PubMed
Metabolomic Profiles Associated with Obesity and Periodontitis during Pregnancy: Cross-Sectional Study with Proton Nuclear Magnetic Resonance (<sup>1</sup>H-NMR)-Based Analysis
Metabolites. 2022 Oct 27;12(11):1029. doi: 10.3390/metabo12111029.ABSTRACTThis study aimed to elucidate the metabolomic signature associated with obesity and periodontitis during pregnancy in plasma and saliva biofluids. Ninety-eight pregnant women were divided into: with obesity and periodontitis (OP = 20), with obesity but without periodontitis (OWP = 27), with normal BMI but with periodontitis (NP = 21), with normal BMI and without periodontitis (NWP = 30). Saliva and plasma were analyzed by 1H-NMR for metabolites identification. Partial Least Squares-Discriminant Analysis (PLS-DA), Sparse PLS-DA (sPLS-DA), and Variable Importance of Projection (VIP) were performed. ANOVA and Pearson's correlation were applied (p < 0.05). Plasmatic analysis indicated the levels of glucose (p = 0.041) and phenylalanine (p = 0.015) were positively correlated with periodontal parameters and BMI, respectively. In saliva, periodontitis was mainly associated with high levels of acetic acid (p = 0.024), isovaleric acid, butyric acid, leucine, valine, isoleucine, and propionic acid (p < 0.001). High salivary concentrations of glycine (p = 0.015), succinic acid (p = 0.015), and lactate (p = 0.026) were associated with obesity. Saliva demonstrated a more elucidative difference than plasma, indicating the glucose-alanine cycle, alanine metabolism, valine, leucine and isoleucine degradation, glutamate metabolism, and Warburg effect as the main metabolic pathways.PMID:36355112 | DOI:10.3390/metabo12111029
Signatures of Mitochondrial Dysfunction and Impaired Fatty Acid Metabolism in Plasma of Patients with Post-Acute Sequelae of COVID-19 (PASC)
Metabolites. 2022 Oct 26;12(11):1026. doi: 10.3390/metabo12111026.ABSTRACTExercise intolerance is a major manifestation of post-acute sequelae of severe acute respiratory syndrome coronavirus infection (PASC, or "long-COVID"). Exercise intolerance in PASC is associated with higher arterial blood lactate accumulation and lower fatty acid oxidation rates during graded exercise tests to volitional exertion, suggesting altered metabolism and mitochondrial dysfunction. It remains unclear whether the profound disturbances in metabolism that have been identified in plasma from patients suffering from acute coronavirus disease 2019 (COVID-19) are also present in PASC. To bridge this gap, individuals with a history of previous acute COVID-19 infection that did not require hospitalization were enrolled at National Jewish Health (Denver, CO, USA) and were grouped into those that developed PASC (n = 29) and those that fully recovered (n = 16). Plasma samples from the two groups were analyzed via mass spectrometry-based untargeted metabolomics and compared against plasma metabolic profiles of healthy control individuals (n = 30). Observational demographic and clinical data were retrospectively abstracted from the medical record. Compared to plasma of healthy controls or individuals who recovered from COVID-19, PASC plasma exhibited significantly higher free- and carnitine-conjugated mono-, poly-, and highly unsaturated fatty acids, accompanied by markedly lower levels of mono-, di- and tricarboxylates (pyruvate, lactate, citrate, succinate, and malate), polyamines (spermine) and taurine. Plasma from individuals who fully recovered from COVID-19 exhibited an intermediary metabolic phenotype, with milder disturbances in fatty acid metabolism and higher levels of spermine and taurine. Of note, depletion of tryptophan-a hallmark of disease severity in COVID-19-is not normalized in PASC patients, despite normalization of kynurenine levels-a tryptophan metabolite that predicts mortality in hospitalized COVID-19 patients. In conclusion, PASC plasma metabolites are indicative of altered fatty acid metabolism and dysfunctional mitochondria-dependent lipid catabolism. These metabolic profiles obtained at rest are consistent with previously reported mitochondrial dysfunction during exercise, and may pave the way for therapeutic intervention focused on restoring mitochondrial fat-burning capacity.PMID:36355108 | DOI:10.3390/metabo12111026
Revealing the Phenolic Acids in <em>Cardamine violifolia</em> Leaves by Transcriptome and Metabolome Analyses
