choice of PN formulation is of great importance. For example, using more modern intravenous lipid emulsions containing medium-chain triglycerides, olive oil, and/or fish oil can provide benefits in terms of liver function during long-term HPN. Internationally, there are wide variations in delivery of HPN, with compounded PN dominating in some countries while others make greater use of marketauthorized multichamber bags (MCBs). Patient-related factors, institutional considerations, and the availability of different MCB formulations, are also contributing factors guiding formulation and delivery system preferences. Conclusion: Education and communication remain key components of a successful HPN process. The information shared here may help to motivate efforts to improve HPN processes and to consider the often-differing perspectives of patients and their healthcare professionals. [ABSTRACT FROM AUTHOR]

Purpose: Parenteral nutrition (PN) is an established therapy when oral/enteral feeding is not sufficient or is contraindicated, but nevertheless PN remains a complex, high-alert medication that is susceptible to errors that may affect patient safety. Over time, considerable progress has been made to make PN practices safer. The purpose of this article is to address ongoing challenges to improve the PN use process from prescription to administration and monitoring, and to outline practical aspects fostering the safety, quality, and cost-effectiveness of PN, as discussed at the International Safety and Quality of PN Summit. Summary: Opportunities to improve the PN use process in clinical practice include the promotion of inter-disciplinary communication, vigilant surveillance for complications, staff education to increase competency, and more consistent use of advanced technologies that allow automated safety checks throughout the PN process. Topics covered include considerations on PN formulations, including the value of intravenous lipid emulsions (ILEs), trends in compounding PN, the current and future role of market-authorized multi-chamber PN bags containing all 3 macronutrients (amino acids, glucose/dextrose, and ILE) in the United States and in Europe, and strategies to cope with the increasing global problem of PN product shortages. Conclusion: This review outlines potential strategies to use in clinical practice to overcome ongoing challenges throughout the PN use process, and ultimately promote PN patient safety. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is a lethal disease with limited effective treatments. A deeper understanding of its molecular mechanisms is crucial to reduce incidence and mortality. Epidemiological evidence suggests a link between diet and disease risk, though dietary recommendations for at‐risk individuals remain debated. Here, we propose that cell‐intrinsic nutrient sensing pathways respond to specific diet‐derived cues to facilitate oncogenic transformation of pancreatic epithelial cells. This review explores how diet influences pancreatic cancer predisposition through nutrient sensing and downstream consequences for (pre‐)cancer cell biology. We also examine experimental evidence connecting specific food intake to pancreatic cancer progression, highlighting nutrient sensing as a promising target for therapeutic development to mitigate disease risk. [ABSTRACT FROM AUTHOR]

Developing new drugs is a complex, time‐consuming, and expensive process, essential to identify potential pharmacokinetic issues in the early stages to avoid investment in nonpromising candidates. Nearly half of all drug targets and key drug‐metabolizing enzymes are found in intracellular environments, compartmentalized by semipermeable barriers, the cell membranes. Inspired by their lipidic bilayer structure, lipid‐based biomimetic platforms are being developed to understand the biochemical and biophysical processes at the cellular membrane level. Considering the pharmaceutical industry's demands for efficient in vitro high throughput screening tools, microfluidic technology emerges as a promising solution to address challenges in lipid biomimetic models for screening applications. This involves the transformation of commonly used lipid‐based biomimetic models, like supported lipid bilayers and lipid vesicles, to miniaturized approachs and their evolution into a new generation of bilayer models. These include pore‐suspended and free‐standing lipid bilayers, black lipid membranes, and droplet interface bilayers. This review provides an overview of both generations of lipid biomimetic models used in drug‐membrane screening applications. Moreover, it delves into the intricacies of their production through microfluidic approaches and examines their screening applications in drug‐membrane interaction. The review concludes with a critical analysis of potential future directions in this rapidly evolving field. [ABSTRACT FROM AUTHOR]

[Display omitted] Conjugating biomolecules, such as antibodies, to bioconjugate moieties on lipid surfaces is a powerful tool for engineering the surface of diverse biomaterials, including cells and nanoparticles. We developed supported lipid bilayers (SLBs) presenting well-defined spatial distributions of functional moieties as models for precisely engineered functional biomolecular-lipid surfaces. We used quartz crystal microbalance with dissipation (QCM-D) and atomic force microscopy (AFM) to determine how vesicles containing a mixture of 1,2-dipalmitoyl- sn - glycero -3-phosphatidylcholine (DPPC) and 1,2-distearoyl- sn - glycero -3-phosphoethanolamine-N-[azido(polyethylene glycol)-2000] (DSPE-PEG-N 3) form SLBs as a function of the lipid phase transition temperature (T m). Above the DPPC T m , DPPC/DSPE-PEG-N 3 vesicles form SLBs with functional azide moieties on SiO 2 substrates via vesicle fusion. Below this T m , DPPC/DSPE-PEG-N 3 vesicles attach to SiO 2 intact. Intact DPPC/DSPE-PEG-N 3 vesicles on the SiO 2 surfaces fuse and rupture to form SLBs when temperature is brought above the DPPC T m. AFM studies show uniform and complete DPPC/DSPE-PEG-N 3 SLB coverage of SiO 2 surfaces for different DSPE-PEG-N 3 concentrations. As the DSPE-PEG-N 3 concentration increases from 0.01 to 6 mol%, the intermolecular spacing of DSPE-PEG-N 3 in the SLBs decreases from 4.6 to 1.0 nm. The PEG moiety undergoes a mushroom to brush transition as DSPE-PEG-N 3 concentration varies from 0.1 to 2.0 mol%. Via copper-free click reaction, IgG was conjugated to SLB surfaces with 4.6 nm or 1.3 nm inter-DSPE-PEG-N 3 spacing. QCM-D and AFM data show; 1) uniform and complete IgG layers of similar mass and thickness on the two types of SLB; 2) a higher-viscosity/less rigid IgG layer on the SLB with 4.6 nm inter-DSPE-PEG-N 3 spacing. Our studies provide a blueprint for SLBs modeling spatial control of functional macromolecules on lipid surfaces, including surfaces of lipid nanoparticles and cells. [ABSTRACT FROM AUTHOR]

