PubMed

J Am Soc Mass Spectrom. 2023 Jul 31. doi: 10.1021/jasms.3c00181. Online ahead of print.ABSTRACTLipid metabolism is implicated in a variety of diseases, including cancer, cell death, and inflammation, but lipidomics has proven to be challenging due to the vast structural diversity over a narrow range of mass and polarity of lipids. Isotope labeling is often used in metabolomics studies to follow the metabolism of exogenously added labeled compounds because they can be differentiated from endogenous compounds by the mass shift associated with the label. The application of isotope labeling to lipidomics has also been explored as a method to track the metabolism of lipids in various disease states. However, it can be difficult to differentiate a single isotopically labeled lipid from the rest of the lipidome due to the variety of endogenous lipids present over the same mass range. Here we report the development of a dual-isotope deuterium labeling method to track the metabolic fate of exogenous polyunsaturated fatty acids, e.g., arachidonic acid, in the context of ferroptosis using hydrophilic interaction-ion mobility-mass spectrometry (HILIC-IM-MS). Ferroptosis is a type of cell death that is dependent on lipid peroxidation. The use of two isotope labels rather than one enables the identification of labeled species by a signature doublet peak in the resulting mass spectra. A Python-based software, D-Tracer, was developed to efficiently extract metabolites with dual-isotope labels. The labeled species were then identified with LiPydomics based on their retention times, collision cross section, and m/z values. Changes in exogenous AA incorporation in the absence and presence of a ferroptosis inducer were elucidated.PMID:37523294 | DOI:10.1021/jasms.3c00181

J Chem Ecol. 2023 Jul 31. doi: 10.1007/s10886-023-01435-0. Online ahead of print.ABSTRACTEucalyptus species are among the most planted trees in forestry production, an ever-increasing commercial activity worldwide. Forestry expansion demands a continuous search for preventive and sanitary measures against pests and diseases. Massive application of phytosanitary products is incompatible with the forestry sector, so forest health management must be based on other principles. In this context, studies on insect plant relationships mediated by plant metabolites may contribute information relevant to plant resistance and genotype selection. In this study, we analyzed the leaf metabolome of four Eucalyptus species commonly planted in southern South America, to correlate this chemical information with feeding preference of Thaumastocoris peregrinus (Hemiptera: Thaumastocoridae), an important pest of eucalypt plantations. Gas chromatography mass spectrometry analyses were performed on polar and non-polar leaf extracts from Eucalyptus globulus, Eucalyptus grandis, Eucalyptus robusta, and Eucalyptus tereticornis (Myrtaceae). Feeding preferences were assessed in two-choice laboratory bioassays resulting in a preference gradient of the four plant species. Moreover, a performance bioassay where we contrasted survival and development time between the most and least preferred plants, showed a clear correlation with preference both in survival and developmental time of the most susceptible nymph instar. We found that species with high or low feeding preferences differ significantly in several foliar metabolites, which may be acting as feeding stimulants or deterrents for T. peregrinus. These findings may provide useful criteria for choosing Eucalyptus genotypes when planting in bronze bug infested areas.PMID:37523036 | DOI:10.1007/s10886-023-01435-0

Endocr Connect. 2023 Jul 1:EC-23-0079. doi: 10.1530/EC-23-0079. Online ahead of print.ABSTRACTPrevious studies, have shown that elevated levels of circulating BCAAs are associated with the development of insulin resistance and its complications, including obesity, type 2 diabetes, cardiovascular disease, and some cancers. However, animal models that can mimic the metabolic state of chronically elevated BCAAs in humans are rare. Therefore, the aim of this study was to establish the above animal model and analyze the metabolic changes associated with high BCAA levels. Sixteen 8-week-old SD rats were randomly divided into two groups and given either a high fructose diet or a normal diet. BCAA levels as well as blood glucose and lipid levels were measured at different time points of feeding. The mRNA expression levels of two key enzymes of BCAA catabolism, ACAD (acyl-CoA dehydrogenase) and BCKDH (branched-chain α-keto acid dehydrogenase), were measured by qPCR, and the protein expression levels of these two enzymes were analyzed by immunohistochemistry. Finally, the metabolite expression differences between the two groups were analyzed by Q300 metabolomics technology. Our study confirms that defects in the catabolic pathways of BCAAs lead to increased levels of circulating BCAAs, resulting in disorders of glucose and lipid metabolism characterized by insulin resistance by affecting metabolic pathways associated with amino acids and bile acids.PMID:37522853 | DOI:10.1530/EC-23-0079

