A Novel Non-Psychoactive Fatty Acid from a Marine Snail, Conus inscriptus, Signals Cannabinoid Receptor 1 (CB1) to Accumulate Apoptotic C16:0 and C18:0 Ceramides in Teratocarcinoma Cell Line PA1.

The cannabinoid-type I (CB1) receptor functions as a double-edged sword to decide cell fate: apoptosis/survival. Elevated CB1 receptor expression is shown to cause acute ceramide accumulation to meet the energy requirements of fast-growing cancers. However, the flip side of continual CB1 activation is the initiation of a second ceramide peak that leads to cell death. In this study, we used ovarian cancer cells, PA1, which expressed CB1, which increased threefold when treated with a natural compound, bis(palmitoleic acid) ester of a glycerol (C2). This novel compound is isolated from a marine snail, Conus inscriptus, using hexane and the structural details are available in the public domain PubChem database (ID: 14275348). The compound induced two acute ceramide pools to cause G0/G1 arrest and killed cells by apoptosis. The compound increased intracellular ceramides (C:16 to 7 times and C:18 to 10 times), both of which are apoptotic inducers in response to CB1 signaling and thus the compound is a potent CB1 agonist. The compound is not genotoxic because it did not induce micronuclei formation in non-cancerous Chinese hamster ovarian (CHO) cells. Since the compound induced the cannabinoid pathway, we tested if there was a psychotropic effect in zebrafish models, however, it was evident that there were no observable neurobehavioral changes in the treatment groups. With the available data, we propose that this marine compound is safe to be used in non-cancerous cells as well as zebrafish. Thus, this anticancer compound is non-toxic and triggers the CB1 pathway without causing psychotropic effects.

Shrimp Waste Upcycling: Unveiling the Potential of Polysaccharides, Proteins, Carotenoids, and Fatty Acids with Emphasis on Extraction Techniques and Bioactive Properties.

Shrimp processing generates substantial waste, which is rich in valuable components such as polysaccharides, proteins, carotenoids, and fatty acids. This review provides a comprehensive overview of the valorization of shrimp waste, mainly shrimp shells, focusing on extraction methods, bioactivities, and potential applications of these bioactive compounds. Various extraction techniques, including chemical extraction, microbial fermentation, enzyme-assisted extraction, microwave-assisted extraction, ultrasound-assisted extraction, and pressurized techniques are discussed, highlighting their efficacy in isolating polysaccharides, proteins, carotenoids, and fatty acids from shrimp waste. Additionally, the bioactivities associated with these compounds, such as antioxidant, antimicrobial, anti-inflammatory, and antitumor properties, among others, are elucidated, underscoring their potential in pharmaceutical, nutraceutical, and cosmeceutical applications. Furthermore, the review explores current and potential utilization avenues for these bioactive compounds, emphasizing the importance of sustainable resource management and circular economy principles in maximizing the value of shrimp waste. Overall, this review paper aims to provide insights into the multifaceted aspects of shrimp waste valorization, offering valuable information for researchers, industries, and policymakers interested in sustainable resource utilization and waste-management strategies.

Evaluation of synergistic/antagonistic antibacterial activities of fatty oils from apricot, date, grape, and black seeds.

The increasing antimicrobial resistance requires continuous investigation of new antimicrobial agents preferably derived from natural sources. New powerful antibacterial agents can be produced by simply combining oils that are known for their antibacterial activities. In this study, apricot seed oil (ASO), date seed oil (DSO), grape seed oil (GSO), and black seed oil (BSO) alone and in binary mixtures were assessed. Fatty acid profiles of individual oils and oil mixtures showed linoleic acid, oleic acid, palmitic acid, stearic acid, and linolenic acid contents. Linoleic acid was the most abundant fatty acid in all samples except for ASO, where oleic acid was the dominant one. GSO showed the highest total phenolic content while ASO showed the lowest one. Antibacterial screening was performed against Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis, and Staphylococcus aureus. Results showed antibacterial activity in all oils against tested strains except for ASO against S. aureus. Highest antibacterial activity recorded was for ASO against P. mirabilis. ASO-GSO mixture (AG) was the best mixture where it showed synergistic interactions against all strains except P. aeruginosa. In conclusion, seed oil mixtures are likely to show promising antibacterial activities against specific strains.