[Display omitted] • High sugar, protein of sludge shows outstanding biodrying potential. • Low ventilation rate improved bio-drying cycle and water removal effect. • Revealed the contribution of different water types to water removal. • Lipid degradation role: Crucial for releasing and transforming bound water. • Energy-saving ventilation changes the degradation sequence of organic matter. The effectiveness of dehydration and utilization processes for citric acid dewatered sludge is hampered by its high concentrations of polysaccharides, proteins, and water-binding properties of microbial extracellular polymers (EPS). This research explores the efficacy and mechanisms involved in extracting water from this type of sludge using biological drying technology, with varying rates of ventilation. Especially pertinent was the use of low ventilation rates as control variables. Our results suggest that a scheduled intermittent ventilation at lower rates allows for the most efficient removal of water, achieving a rate of 41.71 % within eight days, according to the zero-order kinetic model. Remarkably, the peak temperature registered was 60 °C, reaching this threshold in just 0.1 days and maintaining high temperatures for approximately 5.9 days. Component analysis of organic matter illustrated a preferential degradation process for lipids under these ventilation conditions which is pivotal for releasing and transforming bound water for efficient extraction, as well as facilitating the breakdown of easily hydrolysable materials. Further, polysaccharide/protein (EPS) decomposition contributed to water removal, though less significantly. The periodic ventilation strategy allowed for the maximum cumulative temperature to be sustained, demonstrating superior efficiency in harnessing bio-generated heat (82.77 % for water evaporation), resulting in dry sludge suitable for self-sustained combustion at relatively low cost ($26.61/t). Highlighted by this study is the considerable potential of energy-efficient ventilation methods in the biological drying treatment of citric acid fermented sludge and similar industrial waste materials. [ABSTRACT FROM AUTHOR]

Understanding interactions of inorganic nanoparticles with biomolecules is important in many biotechnology, nanomedicine, and toxicological research, however, the size of typical nanoparticles makes their direct modeling by atomistic simulations unfeasible. Here, we present a bottom‐up coarse‐graining approach for modeling titanium dioxide (TiO 2) nanomaterials in contact with phospholipids that uses the inverse Monte Carlo method to optimize the effective interactions from the structural data obtained in small‐scale all‐atom simulations of TiO 2 surfaces with lipids in aqueous solution. The resulting coarse‐grained models are able to accurately reproduce the structural details of lipid adsorption on different titania surfaces without the use of an explicit solvent, enabling significant computational resource savings and favorable scaling. Our coarse‐grained simulations show that small spherical TiO 2 nanoparticles (r=2 nm) can only be partially wrapped by a lipid bilayer with phosphoethanolamine headgroups, however, the lipid adsorption increases with the radius of the nanoparticle. The current approach can be used to study the effect of the size and shape of TiO 2 nanoparticles on their interactions with cell membrane lipids, which can be a determining factor in membrane wrapping as well as the recently discovered phenomenon of nanoquarantining, which involves the formation of layered nanomaterial–lipid structures. [ABSTRACT FROM AUTHOR]

The stemness loss-associated dysregeneration of impaired alveolar type 2 epithelial (AT2) cells abolishes the reversible therapy of idiopathic pulmonary fibrosis (IPF). We here report an inhalable mucus-penetrating lipid nanoparticle (LNP) for codelivering dual mRNAs, promoting realveolarization via restoring AT2 stemness for IPF treatment. Inhalable LNPs were first formulated with dipalmitoylphosphatidylcholine and our in-house-made ionizable lipids for high-efficiency pulmonary mucus penetration and codelivery of dual messenger RNAs (mRNAs), encoding cytochrome b5 reductase 3 and bone morphogenetic protein 4, respectively. After being inhaled in a bleomycin model, LNPs reverses the mitochondrial dysfunction through ameliorating nicotinamide adenine dinucleotide biosynthesis, which inhibits the accelerated senescence of AT2 cells. Concurrently, pathological epithelial remodeling and fibroblast activation induced by impaired AT2 cells are terminated, ultimately prompting alveolar regeneration. Our data demonstrated that the mRNA-LNP system exhibited high protein expression in lung epithelial cells, which markedly extricated the alveolar collapse and prolonged the survival of fibrosis mice, providing a clinically viable strategy against IPF. [ABSTRACT FROM AUTHOR]

Seborrheic dermatitis (SD) is a highly prevalent dermatological condition globally. The condition demonstrates bimodal presentation with what is commonly thought to be two subtypes: adult/adolescent seborrheic dermatitis (ASD) and infantile seborrheic dermatitis (ISD). Despite the common prevalence of ASD and ISD, there remains uncertainty around the underlying pathogenetic mechanisms, risk factors, and appropriate classification of the disease(s). This narrative review summarizes the current understanding of the epidemiology, presentation, and pathogenetic factors like epidermal barrier dysfunction, lipid abnormalities, and cutaneous microbiome for ASD and ISD. Elements such as immune responsiveness, neuroendocrine factors, and genetics in these disease states are also investigated. Throughout our review, we highlight shared features and discrepancies between ASD and ISD that are present in the literature and discuss potential avenues for future research that explore these disease states. We aim to contribute to the medical discourse on ASD and ISD and increase awareness of the need for additional research around these conditions, ultimately informing better targeting of therapeutics moving forward. [ABSTRACT FROM AUTHOR]

