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Biological & Pharmaceutical Bulletin 2024Plasmalogens are a family of glycerophospholipids containing one vinyl-ether bond at the sn-1 position in the glycerol backbone, and play important roles in cellular...
Plasmalogens are a family of glycerophospholipids containing one vinyl-ether bond at the sn-1 position in the glycerol backbone, and play important roles in cellular homeostasis including neural transmission. Therefore, reductions of plasmalogens have been associated with neurodegenerative disorders, such as Alzheimer's disease (AD). To evaluate the potential protective effects of plasmalogens against the pathology of AD, protein expression levels of key factors in amyloid precursor protein (APP) metabolic processes were examined using human neuroblastoma SH-SY5Y cells. Here, phosphatidylcholine-plasmalogen-oleic acid (PC-PLS-18) was shown to reduce protein expression levels of β-site APP cleaving enzyme 1 (BACE1), clusterin, and Tau, factors involved in the amyloid β-associated pathogenesis of AD. Thus, PC-PLS-18 may have preventive effects against AD by delaying the onset risk for a certain period.
Topics: Humans; Amyloid beta-Peptides; Amyloid Precursor Protein Secretases; Plasmalogens; Aspartic Acid Endopeptidases; Oleic Acid; Phosphatidylcholines; Neuroblastoma; Alzheimer Disease; Amyloid beta-Protein Precursor
PubMed: 38233149
DOI: 10.1248/bpb.b23-00787 -
BioRxiv : the Preprint Server For... Jul 2023During demyelination, lipid-rich myelin debris is released in the central nervous system (CNS) and must be phagocytosed and processed before new myelin can form....
During demyelination, lipid-rich myelin debris is released in the central nervous system (CNS) and must be phagocytosed and processed before new myelin can form. Although myelin comprises over 70% lipids, relatively little is known about how the CNS lipidome changes during demyelination and remyelination. In this study, we obtained a longitudinal lipidomic profile of the brain, spinal cord, and serum using a genetic mouse model of demyelination, known as -iCKO- mice. This model has distinct phases of demyelination and remyelination over the course of 24 weeks, in which loss of motor function peaks during demyelination. Using principal component analysis (PCA) and volcano plots, we have demonstrated that the brain and spinal cord have different remyelination capabilities and that this is reflected in different lipidomic profiles over time. We observed that plasmalogens (ether-linked phosphatidylserine and ether-linked phosphatidylcholine) were elevated specifically during the early stages of active demyelination. In addition, we identified lipids in the brain that were altered when mice were treated with a remyelinating drug, which may be CNS biomarkers of remyelination. The results of this study provide new insights into how the lipidome changes in response to demyelination, which will enable future studies to elucidate mechanisms of lipid regulation during demyelination and remyelination.
PubMed: 37546864
DOI: 10.1101/2023.07.24.550351 -
Pharmaceuticals (Basel, Switzerland) Jun 2024The COVID-19 pandemic, caused by infection with the SARS-CoV-2 virus, is associated with cognitive impairment and Alzheimer's disease (AD) progression. Once it enters... (Review)
Review
The COVID-19 pandemic, caused by infection with the SARS-CoV-2 virus, is associated with cognitive impairment and Alzheimer's disease (AD) progression. Once it enters the brain, the SARS-CoV-2 virus stimulates accumulation of amyloids in the brain that are highly toxic to neural cells. These amyloids may trigger neurological symptoms in COVID-19. The meningeal lymphatic vessels (MLVs) play an important role in removal of toxins and mediate viral drainage from the brain. MLVs are considered a promising target to prevent COVID-19-exacerbated dementia. However, there are limited methods for augmentation of MLV function. This review highlights new discoveries in the field of COVID-19-mediated amyloid accumulation in the brain associated with the neurological symptoms and the development of promising strategies to stimulate clearance of amyloids from the brain through lymphatic and other pathways. These strategies are based on innovative methods of treating brain dysfunction induced by COVID-19 infection, including the use of photobiomodulation, plasmalogens, and medicinal herbs, which offer hope for addressing the challenges posed by the SARS-CoV-2 virus.