The Mechanism of the Anti-Obesity Effects of a Standardized Brassica juncea Extract in 3T3-L1 Preadipocytes and High-Fat Diet-Induced Obese C57BL/6J Mice.

Obesity is a global health concern. Recent research has suggested that the development of anti-obesity ingredients and functional foods should focus on natural products without side effects. We examined the effectiveness and underlying mechanisms of Brassica juncea extract (BJE) in combating obesity via experiments conducted in both in vitro and in vivo obesity models. In in vitro experiments conducted in a controlled environment, the application of BJE demonstrated the ability to suppress the accumulation of lipids induced by MDI in 3T3-L1 adipocytes. Additionally, it downregulated adipogenic-related proteins peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT/enhancer-binding protein-α (C/EBP-α), adipocyte protein 2 (aP2), and lipid synthesis-related protein acetyl-CoA carboxylase (ACC). It also upregulated the heat generation protein peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and fatty acid oxidation protein carnitine palmitoyltransferase-1 (CPT-1). The oral administration of BJE decreased body weight, alleviated liver damage, and inhibited the accumulation of lipids in mice with diet-induced obesity resulting from a high-fat diet. The inhibition of lipid accumulation by BJE in vivo was associated with a decreased expression of adipogenic and lipid synthesis proteins and an increased expression of heat generation and fatty acid oxidation proteins. BJE administration improved obesity by decreasing adipogenesis and activating heat generation and fatty acid oxidation in 3T3-L1 cells and in HFD-induced obese C57BL/6J mice. These results suggest that BJE shows potential as a natural method for preventing metabolic diseases associated with obesity.

Maternal Cannabis Use during Lactation and Potential Effects on Human Milk Composition and Production: A Narrative Review.

Cannabis use has increased sharply in the last 20 y among adults, including reproductive-aged women. Its recent widespread legalization is associated with a decrease in risk perception of cannabis use during breastfeeding. However, the effect of cannabis use (if any) on milk production and milk composition is not known. This narrative review summarizes current knowledge related to maternal cannabis use during breastfeeding and provides an overview of possible pathways whereby cannabis might affect milk composition and production. Several studies have demonstrated that cannabinoids and their metabolites are detectable in human milk produced by mothers who use cannabis. Due to their physicochemical properties, cannabinoids are stored in adipose tissue, can easily reach the mammary gland, and can be secreted in milk. Moreover, cannabinoid receptors are present in adipocytes and mammary epithelial cells. The activation of these receptors directly modulates fatty acid metabolism, potentially causing changes in milk fatty acid profiles. Additionally, the endocannabinoid system is intimately connected to the endocrine system. As such, it is probable that interactions of exogenous cannabinoids with the endocannabinoid system might modify release of critical hormones (e.g., prolactin and dopamine) that regulate milk production and secretion. Nonetheless, few studies have investigated effects of cannabis use (including on milk production and composition) in lactating women. Additional research utilizing robust methodologies are needed to elucidate whether and how cannabis use affects human milk production and composition.

Effect of citric acid on cell membrane structure and function of Issatchenkia terricola WJL-G4.

AIMS: This study aimed to investigate the changes of cell membrane structure and function of Issatchenkia terricola under citric acid by performing physiological analysis. METHODS AND RESULTS: The membrane integrity, surface hydrophobicity, structure, fluidity, apoptosis, and fatty acid methyl esters composition of I. terricola WJL-G4 cells were determined by propidium iodide staining, microbial adhesion to hydrocarbon test, transmission electron microscopy analysis, fluorescence anisotropy, flow cytometry, and gas chromatography-mass, respectively. The results showed that with the increasing of citric acid concentrations, the cell vitality, membrane integrity, and fluidity of I. terricola reduced; meanwhile, apoptosis rate, membrane permeable, hydrophobicity, and ergosterol contents augmented significantly. Compared to control, the activities of Na+, K+-ATPase, and Ca2+, Mg2+-ATPase increased by 3.73-fold and 6.70-fold, respectively, when citric acid concentration increased to 20 g l-1. The cells cracked and their cytoplasm effused when the citric acid concentration reached 80 g l-1. CONCLUSIONS: I. terricola could successfully adjust its membrane structure and function below 60 g l-1 of citric acid. However, for citric acid concentrations above 80 g l-1, its structure and function were dramatically changed, which might result in reduced functionality.

Evaluation of a novel triple-action adulticide containing a pyrethroid, macrocyclic lactone, and fatty acid against pyrethroid-resistant Aedes aegypti and Culex quinquefasciatus (Diptera: Culicidae).

