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Beauvericin (BEA), a naturally occurring cyclic peptide with good pharmacological activity, has been widely explored in anticancer research. Although BEA is toxic, studies have demonstrated its antioxidant activity. However, to date, the antioxidant mechanisms of BEA remain unclear. Herein, we conducted a comprehensive and detailed study of the antioxidant mechanism of BEA using an untargeted metabolomics approach, subsequently validating the results. BEA concentrations of 0.5 and 1 μM significantly inhibited H2O2-induced oxidative stress (OS), decreased reactive oxygen species levels in PC-12 cells, and restored the mitochondrial membrane potential. Untargeted metabolomics indicated that BEA was primarily involved in lipid-related metabolism, suggesting its role in resisting OS in PC-12 cells by participating in lipid metabolism. BEA combated OS damage by increasing phosphatidylcholine, phosphatidylethanolamine, and sphingolipid levels. In the current study, BEA upregulated proteins related to the PI3K/AKT/mTOR pathway, thereby promoting cell survival. These findings support the antioxidant activity of BEA at low concentrations, warranting further research into its pharmacological effects.

Egg yolk phospholipids (PLs) extracted by organic solvent are prone to oxidation, while they are quite stable in egg yolk. This study was to verify the decisive role of lutein (naturally present in egg yolk) on the oxidative stability of PLs by constructing liposome. The liposome samples were heated at 100 °C for 10 min, and then the oxidation products of the liposome samples were analyzed by 1H NMR and GC–MS. The results showed that the concentrations of most of the oxidation products in the PLs-liposomes sample were significantly higher than those in the PLs&lutein-liposomes sample. Therefore, lutein could protect egg yolk PLs from oxidation, thus inhibiting the formation of lipid-derived volatile compounds. As those lipid-derived volatile compounds are the key fatty note odorants, this study has confirmed that the removal of lutein is the determining factor in using egg yolk PLs as an ideal precursor of fatty note odorants.

ABSTRACTShifts in the gut microbiota composition, called dysbiosis, have been directly associated with acute and chronic diseases. However, the underlying biological systems connecting gut dysbiosis to systemic inflammatory pathologies are not well understood. Phospholipids (PLs) act as precursors of both, bioactive inflammatory and resolving mediators. Their dysregulation is associated with chronic diseases including cancer. Gut microbial-derived lipids are structurally unique and capable of modulating host’s immunity. Lactobacillus johnsonii N6.2 is a Gram-positive gut symbiont with probiotic characteristics. L. johnsonii N6.2 reduces the incidence of autoimmunity in animal models of Type 1 Diabetes and improves general wellness in healthy volunteers by promoting, in part, local and systemic anti-inflammatory responses. By utilizing bioassay-guided fractionation methods with bone marrow-derived dendritic cells (BMDCs), we report here that L. johnsonii N6.2 purified lipids induce a transcriptional signature that resembles that of migratory (mig) DCs. RNAseq-based analysis showed that BMDCs stimulated with L. johnsonii N6.2 total lipids upregulate maturation-mig related genes Cd86, Cd40, Ccr7, Icam1 along with immunoregulatory genes including Itgb8, Nfkbiz, Jag1, Adora2a, IL2ra, Arg1, and Cd274. Quantitative reverse transcription (qRT)-PCR analysis indicated that PLs are the bioactive lipids triggering the BMDCs response. Antibody-blocking of surface Toll-like receptor (TLR)2 resulted in boosted PL-mediated upregulation of pro-inflammatory Il6. Chemical inhibition of the IKKα kinase from the non-canonical NF-κB pathway specifically restricted upregulation of Il6 and Tnf. Phenotypically, PL-stimulated BMDCs displayed an immature like-phenotype with significantly increased surface ICAM-1. This study provides insight into the immunoregulatory capacity of Gram-positive, gut microbial-derived phospholipids on innate immune responses.

Background: Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and leads to the poorest patient outcomes despite surgery and chemotherapy treatment. Exploring new molecular mechanisms of TNBC that could lead to the development of novel molecular targets are critically important for improving therapeutic options for treating TNBC. Methods: We sought to identify novel therapeutic targets in TNBC by combining genomic and functional studies with lipidomic analysis, which included mechanistic studies to elucidate the pathways that tie lipid profile to critical cancer cell properties. Our studies were performed in a large panel of human breast cancer cell lines and patient samples. Results: Comprehensive lipid profiling revealed that phospholipid metabolism is reprogrammed in TNBC cells. We discovered that patatin-like phospholipase domain-containing lipase 8 (PNPLA8) is overexpressed in TNBC cell lines and tissues from breast cancer patients. Silencing of PNPLA8 disrupted phospholipid metabolic reprogramming in TNBC, particularly affecting the levels of phosphatidylglycerol (PG), phosphatidylcholine (PC), lysophosphatidylcholine (LPC) and glycerophosphocholine (GPC). We showed that PNPLA8 is essential in regulating cell viability, migration and antioxidation in TNBC cells and promoted arachidonic acid and eicosanoid production, which in turn activated PI3K/Akt/Gsk3β and MAPK signaling. Conclusions: Our study highlights PNPLA8 as key regulator of phospholipid metabolic reprogramming and malignant phenotypes in TNBC, which could be further developed as a novel molecular treatment target. [ABSTRACT FROM AUTHOR]

Current research indicates that n-3 polyunsaturated fatty acids (PUFAs) bind to polar lipids (phospholipids and glycolipids) seem to exert a greater bioavailability compared to their neutral forms. The aim of this work was to obtain eicosapentaenoic acid (EPA) rich polar lipids from the saponifiable lipids (SLs) extracted from the microalga Nannochloropsis sp. (33.4 ± 0.1% of EPA; 60 ± 0.6% polar lipids) by fractionation using silica-gel columns and importantly, non-polar and polar (ethanol) non-toxic solvents. Nowadays, few studies have been conducted towards the extraction and purification of polar lipids. Firstly, the solvent type for obtaining the neutral saponifiable lipid (NSL) fraction (ethyl acetate, EA, butyl acetate, BA) and the SL/silica-gel, SL/BA, and SL/ethanol ratios were optimized in a small silica-gel cartridge (0.69 g silica gel). The optimized conditions were an SL/silica-gel ratio of 22.6 mg/g, an SL/BA ratio of 1.56 mg/mL and an SL/ethanol ratio of 0.312 mg/mL. Next, the fractionation scale was increased to a column containing 10 g of silica-gel. At this scale, a BA SL fraction was obtained with 96.2 ± 0.5% of NSLs, and an ethanol SL fraction containing 97.7 ± 0.3% of polar lipids and 44.9 ± 0.2% of EPA. In the ethanol fraction, 86.6 ± 0.2% of the polar lipids and 71.5 ± 0.4% of the EPA from the SL microalgal extract were recovered. Consequently, EPA-rich polar lipids were obtained at high yields and purities, which could be used as a source of n-3 PUFAs with greater bioavailability than those based on neutral lipids. [ABSTRACT FROM AUTHOR]

