The non-enzymatic oxidation of phosphatidylethanolamine and phosphatidylserine and their intriguing roles in inflammation dynamics and diseases.

Phosphatidylethanolamine (PE) and phosphatidylserine (PS), along with phosphatidylcholine (PC), are key phospholipids (PL) in cell membranes and lipoproteins, prone to oxidative modifications. Their oxidized forms, OxPE and OxPS, play significant roles in inflammation and immune response. This review explores their structural oxidative changes under non-enzymatic conditions and their roles in physiological and pathological contexts, influencing inflammation, and immunity. Specific oxidations of PE and PS significantly alter their physicochemical properties, leading to enhanced biological functions, reduced activity, or inactivation. OxPE may show pro-inflammatory actions, similar to well-documented OxPC, while the OxPS pro-inflammatory effects are less noted. However, OxPS and OxPE have also shown an antagonistic effect against lipopolysaccharides (LPS), suggesting a protective role against exacerbated immune responses, similar to OxPC. Further research is needed to deepen our understanding of these less-studied OxPL classes. The role of OxPE and OxPS in disease pathogenesis remains largely unexplored, with limited studies linking them to Alzheimer's disease, diabetes, rheumatoid arthritis, traumatic brain injury, and skin inflammation. These findings highlight the potential of OxPE and OxPS as biomarkers for disease diagnosis, monitoring, and therapeutic targeting.

Insight into the efficiency of microalgae' lipidic extracts as photosensitizers for Antimicrobial Photodynamic Therapy against Staphylococcus aureus.

Antibacterial resistance causes around 1.27 million deaths annually around the globe and has been recognized as a top 3 priority health threat. Antimicrobial photodynamic therapy (aPDT) is considered a promising alternative to conventional antibiotic treatments. Algal lipid extracts have shown antibacterial effects when used as photosensitizers (PSs) in aPDT. In this work we assessed the photodynamic efficiency of lipidic extracts of microalgae belonging to different phyla (Bacillariophyta, Chlorophyta, Cyanobacteria, Haptophyta, Ochrophyta and Rhodophyta). All the extracts (at 1 mg mL-1) demonstrated a reduction of Staphylococcus aureus >3 log10 (CFU mL-1), exhibiting bactericidal activity. Bacillariophyta and Haptophyta extracts were the top-performing phyla against S. aureus, achieving a reduction >6 log10 (CFU mL-1) with light doses of 60 J cm-2 (Bacillariophyta) and 90 J cm-2 (Haptophyta). The photodynamic properties of the Bacillariophyta Phaeodactylum tricornutum and the Haptophyta Tisochrysis lutea, the best effective microalgae lipid extracts, were also assessed at lower concentrations (75 µg mL-1, 7.5 µg mL-1, and 3.75 µg mL-1), reaching, in general, inactivation rates higher than those obtained with the widely used PSs, such as Methylene Blue and Chlorine e6, at lower concentration and light dose. The presence of chlorophyll c, which can absorb a greater amount of energy than chlorophylls a and b; rich content of polyunsaturated fatty acids (PUFAs) and fucoxanthin, which can also produce ROS, e.g. singlet oxygen (1O2), when photo-energized; a lack of photoprotective carotenoids such as ß-carotene, and low content of tocopherol, were associated with the algal extracts with higher antimicrobial activity against S. aureus. The bactericidal activity exhibited by the extracts seems to result from the photooxidation of microalgae PUFAs by the 1O2 and/or other ROS produced by irradiated chlorophylls/carotenoids, which eventually led to bacterial lipid peroxidation and cell death, but further studies are needed to confirm this hypothesis. These results revealed the potential of an unexplored source of natural photosensitizers (microalgae lipid extracts) that can be used as PSs in aPDT as an alternative to conventional antibiotic treatments, and even to conventional PSs, to combat antibacterial resistance.

Metabolomics analysis of human spermatozoa reveals impaired metabolic pathways in asthenozoospermia.

BACKGROUND: Infertility is a major health issue, affecting 15% of reproductive-age couples with male factors contributing to 50% of cases. Asthenozoospermia (AS), or low sperm motility, is a common cause of male infertility with complex aetiology, involving genetic and metabolic alterations, inflammation and oxidative stress. However, the molecular mechanisms behind low motility are unclear. In this study, we used a metabolomics approach to identify metabolic biomarkers and pathways involved in sperm motility. METHODS: We compared the metabolome and lipidome of spermatozoa of men with normozoospermia (n = 44) and AS (n = 22) using untargeted LC-MS and the metabolome of seminal fluid using 1H-NMR. Additionally, we evaluated the seminal fluid redox status to assess the oxidative stress in the ejaculate. RESULTS: We identified 112 metabolites and 209 lipids in spermatozoa and 27 metabolites in the seminal fluid of normozoospermic and asthenozoospermic men. PCA analysis of the spermatozoa's metabolomics and lipidomics data showed a clear separation between groups. Spermatozoa of asthenozoospermic men presented lower levels of several amino acids, and increased levels of energetic substrates and lysophospholipids. However, the metabolome and redox status of the seminal fluid was not altered inAS. CONCLUSIONS: Our results indicate impaired metabolic pathways associated with redox homeostasis and amino acid, energy and lipid metabolism in AS. Taken together, these findings suggest that the metabolome and lipidome of human spermatozoa are key factors influencing their motility and that oxidative stress exposure during spermatogenesis or sperm maturation may be in the aetiology of decreased motility in AS.

