Phospholipid Levels Research Articles

460 Changes in Lipid Profiles with Progression of Pregnancy in Black Women

OBJECTIVES/GOALS: Pregnant African American (Black women) have higher rates of adverse pregnancy outcomes compared to other races and routine monitoring of lipid levels is not currently in practice in prenatal care. We hypothesized that lipid profiles would show variation across pregnancy indicative of specific requirements during gestation and fetal development. METHODS/STUDY POPULATION: We used an untargeted lipidome analysis approach to investigate lipid metabolism with the progression of pregnancy. Pregnant Black women were recruited at prenatal clinics in Midwest (Metro Detroit, Michigan and Columbus, Ohio), women under 18 or above 45 years of age were not enrolled due to metabolic changes associated with these age groups. Women signed the consent forms and plasma samples were collected at 8-18 weeks at (T1), 22-29 weeks (T2) and 30-36 weeks (T3) of pregnancy. Samples from sixty-three women (mean age 27.41 ± 5.61 years) who had term birth (completed 37 weeks of pregnancy) were subjected to “shotgun” Orbitrap high resolution/ accurate mass spectrometry. Mixed-effects models were used to quantify systematic changes in relative lipid abundances over time using R lme4 and ggplot2 packages. RESULTS/ANTICIPATED RESULTS: Total lipids and some major lipid classes showed a significant increase with the progression of pregnancy. Phospholipids and glycerolipids exhibited a gradual increase throughout pregnancy, while sphingolipids and total sterol lipids displayed a more pronounced increase at the T3 timepoint. Acylcarnitines, hydroxy acylcarnitines and Lyso phospholipids levels significantly decrease from T1 to T3. One of the interesting finding was that non-esterified fatty acids decreased from T1 to T2 and increased again from T2 to T3, suggesting a possible role for these lipids during the later stages of pregnancy. The fatty acids showing this trend included key fatty acids- Linoleic Acid, Arachidonic Acid, Alpha-linolenic acid, Eicosapentaenoic acid, Docosapentaenoic acid, Docosahexaenoic acid. DISCUSSION/SIGNIFICANCE: Mapping lipid trends during pregnancy could lend support to a precision health approach to reduce perinatal health disparities among pregnant Black women. The findings from this study will be used to identify biomarkers and study associations with social and environmental factors responsible for adverse perinatal outcome in pregnant Black women.

Analysis of exhaled breath condensate in patients with asthma and recurrent wheezing

Wheezing is the most common clinical symptom of bronchial obstructive syndrome. The functions of pulmonary surfactant (PS) depend directly on the level of total phospholipids (TP). This can be used to assess the integrity of the cell membrane structure. Objective. To determine the level of total phospholipids and calcium in exhaled breath condensate in young children with recurrent wheezing and asthma. Materials and methods. The study included 77 patients divided into 3 groups. Group 1 included 30 patients (20 girls and 10 boys) with no more than 2 episodes of recurrent wheezing in their lifetime; Group 2 -10 patients (6 boys and 4 girls) with more than 3 episodes of recurrent wheezing, and 37 patients (15 girls, 22 boys) with asthma. The control group consisted of 20 conditionally healthy children (11 girls, 9 boys). All patients were aged from 3 months to 6 years. The determination of phospholipid levels and calcium (Ca) in the exhaled breath condensate was performed in dynamics - during the period of clinical manifestations and remission. Results. The level of phospholipids in the exhaled breath condensate was the highest in patients of all groups at the stage of clinical manifestations compared with the period of remission, while its lowest level was noted in the control group. During the peak of the disease, the level of Ca in the exhaled breath condensate was significantly lower compared to the period of remission. The control group had the highest level. Conclusions. The exhaled breath condensate's high level of phospholipids in the first days of the disease confirms cell damage in the presence of inflammation. Additionally, the exhaled breath condensate's Ca level is lowest during this period, possibly indicating its involvement in cell damage

Exploring the potential effect of electroacupuncture on cardiovascular function and lipid profiles in spontaneously hypertensive rats

