PubMed
Complex pectin metabolism by <em>Lactobacillus</em> and <em>Streptococcus</em> suggests an effective control approach for Maillard harmful products in brown fermented milk
Fundam Res. 2022 Dec 17;4(5):1171-1184. doi: 10.1016/j.fmre.2022.12.003. eCollection 2024 Sep.ABSTRACTHarmful Maillard reaction products (HMRPs) derived from brown fermented milk pose a potential threat to human health, but the conversion mechanism during the manufacturing process remains elusive and urgently needs to be controlled. Acrylamide (FC 2.14, adjusted p-value = 0.041), 5-hydroxymethylfurfural (FC 2.61, adjusted p-value = 0.026) and methylglyoxal (FC 2.07, adjusted p-value = 0.019) were identified as the significantly increased HMRPs after browning in this study and the analysis of proteomics integrated with untargeted metabolomics demonstrated that the degradation of HMRPs was jointly accomplished by Streptococcus thermophilus and Lactobacillus bulgaricus. The galactose oligosaccharide metabolism in Streptococcus thermophilus was identified as a key biochemical reaction for HMRPs degradation, and the hydrolysates of pectin could be utilized as prebiotics for Streptococcus thermophilus. Eighteen classes of enzymes of L. bulgaricus and Streptococcus thermophilus related to energy metabolism were upregulated in the pectin-added group, indicating that the entry of acrylamide and methylglyoxal into the tricarboxylic acid cycle was accelerated. NAD-aldehyde dehydrogenase and alanine dehydrogenase are enzymes belonging to Streptococcus thermophilus, and their downregulation accelerated the efflux of acetate, which was beneficial for the proliferation of L. bulgaricus and prevented the conversion of pyruvate to l-alanine, thus facilitating the energy metabolism. The recoveries and relative standard deviations of the intraday and interday precision experiments were 89.1%-112.5%, 1.3%-8.4% and 2.1%-9.4%, respectively, indicating that the developed approach was credible. Sensory evaluation results revealed that the brown fermented milk added with pectin had a better flavor, which was due to the fact that the supplement of polysaccharide promoted the fatty acid metabolism of lactic acid bacteria and increased the aroma substances including octoic acid and valeric acid. This study provided an insight into the formation and degradation mechanism of HMRPs in brown fermented milk, aiming to reduce the intake of advanced glycation end products in the diet.PMID:39431140 | PMC:PMC11489481 | DOI:10.1016/j.fmre.2022.12.003
Allergenic risk assessment of porcine myoglobin expressed by engineered <em>Komagataella Phaffii</em>
Fundam Res. 2024 Jan 27;4(5):1339-1348. doi: 10.1016/j.fmre.2023.11.017. eCollection 2024 Sep.ABSTRACTMyoglobin produced by fermentation using engineered Komagataella phaffii is an important color additive in meat analogue products, but its allergenicity is poorly understood. Here, we initially searched the Allergen Online database and did not find any allergic or cross-reactive proteins in porcine myoglobin (PM). In vitro simulated digestion demonstrated that PM did not exhibit notable acid-base resistance or anti-digestion capabilities. However, sensitization was observed in BALB/c mice, including a significant increase in specific antibodies and biomarkers for allergic reactions, as well as alterations in gut microbiome and serum metabolome. Interestingly, the intensity of sensitization exhibited a negative correlation with the purity of PM. 60% and 88% purities showed weaker sensitization compared to the ovalbumin control group. These allergic reactions were likely due to the non-myoglobin protein portion, highlighting the importance of purification processes and the urgent need to assess the allergenicity of this portion.PMID:39431137 | PMC:PMC11489517 | DOI:10.1016/j.fmre.2023.11.017
Association of glycerolipid metabolism with gut microbiota disturbances in a hamster model of high-fat diet-induced hyperlipidemia
