PubMed

NPJ Microgravity. 2023 Dec 13;9(1):90. doi: 10.1038/s41526-023-00337-5.ABSTRACTThe adverse effects of microgravity exposure on mammalian physiology during spaceflight necessitate a deep understanding of the underlying mechanisms to develop effective countermeasures. One such concern is muscle atrophy, which is partly attributed to the dysregulation of calcium levels due to abnormalities in SERCA pump functioning. To identify potential biomarkers for this condition, multi-omics data and physiological data available on the NASA Open Science Data Repository (osdr.nasa.gov) were used, and machine learning methods were employed. Specifically, we used multi-omics (transcriptomic, proteomic, and DNA methylation) data and calcium reuptake data collected from C57BL/6 J mouse soleus and tibialis anterior tissues during several 30+ day-long missions on the international space station. The QLattice symbolic regression algorithm was introduced to generate highly explainable models that predict either experimental conditions or calcium reuptake levels based on multi-omics features. The list of candidate models established by QLattice was used to identify key features contributing to the predictive capability of these models, with Acyp1 and Rps7 proteins found to be the most predictive biomarkers related to the resilience of the tibialis anterior muscle in space. These findings could serve as targets for future interventions aiming to reduce the extent of muscle atrophy during space travel.PMID:38092777 | DOI:10.1038/s41526-023-00337-5

NPJ Biofilms Microbiomes. 2023 Dec 14;9(1):99. doi: 10.1038/s41522-023-00466-5.ABSTRACTSpinal cord injury (SCI) can reshape gut microbial composition, significantly affecting clinical outcomes in SCI patients. However, mechanisms regarding gut-brain interactions and their clinical implications have not been elucidated. We hypothesized that short-chain fatty acids (SCFAs), intestinal microbial bioactive metabolites, may significantly affect the gut-brain axis and enhance functional recovery in a mouse model of SCI. We enrolled 59 SCI patients and 27 healthy control subjects and collected samples. Thereafter, gut microbiota and SCFAs were analyzed using 16 S rDNA sequencing and gas chromatography-mass spectrometry, respectively. We observed an increase in Actinobacteriota abundance and a decrease in Firmicutes abundance. Particularly, the SCFA-producing genera, such as Faecalibacterium, Megamonas, and Agathobacter were significantly downregulated among SCI patients compared to healthy controls. Moreover, SCI induced downregulation of acetic acid (AA), propionic acid (PA), and butyric acid (BA) in the SCI group. Fecal SCFA contents were altered in SCI patients with different injury course and injury segments. Main SCFAs (AA, BA, and PA) were administered in combination to treat SCI mice. SCFA supplementation significantly improved locomotor recovery in SCI mice, enhanced neuronal survival, promoted axonal formation, reduced astrogliosis, and suppressed microglial activation. Furthermore, SCFA supplementation downregulated NF-κB signaling while upregulating neurotrophin-3 expression following SCI. Microbial sequencing and metabolomics analysis showed that SCI patients exhibited a lower level of certain SCFAs and related bacterial strains than healthy controls. SCFA supplementation can reduce inflammation and enhance nourishing elements, facilitating the restoration of neurological tissues and the improvement of functional recuperation. Trial registration: This study was registered in the China Clinical Trial Registry ( www.chictr.org.cn ) on February 13, 2017 (ChiCTR-RPC-17010621).PMID:38092763 | DOI:10.1038/s41522-023-00466-5