Microbiol Spectr. 2023 Jul 31:e0057723. doi: 10.1128/spectrum.00577-23. Online ahead of print.ABSTRACTPulmonary tuberculosis (PTB) and diabetes mellitus (DM) are common chronic diseases that threaten human health. Patients with DM are susceptible to PTB, an important factor that aggravates the complications of diabetes. However, the molecular regulatory mechanism underlying the susceptibility of patients with DM to PTB infection remains unknown. In this study, healthy subjects, patients with primary PTB, and patients with primary PTB complicated by DM were recruited according to inclusion and exclusion criteria. Peripheral whole blood was collected, and alteration profiles and potential molecular mechanisms were further analyzed using integrated bioinformatics analysis of metabolomics and transcriptomics. Transcriptional data revealed that lipocalin 2 (LCN2), defensin alpha 1 (DEFA1), peptidoglycan recognition protein 1 (PGLYRP1), and integrin subunit alpha 2b (ITGA2B) were significantly upregulated, while chloride intracellular channel 3 (CLIC3) was significantly downregulated in the group with PTB and DM (PTB_DM) in contrast to the healthy control (HC) group. Additionally, the interleukin 17 (IL-17), phosphatidylinositol 3-kinase (PI3K)-AKT, and peroxisome proliferator-activated receptor (PPAR) signaling pathways are important for PTB infection and regulation of PTB-complicated diabetes. Metabolomic data showed that glycerophospholipid metabolism, carbon metabolism, and fat digestion and absorption processes were enriched in the differential metabolic analysis. Finally, integrated analysis of both metabolomic and transcriptomic data indicated that the NOTCH1/JAK/STAT signaling pathway is important in PTB complicated by DM. In conclusion, PTB infection altered the transcriptional and metabolic profiles of patients with DM. Metabolomic and transcriptomic changes were highly correlated in PTB patients with DM. Peripheral metabolite levels may be used as biomarkers for PTB management in patients with DM. IMPORTANCE The comorbidity of diabetes mellitus (DM) significantly increases the risk of tuberculosis infection and adverse tuberculosis treatment outcomes. Most previous studies have focused on the relationship between the effect of blood glucose control and the outcome of antituberculosis treatment in pulmonary tuberculosis (PTB) with DM (PTB_DM); however, early prediction and the underlying molecular mechanism of susceptibility to PTB infection in patients with DM remain unclear. In this study, transcriptome sequencing and untargeted metabolomics were performed to elucidate the key molecules and signaling pathways involved in PTB infection and the susceptibility of patients with diabetes to PTB. Our findings contribute to the development of vital diagnostic biomarkers for PTB or PTB_DM and provide a comprehensive understanding of molecular regulation during disease progression.PMID:37522815 | DOI:10.1128/spectrum.00577-23

Int J Med Mushrooms. 2023;25(6):1-20. doi: 10.1615/IntJMedMushrooms.2023048295.ABSTRACTPleurotus spp. have been gaining popularity as a source for the creation of functional foods, nutraceuticals and novel pharmaceuticals. Despite Pleurotus is a specious genus including 208 legitimate species, only a few of them such as P. ostreatus are commercially accessible. The genetic and metabolic diversity of Pleurotus both at specific and subspecific level is therefore of main concern for many researchers. In addition to the conventional morphological approach, molecular and biochemical markers have been greatly contributing to investigate these issues. In this study, samples from six Pleurotus species (P. eryngii is represented by three varieties) were molecularly identified and the phylogeny was inferred to assess the relationships between the various taxa. Strains in pure culture obtained from 6 out of 7 species were cultivated as mycelium in vitro to investigate the metabolites by untargeted LC-MS/MS-based metabolomics. The results pointed out species-specific metabolite patterns and highlighted a clear difference between the P. eryngii group and P. ostreatus, although the latter appears more versatile depending on the strain. This is the first study pointing out and comparing different metabolite patterns in Italian samples of Pleurotus species, including P. eryngii varieties.PMID:37522529 | DOI:10.1615/IntJMedMushrooms.2023048295

