PubMed

Cancer Med. 2023 Jul 6. doi: 10.1002/cam4.6283. Online ahead of print.ABSTRACTBACKGROUND: The aim of this study is to investigate the profiles of gut microbiota and metabolites in acute myelocytic leukemia (AML) patients treated with/without chemotherapy.METHODS: Herein, high-throughput 16S rRNA gene sequencing was performed to analysis gut microbiota profiles, and liquid chromatography and mass spectrometry were performed to analysis metabolites profiles. The correlation between gut microbiota biomarkers identified by LEfSe and differentially expressed metabolites were determined by spearman association analysis.RESULTS: The results showed the distinguished gut microbiota and metabolites profiles between AML patients and control individuals or AML patients treated with chemotherapy. Compared to normal populations, the ratio of Firmicutes to Bacteroidetes was increased at the phylum level than that in AML patients, and LEfSe analysis identified Collinsella and Coriobacteriaceae as biomarkers of AML patients. Differential metabolite analysis indicated that, compared to AML patients, numerous differential amino acids and analogs could be observed in control individuals and AML patients treated with chemotherapy. Interestingly, spearman association analysis demonstrated that plenty of bacteria biomarkers shows statistical correlations with differentially expressed amino acid metabolites. In addition, we found that both Collinsella and Coriobacteriaceae demonstrate remarkable positive correlation with hydroxyprolyl-hydroxyproline, prolyl-tyrosine, and tyrosyl-proline.CONCLUSION: In conclusion, our present study investigated the role of the gut-microbiome-metabolome axis in AML and revealed the possibility of AML treatment by gut-microbiome-metabolome axis in the further.PMID:37409640 | DOI:10.1002/cam4.6283

J Med Virol. 2023 Jul;95(7):e28898. doi: 10.1002/jmv.28898.ABSTRACTOvarian cancers, especially high-grade serous ovarian cancer (HGSOC), are one of the most lethal age-independent gynecologic malignancies. Although pathogenic microorganisms have been demonstrated to participate in the pathogenesis of multiple types of tumors, their potential roles in the development of ovarian cancer remain unclear. To gain an insight into the microbiome-associated pathogenesis of ovarian cancer and identify potential diagnostic biomarkers, we applied different techniques to analyse the microbiome and serum metabolome of different resources. We found that the vaginal microbiota in ovarian cancer mouse models was under dysbiosis, with altered metabolite configurations that may result from amino acid or lysophospholipid metabolic processes. Local therapeutic intervention with a broad spectrum of antibiotics was effective in reversing microbiota dysbiosis and suppressing carcinogenic progression. As the ovary is situated deeply in the pelvis, it is difficult to directly monitor the ovarian microbial community. Our findings provide alternative options for utilizing the vaginal bacteria as noninvasive biomarkers, such as Burkholderia (area under the curve = 0.8843, 95% confidence interval: 0.743-1.000), which supplement the current invasive diagnostic methods for monitoring ovarian cancer progression and contribute to the development of advanced microbe-based diagnosis and adjuvant therapies.PMID:37409619 | DOI:10.1002/jmv.28898

Food Funct. 2023 Jul 6. doi: 10.1039/d3fo01810e. Online ahead of print.ABSTRACTThe Maillard reaction (MR) is inevitable in food processing and daily cooking, but whether the MR degree would affect the biological activity of the protein in vivo remains unknown. In this study, we used untargeted metabolomics techniques to explore the effects of two different levels of Maillard reaction products (MRPs) of ovalbumin (OVA) on metabolites in colitis mice. Studies have shown that MR could affect protein metabolites in vivo and MRPs of OVA could reduce the concentrations of IL-6 and IL-1β and intestinal permeability. Metabolomics results showed that the degree of MR affected the abundance of oligopeptides and bile acids in vivo. This study revealed that MRPs could regulate the abundance of metabolites such as taurocholic acid and putrescine, and repair the intestinal barrier in colitis mice through signaling pathways such as secondary bile acid biosynthesis, bile secretion and ABC transporters. The investigation has significant implications for the digestion properties and metabolite regulation of MRPs in vivo, and also promotes the application of MRPs in functional foods.PMID:37409580 | DOI:10.1039/d3fo01810e

