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

Impact of the redox-active MnTnHex-2-PyP(5+) and cisplatin on the metabolome of non-small cell lung cancer cells

Sun, 14/07/2024 - 12:00
Biochem Pharmacol. 2024 Jul 12:116424. doi: 10.1016/j.bcp.2024.116424. Online ahead of print.ABSTRACTRedox-based cancer therapeutic strategies aim to raise reactive oxygen species (ROS) levels in cancer cells, thus modifying their redox status, and eventually inducing cell death. Promising compounds, known as superoxide dismutase mimics (SODm), e.g. MnTnHex-2-Py5+ (MnTnHex), could increase intracellular H2O2 in cancer cells with deficient ROS removal systems and therefore enhance radio- and chemotherapy efficacy. We have previously shown that MnTnHex was cytotoxic either alone or combined with cisplatin to non-small cell lung cancer (NSCLC) cells. To gain a deeper understanding of the effects and safety of this compound, it is crucial to analyze the metabolic alterations that take place within the cell. Our goal was thus to study the intracellular metabolome (intracellular metabolites) of NSCLC cells (A549 and H1975) using nuclear magnetic resonance (NMR) spectroscopy-based metabolomics to evaluate the changes in cellular metabolism upon exposure to MnTnHex per se or in combination with cisplatin. 1H NMR metabolomics revealed a higher number of significantly altered metabolites in A549 cells exposed to MnTnHex alone or combined with cisplatin in comparison with non-treated cells (nine dysregulated metabolites), suggesting an impact on aminoacyl-tRNA biosynthesis, glycolysis/gluconeogenesis, and taurine and hypotaurine, glycerophospholipid, pyruvate, arginine and proline metabolisms. In turn, H1975 cells exhibited significant alterations in the levels of six metabolites upon co-treatment with MnTnHex and cisplatin, suggesting dysregulations in aminoacyl-tRNA biosynthesis, arginine and proline metabolism, pyruvate metabolism, and glycolysis/gluconeogenesis. These findings help us understanding the impact of MnTnHex on NSCLC cells. Importantly, specific altered metabolites, such as taurine, may contribute to the chemosensitizing effects of MnTnHex.PMID:39004232 | DOI:10.1016/j.bcp.2024.116424

Metabolomics study on fermentation of Lactiplantibacillus plantarum ST-III with food grade proliferators in milk

Sun, 14/07/2024 - 12:00
J Dairy Sci. 2024 Jul 12:S0022-0302(24)01005-1. doi: 10.3168/jds.2024-25017. Online ahead of print.ABSTRACTMilk is a naturally complex medium that is suitable for the growth of most lactic acid bacteria. Unfortunately, Lactiplantibacillus plantarum ST-III grow poorly in milk without supplementation. To solve this problem, we use fresh pineapple and mung beans juice to develop an edible proliferator for L. plantarum ST-III. Our comparative analysis of metabolomics changes before and after fermentation reveals that amino acids and dipeptides are the most consumed compounds, with other substances including nucleotides and vitamins, implying the mechanism of proliferation. Combining the KEGG metabolic pathway analysis, substances that may promote the growth of L. plantarum ST-III in milk were screened. To explore which component of the proliferator is required for L. plantarum ST-III cultivate, we supplemented with several combinations of molecules aforementioned in milk. The simulation addition experiment results of L. plantarum ST-III in milk show that if any additions are missing, the concentration of viable bacteria is lower. Only when it contains all additives can the highest concentration of viable bacteria be obtained. Compared with the control, the fold change of the viable bacteria is about 32. Thus, it proves that milk primarily lacked available amino acids, dipeptides, uracil, xanthine, nicotinamide, and manganese for the growth of L. plantarum ST-III.PMID:39004129 | DOI:10.3168/jds.2024-25017

Disorders of fatty acid metabolism and imbalance in the ratio of monounsaturated fatty acids promote the development of pulmonary fibrosis