Front Cell Infect Microbiol. 2024 Oct 4;14:1439744. doi: 10.3389/fcimb.2024.1439744. eCollection 2024.ABSTRACTBACKGROUND: High-fat diet (HFD)-induced hyperlipidemia, which is associated with gut microbiota disturbances, remains a major public health challenge. Glycerolipid metabolism is responsible for lipid synthesis and is thus involved in the development of hyperlipidemia. However, possible association between the HFD-modulated gut microbiome and the glycerolipid metabolism pathway remains unclear.METHODS: Hamsters were fed a HFD for 4 weeks to establish a hyperlipidemia model. Fecal, plasma and liver samples collected from hamsters fed a HFD or a normal chow diet (NCD) were used for integrative metagenomic and untargeted metabolomic analyses to explore changes in the composition and functions of the gut microbiota, and relevant metabolites. Spearman rank correlation analysis was used to explore correlations between gut microbes and circulating glycerolipid metabolites, gut microbes and lipids, and circulating glycerolipid metabolites and lipids.RESULTS: The gut microbial composition of HFD hamsters showed significant alterations at the phylum, genus, and species levels that were skewed toward metabolic disorders compared with that of NCD hamsters. Functional characterization by KEGG analysis identified enrichment of the glycerolipid metabolism pathway in the gut microbiome of HFD hamsters. Plasma and liver metabolomics further indicated the upregulation and enrichment of glycerolipid metabolites in HFD hamsters. The Faecalibaculum, Allobaculum, and Eubacterium genera were positively correlated with plasma glycerolipid metabolites and lipid indices.CONCLUSION: The findings of this study suggest an association between glycerolipid metabolism and the HFD-modulated gut microbiome that is involved in the development of hyperlipidemia.PMID:39431056 | PMC:PMC11486926 | DOI:10.3389/fcimb.2024.1439744
Allele-specific dysregulation of lipid and energy metabolism in early-stage hypertrophic cardiomyopathy
J Mol Cell Cardiol Plus. 2024 Jun;8:100073. doi: 10.1016/j.jmccpl.2024.100073. Epub 2024 Mar 31.ABSTRACTINTRODUCTION: Hypertrophic cardiomyopathy (HCM) results from pathogenic variants in sarcomeric protein genes that increase myocyte energy demand and lead to cardiac hypertrophy. However, it is unknown whether a common metabolic trait underlies cardiac phenotype at the early disease stage. To address this question and define cardiac biochemical pathology in early-stage HCM, we studied two HCM mouse models that express pathogenic variants in cardiac troponin T (Tnt2) or myosin heavy chain (Myh6) genes, and have marked differences in cardiac imaging phenotype, mitochondrial function at early disease stage.METHODS: We used a combination of echocardiography, transcriptomics, mass spectrometry-based untargeted metabolomics (GC-TOF, HILIC, CSH-QTOF), and computational modeling (CardioNet) to examine cardiac structural and metabolic remodeling at early disease stage (5 weeks of age) in R92W-TnT+/- and R403Q-MyHC+/- mutant mice. Data from mutants was compared with respective littermate controls (WT).RESULTS: Allele-specific differences in cardiac phenotype, gene expression and metabolites were observed at early disease stage. LV diastolic dysfunction was prominent in TnT mutants. Differentially-expressed genes in TnT mutant hearts were predominantly enriched in the Krebs cycle, respiratory electron transport, and branched-chain amino acid metabolism, whereas MyHC mutants were enriched in mitochondrial biogenesis, calcium homeostasis, and liver-X-receptor signaling. Both mutant hearts demonstrated significant alterations in levels of purine nucleosides, trisaccharides, dicarboxylic acids, acylcarnitines, phosphatidylethanolamines, phosphatidylinositols, ceramides and triglycerides; 40.4 % of lipids and 24.7 % of metabolites were significantly different in TnT mutants, whereas 10.4 % of lipids and 5.8 % of metabolites were significantly different in MyHC mutants. Both mutant hearts had a lower abundance of unsaturated long-chain acyl-carnitines (18:1, 18:2, 20:1), but only TnT mutants showed enrichment of FA18:0 in ceramide and cardiolipin species. CardioNet predicted impaired energy substrate metabolism and greater phospholipid remodeling in TnT mutants than in MyHC mutants.CONCLUSIONS: Our systems biology approach revealed marked differences in metabolic remodeling in R92W-TnT and R403Q-MyHC mutant hearts, with TnT mutants showing greater derangements than MyHC mutants, at early disease stage. Changes in cardiolipin composition in TnT mutants could contribute to impairment of energy metabolism and diastolic dysfunction observed in this study, and predispose to energetic stress, ventricular arrhythmias under high workloads such as exercise.PMID:39430912 | PMC:PMC11485168 | DOI:10.1016/j.jmccpl.2024.100073
Metabolomics Analysis for Unveiling the Toxicological Mechanism of Silver Nanoparticles Using an In Vitro Gastrointestinal Digestion Model
