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

Promoting LC-QToF based non-targeted fingerprinting and biomarker selection with machine learning for the discrimination of black tea geographical origin

Sun, 24/11/2024 - 12:00
Food Chem. 2024 Nov 23;465(Pt 2):142088. doi: 10.1016/j.foodchem.2024.142088. Online ahead of print.ABSTRACTTraceability and mislabelling of black tea for their geographical origin is known as a major fraud concern of the sector. Discrimination among various geographical indications (GIs) can be challenging due to the complexity of chemical fingerprints in multi-class metabolomics analysis. In this study, 302 black tea samples from 9 main cultivation GI regions were collected. A comprehensive non-targeted fingerprinting workflow was built on liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QToF), and a comparison between conventional chemometrics modelling and machine learning was performed. 229 and 145 metabolites were selected as biomarkers and the model robustness/performance were further validated through internal 7-fold cross-validation and external validation, showing 100 % accuracy for discriminating GI origin on both. This research provided a novel solution to enhance transparency and traceability in the black tea supply chain for lab scenarios. Furthermore, the proposed biomarker selection workflow revealed more insights for future machine learning-derived non-targeted metabolomics research.PMID:39581087 | DOI:10.1016/j.foodchem.2024.142088

Correlation analysis of taste phenotype and Gynostemma pentaphyllum saponins using computer virtual screening and UPLC-(HR)MS/MS metabolomics

Sun, 24/11/2024 - 12:00
Food Chem. 2024 Nov 14;465(Pt 2):142050. doi: 10.1016/j.foodchem.2024.142050. Online ahead of print.ABSTRACTGynostemma pentaphyllum, a popular tea ingredient, can be categorized into bitter, sweet, and tasteless varieties based on flavor. However, the metabolic causes of these disparities remain unclear. In this paper, sensory evaluation, untargeted metabolomic analysis using UPLC-QTOF-MS/MS, molecular docking and e-tongue testing were conducted to reveal and verify the structural characteristics and mechanisms underlying these different flavor substances. Component analysis indicated sweet saponins were characterized by glucose chains and protopanaxadiol-type aglycones featuring diagnostic ions m/z 459/475/491 in MS2- spectra; whereas bitter saponins typically featured at least one terminal rhamnose and the higher unsaturated sapogenins with diagnostic ions m/z 473/489/521. Virtual screening on T2R14 and e-tongue testing consistently validated gypenosides with more terminal rhamnoses or higher unsaturated aglycone tended to be more bitter. Docking analysis revealed PHE 172, TYR 159 and ALA 77 were the key amino residue sites in bitterness conduction via hydrophobic and hydrogen bonding interactions.PMID:39581083 | DOI:10.1016/j.foodchem.2024.142050

The effect of ultraviolet-C on the senescence of bitter gourd fruit and the key factors analyzed by transcriptomic and metabolomic analyses

Sun, 24/11/2024 - 12:00
Food Chem. 2024 Nov 14;465(Pt 2):142015. doi: 10.1016/j.foodchem.2024.142015. Online ahead of print.ABSTRACTBitter gourd (Momordica charantia L.) is a tropical and subtropical vegetable that is popular for its rich nutritional content. However, its immature fruit has a short shelf life and spoils easily. This study assessed the effects of ultraviolet-C (UV-C) irradiation on the storage and quality of postharvest bitter gourd fruit. Exposure for 40 s maintained fruit firmness, delayed senescence, increased the antioxidant capacity and minimized damage by reactive oxygen species. Transcriptomic and metabolomic analyses identified 12,733 differentially expressed genes and 282 metabolites during storage. The downregulation of genes for ethylene synthesis and cell wall degradation delayed ripening and senescence, while the upregulation of phenylpropanoid biosynthetic genes enhanced its antioxidant properties. Key transcription factors, such as MYB, bHLH, and bZIP, were implicated in the delayed senescence treatment. This research elucidates the mechanisms of prevention of bitter gourd with UV-C and offers insights into the genetic and metabolite candidates for enhanced strategies of postharvest preservation.PMID:39581081 | DOI:10.1016/j.foodchem.2024.142015

Female zebrafish are more affected than males under polystyrene microplastics exposure

