Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Pyroptotic macrophages induce disruption of glutamate metabolism in periodontal ligament stem cells contributing to their compromised osteogenic potential

Tue, 28/05/2024 - 12:00
Cell Prolif. 2024 May 27:e13663. doi: 10.1111/cpr.13663. Online ahead of print.ABSTRACTMacrophage pyroptosis is of key importance to host defence against pathogen infections and may participate in the progression and recovery of periodontitis. However, the role of pyroptotic macrophages in regulating periodontal ligament stem cells (PDLSCs), the main cell source for periodontium renewal, remains unclear. First, we found that macrophage pyroptosis were enriched in gingiva tissues from periodontitis patients compared with those of healthy people through immunofluorescence. Then the effects of pyroptotic macrophages on the PDLSC osteogenic differentiation were investigated in a conditioned medium (CM)-based coculture system in vitro. CM derived from pyroptotic macrophages inhibited the osteogenic differentiation-related gene and protein levels, ALP activity and mineralized nodule formation of PDLSCs. The osteogenic inhibition of CM was alleviated when pyroptosis was inhibited by VX765. Further, untargeted metabolomics showed that glutamate limitation may be the underlying mechanism. However, exogenous glutamate supplementation aggravated the CM-inhibited osteogenic differentiation of PDLSCs. Moreover, CM increased extracellular glutamate and decreased intracellular glutamate levels of PDLSCs, and enhanced the gene and protein expression levels of system xc - (a cystine/glutamate antiporter). After adding cystine to CM-based incubation, the compromised osteogenic potency of PDLSCs was rescued. Our data suggest that macrophage pyroptosis is related to the inflammatory lesions of periodontitis. Either pharmacological inhibition of macrophage pyroptosis or nutritional supplements to PDLSCs, can rescue the compromised osteogenic potency caused by pyroptotic macrophages.PMID:38803043 | DOI:10.1111/cpr.13663

Circadian light/dark cycle reversal exacerbates the progression of chronic kidney disease in mice

Tue, 28/05/2024 - 12:00
J Pineal Res. 2024 May;76(4):e12964. doi: 10.1111/jpi.12964.ABSTRACTCircadian disruption such as shift work, jet lag, has gradually become a global health issue and is closely associated with various metabolic disorders. The influence and mechanism of circadian disruption on renal injury in chronic kidney disease (CKD) remains inadequately understood. Here, we evaluated the impact of environmental light disruption on the progression of chronic renal injury in CKD mice. By using two abnormal light exposure models to induce circadian disruption, we found that circadian disruption induced by weekly light/dark cycle reversal (LDDL) significantly exacerbated renal dysfunction, accelerated renal injury, and promoted renal fibrosis in mice with 5/6 nephrectomy and unilateral ureteral obstruction (UUO). Mechanistically, RNA-seq analysis revealed significant immune and metabolic disorder in the LDDL-conditioned CKD kidneys. Consistently, renal content of ATP was decreased and ROS production was increased in the kidney tissues of the LDDL-challenged CKD mice. Untargeted metabolomics revealed a significant buildup of lipids in the kidney affected by LDDL. Notably, the level of β-NMN, a crucial intermediate in the NAD+ pathway, was found to be particularly reduced. Moreover, we demonstrated that both β-NMN and melatonin administration could significantly rescue the light-disruption associated kidney dysfunction. In conclusion, environmental circadian disruption may exacerbate chronic kidney injury by facilitating inflammatory responses and disturbing metabolic homeostasis. β-NMN and melatonin treatments may hold potential as promising approaches for preventing and treating light-disruption associated CKD.PMID:38803014 | DOI:10.1111/jpi.12964

Integrating uterine microbiome and metabolome to advance the understanding of the uterine environment in dairy cows with metritis

