Dietary liposomal complexes change the fatty acid composition of hepatic bioactive phospholipids in F1(C57blxDBA2\6) mice, as shown by a lipidomic approach.

Essential polyunsaturated fatty acids (PUFAs) of the n-3 and n-6 classes are crucial for maintaining many physiological functions of the human body. It has previously been suggested that the beneficial effects of n-3 PUFAs are mediated by the action of bioactive lipid components, although it remains unclear which specific lipids are metabolically active. The aim of this study was to assess the impact of various liposomal diets on the content and ratio of liver phospholipids, containing n-3 and n-6 PUFAs, in F1 (C57blxDBA2\6) mice. Lipidomic analysis using chromatography-mass spectrometry was employed to investigate changes in the fatty acid profile of liver phospholipids in six groups of mice. These mice were fed liposomal complexes of different compositions in drinks replacing water for a long-term diet (3 months). Two additional groups of mice, aged 2 and 5 months, were used as control groups. The six liposomal complexes included different combinations of phosphatidylcholine (PC), a natural antioxidant (clove bud essential oil (CEO)), fish oil (FO), and sodium caseinate (SC). The consumption of the PC-CEO-FO-SC liposomal complex significantly increased the amount of liver phospholipids containing n-3 docosahexaenoic acid, including phosphatidylcholines, phosphatidylethanolamines (PE), phosphatidylserines (PS), and lysophosphatidylcholine (LPC). This increase was accompanied by a marked decrease in the amount of phospholipids containing n-6 arachidonic acid. As a result, the weight ratio of phospholipids containing n-6 PUFAs to those containing n-3 PUFAs decreased significantly, especially for PC and PE subclasses. Therefore, the PC-CEO-FO-SC liposomal complex has the potential to enhance resistance to inflammation and reduce the risk of non-communicable diseases.

Characteristics of the Follicular Fluid Extracellular Vesicle Molecular Profile in Women in Different Age Groups in ART Programs.

The aim of this study was to investigate the molecular composition of follicular fluid (FF) extracellular vesicles (EVs) in women of different reproductive ages and its possible relationship to sperm fertilizing ability. FF EVs were obtained by differential centrifugation. The concentration and size distribution of FF EVs were analyzed by nanoparticle tracking analysis. The lipidome and proteome were analyzed by liquid chromatography-mass spectrometry. The isolated FF EVs had a variety of shapes and sizes; their concentration and size distribution did not differ significantly between the age groups. In women younger than 35 years, the concentration of vesicular progesterone was 6.6 times higher than in women older than 35 years, and the total levels of the main lipid classes were increased in younger women. A proteomic analysis revealed that not only FF EV-specific proteins, but also proteins involved in sperm activation were present. New data were obtained on the composition of FF EVs, confirming their importance as molecular indicators of age-related changes in the female reproductive system. In addition, these results shed light on the possible interaction between the FF EVs of women in different age groups and male germ cells. Therefore, studying the transcriptomic and metabolomic profile of FF EVs may be a crucial approach to evaluate the efficacy of ART.

Specific changes in amino acid profiles in monocytes of patients with breast, lung, colorectal and ovarian cancers.

Introduction: Immunometabolism is essential factor of tumor progression, and tumor-associated macrophages are characterized by substantial changes in their metabolic status. In this study for the first time, we applied targeted amino acid LC-MS/MS analysis to compare amino acid metabolism of circulating monocytes isolated from patients with breast, ovarian, lung, and colorectal cancer. Methods: Monocyte metabolomics was analyzed by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/ MS) analysis of amino acid extracts. The targeted analysis of 26 amino acids was conducted by LCMS/MS on an Agilent 6460 triple quadrupole mass spectrometer equipped with an electrospray ionization source and an Agilent 1260 II liquid chromatograph. Results: Comparison of monocytes of cancer patients with monocytes of healthy control individuals demonstrated that in breast cancer most pronounced changes were identified for tryptophan (AUC = 0.76); for ovarian cancer, aminobutyric acid was significantly elevated (AUC= 1.00); for lung cancer significant changes we indented for citrulline (AUC = 0.70). In order to identify key amino acids that are characteristic for monocytes in specific cancer types, we compared each individual cancer with other 3 types of cancer. We found, that aspartic acid and citrulline are specific for monocytes of patients with colorectal cancer (p<0.001, FC = 1.40 and p=0.003, FC = 1.42 respectively). Citrulline, sarcosine and glutamic acid are ovarian cancer-specific amino acids (p = 0.003, FC = 0.78, p = 0.003, FC = 0.62, p = 0.02, FC = 0.78 respectively). Glutamine, methionine and phenylalanine (p = 0.048, FC = 1.39. p = 0.03, FC = 1.27 and p = 0.02, FC = 1.41) are lung cancer-specific amino acids. Ornithine in monocytes demonstrated strong positive correlation (r = 0.63) with lymph node metastasis incidence in breast cancer patients. Methyl histidine and cysteine in monocytes had strong negative correlation with lymph node metastasis in ovarian cancer patients (r = -0.95 and r = -0.95 respectively). Arginine, citrulline and ornithine have strong negative correlation with tumor size (r = -0.78, citrulline) and lymph node metastasis (r = -0.63 for arginine and r = -0.66 for ornithine). Discussion: These alterations in monocyte amino acid metabolism can reflect the reaction of systemic innate immunity on the growing tumor. Our data indicate that this metabolic programming is cancer specific and can be inhibiting cancer progression. Cancer-specific differences in citrulline, as molecular link between metabolic pathways and epigenetic programing, provide new option for the development and validation of anti-cancer therapies using inhibitors of enzymes catalyzing citrullination.