PubMed: 38931455
DOI: 10.3390/ph17060788 -
Frontiers in Microbiology 2023Thermophily is an ancient trait among microorganisms. The molecular principles to sustain high temperatures, however, are often described as , somewhat implying that...
Thermophily is an ancient trait among microorganisms. The molecular principles to sustain high temperatures, however, are often described as , somewhat implying that they evolved from a non-thermophilic background and that thermophiles, i.e., organisms with growth temperature optima (T) above 45°C, evolved from mesophilic organisms (T 25-45°C). On the contrary, it has also been argued that LUCA, the last universal common ancestor of and , may have been a thermophile, and mesophily is the derived trait. In this study, we took an experimental approach toward the evolution of a mesophile from a thermophile. We selected the acetogenic bacterium (T 66°C) since acetogenesis is considered ancient physiology and cultivated it at suboptimal low temperatures. We found that the lowest possible growth temperature (T) under the chosen conditions was 39°C. The bacterium was subsequently subjected to adaptive laboratory evolution (ALE) by serial transfer at 45°C. Interestingly, after 67 transfers (approximately 180 generations), the adapted strain Adpt45_67 did not grow better at 45°C, but a shift in the T to 60°C was observed. Growth at 45°C was accompanied by a change in the morphology as shorter, thicker cells were observed that partially occurred in chains. While the proportion of short-chain fatty acids increased at 50°C vs. 66°C in both strains, Adpt45_67 also showed a significantly increased proportion of plasmalogens. The genome analysis revealed 67 SNPs compared to the type strain, among these mutations in transcriptional regulators and in the cAMP binding protein. Ultimately, the molecular basis of the adaptation of to a lower T remains to be elucidated. The observed change in phenotype is the first experimental step toward the evolution of thermophiles growing at colder temperatures and toward a better understanding of the cold adaptation of thermophiles on early Earth.
PubMed: 37901835
DOI: 10.3389/fmicb.2023.1265216 -
Heliyon Jun 2024Renal calculi (RC) represent a prevalent disease of the urinary system characterized by a high incidence rate. The traditional clinical diagnosis of RC emphasizes...
Renal calculi (RC) represent a prevalent disease of the urinary system characterized by a high incidence rate. The traditional clinical diagnosis of RC emphasizes imaging and stone composition analysis. However, the significance of metabolic status in RC diagnosis and prevention remains unclear. This study aimed to investigate serum metabolites in RC patients to identify those associated with RC and to develop a metabolite-based diagnostic model. We employed nontargeted metabolomics utilizing ultra-performance liquid chromatography‒mass spectrometry (UPLC‒MS) to compare serum metabolites between RC patients and healthy controls. Our findings demonstrated significant disparities in serum metabolites, particularly in fatty acids and glycerophospholipids, between the two groups. Notably, the glycerophospholipid (GP) metabolic pathway in RC patients was significantly disrupted. Logistic regression models using differentially abundant metabolites revealed that elevated levels of 2-butyl-4-methyl phenol and reduced levels of phosphatidylethanolamine (P-16:0/22:6(4Z,7Z,10Z,13Z,16Z,19Z)) had the most substantial effect on RC risk. Overall, our study indicates that RC induces notable alterations in serum metabolites and that the diagnostic model based on these metabolites effectively distinguishes RC. This research offers promising insights and directions for further diagnostic and mechanistic studies on RC.
PubMed: 38912451
DOI: 10.1016/j.heliyon.2024.e32482 -
Journal of Proteome Research Nov 2023During demyelination, lipid-rich myelin debris is released in the central nervous system (CNS) and must be phagocytosed and processed before new myelin can form....