Insecticide resistance in mosquito populations has long been recognized as a significant global public health challenge, motivating the development of new control chemistries. ReMoa Tri is a novel triple-action space spray that employs a different mode of action than traditional adult mosquito control formulations. It combines 3 components: fenpropathrin, a mixed-type I/II pyrethroid; abamectin, a macrocyclic lactone; and C8910, a patented fatty acid chain. As an ultra-low volume adulticide, ReMoa Tri has the potential to target mosquito species that are resistant to pyrethroid and organophosphate-based control materials. To determine whether ReMoa Tri effectively targets resistant mosquito species in Florida's Collier County, United States, we conducted ground-based field cage trials using field-caught pyrethroid-resistant Culex quinquefasciatus (Say) and Aedes aegypti (L.), of which the latter also displayed developing resistance to organophosphates. Trials were also conducted against the same mosquito populations with Merus 3.0, a pyrethrin-based adulticide used by the Collier Mosquito Control District. ReMoa Tri was effective against Collier's pyrethroid-resistant Cx. quinquefasciatus, resulting in more than 95% mortality in semifield cage trials by 24 h postapplication. Similarly, ReMoa Tri applications against Collier's pyrethroid-resistant Ae. aegypti resulted in 72%-89% mortality at 24 h postapplication and 74%-97% mortality at 48 h postapplication. This study represents the first field data on this novel space spray, and its findings shed light on the performance of ReMoa Tri against local mosquito populations that have developed resistance to currently available adulticides.

Fatty acid/monoglyceride type and amount modulate fat-soluble vitamin absorption from mixed assemblies in mice.

We investigated the effects of fatty acid/ monoglyceride type and amount on the absorption of fat-soluble vitamins. Micelles or vesicles made with either caprylic acid (CA) + monocaprylin (MC) or oleic acid (OA) + monoolein (MO) at low or high concentrations were infused in bile duct-ligated mice. Retinol + retinyl ester and γ-tocopherol intestinal mucosa contents were higher in mice infused with CA + MC than with OA + MO (up to + 350 % for vitamin A and up to + 62 %, for vitamin E; p < 0.05). Cholecalciferol intestinal mucosa content was the highest in mice infused with micelles with CA + MC at 5 mg/mL (up to + 105 %, p < 0.05). Retinyl ester plasma response was higher with mixed assemblies formed at low concentration of FA + MG compared to high concentration (up to + 1212 %, p < 0.05), while no difference in cholecalciferol and γ-tocopherol plasma responses were measured. No correlation between size or zeta potential and vitamin absorption was found. The impact of FA and MG on fat-soluble vitamin absorption thus differs from one vitamin to another and should be considered to formulate adequate vitamin oral or enteral supplements.

Efficiency of the fatty acids extracted from the microalga Parachlorella kessleri in wound-healing.

Wound healing is a physiological process that results in the reconstruction and restoration of granulation tissue, followed by scar formation. We explored the impact of fatty acids in the form of oils on wound healing since they are part of membrane phospholipids and participate in the inflammatory response. This work investigated the efficiency of fatty acids extracted from microalga Parachlorella kessleri in treating excisional wounds and burns and evaluated their antioxidant activity. The rationale behind this investigation lies in the integral role fatty acids play in membrane phospholipids and their involvement in the inflammatory response. Among different nitrogen sources, glycine showed the highest biomass and lipid productivity (0.08 g L-1 d-1 and 58.37 µgml-1 day-1, respectively). Based on the percentage of polyunsaturated fatty acids that increased by 50.38 % in the Glycine culture of P. kessleri, both total antioxidant capacity and DPPH radical scavenging activity were higher in the Glycine culture than control culture. In 30 anaesthetized male mice divided into 6 groups, using either a burn or an excision, two identical paravertebral full-thickness skin lesions were created. Either oils of P. kessleri (extracted from control and glycine culture) ointments or the vehicle (placebo cream) were applied twice daily to the excisional wounds of mice, while mebo cream was used for burn wounds as well as P. kessleri oil. P. kessleri oils (control or glycine culture) showed a significant effect on the reduction of excisional wounds and burns. Histopathological analysis showed that angiogenesis, collagen fiber formation, and epidermis creation were some of the healing indicators that improved. The key elements for this healing property are omega -3 fatty acids, and both P. kessleri oils extracted from control and glycine culture have significant wound-healing effects. Oil of glycine culture of P. kessleri, however, displayed superior results in this regard.