ACS Nanosci Au. 2024 Jun 25;4(5):327-337. doi: 10.1021/acsnanoscienceau.4c00012. eCollection 2024 Oct 16.ABSTRACTThe increasing use of silver nanoparticles (AgNPs) in consumer products has led to concerns about potential health risks after oral exposure as a result of the transformation and absorption in the gastrointestinal tract (GIT). However, the intricate condition of the GIT poses challenges in understanding the fate and toxicity of AgNPs as they traverse from the mouth to the rectum. For an in-depth understanding of the nanobio interactions, we employed a simulated digestion model to investigate alterations in the physicochemical properties of AgNPs in vitro. Meanwhile, we investigated the underlying toxicological mechanisms of digested AgNPs in enterocytes through metabolomics analysis. In contrast to route means that primarily apply salt solutions to mimic dietary digestion, this in vitro model is a semidynamic sequential digestion system that includes artificial oral, gastric, and intestinal fluids, which are similar to those under physiological conditions including electrolytes, enzymes, bile, pH, and time of digestion. Our results suggest that the formation of Ag-Cl and Ag-S species within the simulated digestion model can lead to an increase in the size of digested AgNPs and that the acidic condition promotes the release of Ag+ from particles. More critically, the presence of digestive enzymes and high concentrations of salt enhances the uptake of Ag by human colon enterocytes, ultimately promoting ROS generation and exacerbating cytotoxicity. Metabolomics analysis further reveals that the sequentially digested AgNPs may disorder lipid metabolism, including the biosynthesis of unsaturated fatty acids and arachidonic acid metabolism, thus increasing the possibility of ferroptosis activation in enterocytes. These findings offer significant insights into the fate and potential adverse effects of AgNPs in the GIT, providing important implications for assessing the health risks of AgNPs via oral exposure.PMID:39430375 | PMC:PMC11487757 | DOI:10.1021/acsnanoscienceau.4c00012
NMR metabolomics of plant and yeast-based hydrolysates for cell culture media applications - A comprehensive assessment
Curr Res Food Sci. 2024 Sep 21;9:100855. doi: 10.1016/j.crfs.2024.100855. eCollection 2024.ABSTRACTCultivated meat products, generated by growing isolated skeletal muscle and fat tissue, offer the promise of a more sustainable and ethical alternative to traditional meat production. However, with cell culture media used to grow the cells accounting for 55-95% of the overall production cost, achieving true sustainability requires significant media optimization. One means of dealing with these high costs is the use of low-cost complex additives such as hydrolysates to provide a wide range of nutrients, from small molecules (metabolites) to growth factors and peptides. Despite their potential, most hydrolysate products remain poorly characterized and many are thought to suffer from persistent issues of high batch-to-batch variability. Although there have been a number of isolated efforts to determine metabolic profiles for a handful of hydrolysate products, we present the first attempt at a more comprehensive metabolomic characterization of nine different products (four plant and five yeast-based) from two to four different lots each. NMR analysis identified 90 unique metabolites, with only 15 metabolites common to all hydrolysate products (including eight of the nine essential amino acids), and 16 metabolites found in only a single hydrolysate product. The different hydrolysate products were found to have substantial differences in metabolite concentrations (as a fraction of overall mass), ranging from a high of 43% in yeast extract to a low of 14% in soy hydrolysates. The proportion of various metabolites also varied between products, with carbohydrate concentrations particularly high in soy hydrolysates and nucleosides more prominent in two of the yeast products. Overall, yeast extract generally had higher metabolite concentrations than all the other products, whereas both yeast extract and cotton had the largest variety of metabolites. A direct calculation of batch-to-batch variability revealed although there are significant differences between lots, these are largely driven by a relatively small fraction of compounds. This report will hopefully serve as a useful starting point for a more nuanced consideration of hydrolysate products in cell culture media optimization, both in the context of cultivated meat and beyond.PMID:39429919 | PMC:PMC11490674 | DOI:10.1016/j.crfs.2024.100855