Sun, 14/07/2024 - 12:00
Int Immunopharmacol. 2024 Jul 13;139:112671. doi: 10.1016/j.intimp.2024.112671. Online ahead of print.ABSTRACTOBJECTIVE: Although some studies suggested that metabolic abnormalities may contribute to the development of pulmonary fibrosis, there are no studies that have reported a clear causal relationship between them, and the aim of this study was to explore the causal relationship between plasma metabolites and pulmonary fibrosis using Mendelian randomization (MR) combined with metabolomics analysis.METHODS: Firstly, we explored the causal relationship between 1400 metabolites and pulmonary fibrosis using MR analysis, and detected plasma metabolites in mice with pulmonary fibrosis using metabolomics technology, thus validating the results of MR analysis. In addition, we again used MR to explore the causal relationship between the results of the differential metabolite KEGG in metabolomics and pulmonary fibrosis.RESULTS: A total of 52 metabolites were screened for association with pulmonary fibrosis in the MR analysis of 1400 plasma metabolites with pulmonary fibrosis, based on P < 0.05 for the IVW method, with consistent OR directions for all methods. Four of them were validated in the plasma of mice with pulmonary fibrosis, namely carnitine c18:2 levels (negative correlation), Glutamine degradant levels (positive correlation), Propionylcarnitine (c3) levels (negative correlation), carnitine to palmitoylcarnitine (c16) ratio (negative correlation). In addition, KEGG analysis of plasma differential metabolites revealed that the signaling pathway of biosynthetic of unsaturated fatty acids was most affected in mice with pulmonary fibrosis, and MR analysis showed that imbalance in the ratio of monounsaturated fatty acids was significantly associated with pulmonary fibrosis.CONCLUSIONS: Our study suggests that abnormal fatty acid levels due to reduced levels of carnitine-like metabolites, and an imbalance in the ratio of monounsaturated, promote the development of pulmonary fibrosis. This study reveals the marker metabolites and metabolic pathways affecting the development of pulmonary fibrosis to provide a basis for the development of new drugs for the treatment of pulmonary fibrosis.PMID:39003929 | DOI:10.1016/j.intimp.2024.112671

Uncovering the Shuixian tea grades hierarchy in Chinese national standard: From sensory evaluation to microstructure and volatile compounds analysis

Sun, 14/07/2024 - 12:00
Food Chem. 2024 Jul 5;459:140342. doi: 10.1016/j.foodchem.2024.140342. Online ahead of print.ABSTRACTBasic standard samples are integral for ensuring consistency and quality control of tea. Understanding the real reasons behind the hierarchical system of Shuixian tea grades in the Chinese national standard is crucial to the scientific development of tea standardization. In this investigation, different grade samples of Shuixian tea strictly conformed to the Chinese national standard, serving as the research objects. Sensory evaluation, SEM and HS-SPME-GC-MS were employed to comprehensively analyze the aroma characteristics. The odor profiles of special grade samples predominantly featured floral and fruity aromas, which attributed to compounds such as geraniol, indole, phenylethyl alcohol. Additionally, hexanal, (E)-3-hexen-1-ol and other compounds contributed to fruity and sweet aroma in first grade. Notably, the predominant roasted and sweet aromas of second grade were attributed to compounds including pyridine, 2,5-dimethyl-pyrazine. This study lays a solid foundation for the scientific development of Chinese national standards and international standard system.PMID:39003860 | DOI:10.1016/j.foodchem.2024.140342

Mitochondrial Biomarkers and Metabolic Syndrome in Bipolar Disorder

Sun, 14/07/2024 - 12:00
Psychiatry Res. 2024 Jul 6;339:116063. doi: 10.1016/j.psychres.2024.116063. Online ahead of print.ABSTRACTThe object of this study is test whether mitochondrial blood-based biomarkers are associated with markers of metabolic syndrome in bipolar disorder, hypothesizing higher lactate but unchanged cell-free circulating mitochondrial DNA levels in bipolar disorder patients with metabolic syndrome. In a cohort study, primary testing from the FondaMental Advanced Centers of Expertise for bipolar disorder (FACE-BD) was conducted, including 837 stable bipolar disorder patients. The I-GIVE validation cohort consists of 237 participants: stable and acute bipolar patients, non-psychiatric controls, and acute schizophrenia patients. Multivariable regression analyses show significant lactate association with triglycerides, fasting glucose and systolic and diastolic blood pressure. Significantly higher levels of lactate were associated with presence of metabolic syndrome after adjusting for potential confounding factors. Mitochondrial-targeted metabolomics identified distinct metabolite profiles in patients with lactate presence and metabolic syndrome, differing from those without lactate changes but with metabolic syndrome. Circulating cell-free mitochondrial DNA was not associated with metabolic syndrome. This thorough analysis mitochondrial biomarkers indicate the associations with lactate and metabolic syndrome, while showing the mitochondrial metabolites can further stratify metabolic profiles in patients with BD. This study is relevant to improve the identification and stratification of bipolar patients with metabolic syndrome and provide potential personalized-therapeutic opportunities.PMID:39003800 | DOI:10.1016/j.psychres.2024.116063