Environ Sci Technol. 2023 Dec 13. doi: 10.1021/acs.est.3c07515. Online ahead of print.ABSTRACTPer- and polyfluoroalkyl substances (PFAS) are ubiquitous and persistent chemicals associated with multiple adverse health outcomes; however, the biological pathways affected by these chemicals are unknown. To address this knowledge gap, we used data from 264 mother-infant dyads in the Health Outcomes and Measures of the Environment (HOME) Study and employed quantile-based g-computation to estimate covariate-adjusted associations between a prenatal (∼16 weeks' gestation) serum PFAS mixture [perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexanesulfonic acid (PFHxS), and perfluorononanoic acid (PFNA)] and 14,402 features measured in cord serum. The PFAS mixture was associated with four features: PFOS, PFHxS, a putatively identified metabolite (3-monoiodo-l-thyronine 4-O-sulfate), and an unidentified feature (590.0020 m/z and 441.4 s retention time; false discovery rate <0.20). Using pathway enrichment analysis coupled with quantile-based g-computation, the PFAS mixture was associated with 49 metabolic pathways, most notably amino acid, carbohydrate, lipid and cofactor and vitamin metabolism, as well as glycan biosynthesis and metabolism (P(Gamma) <0.05). Future studies should assess if these pathways mediate associations of prenatal PFAS exposure with infant or child health outcomes, such as birthweight or vaccine response.PMID:38091497 | DOI:10.1021/acs.est.3c07515

Environ Sci Pollut Res Int. 2023 Dec 13. doi: 10.1007/s11356-023-31285-y. Online ahead of print.ABSTRACTImidacloprid (IM) is a systemic insecticide persistent in the environment and possesses a negative impact on the non-targeted ecosystem. The objective of the present study was to evaluate the dissipation and degradation mechanism of IM residues in grape rhizosphere soil and to investigate its residual effect on soil enzyme activity at different IM spiking levels. The half-life of IM residue in soil was 27, 36, and 43.5 days at a spiking level of 1, 10, and 50 mg kg-1, respectively following a bi-phasic first + first-order dissipation kinetics. UHPLC-Orbitrap™-MS analysis by targeted metabolomics approach revealed that IM metabolites such as IM-amine analogue, guanidine (reduction), 5-hydroxy IM (hydroxylation), IM-Urea (oxidation), reduced NO analogue of IM (oxidation), and olefin of guanidine IM (dehydrogenation) were identified and proposed the degradation mechanism in grape rhizosphere soil. Toxicity of IM residues on five extracellular enzymes, viz., dehydrogenase, acid phosphatase, alkaline phosphatase, β-glucosidase, and urease revealed that activity of dehydrogenase, acid phosphatase, and alkaline phosphatase remained unaffected at 60th day of sampling. The β-glucosidase and urease were negatively affected throughout the incubation period indicating the influence of IM residues on carbon and nitrogen mineralization in soil. Thus, long-term exposure of IM to grape rhizosphere through soil drenching could affect soil enzyme activity which has a negative effect on the soil nutrient cycle and soil microbiome.PMID:38091217 | DOI:10.1007/s11356-023-31285-y

Naunyn Schmiedebergs Arch Pharmacol. 2023 Dec 13. doi: 10.1007/s00210-023-02864-0. Online ahead of print.ABSTRACTNon-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome. Vitamin E (VE) has antioxidant properties and can mediate lipid metabolism. Non-targeted metabolomics technology was employed to uncover comprehensively the metabolome of VE in NAFLD rats. NAFLD model was created with a high-fat and high-cholesterol diet (HFD) in rats. NAFLD rats in the VE group were given 75 mg/(kg day) VE. The metabolites in the serum of rats were identified via UPLC and Q-TOF/MS analysis. KEGG was applied for the pathway enrichment. VE improved the liver function, lipid metabolism, and oxidative stress in NAFLD rats induced by HFD. Based on the metabolite profile data, 132 differential metabolites were identified between VE group and the HFD group, mainly including pyridoxamine, betaine, and bretylium. According to the KEGG results, biosynthesis of cofactors was a key metabolic pathway of VE in NAFLD rats. VE can alleviate NAFLD induced by HFD, and the underlying mechanism is associated with the biosynthesis of cofactors, mainly including pyridoxine and betaine.PMID:38091076 | DOI:10.1007/s00210-023-02864-0