Neutral conditions are conducive for the yeast to mycelium transformation of C. albicans and inducing biofilm formation. Alternatively, an acidic environment can promote the growth of C. albicans yeast and phospholipase expression, and obviously affect the antifungal activity of ketoconazole (KET). In this study, KET-loaded nanostructure hybrid lipid capsules (KET-nHLCs) comprised of soybean lecithin, HS15 and ethyl α-linolenate were prepared using the thin film hydration method. Additionally, the effect of pH on the release and antifungal activity of KET-nHLCs was investigated. The encapsulation efficiency of KET-nHLCs was determined to be 91.53% ± 1.24%, and the water solubility of KET in the KET-nHLC group was enhanced by 158-fold compared to the crude KET. KET-nHLCs could control the in vitro drug release at pH 4.5/7.4, while its slow-release effect on KET was more obvious at pH 4.5. The MIC50 values of KET-nHLCs and KET were 0.5 and 0.25 μg mL−1 at pH 7.4 and 2 and 4 μg mL−1 pH 4.5, respectively. Interestingly, KET-nHLCs more effectively inhibited the yeast-hyphae transformation and had better antibiofilm activity than crude KET. Thus, the -nHLC delivery system containing soybean lecithin has potential application in the field of fungal infection treatment. [ABSTRACT FROM AUTHOR]

The current consensus holds that optically‐cleared specimens are unsuitable for Magnetic Resonance Imaging (MRI); exhibiting absence of contrast. Prior studies combined MRI with tissue‐clearing techniques relying on the latter's ability to eliminate lipids, thereby fostering the assumption that lipids constitute the primary source of ex vivo MRI‐contrast. Nevertheless, these findings contradict an extensive body of literature that underscores the contribution of other features to contrast. Furthermore, it remains unknown whether non‐delipidating clearing methods can produce MRI‐compatible specimens or whether MRI‐contrast can be re‐established. These limitations hinder the development of multimodal MRI‐light‐microscopy (LM) imaging approaches. This study assesses the relation between MRI‐contrast, and delipidation in optically‐cleared whole brains following different tissue‐clearing approaches. It is demonstrated that uDISCO and ECi‐brains are MRI‐compatible upon tissue rehydration, despite both methods' substantial delipidating‐nature. It is also demonstrated that, whereas Scale‐clearing preserves most lipids, Scale‐cleared brain lack MRI‐contrast. Furthermore, MRI‐contrast is restored to lipid‐free CLARITY‐brains without introducing lipids. Our results thereby dissociate between the essentiality of lipids to MRI‐contrast. A tight association is found between tissue expansion, hyperhydration and loss of MRI‐contrast. These findings then enabled us to develop a multimodal MRI‐LM‐imaging approach, opening new avenues to bridge between the micro‐ and mesoscale for biomedical research and clinical applications. [ABSTRACT FROM AUTHOR]

Background: Shift work has been identified as a risk factor for several chronic health conditions including obesity. This study evaluated the impact of a low-calorie meal replacement (MR) as a dinner substitute on body composition and metabolic parameters in shift workers with overweight and obesity. Methods: An 8-week parallel, randomized controlled trial was conducted on overweight and obese shift workers in a large hospital. An intervention group (IG) (n = 25) was provided with a low-calorie MR shake (∼200 kcal) as a replacement for dinner, every day for 8 weeks, while the control group (CG) (n = 25) continued their habitual diet. Anthropometric measurements, body composition, biochemical, and lifestyle data were assessed at the first and last visits. Analyses were done per protocol (PP) and by intention to treat (ITT). Results: Over the study duration, both groups displayed moderate changes in anthropometric measurements and body composition, although these were not statistically significant according to the PP analysis. In the ITT analysis, apart from the hip circumference (HC), all other anthropometric parameters demonstrated significant group and time interactions, suggesting the advantageous effects of the meal replacement over the study period (P < 0.05). HDL and VLDL cholesterol measures showed significant main effects, influenced by both group (P = 0.031) and time (P = 0.050) respectively. The most pronounced dietary shift in the IG was a reduction in carbohydrate consumption and an increase in protein intake. Throughout the study, the meal replacement was well-tolerated, with no adverse events reported. Conclusions: The meal replacement dietary intervention appears to offer beneficial health effects over time. Extended research is crucial to understand the broader implications of meal replacements across diverse populations. Trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12622000231741. Registered on 09 February 2022. https://www.anzctr.org.au/ACTRN12622000231741.aspx. [ABSTRACT FROM AUTHOR]

Lipopolysaccharide (LPS), a cell surface component of Gram‐negative bacteria, activates innate immunity. Its active principle is the terminal glycolipid lipid A. Acetobacter pasteurianus is a Gram‐negative bacterium used in the fermentation of traditional Japanese black rice vinegar (kurozu). In this study, we focused on A. pasteurianus lipid A, which is a potential immunostimulatory component of kurozu. The active principle structure of A. pasteurianus lipid A has not yet been identified. Herein, we first systematically synthesized three types of A. pasteurianus lipid As containing a common and unique tetrasaccharide backbone. We developed an efficient method for constructing the 2‐trehalosamine skeleton utilizing borinic acid‐catalyzed glycosylation to afford 1,1'‐α,α‐glycoside in high yield and stereoselectivity. A common tetrasaccharide intermediate with an orthogonal protecting group pattern was constructed via [2+2] glycosylation. After introducing various fatty acids, all protecting groups were removed to achieve the first chemical synthesis of three distinct types of A. pasteurianus lipid As. After evaluating their immunological function using both human and murine cell lines, we identified the active principles of A. pasteurianus LPS. We also found the unique anomeric structure of A. pasteurianus lipid A contributes to its high chemical stability. [ABSTRACT FROM AUTHOR]

Lipopolysaccharide (LPS), a cell surface component of Gram‐negative bacteria, activates innate immunity. Its active principle is the terminal glycolipid lipid A. Acetobacter pasteurianus is a Gram‐negative bacterium used in the fermentation of traditional Japanese black rice vinegar (kurozu). In this study, we focused on A. pasteurianus lipid A, which is a potential immunostimulatory component of kurozu. The active principle structure of A. pasteurianus lipid A has not yet been identified. Herein, we first systematically synthesized three types of A. pasteurianus lipid As containing a common and unique tetrasaccharide backbone. We developed an efficient method for constructing the 2‐trehalosamine skeleton utilizing borinic acid‐catalyzed glycosylation to afford 1,1'‐α,α‐glycoside in high yield and stereoselectivity. A common tetrasaccharide intermediate with an orthogonal protecting group pattern was constructed via [2+2] glycosylation. After introducing various fatty acids, all protecting groups were removed to achieve the first chemical synthesis of three distinct types of A. pasteurianus lipid As. After evaluating their immunological function using both human and murine cell lines, we identified the active principles of A. pasteurianus LPS. We also found the unique anomeric structure of A. pasteurianus lipid A contributes to its high chemical stability. [ABSTRACT FROM AUTHOR]