Background: Viral and autoimmune encephalitis may present with similar symptoms, but require different treatments. Thus, there is a need for biomarkers to improve diagnosis and understanding of pathogenesis. We hypothesized that virus-host cell interactions lead to different changes in central nervous system (CNS) metabolism than autoimmune processes and searched for metabolite biomarkers in cerebrospinal fluid (CSF) to distinguish between the two conditions. Methods: We applied a targeted metabolomic/lipidomic analysis to CSF samples from patients with viral CNS infections (n = 34; due to herpes simplex virus [n = 9], varicella zoster virus [n = 15], enteroviruses [n = 10]), autoimmune neuroinflammation (n = 25; autoimmune anti-NMDA-receptor encephalitis [n = 8], multiple sclerosis [n = 17), and non-inflamed controls (n = 31; Gilles de la Tourette syndrome [n = 20], Bell's palsy with normal CSF cell count [n = 11]). 85 metabolites passed quality screening and were evaluated as biomarkers. Standard diagnostic CSF parameters were assessed for comparison. Results: Of the standard CSF parameters, the best biomarkers were: CSF cell count for viral infections vs. controls (area under the ROC curve, AUC = 0.93), Q-albumin for viral infections vs. autoimmune neuroinflammation (AUC = 0.86), and IgG index for autoimmune neuroinflammation vs. controls (AUC = 0.90). Concentrations of 2 metabolites differed significantly (p < 0.05) between autoimmune neuroinflammation and controls, with proline being the best biomarker (AUC = 0.77). In contrast, concentrations of 67 metabolites were significantly higher in viral infections than controls, with SM.C16.0 being the best biomarker (AUC = 0.94). Concentrations of 68 metabolites were significantly higher in viral infections than in autoimmune neuroinflammation, and the 10 most accurate metabolite biomarkers (AUC = 0.89–0.93) were substantially better than Q-albumin (AUC = 0.86). These biomarkers comprised six phosphatidylcholines (AUC = 0.89–0.92), two sphingomyelins (AUC = 0.89, 0.91), and acylcarnitines isobutyrylcarnitine (C4, AUC = 0.92) and isovalerylcarnitine (C5, AUC = 0.93). Elevated C4 and C5 concentrations suggested dysfunctional mitochondrial β-oxidation and correlated only moderately with CSF cell count (Spearman ρ = 0.41 and 0.44), indicating that their increase is not primarily driven by inflammation. Conclusions: Changes in CNS metabolism differ substantially between viral CNS infections and autoimmune neuroinflammation and reveal CSF metabolites as pathophysiologically relevant diagnostic biomarkers for the differentiation between the two conditions. In viral CNS infections, the observed higher concentrations of free phospholipids are consistent with disruption of host cell membranes, whereas the elevated short-chain acylcarnitines likely reflect compromised mitochondrial homeostasis and energy generation. [ABSTRACT FROM AUTHOR]

With an increasing trend of phosphorus limitation in coastal waters, phytoplankton with advantageous strategies to address phosphorus deficiency might be more competitive in their communities. Combining physiological, transcriptomic, and miRNA analyses, the present study analyzed the molecular responses of different intracellular phosphorus components to phosphorus deficiency in the harmful dinoflagellate Karenia mikimotoi, with a specific focus on membrane phospholipid remodeling. The cellular phosphorus components of phospholipids, polyphosphate (polyP), and RNA and the associated gene expression showed dynamic variations over a prolonged phosphorus-stressed period. Under phosphorus deficiency, K. mikimotoi preferred to preserve polyP and RNA but efficiently replaced phospholipids with glycerol glycolipids and a betaine lipid to maintain active growth. This dynamic phospholipid substitution in K. mikimotoi was a combined result of the cessation of phospholipid biosynthesis and an increase in phospholipid breakdown. The expression of the identified miRNAs involved in ATP metabolism indicated that miRNAs may play an important role in regulating energy metabolism in K. mikimotoi. The present study improved the understanding of the molecular mechanism of intracellular phosphorus metabolism in marine phytoplankton and highlighted the strong capability of dinoflagellates to efficiently modulate intracellular phosphorus resources. IMPORTANCE Dinoflagellates are the most common phytoplankton group and account for more than 75% of harmful algal blooms in coastal waters. In recent decades, dinoflagellates seem to prevail in phosphate-depleted waters. However, the underlying acclimation mechanisms and competitive strategies of dinoflagellates in response to phosphorus deficiency are poorly understood, especially in terms of intracellular phosphorus modulation and recycling. Here, we focused on the response of intracellular phosphorus metabolism to phosphorus deficiency in the model dinoflagellate Karenia mikimotoi. Our work reveals the strong capability of K. mikimotoi to efficiently regulate intracellular phosphorus resources, particularly through membrane phospholipid remodeling and miRNA regulation of energy metabolism. Our research improved the understanding of intracellular phosphorus metabolism in marine phytoplankton and underscored the advantageous strategies of dinoflagellates in the efficient modulation of internal phosphorus resources to maintain active physiological activity and growth under unsuitable phosphorus conditions, which help them outcompete other species in coastal phosphate-depleted environments. [ABSTRACT FROM AUTHOR]

Main conclusion: The phosphatidic acid phosphohydrolase of Marchantia polymorpha modulates plastid glycolipid synthesis through the ER pathway and is essential for normal plant development regardless of nutrient availability. Membrane lipid remodeling is one of the strategies plant cells use to secure inorganic phosphate (Pi) for plant growth, but many aspects of the molecular mechanism and its regulation remain unclear. Here we analyzed membrane lipid remodeling using a non-vascular plant, Marchantia polymorpha. The lipid composition and fatty acid profile during Pi starvation in M. polymorpha revealed a decrease in phospholipids and an increase in both galactolipids and betaine lipids. In Arabidopsis thaliana, phosphatidic acid phosphohydrolase (PAH) is involved in phospholipid degradation and is crucial for tolerance to both Pi and nitrogen starvation. We produced two M. polymorpha PAH (MpPAH) knockout mutants (Mppah-1 and Mppah-2) and found that, unlike Arabidopsis mutants, Mppah impaired plant growth with shorter rhizoids compared with wild-type plants even under nutrient-replete conditions. Mutation of MpPAH did not significantly affect the mole percent of each glycerolipid among total membrane glycerolipids from whole plants under both Pi-replete and Pi-deficient conditions. However, the fatty acid composition of monogalactosyldiacylglycerol indicated that the amount of plastid glycolipids produced through the endoplasmic reticulum pathway was suppressed in Mppah mutants. Phospholipids accumulated in the mutants under N starvation. These results reveal that MpPAH modulates plastid glycolipid synthesis through the endoplasmic reticulum pathway more so than what has been observed for Arabidopsis PAH; moreover, unlike Arabidopsis, MpPAH is crucial for M. polymorpha growth regardless of nutrient availability. [ABSTRACT FROM AUTHOR]