BackgroundInvestigating the effects of electroacupuncture (EA) treatment on cardiovascular function and aortic lipid profiles in spontaneously hypertensive rats (SHR) constitutes the foundational focus of this study. The overarching goal is to comprehensively elucidate the alterations brought about by EA treatment and to assess its potential as an alternative therapy for hypertension. MethodsConsecutive EA treatments were administered to SHR, and the effects on systolic blood pressure, cardiac function, and hypertension-related neuronal signals were assessed. Aortic lipid profiles in vehicle-treated SHR and EA-treated SHR groups were analyzed using mass spectrometry-based lipid profiling. Additionally, the expression of Cers2 and GNPAT, enzymes involved in the synthesis of specific aortic lipids, was examined. ResultsThe study demonstrated that consecutive EA treatments restored systolic blood pressure, improved cardiovascular function, and normalized hypertension-related neuronal signals in SHR. Analysis of the aortic lipid profiles revealed distinct differences between the vehicle-treated SHR group and the EA-treated SHR group. Specifically, EA treatment significantly altered the levels of aortic sphingomyelin and phospholipids, including very long-chain fatty acyl-ceramides and ether phosphatidylcholines. These changes in aortic lipid profiles correlated significantly with systolic blood pressure and cardiac function indicators. Furthermore, EA treatment significantly altered the expression of Cers2 and GNPAT. ConclusionsThe findings suggest that EA may influence cardiovascular functions and aortic lipid profiles in SHR.

Abstract 3063: Defining oncogene-specific metabolic vulnerabilities in a mouse model of hepatocellular carcinoma

Abstract Despite the continued success of advanced cancer therapies, hepatocellular carcinoma (HCC) represents a substantial challenge to current treatment modalities that are not sufficiently effective for the management of advanced disease. Metabolic reprogramming is a hallmark of cancer and many oncogenic signaling pathways impact on cellular metabolism. Here, we are investigating changes in metabolism in different oncogene-driven mouse models of liver cancer to identify selective metabolic vulnerabilities associated with HCC that could be implicated in tumor initiation and progression to be exploited for cancer therapy. Transposon-based vectors coding for different combinations of oncogenes, either Myc and Akt1Myr (CaMIA) or Myc and NrasG12V (CaMIN), were transduced by hydrodynamic tail vein injected into C57BL/6 mice. The resulting liver tumors and control livers were subjected to a comprehensive profiling of polar metabolites (metabolomics) and lipids (lipidomics and total fatty acids) as well as changes in gene expression (transcriptomics). Despite similar overall survival, the two models display marked differences in the presentation of the tumors, with CaMIA showing larger aggressive tumors, while CaMIN livers contain numerous small tumor nodules. Both models also showed evidence for the deregulation of intermediate metabolism, indicating activation of aerobic glycolysis and deregulation of glutamine metabolism. Lipidomic analysis revealed substantial lipidome remodeling in both models. Oncogene-specific alterations included elevated levels of lysophosphatidylcholine (LPC) in CaMIN tumors, while CaMIA tumors displayed high levels of ether phospholipids compared to CaMIN and normal liver. Moreover, the fraction of polyunsaturated fatty acids (PUFAs) was enhanced in lipids from CaMIN tumors, while monounsaturated fatty acids (MUFAs) were enriched in CaMIA tumors. Furthermore, tumors from both genotypes produced higher levels of oxylipins, a class of lipid mediators involved in signaling and inflammation, compared to normal liver. Transcriptome analysis confirmed these metabolic alterations and revealed evidence for enhanced inflammatory signaling in CaMIN. In addition, analysis of tumor microenvironment composition disclosed specific differences in stromal components, indicative of immune evasion through checkpoint activation. Experiments in primary murine liver cancer cell lines confirmed oncogene-specific metabolic rearrangements and suggest elevated sensitivity towards inhibitors of lipid remodeling. Future experiments will investigate the role of altered lipid metabolism in tumor development and immune evasion in liver cancer. Citation Format: Kamal Al-Shami, Marteinn Snaebjornsson, Felix Vogel, Lisa Schlicker, Phillip Pöller, Daniel Dauch, Almut Schulze. Defining oncogene-specific metabolic vulnerabilities in a mouse model of hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3063.

Application of Clinical Blood Metabogram to Type 2 Diabetes Mellitus.