Mon, 27/05/2024 - 12:00
Anim Microbiome. 2024 May 27;6(1):30. doi: 10.1186/s42523-024-00314-7.ABSTRACTBACKGROUND: Metritis is a prevalent uterine disease that affects the welfare, fertility, and survival of dairy cows. The uterine microbiome from cows that develop metritis and those that remain healthy do not differ from calving until 2 days postpartum, after which there is a dysbiosis of the uterine microbiome characterized by a shift towards opportunistic pathogens such as Fusobacteriota and Bacteroidota. Whether these opportunistic pathogens proliferate and overtake the uterine commensals could be determined by the type of substrates present in the uterus. The objective of this study was to integrate uterine microbiome and metabolome data to advance the understanding of the uterine environment in dairy cows that develop metritis. Holstein cows (n = 104) had uterine fluid collected at calving and at the day of metritis diagnosis. Cows with metritis (n = 52) were paired with cows without metritis (n = 52) based on days after calving. First, the uterine microbiome and metabolome were evaluated individually, and then integrated using network analyses.RESULTS: The uterine microbiome did not differ at calving but differed on the day of metritis diagnosis between cows with and without metritis. The uterine metabolome differed both at calving and on the day of metritis diagnosis between cows that did and did not develop metritis. Omics integration was performed between 6 significant bacteria genera and 153 significant metabolites on the day of metritis diagnosis. Integration was not performed at calving because there were no significant differences in the uterine microbiome. A total of 3 bacteria genera (i.e. Fusobacterium, Porphyromonas, and Bacteroides) were strongly correlated with 49 metabolites on the day of metritis diagnosis. Seven of the significant metabolites at calving were among the 49 metabolites strongly correlated with opportunistic pathogenic bacteria on the day of metritis diagnosis. The main metabolites have been associated with attenuation of biofilm formation by commensal bacteria, opportunistic pathogenic bacteria overgrowth, tissue damage and inflammation, immune evasion, and immune dysregulation.CONCLUSIONS: The data integration presented herein helps advance the understanding of the uterine environment in dairy cows with metritis. The identified metabolites may provide a competitive advantage to the main uterine pathogens Fusobacterium, Porphyromonas and Bacteroides, and may be promising targets for future interventions aiming to reduce opportunistic pathogenic bacteria growth in the uterus.PMID:38802977 | DOI:10.1186/s42523-024-00314-7

Metabolome-wide Mendelian randomization for age at menarche and age at natural menopause

Mon, 27/05/2024 - 12:00
Genome Med. 2024 May 28;16(1):69. doi: 10.1186/s13073-024-01322-7.ABSTRACTBACKGROUND: The role of metabolism in the variation of age at menarche (AAM) and age at natural menopause (ANM) in the female population is not entirely known. We aimed to investigate the causal role of circulating metabolites in AAM and ANM using Mendelian randomization (MR).METHODS: We combined MR with genetic colocalization to investigate potential causal associations between 658 metabolites and AAM and between 684 metabolites and ANM. We extracted genetic instruments for our exposures from four genome-wide association studies (GWAS) on circulating metabolites and queried the effects of these variants on the outcomes in two large GWAS from the ReproGen consortium. Additionally, we assessed the mediating role of the body mass index (BMI) in these associations, identified metabolic pathways implicated in AAM and ANM, and sought validation for selected metabolites in the Avon Longitudinal Study of Parents and Children (ALSPAC).RESULTS: Our analysis identified 10 candidate metabolites for AAM, but none of them colocalized with AAM. For ANM, 76 metabolites were prioritized (FDR-adjusted MR P-value ≤ 0.05), with 17 colocalizing, primarily in the glycerophosphocholines class, including the omega-3 fatty acid and phosphatidylcholine (PC) categories. Pathway analyses and validation in ALSPAC mothers also highlighted the role of omega and polyunsaturated fatty acids levels in delaying age at menopause.CONCLUSIONS: Our study suggests that metabolites from the glycerophosphocholine and fatty acid families play a causal role in the timing of both menarche and menopause. This underscores the significance of specific metabolic pathways in the biology of female reproductive longevity.PMID:38802955 | DOI:10.1186/s13073-024-01322-7

UHPLC-HRMS-based Multiomics to Explore the Potential Mechanisms and Biomarkers for Colorectal Cancer