Saudi Pharm J. 2024 Jan;32(1):101897. doi: 10.1016/j.jsps.2023.101897. Epub 2023 Dec 6.ABSTRACTThe steady increase in the use of electronic cigarettes (ECs) has reached an epidemic level, increasing mortality and morbidity, mainly due to pulmonary toxicity. Several mechanisms are involved in EC-induced toxicity, including oxidative stress and increased inflammation. Concurrently, the integrity of cellular metabolism is essential for cellular homeostasis and mitigation of toxic insults. However, the effects of EC on cellular metabolism remain largely unknown. In this study, we investigated the metabolic changes induced by EC in human lung epithelial cells (A549) using an untargeted metabolomics approach. A549 cells were exposed to increasing EC vapor extract concentrations, and cell viability, oxidative stress, and metabolomic changes were assessed. Our findings show that ECs induce cell death and increase oxidative stress in a concentration-dependent manner. Metabolomic studies demonstrated that ECs induce unique metabolic changes in key cellular metabolic pathways. Our results revealed that exposure to ECs induced clear segregation in metabolic responses which is driven significantly by number of essential metabolites such as aminoacids, fatty acids, glutathione, and pyruvate. Interstingly, our metabolomics results showed that each concentration of ECs induced unqiues pattern of metabolic changes, suggesting the complexity of ECs induced cytotoxcity. Disrupted metabolites were linked to essential cellular pathways, such as fatty acid biosynthesis, as well as glutathione, pyruvate, nicotinate and nicotinamide, and amino acid metabolisms. These results highlight the potential adverse effects of ECs on cellular metabolism and emphasize the need for further research to fully understand the long-term consequences of EC use. Overall, this study demonstrates that ECs not only induce cell death and oxidative stress but also disrupt cellular metabolism in A549 lung epithelial cells.PMID:38090735 | PMC:PMC10714235 | DOI:10.1016/j.jsps.2023.101897

Front Immunol. 2023 Nov 28;14:1331366. doi: 10.3389/fimmu.2023.1331366. eCollection 2023.ABSTRACT[This corrects the article DOI: 10.3389/fimmu.2023.1149107.].PMID:38090584 | PMC:PMC10715422 | DOI:10.3389/fimmu.2023.1331366

Int J Nanomedicine. 2023 Dec 8;18:7483-7503. doi: 10.2147/IJN.S436866. eCollection 2023.ABSTRACTPURPOSE: Fatty oil of Descurainia Sophia (OIL) has poor stability and low solubility, which limits its pharmacological effects. We hypothesized that fatty oil nanoparticles (OIL-NPs) could overcome this limitation. The protective effect of OIL-NPs against monocrotaline-induced lung injury in rats was studied.METHODS: We prepared OIL-NPs by wrapping fatty oil with polylactic-polyglycolide nanoparticles (PLGA-NPs) and conducted in vivo and in vitro experiments to explore its anti-pulmonary hypertension (PH) effect. In vitro, we induced malignant proliferation of pulmonary artery smooth muscle cells (RPASMC) using anoxic chambers, and studied the effects of OIL-NPs on the malignant proliferation of RPASMC cells and phospholipase C (PLC)/inositol triphosphate receptor (IP3R)/Ca2+ signal pathways. In vivo, we used small animal echocardiography, flow cytometry, immunohistochemistry, western blotting (WB), polymerase chain reaction (PCR) and metabolomics to explore the effects of OIL-NPs on the heart and lung pathological damage and PLC/IP3R/Ca2+ signal pathway of pulmonary hypertension rats.RESULTS: We prepared fatty into OIL-NPs. In vitro, OIL-NPs could improve the mitochondrial function and inhibit the malignant proliferation of RPASMC cells by inhibiting the PLC/IP3R/Ca2+signal pathway. In vivo, OIL-NPs could reduce the pulmonary artery pressure of rats and alleviate the pathological injury and inflammatory reaction of heart and lung by inhibiting the PLC/IP3R/Ca2+ signal pathway.CONCLUSION: OIL-NPs have anti-pulmonary hypertension effect, and the mechanism may be related to the inhibition of PLC/IP3R/Ca2+signal pathway.PMID:38090366 | PMC:PMC10714987 | DOI:10.2147/IJN.S436866