Plant J. 2023 Jul 31. doi: 10.1111/tpj.16406. Online ahead of print.ABSTRACTDiurnal dark to light transition causes profound physiological changes in plant metabolism. These changes require distinct modes of regulation as a unique feature of photosynthetic lifestyle. The activities of several key metabolic enzymes are regulated by light-dependent post-translational modifications (PTM) and have been studied at depth at the level of individual proteins. In contrast, a global picture of the light-dependent PTMome dynamics is lacking, leaving the response of a large proportion of cellular function undefined. Here, we investigated the light-dependent metabolome and proteome changes in Arabidopsis rosettes in a time resolved manner to dissect their kinetic interplay, focusing on phosphorylation, lysine acetylation, and cysteine-based redox switches. Of over 24 000 PTM sites that were detected, more than 1700 were changed during the transition from dark to light. While the first changes, as measured 5 min after onset of illumination, occurred mainly in the chloroplasts, PTM changes at proteins in other compartments coincided with the full activation of the Calvin-Benson cycle and the synthesis of sugars at later timepoints. Our data reveal connections between metabolism and PTM-based regulation throughout the cell. The comprehensive multiome profiling analysis provides unique insight into the extent by which photosynthesis reprograms global cell function and adds a powerful resource for the dissection of diverse cellular processes in the context of photosynthetic function.PMID:37522418 | DOI:10.1111/tpj.16406

Cardiovasc Res. 2023 Jul 31:cvad124. doi: 10.1093/cvr/cvad124. Online ahead of print.ABSTRACTAIMS: Mitochondria play a vital role in cellular metabolism and energetics and support normal cardiac function. Disrupted mitochondrial function and homeostasis cause a variety of heart diseases. Fam210a (family with sequence similarity 210 member A), a novel mitochondrial gene, is identified as a hub gene in mouse cardiac remodeling by multi-omics studies. Human FAM210A mutations are associated with sarcopenia. However, the physiological role and molecular function of FAM210A remain elusive in the heart. We aim to determine the biological role and molecular mechanism of FAM210A in regulating mitochondrial function and cardiac health in vivo.METHODS AND RESULTS: Tamoxifen-induced αMHCMCM-driven conditional knockout of Fam210a in the mouse cardiomyocytes induced progressive dilated cardiomyopathy and heart failure, ultimately causing mortality. Fam210a deficient cardiomyocytes exhibit severe mitochondrial morphological disruption and functional decline accompanied by myofilament disarray at the late stage of cardiomyopathy. Furthermore, we observed increased mitochondrial reactive oxygen species production, disturbed mitochondrial membrane potential, and reduced respiratory activity in cardiomyocytes at the early stage before contractile dysfunction and heart failure. Multi-omics analyses indicate that FAM210A deficiency persistently activates integrated stress response (ISR), resulting in transcriptomic, translatomic, proteomic, and metabolomic reprogramming, ultimately leading to pathogenic progression of heart failure. Mechanistically, mitochondrial polysome profiling analysis shows that FAM210A loss of function compromises mitochondrial mRNA translation and leads to reduced mitochondrial encoded proteins, followed by disrupted proteostasis. We observed decreased FAM210A protein expression in human ischemic heart failure and mouse myocardial infarction tissue samples. To further corroborate FAM210A function in the heart, AAV9-mediated overexpression of FAM210A promotes mitochondrial-encoded protein expression, improves cardiac mitochondrial function, and partially rescues murine hearts from cardiac remodeling and damage in ischemia-induced heart failure.CONCLUSION: These results suggest that FAM210A is a mitochondrial translation regulator to maintain mitochondrial homeostasis and normal cardiomyocyte contractile function. This study also offers a new therapeutic target for treating ischemic heart disease.PMID:37522353 | DOI:10.1093/cvr/cvad124