Psychiatry Investig. 2023 Jul 7. doi: 10.30773/pi.2022.0336. Online ahead of print.ABSTRACTPsychiatric disorders remain one of the most debilitating conditions; however, most patients are never diagnosed and do not seek treatment. Despite its massive burden on modern society and the health system, many hurdles prevent proper diagnosis and management of these disorders. The diagnosis is primarily based on clinical symptoms, and efforts to find appropriate biomarkers have not been practical. Through the past years, researchers have put a tremendous effort into finding biomarkers in "omics" fields: genomics, transcriptomics, proteomics, metabolomics, and epigenomics. This article reviews the evolving field of radiomics and its role in diagnosing psychiatric disorders as the sixth potential "omics." The first section of this paper elaborates on the definition of radiomics and its potential to provide a detailed structural study of the brain. Following that, we have provided the latest promising results of this novel approach in a broad range of psychiatric disorders. Radiomics fits well within the concept of psychoradiology. Besides volumetric analysis, radiomics takes advantage of many other features. This technique may open a new field in psychiatry for diagnosing and classifying psychiatric disorders and treatment response prediction in the era of precision and personalized medicine. The initial results are encouraging, but radiomics in psychiatry is still in its infancy. Despite the extensive burden of psychiatric disorders, there are very few published studies in this field, with small patient populations. The lack of prospective multi-centric studies and heterogeneity of studies in design are the significant barriers against the clinical adaptation of radiomics in psychoradiology.PMID:37409371 | DOI:10.30773/pi.2022.0336

Front Plant Sci. 2023 Jun 12;14:1088537. doi: 10.3389/fpls.2023.1088537. eCollection 2023.ABSTRACTINTRODUCTION: Cotton (Gossypium hirsutum L.) is susceptible to long-term waterlogging stress; however, genomic information of cotton response mechanisms toward long days of waterlogging is quite elusive.METHODS: Here, we combined the transcriptome and metabolome expression level changes in cotton roots after 10 and 20 days of waterlogging stress treatment pertaining to potential resistance mechanisms in two cotton genotypes.RESULTS AND DISCUSSION: Numerous adventitious roots and hypertrophic lenticels were induced in CJ1831056 and CJ1831072. Transcriptome analysis revealed 101,599 differentially expressed genes in cotton roots with higher gene expression after 20 days of stress. Reactive oxygen species (ROS) generating genes, antioxidant enzyme genes, and transcription factor genes (AP2, MYB, WRKY, and bZIP) were highly responsive to waterlogging stress among the two genotypes. Metabolomics results showed higher expressions of stress-resistant metabolites sinapyl alcohol, L-glutamic acid, galactaric acid, glucose 1-phosphate, L-valine, L-asparagine, and melibiose in CJ1831056 than CJ1831072. Differentially expressed metabolites (adenosine, galactaric acid, sinapyl alcohol, L-valine, L-asparagine, and melibiose) significantly correlated with the differentially expressed PRX52, PER1, PER64, and BGLU11 transcripts. This investigation reveals genes for targeted genetic engineering to improve waterlogging stress resistance to enhance abiotic stress regulatory mechanisms in cotton at the transcript and metabolic levels of study.PMID:37409297 | PMC:PMC10319419 | DOI:10.3389/fpls.2023.1088537