Background: The causal associations of lipids and the drug target genes with atrial fibrillation (AF) risk remain obscure. We aimed to investigate the causal associations using genetic evidence. Methods: Mendelian randomization (MR) analyses were conducted using summary-level genome-wide association studies (GWASs) in European and East Asian populations. Lipid profiles (low-density lipoprotein cholesterol, triglyceride, and lipoprotein[a]) and lipid-modifying drug target genes (3-hydroxy-3-methylglutaryl-CoA reductase, proprotein convertase subtilisin/kexin type 9, NPC1-like intracellular cholesterol transporter 1, apolipoprotein C3, angiopoietin-like 3, and lipoprotein[a]) were used as exposures. AF was used as an outcome. The inverse variance weighted method was applied as the primary method. Summary-data-based Mendelian randomization analyses were performed for further validation using expression quantitative trait loci data. Mediation analyses were conducted to explore the indirect effect of coronary heart disease. Results: In the European population, MR analyses demonstrated that elevated levels of lipoprotein(a) increased AF risk. Moreover, analyses focusing on drug targets revealed that the genetically proxied target gene LPA, which simulates the effects of drug intervention by reducing lipoprotein(a), exhibited an association with AF risk. This association was validated in independent datasets. There were no consistent and significant associations observed for other traits when analyzed in different datasets. This finding was also corroborated by Summary-data-based Mendelian randomization analyses between LPA and AF. Mediation analyses revealed that coronary heart disease plays a mediating role in this association. However, in the East Asian population, no statistically significant evidence was observed to support these associations. Conclusions: This study provided genetic evidence that Lp(a) may be a causal factor for AF and that LPA may represent a promising pharmacological target for preventing AF in the European population. [ABSTRACT FROM AUTHOR]

Agonists of Toll like receptors (TLRs) have attracted interest as adjuvants and immune modulators. A crystal structure of TLR4/MD2 with E. coli LPS indicates that the fatty acid at C‐2 of the lipid A component of LPS induces dimerization of two TLR4‐MD2 complexes, which in turn initiates cell signaling leading to the production of (pro)inflammatory cytokines. To probe the importance of the (R)‐3‐hydroxymyristate at C‐2 of lipid A, a range of bis‐ and mono‐phosphoryl lipid A derivatives with different modifications at C‐2 were prepared by a strategy in which 2‐methylnaphthyl ethers were employed as permanent protecting group that could be readily removed by catalytic hydrogenation. The C‐2 amine was protected as 9‐fluorenylmethyloxycarbamate, which at a later stage could be removed to give a free amine that was modified by different fatty acids. LPS and the synthetic lipid As induced the same cytokines, however, large differences in activity were observed. A compound having a hexanoyl moiety at C‐2 still showed agonistic properties, but further shortening to a butanoyl abolished activity. The modifications had a larger influence on monophosphoryl lipid As. The lipid As having a butanoyl moiety at C‐2 could selectively antagonize TRIF associated cytokines induced by LPS or lipid A. [ABSTRACT FROM AUTHOR]

Lipid droplets (LDs) are composed of a core of neutral lipids wrapped by a phospholipid (PL) monolayer containing several hundred proteins that vary between different cells or organisms. How LD proteins target to LDs is still largely unknown. Here, we show that RNAi knockdown or gene mutation of let-767, encoding a member of hydroxysteroid dehydrogenase (HSD), displaced the LD localization of three well-known LD proteins: DHS-3 (dehydrogenase/reductase), PLIN-1 (perilipin), and DGAT-2 (diacylglycerol O-acyltransferase 2), and also prevented LD growth in Caenorhabditis elegans. LET-767 interacts with ARF-1 (ADP-ribosylation factor 1) to prevent ARF-1 LD translocation for appropriate LD protein targeting and lipid homeostasis. Deficiency of LET-767 leads to the release of ARF-1, which further recruits and promotes translocation of ATGL-1 (adipose triglyceride lipase) to LDs for lipolysis. The displacement of LD proteins caused by LET-767 deficiency could be reversed by inhibition of either ARF-1 or ATGL-1. Our work uncovers a unique LET-767 for determining LD protein targeting and maintaining lipid homeostasis. [ABSTRACT FROM AUTHOR]

The essential Golgi protein Sly1 is a member of the Sec1/mammalian Unc-18 (SM) family of SNARE chaperones. Sly1 was originally identified through remarkable gain-of-function alleles that bypass requirements for diverse vesicle tethering factors. Employing genetic analyses and chemically defined reconstitutions of ER-Golgi fusion, we discovered that a loop conserved among Sly1 family members is not only autoinhibitory but also acts as a positive effector. An amphipathic lipid packing sensor (ALPS)-like helix within the loop directly binds high-curvature membranes. Membrane binding is required for relief of Sly1 autoinhibition and also allows Sly1 to directly tether incoming vesicles to the Qa-SNARE on the target organelle. The SLY1-20 mutation bypasses requirements for diverse tethering factors but loses this ability if the tethering activity is impaired. We propose that long-range tethers, including Golgins and multisubunit tethering complexes, hand off vesicles to Sly1, which then tethers at close range to initiate trans-SNARE complex assembly and fusion in the early secretory pathway. [ABSTRACT FROM AUTHOR]