This study was conducted to investigate the effects of dietary phospholipid levels on the sur‐ vival, growth, digestive enzyme activity, biochemical indicators, and Neverland gene expression of Erio⁃ cheir sinensis. Five experimental diets were formulated by including graded levels of soybean lecithin (0, 1%, 2%, 3% and 4%). Each diet was randomly fed to three groups of juvenile E. sinensis [initial body mass: (0.52±0.02) g], and the experimental period lasted for 60 days. The results showed that: ① phos‐ pholipid addition showed no significant effects on the survival rate of juvenile E. sinensis (P>0.05). The addition of phospholipids increased the weight gain rate and specific growth rate of juve‐ nile crabs, but reduced the feed conversion ratio, with the highest growth rate and lowest feed conversion ratio observed in the 1% phospholipid addition group. There is no significant difference compared to the control group and 3% phospholipid group（P< 0.05）. ② The activities of trypsin and amylase in the hepatopancreas of juvenile crabs decreased with the increase of phospholipid level. When the phospholipid level was equal to or above 3%, the activities were significantly lower than that in the 0% and 1% phospholipid groups (P<0.05). The amylase activity showed a similar tendency to weight growth rate with the increase of phospholipid level. The amylase ac‐ tivity was highest in the 1% phospholipid group, which was significantly higher than that in 3% and 4% phospholipid groups (P<0.05). On the contrary, the lipase activity decreased first and then increased, with the lowest value observed in the 2% phospholipid group, which was significantly lower than that in the 0 and 4% phospholipid groups (P<0.05). ③ As phospholipid level increased, triglyceride contents in the he‐ patopancreas of juvenile crabs decreased. When the phospholipid level was equal to or above 3%, the con‐ tents were significantly lower than that in the 0 and 1% phospholipid groups (P<0.05). ④ As phospho‐ lipid level increased to 2%, the expression level of Neverland gene in the hepatopancreas of juvenile crabs significantly increased, and then decreased with further increase of phospholipid level (P<0.05). In conclusion, 1% phospholipid significantly promoted growth performance, 2% phospholipid increased the expression of Neverland gene in the hepatopancreas, while 3%-4% phospholipid decreased the activities of digestive enzymes (trypsin, cellulase and amylase) of crabs. Based on the survival and growth perfor‐ mance, the optimal phospholipids addition level was estimated to be 1% dry diet for juvenile E. sinensis. [ABSTRACT FROM AUTHOR]

Significance: Iron is an essential element for every life on earth as a primary media for electron flow. Sulfur compounds as sulfhydryls counteract catalytic activity of iron whereas sulfur overdose is also toxic. In aerobic organisms, oxygen is the major media for electron transfer with higher intracellular mobility, which cooperates with the iron system. Based on the importance of iron, there is no active pathway to excrete iron outside the body in higher species. Whereas bacterial infection causes a scramble for iron in situ, cancer can be the outcome of the side effects of long use of iron and oxygen. Recent Advances: Ferroptosis is a recently coined cell death, defined as catalytic Fe(II)-dependent regulated necrosis accompanied by lipid peroxidation. Researchers recently recognized that ferroptosis is involved in a variety of physiological and pathological contexts, including embryonic erythropoiesis, aging, neurodegeneration and cancer cell death. Alternatively, carcinogenesis is a process to obtain iron addiction with ferroptosis-resistance, based on rodent animal studies. Critical Issues: Here we propose that ferroptosis is three-dimensionally regulated by iron, sulfur and oxygen, which correspond to oxidants, antioxidants and membrane fluidity with susceptibility to lipid peroxidation, respectively. Future Directions: Whereas life attempts to prevent ferroptosis, ferroptotic cells eventually emit iron-loaded ferritin as extracellular vesicles to maintain monopoly of iron. Antioxid. Redox Signal. 39, 807–815. [ABSTRACT FROM AUTHOR]

Biosurfactants have been found capable of replacing synthetic surfactants which include ongoing bioprospecting of biosurfactant-producing bacteria as well as process optimization for maximum biosurfactant production. In this study, five morphologically distinct actinomycete strains isolated from hydrocarbon-polluted soil collected from an oil spill surface in Southeastern Algeria were tested for their ability to produce biosurfactants using preliminary biosurfactant screening assays. The 7SDS strain was selected as the most promising biosurfactant producer due to its greatest oil displacement diameter (7.83±0.15 cm), emulsification index (59.66±0.44%), and enhanced surface tension reduction (30.04±0.51 mN/m); it was identified as Streptomyces thinghirensis 7SDS using 16S rDNA sequence analysis. The 7SDS strain's biosurfactant production was optimized using the Face-centered central composite design (CCD) based on response surface methodology (RSM). To this end, five independent factors, i.e., residual frying oil, used engine oil, whey, CS filtrate, and incubation time, were assessed. The RSM's model predicted a surface tension of 27.48 mN/m using 2.44% (v/v) residual frying oil, 0.35% (v/v) used motor oil, 0.83% (v/v) whey, 0.39% (v/v) CS filtrate, and an incubation time of 219.3 h. The optimized medium produced 8.79 g/L of biosurfactant. The produced biosurfactant allows one to reduce the surface tension of distilled water from 70.86 mN/m to 27.96 mN/m at a critical micelle concentration of 350 mg/L, even over a wide range of pH (2.0–12.0), temperature (4–120 °C), and salinity (2–12%, W/V). Biochemical (Biuret, phenol-sulfuric acid, and phosphate tests) and compositional (FTIR and GC-MS) characterizations confirmed the phospholipid nature of the produced biosurfactant. Interestingly, the produced BS demonstrated significant antimicrobial activity as well as intriguing activity in removing hydrocarbons from polluted soil. Because of their appealing biological properties, strain 7SDS and its biosurfactant are attractive targets for a variety of applications such as biomedicine and environmental ones. [ABSTRACT FROM AUTHOR]

In this study, the internal relationships among oil bodies (OBs), the protein–phospholipid interactions in aqueous phase, oil–water interface behavior, and the stability of reconstituted OBs were analyzed from the bulk phase, interface, and macro perspectives, and the stability mechanism of OBs was discussed. OB proteins and phospholipids were combined through hydrophobic and electrostatic interactions, resulting in the stretching of protein conformation. OB proteins and phospholipids act synergistically to increase interface pressure and the rate of increase in interface pressure with relatively stable elastic behavior, which is beneficial to the formation and stability of interfacial films. When OBs were reconstituted by an OB protein–phospholipid complex system, phospholipids bound to OB proteins through hydrophobic and electrostatic interactions. OB proteins and phospholipids uniformly covered the oil droplet surface of reconstituted OBs to form a stable interfacial film, which maintained the stability of OBs. The addition of phospholipids significantly reduced the particle size of OBs prepared by OB proteins in a dose-dependent manner, and particle size decreased with the increase in phospholipid content (p < 0.05). Phospholipids increased the net surface charge, enhanced electrostatic repulsion, and improved the physicochemical stability of reconstituted OBs. The stability mechanism elucidated in this study provides a theoretical basis for the demulsification of peanut OBs. [ABSTRACT FROM AUTHOR]

Recently published work showed that members of the PAQR protein family are activated by cell membrane rigidity and contribute to our ability to eat a wide variety of diets. Cell membranes are primarily composed of phospholipids containing dietarily obtained fatty acids, which poses a challenge to membrane properties because diets can vary greatly in their fatty acid composition and could impart opposite properties to the cellular membranes. In particular, saturated fatty acids (SFAs) can pack tightly and form rigid membranes (like butter at room temperature) while unsaturated fatty acids (UFAs) form more fluid membranes (like vegetable oils). Proteins of the PAQR protein family, characterized by the presence of seven transmembrane domains and a cytosolic N‐terminus, contribute to membrane homeostasis in bacteria, yeasts, and animals. These proteins respond to membrane rigidity by stimulating fatty acid desaturation and incorporation of UFAs into phospholipids and explain the ability of animals to thrive on diets with widely varied fat composition. Also see the video abstract here: https://youtu.be/6ckcvaDdbQg [ABSTRACT FROM AUTHOR]