Metabolites. 2022 Oct 26;12(11):1024. doi: 10.3390/metabo12111024.ABSTRACTCardamine violifolia, a species belonging to the Brassicaceae family, is a selenium hyperaccumulator and a nutritious leafy vegetable. Our previous study showed that C. violifolia leaves are rich in total phenolic acids, but the composition and corresponding genes remain unknown. In this study, we investigated the phenolic acid compounds and potential gene regulation network in the outer leaves (OL) and central leaves (CL) of C. violifolia using transcriptome and metabolome analyses. Results showed that the OL contained a higher total phenolic acid content than the CL. Metabolome analysis revealed a total of 115 phenolic acids, 62 of which (e.g., arbutin, rosmarinic acid, hydroxytyrosol acetate, and sinapic acid) were differentially accumulated between the CL and OL of C. violifolia. Transcriptome analysis showed that the differentially expressed genes were significantly enriched in the pathways of secondary metabolite biosynthesis and phenylpropanoid biosynthesis. Conjoint analysis of the transcriptome and metabolome indicated that seven genes (CYP84A1, CYP84A4, CADH9, SGT1, UGT72E1, OMT1, and CCR2) and eight phenolic acids (sinapic acid, sinapyl alcohol, 5-O-caffeoylshikimic acid, sinapoyl malate, coniferin, coniferyl alcohol, L-phenylalanine, and ferulic acid) constituted a possible regulatory network. This study revealed the phenolic acid compounds and possible regulatory network of C. violifolia leaves and deepened our understanding of its nutrient value.PMID:36355107 | DOI:10.3390/metabo12111024
Preliminary Investigation of the Effect of Maceration Procedures on Bone Metabolome and Lipidome
Metabolites. 2022 Oct 25;12(11):1020. doi: 10.3390/metabo12111020.ABSTRACTThe study of post-mortem changes is a crucial component of forensic investigation. Human forensic taphonomic facilities (HFTFs) are the only institutions allowing the design and execution of controlled human decomposition experiments. When bodies are skeletonized, bones are normally stored in skeletal collections and used for anthropological studies. However, HFTFs apply chemical and/or thermal treatments to the remains prior bone long-term storage. These treatments are believed to alter heavily the original biochemical and molecular signature of bone material. The present study aims to evaluate the effect of these procedures on the bone metabolome and lipidome by using an animal bone model. Three intact bovine tibiae were processed using three protocols routinely applied at HFTFs, and their three counterparts were used as non-treated controls. Bone powder samples were subjected to biphasic extraction and both metabolites and lipids were analysed via liquid chromatography tandem mass-spectrometry. Results showed severe reductions in the abundances of both metabolites and lipids, and the presence of contamination introduced by cleaning agents. Despite the preliminary nature of the study, we demonstrated that the biochemical profile of bone is heavily affected by the maceration procedures. Ideally, these treatments should be avoided, or replaced by minimally invasive procedures agreed across HFTFs.PMID:36355103 | DOI:10.3390/metabo12111020
A New Mechanism for Ginsenoside Rb1 to Promote Glucose Uptake, Regulating Riboflavin Metabolism and Redox Homeostasis
Metabolites. 2022 Oct 23;12(11):1011. doi: 10.3390/metabo12111011.ABSTRACTGlucose absorption promoters perform insulin mimic functions to enhance blood glucose transport to skeletal muscle cells and accelerate glucose consumption, thereby reducing blood glucose levels. In our screening exploration of food ingredients for improving glucose transportation and metabolism, we found that the saponins in American ginseng (Panaxquinquefolius L.) showed potential activity to promote glucose uptake, which can be used for stabilizing levels of postprandial blood glucose. The aim of this study was to identify key components of American ginseng with glucose uptake-promoting activity and to elucidate their metabolic regulatory mechanisms. Bio-guided isolation using zebrafish larvae and 2-NBDG indicator identified ginsenoside Rb1 (GRb1) as the most potential promotor of glucose uptake. Using UPLC-QTOF-MS/MS combined with RT-qPCR and phenotypic verification, we found that riboflavin metabolism is the hinge for GRb1-mediated facilitation of glucose transport. GRb1-induced restoration of redox homeostasis was mediated by targeting riboflavin transporters (SLC52A1 and SLC52A3) and riboflavin kinase (RFK).PMID:36355094 | DOI:10.3390/metabo12111011
Integrated Metabolomic and Transcriptomic Analyses Reveal the Basis for Carotenoid Biosynthesis in Sweet Potato (<em>Ipomoea batatas</em> (L.) Lam.) Storage Roots