Dietary Chinese herbal formula supplementation improves yolk fatty acid profile in aged laying hens.

Chinese herbal formula (CHF) has the potential to improve the performance of aged laying hens through integrated regulation of various physiological functions. The present study aimed to investigate the effects of dietary CHF supplementation on the yolk fatty acid profile in aged laying hens. A total of 144 healthy 307-day-old Xinyang black-feather laying hens were randomly allocated into two groups: a control group (CON, fed a basal diet) and a CHF group (fed a basal diet supplemented with 1% CHF; contained 0.30% Leonurus japonicus Houtt., 0.20% Salvia miltiorrhiza Bge., 0.25% Ligustrum lucidum Ait., and 0.25% Taraxacum mongolicum Hand.-Mazz. for 120 days). The fatty acid concentrations in egg yolks were analyzed using a targeted metabolomics technology at days 60 and 120 of the trial. The results showed that dietary CHF supplementation increased (p < .05) the concentrations of several saturated fatty acids (SFA, including myristic acid and stearic acid), monounsaturated fatty acids (MUFA, including petroselinic acid, elaidic acid, trans-11-eicosenoic acid, and cis-11-eicosenoic acid), polyunsaturated fatty acids (PUFA, including linolelaidic acid, linoleic acid, γ-linolenic acid, α-linolenic acid, 11c,14c-eicosadienoic acid, eicosatrienoic acid, homo-γ-linolenic acid, arachidonic acid, and docosapentaenoic acid), and fatty acid indexes (total MUFA, n-3 and n-6 PUFA, PUFA/SFA, hypocholesterolemic/hypercholesterolaemic ratio, health promotion index, and desirable fatty acids) in egg yolks. Collectively, these findings suggest that dietary CHF supplementation could improve the nutritional value of fatty acids in egg yolks of aged laying hens, which would be beneficial for the production of healthier eggs to meet consumer demands.

Exploring the in vitro potential of royal jelly against glioblastoma and neuroblastoma: impact on cell proliferation, apoptosis, cell cycle, and the biomolecular content.

Neuroblastoma and glioblastoma are the most commonly seen nervous system tumors, and their treatment is challenging. Relatively safe and easy acquisition of nutraceutical natural products make them suitable candidates for anticancer research. Royal jelly (RJ), a superfood, has many biological and pharmacological activities. This study was conducted to, for the first time, elucidate its anticancer efficiency, even in high doses, on neuroblastoma and glioblastoma cell lines through cell viability, apoptosis, cell cycle and biomolecular content evaluation. We performed experiments with RJ concentrations in the range of 1.25-10 mg mL-1 for 48 h. Cell viability assays revealed a notable cytotoxic effect of RJ in a concentration-dependent manner. Treatment with a high dose of RJ significantly increased the apoptotic cell population of both cell lines. Furthermore, we observed G0-G1 phase arrest in neuroblastoma cells but G2-M arrest in glioblastoma cells. All these cellular changes are closely associated with the alterations of the macromolecular makeup of the cells, such as decreased saturated lipid, protein, DNA and RNA amounts, protein conformational changes, decreased protein phosphorylation and increased protein carbonylation. These cellular changes are associated with RJ triggered-ROS formation. The clear segregation between the control and the RJ-treated groups proved these changes, obtained from the unsupervised and supervised chemometric analysis. RJ has good anticancer activity against nervous system cancers and could be safely used with current treatment strategies.

Dietary Resveratrol Ameliorates Hepatic Fatty Acid Metabolism and Jejunal Barrier in Offspring Induced by Maternal Oxidized Soybean Oil Challenge.

Increasing evidence indicates that maternal exposure to oxidized soybean oil (OSO) causes damage to the mother and offspring. The antioxidant resveratrol (Res) has a variety of health benefits. However, the protective effect of Res on mitigating offspring damage after maternal exposure to OSO and its mechanism remains unclear. Therefore, this study aimed to investigate the effect of Res on hepatic fatty acid metabolism and the jejunal barrier in suckling piglets after maternal OSO exposure. A total of 18 sows in late gestation were randomly assigned to three treatments. The sows were fed with a fresh soybean oil (FSO) diet, an OSO diet, or the OSO diet supplemented with 300 mg/kg Res (OSO + Res), respectively. The results showed that maternal supplementation of Res restored the mRNA levels of genes related to fatty acid metabolism and increased the activities of catalase (CAT) and total superoxide dismutase (T-SOD) in suckling piglets' livers under the OSO challenge. Moreover, the OSO + Res group restored the mRNA levels of occludin and claudin 4 in suckling piglet jejunum compared with the results of the OSO challenges. In summary, supplementation with Res improves hepatic fatty acid metabolism and intestinal barrier function of suckling piglets after maternal OSO challenge during late gestation and lactation.

