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Microbial Biotechnology Feb 2022Biofilms are communities of bacteria, fungi or yeasts that form on diverse biotic or abiotic surfaces, and play important roles in pathogenesis and drug resistance. A...
Biofilms are communities of bacteria, fungi or yeasts that form on diverse biotic or abiotic surfaces, and play important roles in pathogenesis and drug resistance. A generic saw palmetto oil inhibited biofilm formation by Staphylococcus aureus, Escherichia coli O157:H7 and fungal Candida albicans without affecting their planktonic cell growth. Two main components of the oil, lauric acid and myristic acid, are responsible for this antibiofilm activity. Their antibiofilm activities were observed in dual-species biofilms as well as three-species biofilms of S. aureus, E. coli O157:H7 and C. albicans. Transcriptomic analysis showed that lauric acid and myristic acid repressed the expressions of haemolysin genes (hla and hld) in S. aureus, several biofilm-related genes (csgAB, fimH and flhD) in E. coli and hypha cell wall gene HWP1 in C. albicans, which supported biofilm inhibition. Also, saw palmetto oil, lauric acid and myristic acid reduced virulence of three microbes in a nematode infection model and exhibited minimal cytotoxicity. Furthermore, combinatorial treatment of fatty acids and antibiotics showed synergistic antibacterial efficacy against S. aureus and E. coli O157:H7. These results demonstrate that saw palmetto oil and its main fatty acids might be useful for controlling bacterial infections as well as multispecies biofilms.
Topics: Anti-Bacterial Agents; Biofilms; Candida albicans; Escherichia coli O157; Lauric Acids; Myristic Acid; Plant Extracts; Serenoa; Staphylococcus aureus
PubMed: 34156757
DOI: 10.1111/1751-7915.13864 -
Frontiers in Molecular Biosciences 2022Gestational diabetes mellitus (GDM) is a disorder which manifests itself for the first time during pregnancy and is mainly connected with glucose metabolism. It is also...
Gestational diabetes mellitus (GDM) is a disorder which manifests itself for the first time during pregnancy and is mainly connected with glucose metabolism. It is also known that fatty acid profile changes in erythrocyte membranes and plasma could be associated with obesity and insulin resistance. These factors can lead to the development of diabetes. In the reported study, we applied the untargeted analysis of plasma in GDM against standard glucose-tolerant (NGT) women to identify the differences in metabolomic profiles between those groups. We found higher levels of 2-hydroxybutyric and 3-hydroxybutyric acids. Both secondary metabolites are associated with impaired glucose metabolism. However, they are products of different metabolic pathways. Additionally, we applied lipidomic profiling using gas chromatography to examine the fatty acid composition of cholesteryl esters in the plasma of GDM patients. Among the 14 measured fatty acids characterizing the representative plasma lipidomic cluster, myristic, oleic, arachidonic, and α-linoleic acids revealed statistically significant changes. Concentrations of both myristic acid, one of the saturated fatty acids (SFAs), and oleic acid, which belong to monounsaturated fatty acids (MUFAs), tend to decrease in GDM patients. In the case of polyunsaturated fatty acids (PUFAs), some of them tend to increase (e.g., arachidonic), and some of them tend to decrease (e.g., α-linolenic). Based on our results, we postulate the importance of hydroxybutyric acid derivatives, cholesteryl ester composition, and the oleic acid diminution in the pathophysiology of GDM. There are some evidence suggests that the oleic acid can have the protective role in diabetes onset. However, metabolic alterations that lead to the onset of GDM are complex; therefore, further studies are needed to confirm our observations.
PubMed: 36685282
DOI: 10.3389/fmolb.2022.997436 -
International Journal of Molecular... Jan 2018Acute fatty liver of pregnancy (AFLP), a catastrophic illness for both the mother and the unborn offspring, develops in the last trimester of pregnancy with significant... (Review)
Review
Acute fatty liver of pregnancy (AFLP), a catastrophic illness for both the mother and the unborn offspring, develops in the last trimester of pregnancy with significant maternal and perinatal mortality. AFLP is also recognized as an obstetric and medical emergency. Maternal AFLP is highly associated with a fetal homozygous mutation (1528G>C) in the gene that encodes for mitochondrial long-chain hydroxy acyl-CoA dehydrogenase (LCHAD). The mutation in LCHAD results in the accumulation of 3-hydroxy fatty acids, such as 3-hydroxy myristic acid, 3-hydroxy palmitic acid and 3-hydroxy dicarboxylic acid in the placenta, which are then shunted to the maternal circulation leading to the development of acute liver injury observed in patients with AFLP. In this review, we will discuss the mechanistic role of increased 3-hydroxy fatty acid in causing lipotoxicity to the liver and in inducing oxidative stress, mitochondrial dysfunction and hepatocyte lipoapoptosis. Further, we also review the role of 3-hydroxy fatty acids in causing placental damage, pancreatic islet β-cell glucolipotoxicity, brain damage, and retinal epithelial cells lipoapoptosis in patients with LCHAD deficiency.