Front Public Health. 2023 Jul 13;11:1147403. doi: 10.3389/fpubh.2023.1147403. eCollection 2023.ABSTRACTBACKGROUND: Protecting and improving the personal health of healthcare workers is critical to improving the efficiency and quality of care. To effectively meet the needs of the emergency service system, emergency physicians need to be in a good state of health. However, due to the special characteristics of work in the emergency department, emergency physicians have to face various psychosocial pressures, which may bring them physical and mental distress. Therefore, this study aims to explore the emergency physicians' self-rated health status and its related factors, to provide an empirical study for the improvement of emergency physicians' self-rated health status.METHOD: A cross-sectional survey of emergency physicians was conducted in China between July and August 2018. The questionnaires contained items on demographic characteristics, behavioral lifestyle and job-related factors, as well as self-rated health. The generalized ordinal logistic model was used to identify related factors of emergency physicians' self-rated health status.RESULTS: Only 14.4% of Chinese emergency physicians considered themselves in good health status. Results showed that emergency physicians who never exercised (β = 0.76, p < 0.001) and exercised <2 times per week (β = 0.34, p < 0.001) were more likely to report poor health status. In addition, emergency physicians with good sleep quality (β = -3.84, p < 0.001), fewer night work shifts (β = -0.47, p < 0.001), less frequency of visiting patients (β = -0.33, p < 0.001), never suffered the workplace violence (β = -0.47, p < 0.001) and never perceived effort-reward imbalance (β = -0.68, p < 0.001) were more likely to report good self-rated health.CONCLUSION: Chinese emergency physicians' self-rated health status was not optimistic. Self-rated health is associated with multiple domains of work-related factors and personal lifestyle. Feasible measures should be taken to improve the working environment of emergency physicians, develop acceptable shift schedules for employees, monitor and maintain the health status of emergency department physicians.PMID:37521980 | PMC:PMC10372430 | DOI:10.3389/fpubh.2023.1147403

Front Med (Lausanne). 2023 Jul 13;10:1162808. doi: 10.3389/fmed.2023.1162808. eCollection 2023.ABSTRACTWe independently analyzed two large public domain datasets that contain 1H-NMR spectral data from lung cancer and sex studies. The biobanks were sourced from the Karlsruhe Metabolomics and Nutrition (KarMeN) study and Bayesian Automated Metabolite Analyzer for NMR data (BATMAN) study. Our approach of applying novel artificial intelligence (AI)-based algorithms to NMR is an attempt to globalize metabolomics and demonstrate its clinical applications. The intention of this study was to analyze the resulting spectra in the biobanks via AI application to demonstrate its clinical applications. This technique enables metabolite mapping in areas of localized enrichment as a measure of true activity while also allowing for the accurate categorization of phenotypes.PMID:37521348 | PMC:PMC10373878 | DOI:10.3389/fmed.2023.1162808

Front Immunol. 2023 Jul 14;14:1205616. doi: 10.3389/fimmu.2023.1205616. eCollection 2023.ABSTRACTINTRODUCTION: Assessing labial salivary gland exocrinopathy is a cornerstone in primary Sjögren's syndrome. Currently this relies on the histopathologic diagnosis of focal lymphocytic sialadenitis and computing a focus score by counting lym=phocyte foci. However, those lesions represent advanced stages of primary Sjögren's syndrome, although earlier recognition of primary Sjögren's syndrome and its effective treatment could prevent irreversible damage to labial salivary gland. This study aimed at finding early biomarkers of primary Sjögren's syndrome in labial salivary gland combining metabolomics and machine-learning approaches.METHODS: We used a standardized targeted metabolomic approach involving high performance liquid chromatography coupled with mass spectrometry among newly diagnosed primary Sjögren's syndrome (n=40) and non- primary Sjögren's syndrome sicca (n=40) participants in a prospective cohort. A metabolic signature predictive of primary Sjögren's syndrome status was explored using linear (logistic regression with elastic-net regularization) and non-linear (random forests) machine learning architectures, after splitting the data set into training, validation, and test sets.RESULTS: Among 126 metabolites accurately measured, we identified a discriminant signature composed of six metabolites with robust performances (ROC-AUC = 0.86) for predicting primary Sjögren's syndrome status. This signature included the well-known immune-metabolite kynurenine and five phospholipids (LysoPC C28:0; PCaa C26:0; PCaaC30:2; PCae C30:1, and PCaeC30:2). It was split into two main components: the first including the phospholipids was related to the intensity of lymphocytic infiltrates in salivary glands, while the second represented by kynurenine was independently associated with the presence of anti-SSA antibodies in participant serum.CONCLUSION: Our results reveal an immuno-lipidomic signature in labial salivary gland that accurately distinguishes early primary Sjögren's syndrome from other causes of sicca symptoms.PMID:37520535 | PMC:PMC10375713 | DOI:10.3389/fimmu.2023.1205616