Metabolites. 2022 Oct 23;12(11):1010. doi: 10.3390/metabo12111010.ABSTRACTCarotenoids are important compounds of quality and coloration within sweet potato storage roots, but the mechanisms that govern the accumulation of these carotenoids remain poorly understood. In this study, metabolomic and transcriptomic analyses of carotenoids were performed using young storage roots (S2) and old storage roots (S4) from white-fleshed (variety S19) and yellow-fleshed (variety BS) sweet potato types. S19 storage roots exhibited significantly lower total carotenoid levels relative to BS storage roots, and different numbers of carotenoid types were detected in the BS-S2, BS-S4, S19-S2, and S19-S4 samples. β-cryptoxanthin was identified as a potential key driver of differences in root coloration between the S19 and BS types. Combined transcriptomic and metabolomic analyses revealed significant co-annotation of the carotenoid and abscisic acid (ABA) metabolic pathways, PSY (phytoene synthase), CHYB (β-carotene 3-hydroxylase), ZEP (zeaxanthin epoxidase), NCED3 (9-cis-epoxycarotenoid dioxygenase 3), ABA2 (xanthoxin dehydrogenase), and CYP707A (abscisic acid 8'-hydroxylase) genes were found to be closely associated with carotenoid and ABA content in these sweet potato storage roots. The expression patterns of the transcription factors OFP and FAR1 were associated with the ABA content in these two sweet potato types. Together, these results provide a valuable foundation for understanding the mechanisms governing carotenoid biosynthesis in storage roots, and offer a theoretical basis for sweet potato breeding and management.PMID:36355093 | DOI:10.3390/metabo12111010
Computational Metabolomics Tools Reveal Subarmigerides, Unprecedented Linear Peptides from the Marine Sponge Holobiont <em>Callyspongia subarmigera</em>
Mar Drugs. 2022 Oct 27;20(11):673. doi: 10.3390/md20110673.ABSTRACTA detailed examination of a unique molecular family, restricted to the Callyspongia genus, in a molecular network obtained from an in-house Haplosclerida marine sponge collection (including Haliclona, Callyspongia, Xestospongia, and Petrosia species) led to the discovery of subarmigerides, a series of rare linear peptides from Callyspongia subarmigera, a genus mainly known for polyacetylenes and lipids. The structure of the sole isolated peptide, subarmigeride A (1) was elucidated through extensive 1D and 2D NMR spectroscopy, HRMS/MS, and Marfey's method to assign its absolute configuration. The putative structures of seven additional linear peptides were proposed by an analysis of their respective MS/MS spectra and a comparison of their fragmentation patterns with the heptapeptide 1. Surprisingly, several structurally related analogues of subarmigeride A (1) occurred in one distinct cluster from the molecular network of the cyanobacteria strains of the Guadeloupe mangroves, suggesting that the true producer of this peptide family might be the microbial sponge-associated community, i.e., the sponge-associated cyanobacteria.PMID:36354996 | DOI:10.3390/md20110673
New Insights into the Mechanism of <em>Trichoderma virens</em>-Induced Developmental Effects on <em>Agrostis stolonifera</em> Disease Resistance against Dollar Spot Infection
J Fungi (Basel). 2022 Nov 10;8(11):1186. doi: 10.3390/jof8111186.ABSTRACTTrichoderma is internationally recognized as a biocontrol fungus for its broad-spectrum antimicrobial activity. Intriguingly, the crosstalk mechanism between the plant and Trichoderma is dynamic, depending on the Trichoderma strains and the plant species. In our previous study, the Trichoderma virens 192-45 strain showed better pathogen inhibition through the secretive non-volatile and volatile substrates. Therefore, we studied transcriptional and metabolic responses altered in creeping bentgrass (Agrostis stolonifera L.) with T. virens colonization prior to a challenge with Clarireedia homoeocarpa. This fungal pathogen causes dollar spot on various turfgrasses. When the pathogen is deficient, the importance of T. virens to the enhancement of plant growth can be seen in hormonal production and microbe signaling, such as indole-3-acrylic acid. Therefore, these substrates secreted by T. virens and induced genes related to plant growth can be the 'pre-defense' for ensuing pathogen attacks. During C. homoeocarpa infection, the Trichoderma-plant interaction activates defense responses through the SA- and/or JA-dependent pathway, induced by T. virens and its respective exudates, such as oleic, citric, and stearic acid. Thus, we will anticipate a combination of genetic engineering and exogenous application targeting these genes and metabolites, which could make creeping bentgrass more resistant to dollar spot and other pathogens.PMID:36354953 | DOI:10.3390/jof8111186
Morphological, Molecular and Metabolic Characterization of the Pigmented Fungus <em>Subramaniula asteroids</em>