Mass Spectrom (Tokyo). 2023;12(1):A0138. doi: 10.5702/massspectrometry.A0138. Epub 2023 Dec 8.ABSTRACTNon-targeted metabolome analysis studies comprehensively acquire product ion spectra from the observed ions by the data-dependent acquisition (DDA) mode of tandem mass spectrometry (MS). A DDA dataset redundantly contains closely similar product ion spectra of metabolites commonly existing among the biological samples analyzed in a metabolome study. Moreover, a single DDA data file often includes two or more closely similar raw spectra obtained from an identical precursor ion. The redundancy of product ion spectra has been used to generate an averaged product ion spectrum from a set of similar product ion spectra recorded in a DDA dataset. The spectral averaging improved the accuracy of m/z values and signal-to-noise levels of product ion spectra. However, the origins of redundancy, variations among datasets, and these effects on the spectral averaging procedure needed to be better characterized. This study investigated the nature of the redundancy by comparing the averaging results of eight DDA datasets of non-targeted metabolomics studies. The comparison revealed a significant variation in redundancy among datasets. The DDA datasets obtained by the quadrupole (Q)-Orbitrap-MS datasets had more significant intrafile redundancy than that of the Q-time-of-flight-MS. For evaluating the similarity score between two production spectra, the optimal threshold level of the cosine-product method was approximately 0.8-0.9. Moreover, contamination of biological samples such as plasticizers was another origin of spectral redundancy. The results will be the basis for further development of methods for processing of product ion spectra data. Copyright © 2023 Fumio Matsuda. This is an open-access article distributed under the terms of Creative Commons Attribution Non-Commercial 4.0 International License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. Please cite this article as: Mass Spectrom (Tokyo) 2023; 12(1): A0138.PMID:38090113 | PMC:PMC10713281 | DOI:10.5702/massspectrometry.A0138

Cureus. 2023 Dec 11;15(12):e50318. doi: 10.7759/cureus.50318. eCollection 2023 Dec.ABSTRACTAntibiotic therapy is a cornerstone of modern medicine, yet the development of antibiotic resistance threatens to render these therapies ineffective. The gut microbiota, a complex ecosystem of microorganisms residing in the gastrointestinal tract, plays a critical role in modulating antibiotic efficacy and resistance. This review delves into the intricate relationship between gut microbiota, antibiotic therapy, and resistance and discusses the potential applications of gut microbiota research in guiding personalized antibiotic therapy and resistance mitigation strategies. Recent advancements in metagenomics, metatranscriptomics, and metabolomics have demonstrated the potential for tailored antibiotic regimens that minimize collateral damage to commensal bacteria and reduce the risk of resistance. Adjuvant therapies, such as probiotics, prebiotics, and synbiotics, have shown promise in restoring gut microbial balance and mitigating the adverse effects of antibiotic therapy. We address the challenges associated with this emerging field, including the need for standardized methodologies, ethical considerations, and interdisciplinary collaboration. With continued interdisciplinary collaboration and the implementation of standardized methodologies, gut microbiota research can contribute to the global fight against antibiotic resistance and improve patient outcomes.PMID:38089944 | PMC:PMC10714069 | DOI:10.7759/cureus.50318