Carnitine is a friend in HFpEF and foe in HFrEF
iScience. 2024 Sep 23;27(10):111018. doi: 10.1016/j.isci.2024.111018. eCollection 2024 Oct 18.ABSTRACTHeart failure (HF) is a global concern, particularly HF with preserved ejection fraction (HFpEF), lacking effective treatments. Understanding the differences of metabolic profiles between HFpEF and HFrEF (heart failure with reduced ejection fraction) patients is crucial for therapeutic advancements. In this study, pseudotargeted metabolomics was employed to analyze for disparities of plasma metabolic profiles between HFpEF and HFrEF in two cohorts: discovery (n = 514) and validation (n = 3368). Plasma-free carnitine levels were significant changed in HF patients. A non-linear and U-shaped (for HFpEF) or J-shaped (for HFrEF) association between circulating free carnitine levels and the composite risk of cardiac events were observed. Interestingly, HFpEF patients with low free carnitine (≤40.18 μmol/L) displayed a poorer survival, contrasting with HFrEF where higher levels (≥35.67 μmol/L) were linked to poorer outcomes, indicating distinct metabolism pathways. In conclusion, these findings offer insights into HFpEF metabolic profiles, suggesting potential therapeutic targets.PMID:39429785 | PMC:PMC11490723 | DOI:10.1016/j.isci.2024.111018
GPC3-mediated metabolic rewiring of diabetic mesenchymal stromal cells enhances their cardioprotective functions via PKM2 activation
iScience. 2024 Sep 24;27(10):111021. doi: 10.1016/j.isci.2024.111021. eCollection 2024 Oct 18.ABSTRACTMesenchymal stromal cells (MSC) are promising stem cell therapy for treating cardiovascular and other degenerative diseases. Diabetes affects the functional capability of MSC and impedes cell-based therapy. Despite numerous studies, the impact of diabetes on MSC myocardial reparative activity, metabolic fingerprint, and the mechanism of dysfunction remains inadequately perceived. We demonstrated that the transplantation of diabetic-MSC (db/db-MSC) into the ischemic myocardium of mice does not confer cardiac benefit post-MI. Metabolomic studies identified defective energy metabolism in db/db-MSC. Furthermore, we found that glypican-3 (GPC3), a heparan sulfate proteoglycan, is highly upregulated in db/db-MSC and is involved in metabolic alterations in db/db-MSC via pyruvate kinase M2 (PKM2) activation. GPC3-knockdown reprogrammed-db/db-MSC restored their energy metabolic rates, immunomodulation, angiogenesis, and cardiac reparative activities. Together, these data indicate that GPC3-metabolic reprogramming in diabetic MSC may represent a strategy to enhance MSC-based therapeutics for myocardial repair in diabetic patients.PMID:39429777 | PMC:PMC11490746 | DOI:10.1016/j.isci.2024.111021
Immunogenic cell death inducers and PD-1 blockade as neoadjuvant therapy for rectal cancer
Oncoimmunology. 2024 Oct 17;13(1):2416558. doi: 10.1080/2162402X.2024.2416558. eCollection 2024.ABSTRACTImmuno-oncological cancer management is shifting to neoadjuvant treatments. In patients with gastrointestinal cancers, particularly locally advanced rectal cancer, neoadjuvant chemoimmunotherapy often induce complete responses, hence avoiding surgical intervention. Recent clinical trials indicate that combinations of oxaliplatin-based chemotherapy and PD-1/PD-L1-targeting immunotherapy can be safely administered before surgery with curative intent.PMID:39429516 | PMC:PMC11487966 | DOI:10.1080/2162402X.2024.2416558
Changes in Microbial Ecosystems and Serum Metabolomics by Diet Supplementation With Enramycin in Weaning Piglets
J Anim Physiol Anim Nutr (Berl). 2024 Oct 21. doi: 10.1111/jpn.14059. Online ahead of print.ABSTRACTAntibiotics are used in swine production for growth promotion and disease prevention, raising concerns about environmental contamination and antibiotic resistance. In this study, we investigated the effects of enramycin supplementation on piglet growth, gut microbiota and blood metabolites. Enramycin promotes piglet growth and temporarily reduces diarrhoea. Gut microbiota analysis revealed changes in microbial composition, including an increase in the abundance of Limosilactobacillus reuteri. Metabolomic analysis has identified elevated levels of dimethylglycine, a known growth-promoting factor, in the enramycin group. Liver gene expression analysis revealed increased mRNA levels of ALDH and dimethylglycine dehydrogenase, which are enzymes involved in dimethylglycine metabolism. The enramycin-treated group had a higher concentration of acetic acid in caecal contents, and their caecal acetic acid concentrations were positively correlated with the abundance of L. reuteri and the content of serum dimethylglycine, respectively. These findings suggest that the promotion effect of enramycin on piglet growth is related to the gut microbiota, blood metabolites and liver gene expression, which provide insights into antibiotic alternatives for swine production.PMID:39428819 | DOI:10.1111/jpn.14059