Among various types children's health challenges, neuroblastoma is the most serious solid neoplasm forming outside the cranium. Scomberomorus niphonius is a valuable edible fish that has been widely used for a meal. In this study, we obtained phospholipid extract from the bone of S. niphonius with the supercritical CO2 extraction method and tested anticancer activity with a cell viability assay. The phospholipid showed anticancer activity on neuroblastoma SK‐N‐SH cells, and the anticancer activity was presented with an IC50 of 710.25 ± 28.31 μg/ml, but did not show a significant toxicity on HUVEC cell lines. Western blot was used to detect signaling proteins; Bak, caspase‐9, caspase‐8, caspase‐3, Bax, and IκBα were increased, whereas IKKβ and NFκB were downregulated in experimental groups compared to untreated groups. Gene expression was revealed by RT‐qPCR, and the fold ratio of Apaf‐1, cytochrome‐c, caspase‐9, caspase‐3, and Bax genes' expression was raised in treated groups, implying apoptosis. Gel electrophoresis revealed that the experimental groups had more fragmented DNA than the control group. The study shows that a phospholipid extract from S. niphonius' bone could be used as a biological origin of anticancer activity in neuroblastoma SK‐N‐SH cells. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to produce lipid complex-ITR (CL-ITR) to enhance the solubility of ITR which is then made into an in situ vaginal gel to maximize the local therapeutic effect of vulvovaginal candidiasis. Methods: The CL-ITR was prepared by mixing ITR with Phospholipon 90G® (P90G) in different concentrations with solvent-evaporated methods. CL-ITR optimization was carried out by determining the solubility of ITR in CL-ITR and then characterized through FTIR, DSC, SEM, and profile release of ITR. Furthermore, the optimal CL-ITR formula was mixed into the gel base using Poloxamer (PF127 and PF68) and sodium alginate (SA) as gelling agents with various concentrations. The gel characteristics were then determined through Tsol-gel, pH, viscosity, time and mucoadhesive strength, and stability tests. Ex vivo evaluation was carried out using the porcine's model to determine ITR that was permeated and retained on the vaginal mucosa and antifungal activity assay. Results: The F5 with an ITR:P90G concentration of 1:5 is an optimized CL-ITR that is soluble ITR at 1275 ± 10.24 mg/mL. The G3 is the formula gel that retained the highest ITR, namely 4.72 ± 0.06 mg, and it had the lowest permeation of 1.90 ± 0.02 mg at 24 h. Furthermore, the time-killing test showed that G3 is the superlative formula against C. albicans, namely 3.58 ± 0.03 CFU/mL at 24 h. Conclusion: ITR was successfully administered vaginally in the form of an in situ gel and had desirable values in every evaluation that was performed. Therefore, it can be an alternative to improve the effectiveness of ITR therapy for the treatment of vulvovaginal candidiasis. [ABSTRACT FROM AUTHOR]

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为进一步验证SiO2脱胶工艺的可行性，以浓香菜籽原油为研究对象，以磷脂脱除率为评价指标，采用单因素实验和响应面实验对SiO2脱胶工艺进行优化，并对比分析了SiO2脱胶工艺与传统水化脱胶工艺得到的脱胶浓香菜籽油品质。结果表明：在SiO2添加量2.25%、脱胶温度35 ℃、脱胶时间22 min、搅拌速度107 r/min条件下，脱胶效果最优，此时脱胶油中磷脂含量为1 719.61 mg/kg，磷脂脱除率达到86.1%；SiO2脱胶油与水化脱胶油的酸值、过氧化值、水分及挥发物含量均无显著差异（p＞0.05），而SiO2脱胶油中总酚及Canolol含量均显著低于水化脱胶油的（p＜0.05），SiO2脱胶油的亮度和磷脂脱除率均显著高于水化脱胶油的（p＜0.05）。对于非水化磷脂比例较高的浓香菜籽油，SiO2脱胶相比于传统水化脱胶可能具有更好的脱胶效果，可以作为传统水化脱胶方法的补充。 To further verify the feasibility of SiO2 degumming process, the crude fragrant rapeseed oil was taken as the object of study, and the phospholipid removal rate was used as the evaluation index to optimize the degumming process using single factor experiment and response surface methodology. The quality of the degummed fragrant rapeseed oil obtained by SiO2 degumming process was compared with that obtained by the traditional hydration degumming process. The results showed that the optimal phospholipid removal rate reached 86.1% when the SiO2 dosage was 2.25%, the degumming temperature was 35 ℃, the degumming time was 22 min, and the stirring speed was 107 r/min, and the phospholipid content in the degummed oil was 1 719.61 mg/kg. There was no significant difference in acid value, peroxide value, and moisture and volatile content between SiO2-degummed oil and hydration-degummed oil (p>0.05). The contents of total phenols and Canolol in the SiO2-degummed oil was significantly lower than that in the hydration-degummed oil(p

The evolution of unicellular to multicellular life is considered to be an important step in the origin of life, and it is crucial to study the influence of environmental factors on this process through cell models in the laboratory. In this paper, we used giant unilamellar vesicles (GUVs) as a cell model to investigate the relationship between environmental temperature changes and the evolution of unicellular to multicellular life. The zeta potential of GUVs and the conformation of the headgroup of phospholipid molecules at different temperatures were examined using phase analysis light scattering (PALS) and attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR), respectively. In addition, the effect of increasing temperature on the aggregation of GUVs was further investigated in ionic solutions, and the possible mechanisms involved were explored. The results showed that increasing temperature reduced the repulsive forces between cells models and promoted their aggregation. This study could effectively contribute to our understanding of the evolution of primitive unicellular to multicellular life.

BackgroundThe lipoprotein insulin resistance (LPIR) score was shown to predict insulin resistance (IR) and type 2 diabetes (T2D) in healthy adults. However, the molecular basis underlying the LPIR utility for classification remains unclear.ObjectiveTo identify small molecule lipids associated with variation in the LPIR score, a weighted index of lipoproteins measured by nuclear magnetic resonance, in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study (n = 980).MethodsLinear mixed effects models were used to test the association between the LPIR score and 413 lipid species and their principal component analysis-derived groups. Significant associations were tested for replication with homeostatic model assessment-IR (HOMA-IR), a phenotype correlated with the LPIR score (r = 0.48, p

Lysophosphatidic acid (LPA) is a phospholipid that displays potent signalling activities that are regulated in both an autocrine and paracrine manner. It can be found both extra- and intracellularly, where it interacts with different receptors to activate signalling pathways that regulate a plethora of cellular processes, including mitosis, proliferation and migration. LPA metabolism is complex, and its biosynthesis and catabolism are under tight control to ensure proper LPA levels in the body. In cancer patient specimens, LPA levels are frequently higher compared to those of healthy individuals and often correlate with poor responses and more aggressive disease. Accordingly, LPA, through promoting cancer cell migration and invasion, enhances the metastasis and dissemination of tumour cells. In this review, we summarise the role of LPA in the regulation of critical aspects of tumour biology and further discuss the available pre-clinical and clinical evidence regarding the feasibility and efficacy of targeting LPA metabolism for effective anticancer therapy.