Front Plant Sci. 2023 Nov 16;14:1287997. doi: 10.3389/fpls.2023.1287997. eCollection 2023.ABSTRACTINTRODUCTION: Paprika (Capsicum annuum L.) is prone to chilling injury (CI) during low-temperature storage. Although recent findings suggest that CO2 treatment may protect against CI, the effects of short-term CO2 treatment on CI and the underlying molecular mechanisms in paprika remain unknown. Therefore, this study aimed to examine the effect of short-term CO2 treatment on CI and postharvest quality in paprika during storage at cold storage and retail condition at physio-biochemical-molecular level.METHODS: Paprika was treated with 20 and 30% CO2 for 3 h and stored at 4°C for 14 days, followed by additional storage for 2 days at 20°C (retail condition). Fruit quality parameters, including weight loss, firmness, color, and pitting were assessed, and the molecular mechanism of the treatment was elucidated using transcriptomic and metabolomic analyses.RESULTS: Short-term treatment with 20 and 30% CO2 effectively maintained paprika quality during cold storage and retailer conditions, with reduced surface pitting, a common symptom of CI. Additionally, transcriptomic and metabolomic analyses revealed that 20% CO2 treatment induced genes associated with biosynthesis of phosphatidic acid (PA), diacylglycerol, triacylglycerol, and stress response, metabolites associated with phasphatidyl inositol signaling, inositol phosphate metabolism, and starch and sucrose metabolism.CONCLUSION: CO2 treatment activates PA biosynthesis through PLD and PLC-DGK pathways, and induces inositol phosphate, starch, and sucrose metabolism, thereby regulating chilling stress response via the ICE-CBF pathway. These findings suggest that short-term CO2 treatment enhances resistance to cold-induced injury and preserves postharvest quality in non-climacteric fruits, such as paprika, through activation of PA signaling, which improves membrane stability during cold storage and distribution.PMID:38089806 | PMC:PMC10711834 | DOI:10.3389/fpls.2023.1287997

Front Plant Sci. 2023 Nov 28;14:1277762. doi: 10.3389/fpls.2023.1277762. eCollection 2023.ABSTRACTINTRODUCTION: Salt stress is a major constraint affecting crop productivity worldwide. Investigation of halophytes could provide valuable information for improving economically important crops to tolerate salt stress and for more effectively using halophytes to remediate saline environments. Sesuvium portulacastrum L. is a halophyte species widely distributed in tropical and subtropical coastal regions and can absorb a large amount of sodium (Na). This study was to analyze S. portulacastrum responses to salt stress at morphological, physiological, proteomic, and metabolomic levels and pursue a better understanding of mechanisms behind its salt tolerance.METHODS: The initial experiment evaluated morphological responses of S. portulacastrum to different concentrations of NaCl in a hydroponic system, and subsequent experiments compared physiological, proteomic, and metabolomic changes in S. portulacastrum after being exposed to 0.4 M NaCl for 24 h as immediate salt stress (IS) to 14 days as adaptive salt stress (AS). Through these analyses, a working model to illustrate the integrative responses of S. portulacastrum to salt stress was proposed.RESULTS: Plants grown in 0.4 M NaCl were morphologically comparable to those grown in the control treatment. Physiological changes varied in control, IS, and AS plants based on the measured parameters. Proteomic analysis identified a total of 47 and 248 differentially expressed proteins (DEPs) in leaves and roots, respectively. KEGG analysis showed that DEPs, especially those occurring in roots, were largely related to metabolic pathways. Root metabolomic analysis showed that 292 differentially expressed metabolites (DEMs) occurred in IS plants and 371 in AS plants. Among them, 20.63% of upregulated DEMs were related to phenolic acid metabolism.DISCUSSION: Based on the integrative analysis of proteomics and metabolomics, signal transduction and phenolic acid metabolism appeared to be crucial for S. portulacastrum to tolerate salt stress. Specifically, Ca2+, ABA, and JA signalings coordinately regulated salt tolerance in S. portulacastrum. The stress initially activated phenylpropanoid biosynthesis pathway through Ca2+ signal transduction and increased the content of metabolites, such as coniferin. Meanwhile, the stress inhibited MAPK signaling pathway through ABA and JA signal transduction, which promoted Na sequestration into the vacuole to maintain ROS homeostasis and enhanced S. portulacastrum tolerance to salt stress.PMID:38089796 | PMC:PMC10714944 | DOI:10.3389/fpls.2023.1277762