J Fungi (Basel). 2022 Oct 29;8(11):1149. doi: 10.3390/jof8111149.ABSTRACTChaetomiaceae fungi are ascosporulating fungi whose importance as human pathogens has been frequently ignored. In the current study, a new isolate of the genus Subramaniula was described. The fungus was isolated from the soil of Wadi Om Nefa'a, Hurghada in the Red Sea Governorate, Egypt. Previously, Subramaniula were misidentified as Papulaspora spp. According to molecular analysis, the fungus was identified as Subramaniula asteroids OP484336. Remarkably, this species has been found among other fungi responsible for keratitis in humans and has been recorded for the first time in Egypt. Analysing the Subramaniula asteroids' metabolic profile was one of the objectives of the current study because little is known about this family's metabolome. The fungal extract's untargeted metabolic profiling was carried out by gas chromatography-mass spectroscopy (GC/MS), 1H and 1H-HSQC nuclear magnetic resonance (NMR) data, and their corresponding databases. In total, fifty-nine metabolites have been reported in the polar and non-polar extracts. The majority of polar metabolites are amino acids and carbohydrates. The non-polar extract's main components were 1-dodecanamine, N,N-dimethyl-, 1-tetradecanamine, N,N-dimethyl-, and 9-octadecenoic acid ethyl ester. The current study is the first to provide a metabolic profile of Subramaniula asteroids, which can be used in chemotaxonomical classification, antifungal drug development, and biological activity investigation of the studied species.PMID:36354915 | DOI:10.3390/jof8111149
Remodeling of the Enterococcal Cell Envelope during Surface Penetration Promotes Intrinsic Resistance to Stress
mBio. 2022 Nov 10:e0229422. doi: 10.1128/mbio.02294-22. Online ahead of print.ABSTRACTEnterococcus faecalis is a normal commensal of the human gastrointestinal tract (GIT). However, upon disruption of gut homeostasis, this nonmotile bacterium can egress from its natural niche and spread to distal organs. While this translocation process can lead to life-threatening systemic infections, the underlying mechanisms remain largely unexplored. Our prior work showed that E. faecalis migration across diverse surfaces requires the formation of matrix-covered multicellular aggregates and the synthesis of exopolysaccharides, but how enterococcal cells are reprogrammed during this process is unknown. Whether surface penetration endows E. faecalis with adaptive advantages is also uncertain. Here, we report that surface penetration promotes the generation of a metabolically and phenotypically distinct E. faecalis population with an enhanced capacity to endure various forms of extracellular stress. Surface-invading enterococci demonstrated major ultrastructural alterations in their cell envelope characterized by increased membrane glycolipid content. These changes were accompanied by marked induction of specific transcriptional programs enhancing cell envelope biogenesis and glycolipid metabolism. Notably, the surface-invading population demonstrated superior tolerance to membrane-damaging antimicrobials, including daptomycin and β-defensins produced by epithelial cells. Genetic mutations impairing glycolipid biosynthesis sensitized E. faecalis to envelope stressors and reduced the ability of this bacterium to penetrate semisolid surfaces and translocate through human intestinal epithelial cell monolayers. Our study reveals that surface penetration induces distinct transcriptional, metabolic, and ultrastructural changes that equip E. faecalis with enhanced capacity to resist external stressors and thrive in its surrounding environment. IMPORTANCE Enterococcus faecalis inhabits the GIT of multiple organisms, where its establishment could be mediated by the formation of biofilm-like aggregates. In susceptible individuals, this bacterium can overgrow and breach intestinal barriers, a process that may lead to lethal systemic infections. While the formation of multicellular aggregates promotes E. faecalis migration across surfaces, little is known about the metabolic and physiological states of the enterococci encased in these surface-penetrating structures. The present study reveals that E. faecalis cells capable of migrating through semisolid surfaces genetically reprogram their metabolism toward increased cell envelope and glycolipid biogenesis, which confers superior tolerance to membrane-damaging agents. E. faecalis's success as a pathobiont depends on its antimicrobial resistance, as well as on its rapid adaptability to overcome multiple environmental challenges. Thus, targeting adaptive genetic and/or metabolic pathways induced during E. faecalis surface penetration may be useful to better confront infections by this bacterium in the clinic.PMID:36354750 | DOI:10.1128/mbio.02294-22
OMICS in Fodder Crops: Applications, Challenges, and Prospects