Front Immunol. 2023 Jul 14;14:1168308. doi: 10.3389/fimmu.2023.1168308. eCollection 2023.ABSTRACTINTRODUCTION: To control the COVID-19 pandemic, great efforts have been made to realize herd immunity by vaccination since 2020. Unfortunately, most of the vaccines against COVID-19 were approved in emergency without a full-cycle and comprehensive evaluation process as recommended to the previous vaccines. Metabolome has a close tie with the phenotype and can sensitively reflect the responses to stimuli, rendering metabolomic analysis have the potential to appraise and monitor vaccine effects authentically.METHODS: In this study, a retrospective study was carried out for 330 Chinese volunteers receiving recommended two-dose CoronaVac, a vaccine approved in emergency in 2020. Venous blood was sampled before and after vaccination at 5 separate time points for all the recipients. Routine clinical laboratory analysis, metabolomic and lipidomic analysis data were collected.RESULTS AND DISCUSSION: It was found that the serum antibody-positive rate of this population was around 81.82%. Most of the laboratory parameters were slightly perturbated within the relevant reference intervals after vaccination. The metabolomic and lipidomic analyses showed that the metabolic shift after inoculation was mainly in the glycolysis, tricarboxylic acid cycle, amino acid metabolism, urea cycle, as well as microbe-related metabolism (bile acid metabolism, tryptophan metabolism and phenylalanine metabolism). Time-course metabolome changes were found in parallel with the progress of immunity establishment and peripheral immune cell counting fluctuation, proving metabolomics analysis was an applicable solution to evaluate immune effects complementary to traditional antibody detection. Taurocholic acid, lysophosphatidylcholine 16:0 sn-1, glutamic acid, and phenylalanine were defined as valuable metabolite markers to indicate the establishment of immunity after vaccination. Integrated with the traditional laboratory analysis, this study provided a feasible metabolomics-based solution to relatively comprehensively evaluate vaccines approved under emergency.PMID:37520533 | PMC:PMC10375237 | DOI:10.3389/fimmu.2023.1168308

Front Mol Neurosci. 2023 Jul 13;16:1215637. doi: 10.3389/fnmol.2023.1215637. eCollection 2023.ABSTRACTINTRODUCTION: Vascular dementia (VaD) is one of the most common causes of dementia among the elderly. Despite this, the molecular basis of VaD remains poorly characterized when compared to other age-related dementias. Pervasive cerebral elevations of urea have recently been reported in several dementias; however, a similar analysis was not yet available for VaD.METHODS: Here, we utilized ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) to measure urea levels from seven brain regions in post-mortem tissue from cases of VaD (n = 10) and controls (n = 8/9). Brain-urea measurements from our previous investigations of several dementias were also used to generate comparisons with VaD.RESULTS: Elevated urea levels ranging from 2.2- to 2.4-fold-change in VaD cases were identified in six out of the seven regions analysed, which are similar in magnitude to those observed in uremic encephalopathy. Fold-elevation of urea was highest in the basal ganglia and hippocampus (2.4-fold-change), consistent with the observation that these regions are severely affected in VaD.DISCUSSION: Taken together, these data not only describe a multiregional elevation of brain-urea levels in VaD but also imply the existence of a common urea-mediated disease mechanism that is now known to be present in at least four of the main age-related dementias.PMID:37520429 | PMC:PMC10372345 | DOI:10.3389/fnmol.2023.1215637

Front Microbiol. 2023 Jul 13;14:1210288. doi: 10.3389/fmicb.2023.1210288. eCollection 2023.ABSTRACTIn this study, the function of a non-ribosomal peptide synthetase-like (NRPS-like) encoding gene AOL_s00188g306 (g306) was investigated to reveal the association between NRPS and nematocidal activity in the nematode-trapping fungus Arthrobotrys oligospora. Sequence analysis indicated that the encoded product of g306 is an adenylation domain of non-ribosomal peptide synthetases and extended short-chain dehydrogenase/reductase domain-containing proteins, and displays a wide substrate spectrum. The Δg306 mutants were more sensitive to chemical stressors than the wild type. Disruption of g306 impeded the nematocidal efficiency of A. oligospora. Metabolomics analysis showed that secondary metabolite biosynthesis and lipid metabolism were altered in the mutants. The phenotypic changes in the mutants can be attributed to the down-regulation of various metabolites, including fatty acyls, prenol lipids, steroidsand steroid derivative, and amino acid derivatives, identified in the present study. This study investigated the association between the non-ribosomal polypeptide-encoding gene g306 and nematicidal activity in A. oligospora, providing a reference for resolving the predation mechanism of nematode-trapping fungus.PMID:37520361 | PMC:PMC10373296 | DOI:10.3389/fmicb.2023.1210288