The clinical blood metabogram (CBM) was developed to match a tailored analysis of the blood metabolome to the time, cost, and reproducibility constraints of clinical laboratory testing. By analyzing the main blood metabolite groups, CBM offers clinically relevant information about the intake of low-molecular substances into the organism, humoral regulation, liver function, amino acid level, and the lipid and carbohydrate metabolism. The purpose of this work was to investigate the relevance of using the CBM in patients with diabetes mellitus. For this, a CBM was obtained for 18 healthy individuals, 12 individuals with prediabetes, and 64 individuals with type 2 diabetes mellitus, separated into groups according to fasting blood glucose and oral glucose tolerance tests. The results showed that the CBM reveals diabetes-associated metabolic alterations in the blood, including changes in the levels of carbohydrates, ketone bodies, eicosanoids, phospholipids, and amino acids, which are consistent with the scientific data available to date. The CBM enabled the separation of diabetic patients according to their metabolic metabotypes, providing both a general overview of their metabolic alterations and detailing their individual metabolic characteristics. It was concluded that the CBM is a precise and clinically applicable test for assessing an individual's metabolic status in diabetes mellitus for diagnostic and treatment purposes.

Altered myocardial lipid regulation in junctophilin-2-associated familial cardiomyopathies.

Myocardial lipid metabolism is critical to normal heart function, whereas altered lipid regulation has been linked to cardiac diseases including cardiomyopathies. Genetic variants in the JPH2 gene can cause hypertrophic cardiomyopathy (HCM) and, in some cases, dilated cardiomyopathy (DCM). In this study, we tested the hypothesis that JPH2 variants identified in patients with HCM and DCM, respectively, cause distinct alterations in myocardial lipid profiles. Echocardiography revealed clinically significant cardiac dysfunction in both knock-in mouse models of cardiomyopathy. Unbiased myocardial lipidomic analysis demonstrated significantly reduced levels of total unsaturated fatty acids, ceramides, and various phospholipids in both mice with HCM and DCM, suggesting a common metabolic alteration in both models. On the contrary, significantly increased di- and triglycerides, and decreased co-enzyme were only found in mice with HCM. Moreover, mice with DCM uniquely exhibited elevated levels of cholesterol ester. Further in-depth analysis revealed significantly altered metabolites from all the lipid classes with either similar or opposing trends in JPH2 mutant mice with HCM or DCM. Together, these studies revealed, for the first time, unique alterations in the cardiac lipid composition-including distinct increases in neutral lipids and decreases in polar membrane lipids-in mice with HCM and DCM were caused by distinct JPH2 variants. These studies may aid the development of novel biomarkers or therapeutics for these inherited disorders.

Hypertension Increases Susceptibility to Experimental Malaria in Mice.

Global prevalence of hypertension is on the rise, burdening healthcare, especially in developing countries where infectious diseases, such as malaria, are also rampant. Whether hypertension could predispose or increase susceptibility to malaria, however, has not been extensively explored. Previously, we reported that hypertension is associated with abnormal red blood cell (RBC) physiology and anemia. Since RBC are target host cells for malarial parasite, Plasmodium, we hypothesized that hypertensive patients with abnormal RBC physiology are at greater risk or susceptibility to Plasmodium infection. To test this hypothesis, normotensive (BPN/3J) and hypertensive (BPH/2J) mice were characterized for their RBC physiology and subsequently infected with Plasmodium yoelii (P. yoelii), a murine-specific non-lethal strain. When compared to BPN mice, BPH mice displayed microcytic anemia with RBC highly resistant to osmotic hemolysis. Further, BPH RBC exhibited greater membrane rigidity and an altered lipid composition, as evidenced by higher levels of phospholipids and saturated fatty acid, such as stearate (C18:0), along with lower levels of polyunsaturated fatty acid like arachidonate (C20:4). Moreover, BPH mice had significantly greater circulating Ter119+ CD71+ reticulocytes, or immature RBC, prone to P. yoelii infection. Upon infection with P. yoelii, BPH mice experienced significant body weight loss accompanied by sustained parasitemia, indices of anemia, and substantial increase in systemic pro-inflammatory mediators, compared to BPN mice, indicating that BPH mice were incompetent to clear P. yoelii infection. Collectively, these data demonstrate that aberrant RBC physiology observed in hypertensive BPH mice contributes to an increased susceptibility to P. yoelii infection and malaria-associated pathology.

NMR-Based Analysis of Plasma Lipoprotein Subclass and Lipid Composition Demonstrate the Different Dietary Effects in ApoE-Deficient Mice.