Mon, 27/05/2024 - 12:00
BMC Cancer. 2024 May 27;24(1):644. doi: 10.1186/s12885-024-12321-7.ABSTRACTBACKGROUND: Understanding the metabolic changes in colorectal cancer (CRC) and exploring potential diagnostic biomarkers is crucial for elucidating its pathogenesis and reducing mortality. Cancer cells are typically derived from cancer tissues and can be easily obtained and cultured. Systematic studies on CRC cells at different stages are still lacking. Additionally, there is a need to validate our previous findings from human serum.METHODS: Ultrahigh-performance liquid chromatography tandem high-resolution mass spectrometry (UHPLC-HRMS)-based metabolomics and lipidomics were employed to comprehensively measure metabolites and lipids in CRC cells at four different stages and serum samples from normal control (NR) and CRC subjects. Univariate and multivariate statistical analyses were applied to select the differential metabolites and lipids between groups. Biomarkers with good diagnostic efficacy for CRC that existed in both cells and serum were screened by the receiver operating characteristic curve (ROC) analysis. Furthermore, potential biomarkers were validated using metabolite standards.RESULTS: Metabolite and lipid profiles differed significantly among CRC cells at stages A, B, C, and D. Dysregulation of glycerophospholipid (GPL), fatty acid (FA), and amino acid (AA) metabolism played a crucial role in the CRC progression, particularly GPL metabolism dominated by phosphatidylcholine (PC). A total of 46 differential metabolites and 29 differential lipids common to the four stages of CRC cells were discovered. Eight metabolites showed the same trends in CRC cells and serum from CRC patients compared to the control groups. Among them, palmitoylcarnitine and sphingosine could serve as potential biomarkers with the values of area under the curve (AUC) more than 0.80 in the serum and cells. Their panel exhibited excellent performance in discriminating CRC cells at different stages from normal cells (AUC = 1.00).CONCLUSIONS: To our knowledge, this is the first research to attempt to validate the results of metabolism studies of serum from CRC patients using cell models. The metabolic disorders of PC, FA, and AA were closely related to the tumorigenesis of CRC, with PC being the more critical factor. The panel composed of palmitoylcarnitine and sphingosine may act as a potential biomarker for the diagnosis of CRC, aiding in its prevention.PMID:38802800 | DOI:10.1186/s12885-024-12321-7

USP9X-mediated REV1 deubiquitination promotes lung cancer radioresistance via the action of REV1 as a Rad18 molecular scaffold for cystathionine γ-lyase

Mon, 27/05/2024 - 12:00
J Biomed Sci. 2024 May 28;31(1):55. doi: 10.1186/s12929-024-01044-3.ABSTRACTBACKGROUND: Radioresistance is a key clinical constraint on the efficacy of radiotherapy in lung cancer patients. REV1 DNA directed polymerase (REV1) plays an important role in repairing DNA damage and maintaining genomic stability. However, its role in the resistance to radiotherapy in lung cancer is not clear. This study aims to clarify the role of REV1 in lung cancer radioresistance, identify the intrinsic mechanisms involved, and provide a theoretical basis for the clinical translation of this new target for lung cancer treatment.METHODS: The effect of targeting REV1 on the radiosensitivity was verified by in vivo and in vitro experiments. RNA sequencing (RNA-seq) combined with nontargeted metabolomics analysis was used to explore the downstream targets of REV1. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to quantify the content of specific amino acids. The coimmunoprecipitation (co-IP) and GST pull-down assays were used to validate the interaction between proteins. A ubiquitination library screening system was constructed to investigate the regulatory proteins upstream of REV1.RESULTS: Targeting REV1 could enhance the radiosensitivity in vivo, while this effect was not obvious in vitro. RNA sequencing combined with nontargeted metabolomics revealed that the difference result was related to metabolism, and that the expression of glycine, serine, and threonine (Gly/Ser/Thr) metabolism signaling pathways was downregulated following REV1 knockdown. LC-MS/MS demonstrated that REV1 knockdown results in reduced levels of these three amino acids and that cystathionine γ-lyase (CTH) was the key to its function. REV1 enhances the interaction of CTH with the E3 ubiquitin ligase Rad18 and promotes ubiquitination degradation of CTH by Rad18. Screening of the ubiquitination compound library revealed that the ubiquitin-specific peptidase 9 X-linked (USP9X) is the upstream regulatory protein of REV1 by the ubiquitin-proteasome system, which remodels the intracellular Gly/Ser/Thr metabolism.CONCLUSION: USP9X mediates the deubiquitination of REV1, and aberrantly expressed REV1 acts as a scaffolding protein to assist Rad18 in interacting with CTH, promoting the ubiquitination and degradation of CTH and inducing remodeling of the Gly/Ser/Thr metabolism, which leads to radioresistance. A novel inhibitor of REV1, JH-RE-06, was shown to enhance lung cancer cell radiosensitivity, with good prospects for clinical translation.PMID:38802791 | DOI:10.1186/s12929-024-01044-3