Front Plant Sci. 2023 Jun 20;14:1210134. doi: 10.3389/fpls.2023.1210134. eCollection 2023.ABSTRACTAutotetraploid rice is developed from diploid rice by doubling the chromosomes, leading to higher nutritional quality. Nevertheless, there is little information about the abundances of different metabolites and their changes during endosperm development in autotetraploid rice. In this research, two different kinds of rice, autotetraploid rice (AJNT-4x) and diploid rice (AJNT-2x), were subjected to experiments at various time points during endosperm development. A total of 422 differential metabolites, were identified by applying a widely used metabolomics technique based on LC-MS/MS. KEGG classification and enrichment analysis showed the differences in metabolites were primarily related to biosynthesis of secondary metabolites, microbial metabolism in diverse environments, biosynthesis of cofactors, and so on. Twenty common differential metabolites were found at three developmental stages of 10, 15 and 20 DAFs, which were considered the key metabolites. To identify the regulatory genes of metabolites, the experimental material was subjected to transcriptome sequencing. The DEGs were mainly enriched in starch and sucrose metabolism at 10 DAF, and in ribosome and biosynthesis of amino acids at 15 DAF, and in biosynthesis of secondary metabolites at 20 DAF. The numbers of enriched pathways and the DEGs gradually increased with endosperm development of rice. The related metabolic pathways of rice nutritional quality are cysteine and methionine metabolism, tryptophan metabolism, lysine biosynthesis and histidine metabolism, and so on. The expression level of the genes regulating lysine content was higher in AJNT-4x than in AJNT-2x. By applying CRISPR/Cas9 gene-editing technology, we identified two novel genes, OsLC4 and OsLC3, negatively regulated lysine content. These findings offer novel insight into dynamic metabolites and genes expression variations during endosperm development of different ploidy rice, which will aid in the creation of rice varieties with better grain nutritional quality.PMID:37409294 | PMC:PMC10319422 | DOI:10.3389/fpls.2023.1210134

Front Plant Sci. 2023 Jun 20;14:1216337. doi: 10.3389/fpls.2023.1216337. eCollection 2023.NO ABSTRACTPMID:37409292 | PMC:PMC10318926 | DOI:10.3389/fpls.2023.1216337

Front Plant Sci. 2023 Jun 20;14:1226864. doi: 10.3389/fpls.2023.1226864. eCollection 2023.NO ABSTRACTPMID:37409288 | PMC:PMC10319101 | DOI:10.3389/fpls.2023.1226864

iScience. 2023 Jun 15;26(7):107136. doi: 10.1016/j.isci.2023.107136. eCollection 2023 Jul 21.ABSTRACTExcessive exposure to manganese (Mn) can cause neurological abnormalities, but the mechanism of Mn neurotoxicity remains unclear. Previous studies have shown that abnormal mitochondrial metabolism is a crucial mechanism underlying Mn neurotoxicity. Therefore, improving neurometabolic in neuronal mitochondria may be a potential therapy for Mn neurotoxicity. Here, single-cell sequencing revealed that Mn affected mitochondrial neurometabolic pathways and unfolded protein response in zebrafish dopaminergic neurons. Metabolomic analysis indicated that Mn inhibited the glutathione metabolic pathway in human neuroblastoma (SH-SY5Y) cells. Mechanistically, Mn exposure inhibited glutathione (GSH) and mitochondrial unfolded protein response (UPRmt). Furthermore, supplementation with glutamine (Gln) can effectively increase the concentration of GSH and triggered UPRmt which can alleviate mitochondrial dysfunction and counteract the neurotoxicity of Mn. Our findings highlight that UPRmt is involved in Mn-induced neurotoxicity and glutathione metabolic pathway affects UPRmt to reverse Mn neurotoxicity. In addition, Gln supplementation may have potential therapeutic benefits for Mn-related neurological disorders.PMID:37408687 | PMC:PMC10318524 | DOI:10.1016/j.isci.2023.107136