Curr Issues Mol Biol. 2022 Nov 3;44(11):5440-5473. doi: 10.3390/cimb44110369.ABSTRACTBiomass yield and quality are the primary targets in forage crop improvement programs worldwide. Low-quality fodder reduces the quality of dairy products and affects cattle's health. In multipurpose crops, such as maize, sorghum, cowpea, alfalfa, and oat, a plethora of morphological and biochemical/nutritional quality studies have been conducted. However, the overall growth in fodder quality improvement is not on par with cereals or major food crops. The use of advanced technologies, such as multi-omics, has increased crop improvement programs manyfold. Traits such as stay-green, the number of tillers per plant, total biomass, and tolerance to biotic and/or abiotic stresses can be targeted in fodder crop improvement programs. Omic technologies, namely genomics, transcriptomics, proteomics, metabolomics, and phenomics, provide an efficient way to develop better cultivars. There is an abundance of scope for fodder quality improvement by improving the forage nutrition quality, edible quality, and digestibility. The present review includes a brief description of the established omics technologies for five major fodder crops, i.e., sorghum, cowpea, maize, oats, and alfalfa. Additionally, current improvements and future perspectives have been highlighted.PMID:36354681 | DOI:10.3390/cimb44110369
The Microbial and Metabolic Signatures of Patients with Stable Coronary Artery Disease
Microbiol Spectr. 2022 Nov 10:e0246722. doi: 10.1128/spectrum.02467-22. Online ahead of print.ABSTRACTGrowing evidence indicates an association between gut dysbiosis and coronary artery disease (CAD). However, the underlying mechanisms relevant to stable CAD (SCAD) pathogenesis, based on microbe-host metabolism interactions, are poorly explored. Here, we constructed a quasi-paired cohort based on the metabolic background of metagenomic samples by the propensity score matching (PSM) principle. Compared to healthy controls (HCs), gut microbiome disturbances were observed in SCAD patients, accompanied by differences in serum metabolome, mainly including elevated acylcarnitine and decreased unsaturated fatty acids in SCAD patients, which implicated the reduced cardiac fatty acid oxidation. Moreover, we identified Ralstonia pickettii as the core strain responsible for impaired microbial homeostasis in SCAD patientsm and may be partly responsible for the decrease of host unsaturated fatty acid levels. These findings highlight the importance of unsaturated fatty acids, R. pickettii, and their interaction in the pathogenesis of SCAD. IMPORTANCE Stable coronary artery disease (SCAD) is an early stage of CAD development. It is important to understand the pathogenesis of SCAD and find out the possible prevention and control targets for delaying the progression of CAD. We observed reduced levels of unsaturated fatty acids (USFAs) in SCAD patients. However, the reduced USFAs may be related to Ralstonia Pickettii, which was the core strain responsible for the impaired gut microbial function in SCAD patients, and further affected the host's cardiovascular health by altering amino acids, vitamin B metabolism, and LPS biosynthesis. These findings not only emphasized the importance of USFAs for cardiovascular health, but also R. Pickettii for maintaining microbial function homeostasis. More importantly, our study revealed, for the first time, that enriched R. Pickettii might be responsible for the reduced USFAs in SCAD patients, which adds new evidence on the role of altered gut microbiota for SCAD formation.PMID:36354350 | DOI:10.1128/spectrum.02467-22
Causality Verification for the Correlation between the Presence of Nonstarter Bacteria and Flavor Characteristics in Soft-Type Ripened Cheeses
Microbiol Spectr. 2022 Nov 10:e0289422. doi: 10.1128/spectrum.02894-22. Online ahead of print.ABSTRACTFlavor characteristics of ripened cheese are established by various bacteria, such as lactic acid bacteria, Actinobacteria, and Proteobacteria, which spontaneously develop during the cheese-manufacturing process. We previously revealed the relationship between bacterial microbiota and flavor components in soft-type ripened cheeses by using a multiomics approach that combined metagenomics and metabolomics; however, we could not establish a causal relationship. This study aimed to substantiate the causal nature of the correlations revealed by the multiomics approach by using cheese-ripening tests with single isolate inoculation. The bacterial diversity and composition in surface mold-ripened cheeses from Japan and France varied, depending on the differences between the milks (pasteurized or raw), cheese positions (core or rind), and manufacturers. Although the volatile compounds did not clearly reflect the distinctive characteristics of the cheese samples, nonstarter lactic acid bacteria, Actinobacteria, and Proteobacteria positively correlated with ketones and sulfur compounds, as evidenced by a Spearman's correlation analysis. Cheese-ripening tests conducted after inoculation with single bacterial strains belonging to the above-mentioned taxa confirmed that these