Nanodiscs belong to a category of water-soluble lipid bilayer nanoparticles. In vivo nanodisc platforms are useful for studying isolated membrane proteins in their native lipid environment. Thus, the development of a practical method for nanodisc reconstruction has garnered consider-able research interest. This paper reports the self-assembly of a mixture of bio-derived cyclic peptide, surfactin (SF), and l-α-dimyristoylphosphatidylcholine (DMPC). We found that SF induced the solubilization of DMPC multilamellar vesicles to form their nanodiscs, which was confirmed by size-exclusion chromatography, dynamic light scattering, and transmission electron microscopy analyses. Owing to its amphiphilic nature, the self-assembled structure prevents the exposure of the hydrophobic lipid core to aqueous media, thus embedding ubiquinol (CoQ10) as a hydrophobic model compound within the inner region of the nanodiscs. These results highlight the feasibility of preparing nanodiscs without the need for laborious procedures, thereby showcasing their potential to serve as promising carriers for membrane proteins and various organic compounds. Additionally, the regulated self-assembly of the DMPC/SF mixture led to the formation of fibrous architectures. These results show the potential of this mixture to function as a nanoscale membrane surface for investigating molecular recognition events.

Summary: Among the phospholipase A2 (PLA2) superfamily, which typically catalyzes the sn‐2 hydrolysis of phospholipids to yield fatty acids and lysophospholipids, the secreted PLA2 (sPLA2) family contains 11 isoforms in mammals. Individual sPLA2s have unique enzymatic specificity toward fatty acids and polar heads of phospholipid substrates and display distinct tissue/cellular distributions, suggesting their distinct physiological functions. Recent studies using knockout and/or transgenic mice for a full set of sPLA2s have revealed their roles in modulation of immunity and related disorders. Application of mass spectrometric lipidomics to these mice has enabled to identify target substrates and products of individual sPLA2s in given tissue microenvironments. sPLA2s hydrolyze not only phospholipids in the plasma membrane of activated, damaged or dying mammalian cells, but also extracellular phospholipids such as those in extracellular vesicles, microbe membranes, lipoproteins, surfactants, and dietary phospholipids, thereby exacerbating or ameliorating various diseases. The actions of sPLA2s are dependent on, or independent of, the generation of fatty acid‐ or lysophospholipid‐derived lipid mediators according to the pathophysiological contexts. In this review, we make an overview of our current understanding of the roles of individual sPLA2s in various immune responses and associated diseases. [ABSTRACT FROM AUTHOR]

[Display omitted] • Fisetin (FIS) has been successfully complexed with phospholipid into phytosomes (PHYs) at different molar ratios using simple preparation technique. • The prepared PHYs exhibited promising invitro physicochemical properties including 100 % drug complexation efficacy, homogenous nanometric vesicular size along with controlled drug release. • The optimized PHY showed superior cytotoxicity over free FIS against breast cancer cell line (MDA-MB-231). • Ehrlich ascites induced breast carcinoma in mice confirmed significant higher anticancer potential of FIS phytosomes when compared with free drug. Nowadays, fisetin (FIS) is extensively studied as potent anticancer surrogate with a multitarget actions against various types of cancers including breast cancer. However, its poor aqueous solubility handicapped its clinical utility. The current work endeavored, for the first time, to develop FIS phytosomes (FIS-PHY) for improving its physicochemical properties and subsequently its anticancer activity. Optimization of FIS- phytosomes involved different preparation techniques (Thin film hydration and ethanol injection) and different FIS: phospholipid molar ratios (1:1, 1:2, and 1:3). Complex formation was confirmed by complexation efficiency, infrared spectroscopy (IR), solubility studies and transmission electron microscope. The optimized FIS-PHY of 1:1 M ratio (PHY1) exhibited a nanometric particle size of 233.01 ± 9.46 nm with homogenous distribution (PDI = 0.27), negative zeta potential of − 29.41 mV, 100% complexation efficiency and controlled drug release over 24 h. In-vitro cytotoxicity study showed 2.5-fold decrease in IC50 of PHY1 compared with free FIS. Also, pharmacodynamic studies confirmed the promoted cytotoxicity of PHY1 against breast cancer through modulating TGF-β1/MMP-9 molecular pathways of tumorigenesis. Overall, overcoming FIS drawbacks were successfully achieved through development of innovative biocompatible phytosomal system. [ABSTRACT FROM AUTHOR]

SUMMARY: Two parallel pathways compartmentalized in the chloroplast and the endoplasmic reticulum contribute to thylakoid lipid synthesis in plants, but how these two pathways are coordinated during thylakoid biogenesis and remodeling remains unknown. We report here the molecular characterization of a homologous ADIPOSE TRIGLYCERIDE LIPASE‐LIKE gene, previously referred to as ATGLL. The ATGLL gene is ubiquitously expressed throughout development and rapidly upregulated in response to a wide range of environmental cues. We show that ATGLL is a chloroplast non‐regioselective lipase with a hydrolytic activity preferentially towards 16:0 of diacylglycerol (DAG). Comprehensive lipid profiling and radiotracer labeling studies revealed a negative correlation of ATGLL expression and the relative contribution of the chloroplast lipid pathway to thylakoid lipid biosynthesis. Additionally, we show that genetic manipulation of ATGLL expression resulted in changes in triacylglycerol levels in leaves. We propose that ATGLL, through affecting the level of prokaryotic DAG in the chloroplast, plays important roles in balancing the two glycerolipid pathways and in maintaining lipid homeostasis in plants. Significance Statement: This study reveals that the ADIPOSE TRIGLYCERIDE LIPASE‐LIKE gene encodes a chloroplast diacylglycerol lipase which plays important roles in modulating glycerolipid pathway balance and in maintaining lipid homeostasis in Arabidopsis. [ABSTRACT FROM AUTHOR]

Citrus sinensis seedlings were supplied with a nutrient solution containing 15 (control) or 0 (nitrogen (N) deficiency) mM N for 10 weeks. Extensive metabolic and gene reprogramming occurred in 0 mM N-treated roots (RN0) to cope with N deficiency, including: (a) enhancing the ability to keep phosphate homeostasis by elevating the abundances of metabolites containing phosphorus and the compartmentation of phosphate in plastids, and/or downregulating low-phosphate-inducible genes; (b) improving the ability to keep N homeostasis by lowering the levels of metabolites containing N but not phosphorus, upregulating N compound degradation, the root/shoot ratio, and the expression of genes involved in N uptake, and resulting in transitions from N-rich alkaloids to carbon (C)-rich phenylpropanoids and phenolic compounds (excluding indole alkaloids) and from N-rich amino acids to C-rich carbohydrates and organic acids; (c) upregulating the ability to maintain energy homeostasis by increasing energy production (tricarboxylic acid cycle, glycolysis/gluconeogenesis, oxidative phosphorylation, and ATP biosynthetic process) and decreasing energy utilization for amino acid and protein biosynthesis and new root building; (d) elevating the transmembrane transport of metabolites, thus enhancing the remobilization and recycling of useful compounds; and (e) activating protein processing in the endoplasmic reticulum. RN0 had a higher ability to detoxify reactive oxygen species and aldehydes, thus protecting RN0 against oxidative injury and delaying root senescence. [ABSTRACT FROM AUTHOR]