A comparison between the role of enniatins and deoxynivalenol in Fusarium virulence on different tissues of common wheat

Mon, 27/05/2024 - 12:00
BMC Plant Biol. 2024 May 27;24(1):463. doi: 10.1186/s12870-024-04945-5.ABSTRACTBACKGROUND: Fusarium graminearum and Fusarium avenaceum are two of the most important causal agents of Fusarium head blight (FHB) of wheat. They can produce mycotoxins that accumulate in infected wheat heads, including deoxynivalenol (DON) and enniatins (ENNs), produced by F. graminearum and F. avenaceum, respectively. While the role of DON as a virulence factor in F. graminearum toward wheat is well known, ENNs in F. avenaceum has been poorly explored. Results obtained to-date indicate that ENNs may confer an advantage to F. avenaceum only on particular hosts.RESULTS: In this study, with the use of ENN-producing and ENN non-producing F. avenaceum strains, the role of ENNs on F. avenaceum virulence was investigated on the root, stem base and head of common wheat, and compared with the role of DON, using DON-producing and DON non-producing F. graminearum strains. The DON-producing F. graminearum strain showed a significantly higher ability to cause symptoms and colonise each of the tested tissues than the non-producing strain. On the other hand, the ability to produce ENNs increased initial symptoms of the disease and fungal biomass accumulation, measured by qPCR, only in wheat heads, and not in roots or stem bases. LC-MS/MS analysis was used to confirm the presence of ENNs and DON in the different strains, and results, both in vitro and in wheat heads, were consistent with the genetics of each strain.CONCLUSION: While the key role of DON on F. graminearum virulence towards three different wheat tissues was noticeable, ENNs seemed to have a role only in influencing F. avenaceum virulence on common wheat heads probably due to an initial delay in the appearance of symptoms.PMID:38802782 | DOI:10.1186/s12870-024-04945-5

Water deprivation modifies the metabolic profile of lavender (Lavandula angustifolia Mill.) leaves

Mon, 27/05/2024 - 12:00
Physiol Plant. 2024 May-Jun;176(3):e14365. doi: 10.1111/ppl.14365.ABSTRACTLavender plantation is globally expanded due to the increasing demand of its essential oil and its popularity as an ornamental species. However, lavender plantations, and consequently essential oil industries, are threatened by more frequent and severe drought episodes in a globally changing climate. Still little is known about the changes in the general metabolome, which provides the precursors of essential oil production, by extended drought events. Prolonged drought fundamentally results in yield losses and changing essential oil composition. In the present study, the general metabolome of a main cultivated lavender species (Lavandula angustifolia Mill.) in response to water deprivation (WD) and re-watering was analyzed to identify the metabolomics responses. We found prolonged WD resulted in significant accumulations of glucose, 1,6-anhydro-β-D-glucose, sucrose, melezitose and raffinose, but declines of allulose, β-D-allose, altrose, fructose and D-cellobiose accompanied by decreased organic acids abundances. Amino acids and aromatic compounds of p-coumaric acid, hydrocaffeic acid and caffeic acid significantly accumulated at prolonged WD, whereas aromatics of cis-ferulic acid, taxifolin and two fatty acids (i.e., palmitic acid and stearic acid) significantly decreased. Prolonged WD also resulted in decreased abundances of polyols, particularly myo-inositol, galactinol and arabitol. The altered metabolite profiles by prolonged WD were mostly not recovered after re-watering, except for branched-chain amino acids, proline, serine and threonine. Our study illustrates the complex changes of leaf primary and secondary metabolic processes of L. angustifolia by drought events and highlights the potential impact of these precursors of essential oil production on the lavender industry.PMID:38802725 | DOI:10.1111/ppl.14365

A fundamental study on postmortem submersion interval estimation by metabolomics analyzing of gastrocnemius muscle from submersed rat models in freshwater