bacteria formed volatile compounds, in agreement with the correlations observed. In particular, various flavor compounds, such as acids, esters, ketones, and sulfur compounds, were detected in cheese inoculated with Pseudoalteromonas sp. TS-4-4 strain. These findings provide important insights into the role of nonstarter bacteria in the development of cheese flavor and into the effectiveness of the multiomics approach in screening for bacteria that can improve the quality of cheese products. IMPORTANCE Our previous study revealed that the existence of various bacteria, such as lactic acid bacteria, Actinobacteria, and Proteobacteria, clearly correlated with the abundance of flavor components, such as volatile compounds, in soft-type ripened cheeses via a multiomics approach that used 16S rRNA gene amplicon sequencing and headspace gas chromatography-mass spectrometry. However, this approach only showed correlations derived from statistical analyses rather than causal relationships. Therefore, in the present study, we performed cheese-ripening tests using nonstarter bacteria to substantiate the correlations revealed by the multiomics approach in soft-type ripened cheese. Our results suggest the capability of nonstarter bacteria, such as Proteobacteria, to impart flavor to cheese and the effectiveness of the multiomics approach in screening for microbial isolates that can improve the quality of cheese. Overall, our research provides new insights into the importance of bacteria in cheese production.PMID:36354338 | DOI:10.1128/spectrum.02894-22
Positively Charged Microplastics Induce Strong Lettuce Stress Responses from Physiological, Transcriptomic, and Metabolomic Perspectives
Environ Sci Technol. 2022 Nov 10. doi: 10.1021/acs.est.2c06054. Online ahead of print.ABSTRACTMicroplastics (MPs) can enter plants through the foliar pathway and are potential hazards to ecosystems and human health. However, studies related to the molecular mechanisms underlying the impact of foliar exposure to differently charged MPs to leafy vegetables are limited. Because the surfaces of MPs in the environment are often charged, we explored the uptake pathways, accumulation concentration of MPs, physiological responses, and molecular mechanisms of lettuce foliarly exposed to MPs carrying positive (MP+) and negative charges (MP-). MPs largely accumulated in the lettuce leaves, and stomatal uptake and cuticle entry could be the main pathways for MPs to get inside lettuce leaves. More MP+ entered lettuce leaves and induced physiological, transcriptomic, and metabolomic changes, including a decrease in biomass and photosynthetic pigments, an increase in reactive oxygen species and antioxidant activities, a differential expression of genes, and a change of metabolite profiles. In particular, MP+ caused the upregulation of circadian rhythm-related genes, and this may play a major role in the greater physiological toxicity of MP+ to lettuce, compared to MP-. These findings provide direct evidence that MPs can enter plant leaves following foliar exposure and a molecular-scale perspective on the response of leafy vegetables to differently charged MPs.PMID:36354282 | DOI:10.1021/acs.est.2c06054
Oral magnesium sulphate administration in rats with minimal hepatic encephalopathy: NMR-based metabolic characterization of the brain
Magnes Res. 2022 Apr 1;35(2):39-50. doi: 10.1684/mrh.2022.0500.ABSTRACTOBJECTIVE: To investigate the metabolic changes in rats with minimal hepatic encephalopathy (MHE) treated with oral magnesium sulphate administration.MATERIALS AND METHODS: A total of 30 Sprague-Dawley rats were divided into a control group and MHE group (further divided into an MHE group and an MHE-Mg group treated with oral administration of 124 mg/kg/day magnesium sulphate). Morris water maze (MWM), Y maze and narrow beam walking (NBW) were used to evaluate cognitive and motor functions. Brain manganese and magnesium content were measured. The metabolic changes in rats with MHE were investigated using hydrogen-nuclear magnetic resonance. Metabolomic signatures were identified with enrichment and pathway analysis.RESULTS: A significantly decreased number of entries into the MWM within the range of interest, longer latency and total time during NBW, and higher brain manganese content were found in rats with MHE. After magnesium sulphate treatment, the rats with MHE had better behavioural performance and lower brain manganese content. The 25 and 26 metabolomic signatures were identified in the cortex and striatum of rats with MHE. The pathway analysis revealed alanine, aspartate and glutamate metabolism as the major abnormal metabolic pathways associated with these metabolomic signatures.CONCLUSION: Alanine, aspartate and glutamate metabolism are major abnormal metabolic pathways in rats with MHE, which could be restored by magnesium sulphate treatment.PMID:36354241 | DOI:10.1684/mrh.2022.0500