Knowledge of the physical and chemical properties of phospholipids, such as phase transition temperatures (Tc), is of great importance in order to reveal the functionalities of biological and artificial membranes. Our research group developed an oscillatory rheological method for the simple and rapid determination of phase transition temperatures (Tc). The phospholipids constructing the membranes undergo conformational changes at their Tc, which cause alterations of viscoelastic properties of the molecules. The oscillatory technique recommended by us proved to be appropriate to reveal the altered molecular properties of phospholipids as tracking the slightest changes in the viscoelasticity. Our study demonstrates the abrupt changes in rheological properties at Tc for the following phospholipids: 1,2-Dimyristoyl-sn-glycero-3-Phosphocholine (DMPC), 1,2-Dipalmitoyl-sn-glycero-3-Phosphatidylcholine (DPPC), and 1,2-Distearoyl-sn-glycero-3-Phosphocholine (DSPC), proving that the applied methodology is adequate for determining the Tc of phospholipids. [ABSTRACT FROM AUTHOR]

Organic biomarker distribution and stable isotope composition was used to investigate biogeochemical carbon cycling in the anoxic basin of Lake Untersee, Antarctica. Phospholipid fatty acid (PLFA) concentrations indicative of microbial abundances were low in the oxic water column overlying the basin but rose in the suboxic transition zone and further increased within the underlying anoxic water, with the highest abundances near the sediment water interface. Archaeol (up to 24.8 mg/kg) and glycerol dialkyl glycerol tetraethers were only detected within the deepest water sample and sediment. High methane (CH4) concentrations (ca. 172 mg/L or 11 mmol/L) were observed in the deepest water samples and produced via hydrogenotrophy (CO2-reduction) based on methane isotopes and highly 13C-enriched dissolved inorganic carbon. Methane concentration slowly decreased away from the sediment, across the anoxic water column and then decreased rapidly at the oxic/anoxic interface (78–68 m). Here a ca. 10‰ increase in δ13CCH4 values combined with δ13CPLFA values that decreased as CH4 concentrations rapidly declined indicated an aerobic methanotrophy fueled microbial community. Findings suggest that upward methane diffusion drives microbial productivity within the suboxic/anoxic zones resulting in the observed high PLFA biomass. Subsequent sinking of detrital material from these communities supports heterotrophic microbes throughout the anoxic water column and potentially supplied nutrients to support phototrophy in the upper suboxic transition zone, itself contributing to sinking detrital material and accumulation of sedimentary organic material. Notably, while a clear biosignature of methane oxidation is present in suboxic zone PLFA, this signature is not recognizable within the sediments. [ABSTRACT FROM AUTHOR]

The antihypertensive drug valsartan, has an imperfect bioavailability due to its low solubility, permeability and excessive first pass hepatic metabolism. So, the goal of this article is to improve the physicochemical properties of valsartan to increase its bioavailability. In order to achieve this goal, valsartan-phospholipid complexsomes (VAL-PLC) were developed by the technique of solvent evaporation using Box-Behnken experimental design to optimize variables in the production process. The box-Behnken design revealed that the formula F3 prepared using 60% lipid percentage at 60 0C reaction temperature for 2h reaction time offered the optimum conditions for VAL-PLC preparation where the percent drug content reached 92.24%, average particle diameter was 189.17nm and polydispersity index was 0.289. Drug release experiment indicated that the dissolution of both raw valsartan and its commercial dosage form was dependent upon pH where it was extremely low at pH 1.2 and low in distilled water and it had a high dissolution at pH 6.8. On the contrary, the optimized VAL-PLC formula showed a high and pH-independent dissolution rate whatever the type of dissolution medium was. Therefore, it was concluded that valsartan-complexsomes may be considered as an encouraging approach for improving physicochemical properties and increasing bioavailability of valsartan. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) is a global health problem, and EPA/DHA-enriched phospholipids (EPA/DHA-PLs) have been found to have positive effects on MetS improvement. Currently, research on EPA/DHA-PL mainly focuses on special and rare seafood, such as phospholipids derived from krill, sea cucumber, squid, and fish roe. However, it has been recently demonstrated that abundant EPA/DHA-PL can also be found in bulk fish and its by-products. Nonetheless, there is still limited research on the biological activities of EPA/DHA-PL derived from these sources. The aim of this study was to investigate the effect of phospholipid extracts from the heads of salmon and silver carp (S-PLE and SC-PLE) on the high-fat-diet-induced MetS in C57/BL mice. After an 8-week intervention, both SC-PLE and S-PLE had a significant ameliorating effect on MetS. Moreover, SC-PLE was more effective than S-PLE in reducing liver inflammation and fasting glucose. Both of the PL extracts were able to regulate the expression of key genes in lipid synthesis, fatty acid β-oxidation, and insulin signaling pathways. Compared with S-PLE, dietary SC-PLE had a greater influence on liver metabolomics. Pathway enrichment analysis showed that the differential metabolites of SC-PLE were mainly involved in arachidonic acid metabolism and glutathione metabolism. The results indicated that the different metabolic regulation methods of S-PLE and SC-PLE could be related to their variant molecular composition in EPA/DHA-PL. [ABSTRACT FROM AUTHOR]

The Gram-negative bacterial cell envelope is a complex multilayered structure comprising a bilayered phospholipid (PL) membrane that surrounds the cytoplasm (inner membrane or IM) and an asymmetric outer membrane (OM) with PLs in the inner leaflet and lipopolysaccharides in the outer leaflet. Between these two layers is the periplasmic space, which contains a highly cross-linked mesh-like glycan polymer, peptidoglycan (PG). During cell expansion, coordinated synthesis of each of these components is required to maintain the integrity of the cell envelope; however, it is currently not clear how such coordination is achieved. In this study, we show that a cross-link-specific PG hydrolase couples the expansion of PG sacculus with that of PL synthesis in the Gram-negative model bacterium, Escherichia coli. We find that unregulated activity of a PG hydrolytic enzyme, MepS is detrimental for growth of E. coli during fatty acid (FA)-limiting conditions. Further genetic and biochemical analyses revealed that cellular availability of FA or PL alters the post-translational stability of MepS by modulating the proteolytic activity of a periplasmic adaptor-protease complex, NlpI-Prc toward MepS. Our results indicate that loss of OM lipid asymmetry caused by alterations in PL abundance leads to the generation of a signal to the NlpI-Prc complex for the stabilization of MepS, which subsequently cleaves the cross-links to facilitate expansion of PG. In summary, our study shows the existence of a molecular cross-talk that enables coordinated expansion of the PG sacculus with that of membrane synthesis for balanced cell-envelope biogenesis. [ABSTRACT FROM AUTHOR]