Front Plant Sci. 2023 Nov 27;14:1260429. doi: 10.3389/fpls.2023.1260429. eCollection 2023.ABSTRACTSpaceflight presents a unique environment with complex stressors, including microgravity and radiation, that can influence plant physiology at molecular levels. Combining transcriptomics and proteomics approaches, this research gives insights into the coordination of transcriptome and proteome in Arabidopsis' molecular and physiological responses to Spaceflight environmental stress. Arabidopsis seedlings were germinated and grown in microgravity (µg) aboard the International Space Station (ISS) in NASA Biological Research in Canisters - Light Emitting Diode (BRIC LED) hardware, with the ground control established on Earth. At 10 days old, seedlings were frozen in RNA-later and returned to Earth. RNA-seq transcriptomics and TMT-labeled LC-MS/MS proteomic analysis of cellular fractionates from the plant tissues suggest the alteration of the photosynthetic machinery (PSII and PSI) in spaceflight, with the plant shifting photosystem core-regulatory proteins in an organ-specific manner to adapt to the microgravity environment. An overview of the ribosome, spliceosome, and proteasome activities in spaceflight revealed a significant abundance of transcripts and proteins involved in protease binding, nuclease activities, and mRNA binding in spaceflight, while those involved in tRNA binding, exoribonuclease activity, and RNA helicase activity were less abundant in spaceflight. CELLULOSE SYNTHASES (CESA1, CESA3, CESA5, CESA7) and CELLULOSE-LIKE PROTEINS (CSLE1, CSLG3), involved in cellulose deposition and TUBULIN COFACTOR B (TFCB) had reduced abundance in spaceflight. This contrasts with the increased expression of UDP-ARABINOPYRANOSE MUTASEs, involved in the biosynthesis of cell wall non-cellulosic polysaccharides, in spaceflight. Both transcripts and proteome suggested an altered polar auxin redistribution, lipid, and ionic intracellular transportation in spaceflight. Analyses also suggest an increased metabolic energy requirement for plants in Space than on Earth, hence, the activation of several shunt metabolic pathways. This study provides novel insights, based on integrated RNA and protein data, on how plants adapt to the spaceflight environment and it is a step further at achieving sustainable crop production in Space.PMID:38089794 | PMC:PMC10712242 | DOI:10.3389/fpls.2023.1260429

iScience. 2023 Nov 23;26(12):108546. doi: 10.1016/j.isci.2023.108546. eCollection 2023 Dec 15.ABSTRACTEnvironmental variation selects for the adaptive plasticity of maternal provisioning. Even though developing honeybees find themselves in a protected colony environment, their reproductively specialized queens actively adjust their maternal investment, even among worker-destined eggs. However, the potentially adaptive consequences of this flexible provisioning strategy and their mechanistic basis are unknown. Under natural conditions, we find that the body size of larvae hatching from small eggs in large colonies converges with that of initially larger larvae hatching from large eggs typically produced in small colonies. However, large eggs confer a persistent body size advantage when small and large eggs are cross-fostered in small and large colonies, respectively. We substantiate the increased maternal investment by identifying growth-promoting metabolomes and proteomes in large eggs compared to small eggs, which are primarily enriched in amino acid metabolism and cell maturation. Thus, our study provides a comprehensive adaptive explanation for the worker egg size plasticity of honeybees.PMID:38089582 | PMC:PMC10711493 | DOI:10.1016/j.isci.2023.108546

Front Physiol. 2023 Nov 27;14:1274416. doi: 10.3389/fphys.2023.1274416. eCollection 2023.ABSTRACTThe eusocial pest, red imported fire ant (Solenopsis invicta), is a highly invasive species that poses significant threats to public safety, agriculture, and the ecological environment. Cycloxaprid, a newly identified effective, slow-acting, and non-repellent insecticide against S. invicta, allows contaminated individuals to transfer the insecticide among nestmates through body contact. However, the molecular-level changes occurring in S. invicta post cycloxaprid exposure and any molecular alterations contributing to the slow demise or decreased sensitivity remain unclear. In this study, transcriptomic and metabolomic techniques were used to investigate the molecular mechanisms of S. invicta exposed to cycloxaprid. Differential analysis results revealed 275, 323, and 536 differentially expressed genes at 12, 24, and 48 h, respectively. Genes involved in lipid and energy metabolism, DNA integration, and hormone synthesis were largely upregulated at 12 h, suggesting S. invicta might actively resist cycloxaprid impacts, and predominantly downregulated at 48 h, indicating further functional impairment and impending death. Also, we observed an imbalance in olfactory perception pathways at 12 h, which may indicate a disruption in the olfactory system of S. invicta. Metabolomic results showed that the regulation of most differential metabolites (DMs) was consistent with the expression changes of their related DEGs at different time points. Our study provides insights into the mechanism underlying slow-acting and non-repellent properties of cycloxaprid against S. invicta.PMID:38089477 | PMC:PMC10711210 | DOI:10.3389/fphys.2023.1274416