Topics: Acyl-CoA Dehydrogenase, Long-Chain; Fatty Acids; Fatty Liver; Female; Humans; Lipid Metabolism; Lipid Metabolism, Inborn Errors; Maternal Exposure; Mutation; Oxidation-Reduction; Oxidative Stress; Phenotype; Pregnancy; Pregnancy Complications
PubMed: 29361796
DOI: 10.3390/ijms19010322 -
Frontiers in Endocrinology 2023Dyslipidemia is a feature of polycystic ovary syndrome (PCOS) that may augment metabolic disturbances. Serum fatty acids are important biomedical indicators of...
PURPOSE
Dyslipidemia is a feature of polycystic ovary syndrome (PCOS) that may augment metabolic disturbances. Serum fatty acids are important biomedical indicators of dyslipidemia. The aim of this study was to determine the distinct serum fatty acids in various PCOS subtypes and their association with metabolic risk in women with PCOS.
METHODS
Fatty acids in the serum of 202 women with PCOS were measured using gas chromatography-mass spectrometry. Fatty acids were compared between PCOS subtypes and correlated with glycemic parameters, adipokines, homocysteine, sex hormones, and sex hormone-binding globulin (SHBG).
RESULTS
The levels of total monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs) in the reproductive subtype of PCOS were lower than those in the metabolic subtype. Docosahexaenoic acid, a PUFA, was associated with higher SHBG after correction for multiple comparisons. Eighteen species of fatty acids emerged as potential biomarkers associated with the metabolic risk factors measured, independent of body mass index (BMI). Among them, myristic acid (C14:0), palmitoleic acid (C16:1), oleic acid (C18:1n-9C), cis-vaccenic acid (C18:1n-7), and homo-gamma-linolenic acid (C20:3n-6) were the strongest lipid species that were consistently associated with metabolic risk factors, particularly insulin-related parameters in women with PCOS. As for adipokines, 16 fatty acids were positively associated with serum leptin. Among them, C16:1 and C20:3n-6were significantly associated with leptin levels.
CONCLUSION
Our data demonstrated that a distinct fatty acid profile comprising high C14:0, C16:1, C18:1n-9C, C18:1n-7, and C20:3n-6levels is associated with metabolic risk in women with PCOS, independent of BMI.
Topics: Humans; Female; Fatty Acids; Polycystic Ovary Syndrome; Leptin; Fatty Acids, Unsaturated; Insulin
PubMed: 37065734
DOI: 10.3389/fendo.2023.1077590 -
Frontiers in Oncology 2023Urine metabolomics has been a promising technique in the liquid biopsy of urothelial cancer (UC). The comparison of upper tract urothelial cancer (UTUC), lower tract...
INTRODUCTION
Urine metabolomics has been a promising technique in the liquid biopsy of urothelial cancer (UC). The comparison of upper tract urothelial cancer (UTUC), lower tract urothelial cancer (BCa), and healthy controls (HCs) need to be performed to find related biomarkers.
METHODS
In our investigation, urine samples from 35 UTUCs, 44 BCas, and 53 gender- and age-matched HCs were analyzed using liquid chromatography-high resolution mass spectrometry (LC-HRMS). In different groups, the differential metabolites and the disturbed metabolism pathways were explored. Transcriptomics and urine metabolomics are combined to identify the probably disturbed gene in BCa.
RESULTS
With an area under the curve (AUC) of 0.815, the panel consisting of prostaglandin I2, 5-methyldeoxycytidine, 2,6-dimethylheptanoyl carnitine, and deoxyinosine was able to discriminate UC from HCs. With an AUC of 0.845, the validation group also demonstrated strong predictive ability. UTUC and BCa without hematuria could be distinguished using the panel of 5'-methylthioadenosine, L-beta-aspartyl-L-serine, dehydroepiandrosterone sulfate, and N'-formylkynurenine (AUC=0.858). The metabolite panel comprising aspartyl-methionine, 7-methylinosine, and alpha-CEHC glucuronide could discriminate UTUC from BCa with hematuria with an AUC of 0.83. Fatty acid biosynthesis, purine metabolism, tryptophan metabolism, pentose and glucuronate interconversions, and arachidonic acid metabolism were dysregulated when comparing UC with HCs. PTGIS and BCHE, the genes related to the metabolism of prostaglandin I2 and myristic acid respectively, were significantly associated with the survival of BCa.