Transfus Med Hemother. 2023 May 25;50(3):198-207. doi: 10.1159/000530870. eCollection 2023 Jun.ABSTRACTBACKGROUND: Omics technologies represent a new analytical approach that allows a full cellular readout through the simultaneous analysis of thousands of molecules. The application of such technologies represents a flourishing field of research in human medicine, especially in transfusion medicine, while their application in veterinary medicine still needs to be developed.SUMMARY: Omics technologies, especially proteomics, metabolomics, and lipidomics, are currently applied in several fields of human medicine. In transfusion medicine, the creation and integration of multiomics datasets have uncovered intricate molecular pathways occurring within blood bags during storage. In particular, the research has been directed toward the study of storage lesions (SLs), i.e., those biochemical and structural changes that red blood cells (RBCs) undergo during hypothermic storage, their causes, and the development of new strategies to prevent them. However, due to their challenges to perform and high costs, these technologies are hardly accessible to veterinary research, where their application dates back only to the last few years and thus a great deal of progress still needs to be made. As regards veterinary medicine, there are only a few studies that have focused mainly on fields such as oncology, nutrition, cardiology, and nephrology. Other studies have suggested omics datasets that provide important insights for future comparative investigations between human and nonhuman species. Regarding the study of storage lesions and, more generally, the veterinary transfusion field, there is a marked lack of available omics data and results with relevance for clinical practice.KEY MESSAGES: The use of omics technologies in human medicine is well established and has led to promising results in blood transfusion and related practices knowledge. Transfusion practice is a burgeoning field in veterinary medicine, but, to date, there are no species-specific procedures and techniques for the collection and storage of blood units and those validated in the human species are univocally pursued. Multiomics analysis of the species-specific RBCs' biological characteristics could provide promising results both from a comparative perspective, by increasing our understanding of species suitable to be used as animal models, and in a strictly veterinary view, by contributing to the development of animal-targeted procedures.PMID:37408648 | PMC:PMC10319093 | DOI:10.1159/000530870

Int J Chron Obstruct Pulmon Dis. 2023 Jun 30;18:1353-1365. doi: 10.2147/COPD.S410387. eCollection 2023.ABSTRACTChronic obstructive pulmonary disease (COPD) is a common heterogeneous respiratory disease which is characterized by persistent and incompletely reversible airflow limitation. Due to the heterogeneity and phenotypic complexity of COPD, traditional diagnostic methods provide limited information and pose a great challenge to clinical management. In recent years, with the development of omics technologies, proteomics, metabolomics, transcriptomics, etc., have been widely used in the study of COPD, providing great help to discover new biomarkers and elucidate the complex mechanisms of COPD. In this review, we summarize the prognostic biomarkers of COPD based on proteomic studies in recent years and evaluate their association with COPD prognosis. Finally, we present the prospects and challenges of COPD prognostic-related studies. This review is expected to provide cutting-edge evidence in prognostic evaluation of clinical patients with COPD and to inform future proteomic studies on prognostic biomarkers of COPD.PMID:37408604 | PMC:PMC10319291 | DOI:10.2147/COPD.S410387

Front Cell Dev Biol. 2023 Jun 20;11:1199902. doi: 10.3389/fcell.2023.1199902. eCollection 2023.ABSTRACTBackground: The effect of exercise on human metabolism is obvious. However, the effect of chronic exercise on liver metabolism in mice is less well described. Methods: The healthy adult mice running for 6 weeks as exercise model and sedentary mice as control were used to perform transcriptomic, proteomic, acetyl-proteomics, and metabolomics analysis. In addition, correlation analysis between transcriptome and proteome, and proteome and metabolome was conducted as well. Results: In total, 88 mRNAs and 25 proteins were differentially regulated by chronic exercise. In particular, two proteins (Cyp4a10 and Cyp4a14) showed consistent trends (upregulated) at transcription and protein levels. KEGG enrichment analysis indicated that Cyp4a10 and Cyp4a14 are mainly involved in fatty acid degradation, retinol metabolism, arachidonic acid metabolism and PPAR signaling pathway. For acetyl-proteomics analysis, 185 differentially acetylated proteins and 207 differentially acetylated sites were identified. Then, 693 metabolites in positive mode and 537 metabolites in negative mode were identified, which were involved in metabolic pathways such as fatty acid metabolism, citrate cycle and glycolysis/gluconeogenesis. Conclusion: Based on the results of transcriptomic, proteomics, acetyl-proteomics and metabolomics analysis, chronic moderate intensity exercise has certain effects on liver metabolism and protein synthesis in mice. Chronic moderate intensity exercise may participate in liver energy metabolism by influencing the expression of Cyp4a14, Cyp4a10, arachidonic acid and acetyl coenzyme A and regulating fatty acid degradation, arachidonic acid metabolism, fatty acyl metabolism and subsequent acetylation.PMID:37408533 | PMC:PMC10318136 | DOI:10.3389/fcell.2023.1199902