During demyelination, lipid-rich myelin debris is released in the central nervous system (CNS) and must be phagocytosed and processed before new myelin can form. Although myelin comprises over 70% lipids, relatively little is known about how the CNS lipidome changes during demyelination and remyelination. In this study, we obtained a longitudinal lipidomic profile of the brain, spinal cord, and serum using a genetic mouse model of demyelination, known as -iCKO-. The mass spectrometry data is available at the Metabolomics Workbench, where it has been assigned Study ID ST002958. This model has distinct phases of demyelination and remyelination over the course of 24 weeks, in which loss of motor function peaks during demyelination. Using principal component analysis (PCA) and volcano plots, we have demonstrated that the brain and spinal cord have different remyelination capabilities and that this is reflected in different lipidomic profiles over time. We observed that plasmalogens (ether-linked phosphatidylserine and ether-linked phosphatidylcholine) were elevated specifically during the early stages of active demyelination. In addition, we identified lipids in the brain that were altered when mice were treated with a remyelinating drug, which may be CNS biomarkers of remyelination. The results of this study provide new insights into how the lipidome changes in response to demyelination, which will enable future studies to elucidate mechanisms of lipid regulation during demyelination and remyelination.
PubMed: 38018851
DOI: 10.1021/acs.jproteome.3c00443 -
BioRxiv : the Preprint Server For... Mar 2024Traumatic brain injury (TBI) is a global public health problem with 50-60 million incidents per year, most of which are considered mild (mTBI) and many of these...
Traumatic brain injury (TBI) is a global public health problem with 50-60 million incidents per year, most of which are considered mild (mTBI) and many of these repetitive (rmTBI). Despite their massive implications, the pathologies of mTBI and rmTBI are not fully understood, with a paucity of information on brain lipid dysregulation following mild injury event(s). To gain more insight on mTBI and rmTBI pathology, a non-targeted spatial lipidomics workflow utilizing ultrahigh resolution mass spectrometry imaging was developed to map brain region-specific lipid alterations in rats following injury. Discriminant multivariate models were created for regions of interest including the hippocampus, cortex, and corpus callosum to pinpoint lipid species that differentiated between injured and sham animals. A multivariate model focused on the hippocampus region differentiated injured brain tissues with an area under the curve of 0.994 using only four lipid species. Lipid classes that were consistently discriminant included polyunsaturated fatty acid-containing phosphatidylcholines (PC), lysophosphatidylcholines (LPC), LPC-plasmalogens (LPC-P) and PC potassium adducts. Many of the polyunsaturated fatty acid-containing PC and LPC-P selected have never been previously reported as altered in mTBI. The observed lipid alterations indicate that neuroinflammation, oxidative stress and disrupted sodium-potassium pumps are important pathologies that could serve to explain cognitive deficits associated with rmTBI. Therapeutics which target or attenuate these pathologies may be beneficial to limit persistent damage following a mild brain injury event.
PubMed: 38328252
DOI: 10.1101/2024.01.25.577203 -
The Journal of Organic Chemistry Oct 2023Plasmalogens (Pls) are vinyl ether-containing glycerophospholipids of broad biological interest. Their abnormal levels are associated with neurological disorders and...
Plasmalogens (Pls) are vinyl ether-containing glycerophospholipids of broad biological interest. Their abnormal levels are associated with neurological disorders and cardiovascular diseases. The intricacy of analyzing Pls in lipid samples arises from the wide variety of other coexisting lipid species, which underscores the urgent need for a Pls-specific labeling reaction. To address this challenge, we report an efficient hetero-Diels-Alder cycloaddition reaction between nonterminal vinyl ethers of Pls and -quinolinone quinone methide probes under mild conditions. On the basis of this mechanism, a selective fluorescent labeling method for Pls is developed. The application of this method permits the exclusive derivatization of Pls over other human plasma lipids. The process also imparts labeled Pls with distinct fluorescence emission and chromatographic retention properties. By integrating this method with high-performance liquid chromatography, we are able to identify individual chromatographic signatures of Pls from 10 different human plasma samples. This Pls signature analytical technique, empowered by the Pls-specific labeling reaction, is cost-effective and simple in terms of instrumentation, suggesting its promising potential for the early screening and diagnosis of diseases linked to Pls abnormalities.
PubMed: 37710996
DOI: 10.1021/acs.joc.3c01380 -
Lipids in Health and Disease Jun 2024Lipids, including phospholipids and bile acids, exert various signaling effects and are thought to contribute to the development of coronary artery disease (CAD). Here,... (Observational Study)
Observational Study
BACKGROUND
Lipids, including phospholipids and bile acids, exert various signaling effects and are thought to contribute to the development of coronary artery disease (CAD). Here, we aimed to compare lipidomic and bile acid profiles in the blood of patients with and without CAD stratified by sex.