Plasma lipid levels are commonly measured using traditional methods such as triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and cholesterol (CH). However, the use of newer technologies, such as nuclear magnetic resonance (NMR) with post-analysis platforms, has made it easier to assess lipoprotein profiles in research. In this study involving ApoE-deficient mice that were fed high-fat diets, significant changes were observed in TG, CH, free cholesterol (FC), and phospholipid (PL) levels within the LDL fraction. The varied proportions of TG in wild-type mice and CH, FC, and PL in ApoE-/- mice were strikingly different in very low-density lipoproteins (VLDL), LDL, intermediate-density lipoprotein (IDL), and HDL. This comprehensive analysis expands our understanding of lipoprotein subfractions and the impacts of the APOE protein and high-fat diet in mouse models. The new testing method allows for a complete assessment of plasma lipids and their correlation with genetic background and diet in mice.

A41 IDENTIFICATION OF MICROBIAL LYSOPHOSPHATIDYLCHOLINE (LPC) AND LYSOPHOSPHATIDIC ACID (LPA) PRODUCERS AND THEIR EFFECTS ON THE HOST

Abstract Background Gut microbiota plays a key role in shaping our immune system, producing a myriad of molecules with neuro- and immunomodulatory properties. Many of these bioactive molecules are generated by bacterial metabolism of common dietary components. We have recently found that fecal samples of patients with chronic abdominal pain contain high levels of inflammatory phospholipids, lysophosphatidylcholine (LPC) and its active metabolite lysophosphatidic acid (LPA). Both phospholipids have been previously linked to genesis and maintenance of chronic neuropathic pain. In addition, they appear to have pro-inflammatory properties. Aims To investigate whether gut bacteria can produce LPC and LPA from dietary precursor phosphatidylcholine (PC), and whether these phospholipids can induce inflammatory responses in the host. Methods Fecal samples from patients with chronic abdominal pain were analyzed for microbial profiles using 16S rRNA (Illumina) analysis, and abundance of individual bacteria was correlated with fecal LPC and LPA levels as measured by ELISA. To confirm ability to produce these lipids, identified bacteria were incubated with either phosphatidylcholine (PC) or LPC (the immediate precursors of LPC and LPA, respectively) and LPC and LPA levels measured using liquid chromatography-mass spectrometry. To investigate pro-inflammatory effect of LPC and LPA, mouse splenocytes were incubated with LPC and/or LPA in vitro, and tested for cytokine production. Results Higher abundance of several bacterial species was associated with higher fecal levels of LPC and LPA. Among them, a bacterium from family Oscillospiraceae was identified as the most likely producer of both LPA and LPC; its abundance also correlated with high pain scores. Culturing and incubating this bacterium with PC and LPC resulted in a significant production of LPC and LPA. Additionally, LPA, but not LPC, resulted in increased levels of IL-6 production by splenocytes in vitro compared to the PBS only control. Interestingly, LPA induced IL-6 secretion was inhibited in the presence of LPC. Conclusions We have identified several bacterial producers of LPC and LPA, among them a bacterium from family Oscillospiraceae, which was also associated with high abdominal pain scores. LPA, but not LPC, seems to induce proinflammatory responses in the host. Further experiments are needed to identify the specific mechanisms by which these bioactive phospholipids induce abdominal pain and immune responses in the host. Funding Agencies CIHRFarncombe Family Digestive Health Research Institute

Fatty acid unsaturation improves germination of upland cotton (Gossypium hirsutum) under cold stress.

The level of fatty acid unsaturation in seeds is one of the major determinants of cold germination ability, particularly in oilseeds. The presence of cis double bonds in unsaturated fatty acids creates bends that lowers their melting temperatures compared to saturated fatty acids. Unsaturated fatty acids with low melting points mobilize faster at low temperatures providing seeds with sufficient energy for germination. To investigate the effects of fatty acid unsaturation on the ability of cotton seeds to germinate under cold conditions, four recombinant inbred lines (RILs) of cotton with unique fatty acid profiles were evaluated using a set of developmental and biochemical assays at 12°C (critically low temperature), 15°C (cardinal minimum temperature) and 30°C (optimum temperature). Furthermore, whole seed lipidome profiling using liquid chromatography with mass spectrometry was done to compare the lipid compositional changes at 12°C and 30°C after imbibing cotton seeds of all the six genotypes for 0 hours, 3 hours and 6 hours. The RILs with higher unsaturation/saturation ratios registered robust germination performance, lower solute leakage, and optimum water uptake rates under cold stress. Imbibition at 30°C for 8 hours before cold exposure significantly improved the germination of cold sensitive genotypes, indicating that the first few hours of water uptake are critical for cold stress. Whole seed lipidome profiling of all the genotypes specifically associated cold germination ability with higher unsaturation levels of phospholipids during early imbibition. The presence of cis double bonds in phospholipids creates kinks that maintain the fluidity of cell membranes under low temperature. Membrane flexibility under cold conditions is essential for facilitating key germination events including membrane organization and respiration. The current results highlight the importance of fatty acid composition in cold germination ability of upland cotton.