Chronic feeding of a high fat diet (HFD) in preclinical species induces broad metabolic dysfunction characterized by body weight gain, hyperinsulinemia, dyslipidemia and impaired insulin sensitivity. The plasma lipidome is not well characterized in dogs with HFD-induced metabolic dysfunction. We therefore aimed to describe the alterations that occur in the plasma lipid composition of dogs that are fed a HFD and examine the association of these changes with the clinical signs of metabolic dysfunction. Dogs were fed a normal diet (ND) or HFD for 12 weeks. Insulin sensitivity (SI) and beta cell compensation (AIRG) were assessed through an intravenous glucose tolerance test (IVGTT) and serum biochemistry was analyzed before the introduction of HFD and again after 12 weeks of continued ND or HFD feeding. Plasma lipidomics were conducted prior to the introduction of HFD and again at week 8 in both ND and HFD-fed dogs. 12 weeks of HFD feeding resulted in impaired insulin sensitivity and increased beta cell compensation measured by SI (ND mean: 11.5 [mU/l]–1 min–1, HFD mean: 4.7 [mU/l]–1 min–1) and AIRG (ND mean: 167.0 [mU/l]min, HFD mean: 260.2 [mU/l]min), respectively, compared to dogs fed ND over the same duration. Chronic HFD feeding increased concentrations of plasma lipid species and deleterious fatty acids compared to dogs fed a ND. Saturated fatty acid (SFA) concentrations were significantly associated with fasting insulin (R2 = 0.29), SI (R2 = 0.49) and AIRG (R2 = 0.37) in all dogs after 12 weeks, irrespective of diet. Our results demonstrate that chronic HFD feeding leads to significant changes in plasma lipid composition and fatty acid concentrations associated with metabolic dysfunction. High SFA concentrations may be predictive of deteriorated insulin sensitivity in dogs. [ABSTRACT FROM AUTHOR]

Extracting membrane proteins from the hydrophobic environment of the biological membrane, in a physiologically relevant and stable state, suitable for downstream analysis remains a challenge. The traditional route to membrane protein extraction has been to use detergents and the last 15 years or so have seen a veritable explosion in the development of novel detergents with improved properties, making them more suitable for individual proteins and specific applications. There have also been significant advances in the development of encapsulation of membrane proteins in lipid based nanodiscs, either directly from the native membrane using polymers allowing effective capture of the protein and protein‐associated membrane lipids, or via reconstitution of detergent extracted and purified protein into nanodiscs of defined lipid composition. All of these advances have been successfully applied to the study of membrane proteins via a range of techniques and there have been some spectacular membrane protein structures solved. In addition, the first detailed structural and biophysical analyses of membrane proteins retained within a biological membrane have been reported. Here we summarise and review the recent advances with respect to these new agents and systems for membrane protein extraction, reconstitution and analysis. [ABSTRACT FROM AUTHOR]

Physical activity (PA) positively influences pregnancy, a critical period for health promotion, and affects placental structure and function in ways previously overlooked. Here, we summarize the current body of literature examining the association between PA, placenta biology, and physiology while also highlighting areas where gaps in knowledge exist. PA during pregnancy induces metabolic changes, influencing nutrient availability and transporter expression in the placenta. Hormones and cytokines secreted during PA contribute to health benefits, with intricate interactions in pro‐ and anti‐inflammatory markers. Extracellular vesicles and placental "‐omics" data suggest that gestational PA can shape placental biology, affecting gene expression, DNA methylation, metabolite profiles, and protein regulation. However, whether cytokines that respond to PA alter placental proteomic profiles during pregnancy remains to be elucidated. The limited research on placenta mitochondria of physically active gestational parents (gesP), has shown improvements in mitochondrial DNA and antioxidant capacity, but the relationship between PA, placental mitochondrial dynamics, and lipid metabolism remains unexplored. Additionally, PA influences the placenta‐immune microenvironment, angiogenesis, and may confer positive effects on neurodevelopment and mental health through placental changes, vascularization, and modulation of brain‐derived neurotrophic factor. Ongoing exploration is crucial for unraveling the multifaceted impact of PA on the intricate placental environment. [ABSTRACT FROM AUTHOR]

Background: Non-alcoholic fatty liver disease (NAFLD) is a significant hepatic condition that has gained worldwide attention. Kaempferol (Kae), renowned for its diverse biological activities, including anti-inflammatory, antioxidant, anti-aging, and cardio-protective properties, has emerged as a potential therapeutic candidate for non-alcoholic steatohepatitis (NASH). Despite its promising therapeutic potential, the precise underlying mechanism of Kae's beneficial effects in NASH remains unclear. Therefore, this study aims to clarify the mechanism by conducting comprehensive in vivo and in vitro experiments. Results: In this study, a murine model of non-alcoholic steatohepatitis (NASH) was established by feeding C57BL/6 female mice a high-fat diet for 12 weeks. Kaempferol (Kae) was investigated for its ability to modulate systemic inflammatory responses and lipid metabolism in this model (20 mg/kg per day). Notably, Kae significantly reduced the expression of NLRP3-ASC/TMS1-Caspase 3, a crucial mediator of liver tissue inflammation. Additionally, in a HepG2 cell model induced with palmitic acid/oleic acid (PA/OA) to mimic NASH conditions, Kae demonstrated the capacity to decrease lipid droplet accumulation and downregulate the expression of NLRP3-ASC/TMS1-Caspase 3 (20 µM and the final concentration to 20 nM). These findings suggest that Kae may hold therapeutic potential in the treatment of NASH by targeting inflammatory and metabolic pathways. Conclusions: These findings suggest that kaempferol holds potential as a promising therapeutic intervention for ameliorating non-alcoholic fatty liver disease (NAFLD). [ABSTRACT FROM AUTHOR]