Camellia oil with its rich in fatty acids enhances post-thawed boar sperm quality.

BACKGROUND: Boar sperm are highly susceptible to specific conditions during cryopreservation, leading to a significant decrease in their fertilizing potential due to damage to their membranes. Camellia oil, known for its fatty acids with antioxidant and biological properties, has not been previously explored for the cryopreservation of boar semen. This study aimed to examine the effects of camellia oil on post-thawed boar sperm quality. Boar semen ejaculates (n = 9) were collected and divided into six equal aliquots based on camellia oil concentrations (0, 0.5, 1, 1.5, 2 and 2.5% v/v) in the freezing extender. Semen samples were processed and cryopreserved using the liquid nitrogen vapor method. Thereafter, frozen semen samples were thawed at 50 °C for 12 s and evaluated for sperm morphology by scanning electron microscope, sperm motility using a computer-assisted sperm analyzer, sperm viability, acrosome integrity, mitochondrial function, MDA level and total antioxidant capacity. RESULTS: The results demonstrated that the supplementation of 1.5% (v/v) camellia oil showed superior post-thaw sperm qualities such as improved sperm morphology, motility, acrosome integrity and mitochondrial function by 14.3%, 14.3% and 11.7%, respectively, when compared to the control group. Camellia oil at a concentration of 1.5% (v/v) showed the lowest level of MDA (18.3 ± 2.1 µmol/L) compared to the other groups. CONCLUSIONS: In conclusion, adding 1.5% (v/v) camellia oil in the freezing extender reduced the oxidative damage associated with cryopreservation and resulted in a higher post-thawed sperm quality.

Fish oil consumption prevents hepatic lipid accumulation induced by high-cholesterol feeding in obese KK mice.

Fish oil (FO) is rich in the n-3 polyunsaturated fatty acids. It has been demonstrated that FO intake possesses lipid-lowering properties. Conversely, a high-cholesterol (CH) diet promotes lipid accumulation in the liver and induces fatty liver. This study investigated the effects of FO feeding on hepatic lipid accumulation induced by high-cholesterol feeding in KK mice. All experimental diets had a fat energy ratio of 25%, the SO group had all fat sources as safflower oil (SO), the 12.5 FO group had half of the SO replaced with FO, and the 25 FO group had all of the SO replaced with FO, each with or without 2 weight % (wt%) cholesterol (SO/CH, 12.5 FO/CH, and 25 FO/CH groups, respectively), for 8 weeks. The hepatic triglyceride and total cholesterol levels were significantly lower in the 25 FO/CH group than in the SO/CH group. The hepatic mRNAs of fatty acid synthesis-related genes were downregulated by the FO feeding groups. In view of importance to establish the benefit of FO for preventing severe NAFLD, our results suggest that FO intake prevents excessive hepatic fat accumulation induced by a high-cholesterol diet in obese KK mice through the inhibition of fatty acid synthesis.

Palmitic acid, but not other long-chain saturated fatty acids, increases S100B protein and TNF-α secretion by astrocytes.

Obesity is a health problem that involves fat accumulation in adipose and other tissues and causes cell dysfunction. Long-chain saturated fatty acids can induce and propagate inflammation, which may also contribute to the brain alterations found in individuals with obesity. Fatty acids accumulate in astrocytes in situations of blood‒brain barrier disruption, such as inflammatory conditions. Furthermore, the increase in tumor necrosis factor-alpha (TNF-α) and S100 calcium-binding protein B (S100B) secretion is considered an essential component of the inflammatory response. We hypothesize that through their action on astrocytes, long-chain saturated fatty acids mediate some of the brain alterations observed in individuals with obesity. Here, we investigate the direct effect of long-chain fatty acids on astrocytes. Primary astrocyte cultures were incubated for 24 hours with myristic, palmitic, stearic, linoleic, or α-linolenic acids (25-100 µM). All saturated fatty acids tested led to an increase in TNF-α secretion, but only palmitic acid, one of the most common fatty acids, increased S100B secretion, indicating that S100B secretion is probably not caused in response to TNF-α release. Palmitic acid also caused nuclear migration of nuclear factor kappa B. Long-chain saturated fatty acids did not alter cell viability or redox status. In conclusion, long-chain saturated fatty acids can alter astrocytic homeostasis and may contribute to brain disorders associated with obesity, such as neuroinflammation.