Gut Microbes. 2023 Jan-Dec;15(1):2228045. doi: 10.1080/19490976.2023.2228045.ABSTRACTCompelling evidence has tightly linked gut microbiota with host metabolism homeostasis and inspired novel therapeutic potentials against metabolic diseases (e.g., hyperlipidemia). However, the regulatory profile of individual bacterial species and strain on lipid homeostasis remains largely unknown. Herein, we performed a large-scale screening of 2250 human gut bacterial strains (186 species) for the lipid-decreasing activity. Different strains in the same species usually displayed distinct lipid-modulatory actions, showing evident strain-specificity. Among the tested strains, Blautia producta exhibited the most potency to suppress cellular lipid accumulation and effectively ameliorated hyperlipidemia in high fat diet (HFD)-feeding mice. Taking a joint comparative approach of pharmacology, genomics and metabolomics, we identified an anteiso-fatty acid, 12-methylmyristic acid (12-MMA), as the key active metabolite of Bl. Producta. In vivo experiment confirmed that 12-MMA could exert potent hyperlipidemia-ameliorating efficacy and improve glucose metabolism via activating G protein-coupled receptor 120 (GPR120). Altogether, our work reveals a previously unreported large-scale lipid-modulatory profile of gut microbes at the strain level, emphasizes the strain-specific function of gut bacteria, and provides a possibility to develop microbial therapeutics against hyperlipidemia based on Bl. producta and its metabolite.PMID:37408362 | DOI:10.1080/19490976.2023.2228045

Cells. 2023 May 17;12(10):1410. doi: 10.3390/cells12101410.ABSTRACTInsect sex pheromones are volatile chemicals that induce mating behavior between conspecific individuals. In moths, sex pheromone biosynthesis is initiated when pheromone biosynthesis-activating neuropeptide (PBAN) synthesized in the suboesophageal ganglion binds to its receptor on the epithelial cell membrane of the pheromone gland. To investigate the function of PBAN receptor (PBANR), we identified two PBANR isoforms, MviPBANR-B and MviPBANR-C, in the pheromone glands of Maruca vitrata. These two genes belong to G protein-coupled receptors (GPCRs) and have differences in the C-terminus but share a 7-transmembrane region and GPCR family 1 signature. These isoforms were expressed in all developmental stages and adult tissues. MviPBANR-C had the highest expression level in pheromone glands among the examined tissues. Through in vitro heterologous expression in HeLa cell lines, only MviPBANR-C-transfected cells responded to MviPBAN (≥5 µM MviPBAN), inducing Ca2+ influx. Sex pheromone production and mating behavior were investigated using gas chromatography and a bioassay after MviPBANR-C suppression by RNA interference, which resulted in the major sex pheromone component, E10E12-16:Ald, being quantitatively reduced compared to the control, thereby decreasing the mating rate. Our findings indicate that MviPBANR-C is involved in the signal transduction of sex pheromone biosynthesis in M. vitrata and that the C-terminal tail plays an important role in its function.PMID:37408245 | DOI:10.3390/cells12101410

Cells. 2023 May 16;12(10):1397. doi: 10.3390/cells12101397.ABSTRACTMelatonin (N-acetyl-5-methoxytryptamine) plays an important role in plant growth and development, and in the response to various abiotic stresses. However, its role in the responses of barley to low phosphorus (LP) stress remains largely unknown. In the present study, we investigated the root phenotypes and metabolic patterns of LP-tolerant (GN121) and LP-sensitive (GN42) barley genotypes under normal P, LP, and LP with exogenous melatonin (30 μM) conditions. We found that melatonin improved barley tolerance to LP mainly by increasing root length. Untargeted metabolomic analysis showed that metabolites such as carboxylic acids and derivatives, fatty acyls, organooxygen compounds, benzene and substituted derivatives were involved in the LP stress response of barley roots, while melatonin mainly regulated indoles and derivatives, organooxygen compounds, and glycerophospholipids to alleviate LP stress. Interestingly, exogenous melatonin showed different metabolic patterns in different genotypes of barley in response to LP stress. In GN42, exogenous melatonin mainly promotes hormone-mediated root growth and increases antioxidant capacity to cope with LP damage, while in GN121, it mainly promotes the P remobilization to supplement phosphate in roots. Our study revealed the protective mechanisms of exogenous MT in alleviating LP stress of different genotypes of barley, which can be used in the production of phosphorus-deficient crops.PMID:37408231 | DOI:10.3390/cells12101397