The glucagon receptor family are typical class B1 G protein-coupled receptors (GPCRs) with important roles in metabolism, including the control of pancreas, brain, and liver function. As proteins with seven transmembrane domains, GPCRs are intimately in contact with lipid bilayers and therefore can be putatively regulated by interactions with their lipidic components, including cholesterol, sphingolipids, and other lipid species. Additionally, these receptors, as well as the agonists they bind to, can undergo lipid modifications, which can influence their binding capacity and/or elicit modified or biased signalling profiles. While the effect of lipids, and in particular cholesterol, has been widely studied for other GPCR classes, information about their role in regulating the glucagon receptor family is only beginning to emerge. Here we summarise our current knowledge on the effects of cholesterol modulation of glucagon receptor family signalling and trafficking profiles, as well as existing evidence for specific lipid-receptor binding and indirect effects of lipids via lipid modification of cognate agonists. Finally, we discuss the different methodologies that can be employed to study lipid-receptor interactions and summarise the importance of this area of investigation to increase our understanding of the biology of this family of metabolically relevant receptors. [ABSTRACT FROM AUTHOR]

While edible algae might seem low in fat, the lipids they contain are crucial for good health and preventing chronic diseases. This study introduces a binary matrix to analyze all the polar lipids in both macroalgae (Wakame—Undaria pinnatifida, Dulse—Palmaria palmata, and Nori—Porphyra spp.) and microalgae (Spirulina—Arthrospira platensis, and Chlorella—Chlorella vulgaris) using matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS). The key lies in a new dual matrix made by combining equimolar amounts of 1,5-diaminonaphthalene (DAN) and 9-aminoacridine (9AA). This combination solves the limitations of single matrices: 9AA is suitable for sulfur-containing lipids and acidic phospholipids, while DAN excels as an electron-transfer secondary reaction matrix for intact chlorophylls and their derivatives. By employing the equimolar binary matrix, a wider range of algal lipids, including free fatty acids, phospholipids, glycolipids, pigments, and even rare arsenosugarphospholipids were successfully detected, overcoming drawbacks related to ion suppression from readily ionizable lipids. The resulting mass spectra exhibited a good signal-to-noise ratio at a lower laser fluence and minimized background noise. This improvement stems from the binary matrix's ability to mitigate in-source decay effects, a phenomenon often encountered for certain matrices. Consequently, the data obtained are more reliable, facilitating a faster and more comprehensive exploration of algal lipidomes using high-throughput MALDI-MS/MS analysis. [ABSTRACT FROM AUTHOR]

A better understanding of how emulsifier type could differently influence the behavior of nanostructured lipid carriers (NLC) under the gastrointestinal digestion process, as well as at the cellular level, is of utmost importance for the NLC‐based formulations' optimization and risk assessment in the food field. In this study, NLC composed by fully hydrogenated soybean and high‐oleic sunflower oils were prepared using soy lecithin (NLC Lβ) or Tween 80 (NLC Tβ) as an emulsifier. β‐Carotene was entrapped within NLC developed as a promising strategy to overcome β‐carotene's low bioavailability and stability. The effect of emulsifier type on the digestibility of β‐carotene‐loaded NLC was evaluated using an in vitro dynamic digestion model mimicking peristalsis motion. The influence of β‐carotene‐loaded NLC on cell viability was assessed using Caco‐2 cells in vitro. NLC Tβ remained stable in the gastric compartment, presenting particle size (PS) similar to the initial NLC (PS: 245.68 and 218.18 nm, respectively), while NLC Lβ showed lower stability (PS > 1000 nm) in stomach and duodenum phases. NLC Tβ also provided high β‐carotene protection and delivery capacity (i.e., β‐carotene bioaccessibility increased 10‐fold). Based on the results of digestion studies, NLC Tβ has shown better physical stability during the passage through the in vitro dynamic gastrointestinal system than NLC Lβ. Moreover, the developed NLC did not compromise cell viability up to 25 µg/mL of β‐carotene. Thus, the NLC developed proved to be a biocompatible structure and able to incorporate and protect β‐carotene for further food applications. Practical Application: The findings of this study hold significant implications for industrial applications in terms of developing nanostructured lipid carriers from natural raw materials widely available and used to produce other lipid‐based products in the food industry, as an alternative to synthetic ones. In this respect, the β‐carotene‐loaded NLC developed in this study would find a great industrial application in the food industry, which is in constant search to develop functional foods capable of increasing the bioavailability of bioactive compounds. [ABSTRACT FROM AUTHOR]

Lipids are crucial substances for the formation and retention of volatile compounds (VOCs). The lipid and VOC profiles of boiled donkey meat were investigated by lipidomics and volatilomics. In total, 4277 lipids belonging to 39 subclasses were identified, comprising 26.93% triglycerides (TGs), 15.74% phosphatidylcholins (PCs), and 9.40% phosphatidylethanolamines. The relative percentage of TG in the meat significantly decreases (p < 0.001) from 0 to 40 min, after which there is no significant change, whereas PCs, sphingomyelins, and methyl phosphatidylcholines (MePCs) show the opposite trend. TG(16:1_18:1_18:2) and TG(16:0_16:1_18:2) appear to be key lipids for retaining VOCs in boiled donkey meat. Furthermore, PC(18:3e_16:0) and MePC(31:0e) were found to be potential markers for discriminating donkey meat. A total of 83 VOCs were detected, including 25.30% aldehydes, 18.07% hydrocarbons, 14.46% ketones, and 13.25% alcohols. Eleven characteristic VOCs with relative odor activity values >1 were identified as the predominant flavor compounds in boiled donkey meat, mainly hexanal and 1‐octen‐3‐ol. Of the 258 differential lipids, 72 of them, especially polyunsaturated‐fatty acid–rich lipids, are the main contributors to the formation of VOCs. Together, the key lipids for retention and formation of VOCs in donkey meat were revealed, providing a theoretical basis for VOC regulation. [ABSTRACT FROM AUTHOR]