Gypenoside XIII regulates lipid metabolism in HepG2 hepatocytes and ameliorates nonalcoholic steatohepatitis in mice.

Gypenoside XIII is isolated from Gynostemma pentaphyllum (Thunb.) Makino. In mice, G. pentaphyllum extract and gypenoside LXXV have been shown to improve non-alcoholic steatohepatitis (NASH). This study investigated whether gypenoside XIII can regulate lipid accumulation in fatty liver cells or attenuate NASH in mice. We used HepG2 hepatocytes to establish a fatty liver cell model using 0.5 mM oleic acid. Fatty liver cells were treated with different concentrations of gypenoside XIII to evaluate the molecular mechanisms of lipid metabolism. In addition, a methionine/choline-deficient diet induced NASH in C57BL/6 mice, which were given 10 mg/kg gypenoside XIII by intraperitoneal injection. In fatty liver cells, gypenoside XIII effectively suppressed lipid accumulation and lipid peroxidation. Furthermore, gypenoside XIII significantly increased SIRT1 and AMPK phosphorylation to decrease acetyl-CoA carboxylase phosphorylation, reducing fatty acid synthesis activity. Gypenoside XIII also decreased lipogenesis by suppressing sterol regulatory element-binding protein 1c and fatty acid synthase production. Gypenoside XIII also increased lipolysis and fatty acid ß-oxidation by promoting adipose triglyceride lipase and carnitine palmitoyltransferase 1, respectively. In an animal model of NASH, gypenoside XIII effectively decreased the lipid vacuole size and number and reduced liver fibrosis and inflammation. These findings suggest that gypenoside XIII can regulate lipid metabolism in fatty liver cells and improve liver fibrosis in NASH mice. Therefore, gypenoside XIII has potential as a novel agent for the treatment of NASH.

Jelleine, a Family of Peptides Isolated from the Royal Jelly of the Honey Bees (Apis mellifera), as a Promising Prototype for New Medicines: A Narrative Review.

The jelleine family is a group of four peptides (jelleines I-IV) originally isolated from the royal jelly of honey bee (Apis mellifera), but later detected in some honey samples. These oligopeptides are composed of 8-9 amino acid residues, positively charged (+2 to +3 at pH 7.2), including 38-50% of hydrophobic residues and a carboxamide C-terminus. Jelleines, generated by processing of the C-terminal region of major royal jelly proteins 1 (MRJP-1), play an important biological role in royal jelly conservation as well as in protecting bee larvae from potential pathogens. Therefore, these molecules present numerous benefits for human health, including therapeutic purposes as shown in preclinical studies. In this review, we aimed to evaluate the biological effects of jelleines in addition to characterising their toxicities and stabilities. Jelleines I-III have promising antimicrobial activity and low toxicity (LD50 > 1000 mg/Kg). However, jelleine-IV has not shown relevant biological potential. Jelleine-I, but not the other analogues, also has antiparasitic, healing, and pro-coagulant activities in addition to indirectly modulating tumor cell growth and controlling the inflammatory process. Although it is sensitive to hydrolysis by proteases, the addition of halogens increases the chemical stability of these molecules. Thus, these results suggest that jelleines, especially jelleine-I, are a potential target for the development of new, effective and safe therapeutic molecules for clinical use.

Asymmetric Synthesis of Saturated and Unsaturated Hydroxy Fatty Acids (HFAs) and Study of Their Antiproliferative Activity.