Front Microbiol. 2023 Jul 13;14:1218152. doi: 10.3389/fmicb.2023.1218152. eCollection 2023.ABSTRACTINTRODUCTION: The Chinese mitten crab (Eriocheir sinensis) is a highly valued freshwater crustacean in China. While the natural shell color of E. sinensis is greenish brown (GH), we found a variety with a brownish-orange shell color (RH). Although RH is more expensive, it exhibits a lower molting frequency and growth rate compared with GH, which significantly reduces its yield and hinders large-scale farming. The growth and development of animals are closely related to their gut microbiota and gut tissue metabolic profiles.METHODS: In this study, we compared the gut microbiome communities and metabolic profiles of juvenile RH and GH crabs using 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC-MS), respectively.RESULTS: Our findings indicated that the intestinal microbial composition and metabolic characteristics of E. sinensis differed significantly between RH and GH. At the operational taxonomic unit (OTU) level, the α-diversity of the gut microbiota did not differ significantly between RH and GH, while the β-diversity of the RH gut microbiota was higher than that of the GH gut microbiota. At the species level, the richness of unclassified_c_Alphaproteobacteria was significantly higher in the GH group, while the RH group had a significantly higher richness of three low-abundance species, Flavobacteria bacterium BAL38, Paraburkholderia ferrariae, and uncultured_bacterium_g__Legionella. In the current study, 598 gut tissue metabolites were identified, and 159 metabolites were significantly different between GH and RH. The metabolite profile of RH was characteristic of a low level of most amino acids and lipid metabolites and a high level of several pigments compared with that of GH. These metabolites were enriched in 102 KEGG pathways. Four pathways, including (1) Central carbon metabolism in cancer, (2) protein digestion and absorption, (3) alanine, aspartate and glutamate metabolism, and (4) aminoacyl-tRNA biosynthesis, were significantly enriched. The correlation analysis between metabolites and microbiotas indicated that most key differential metabolites were positively correlated with the abundance of Shewanella_sp_MR-7.DISCUSSION: This research provided a greater understanding of the physiological conditions of E. sinensis varieties with different shell colors by comparing the gut microbiota and gut tissue metabolome.PMID:37520354 | PMC:PMC10374289 | DOI:10.3389/fmicb.2023.1218152

Front Microbiol. 2023 Jul 14;14:1224096. doi: 10.3389/fmicb.2023.1224096. eCollection 2023.ABSTRACTTranscription factors in phytopathogenic fungi are key players due to their gene expression regulation leading to fungal growth and pathogenicity. The KilA-N family encompasses transcription factors unique to fungi, and the Bqt4 subfamily is included in it and is poorly understood in filamentous fungi. In this study, we evaluated the role in growth and pathogenesis of the homologous of Bqt4, FspTF, in Fusarium sp. isolated from the ambrosia beetle Xylosandrus morigerus through the characterization of a CRISPR/Cas9 edited strain in Fsptf. The phenotypic analysis revealed that TF65-6, the edited strain, modified its mycelia growth and conidia production, exhibited affectation in mycelia and culture pigmentation, and in the response to certain stress conditions. In addition, the plant infection process was compromised. Untargeted metabolomic and transcriptomic analysis, clearly showed that FspTF may regulate secondary metabolism, transmembrane transport, virulence, and diverse metabolic pathways such as lipid metabolism, and signal transduction. These data highlight for the first time the biological relevance of an orthologue of Bqt4 in Fusarium sp. associated with an ambrosia beetle.PMID:37520351 | PMC:PMC10375492 | DOI:10.3389/fmicb.2023.1224096