Causal association of lipoprotein-associated phospholipids on the risk of sepsis: a Mendelian randomization study.

Many previous studies have revealed a close relationship between lipoprotein metabolism and sepsis, but their causal relationship has, until now, remained unclear. Therefore, we performed a two-sample Mendelian randomization analysis to estimate the causal relationship of lipoprotein-associated phospholipids with the risk of sepsis. A two-sample Mendelian randomization (MR) analysis was performed to investigate the causal relationship between lipoprotein-associated phospholipids and sepsis based on large-scale genome-wide association study (GWAS) summary statistics. MR analysis was performed using a variety of methods, including inverse variance weighted as the primary method, MR Egger, weighted median, simple mode, and weighted mode as complementary methods. Further sensitivity analyses were used to test the robustness of the data. After Bonferroni correction, the results of the MR analysis showed that phospholipids in medium high-density lipoprotein (HDL; ORIVW = 0.82, 95% CI 0.71-0.95, P = 0.0075), large HDL (ORIVW = 0.92, 95% CI 0.85-0.98, P = 0.0148), and very large HDL (ORMR Egger = 0.83, 95% CI 0.72-0.95, P = 0.0134) had suggestive causal relationship associations with sepsis. Sensitivity testing confirmed the accuracy of these findings. There was no clear association between other lipoprotein-associated phospholipids and sepsis risk. Our MR analysis data suggestively showed a correlation between higher levels of HDL-associated phospholipids and reduced risk of sepsis. Further studies are required to determine the underlying mechanisms behind this relationship.

Protein Phosphatase 1 Regulatory Subunit 3 Beta rs4240624 Genotype Is Associated With Gallstones and With Significant Changes in Bile Lipidome

Gallstone disease (GSD) associates with significant morbidity and mortality. Decreased secretion of bile acids has been suggested as a driving factor for GSD. Recently, we linked the protein phosphatase 1 regulatory subunit 3 beta (PPP1R3B) rs4240624 genotype to decreased bile acid levels in bile. In this study, we investigated whether these individuals had an increased risk for GSD as well as the differences in the lipid composition of the gallbladder bile of these individuals compared to controls and patients with GSD. Bile acids, cholesterol, and phospholipid levels in gallbladder bile samples were enzymatically measured in 46 patients (34 female, age 45.7 ± 9.8 years, BMI 41.3 ± 4.4 kg/m2) who underwent elective laparoscopic Roux-en-Y gastric bypass. The lipidome of gallbladder bile was analyzed using high-performance liquid chromatography-mass spectrometry. Gallstone status was evaluated using abdominal ultrasonography before the surgery. The G allele of PPP1R3B rs4240624 was significantly associated with GSD in patients with obesity. We validated this association in the UK Biobank. Bile lipidomics demonstrated that 13 of the 17 minor lipid classes measured were higher in individuals with the G allele. The concentrations of bile acids, cholesterol, and phospholipids, as well as the cholesterol saturation index, were lower in patients with GSD than in those without gallstones. GSD had an effect similar to that of PPP1R3B genotype on minor lipids. The PPP1R3B rs4240624 genotype is associated with gallstones and with changes in gallbladder bile similar to those observed in patients with gallstones, suggesting that the PPP1R3B genotype contributes to the risk of gallstones by altering the bile lipidome.

Selenoprotein H mediates low selenium-related cognitive decline through impaired oligodendrocyte myelination with disrupted hippocampal lipid metabolism in female mice.