Plasma lipidomics analysis reveals altered profile of triglycerides and phospholipids in children with Medium-Chain Acyl-CoA dehydrogenase deficiency.

Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is the most prevalent mitochondrial fatty acid ß-oxidation disorder. In this study, we assessed the variability of the lipid profile in MCADD by analysing plasma samples obtained from 25 children with metabolically controlled MCADD (following a normal diet with frequent feeding and under l-carnitine supplementation) and 21 paediatric control subjects (CT). Gas chromatography-mass spectrometry was employed for the analysis of esterified fatty acids, while high-resolution C18-liquid chromatography-mass spectrometry was used to analyse lipid species. We identified a total of 251 lipid species belonging to 15 distinct lipid classes. Principal component analysis revealed a clear distinction between the MCADD and CT groups. Univariate analysis demonstrated that 126 lipid species exhibited significant differences between the two groups. The lipid species that displayed the most pronounced variations included triacylglycerols and phosphatidylcholines containing saturated and monounsaturated fatty acids, specifically C14:0 and C16:0, which were found to be more abundant in MCADD. The observed changes in the plasma lipidome of children with non-decompensated MCADD suggest an underlying alteration in lipid metabolism. Therefore, longitudinal monitoring and further in-depth investigations are warranted to better understand whether such alterations are specific to MCADD children and their potential long-term impacts.

Differences and Similarities in Lipid Composition, Nutritional Value, and Bioactive Potential of Four Edible Chlorella vulgaris Strains.

The microalga Chlorella vulgaris is a popular food ingredient widely used in the industry, with an increasing market size and value. Currently, several edible strains of C. vulgaris with different organoleptic characteristics are commercialized to meet consumer needs. This study aimed to compare the fatty acid (FA) and lipid profile of four commercialized strains of C. vulgaris (C-Auto, C-Hetero, C-Honey, and C-White) using gas- and liquid-chromatography coupled to mass-spectrometry approaches, and to evaluate their antioxidant and anti-inflammatory properties. Results showed that C-Auto had a higher lipid content compared to the other strains and higher levels of omega-3 polyunsaturated FAs (PUFAs). However, the C-Hetero, C-Honey, and C-White strains had higher levels of omega-6 PUFAs. The lipidome signature was also different between strains, as C-Auto had a higher content of polar lipids esterified to omega-3 PUFAs, while C-White had a higher content of phospholipids with omega-6 PUFAs. C-Hetero and C-Honey showed a higher content of triacylglycerols. All extracts showed antioxidant and anti-inflammatory activity, highlighting C-Auto with greater potential. Overall, the four strains of C. vulgaris can be selectively chosen as a source of added-value lipids to be used as ingredients in food and nutraceutical applications for different market needs and nutritional requirements.

Algal Lipids as Modulators of Skin Disease: A Critical Review.

The prevalence of inflammatory skin diseases continues to increase with a high incidence in children and adults. These diseases are triggered by environmental factors, such as UV radiation, certain chemical compounds, infectious agents, and in some cases, people with a genetic predisposition. The pathophysiology of inflammatory skin diseases such as psoriasis or atopic dermatitis, but also of skin cancers, is the result of the activation of inflammation-related metabolic pathways and the overproduction of pro-inflammatory cytokines observed in in vitro and in vivo studies. Inflammatory skin diseases are also associated with oxidative stress, overproduction of ROS, and impaired antioxidant defense, which affects the metabolism of immune cells and skin cells (keratinocytes and fibroblasts) in systemic and skin disorders. Lipids from algae have been scarcely applied to modulate skin diseases, but they are well known antioxidant and anti-inflammatory agents. They have shown scavenging activities and can modulate redox homeostasis enzymes. They can also downmodulate key inflammatory signaling pathways and transcription factors such as NF-κB, decreasing the expression of pro-inflammatory mediators. Thus, the exploitation of algae lipids as therapeutical agents for the treatment of inflammatory skin diseases is highly attractive, being critically reviewed in the present work.

Multi-Omic Profiling of Macrophages Treated with Phospholipids Containing Omega-3 and Omega-6 Fatty Acids Reveals Complex Immunomodulatory Adaptations at Protein, Lipid and Metabolic Levels.

In recent years, several studies have demonstrated that polyunsaturated fatty acids have strong immunomodulatory properties, altering several functions of macrophages. In the present work, we sought to provide a multi-omic approach combining the analysis of the lipidome, the proteome, and the metabolome of RAW 264.7 macrophages supplemented with phospholipids containing omega-3 (PC 18:0/22:6; ω3-PC) or omega-6 (PC 18:0/20:4; ω6-PC) fatty acids, alone and in the presence of lipopolysaccharide (LPS). Supplementation of macrophages with ω3 and ω6 phospholipids plus LPS produced a significant reprogramming of the proteome of macrophages and amplified the immune response; it also promoted the expression of anti-inflammatory proteins (e.g., pleckstrin). Supplementation with the ω3-PC and ω6-PC induced significant changes in the lipidome, with a marked increase in lipid species linked to the inflammatory response, attributed to several pro-inflammatory signalling pathways (e.g., LPCs) but also to the pro-resolving effect of inflammation (e.g., PIs). Finally, the metabolomic analysis demonstrated that supplementation with ω3-PC and ω6-PC induced the expression of several metabolites with a pronounced inflammatory and anti-inflammatory effect (e.g., succinate). Overall, our data show that supplementation of macrophages with ω3-PC and ω6-PC effectively modulates the lipidome, proteome, and metabolome of these immune cells, affecting several metabolic pathways involved in the immune response that are triggered by inflammation.