Mon, 27/05/2024 - 12:00
Int J Legal Med. 2024 May 28. doi: 10.1007/s00414-024-03258-4. Online ahead of print.ABSTRACTIn forensic practice, determining the postmortem submersion interval (PMSI) and cause-of-death of cadavers in aquatic ecosystems has always been challenging task. Traditional approaches are not yet able to address these issues effectively and adequately. Our previous study proposed novel models to predict the PMSI and cause-of-death based on metabolites of blood from rats immersed in freshwater. However, with the advance of putrefaction, it is hardly to obtain blood samples beyond 3 days postmortem. To further assess the feasibility of PMSI estimation and drowning diagnosis in the later postmortem phase, gastrocnemius, the more degradation-resistant tissue, was collected from drowned rats and postmortem submersion model in freshwater immediately after death, and at 1 day, 3 days, 5 days, 7 days, and 10 days postmortem respectively. Then the samples were analyzed with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to investigate the dynamic changes of the metabolites. A total of 924 metabolites were identified. Similar chronological changes of gastrocnemius metabolites were observed in the drowning and postmortem submersion groups. The difference in metabolic profiles between drowning and postmortem submersion groups was only evident in the initial 1 day postmortem, which was faded as the PMSI extension. Nineteen metabolites representing temporally-dynamic patterns were selected as biomarkers for PMSI estimation. A regression model was built based on these biomarkers with random forest algorithm, which yielded a mean absolute error (± SE) of 5.856 (± 1.296) h on validation samples from an independent experiment. These findings added to our knowledge of chronological changes in muscle metabolites from submerged vertebrate remains during decomposition, which provided a new perspective for PMSI estimation.PMID:38802694 | DOI:10.1007/s00414-024-03258-4

LncRNA TUG1 mediates microglial inflammatory activation by regulating glucose metabolic reprogramming

Mon, 27/05/2024 - 12:00
Sci Rep. 2024 May 27;14(1):12143. doi: 10.1038/s41598-024-62966-4.ABSTRACTMicroglia are natural immune cells in the central nervous system, and the activation of microglia is accompanied by a reprogramming of glucose metabolism. In our study, we investigated the role of long non-coding RNA taurine-upregulated gene 1 (TUG1) in regulating microglial glucose metabolism reprogramming and activation. BV2 cells were treated with Lipopolysaccharides (LPS)/Interferon-γ (IFN-γ) to establish a microglial activation model. The glycolysis inhibitor 2-Deoxy-D-glucose (2-DG) was used as a control. The expression levels of TUG1 mRNA and proinflammatory cytokines such as Interleukin-1β (IL-1β), Interleukin -6, and Tumor Necrosis Factor-α mRNA and anti-inflammatory cytokines such as IL-4, Arginase 1(Arg1), CD206, and Ym1 were detected by RT-qPCR. TUG1 was silenced using TUG1 siRNA and knocked out using CRISPR/Cas9. The mRNA and protein expression levels of key enzymes involved in glucose metabolism, such as Hexokinase2, Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), Lactate dehydrogenase, Glucose 6 phosphate dehydrogenase, and Pyruvate dehydrogenase (PDH), were determined by RT-qPCR and Western blotting. The glycolytic rate of microglial cells was measured using Seahorse. Differential metabolites were determined by metabolomics, and pathway enrichment was performed using these differential metabolites. Our findings revealed that the expression of TUG1 was elevated in proinflammatory-activated microglia and positively correlated with the levels of inflammatory factors. The expression of anti-inflammatory cytokines such as IL-4, Arg1, CD206, and Ym1 were decreased when induced with LPS/IFN-γ. However, this decrease was reversed by the treatment with 2-DG. Silencing of GAPDH led to an increase in the expression of TUG1 and inflammatory factors. TUG1 knockout (TUG1KO) inhibited the expression of glycolytic key enzymes and promoted the expression of oxidative phosphorylation key enzymes, shifting the metabolic profile of activated microglia from glycolysis to oxidative phosphorylation. Additionally, TUG1KO reduced the accumulation of metabolites, facilitating the restoration of the tricarboxylic acid cycle and enhancing oxidative phosphorylation in microglia. Furthermore, the downregulation of TUG1 was found to reduce the expression of both proinflammatory and anti-inflammatory cytokines under normal conditions. Interestingly, when induced with LPS/IFN-γ, TUG1 downregulation showed a potentially beneficial effect on microglia in terms of inflammation. Downregulation of TUG1 expression inhibits glycolysis and facilitates the shift of microglial glucose metabolism from glycolysis to oxidative phosphorylation, promoting their transformation towards an anti-inflammatory phenotype and exerting anti-inflammatory effects in BV2.PMID:38802677 | DOI:10.1038/s41598-024-62966-4