Low selenium levels are closely associated with reduced cognitive performance and lipid dysregulation, yet the mechanism of action remains unclear. The physiological function of selenium is primarily mediated by selenoproteins. Selenoprotein H (SELENOH), as one of the selenium-containing proteins, has an unelucidated role in regulating cognitive status and lipid metabolism. In this study, we established a Selenoh gene knockout (HKO) mouse model to investigate whether Selenoh mediates the impact of selenium on cognitive function. We found that HKO mice showed a significant decline in cognition compared with the wild-type (HWT) littermates, and were not affected by deficient or excessive selenium, while no differences in anxiety and depression behavior were observed. HKO mice showed reduced myelin basic protein expression in hippocampal oligodendrocytes, with decreased glycolipid levels and increased phospholipid and sphingolipid levels in the hippocampus. Furthermore, the high-fat diet (HFD) exerted no effect on cognition and limited impact on the gene profile in the hippocampus of HKO mice. Compared with those of HWT mice, the myelination pathways in the hippocampus of HKO mice were downregulated as revealed by RNA-seq, which was further confirmed by the reduced expression levels of myelin-related proteins. Finally, HKO increased the expression of hippocampal fatty acid transporter (FATP) 4, and HFD increased the FATP4 expression in HWT mice but not in HKO mice. In summary, our study demonstrated that HKO induced cognitive decline by impairing myelination in oligodendrocytes with disrupted hippocampal lipid metabolism, which provided a novel viewpoint on the selenoprotein-mediated neurodegenerative diseases of selenium.

Investigating the effects of PFOA accumulation and depuration on specific phospholipids in zebrafish through imaging mass spectrometry.

Perfluorooctanoic acid (PFOA) is an emerging persistent organic pollutant. Exposure to PFOA was observed to have a correlation with the expression levels of phospholipids. However, there are currently no studies that directly visualize the effects of PFOA on phospholipids. To this end, matrix-assisted laser desorption/ionization time of flight imaging mass spectrometry (MALDI-TOF-IMS) was used to visualize changes in phospholipids in the different tissues of zebrafish following exposure to PFOA. This study found that the major perturbed phospholipids were phosphatidylcholine (PC), diacylglycerol (DG), phosphatidic acid (PA), phosphatidylglycerol (PG), sphingomyelin (SM), and triacylglycerol (TG). These perturbed phospholipids caused by PFOA were reversible in some tissues (liver, gill, and brain) and irreversible in others (such as the highly exposed intestine). Moreover, the spatial distribution of perturbed phospholipids was mainly located around the edge or center of the tissues, implying that these tissue regions need special attention. This study provides novel insight into the biological toxicity and toxicity mechanisms induced by emerging environmental pollutants.

MFGM-enriched whey displays antiviral activity against common pediatric viruses in vitro.

Among the most common mucosal viral infections in infants are rotavirus, one of the main causes of severe gastroenteritis in infants and children up to 5 years, and respiratory syncytial virus (RSV), one of the leading causes of lower respiratory tract infections. Both human milk and bovine milk derived factors may provide protection against mucosal viral infections. More recently, a similar activity of milk derived proteins was suggested for SARS-CoV-2. The goal of the current study was to test antiviral activity of the bovine milkfat globule membrane (MFGM) against rotavirus, RSV and SARS-CoV-2 and to further characterize MFGM-enriched whey to identify which components in MFGM-enriched whey may contribute to the inhibitory activity. The effects of MFGM-enriched whey, its whey protein isolate counterpart (WPI, obtained from the same production process) and a conventional whey protein concentrate (WPC) on rotavirus (strains Wa and SA114F), RSV (strain RSV-A2) and SARS-CoV-2 (Alpha variant) infectivity were determined using MA104 cells, human alveolar basal epithelial (A549) cells and monkey kidney (Vero E6) cells, respectively. The compounds were characterized in detail by LC-MS/MS and 31P-NMR to determine protein and phospholipid composition, respectively. Relative to its WPI counterpart, MFGM-enriched whey demonstrated a dose-dependent inhibition for both rotavirus and RSV whereas for SARS-CoV-2 inhibition was only observed at the highest concentration tested. Label-free quantification (LFQ) and intensity based absolute quantification (iBAQ) of identified proteins revealed a clear difference between MFGM-enriched whey and its controls including enrichment of known MFGM proteins and non-MFGM proteins that are enriched simultaneously, some of which have previously been demonstrated to display anti-viral activity. Although not completely absent from other whey protein preparations, MFGM-enriched whey had the highest specific and total phospholipid levels. MFGM-enriched whey displayed antiviral activity against multiple viruses of clinical importance. This study provides insights into the active components in MFGM-enriched whey and may contribute to previous clinical observations with MFGM-enriched formula demonstrating reduced respiratory and gastrointestinal infections in formula fed infants.