Cells. 2023 May 13;12(10):1379. doi: 10.3390/cells12101379.ABSTRACTThe metabolism of the model microalgae Chlamydomonas reinhardtii under nitrogen deprivation is of special interest due to its resulting increment of triacylglycerols (TAGs), that can be applied in biotechnological applications. However, this same condition impairs cell growth, which may limit the microalgae's large applications. Several studies have identified significant physiological and molecular changes that occur during the transition from an abundant to a low or absent nitrogen supply, explaining in detail the differences in the proteome, metabolome and transcriptome of the cells that may be responsible for and responsive to this condition. However, there are still some intriguing questions that reside in the core of the regulation of these cellular responses that make this process even more interesting and complex. In this scenario, we reviewed the main metabolic pathways that are involved in the response, mining and exploring, through a reanalysis of omics data from previously published datasets, the commonalities among the responses and unraveling unexplained or non-explored mechanisms of the possible regulatory aspects of the response. Proteomics, metabolomics and transcriptomics data were reanalysed using a common strategy, and an in silico gene promoter motif analysis was performed. Together, these results identified and suggested a strong association between the metabolism of amino acids, especially arginine, glutamate and ornithine pathways to the production of TAGs, via the de novo synthesis of lipids. Furthermore, our analysis and data mining indicate that signalling cascades orchestrated with the indirect participation of phosphorylation, nitrosylation and peroxidation events may be essential to the process. The amino acid pathways and the amount of arginine and ornithine available in the cells, at least transiently during nitrogen deprivation, may be in the core of the post-transcriptional, metabolic regulation of this complex phenomenon. Their further exploration is important to the discovery of novel advances in the understanding of microalgae lipids' production.PMID:37408213 | DOI:10.3390/cells12101379

Cells. 2023 May 12;12(10):1374. doi: 10.3390/cells12101374.ABSTRACTThyroid cancer is the most common endocrine neoplasm, and despite its overall high survival rate, patients with metastatic disease or tumors that resist radioactive iodine experience a significantly worse prognosis. Helping these patients requires a better understanding of how therapeutics alter cellular function. Here, we describe the change in metabolite profiles after treating thyroid cancer cells with the kinase inhibitors dasatinib and trametinib. We reveal alterations to glycolysis, the TCA cycle, and amino acid levels. We also highlight how these drugs promote short-term accumulation of the tumor-suppressive metabolite 2-oxoglutarate, and demonstrate that it reduces the viability of thyroid cancer cells in vitro. These results show that kinase inhibition profoundly alters the metabolome of cancer cells and highlight the need to better understand how therapeutics reprogram metabolic processes, and ultimately, cancer cell behavior.PMID:37408209 | DOI:10.3390/cells12101374

J Adv Res. 2023 Jul 3:S2090-1232(23)00180-7. doi: 10.1016/j.jare.2023.07.001. Online ahead of print.ABSTRACTINTRODUCTION: Folic acid (FA) is a critical metabolite in all living organisms and an important nutritional component of broccoli. Few studies have been conducted on the impact of an exogenous application of FA on the postharvest physiology of fruits and vegetables during storage. In this regard, the mechanism by which an exogenous application of FA extends the postharvest quality of broccoli is unclear.OBJECTIVE: This study utilized a multicomponent analysis to investigate how an exogenous application of FA effects the postharvest quality of broccoli.METHODS: Broccoli was soaked in 5 mg L-1 FA for 10 min and the effect of the treatment on the appearance and nutritional quality of broccoli was evaluated. These data were combined with transcriptomic, metabolomic, and DNA methylation data to provide insight into the potential mechanism by which FA delays senescence.RESULTS: The FA treatment inhibited the yellowing of broccoli during storage. CHH methylation was identified as the main type of methylation that occurs in broccoli and the FA treatment was found to inhibit DNA methylation, promote the accumulation of endogenous FA and chlorophyl, and inhibit ethylene biosynthesis in stored broccoli. The FA treatment also prevented the formation of off-odors by inhibiting the degradation of glucosinolate.CONCLUSIONS: FA treatment inhibited the loss of nutrients during the storage of broccoli, delayed its yellowing, and inhibited the generation of off-odors. Our study provides deeper insight into the mechanism by which the postharvest application of FA delays postharvest senescence in broccoli and provides the foundation for further studies of postharvest metabolism in broccoli.PMID:37406731 | DOI:10.1016/j.jare.2023.07.001