Metabolomics-based profiling of five Salvia L. (Lamiaceae) species using untargeted data analysis workflow

Sun, 14/07/2024 - 12:00
Phytochem Anal. 2024 Jul 14. doi: 10.1002/pca.3423. Online ahead of print.ABSTRACTINTRODUCTION: The genus Salvia L., a member of the family Lamiaceae, is a keystone genus with a wide range of medicinal properties. It possesses a rich metabolite source that has long been used to treat different disorders.OBJECTIVES: Due to a deficiency of untargeted metabolomic profiling in the genus Salvia, this work attempts to investigate a comprehensive mass spectral library matching, computational data annotations, exclusive biomarkers, specific chemotypes, intraspecific metabolite profile variation, and metabolite enrichment by a case study of five medicinal species of Salvia.MATERIAL AND METHODS: Aerial parts of each species were subjected to QTRAP liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis workflow based on untargeted metabolites. A comprehensive and multivariate analysis was acquired on the metabolite dataset utilizing MetaboAnalyst 6.0 and the Global Natural Products Social Molecular Networking (GNPS) Web Platform.RESULTS: The untargeted approach empowered the identification of 117 metabolites by library matching and 92 nodes annotated by automated matching. A machine learning algorithm as substructural topic modeling, MS2LDA, was further implemented to explore the metabolite substructures, resulting in four Mass2Motifs. The automated library newly discovered a total of 23 metabolites. In addition, 87 verified biomarkers of library matching, 58 biomarkers of GNPS annotations, and 11 specific chemotypes were screened.CONCLUSION: Integrative spectral library matching and automated annotation by the GNPS platform provide comprehensive metabolite profiling through a workflow. In addition, QTRAP LC-MS/MS with multivariate analysis unveiled reliable information about inter and intraspecific levels of differentiation. The rigorous investigation of metabolite profiling presents a large-scale overview and new insights for chemotaxonomy and pharmaceutical studies.PMID:39003613 | DOI:10.1002/pca.3423

--Redox Transformations of the OX063 Radical in Biological Media: Oxidative Decay of Initial Trityl with Further Formation of Structurally-Modified TAM

Sun, 14/07/2024 - 12:00
Chemistry. 2024 Jul 14:e202400718. doi: 10.1002/chem.202400718. Online ahead of print.ABSTRACTBeing a low-toxic and hydrophilic representative of TAM, OX063 has shown its suitability for in-vivo and in-cell EPR experiments and design of spin labels. Using 13C labeling, we investigated the course of oxidative degradation of OX063 into quinone-methide (QM) under the influence of superoxide as well as further thiol-promoted reduction of QM into TAM radical, which formally corresponds to substitution of a carboxyl function by a hydroxyl group. We found these transformations being quantitative in model reactions mimicking specific features of biological media and confirmed the presence of these reactions in the blood and liver homogenate of mice in vitro. The emergence of the trityl with the hydroxyl group can be masked by an initial TAM in EPR spectra and may introduce distortions into EPR-derived oximetry data if they have been obtained for objects under hypoxia. 13C labeling allows one to detect its presence, considering its different hyperfine splitting constant on 13C1 (2.04 mT) as compared to OX063 (2.30 mT). The potential involvement of these reactions should be considered when using TAM in spin-labeling of biopolymers intended for subsequent EPR experiments, as well as in the successful application of TAM in experiments in vivo and in cell.PMID:39003595 | DOI:10.1002/chem.202400718

Cryogenic electron microscopy reveals morphologically distinct subtypes of extracellular vesicles among porcine ejaculate fractions