Lambda-cyhalothrin'nin Oreochromis niloticus’un Solungaç Fosfolipid (PL) Alt Sınıfı Üzerine Etkisi

Fatty acids have a crucial role in providing energy and performing essential functions in living organisms. Moreover, these substances exhibit the most significant alterations in their structure based on ecotoxicological parameters when viewed from a biochemical perspective. These bioactive chemicals are present in the cellular architecture. The study of these fatty acids, crucial for maintaining the integrity and permeability of cell membranes, holds great significance for all living organisms. Consequently, doing fatty acid analysis specifically at the phospholipid level holds significant importance.
 The impact of lambda cyhalothrin on the fatty acid content of several phospholipid subclasses (phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), and phosphatidylserine (PS) in the gill tissue of O. niloticus (Perciformes: Cichlidae) was assessed using gas chromatography. The alterations in the fatty acid composition was analyzed 21 days after exposure.
 Following the complete extraction of lipids from gill tissue, the tissue was subsequently separated into different subclasses of phospholipids using thin layer chromatography. The samples were subjected to methylation and then evaluated using Gas Chromatography to determine the percentage of the fatty acid. After doing the analysis, a grand total of 16 fatty acids were identified. The research revealed that the primary fatty acids were 16:0 and 18:0 of saturated fatty acids, monounsaturated 18:1n-9, and polyunsaturated 18:2n-6, 20:4n-6, and 22:6n-6. Upon analyzing the distribution of fatty acids, it was observed that PC, PE, and PI included 16:0, PE contained 18:1, PE and PS contained C18:2n-6 and 20:4n-6, and significant alterations in C22:6n-3 were detected in PE. Our investigation revealed that the n-3/n-6 ratio of fish in the PE subclass was the lowest when compared to PC, PI, and PS.

Molluscicidal activity of calcium borate nanoparticles with kodom ball-flower structure on hematological, histological and biochemical parameters of Eobania vermiculata snails

Land snails are the most harmful pests in agricultural fields. Eobania vermiculata is a widespread snail species that causes massive damage to all agricultural crops. Thus, the molluscicidal activity of calcium borate nanoparticles (CB-NPs) against Eobania vermiculata was evaluated and compared with metaldehyde (Gastrotox® E 5% G). The amorphous phase of CB-NPs was obtained after thermal treatment at a low temperature (500 °C) which conformed by X-ray diffraction (XRD) analysis. CB-NPs are composed of aggregated nano-sheets with an average thickness of 54 nm which enhanced their molluscicidal activity. These nano-sheets displayed meso-porous network architecture with pore diameters of 13.65 nm, and a 9.46 m2/g specific surface area. CB-NPs and metaldehyde (Gastrotox® E 5% G) exhibited molluscicidal effects on Eobania vermiculata snails with median lethal concentrations LC50 of 175.3 and 60.5 mg/l, respectively, after 72 h of exposure. The results also showed significant reductions of Eobania vermiculata snails hemocytes' mean total number, the levels of Testosterone (T) and Estrogen (E), alkaline phosphatase, acid phosphatase, albumin, and protein concentrations, succinate dehydrogenase, glucose, triglycerides and phospholipids levels, while significant increases in the phagocytic index and mortality index, both transaminases (ALT and AST) and glycogen phosphorylase concentration were observed after the exposure to LC50 of CB-NPs or metaldehyde (Gastrotox® E 5% G) compared to the control group. Therefore, CB-NPs could be used as an alternative molluscicide for controlling Eobania vermiculata, but further studies are needed to assess their effects on non-target organisms.