Front Mol Biosci. 2023 Jul 13;10:1233586. doi: 10.3389/fmolb.2023.1233586. eCollection 2023.ABSTRACTIntroduction: Anisakis simplex are parasitic nematodes that cause anisakiasis. The possibility of infection with this parasite is through consumption of raw or undercooked fish products. A. simplex infections are often misdiagnosed, especially in subclinical cases that do not present with typical symptoms such as urticaria, angioedema, and gastrointestinal allergy. The resulting allergic reactions range from rapid-onset and potentially fatal anaphylactic reactions to chronic, debilitating conditions. While there have been numerous published studies on the genomes and proteomes of A. simplex, less attention has been paid to the metabolomes. Metabolomics is concerned with the composition of metabolites in biological systems. Dynamic responses to endogenous and exogenous stimuli are particularly well suited for the study of holistic metabolic responses. In addition, metabolomics can be used to determine metabolic activity at different stages of development or during growth. Materials and methods: In this study, we reveal for the first time the metabolomes of infectious stages (L3 and L4) of A. simplex using untargeted metabolomics by ultra-performance liquid chromatography-mass spectrometry. Results: In the negative ionization mode (ESI-), we identified 172 different compounds, whereas in the positive ionization mode (ESI+), 186 metabolites were found. Statistical analysis showed that 60 metabolites were found in the ESI- mode with different concentration in each group, of which 21 were more enriched in the L3 larvae and 39 in the L4 stage of A. simplex. Comparison of the individual developmental stages in the ESI + mode also revealed a total of 60 differential metabolites, but 32 metabolites were more enriched in the L3 stage larvae, and 28 metabolites were more concentrated in the L4 stage. Discussion: The metabolomics study revealed that the developmental stages of A. simplex differed in a number of metabolic pathways, including nicotinate and nicotinamide metabolism. In addition, molecules responsible for successful migration within their host, such as pyridoxine and prostaglandins (E1, E2, F1a) were present in the L4 stage. In contrast, metabolic pathways for amino acids, starch, and sucrose were mainly activated in the L3 stage. Our results provide new insights into the comparative metabolome profiles of two different developmental stages of A. simplex.PMID:37520327 | PMC:PMC10373882 | DOI:10.3389/fmolb.2023.1233586

Plant Phenomics. 2023 Jul 28;5:0071. doi: 10.34133/plantphenomics.0071. eCollection 2023.ABSTRACTCurrently, the presence of genetically modified (GM) organisms in agro-food markets is strictly regulated by enacted legislation worldwide. It is essential to ensure the traceability of these transgenic products for food safety, consumer choice, environmental monitoring, market integrity, and scientific research. However, detecting the existence of GM organisms involves a combination of complex, time-consuming, and labor-intensive techniques requiring high-level professional skills. In this paper, a concise and rapid pipeline method to identify transgenic rice seeds was proposed on the basis of spectral imaging technologies and the deep learning approach. The composition of metabolome across 3 rice seed lines containing the cry1Ab/cry1Ac gene was compared and studied, substantiating the intrinsic variability induced by these GM traits. Results showed that near-infrared and terahertz spectra from different genotypes could reveal the regularity of GM metabolic variation. The established cascade deep learning model divided GM discrimination into 2 phases including variety classification and GM status identification. It could be found that terahertz absorption spectra contained more valuable features and achieved the highest accuracy of 97.04% for variety classification and 99.71% for GM status identification. Moreover, a modified guided backpropagation algorithm was proposed to select the task-specific characteristic wavelengths for further reducing the redundancy of the original spectra. The experimental validation of the cascade discriminant method in conjunction with spectroscopy confirmed its viability, simplicity, and effectiveness as a valuable tool for the detection of GM rice seeds. This approach also demonstrated its great potential in distilling crucial features for expedited transgenic risk assessment.PMID:37519936 | PMC:PMC10380542 | DOI:10.34133/plantphenomics.0071

Front Oncol. 2023 Jul 13;13:1213273. doi: 10.3389/fonc.2023.1213273. eCollection 2023.ABSTRACTThe joint analysis of single-cell transcriptomics, proteomics, lipidomics, metabolomics and spatial metabolomics is continually transforming our understanding of the mechanisms of metabolic reprogramming in tumor cells. Since head and neck tumor is the sixth most common tumor in the world, the study of the metabolic mechanism of its occurrence, development and prognosis is still undeveloped. In the past decade, this field has witnessed tremendous technological revolutions and considerable development that enables major breakthroughs to be made in the study of human tumor metabolism. In this review, a comprehensive comparison of traditional metabolomics and spatial metabolomics has been concluded, and the recent progress and challenges of the application of spatial metabolomics combined multi-omics in the research of metabolic reprogramming in tumors are reviewed. Furthermore, we also highlight the advances of spatial metabolomics in the study of metabolic mechanisms of head and neck tumors, and provide an outlook of its application prospects.PMID:37519782 | PMC:PMC10374363 | DOI:10.3389/fonc.2023.1213273