Gerogenes and gerosuppression: the pillars of precision geromedicine

Mon, 27/05/2024 - 12:00
Cell Res. 2024 May 27. doi: 10.1038/s41422-024-00977-6. Online ahead of print.NO ABSTRACTPMID:38802575 | DOI:10.1038/s41422-024-00977-6

METLIN-CCS Lipid Database: An authentic standards resource for lipid classification and identification

Mon, 27/05/2024 - 12:00
Nat Metab. 2024 May 27. doi: 10.1038/s42255-024-01058-z. Online ahead of print.NO ABSTRACTPMID:38802544 | DOI:10.1038/s42255-024-01058-z

Phenotypical and biochemical characterization of tomato plants treated with triacontanol

Mon, 27/05/2024 - 12:00
Sci Rep. 2024 May 27;14(1):12096. doi: 10.1038/s41598-024-62398-0.ABSTRACTBiostimulants are heterogeneous products designed to support plant development and to improve the yield and quality of crops. Here, we focused on the effects of triacontanol, a promising biostimulant found in cuticle waxes, on tomato growth and productivity. We examined various phenological traits related to vegetative growth, flowering and fruit yield, the metabolic profile of fruits, and the response of triacontanol-treated plants to salt stress. Additionally, a proteomic analysis was conducted to clarify the molecular mechanisms underlying triacontanol action. Triacontanol application induced advanced and increased blooming without affecting plant growth. Biochemical analyses of fruits showed minimal changes in nutritional properties. The treatment also increased the germination rate of seeds by altering hormone homeostasis and reduced salt stress-induced damage. Proteomics analysis of leaves revealed that triacontanol increased the abundance of proteins related to development and abiotic stress, while down-regulating proteins involved in biotic stress resistance. The proteome of the fruits was not significantly affected by triacontanol, confirming that biostimulation did not alter the nutritional properties of fruits. Overall, our findings provide evidence of the effects of triacontanol on growth, development, and stress tolerance, shedding light on its mechanism of action and providing new insights into its potential in agricultural practices.PMID:38802434 | DOI:10.1038/s41598-024-62398-0

Metabolomic-derived endotypes of age-related macular degeneration (AMD): a step towards identification of disease subgroups

Mon, 27/05/2024 - 12:00
Sci Rep. 2024 May 27;14(1):12145. doi: 10.1038/s41598-024-59045-z.ABSTRACTAge-related macular degeneration (AMD) is a leading cause of blindness worldwide, with a complex pathophysiology and phenotypic diversity. Here, we apply Similarity Network Fusion (SNF) to cluster AMD patients into putative metabolomics-derived endotypes. Using a discovery cohort of 163 AMD patients from Boston, US, and a validation cohort of 214 patients from Coimbra, Portugal, we identified four distinct metabolomics-derived endotypes with varying retinal structural and functional characteristics, confirmed across both cohorts. Patients clustered into Endotype 1 exhibited a milder form of AMD and were characterized by low levels of amino acids in specific metabolic pathways. Meanwhile, patients clustered into both Endotype 3 and 4 were associated with more severe AMD and exhibited low levels of fatty acid metabolites and elevated levels of sphingomyelins and fatty acid metabolites, respectively. These preliminary findings indicate that metabolomics-derived endotyping may offer a refined strategy for categorizing AMD patients based on their specific pathophysiological underpinnings, rather than relying solely on traditional observational clinical indicators.PMID:38802406 | DOI:10.1038/s41598-024-59045-z