Sat, 13/07/2024 - 12:00
Sci Rep. 2024 Jul 13;14(1):16175. doi: 10.1038/s41598-024-67229-w.ABSTRACTSeminal plasma (SP) is rich in extracellular vesicles (EVs), which are still poorly studied, especially in livestock species. To better understand their functional role in both spermatozoa and endometrial epithelial cells, proper characterization of EVs is an essential step. The objective was to phenotypically characterize porcine seminal EVs (sEVs) using cryogenic electron microscopy (cryo-EM), which allows visualization of EVs in their native state. Porcine ejaculates are released in fractions, each containing SP from different source. This allows characterization sEVs released from various male reproductive tissues. Two experiments were performed, the first with SP from the entire ejaculate (n:6) and the second with SP from three ejaculate fractions (n:15): the first 10 mL of the sperm-rich ejaculate fraction (SRF-P1) with SP mainly from the epididymis, the remainder of the SRF (SRF-P2) with SP mainly from the prostate, and the post-SRF with SP mainly from the seminal vesicles. The sEVs were isolated by size exclusion chromatography and 1840 cryo-EM sEV images were acquired using a Jeol-JEM-2200FS/CR-EM. The size, electron density, complexity, and peripheral corona layer were measured in each sEV using the ImageJ software. The first experiment showed that sEVs were structurally and morphologically heterogeneous, although most (83.1%) were small (less than 200 nm), rounded, and poorly electrodense, and some have a peripheral coronal layer. There were also larger sEVs (16.9%) that were irregularly shaped, more electrodense, and few with a peripheral coronal layer. The second experiment showed that small sEVs were more common in SRF-P1 and SRF-P2, indicating that they originated mainly from the epididymis and prostate. Large sEVs were more abundant in post-SRF, indicating that they originated mainly from seminal vesicles. Porcine sEVs are structurally and morphologically heterogeneous. This would be explained by the diversity of reproductive organs of origin.PMID:39003421 | DOI:10.1038/s41598-024-67229-w

Transcriptomic and metabolomic data of goat ovarian and uterine tissues during sexual maturation

Sat, 13/07/2024 - 12:00
Sci Data. 2024 Jul 13;11(1):777. doi: 10.1038/s41597-024-03565-w.ABSTRACTThe ovaries and uterus are crucial reproductive organs in mammals, and their coordinated development ensures the normal development of sexual maturity and reproductive capacity. This study aimed to comprehensively capture the different physiological stages of the goat's sexual maturation by selecting four specific time points. We collected samples of ovarian and uterine tissues from five female Jining Gray goats at each time point: after birth (D1), 2-month-old (M2), 4-month-old (M4), and 6-month-old (M6). By combining transcriptomic sequencing of 40 samples (including rRNA-depleted RNA-seq libraries with 3607.8 million reads and miRNA-seq libraries with 444.0 million reads) and metabolomics analysis, we investigated the transcriptomic mechanisms involved in reproductive regulation in the ovary and uterus during sexual maturation, as well as the changes in metabolites and their functional potential. Additionally, we analyzed blood hormone indices and uterine tissue sections to examine temporal changes. These datasets will provide a valuable reference for the reproductive regulation of the ovary and uterus, as well as the regulation of metabolites during sexual maturation in goats.PMID:39003290 | DOI:10.1038/s41597-024-03565-w

The ubiquitin-like protein UBTD1 promotes colorectal cancer progression by stabilizing c-Myc to upregulate glycolysis

Sat, 13/07/2024 - 12:00
Cell Death Dis. 2024 Jul 13;15(7):502. doi: 10.1038/s41419-024-06890-5.ABSTRACTDysfunction of the ubiquitin-proteasome system (UPS) is involved in the pathogenesis of various malignancies including colorectal cancer (CRC). Ubiquitin domain containing 1 (UBTD1), a ubiquitin-like protein, regulates UPS-mediated protein degradation and tumor progression in some cancer types. However, the biological function and mechanism of UBTD1 are far from being well elucidated, and its role in CRC has not been explored yet. In our study, we analyzed CRC patients' clinical information and UBTD1 expression data, and found that the expression of UBTD1 in cancer tissue was significantly higher than that in adjacent normal tissue. Higher UBTD1 expression was significantly associated with poorer survival and more lymph node metastasis. Overexpression of UBTD1 could facilitate, while knockdown could inhibit CRC cell proliferation and migration, respectively. RNA-seq and proteomics indicated that c-Myc is an important downstream target of UBTD1. Metabolomics showed the products of the glycolysis pathway were significantly increased in UBTD1 overexpression cells. In vitro, we verified UBTD1 upregulating c-Myc protein and promoting CRC cell proliferation and migration via regulating c-Myc. UBTD1 promoted CRC cells' glycolysis, evidenced by the increased lactate production and glucose uptake following UBTD1 overexpression. Mechanistically, UBTD1 prolonged the half-life of the c-Myc protein by binding to E3 ligase β-transducin repeat-containing protein (β-TrCP), thereby upregulated the expression of glycolysis rate-limiting enzyme hexokinase II (HK2), and enhanced glycolysis and promoted CRC progression. In conclusion, our study revealed that UBTD1 promotes CRC progression by upregulating glycolysis via the β-TrCP/c-Myc/HK2 pathway, suggesting its potential as a prognostic biomarker and therapeutic target in CRC.PMID:39003255 | DOI:10.1038/s41419-024-06890-5