Assessment of amino acids and metabolites in the supernatant of stored concentrates blood from sickle cell trait (SCT) and reference (non-SCT) donors
Vox Sang. 2024 Oct 20. doi: 10.1111/vox.13753. Online ahead of print.ABSTRACTBACKGROUND AND OBJECTIVES: Sickle cell trait (SCT) persons are significant donors, and discarding these blood units reduces their supplies, mainly in the third-world countries. This work focused on 12 metabolites associated with the red blood cell (RBC) storage lesion and 23 amino acids in the supernatants of packed RBC units from SCT and reference (non-SCT) donors stored in the same conditions.MATERIALS AND METHODS: All samples of RBC concentrates were collected and separated from the storage of Colsan (Beneficient Association of Blood Collection), where they were routinely processed and separated as packed RBC units and stored in the refrigerator (2°-6°C). The supernatant samples of each packed RBC bag were separated by centrifugation at days 1, 7, 14, 21, 28 and 35 of storage and kept at -80°C till the metabolite analysis together.RESULTS: The quantitation of metabolites and amino acids examined in the supernatant of SCT and reference donors showed no statistical differences along the cold storage. Lactic acid and malic acid releases occur in three phases during RBC storage. Basic and acid amino acids and corresponding amides have low and stable values during the first 14 days of storage, followed by a steep increase.CONCLUSION: Our metabolomic results give elements that seem not to contraindicate the transfusion of RBC with SCT, besides its more structural fragility.PMID:39428582 | DOI:10.1111/vox.13753
Low blood S-methyl-5-thioadenosine is associated with postoperative delayed neurocognitive recovery
Commun Biol. 2024 Oct 20;7(1):1356. doi: 10.1038/s42003-024-07086-5.ABSTRACTElderly individuals display metabolite alterations that may contribute to development of cognitive impairment following surgery and anesthesia. However, these relationships remain largely unexplored. The study aims to assess the S-methyl-5-thioadenosine (MTA) is associated with postoperative delayed neurocognitive recovery (dNCR). We assess altered metabolites following anesthesia/surgery in both mice and patients to identify blood biomarkers of dNCR. Preoperative and postoperative plasma metabolites are determined by widely targeted metabolomics. The brains of mice with anesthesia/surgery show decreased MTA and activated MTA phosphorylase. Mice also show that preoperative administration of MTA can prevent inflammation and cognitive decline. In clinical patients, we detect lower preoperative serum MTA levels in those who developed dNCR. Both low preoperative and postoperative blood MTA levels are associated with increased risk of postoperative dNCR. These results suggest that anesthesia/surgery induces cognitive decline through methionine synthesis pathways and that MTA could be a perioperative predictor of dNCR.PMID:39428444 | DOI:10.1038/s42003-024-07086-5
Unravelling the physiological and molecular mechanisms of leaf color change in Acer griseum through multi-omics analysis
Plant Physiol Biochem. 2024 Oct 16;216:109198. doi: 10.1016/j.plaphy.2024.109198. Online ahead of print.ABSTRACTPaperbark maple (Acer griseum), an endemic and endangered wild plant in China, has red-colored autumn leaves of high ornamental and garden application value. Leaf color change serves as a crucial indicator for evaluating garden tree aesthetics; however, research on A. griseum's leaf color change remains limited. This study aims to elucidate the physiological and molecular mechanisms underlying leaf color change in maple leaves through physiological, transcriptional, and metabolic assays. Data analysis encompasses gene expression levels and metabolite changes in three distinct states of maple leaves: green, half-red, and red. The progessive decrease of chlorophyll and carotenoids and the continuous accumulation of anthocyanidins caused a sharp change in leaf