Research progress on pneumoconiosis markers based on multi-omics analysis

Mon, 27/05/2024 - 12:00
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2024 May 20;42(5):384-395. doi: 10.3760/cma.j.cn121094-20230321-00089.ABSTRACTThe etiology of pneumoconiosis is relatively clear, but the pathogenic mechanism is not fully understood, and there is no effective cure for pneumoconiosis. Clarifying the pathogenesis of pneumoconiosis and exploring relevant markers can help screen high-risk groups of dust exposure, and relevant markers can also be used as targets to intervene in the process of pulmonary fibrosis. The in-depth development of genomics, transcriptomics and proteomics has provided a new way to discover more potential markers of pneumoconiosis. In the future, the combination of multi-omics and multi-stage interactive analysis can systematically and comprehensively identify key genes (proteins) , metabolites and metabolic pathways in the occurrence and development of pneumoconiosis, build a core regulatory network, and then screen out sensitive markers related to early diagnosis and treatment of pneumoconiosis. This article summarizes the research progress of pneumoconiosis markers from the perspective of multi-omics, hoping to provide more basic data for the early prevention and diagnosis of pneumoconiosis, pathogenesis research, and therapeutic intervention.PMID:38802314 | DOI:10.3760/cma.j.cn121094-20230321-00089

From use of omics to systems biology: Identifying therapeutic targets for amyotrophic lateral sclerosis

Mon, 27/05/2024 - 12:00
Int Rev Neurobiol. 2024;176:209-268. doi: 10.1016/bs.irn.2024.02.001. Epub 2024 May 22.ABSTRACTAmyotrophic lateral sclerosis (ALS) is a heterogeneous progressive neurodegenerative disorder with available treatments such as riluzole and edaravone extending survival by an average of 3-6 months. The lack of highly effective, widely available therapies reflects the complexity of ALS. Omics technologies, including genomics, transcriptomic and proteomics have contributed to the identification of biological pathways dysregulated and targeted by therapeutic strategies in preclinical and clinical trials. Integrating clinical, environmental and neuroimaging information with omics data and applying a systems biology approach can further improve our understanding of the disease with the potential to stratify patients and provide more personalised medicine. This chapter will review the omics technologies that contribute to a systems biology approach and how these components have assisted in identifying therapeutic targets. Current strategies, including the use of genetic screening and biosampling in clinical trials, as well as the future application of additional technological advances, will also be discussed.PMID:38802176 | DOI:10.1016/bs.irn.2024.02.001

Differences in (1)HNMR Based Metabolomic Patterns of Malignant and Benign Pleural Effusions

Mon, 27/05/2024 - 12:00
Ann Clin Lab Sci. 2024 Mar;54(2):201-210.ABSTRACTOBJECTIVE: Malignant pleural effusion (MPE) is a common complication of lung cancer with poor prognosis. Benign pleural effusion (BPE), such as tuberculous and pneumonic pleural effusion, usually has a good prognosis. Differential diagnosis between MPE and BPE remains a clinical challenge.METHODS: 52 MPE, 93 BPE, and their corresponding serum samples were analyzed by hydrogen nuclear magnetic resonance (1HNMR) based metabolomics.RESULTS: The 1HNMR study showed that some amino acids and betaine in MPE are significantly altered in pleural effusion and serum compared to BPE patients. Levels of serum glucose and glutamine have strong positive correlation with those in pleural effusion (r>0.6) for MPE patients. The area under the receiver operating characteristic curve (AUROC) values of metabolites in pleural effusion or serum were less than 0.805 in differentiating MPE from BPE. Improved an AUROC value of 0.901 was observed using pleural effusion-serum ratios of glutamic acid in differentiating MPE from BPE, which was further validated by 15 double-blind samples.CONCLUSIONS: Compared with BPE patients, amino acids and betaine in MPE are significantly altered in pleural effusion and serum. Pleural effusion-serum ratio of glutamic acid may contribute to the rapid diagnosis of MPE from BPE by 1HNMR analysis.PMID:38802158

Gas chromatography/mass spectrometry-based metabolite profiling of chia and quinoa seeds in comparison with wheat and oat