Comput Struct Biotechnol J. 2023 Nov 28;23:96-105. doi: 10.1016/j.csbj.2023.11.045. eCollection 2024 Dec.ABSTRACTImmune-mediated inflammatory diseases (IMIDs) comprise a complex group of pathologies with diverse etiologies and clinical manifestations. In particular, omics technologies have remodeled our understanding of a set of IMIDs such as systemic autoimmune rheumatic diseases (SARDs), generating vast amounts of data on the genome, epigenome, transcriptome, proteome and metabolome of immune cells and SARDs patients. However, the integration of omics data to advance our knowledge of these diseases is challenging, requiring advanced bioinformatic tools. This review explores different multi-omic integrative tools for refining previous research, exploring the biological relevance of datasets within different contexts, or translating omics results into clinical advances. We also discuss relevant multi-omic studies in SARDs research and the potential of omics data from available repositories to complement ongoing investigation in this field.PMID:38089468 | PMC:PMC10714331 | DOI:10.1016/j.csbj.2023.11.045

Diabetes Metab Syndr Obes. 2023 Dec 7;16:4013-4024. doi: 10.2147/DMSO.S428864. eCollection 2023.ABSTRACTOBJECTIVE: Previous studies have shown that oxymatrine (OMT) can improve high-fat-high-fructose-diet-induced non-alcoholic fatty liver disease (NAFLD), and our study aimed to explore its possible metabolic potential mechanisms.METHODS: Wistar rats were fed a high-fat-high-fructose diet for 8 weeks and treated with oxymatrine by gavage for the last 4 weeks. We measured biochemical indicators and pathological changes in each group and used liquid chromatography-mass spectrometry (LC-MS) to analyze changes in metabolites in the serum and liver of the rats.RESULTS: The results showed that OMT can alleviate the high-fat-high-fructose-induced weight gain and hepatic lipid deposition in rats. Metabolomic analysis showed that the level of eicosapentaenoic acid (EPA) was downregulated and levels of desmosterol and d-galactose were upregulated in livers fed with HFDHFr. The levels of L-isoleucine, L-valine, arachidonic acid (AA), taurocholic acid (TCA), chenodeoxycholyltaurine (TDCA), isocitrate, and glutathione (GSH) were downregulated in the liver, whereas those of linoleic acid (LA), phosphocholine (PC), glycerophosphocholine (GPC), and oxidized glutathione (GSSG) were upregulated in the serum treated with OMT.CONCLUSION: In summary, OMT can improve HFDHFr-induced NAFLD, and metabolomic analysis can provide an early warning for the development of NAFLD as well as provide a rationale for therapeutic targets.PMID:38089430 | PMC:PMC10712261 | DOI:10.2147/DMSO.S428864