Heliyon. 2023 Jul 17;9(7):e18360. doi: 10.1016/j.heliyon.2023.e18360. eCollection 2023 Jul.ABSTRACTLentinula edodes, one of the most highly regarded edible mushrooms in China, is susceptible to damage from high temperatures. However, a mutant strain derived from L. edodes, known as Le023M, has shown exceptional thermotolerance. Compared to the original strain Le023, Le023M exhibited accelerated mycelial recovery following heat stress. Through RNA-seq analysis, the majority of differentially expressed genes (DEGs) were found to be associated with functions such as "protein refolding", "protein unfolding", "protein folding", and "response to heat", all of which are closely linked to heat shock proteins. Furthermore, qRT-PCR results revealed significant accumulation of heat shock-related genes in Le023M under heat stress. GC-MS analysis indicated elevated levels of trehalose, aspartate, and glutamate in Le023M when subjected to heat stress. The highly expressed genes involved in these metabolic pathways were predominantly found in Le023M. Collectively, these findings highlight the following: (i) the crucial role of heat shock proteins (HSPs) in the thermo-resistant mechanisms of Le023M; (ii) the potential of trehalose accumulation in Le023M to enhance mycelium resistance to heat stress; and (iii) the induction of aspartate and glutamate accumulation in response to heat stress. These results shed light on the molecular mechanisms underlying the thermotolerance of Le023M, providing valuable insights for further understanding and improving heat stress response in L. edodes. The findings also highlight the potential applications of Le023M in the cultivation and production of L. edodes under high-temperature conditions.PMID:37519752 | PMC:PMC10372740 | DOI:10.1016/j.heliyon.2023.e18360

Heliyon. 2023 Jul 11;9(7):e18046. doi: 10.1016/j.heliyon.2023.e18046. eCollection 2023 Jul.ABSTRACTBreast cancer is one of the most common cancers. Oridonin, a traditional Chinese medicine, is believed to inhibit tumor growth, but its particular effects on breast cancer remain unknown. In this study, we examined oridonin's effects on 4T1, MCF-7, and MDAMB-231 cellular activity using CCK8. Scratch assays were used to detect oridonin's effects on cellular migration. Oridonin's effects on the breast cancer cell cycle were studied using flow cytometry, and expression of cell cycle related proteins p53, CDK2, and p21 was detected using Western blot assays. Metabolomics assays were used to detect changes in small molecule metabolites and metabolic pathways in breast cancer cells after treatment with oridonin. Oridonin's effects on breast cancer growth were also studied using xenograft mice. Metabolomics assays were used to detect changes in metabolites and metabolic pathways in xenograft mouse plasma in a control group, model group, and drug administration group. Experimental results showed that oridonin could significantly inhibit breast cancer growth both in vivo and in vitro. Scratch experiments showed that oridonin could inhibit breast cancer cell migration. Oridonin was also able to arrest cells in S phase by affecting several cell cycle-related proteins, including p53, CDK2, and p21. Metabolomic analysis of 4T1 cells identified a total of 33 differential metabolites, including multiple amino acids (such as l-Glutamic acid, l-Asparagine, l-Histidine, l-Valine, and l-Isoleucine). KEGG pathway enrichment analysis showed significant changes in aminoacyl-tRNA biosynthesis, and in multiple amino acid metabolic pathways. Plasma metabolomic analyses of xenograft mice revealed 28 differentially-expressed metabolites between the different animal model groups, including multiple amino acids. KEGG pathway analysis showed significant alterations in multiple amino acid metabolic pathways in oridonin-treated mice. Additionally, changes in the expression of PI3K, AKT and mTOR proteins, as well as in branched amino acids, suggest that oridonin affects the PI3K/AKT/mTOR signaling pathway by inhibiting the biosynthesis of valine, leucine and isoleucine. Taken together, our results suggest that oridonin has strong anti-tumor activity in vitro and in vivo, and has potential as an adjuvant to breast cancer treatment regimens.PMID:37519735 | PMC:PMC10372243 | DOI:10.1016/j.heliyon.2023.e18046