Acid sphingomyelinase deficiency (ASMD) is a lysosomal storage disorder caused by mutations in the gene-encoding acid sphingomyelinase (ASM). ASMD impacts peripheral organs in all patients, including the liver and spleen. The infantile and chronic neurovisceral forms of the disease also lead to neuroinflammation and neurodegeneration for which there is no effective treatment. Cellular accumulation of sphingomyelin (SM) is a pathological hallmark in all tissues. SM is the only sphingolipid comprised of a phosphocholine group linked to ceramide. Choline is an essential nutrient that must be obtained from the diet and its deficiency promotes fatty liver disease in a process dependent on ASM activity. We thus hypothesized that choline deprivation could reduce SM production and have beneficial effects in ASMD. Using acid sphingomyelinase knock-out (ASMko) mice, which mimic neurovisceral ASMD, we have assessed the safety of a choline-free diet and its effects on liver and brain pathological features such as altered sphingolipid and glycerophospholipid composition, inflammation and neurodegeneration. We found that the choline-free diet was safe in our experimental conditions and reduced activation of macrophages and microglia in the liver and brain, respectively. However, there was no significant impact on sphingolipid levels and neurodegeneration was not prevented, arguing against the potential of this nutritional strategy to assist in the management of neurovisceral ASMD patients. [ABSTRACT FROM AUTHOR]

A lot of applications for (semi-)crystalline triacylglycerol (TAG)-in-water dispersions exist in the life science and pharmaceutical industries. Unfortunately, during storage, these dispersions are often prone to changes in particle size due to unforeseen crystallization and recrystallization events. This results in the alterations of important product properties, such as viscosity and mouthfeel, or the premature release of encapsulated material. In this study, we investigated the effects and interplay of formulation, i.e., emulsifier combination, and processing parameters, i.e., cooling rate, on the colloidal stability of dispersed TAGs and aimed to improve their colloidal stability. We chose phospholipids (PLs) and β-lactoglobulin (β-lg) as the emulsifiers for our model systems, which are commonly applied in many food systems. When dispersions were characterized directly after cooling, we obtained smaller particles and narrower size distributions after fast cooling. Over the course of eleven weeks, the creaming behavior, particle size, melting behavior and polymorphism were characterized. The dispersions stabilized with solely β-lg exhibited a slight increase in particle size, whereas a decrease in size was found when PLs were added. Our results indicate that mass transport phenomena between TAG droplets and particles took place during storage. This migration of TAG molecules changed the composition and size distribution of the dispersed phase, especially at higher PL concentration (0.1 wt%). In our case, this could be prevented by using a lower concentration of PLs, i.e., 0.05 wt%. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Henan University of Technology Natural Science Edition is the property of Henan University of Technology Journal Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Henan University of Technology Natural Science Edition is the property of Henan University of Technology Journal Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

为探究黑老虎种子作为新兴植物油料资源的潜力，利用广泛靶向代谢组学技术检测分析其氨基酸和脂质组分。结果表明：在基于鉴定出的代谢物结构配置分类下，黑老虎种子含脂质类、氨基酸及衍生物类化合物分别为121种和89种，前者数量和相对含量（30.7%）在11类成分中最高，后者数量居其次，相对含量（17.8%）位于第三；鉴定出20种基础氨基酸和8种人体必需氨基酸，其中L-脯氨酸、L-天冬氨酸、L-丝氨酸等7种药效氨基酸和L-亮氨酸、L-苏氨酸、L-异亮氨酸、L-苯丙氨酸和L-赖氨酸5种人体必需氨基酸含量较高；黑老虎种子中富含亚油酸、γ-亚麻酸、α-亚麻酸等脂肪酸和以溶血磷脂酰胆碱18∶ 2和18∶ 2（2n异构）为主的磷脂。黑老虎种子氨基酸类和脂质类组分丰富，多种高度富集成分具有突出的营养功能、活性作用和药用功效，在优质植物油脂开发等领域具有较高的价值。 In order to explore the potential of Kadsura coccinea seed as a new plant oil resource, the amino acids and lipids were detected and analyzed by widely targeted metabolomics. The results showed that under the classification based on the identified metabolite structure configuration, the Kadsura coccinea seed contained 121 lipid and 89 amino acid and derivative compounds, respectively, and the number and the relative content (30.7%) of the former was the highest among the 11 types of components, the number of the latter was the second, and the relative content (17.8%) was the third. 20 kinds of basic amino acids and 8 kinds of essential amino acids were identified. The contents of 7 kinds of medicinal amino acids (such as L-proline, L-aspartic acid and L-serine) and 5 kinds of essential amino acids (such as L-leucine, L-threonine, L-isoleucine, L-phenylalanine and L-lysine) were higher. Kadsura coccinea seed was rich in fatty acids such as linoleic acid, γ-linolenic acid and α-linolenic acid, as well as phospholipids dominated by lysophosphatidylcholines 18∶ 2 and 18∶ 2 (2n isomer). In conclusion，Kadsura coccinea seed is rich in amino acids and lipids, and a variety of highly enriched components have outstanding nutritional functions, activities and medicinal effects, and have high value in the development of high-quality vegetable oils and other fields.

In the present study, the alcohol extraction conditions of Antarctic krill oil were optimized using a single factor experiment and response surface methodology. And the effects of extracting solvent, the ratio of liquid to sample and extraction time on yield of Antarctic krill oil, contents of phospholipid and total astaxanthins were investigated. Then, the main bioactive components of Antarctic krill oil, were prepared under the optimal conditions and were determined by HPLC and GC/MS. Furthermore, the effects of various antioxidants on the stability of astaxanthins in Antarctic krill oil were explored during the heat treatment test. The results suggested that the optimum extraction condition of Antarctic krill oil was achieved at a ratio of liquid to sample 10 mL/g with an extraction time of 137.3 min, using 95% ethanol-water solution as extraction solvent. Under the optimized condition, the yield of Antarctic krill oil, contents of phospholipid and total astaxanthins were 13.6%±1.2%, 33.62%±2.48% and 210.46±5.95 mg/kg, respectively. While the polyunsaturated fatty acid accounted for 41.58% of the total fatty acid, in addition, the krill oil was rich in vitamin E and vitamin A. Moreover, the hydrothermal stability of astaxanthins was effectively improved by the addition of antioxidants to the Antarctic krill oil. The effectiveness of the additives that inhibiting the degradation of the astaxanthins were evaluated, with rosemary extract (0.02%, w/v) combined with tocopherol (0.02%, w/v) ranked first, t-butylhydroquinone (0.02%, w/v) ranked second, rosemary extract (0.02%, w/v) ranked third and tocopherol (0.02 %, w/v) was the least effective additive. These results provide important evidence for the industrialization of Antarctic krill oil, as well as improving its stability during long-term storage.