Front Pharmacol. 2023 Nov 27;14:1243505. doi: 10.3389/fphar.2023.1243505. eCollection 2023.ABSTRACTBackground: We hypothesize that the poor survival outcomes of end-stage kidney disease (ESKD) patients undergoing hemodialysis are associated with a low filtering efficiency and selectivity. The current gold standard criteria using single or several markers show an inability to predict or disclose the treatment effect and disease progression accurately. Methods: We performed an integrated mass spectrometry-based metabolomic and proteomic workflow capable of detecting and quantifying circulating small molecules and proteins in the serum of ESKD patients. Markers linked to cardiovascular disease (CVD) were validated on human induced pluripotent stem cell (iPSC)-derived cardiomyocytes. Results: We identified dozens of elevated molecules in the serum of patients compared with healthy controls. Surprisingly, many metabolites, including lipids, remained at an elevated blood concentration despite dialysis. These molecules and their associated physical interaction networks are correlated with clinical complications in chronic kidney disease. This study confirmed two uremic toxins associated with CVD, a major risk for patients with ESKD. Conclusion: The retained molecules and metabolite-protein interaction network address a knowledge gap of candidate uremic toxins associated with clinical complications in patients undergoing dialysis, providing mechanistic insights and potential drug discovery strategies for ESKD.PMID:38089059 | PMC:PMC10715419 | DOI:10.3389/fphar.2023.1243505

Anal Chem. 2023 Dec 13. doi: 10.1021/acs.analchem.3c03765. Online ahead of print.ABSTRACTSpatially resolved lipidomics is pivotal for detecting and interpreting lipidomes within spatial contexts using the mass spectrometry imaging (MSI) technique. However, comprehensive and efficient lipid identification in MSI remains challenging. Herein, we introduce a high-coverage, database-driven approach combined with air-flow-assisted desorption electrospray ionization (AFADESI)-MSI to generate spatial lipid profiles across whole-body mice. Using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), we identified 2868 unique lipids in the serum and various organs of mice. Subsequently, we systematically evaluated the distinct ionization properties of the lipids between LC-MS and MSI and created a detailed MSI database containing 14 123 ions. This method enabled the visualization of aberrant fatty acid and phospholipid metabolism across organs in a diabetic mouse model. As a powerful extension incorporated into the MSIannotator tool, our strategy facilitates the rapid and accurate annotation of lipids, providing new research avenues for probing spatially resolved heterogeneous metabolic changes in response to diseases.PMID:38088904 | DOI:10.1021/acs.analchem.3c03765

Clin Cancer Res. 2023 Dec 13. doi: 10.1158/1078-0432.CCR-23-2025. Online ahead of print.ABSTRACTPURPOSE: Thyroid cancer (TC) metabolic characteristics vary depending on the molecular subtype determined by mutational status. We aimed to investigate the molecular subtype-specific metabolic characteristics of TCs.EXPERIMENTAL DESIGN: An integrative multi-omics analysis was conducted, incorporating transcriptomics, metabolomics, and proteomics data obtained from human tissues representing distinct molecular characteristics of TCs; BRAF-like (papillary TC with BRAFV600E mutation; PTC-B), RAS-like (follicular TC with RAS mutation; FTC-R), and ATC-like (anaplastic TC with BRAFV600E or RAS mutation; ATC-B or ATC-R). To validate our findings, we employed tissue microarray of human TC tissues and performed in vitro analyses of cancer cell phenotypes and metabolomic assays after inducing genetic knockdown.RESULTS: Metabolic properties differed between differentiated TCs of PTC-B and FTC-R, but were similar in de-differentiated TCs of ATC-B/R, regardless of their mutational status. Tricarboxylic acid (TCA) intermediates and branched-chain amino acids (BCAA) were enriched with the activation of TCA cycle only in FTC-R, whereas one-carbon metabolism and pyrimidine metabolism increased in both PTC-B and FTC-R and to a great extent in ATC-B/R. However, the protein expression levels of the BCAA transporter (SLC7A5) and a key enzyme in one-carbon metabolism (SHMT2) increased in all TCs and were particularly high in ATC-B/R. Knockdown of SLC7A5 or SHMT2 inhibited the migration and proliferation of TC cell lines differently, depending on the mutational status.CONCLUSIONS: These findings define the metabolic properties of each molecular subtype of TCs and identify metabolic vulnerabilities, providing a rationale for therapies targeting its altered metabolic pathways in advanced TC.PMID:38088902 | DOI:10.1158/1078-0432.CCR-23-2025