DISCUSSION
Not only could LC-HRMS urine metabolomic investigations distinguish UC from HCs, but they could also identify UTUC from BCa. Additionally, urine metabolomics combined with transcriptomics can find out the potential aberrant genes in the metabolism.
PubMed: 37256175
DOI: 10.3389/fonc.2023.1160965 -
Novel Interactions of Myristic Acid and Variants Predict Atopic Dermatitis among Indonesian Infants.Nutrients Nov 2022Fatty acids exert a range of different biological activities that could be relevant in the development of atopic dermatitis (AD). This study investigated the association...
Fatty acids exert a range of different biological activities that could be relevant in the development of atopic dermatitis (AD). This study investigated the association of glycerophospholipid fatty acids (GPL-FA) with AD, and their interactions with single nucleotide polymorphisms (SNP) of the gene cluster. Among 390 infants of the Indonesian ISADI study, GPL-FA were measured in umbilical plasma (P-0y) and in buccal cells at birth (B-0y), and again in buccal cells at AD onset or one year (B-1y). Prospective and cross-sectional associations with AD were assessed by logistic regression. Interactions of GPL-FA with 14 SNP were tested assuming an additive model. AD was diagnosed in 15.4% of participants. In B-1y, C18:2n-6 was inversely associated with AD; and positive associations were observed for C18:1n-9, C20:4n-6, C22:6n-3 and C20:4n-6/C18:2n-6. There were no prospective associations with AD, however, a significant interaction between the SNP rs174449 and B-0y C14:0 (myristic acid) was observed. This study indicates that Indonesian infants with AD have increased rates of endogenous long-chain polyunsaturated fatty acid production, as well as higher C18:1n-9 levels. GPL-FA measured at birth do not predict later AD incidence; however, genotype interactions reveal novel effects of myristic acid, which are modified by a variant.
Topics: Infant; Infant, Newborn; Humans; Dermatitis, Atopic; Cross-Sectional Studies; Myristic Acid; Indonesia; Mouth Mucosa; Fatty Acids; Glycerophospholipids; Fatty Acid Desaturases
PubMed: 36364938
DOI: 10.3390/nu14214676 -
Scientific Reports Aug 2016Protein N-myristoylation is catalysed by N-myristoyltransferase (NMT), an essential and druggable target in Trypanosoma cruzi, the causative agent of Chagas' disease....
Protein N-myristoylation is catalysed by N-myristoyltransferase (NMT), an essential and druggable target in Trypanosoma cruzi, the causative agent of Chagas' disease. Here we have employed whole cell labelling with azidomyristic acid and click chemistry to identify N-myristoylated proteins in different life cycle stages of the parasite. Only minor differences in fluorescent-labelling were observed between the dividing forms (the insect epimastigote and mammalian amastigote stages) and the non-dividing trypomastigote stage. Using a combination of label-free and stable isotope labelling of cells in culture (SILAC) based proteomic strategies in the presence and absence of the NMT inhibitor DDD85646, we identified 56 proteins enriched in at least two out of the three experimental approaches. Of these, 6 were likely to be false positives, with the remaining 50 commencing with amino acids MG at the N-terminus in one or more of the T. cruzi genomes. Most of these are proteins of unknown function (32), with the remainder (18) implicated in a diverse range of critical cellular and metabolic functions such as intracellular transport, cell signalling and protein turnover. In summary, we have established that 0.43-0.46% of the proteome is N-myristoylated in T. cruzi approaching that of other eukaryotic organisms (0.5-1.7%).
Topics: Myristic Acid; Protein Processing, Post-Translational; Proteome; Protozoan Proteins; Trypanosoma cruzi
PubMed: 27492267
DOI: 10.1038/srep31078 -
The Journal of Maternal-fetal &... Jul 2020Unbound free fatty acids (FFAu) are the bioactive fraction of plasma free fatty acids (FFA). Most plasma FFA are bound to albumin. Only when FFA dissociate from...