Effect of relative humidity on the quality and safety of peeled almond kernels (Prunus dulcis Mill.) during simulated maritime transport/storage
J Food Sci. 2022 Nov 9. doi: 10.1111/1750-3841.16369. Online ahead of print.ABSTRACTLong-term transport and storage of peeled almonds under unsuitable conditions may cause the product's rejection. To get knowledge in this topic, peeled almonds were stored at 25°C and 60, 70, and 80% relative humidity (RH). The maintenance of high RH (80%) caused some visual defects after 4 months. Even though the 60, 70, and 80% RH did not clearly affect the production of primary and secondary products formed in the lipid oxidation during the 6 months of storage, sometimes an increase in the values of the specific extinction at the wavelength of 268 nm (K268 ) was observed at 80% RH, suggesting the occurrence to some extent of secondary oxidation. Concerning microbial counts, the almonds stored at 60 and 70% RH presented a satisfactory microbial quality until 6 months; however, at 80% RH, the mold counts were higher than the reference values after 2 months. Several mycotoxins were detected at low levels, including aflatoxins B1 and G1, although some showed higher amounts at 80% RH. In general, it is recommended that almond producers and industrials should consider the use of low RH (< 80%) for maritime transport and long-term storage of almond kernels. PRACTICAL APPLICATION: High levels of relative humidity during storage/transport of almond kernels favor fungal growth, mycotoxin production, and secondary oxidation (rancidity). It is recommended to keep the almond kernels under low RH (< 80%) in maritime transport and long storage, especially in tropical countries.PMID:36353800 | DOI:10.1111/1750-3841.16369
Widely Targeted Metabolomics Analysis of Different Parts of Kudzu
Biomed Chromatogr. 2022 Nov 9:e5545. doi: 10.1002/bmc.5545. Online ahead of print.ABSTRACTPueraria lobata is a traditional medicinal and edible plant, its root is often used as a nutritional supplement, but its stems and leaves are often discarded. In this study, the types and contents of compounds in roots, stems and leaves of kudzu were studied by ultra-high-performance liquid chromatography electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS). A total of 446 metabolites were identified, which were mainly divided into 8 categories, forty unique compounds were detected in roots. Multivariate statistical analysis showed that there were significant differences in the contents of metabolites in the roots, stems and leaves of kudzu, and the most significant differences were found in the roots and stems. Most flavonoids and terpenoids accumulated in roots, while alkaloids, flavonoid glycosides, lignans and coumarins accumulated in stems and leaves. In addition, isoflavones accumulated least in stems and most in roots. These results improved our understanding of the accumulation of metabolites in kudzu and provided a reference for the full study of the medicinal value of different parts of kudzu.PMID:36353775 | DOI:10.1002/bmc.5545
Microbiota independent effects of oligosaccharides on Caco-2 cells -A semi-targeted metabolomics approach using DI-FT-ICR-MS coupled with pathway enrichment analysis
Front Mol Biosci. 2022 Oct 24;9:968643. doi: 10.3389/fmolb.2022.968643. eCollection 2022.ABSTRACTMilk oligosaccharides (MOS) and galactooligosaccharides (GOS) are associated with many benefits, including anti-microbial effects and immune-modulating properties. However, the cellular mechanisms of these are largely unknown. In this study, the effects of enriched GOS and MOS mixtures from caprine and bovine milk consisting mainly 6'-galactosyllactose, 3'-sialyllactose, and 6'-sialyllactose on Caco-2 cells were investigated, and the treatment-specific metabolomes were described. In the control, the cells were treated with a sugar mix consisting of one-third each of glucose, galactose and lactose. A local metabolomics workflow with pathway enrichment was established, which specifically addresses DI-FT-ICR-MS analyses and includes adaptations in terms of measurement technology and sample matrices. By including quality parameters, especially the isotope pattern, we increased the precision of annotation. The independence from online tools, the fast adaptability to changes in databases, and the specific adjustment to the measurement technology and biomaterial used, proved to be a great advantage. For the first time it was possible to find 71 active pathways in a Caco-2 cell experiment. These pathways were assigned to 12 main categories, with amino acid metabolism and carbohydrate metabolism being the most dominant categories in terms of the number of metabolites and metabolic pathways. Treatment of Caco-2 cells with high GOS and glucose contents resulted in significant effects on several metabolic pathways, whereas the MOS containing treatments resulted only for individual metabolites in significant changes. An effect based on bovine or caprine origin alone could not be observed. Thus, it was shown that MOS and GOS containing treatments can exert microbiome-independent effects on the metabolome of Caco-2 cells.PMID:36353731 | PMC:PMC9638022 | DOI:10.3389/fmolb.2022.968643