coloration, which was most drastic in the green to half-red period. Subsequently, targeted metabolomics analysis was performed, and a total of 71 anthocyanidins were detected, and the content of eight types of anthocyanidins increased significantly in the half-red and red periods, compared with that in the green period; of which the multiplicative difference was the largest for cyanidin-3,5-O diglucoside, delivering the largest multiplicative difference. Thus, it was plausible that cyanidin-3,5-O-diglucoside-dominated compoundswere likely to be the main metabolites associated with leaf reddening. Correlation analysis revealed that 12 key transcription factors (TFs) were significantly correlated with the anthocyanin-related metabolites and structural genes, which play important regulatory roles during the biosynthesis of anthocyanosides in A. griseum. These findings offered useful insights into the molecular basis of leaf color variation in A. griseum; providing valuable information to guide targeted genetic breeding and varietal improvement strategies.PMID:39427360 | DOI:10.1016/j.plaphy.2024.109198
A comprehensive study on the digestion, absorption, and metabolization of tropane alkaloids in human cell models
J Hazard Mater. 2024 Oct 17;480:136192. doi: 10.1016/j.jhazmat.2024.136192. Online ahead of print.ABSTRACTTropane alkaloids (TAs) are toxic compounds with potent anticholinergic effects. Herbal infusions are among the most contaminated food commodities; however, the fate of TAs after ingestion remains poorly understood. This study presents a comprehensive investigation into the absorption, and metabolism of five TAs (atropine, scopolamine, tropine, homatropine, and apoatropine) following the digestion of contaminated tea. In vitro human cell models were employed, including gastric (NCI-N87), intestinal (Caco-2:HT29-MTX), and hepatic (HEP-G2) cells. TAs were found to be highly absorbed in the intestinal epithelium, while gastric cells exhibited poor absorption. Metabolism was studied using a custom-made database, revealing that it occurs predominantly in intestinal cells, involving hydroxylation and methylation reactions. Cell metabolomics was conducted using annotation, fragment simulation, and statistical software platforms. Significant statistical differences were observed for 40 tentatively identified compounds. MetaboAnalyst 5.0 was employed to discern the most disturbed metabolic pathways, with amoniacids biosynthesis pathways and TCA cycles being the most affected. These pathways are involved in responses to cellular metabolic stress, neurotransmitter production, cellular energy generation, and the regulation of oxidative stress response. The findings of this study enhance our understanding of the fate of TAs after ingestion, their metabolization and their effects at the cellular level.PMID:39427354 | DOI:10.1016/j.jhazmat.2024.136192
Dried blood spots-based metabolomic analysis in preterm infants with necrotizing enterocolitis
J Matern Fetal Neonatal Med. 2024 Dec;37(1):2416610. doi: 10.1080/14767058.2024.2416610. Epub 2024 Oct 20.ABSTRACTOBJECTIVE: Necrotizing enterocolitis (NEC) is the leading cause of death among premature infants, and there is a lack of specific early diagnostic markers. Blood sampling is expected to better reflect pathophysiological and metabolic changes in systematic illness, but there is a risk of iatrogenic anemia, especially in premature infants. Dried blood spots technique seems to have important advantages compared to whole blood sampling as it requires only 12-15 μL as sample volume. This study aimed to investigate the special metabolomics of preterm neonates at high risk of NEC using dried blood spots.METHODS: Cases and controls were strictly matched 1:1. Dried blood spots (n = 32, 16 cases-16 controls) from newborn screening were subjected to LC-MS/MS. Metabolomic data were analyzed by orthogonal partial least squares-discriminant analysis (OPLS-DA) and univariate/multivariate statistical analysis.RESULTS: Compared to the control group, the NEC group had a significant reduction in seven amino acids (glycine, alanine, threonine, proline, ornithine, lysine, and asparagine).CONCLUSIONS: The metabolic profile of neonates with NEC differs significantly from that of controls, making possible their separation with the use of targeted (LC-MS/MS) dried blood spots-based metabolomic analysis. Seven specific markers were identified for early detection and intervention.PMID:39428341 | DOI:10.1080/14767058.2024.2416610