Unbound free fatty acids (FFAu) are the bioactive fraction of plasma free fatty acids (FFA). Most plasma FFA are bound to albumin. Only when FFA dissociate from albumin, do they become biologically active. To measure the first FFAu profiles in human infants and to measure these profiles before and during intravenous administration of the soybean lipid, intralipid (IL). The study population was 16 premature infants, from a parent study of 130 infants with birth weights 500-2000 g and gestational age 23-34 weeks. The infants chosen had plasma samples of ≥120 µL (volume needed for each FFAu profile measurement) in the first day of life. Infants received IL infusions starting in the second day of life at 1 g/kg/day, increasing by 1-g/kg/day daily up to 3 g/kg/day. FFAu profiles were determined during IL infusion when plasma was available. Profiles are the concentrations of the nine most abundant long-chain FFAu and were determined using novel fluorescent probes. Before intralipid infusion unbound myristic acid was the dominant FFAu, as high as 78% of the total FFAu (sum of the 9 FFAu). In contrast, unbound linoleic acid was 0% in all infants. With increasing infusion of IL to 3 g/kg/day, unbound linoleic increased to 26% of the total FFAu, with unbound oleic, myristic, and linolenic acid the second, third and fourth most abundant. The average total FFAu concentration also increased from 4 nM before intralipid to 53 nM at 3 g/kg/day. During IL infusion the FFAu profiles approached the fatty acid composition of intralipid at 3 g/kg/day. This first study of FFAu profiles in neonates revealed that before IL infusion unbound linoleic acid was zero in all 16 infants and levels of myristic acid were exceptionally large, as much as 78% of the total FFAu profile. These results suggest important and previously unrecognized roles of lipid metabolism in early development. Zero unbound linoleic acid before IL infusion may help promote closure of the ductus arteriosus but after IL infusion, synthesis of arachidonic from linoleic acid may tend to promote patency. The high levels of unbound myristate may be needed for immediate neonatal energy needs.
Topics: Bilirubin; Emulsions; Fat Emulsions, Intravenous; Fatty Acids, Nonesterified; Humans; Infant, Extremely Premature; Infant, Newborn; Infant, Very Low Birth Weight; Linoleic Acid; Myristic Acid; Phospholipids; Soybean Oil
PubMed: 30554540
DOI: 10.1080/14767058.2018.1548599 -
Materials (Basel, Switzerland) Aug 2023This study aimed to address the issue of high-temperature challenges in asphalt pavement by developing two types of phase change materials (PCMs) for temperature...
This study aimed to address the issue of high-temperature challenges in asphalt pavement by developing two types of phase change materials (PCMs) for temperature control. Encapsulated paraffin wax particles (EPWP) and encapsulated myristic acid particles (EMAP) were synthesized using acid-etched ceramsite (AECS) as the carrier, paraffin wax (PW) or myristic acid (MA) as the core material, and a combination of epoxy resin and cement as the encapsulation material. The investigation encompassed leakage tests on PCMs; rutting plate rolling forming tests; SEM, FTIR, XRD, and TG-DSC microscopic tests; as well as heat storage and release tests and temperature control assessments using a light heating device. The study revealed the following key findings. Both types of PCMs exhibited no PCM leakage even under high temperatures and demonstrated low crushing ratios during rut-forming tests. Microscopic evaluations confirmed the chemical stability and phase compatibility of the constituents within the two types of PCMs. Notably, the phase change enthalpies of EPWP and EMAP were relatively high, measuring 133.31 J/g and 138.52 J/g, respectively. The utilization of AECS as the carrier for PCMs led to a substantial 4.61-fold increase in the adsorption rate. Moreover, the PCMs showcased minimal mass loss at 180 °C, rendering them suitable for asphalt pavement applications. The heat storage and release experiments further underscored the PCMs' capacity to regulate ambient temperatures through heat absorption and release. When subjected to light heating, the maximum temperatures of the two types of phase change Marshall specimens were notably lower by 6.6 °C and 4.8 °C, respectively, compared to standard Marshall specimens. Based on comprehensive testing, EPWP displayed enhanced adaptability and demonstrated substantial potential for practical implementation in asphalt pavements.
PubMed: 37687694
DOI: 10.3390/ma16176002 -
Chemical Science Mar 2023Protein-protein interactions (PPIs) are essential and pervasive regulatory elements in biology. Despite the development of a range of techniques to probe PPIs in living...
Protein-protein interactions (PPIs) are essential and pervasive regulatory elements in biology. Despite the development of a range of techniques to probe PPIs in living systems, there is a dearth of approaches to capture interactions driven by specific post-translational modifications (PTMs). Myristoylation is a lipid PTM added to more than 200 human proteins, where it may regulate membrane localization, stability or activity. Here we report the design and synthesis of a panel of novel photocrosslinkable and clickable myristic acid analog probes, and their characterization as efficient substrates for human -myristoyltransferases NMT1 and NMT2, both biochemically and through X-ray crystallography. We demonstrate metabolic incorporation of probes to label NMT substrates in cell culture and intracellular photoactivation to form a covalent crosslink between modified proteins and their interactors, capturing a snapshot of interactions in the presence of the lipid PTM. Proteomic analyses revealed both known and multiple novel interactors of a series of myristoylated proteins, including ferroptosis suppressor protein 1 (FSP1) and spliceosome-associated RNA helicase DDX46. The concept exemplified by these probes offers an efficient approach for exploring the PTM-specific interactome without the requirement for genetic modification, which may prove broadly applicable to other PTMs.
PubMed: 36873846
DOI: 10.1039/d2sc06116c