Anal Chem. 2023 Jul 5. doi: 10.1021/acs.analchem.2c04995. Online ahead of print.ABSTRACTDirect-infusion Fourier transform ion cyclotron resonance mass spectrometry (DI-FTICR MS) shows great promise for metabolomic analysis due to ultrahigh mass accuracy and resolution. However, most of the DI-FTICR MS approaches focused on high-throughput metabolomics analysis at the expense of sensitivity and resolution and the potential for metabolome characterization has not been fully explored. Here, we proposed a novel deep characterization approach of serum metabolome using a segment-optimized spectral-stitching DI-FTICR MS method integrated with high-confidence and database-independent formula assignments. With varied acquisition parameters for each segment, a highly efficient acquisition was achieved for the whole mass range with sub-ppm mass accuracy. In a pooled human serum sample, thousands of features were assigned with unambiguous formulas and possible candidates based on highly accurate mass measurements. Furthermore, a reaction network was used to select confidently unique formulas from possible candidates, which was constructed by unambiguous formulas and possible candidates connected by the formula differences resulting from biochemical and MS transformation. Compared with full-range and conventional segment acquisition, 8- and 1.2-fold increases in observed features were achieved, respectively. Assignment accuracy was 93-94% for both a standard mixture containing 190 metabolites and a spiked serum sample with the root mean square mass error of 0.15-0.16 ppm. In total, 3534 unequivocal neutral molecular formulas were assigned in the pooled serum sample, 35% of which are contained in the HMDB. This method offers great enhancement in the deep characterization of serum metabolome by DI-FTICR MS.PMID:37406615 | DOI:10.1021/acs.analchem.2c04995

Placenta. 2023 Jun 16;139:159-171. doi: 10.1016/j.placenta.2023.05.019. Online ahead of print.ABSTRACTINTRODUCTION: Fetal growth restriction (FGR) is a common complication of pregnancy. Lipid metabolism and distribution may contribute to the progression of FGR. However, the metabolism-related mechanisms of FGR remain unclear. The aim of this study was to identify metabolic profiles associated with FGR, as well as probable genes and signaling pathways.METHODS: Metabolomic profiles at the maternal-fetal interface (including the placenta, maternal and fetal serum) from pregnant women with (n = 35) and without (n = 35) FGR were analyzed by gas chromatography-mass spectrometry (GC-MS). Combined with differentially expressed genes (DEGs) from the GSE35574 dataset, analysis was performed for differential metabolites, and identified by the Metabo Analyst dataset. Finally, the pathology and screened DEGs were further identified.RESULTS: The results showed that fatty acids (FAs) accumulated in the placenta and decreased in fetal blood in FGR cases compared to controls. The linoleic acid metabolism was the focus of placental differential metabolites and genes enrichment analysis. In this pathway, phosphatidylcholine can interact with PLA2G2A and PLA2G4C, and 12(13)-EpOME can interact with CYP2J2. PLA2G2A and CYP2J2 were elevated, and PLA2G4C was decreased in the FGR placenta.DISCUSSION: In conclusion, accumulation of FAs in the placental ischemic environments, may involve linoleic acid metabolism, which may be regulated by PLA2G2A, CYP2J2, and PLA2G4C. This study may contribute to understanding the underlying metabolic and molecular mechanisms of FGR.PMID:37406553 | DOI:10.1016/j.placenta.2023.05.019