Ecological roles of secondary metabolites of <em>Saposhnikovia divaricata</em> in adaptation to drought stress
PeerJ. 2022 Nov 4;10:e14336. doi: 10.7717/peerj.14336. eCollection 2022.ABSTRACTSaposhnikovia divaricata is a traditional Chinese herb that mainly grows in arid grasslands and strongly adapts to various stresses. Drought is not only a major abiotic stress factor but also a typical feature conducive to producing high-quality medicinal material. The present study investigated by treating S. divaricata plants with polyethylene glycol (PEG-6000). Ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) identified 146 compounds from the roots of S. divaricata, among which seven primary metabolites and 28 secondary metabolites showed significant changes after drought treatment. UV-Vis spectrophotometer detected the activity of antioxidant enzymes and the content of superoxide anion (O2 -.) and malondialdehyde (MDA). The differential primary metabolites revealed that drought promotes glycolysis, reducing primary metabolism and enhancing secondary metabolism. Meanwhile, the differential secondary metabolites showed an increase in the content of compounds upstream of the secondary metabolic pathway, and other glycosides and increased that of the corresponding aglycones. The activities of antioxidant enzymes and the content of O2 -. and MDA shown different changes duing the drought treatment. These observations indicate that drought promotes the biosynthesis and transformation of the secondary metabolites and activity of antioxidant enzymes, improving plant adaptability. The present study also analyzed a few primary and secondary metabolites of S. divaricata under different degrees and durations of drought and speculated on the metabolic pathways in an arid environment. The findings indicate the biological nature, diversity, and complexity of secondary metabolites and the mechanisms of plant adaptation to ecological stress.PMID:36353606 | PMC:PMC9639429 | DOI:10.7717/peerj.14336
Metabolic biomarkers of radiotherapy response in plasma and tissue of an IDH1 mutant astrocytoma mouse model
Front Oncol. 2022 Oct 24;12:979537. doi: 10.3389/fonc.2022.979537. eCollection 2022.ABSTRACTAstrocytomas are the most common subtype of brain tumors and no curative treatment exist. Longitudinal assessment of patients, usually via Magnetic Resonance Imaging (MRI), is crucial since tumor progression may occur earlier than clinical progression. MRI usually provides a means for monitoring the disease, but it only informs about the structural changes of the tumor, while molecular changes can occur as a treatment response without any MRI-visible change. Radiotherapy (RT) is routinely performed following surgery as part of the standard of care in astrocytomas, that can also include chemotherapy involving temozolomide. Monitoring the response to RT is a key factor for the management of patients. Herein, we provide plasma and tissue metabolic biomarkers of treatment response in a mouse model of astrocytoma that was subjected to radiotherapy. Plasma metabolic profiles acquired over time by Liquid Chromatography Mass Spectrometry (LC/MS) were subjected to multivariate empirical Bayes time-series analysis (MEBA) and Receiver Operating Characteristic (ROC) assessment including Random Forest as the classification strategy. These analyses revealed a variation of the plasma metabolome in those mice that underwent radiotherapy compared to controls; specifically, fumarate was the best discriminatory feature. Additionally, Nuclear Magnetic Resonance (NMR)-based 13C-tracing experiments were performed at end-point utilizing [U-13C]-Glutamine to investigate its fate in the tumor and contralateral tissues. Irradiated mice displayed lower levels of glycolytic metabolites (e.g. phosphoenolpyruvate) in tumor tissue, and a higher flux of glutamine towards succinate was observed in the radiation cohort. The plasma biomarkers provided herein could be validated in the clinic, thereby improving the assessment of brain tumor patients throughout radiotherapy. Moreover, the metabolic rewiring associated to radiotherapy in tumor tissue could lead to potential metabolic imaging approaches for monitoring treatment using blood draws.PMID:36353533 | PMC:PMC9638021 | DOI:10.3389/fonc.2022.979537