4-Nitrophenol at environmentally relevant concentrations mediates reproductive toxicity in Caenorhabditis elegans via metabolic disorders-induced estrogen signaling pathway

Sat, 13/07/2024 - 12:00
J Environ Sci (China). 2025 Jan;147:244-258. doi: 10.1016/j.jes.2023.09.032. Epub 2023 Oct 3.ABSTRACT4-Nitrophenol (4-NP), as a toxic and refractory pollutant, has generated significant concern due to its adverse effects. However, the potential toxic effects and mechanism remained unclear. In this study, the reproduction, development, locomotion and reactive oxygen species (ROS) production of Caenorhabditis elegans were investigated to evaluate the 4-NP toxicity. We used metabolomics to assess the potential damage mechanisms. The role of metabolites in mediating the relationship between 4-NP and phenotypes was examined by correlation and mediation analysis. 4-NP (8 ng/L and 8 µg/L) caused significant reduction of brood size, ovulation rate, total germ cells numbers, head thrashes and body bends, and an increase in ROS. However, the oosperm numbers in uterus, body length and body width were decreased in 8 µg/L. Moreover, 36 differential metabolites were enriched in the significant metabolic pathways, including lysine biosynthesis, β-alanine metabolism, tryptophan metabolism, pentose phosphate pathway, pentose and glucuronate interconversions, amino sugar and nucleotide sugar metabolism, starch and sucrose metabolism, galactose metabolism, propanoate metabolism, glycerolipid metabolism, and estrogen signaling pathway. The mechanism of 4-NP toxicity was that oxidative stress caused by the perturbation of amino acid, which had effects on energy metabolism through disturbing carbohydrate and lipid metabolism, and finally affected the estrogen signaling pathway to exert toxic effects. Moreover, correlation and mediation analysis showed glycerol-3P, glucosamine-6P, glucosamine-1P, UDP-galactose, L-aspartic acid, and uracil were potential markers for the reproduction and glucose-1,6P2 for developmental toxicity. The results provided insight into the pathways involved in the toxic effects caused by 4-NP and developed potential biomarkers to evaluate 4-NP toxicity.PMID:39003044 | DOI:10.1016/j.jes.2023.09.032

Insights into the nature of ichthyotoxins from the Chrysochromulina leadbeateri blooms in Northern Norwegian fjords

Sat, 13/07/2024 - 12:00
Harmful Algae. 2024 Aug;137:102681. doi: 10.1016/j.hal.2024.102681. Epub 2024 Jun 20.ABSTRACTIn May-June 2019, the microalga Chrysochromulina leadbeateri caused a massive fish-killing event in several fjords in Northern Norway, resulting in the largest direct impact ever on aquaculture in northern Europe due to toxic algae. Motivated by the fact that no algal toxins have previously been described from C. leadbeateri, we set out to investigate the chemical nature and toxicity of secondary metabolites in extracts of two strains (UIO 393, UIO 394) isolated from the 2019 bloom, as well as one older strain (UIO 035) isolated during a bloom in Northern Norway in 1991. Initial LC-DAD-MS/MS-based molecular networking analysis of the crude MeOH extracts of the cultivated strains showed that their profiles of small organic molecules, including a large number of known lipids, were very similar, suggesting that the same class of toxin(s) were likely the causative agents of the two harmful algal bloom (HAB) events. Next, bioassay-guided fractionation using the RTgill-W1 cell line and metabolomics analysis pointed to a major compound affording [M + H]+ ions at m/z 1399.8333 as a possible toxin, corresponding to a compound with the formula C67H127ClO27. Moreover, our study unveiled a series of minor analogues exhibiting distinct patterns of chlorination and sulfation, together defining a new family of compounds, which we propose to name leadbeaterins. Remarkably, these suspected toxins were detected in situ in samples collected during the 2019 bloom close to Tromsø, thereby consistent with a role in fish kills. The elemental compositions of the putative C. leadbeateri ichthyotoxins strongly indicate them to be long linear polyhydroxylated polyketides, structurally similar to sterolysins reported from a number of dinoflagellates.PMID:39003025 | DOI:10.1016/j.hal.2024.102681

Untargeted faecal metabolomics for the discovery of biomarkers and treatment targets for inflammatory bowel diseases