Hydroxy fatty acids (HFAs) constitute a class of lipids, distinguished by the presence of a hydroxyl on a long aliphatic chain. This study aims to expand our insights into HFA bioactivities, while also introducing new methods for asymmetrically synthesizing unsaturated and saturated HFAs. Simultaneously, a procedure previously established by us was adapted to generate new HFA regioisomers. An organocatalytic step was employed for the synthesis of chiral terminal epoxides, which either by alkynylation or by Grignard reagents resulted in unsaturated or saturated chiral secondary alcohols and, ultimately, HFAs. 7-(S)-Hydroxyoleic acid (7SHOA), 7-(S)-hydroxypalmitoleic acid (7SHPOA) and 7-(R)- and (S)-hydroxymargaric acids (7HMAs) were synthesized for the first time and, together with regioisomers of (R)- and (S)-hydroxypalmitic acids (HPAs) and hydroxystearic acids (HSAs), whose biological activity has not been tested so far, were studied for their antiproliferative activities. The unsaturation of the long chain, as well as an odd-numbered (C17) fatty acid chain, led to reduced activity, while the new 6-(S)-HPA regioisomer was identified as exhibiting potent antiproliferative activity in A549 cells. 6SHPA induced acetylation of histone 3 in A549 cells, without affecting acetylated α-tubulin levels, suggesting the selective inhibition of histone deacetylase (HDAC) class I enzymes, and was found to inhibit signal transducer and activator of transcription 3 (STAT3) expression.

Membrane-Disruptive Effects of Fatty Acid and Monoglyceride Mitigants on E. coli Bacteria-Derived Tethered Lipid Bilayers.

We report electrochemical impedance spectroscopy measurements to characterize the membrane-disruptive properties of medium-chain fatty acid and monoglyceride mitigants interacting with tethered bilayer lipid membrane (tBLM) platforms composed of E. coli bacterial lipid extracts. The tested mitigants included capric acid (CA) and monocaprin (MC) with 10-carbon long hydrocarbon chains, and lauric acid (LA) and glycerol monolaurate (GML) with 12-carbon long hydrocarbon chains. All four mitigants disrupted E. coli tBLM platforms above their respective critical micelle concentration (CMC) values; however, there were marked differences in the extent of membrane disruption. In general, CA and MC caused larger changes in ionic permeability and structural damage, whereas the membrane-disruptive effects of LA and GML were appreciably smaller. Importantly, the distinct magnitudes of permeability changes agreed well with the known antibacterial activity levels of the different mitigants against E. coli, whereby CA and MC are inhibitory and LA and GML are non-inhibitory. Mechanistic insights obtained from the EIS data help to rationalize why CA and MC are more effective than LA and GML at disrupting E. coli membranes, and these measurement capabilities support the potential of utilizing bacterial lipid-derived tethered lipid bilayers for predictive assessment of antibacterial drug candidates and mitigants.

Proteomic, Metabolomic, and Fatty Acid Profiling of Small Extracellular Vesicles from Glioblastoma Stem-Like Cells and Their Role in Tumor Heterogeneity.

Glioblastoma is a deadly brain tumor for which there is no cure. The presence of glioblastoma stem-like cells (GSCs) contributes to the heterogeneous nature of the disease and makes developing effective therapies challenging. Glioblastoma cells have been shown to influence their environment by releasing biological nanostructures known as extracellular vesicles (EVs). Here, we investigated the role of GSC-derived nanosized EVs (<200 nm) in glioblastoma heterogeneity, plasticity, and aggressiveness, with a particular focus on their protein, metabolite, and fatty acid content. We showed that conditioned medium and small extracellular vesicles (sEVs) derived from cells of one glioblastoma subtype induced transcriptomic and proteomic changes in cells of another subtype. We found that GSC-derived sEVs are enriched in proteins playing a role in the transmembrane transport of amino acids, carboxylic acids, and organic acids, growth factor binding, and metabolites associated with amino acid, carboxylic acid, and sugar metabolism. This suggests a dual role of GSC-derived sEVs in supplying neighboring GSCs with valuable metabolites and proteins responsible for their transport. Moreover, GSC-derived sEVs were enriched in saturated fatty acids, while their respective cells were high in unsaturated fatty acids, supporting that the loading of biological cargos into sEVs is a highly regulated process and that GSC-derived sEVs could be sources of saturated fatty acids for the maintenance of glioblastoma cell metabolism. Interestingly, sEVs isolated from GSCs of the proneural and mesenchymal subtypes are enriched in specific sets of proteins, metabolites, and fatty acids, suggesting a molecular collaboration between transcriptionally different glioblastoma cells. In summary, this study revealed the complexity of GSC-derived sEVs and unveiled their potential contribution to tumor heterogeneity and critical cellular processes commonly deregulated in glioblastoma.