Advances in intelligent mass spectrometry data processing technology for in vivo analysis of natural medicines
Chin J Nat Med. 2024 Oct;22(10):900-913. doi: 10.1016/S1875-5364(24)60687-4.ABSTRACTNatural medicines (NMs) are crucial for treating human diseases. Efficiently characterizing their bioactive components in vivo has been a key focus and challenge in NM research. High-performance liquid chromatography-high-resolution mass spectrometry (HPLC-HRMS) systems offer high sensitivity, resolution, and precision for conducting in vivo analysis of NMs. However, due to the complexity of NMs, conventional data acquisition, mining, and processing techniques often fail to meet the practical needs of in vivo NM analysis. Over the past two decades, intelligent spectral data-processing techniques based on various principles and algorithms have been developed and applied for in vivo NM analysis. Consequently, improvements have been achieved in the overall analytical performance by relying on these techniques without the need to change the instrument hardware. These improvements include enhanced instrument analysis sensitivity, expanded compound analysis coverage, intelligent identification, and characterization of nontargeted in vivo compounds, providing powerful technical means for studying the in vivo metabolism of NMs and screening for pharmacologically active components. This review summarizes the research progress on in vivo analysis strategies for NMs using intelligent MS data processing techniques reported over the past two decades. It discusses differences in compound structures, variations among biological samples, and the application of artificial intelligence (AI) neural network algorithms. Additionally, the review offers insights into the potential of in vivo tracking of NMs, including the screening of bioactive components and the identification of pharmacokinetic markers. The aim is to provide a reference for the integration and development of new technologies and strategies for future in vivo analysis of NMs.PMID:39428182 | DOI:10.1016/S1875-5364(24)60687-4
Omics detection and treatment of syphilis
Clin Chim Acta. 2024 Oct 18:120008. doi: 10.1016/j.cca.2024.120008. Online ahead of print.ABSTRACTTreponema pallidum is the source of the chronic systemic sexually transmitted illness syphilis. T. pallidum can evade immunity and spread. A hard chancre, enlarged lymph nodes, and a syphilis rash are the primary clinical signs. The condition may affect the nervous or cardiovascular system and even become fatal after being neglected. Omics technology is a cutting-edge technique that maps the entire regulatory network of gene and protein metabolism using high-throughput sequencing and other techniques, such as transcriptomics, proteomics, metabolomics, and genomics, to perform more efficient and methodical research on biological samples. Owing to the diverse and intricate biological roles and gene expression of T. pallidum, a single omics study is frequently insufficient and limited. This review focused on and summarized the use of several omics methods for investigating T. pallidum by referencing several different studies in the literature.PMID:39427935 | DOI:10.1016/j.cca.2024.120008
Polyvinyl chloride microplastics and drought co-exposure alter rice growth by affecting metabolomics and proteomics
Sci Total Environ. 2024 Oct 18:177002. doi: 10.1016/j.scitotenv.2024.177002. Online ahead of print.ABSTRACTMicroplastics, interacting with drought stress, have become threat to crops by altering soil environment. Currently, the effect of combined microplastic and drought stress on crop growth remain poorly understood. In this work, the mechanism of multi-stress responses was investigated under the exposure of polvinylchloride microplastic (PV) and drought (D) individually and in combination (DPV) on rice varieties Hanyou73 and Q280 through proteomics and metabolomic analysis. All treatments negatively affect chlorophyll content, antioxidant enzyme activities, rice grain composition, metabolome and proteomic profiling of both rice varieties. Full rice grain yield was decreased under all treatments except PV treatment in which it was increased in both rice varieties. DPV treatment shows the lowest grain yield and more adverse effects on metabolome by affecting glycerophospholipid metabolism, tryptophan metabolism and alanine, aspartate and glutamate metabolism. Soluble sugar contents were decreased in H73 but in Q280 increased by 159 % under DPV and 123 % in PV treatment, compared to their control group. The results from metabolomics illustrate that glycerophospholipid metabolism is commonly altered in both rice types under all treatments. PV and drought alone and in combination induce extensive alterations in proteomics of rice leaves especially impacting proteins related to binding, translation and photosynthetic process. The results reveal that PV and DPV treatments highly distort the abundance of metabolites and proteins in both rice types, demonstrating that microplastic toxicity effects on rice plants become more severe when combined with drought stress.PMID:39427893 | DOI:10.1016/j.scitotenv.2024.177002