• Cardiometabolic health benefits of dairy foods vary by fat content and product fermentation • Dairy fat intakes are associated with neutral to beneficial cardiometabolic activities • Full-fat dairy intakes have no demonstrated adverse impact on cardiovascular risk • Fermented dairy intakes positively influence lipid profiles • Milk polar lipids contribute to improved blood lipid profiles • Dietary recommendations concerning dairy likely require greater precision Bovine dairy milk is a nutrient-rich matrix, but consumption of full-fat dairy food varieties has been claimed historically to be associated with poorer cardiometabolic health, a notion often attributed to the saturated fat content. However, continued investigation that includes observational studies and randomized controlled trials (RCTs) provide evidence that favorably supports full-fat dairy foods and their bioactive components on cardiometabolic health. This review addresses this controversy by examining the evidence surrounding full-fat dairy foods and their implications for human health. Dairy foods are heterogeneous, not just in their fat content but also in other compositional aspects within and between fermented (e.g., yogurt, cheese) and nonfermented products (e.g., milk) that could differentially influence cardiometabolic health. Drawing from complementary lines of evidence from epidemiological studies and RCTs, this review describes the health effects of dairy foods regarding their fat content, as well as their polar lipids that are concentrated in the milk fat globule fraction. Observational studies have limitedly supported the consumption of full-fat dairy to protect against cardiometabolic disorders. However, this framework has been disputed by RCTs indicating that dairy foods, regardless of their fat content or fermentation, are not detrimental to cardiometabolic health and may instead alleviate certain cardiometabolic risk factors. As dietary recommendations evolve, which currently indicate to avoid full-fat dairy foods, it is essential to consider the totality of evidence, especially from RCTs, while also recognizing that investigation is needed to evaluate the complexity of dairy foods within diverse dietary patterns and their impacts on cardiometabolic health. This review examines the cardiometabolic effects of dairy, comparing full-fat and low-fat types. It starts with observational study findings on total dairy intake and its fat content, then explores the health benefits of specific dairy types, considering fat content and whether they are fermented. Next, it presents evidence from controlled trials to establish efficacy of the correlative outcomes suggested by observational studies. This approach offers insights for future dietary recommendations. [Display omitted] [ABSTRACT FROM AUTHOR]

Simple Summary: This review aims to deepen the understanding of buffalo farming in the Amazon, presenting the quality and nutritional value of buffalo meat and liver. We will explore the characteristics of nutrients and their influence on human health, with a special focus and particular emphasis in vitamins, minerals, and lipids. By investigating fatty acids and cholesterol, we seek to understand the complexity of lipids and their contribution to nutritional quality. The main objective of this study was to provide subsidies to improve buffalo farming practices, promote a healthier human diet and contribute to environmental sustainability in the Amazon region. Thus, this review aims to deepen the understanding of buffalo farming in the Amazon, presenting the quality and nutritional value of buffalo meat and liver. This information serves as a subsidy to improve practices related to the breeding system, nutrition, health and sustainability associated with aquatic buffaloes. For this, a review of the databases was carried out using the descriptors "nutritional value of buffalo meat", "nutritional value of buffalo liver" and "buffalo breeding in the Amazon". Thus, the consumption of foods derived from aquatic buffaloes has important nutritional value for human consumption. In view of this, it is possible to conclude that the nutrition of these animals is influenced by the biodiversity of the Amazon, giving unique characteristics to its products, also highlighting the importance of carrying out research that aims to value the potential use of this species and strengthen the economy of the region. [ABSTRACT FROM AUTHOR]

Simple Summary: Cholesterol and cholesterol derivatives accumulate in prostate cancer cells. Epidemiologic studies about diet and/or treatment with cholesterol-lowering drugs indicate that this metabolite plays a role in cancer progression, but they do not discriminate its possible role in cancer incidence. The goal of this study is so to determine whether cholesterol availability impacts tumor formation itself. Using a drosophila model specifically dedicated to the study of early epithelial tumorigenesis, we find that basal extrusion, a critical step of tumor formation, directly depends on cholesterol availability through dietary intake, and on cholesterol metabolization by the tumor cells. As we find that many genes related to cholesterol homeostasis and metabolism are ill-expressed in primary prostate cancer samples, this work indicates that cholesterol levels and metabolism could play a crucial role in the early phases of prostate cancer as well. Epidemiological studies point to cholesterol as a possible key factor for both prostate cancer incidence and progression. It could represent a targetable metabolite as the most aggressive tumors also appear to be sensitive to therapies designed to decrease hypercholesterolemia, such as statins. However, it remains unknown whether and how cholesterol, through its dietary uptake and its metabolism, could be important for early tumorigenesis. Oncogene clonal induction in the Drosophila melanogaster accessory gland allows us to reproduce tumorigenesis from initiation to early progression, where tumor cells undergo basal extrusion to form extra-epithelial tumors. Here we show that these tumors accumulate lipids, and especially esterified cholesterol, as in human late carcinogenesis. Interestingly, a high-cholesterol diet has a limited effect on accessory gland tumorigenesis. On the contrary, cell-specific downregulation of cholesterol uptake, intracellular transport, or metabolic response impairs the formation of such tumors. Furthermore, in this context, a high-cholesterol diet suppresses this impairment. Interestingly, expression data from primary prostate cancer tissues indicate an early signature of redirection from cholesterol de novo synthesis to uptake. Taken together, these results reveal that during early tumorigenesis, tumor cells strongly increase their uptake and use of dietary cholesterol to specifically promote the step of basal extrusion. Hence, these results suggest the mechanism by which a reduction in dietary cholesterol could lower the risk and slow down the progression of prostate cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Cervical cancer is the fourth most prominent cancer in women worldwide. Early cancer detection, timely treatment, and prognostic marker identification are vital to ensure that patients have improved outcomes. Magnetic resonance spectroscopy (MRS) is a powerful tool for detecting metabolites in vivo. This review article covers the role of MRS for cervical cancer for diagnosis, treatment response evaluation, and future applications of this technology. This review article investigates the utilization of MRS in the setting of cervical cancer. A variety of different techniques have been used in this space including single-voxel techniques such as point-resolved spectroscopy (PRESS) and stimulated echo acquisition mode spectroscopy (STEAM). Furthermore, the experimental parameters for these acquisitions including field strength, repetition times (TR), and echo times (TE) vary greatly. This study critically examines eleven MRS studies that focus on cervical cancer. Out of the eleven studies, ten studies utilized PRESS acquisition, while the remaining study used STEAM acquisition. These studies generally showed that the choline signal is altered in cervical cancer (4/11 studies), the lipid signal is generally increased in cervical cancer or the lipid distribution is changed (5/11 studies), and that diffusion-weighted imaging (DWI) can quantitatively detect lower apparent diffusion coefficient (ADC) values in cervical cancer (2/11 studies). Two studies also investigated the role of MRS for monitoring treatment response and demonstrated mixed results regarding choline signal, and one of these studies showed increased lipid signal for non-responders. There are several new MRS technologies that have yet to be implemented for cervical cancer including advanced spectroscopic imaging and artificial intelligence, and those technologies are also discussed in the article. [ABSTRACT FROM AUTHOR]