Sıçanlarda sirkadiyen ritim bozuklukları ile ilgili çeşitli koşulların plazma ve eritrosit lipidleri üzerindeki etkileri: peroksizomal bir bakış açısı

Purpose: Lipidomics studies of sleep restriction, which is known to be associated with circadian perturbations, revealed alterations in some plasma phospholipid levels including plasmalogens which are partly synthesized in liver peroxisomes. To this end it was aimed to investigate effects of various conditions known to cause circadian rhythm disturbances on various peroxisomal parameters and to compare those effects with that of fenofibrate, a peroxisome proliferator-activated receptor alpha agonist.
 Materials and Methods: Plasmalogens and some fatty acids in erythrocyte lysates were analyzed by GC. Peroxisomal metabolites including very long chain fatty acids as well as phytanic and pristanic acids in plasma were measured by GC-MS. Immunohistological analyses by catalase antibodies were conducted on liver sections. 
 Results: All the conditions tested exhibited increased catalase immunoreactivity in liver sections compared to that of controls. Both calorie restriction, time-restricted feeding, as well as fenofibrate treatment exhibited lower C18:0 plasmalogen contents of erythrocyte lysates. As plasmalogens are known to be synthesized by peroxisomes, the present results suggest that the peroxisomal lipid content in membranes might be affected by conditions co-occuring with circadian perturbations.
 Conclusion: Shared effects of conditions associated with circadian rhythm disturbances and peroxisomal induction by fenofibrate on erythrocyte membrane lipids might indicate a link between them.

The effectiveness of feeding the pancreas of pigs to calves of the weaning period of growing

Relevance. The study of the physiological effect of the pancreas, which is a slaughter waste, on the body of calves of early weaning during the formation of digestive activity of the gastrointestinal type to improve the adaptive capabilities of the body of calves is of scientific and practical interest.Methods. Scientific and production experience was carried out on calves of the weaning period for 90 days. The pancreas of pigs (pancreas) was fed, obtained from the waste of the slaughterhouse production, dried with the use of lyophilization. Calves – analogs by breed, age, live weight – were formed into two groups (n = 8), the animals of the experimental group were given a feed product at the rate of 40 mg/kg of live weight daily with compound feed with group loose content. Live weight accounting (n = 8) and analysis of biochemical and hematological composition of blood (n = 5) were carried out.Results. Higher live weight gains of calves treated with PHC were established with improvement of biochemical and hematological blood parameters (without negative aftereffect). With a tendency to increase the level of total protein due to the albumin fraction, a lower level of urea is also positive evidence of an improvement in nitrogen metabolism. Higher creatinine levels in combination with glucose and alkaline phosphatase levels characterize an increase in the availability of energy exchange processes in the body of calves under the influence of a feed product. Positive differences in the levels of phospholipids, triglycerides, cholesterol against the background of lower bilirubin levels indicate an improvement in lipid metabolism, but also (indirectly) lipotropic liver function. Positive trends have been established in hematological indicators of blood, higher levels of erythrocytes, hemoglobin, hematocrit, lower levels of leukocytes.

Extraction process optimization of alisol B 23-acetate from Alismatis Rhizoma and its protection against carbon tetrachloride-induced acute liver injury

Alisol B 23-acetate (AB23A) is an important pharmacodynamic compound found in Alismatis Rhizoma. In this study, response surface methodology (RSM) and Box- Behnken design (BBD) were used to optimize the extraction parameters of the AB23A. The optimal conditions included a solid–liquid ratio of 1:13, a reflux extraction of 70% ethanol, an extraction time of 2 h, and an extraction cycle of 3 cycles. Furthermore, a rat model of acute liver injury was established using carbon tetrachloride (CCl4), and a comprehensive analysis combining histopathology, lipidomics, and metabolomics was conducted to elucidate the hepatoprotective effect of AB23A. The findings revealed that AB23A significantly reduced the levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP), and restored the abnormal morphology of hepatocytes. Furthermore, AB23A exhibited the ability to attenuate CCl4-induced lipid peroxidation, as evidenced by the upregulation of glutathione (GSH) and glutathione peroxidase 4 (GPX4) levels, along with a reduction in malondialdehyde (MDA) content in the liver. Omics results and immunohistochemistry analyses demonstrated a decrease in inflammatory reaction and oxidized phospholipid levels following AB23A administration, indicating an enhanced anti-inflammatory and antioxidant capacities of hepatocytes. Differential metabolite analysis revealed that AB23A improved anti-inflammatory and antioxidant capacities by modulating liver sphingolipid metabolism and purine metabolism, thereby enhancing hepatocyte recovery and counteracting acute liver injury induced by CCl4.