METHODS
From 2015 to 2022, 3,012 patients who underwent coronary angiography were recruited in the INTERCATH cohort. From the overall cohort, subgroups were defined using patient characteristics such as CAD vs. no CAD, 1st vs. 3rd tertile of LDL-c, and female vs. male sex. Hereafter, a matching algorithm based on age, BMI, hypertension status, diabetes mellitus status, smoking status, the Mediterranean diet score, and the intake of statins, triglycerides, HDL-c and hs-CRP in a 1:1 ratio was implemented. Lipidomic analyses of stored blood samples using the Lipidyzer platform (SCIEX) and bile acid analysis using liquid chromatography with tandem mass spectrometry (LC‒MS/MS) were carried out.
RESULTS
A total of 177 matched individuals were analyzed; the median ages were 73.5 years (25th and 75th percentile: 64.1, 78.2) and 71.9 years (65.7, 77.2) for females and males with CAD, respectively, and 67.6 years (58.3, 75.3) and 69.2 years (59.8, 76.8) for females and males without CAD, respectively. Further baseline characteristics, including cardiovascular risk factors, were balanced between the groups. Women with CAD had decreased levels of phosphatidylcholine and diacylglycerol, while no differences in bile acid profiles were detected in comparison to those of female patients without CAD. In contrast, in male patients with CAD, decreased concentrations of the secondary bile acid species glycolithocholic and lithocholic acid, as well as altered levels of specific lipids, were detected compared to those in males without CAD. Notably, male patients with low LDL-c and CAD had significantly greater concentrations of various phospholipid species, particularly plasmalogens, compared to those in high LDL-c subgroup.
CONCLUSIONS
We present hypothesis-generating data on sex-specific lipidomic patterns and bile acid profiles in CAD patients. The data suggest that altered lipid and bile acid composition might contribute to CAD development and/or progression, helping to understand the different disease trajectories of CAD in women and men.
REGISTRATION
https://clinicaltrials.gov/ct2/show/NCT04936438 , Unique identifier: NCT04936438.
Topics: Aged; Female; Humans; Male; Middle Aged; Bile Acids and Salts; Cholesterol, HDL; Cholesterol, LDL; Coronary Artery Disease; Lipidomics; Sex Characteristics; Sex Factors; Tandem Mass Spectrometry; Triglycerides; Cohort Studies
PubMed: 38926753
DOI: 10.1186/s12944-024-02184-z -
Frontiers in Chemistry 2024Traumatic brain injury (TBI) is a global public health problem with 50-60 million incidents per year, most of which are considered mild (mTBI) and many of these...
Traumatic brain injury (TBI) is a global public health problem with 50-60 million incidents per year, most of which are considered mild (mTBI) and many of these repetitive (rmTBI). Despite their massive implications, the pathologies of mTBI and rmTBI are not fully understood, with a paucity of information on brain lipid dysregulation following mild injury event(s). To gain more insight on mTBI and rmTBI pathology, a non-targeted spatial lipidomics workflow utilizing high resolution mass spectrometry imaging was developed to map brain region-specific lipid alterations in rats following injury. Discriminant multivariate models were created for regions of interest including the hippocampus, cortex, and corpus callosum to pinpoint lipid species that differentiated between injured and sham animals. A multivariate model focused on the hippocampus region differentiated injured brain tissues with an area under the curve of 0.99 using only four lipid species. Lipid classes that were consistently discriminant included polyunsaturated fatty acid-containing phosphatidylcholines (PC), lysophosphatidylcholines (LPC), LPC-plasmalogens (LPC-P) and PC potassium adducts. Many of the polyunsaturated fatty acid-containing PC and LPC-P selected have never been previously reported as altered in mTBI. The observed lipid alterations indicate that neuroinflammation and oxidative stress are important pathologies that could serve to explain cognitive deficits associated with rmTBI. Therapeutics which target or attenuate these pathologies may be beneficial to limit persistent damage following a mild brain injury event.
PubMed: 38873407
DOI: 10.3389/fchem.2024.1394064