Simple Summary: Cell–cell communication mechanisms are gathering growing scientific interest, particularly in the context of cancer cells and the tumor microenvironment. Extracellular vesicles are gaining increased interest due to their relevance in tumor molecular characterization, classification, diagnosis, prognosis evaluation, and response to treatment. Many advances have been made in the clinical and therapeutic fields, exploiting increasingly precise biomolecular engineering strategies. This review aims to focus on the role of extracellular vesicles (EVs) as diagnostic and therapeutic tools in lung cancer. Lung cancer represents the leading cause of cancer-related mortality worldwide, with around 1.8 million deaths in 2020. For this reason, there is an enormous interest in finding early diagnostic tools and novel therapeutic approaches, one of which is extracellular vesicles (EVs). EVs are nanoscale membranous particles that can carry proteins, lipids, and nucleic acids (DNA and RNA), mediating various biological processes, especially in cell–cell communication. As such, they represent an interesting biomarker for diagnostic analysis that can be performed easily by liquid biopsy. Moreover, their growing dataset shows promising results as drug delivery cargo. The aim of our work is to summarize the recent advances in and possible implications of EVs for early diagnosis and innovative therapies for lung cancer. [ABSTRACT FROM AUTHOR]

Sausage is susceptible to oxidative changes in lipids and microbial spoilage due to the presence of water, fat, protein, and vitamins. Bee pollen (BP) as a source of potential antioxidants and antibacterial compounds can effectively prevent lipid peroxidation and microbial spoilage in meat products. The aim of the present study was to investigate the antibacterial and antioxidant activities of BP and the effects of nano/microparticles of bee pollen extract (n/m BP) at a concentration of 125 and 250 mg/100 g meat on the oxidative stability and microbial growth of high‐fat sausage during 30 days of storage at 4°C. The formation of BP particles in the nano/micro range was confirmed by scanning electron microscopy. High concentrations of total phenolic compounds (28.26 ± 0.10 mg GAE/g BP) with antioxidant activity (EC50 = 5.4 ± 0.07 mg/mL) were detected in BP. Based on the microdilution assay, the minimum inhibitory concentration of n/m BP for all test bacteria was 1000 (μg/mL) and the minimum bactericidal concentration of n/m BP was 2000 (μg/mL) for Staphylococcus aureus and Bacillus cereus and 4000 (μg/mL) for Escherichia coli and Pseudomonas aeruginosa. The n/m BP treatment (250 mg/100 g meat) showed a higher pH value (p <.05) and lower TBARS values (p <.05) than the ascorbic acid treatment (100 mg/100 g meat) and the control during the storage period. The microbial analysis showed that the addition of n/m BP led to a significant decrease (p <.05) in the total bacterial count, coliforms, S. aureus, and fungal population compared to the other samples. The results show that the addition of n/m BP (125 mg/100 g) can improve the texture, taste, and overall acceptability of the sausage compared to the control sample. In conclusion, this study suggests that BP can replace synthetic antioxidants in high‐fat sausages at the nano/microparticle level. [ABSTRACT FROM AUTHOR]

Health concerns regarding fat consumption, as well as shifts in customer preference, have prompted substantial studies into low‐fat products. This study examined the nutritional, color, functional, and antioxidant properties of Bambara groundnut (BGN) flour varieties (cream, brown, and red‐coated) grains as well as their influence on the physicochemical properties, lipid oxidation, and sensory acceptability of low‐fat mutton patties. The patties were formulated with 2.5%, 5%, 7.5%, and 10% of BGN flour for each variety, and 100% mutton patties were used as a control. The BGN flours showed significant (p <.05) differences in their nutritional composition (except for ash content), color, functional (excluding emulsion stability), and antioxidant properties. The increase in the percentage of substitution of BGN flours significantly increased the fiber (0.00% to 0.79%), ash (1.16% to 1.99%), and carbohydrates (2.14% to 1.99%) contents of the formulated mutton patties. However, moisture and protein contents decreased. The cooking yield of the formulated patties significantly increased with the increase in the percentage substitution of BGN flours (2.5%–10%), with values ranging from 76.39% to 86.80%, but the diameter reduction was limited. The increase in the inclusion of BGN flours significantly increased the lightness, hue angle, color difference, and whiteness of patties. Nevertheless, the redness, yellowness, chroma, and yellowness index of the patties decreased. The hardness and resilience of formulated patties significantly increased, with values varying from 16.41 to 17.66 N, and from 0.35 to 0.48 J/J, respectively, whereas the springiness, cohesiveness, and chewiness decreased. The lipid oxidation of formulated mutton patties significantly increased from Days 7 to 21, but was still less than that of the control sample within storage days. The sensory properties of formulated patties were not significantly different from the control sample and were above the acceptable score of five. All BGN varieties had positive effects on the mutton patties, more especially red, followed by brown, and cream, respectively. The inclusion of a 10% red BGN flour variety is highly recommended due to its significant impact on mutton patties. Nevertheless, different types of BGN varieties can each be used as additives in mutton patties without having detrimental effects on the quality parameters of the patties. [ABSTRACT FROM AUTHOR]

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]