Multiomics approach discloses lipids and metabolites profiles associated to Parkinson's disease stages and applied therapies
Neurobiol Dis. 2024 Oct 18:106698. doi: 10.1016/j.nbd.2024.106698. Online ahead of print.ABSTRACTProfiling circulating lipids and metabolites in Parkinson's disease (PD) patients could be useful not only to highlight new pathways affected in PD condition but also to identify sensitive and effective biomarkers for early disease detection and potentially effective therapeutic interventions. In this study we adopted an untargeted omics approach in three group of patients (No L-Dopa, L-Dopa and DBS) to disclose whether long-term levodopa treatment with or without deep brain stimulation (DBS) could reflect a characteristic lipidomic and metabolomic signature at circulating level. Our findings disclosed a wide up regulation of the majority of differentially regulated lipid species that increase with disease progression and severity. We found a relevant modulation of triacylglycerols and acyl-carnitines, together with an altered profile in adiponectin and leptin, that can differentiate the DBS treated group from the others PD patients. We found a highly significant increase of exosyl ceramides (Hex2Cer) and sphingoid bases (SPB) in PD patients mainly in DBS group (p < 0.0001), which also resulted in a highly accurate diagnostic performance. At metabolomic level, we found a wide dysregulation of pathways involved in the biosynthesis and metabolism of several amino acids acids. The most interesting finding was the identification of a specific modulation of L-glutamic acid in the three groups of patients. L-glutamate levels increased slightly in No L-Dopa and highly in L-Dopa patients while decreased in DBS, suggesting that DBS therapy might have a beneficial effect on the glutamatergic cascade. All together, these data provide novel insights into the molecular and metabolic alterations underlying PD therapy and might be relevant for PD prediction, diagnosis and treatment.PMID:39427845 | DOI:10.1016/j.nbd.2024.106698
Auricularia auricula polysaccharide alleviates cyclophosphamide-induced liver injury in mice involving remodeling of the gut bacteriome, mycobiome, and metabolome
Int J Biol Macromol. 2024 Oct 18:136703. doi: 10.1016/j.ijbiomac.2024.136703. Online ahead of print.ABSTRACTIn this study, a novel polysaccharide (AHP) from Auricularia auricula was isolated and purified, showing protective effects against CTX-induced liver injury in mice. To study the action mechanism of AHP, a liver injury model was established by intraperitoneally injection 80 mg/kg of CTX for 3 consecutive days. The focus was on how AHP regulated the gut bacteriome and mycobiome to help alleviate metabolic disorders associated with liver injury. Results showed that AHP amended liver injury by improving liver function, stabilizing oxidative stress homeostasis, reducing inflammatory invasion and activating Akt/GSK3β/Nrf-2/HO-1 signaling pathway. The 16S ribosomal DNA (16S rDNA) and Internal Transcribed Spacer-1 (ITS1) sequencing results demonstrated that AHP supplementation significantly restored the gut bacteriome and mycobiome composition in CTX-induced liver injury mice, by enriching the abundance of beneficial bacteriome (unclassified_Muribaculaceae, Faecalibaculum and Alloprevotella) and mycobiome (Fusarium), reducing the abundance of harmful bacteriome (Akkermanisa) and mycobiome (Fusicolla and Cladosporium). Analysis of untargeted metabolomics indicated that AHP altered the levels of metabolites associated with both bile acid and arachidonic acid metabolism, showing a significant connection to the AHP-regulated bacteriome and mycobiome. To conclude, the findings suggested that AHP was a viable and secure candidate for use as a hepatoprotective medication.PMID:39427797 | DOI:10.1016/j.ijbiomac.2024.136703