Sat, 13/07/2024 - 12:00
Gut. 2024 Jul 13:gutjnl-2023-329969. doi: 10.1136/gutjnl-2023-329969. Online ahead of print.ABSTRACTThe gut microbiome has been recognised as a key component in the pathogenesis of inflammatory bowel diseases (IBD), and the wide range of metabolites produced by gut bacteria are an important mechanism by which the human microbiome interacts with host immunity or host metabolism. High-throughput metabolomic profiling and novel computational approaches now allow for comprehensive assessment of thousands of metabolites in diverse biomaterials, including faecal samples. Several groups of metabolites, including short-chain fatty acids, tryptophan metabolites and bile acids, have been associated with IBD. In this Recent Advances article, we describe the contribution of metabolomics research to the field of IBD, with a focus on faecal metabolomics. We discuss the latest findings on the significance of these metabolites for IBD prognosis and therapeutic interventions and offer insights into the future directions of metabolomics research.PMID:39002973 | DOI:10.1136/gutjnl-2023-329969

Integrated transcriptomic and metabolomic analysis reveals the underlying mechanisms for male reproductive toxicity of polystyrene nanoplastics in mouse spermatocyte-derived GC-2spd(ts) cells

Sat, 13/07/2024 - 12:00
Toxicol In Vitro. 2024 Jul 11:105893. doi: 10.1016/j.tiv.2024.105893. Online ahead of print.ABSTRACTBACKGROUND: Polystyrene nanoplastics (PS-NPs), are ubiquitous pollution sources in human environments, posing significant biosafety and health risks. While recent studies, including our own, have illustrated that PS-NPs can breach the blood-testis barrier and impact germ cells, there remains a gap in understanding their effects on specific spermatogenic cells such as spermatocytes.METHODS AND RESULTS: Herein, we employed an integrated approach encompassing phenotype, metabolomics, and transcriptomics analyses to assess the molecular impact of PS-NPs on mouse spermatocyte-derived GC-2spd(ts) cells. Optimal exposure conditions were determined as 24 h with 50 nm PS-NPs at 12.5 μg/mL and 90 nm PS-NPs at 50 μg/mL for subsequent multi-omics analysis. Our findings revealed that PS-NPs significantly influenced proliferation and viability, causing alterations in transcriptome and metabolome profiles. Transcriptomics analysis of GC-2spd(ts) cells exposed to PS-NPs indicated the pivotal involvement of cell proliferation and cycle, autophagy, ferroptosis, and redox reaction pathways in PS-NP-induced effects on the proliferation and viability of GC-2spd(ts) cells. Furthermore, metabolomics analysis identified major changes in amino acid metabolism, cyanoamino acid metabolism, and purine and pyrimidine metabolism following PS-NP exposure.CONCLUSION: Our integrated approach, combining metabolomics and transcriptomics profiles with phenotype data, enhances our understanding of the adverse effects of PS-NPs on germ cells.PMID:39002813 | DOI:10.1016/j.tiv.2024.105893

Genome and metabolome analysis of Bacillus sp. Hex-HIT36: a newly screened functional microorganism for the degradation of 1-Hexadecene in industrial wastewater

Sat, 13/07/2024 - 12:00
Environ Res. 2024 Jul 11:119594. doi: 10.1016/j.envres.2024.119594. Online ahead of print.ABSTRACT1-Hexadecene has been detected at a level of mg/L in both influent and effluent of wastewater treatment plants situated in chemical/pharmaceutical industrial parks, which poses a potential threat to the environment. However, few reports are available on aerobic metabolic pathways and microorganisms involved in 1-Hexadecene degradation. In this study, a new strain of 1-Hexadecene-degrading bacteria, Bacillus sp. Hex-HIT36 (HIT36), was isolated from the activated sludge of a wastewater treatment plants located in an industrial park. The physicochemical properties and degradation efficacy of HIT36 were investigated. HIT36 was cultured on a medium containing 1-Hexadecene as a sole carbon source; it was found to remove ∼67% of total organic carbon as confirmed by mass spectrometric analysis of intermediate metabolites. Metabolomic and genomic analysis showed that HIT36 possesses various enzymes, namely, pyruvate dehydrogenase, dihydropolyhydroxyl dehydrogenase, and 2-oxoglutarate-2-oxoiron oxidoreductase (subunit alpha), which assist in the metabolization of readily available carbon source or long chain hydrocarbons present in the growth medium/vicinity. This suggests that HIT36 has efficient long-chain alkane degradation efficacy, and understanding the alkane degradation mechanism of this strain can help in developing technologies for the degradation of long-chain alkanes present in wastewater, thereby assisting in the bioremediation of environment.PMID:39002630 | DOI:10.1016/j.envres.2024.119594