Mon, 27/05/2024 - 12:00
Phytochem Anal. 2024 May 27. doi: 10.1002/pca.3398. Online ahead of print.ABSTRACTINTRODUCTION: With an increasing interest in healthy and affordable cereal intake, efforts are made toward exploiting underutilized cereals with high nutritional values.OBJECTIVES: The current study aims to explore the metabolome diversity in 14 cultivars of chia and quinoa collected from Germany, Austria, and Egypt, compared with wheat and oat as major cereals.MATERIAL AND METHODS: The samples were analyzed using gas chromatography-mass spectrometry (GC-MS). Multivariate data analysis (MVA) was employed for sample classification and markers characterization.RESULTS: A total of 114 metabolites were quantified (sugars, alcohols, organic and amino acids/nitrogenous compounds, fatty acids/esters), but the inorganic and phenolic acids were only identified. Fatty acids were the major class followed by amino acids in quinoa and chia. Chia and oats were richer in sucrose. Quinoa encompassed higher amino acids. Quinoa and chia were rich in essential amino acids. Higher levels of unsaturated fatty acids especially omega 6 and omega 9 were detected in quinoa versus omega 3 in chia compared with oat and wheat, whereas ω6/ω3 fatty acid ratio of chia was the lowest. To the best of our knowledge, this is the first comprehensive metabolite profiling of these pseudo cereals.CONCLUSION: Quinoa and chia, especially red chia, are more nutritionally valuable compared with oat and wheat because of their compositional profile of free amino acids, organic acids, and essential fatty acids, besides their low ω6/ω3 fatty acid ratio. Such results pose them as inexpensive alternative to animal proteins and encourage their inclusion in infant formulas.PMID:38802070 | DOI:10.1002/pca.3398

Loss of temporal coherence in the circadian metabolome across multiple tissues during ageing in mice

Mon, 27/05/2024 - 12:00
Eur J Neurosci. 2024 May 27. doi: 10.1111/ejn.16428. Online ahead of print.ABSTRACTCircadian clock function declines with ageing, which can aggravate ageing-related diseases such as type 2 diabetes and neurodegenerative disorders. Understanding age-related changes in the circadian system at a systemic level can contribute to the development of strategies to promote healthy ageing. The goal of this study was to investigate the impact of ageing on 24-h rhythms in amine metabolites across four tissues in young (2 months of age) and old (22-25 months of age) mice using a targeted metabolomics approach. Liver, plasma, the suprachiasmatic nucleus (SCN; the location of the central circadian clock in the hypothalamus) and the paraventricular nucleus (PVN; a downstream target of the SCN) were collected from young and old mice every 4 h during a 24-h period (n = 6-7 mice per group). Differential rhythmicity analysis revealed that ageing impacts 24-h rhythms in the amine metabolome in a tissue-specific manner. Most profound changes were observed in the liver, in which rhythmicity was lost in 60% of the metabolites in aged mice. Furthermore, we found strong correlations in metabolite levels between the liver and plasma and between the SCN and the PVN in young mice. These correlations were almost completely abolished in old mice. These results indicate that ageing is accompanied by a severe loss of the circadian coordination between tissues and by disturbed rhythmicity of metabolic processes. The tissue-specific impact of ageing may help to differentiate mechanisms of ageing-related disorders in the brain versus peripheral tissues and thereby contribute to the development of potential therapies for these disorders.PMID:38802069 | DOI:10.1111/ejn.16428

Optimizing polystyrene degradation, microbial community and metabolite analysis of intestinal flora of yellow mealworms, Tenebrio molitor

Mon, 27/05/2024 - 12:00
Bioresour Technol. 2024 May 25:130895. doi: 10.1016/j.biortech.2024.130895. Online ahead of print.ABSTRACTThis study explored a direct feeding of expanded polystyrene as the sole diet for breeding Tenebrio molitor larvae. Temperature and relative humidity were manipulated to evaluate polystyrene biodegradation efficiency, survival rate, and formation of micro-polystyrene residue. Efficient conditions were at temperature of 25 °C with a humidity of 65 ± 5 %. Comparative metabolomic and metabolic-metabolic network analyses was performed for visualizing detailed pathway. Possibility of forming 4 (p)-hydroxyphenylacetic acid from phenylacetic acid with further conversion to 4-methylphenol, 4-hydroxybenzaldehyde, and 4-hydroxybenzoate could be seen as a side chain route for further biodegrading process. Key species identified in the gut of T. molitor larvae included Citrobacter sp., Serratia marcescens, Klebsiella aerogenes, and Klebsiella oxytoca. Pseudomonas aeruginosa was detected only under an anaerobic condition whereas Acinetobacter sp. was present only under an aerobic condition. These results demonstrate the potential to decrease micro-polystyrene by optimizing breeding conditions and biodegradation process of polystyrene.PMID:38801953 | DOI:10.1016/j.biortech.2024.130895

Pages