Abstract Background Lysophosphatidic acid acyltransferase (LPAAT) is a phospholipid biosynthesis enzyme that introduces a particular set of fatty acids at the sn-2 position of phospholipids. Many bacteria have multiple LPAAT paralogs, and these enzymes are considered to have different fatty acid selectivities and to produce diverse phospholipids with distinct fatty acid compositions. This feature is advantageous for controlling the physicochemical properties of lipid membranes to maintain membrane integrity in response to the environment. However, it remains unclear how LPAAT paralogs are functionally differentiated and biologically significant. Results To better understand the division of roles of the LPAAT paralogs, we analyzed the functions of two LPAAT paralogs, PlsC4 and PlsC5, from the psychrotrophic bacterium Shewanella livingstonensis Ac10. As for their enzymatic function, lipid analysis of plsC4- and plsC5-inactivated mutants revealed that PlsC4 prefers iso-tridecanoic acid (C12-chain length, methyl-branched), whereas PlsC5 prefers palmitoleic acid (C16-chain length, monounsaturated). Regarding the physiological role, we found that plsC4, not plsC5, contributes to tolerance to cold stress. Using bioinformatics analysis, we demonstrated that orthologs of PlsC4/PlsC5 and their close relatives, constituting a new clade of LPAATs, are present in many γ-proteobacteria. We also found that LPAATs of this clade are phylogenetically distant from principal LPAATs, such as PlsC1 of S. livingstonensis Ac10, which are universally conserved among bacteria, suggesting the presence of functionally differentiated LPAATs in these bacteria. Conclusions PlsC4 and PlsC5, which are LPAAT paralogs of S. livingstonensis Ac10, play different roles in phospholipid production and bacterial physiology. An enzyme belonging to PlsC4/PlsC5 subfamilies and their close relatives are present, in addition to principal LPAATs, in many γ-proteobacteria, suggesting that the division of roles is more common than previously thought. Thus, both principal LPAATs and PlsC4/PlsC5-related enzymes should be considered to decipher the metabolism and physiology of bacterial cell membranes.

Phospholipids, as fundamental building blocks of the cell membrane, play important roles for molecule transportation, cell recognition, etc. However, due to the structural diversity and amphipathic nature, there are few methods for the specific recognition of lipids as compared to other biomolecules such as proteins and glycans. Herein, we developed a molecular imprinting strategy for controllable imprinting toward the polar head of phospholipid exposed on the surface of cellular membranes for recognition. Phosphatidylserine, as unique lipid on the outer membrane leaflet of exosome and also hallmark for cell apoptosis, was imprinted with the developed method. The phosphatidylserine imprinted materials showed high efficiency and specific targeting capability not only for apoptotic cell imaging but also for the isolation of exosomes. Collectively, the synthesized molecularly imprinted materials have great potential for selective plasma membrane recognition for targeted drug delivery and biomarker discovery. [ABSTRACT FROM AUTHOR]

This study was intended to explore and evaluate the appropriate methods for preparation of Amphotericin B (AmB) liposomes with acceptable characteristics. This project provides pre-formulations for industrial manufacturing of liposomal AmB which confers improved properties, besides reduced toxicity compared with the plain drug. At first, Solubility screening tests were performed, and in the following, three liposome preparation methods including ethanol injection, solvent evaporation, and solvent-free method were examined. In the following, the physicochemical characteristics of the prepared liposomes as well as size, size distribution, zeta potential (ZP), morphology, drug loading, loading capacity, physicochemical stability, and drug-lipid interaction studies were investigated. HPLC was applied for analyzing AmB. In all three methods, liposomes with acceptable characteristics were obtained. The size range of liposomes was 150.3 to 263.9 nm and polydispersity index ≤0.32. In morphologic evaluations, the liposomes have appeared as spherical and separate vesicles. A physical loading of AmB without specific interaction between components was achieved. The lyophilized powder in the solvent-free method was physicochemically stable for 6 months without changes in appearance; the remaining drug after 6-month storage at 25 °C and 60% RH, accounts for 91.5 ± 0.5% compared with the initial drug loaded in liposomes, and degradation pattern follows a linear order. As a result, AmB-loaded liposomes were prepared in three applicable methods. The solvent-free method can be considered the most economical and environmental-friendly. [ABSTRACT FROM AUTHOR]

Ferroptosis is a mode of cell death regulated by iron-dependent lipid peroxidation. Growing evidence suggests ferroptosis induction as a novel anti-cancer modality that could potentially overcome therapy resistance in cancers. The molecular mechanisms involved in the regulation of ferroptosis are complex and highly dependent on context. Therefore, a comprehensive understanding of its execution and protection machinery in each tumor type is necessary for the implementation of this unique cell death mode to target individual cancers. Since most of the current evidence for ferroptosis regulation mechanisms is based on solid cancer studies, the knowledge of ferroptosis with regard to leukemia is largely lacking. In this review, we summarize the current understanding of ferroptosis-regulating mechanisms with respect to the metabolism of phospholipids and iron as well as major anti-oxidative pathways that protect cells from ferroptosis. We also highlight the diverse impact of p53, a master regulator of cell death and cellular metabolic processes, on the regulation of ferroptosis. Lastly, we discuss recent ferroptosis studies in leukemia and provide a future perspective for the development of promising anti-leukemia therapies implementing ferroptosis induction. [ABSTRACT FROM AUTHOR]

Hesperidin and hesperetin are two important plant flavanones abundantly found in citrus fruit. They have discovered many biological activities to treat diseases, including cancer, diabetes, and Alzheimer's disease. Despite their various benefits, they have poor solubility, which reduces their bioavailability and absorption. In this study, nanophytosomes have been utilized to improve their payload's solubility and bioavailability. In the current study, hesperetin or hesperidin was complexed with Phospholipon 90G with a 2:1 or 3:1 molar ratio, respectively. The formation of associations between active compounds and phospholipid were confirmed by X‐ray diffraction (XRD), Fourier‐transform infrared spectroscopy (FTIR), and nuclear magnetic resonance (NMR) techniques. Dynamic light scattering data show that the prepared associations in the presence of body fluids can make nanoparticles in the range of 200–250 nm. In addition, oral administration demonstrated that Cmax of hesperidin and hesperetin was increased (up to four times) after complexation with the lipid. It is concluded that phospholipid association may be used as a suitable and straightforward strategy to improve therapeutic activities of hesperidin and hesperetin by increasing their solubility and bioavailability. [ABSTRACT FROM AUTHOR]

In this paper, thermal stability of phospholipid-decorated gold nanorods and their photothermal activity against Staphylococcus epidermidis were experimentally studied. For this aim, cetyl trimethyl ammonium bromide (CTAB) stabilized gold nanostructures were first synthesized, and then the chemical bilayers were exchanged with phospholipid (DMPC). The effects of this replacement on the shape and spectral properties of gold nanorods were analyzed by UV–vis and FTIR as well as transmission electron microscopy (TEM). In addition, thermal heating at 95 ± 2 °C caused CTAB-decorated gold nanorods to decompose in less than half an hour, whereas the phospholipid-modified gold nanorods maintained their spectral characteristics for up to 5 h. Furthermore, while the minimum inhibitory concentration (MIC) for CTAB-AuNRs was obtained equal to 5 μg/ml, DMPC-AuNRs did not indicate significant toxicity in concentrations below 20 μg/ml. The photothermal-induced bactericidal activity of DMPC-gold nanorods was investigated through illumination by a laser with the wavelength of 808 nm. It was demonstrated that treating Staphylococcus epidermidis with the nontoxic concentration of phospholipid-stabilized gold nanorod suspension followed by the laser beam exposure for 15 min resulted in a 4.6 log reduction in the bacterial viable count. [ABSTRACT FROM AUTHOR]