Coordinated responses of rice (Oryza sativa) to the stresses of benzotriazole ultraviolet stabilizers (BZT-UVs): Antioxidative system, photosynthetic activity, and metabolic regulation

Sat, 13/07/2024 - 12:00
J Hazard Mater. 2024 Jul 10;476:135157. doi: 10.1016/j.jhazmat.2024.135157. Online ahead of print.ABSTRACTMassive use of plastic products has caused their accumulation in soils, releasing large amounts of endogenous plastic additives (e.g., benzotriazole ultraviolet stabilizers, in short BZT-UVs) into terrestrial ecosystems. However, their plant toxicity is little known. Herein, we investigated the occurrence of BZT-UVs in contaminated farmland and selected three BZT-UV congeners to explore their toxic effects on the antioxidant, photosynthetic, and metabolic perturbation on rice (Oryza sativa). Results showed that the mean concentrations of ∑BZT-UVs in soil and plant samples were 180.7 ng/g dw and 156.4 ng/g dw, respectively. UV-P, UV-327 and UV-328 were the dominant BZT-UV congeners in both of soils and plants. Three BZT-UV congeners caused oxidative damages to rice in a dose-dependent manner, especially for UV-328. Functional genes involved in chlorophyll synthetases was inhibited by over 50 % under the stress of BZT-UVs, whereas those responsible for chlorophyll degradation were obviously promoted. The chlorophyll content was thus decreased, leading to a weakened photosynthesis system and an unbalanced carbon metabolism. The transcriptome and metabolome proved that the flux of carbohydrate metabolism and amino acid metabolism were obviously promoted in plants induced by BZT-UVs, which could inhibit the growth of rice. These findings offered insights into the coordinated responses of plants and advanced our understanding of potential ecological risks of BZT-UVs to terrestrial ecosystems.PMID:39002488 | DOI:10.1016/j.jhazmat.2024.135157

Combined metabolomics and proteomics to reveal the mechanism of S. oneidensis MR-1 degradation malathion enhanced by FeO/C

Sat, 13/07/2024 - 12:00
J Hazard Mater. 2024 Jul 10;476:135162. doi: 10.1016/j.jhazmat.2024.135162. Online ahead of print.ABSTRACTIron oxide @ biochar (FeO/C) promotes bacterial growth and facilitates electron transfer, thereby effectively promoting malathion degradation by Shewanella oneidensis MR-1 (S. oneidensis MR-1). This study elucidated the underlying mechanism of FeO/C-enhanced malathion degradation by S. oneidensis MR-1 through a combination of metabolomics and proteomics analysis. The kinetic fitting results from the degradation experiment indicated that 0.1 g/L FeO/C exerted the most significant enhancement effect on malathion degradation by S. oneidensis MR-1. Observations from Scanning Electron Microscopy and Laser Scanning Confocal Microscopy, along with physiological and biochemical analysis, showed that FeO/C enhanced the growth and oxidative response of S. oneidensis MR-1 under malathion stress. In addition, metabolomics and proteomics analysis revealed an increase in certain electron transfer related metabolites, such as coenzymes, and the upregulation of proteins, including coenzyme A, sdhD, and petC. Overall, spectroscopic analysis suggested that Fe2+, which was reduced from Fe3+ by S. oneidensis MR-1 in FeO/C, promoted electron transfer in S. oneidensis MR-1 to enhance the degradation of malathion. This study offers enhanced strategies for efficient removal of malathion contaminants.PMID:39002482 | DOI:10.1016/j.jhazmat.2024.135162

Environmentally relevant concentrations of microplastics from agricultural mulch and cadmium negatively impact earthworms by triggering neurotoxicity and disrupting homeostasis

Sat, 13/07/2024 - 12:00
J Hazard Mater. 2024 Jul 10;476:135158. doi: 10.1016/j.jhazmat.2024.135158. Online ahead of print.ABSTRACTRecent research has highlighted the ecological risk posed by microplastics (MPs) from mulching film and heavy metals to soil organisms. However, most studies overlooked real environmental levels of MPs and heavy metals. To address this gap, pristine and aged polyethylene (PE) mulching film-derived MPs (PMPs, 500 mg/kg; AMPs, 500 mg/kg) were combined with cadmium (Cd, 0.5 mg/kg) to assess the acute toxicity to earthworms and investigate associated molecular mechanisms (oxidative stress, osmoregulation pressure, gut microbiota, and metabolic responses) at environmentally relevant concentrations. Compared to Cd alone and Cd + PMPs treatments (11.15 ± 4.19 items/g), Cd + AMPs treatment resulted in higher MPs bioaccumulation (23.73 ± 13.14 items/g), more severe tissue lesions, and increased cell membrane osmotic pressure in earthworms' intestines. Cd + AMPs induced neurotoxicity through elevated levels of glutamate and acetylcholinesterase. Earthworm intestines (0.98 ± 0.49 to 3.33 ± 0.37 mg/kg) exhibited significantly higher Cd content than soils (0.19 ± 0.01 to 0.51 ± 0.06 mg/kg) and casts (0.15 ± 0.01 to 0.25 ± 0.05 mg/kg), indicating PE-MPs facilitated Cd transport in earthworms' bodies. Metabolomic analysis showed Cd + AMPs exposure depleted energy and nucleotide metabolites, disrupted cell homeostasis more profoundly than Cd and Cd + PMPs treatments. Overall, co-exposure to AMPs + Cd induced more severe neurotoxicity and disruption of homeostasis in earthworm than Cd and PMPs + Cd treatments. Our study, using Cd and MPs with environmental relevance, underscores MPs' role in amplifying Cd accumulation and toxicity in earthworms.PMID:39002475 | DOI:10.1016/j.jhazmat.2024.135158

Alterations and associations between lung microbiota and metabolite profiles in silica-induced lung injury

Sat, 13/07/2024 - 12:00
Ecotoxicol Environ Saf. 2024 Jul 12;282:116711. doi: 10.1016/j.ecoenv.2024.116711. Online ahead of print.ABSTRACTSilicosis, caused by silica exposure, is the most widespread and deadliest occupational disease. However, effective treatments are lacking. Therefore, it is crucial to elucidate the mechanisms and targets involved in the development of silicosis. We investigated the basic processes of silicosis development and onset at different exposure durations (2 or 4 weeks) using various techniques such as histopathology, immunohistochemistry, Enzyme linked immunosorbent assay(ELISA),16 S rRNA, and untargeted metabolomics.These results indicate that exposure to silica leads to progressive damage to lung tissue with significant deterioration observed over time. Time-dependent cytokines such as the IL-4, IL-13, and IL-6 are detected in lung lavage fluid, the model group consistently exhibited elevated levels of these cytokines, indicating a persistent and worsening inflammatory response in the lungs. Meanwhile, HE and Masson results show that 4-week exposure to silica causes more obvious lung injury and pulmonary fibrosis. Besides, the model group consistently exhibited a distinct lung bacterial population, known as the Lachnospiraceae_NK4A136_group, regardless of exposure duration. However, with increasing exposure duration, specific temporal changes were observed in lung bacterial populations, including Haliangium, Allobaculum, and Sandaracinus (at 4 weeks; p < 0.05). Furthermore, our study revealed a strong correlation between the mechanism of silica-induced lung injury and three factors: oxidative stress, impaired lipid metabolism, and imbalanced amino acid metabolism. We observed a close correlation between cytokine levels, changes in lung microbiota, and metabolic disturbances during various exposure periods. These findings propose that a possible mechanism of silica-induced lung injury involves the interplay of cytokines, lung microbiota, and metabolites.PMID:39002383 | DOI:10.1016/j.ecoenv.2024.116711

Progress and perspectives of metabolic biomarkers in human aortic dissection

Sat, 13/07/2024 - 12:00
Metabolomics. 2024 Jul 13;20(4):76. doi: 10.1007/s11306-024-02140-z.ABSTRACTBACKGROUND: Aortic dissection (AD) significantly threated human cardiovascular health, extensive clinical-scientific research programs have been executed to uncover the pathogenesis and prevention. Unfortunately, no specific biomarker was identified for the causality or development of human AD.AIM OF REVIEW: Metabolomics, a high-throughput technique capable of quantitatively detecting metabolites, holds considerable promise in discovering specific biomarkers and unraveling the underlying pathways involved. Aiming to provide a metabolite prediction in human AD, we collected the metabolomics data from 2003 to 2023, and diligently scrutinized with the online system MetaboAnalyst 6.0.KEY SCIENTIFIC CONCEPTS OF REVIEW: Based on the data obtained, we have concluded the metabolic dynamics were highly correlated with human AD. Such metabolites (choline, serine and uridine) were frequently involved in the AD. Besides, the pathways, including amino acids metabolism and lipids metabolism, were also dysregulated in the disease. Due to the current limitation of metabolism analysis, the integrative omics data including genomics, transcriptomics, and proteomics were required for developing the specific biomarker for AD.PMID:39002042 | DOI:10.1007/s11306-024-02140-z

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