Sun, 24/11/2024 - 12:00
J Hazard Mater. 2024 Nov 23;482:136616. doi: 10.1016/j.jhazmat.2024.136616. Online ahead of print.ABSTRACTMicroplastics are ubiquitous in freshwater and can be absorbed into fish skin and gills, accumulate in the gut, and be transported to other tissues, thus posing a risk to fish health. Further studies are needed, however, to investigate effects such as endocrine disruption and multi-tissue toxicity. In this study, zebrafish were exposed to polystyrene (PS) microplastics and health-related indicators were measured, including skin mucus, gut damage, oxidative stress, stable isotope composition and reproduction as well as an assessment of changes to metabolites using a metabolomics approach. Results showed that concentrations of PS microplastics were higher in gills than those in the gut. Minimal impact to immunoglobulin M level and lysozyme activity in mucus indicated, however, that microplastic toxicity primarily stemmed from ingestion rather than disruption of skin mucus immunity. Female zebrafish were more affected by PS microplastics. Gut microbiota dysbiosis was induced, especially in females. Significant alterations in pathways associated with lipid and energy metabolism were observed in the liver of female fish. PS microplastics also induced sex steroid hormone disorder and reduced female egg production, possibly linked to the alteration of gut microbiota and hepatic metabolism. Combined, these results highlight the gender-specific toxicity of PS microplastics to zebrafish health, potentially harming their population.PMID:39581033 | DOI:10.1016/j.jhazmat.2024.136616

An optimization protocol of the volatile organic compounds analysis in earwax samples for untargeted volatilomics

Sun, 24/11/2024 - 12:00
J Chromatogr A. 2024 Nov 17;1739:465538. doi: 10.1016/j.chroma.2024.465538. Online ahead of print.ABSTRACTRecent studies have highlighted the potential of earwax or cerumen, a non-conventional biomatrix, in volatilomics research as a valuable matrix for disease biomarker discovery. Despite that, there are still gaps in using non-conventional biomatrices in metabolomics research. In this sense, this study aimed to elucidate the main analytical factors involved in the extraction and analysis of volatile organic compounds (VOCs) in cerumen by headspace/gas chromatography-mass spectrometry (HS/GC-MS) using Design of Experiments (DoE) approaches. Furthermore, we present a repeatability study for the proposed method as a quality control process for cerumenomic assays. By applying factorial designs, it was possible to determine that the sample mass, splitless injector sampling time, headspace extraction time, headspace extraction temperature, injection volume, and vial volume were significant factors for the cerumen VOC analysis by HS/GC-MS. Throughout univariate and multivariate statistical approaches, we demonstrate that different analytical conditions lead to distinct chemical profiling of a sample. The most suitable analytical condition was determined after the optimization steps, and the proposed method's repeatability was evaluated by the metabolites coefficient variation (CV) calculation. Seventy-one earwax VOCs reached a CV considered adequate for untargeted metabolomics studies via GC-MS. In summary, this study describes a protocol for analysis optimization of a non-conventional biomatrix and also reports a quality control process in untargeted volatilomics assays using earwax. Our findings shed light on the potential of using earwax in volatolomic studies and establish analytical criteria to ensure quality in cerumenomic assays.PMID:39580983 | DOI:10.1016/j.chroma.2024.465538

Prostate cancer risk biomarkers from large cohort and prospective metabolomics studies: A systematic review

Sun, 24/11/2024 - 12:00
Transl Oncol. 2024 Nov 23;51:102196. doi: 10.1016/j.tranon.2024.102196. Online ahead of print.ABSTRACTProstate cancer (PCa) is one of the leading causes of cancer-related deaths among men. The heterogeneous nature of this disease presents challenges in its diagnosis, prognosis, and treatment. Numerous potential predictive, diagnostic, prognostic, and risk assessment biomarkers have been proposed through various population studies. However, to date, no metabolite biomarker has been approved or validated for the diagnosis, prognosis, or risk assessment of PCa. Recognizing that systematic reviews of case reports or heterogenous studies cannot reliably establish causality, this review analyzed 29 large prospective metabolomics studies that utilized harmonized criteria for patient selection, consistent methodologies for blood sample collection and storage, data analysis, and that are available in public repositories. By focusing on these large prospective studies, we identified 42 metabolites that were consistently replicated by different authors and across cohort studies. These metabolites have the potential to serve as PCa risk-assessment or predictive biomarkers. A discussion on their associations with dietary sources or dietary patterns is also provided. Further detailed exploration of the relationship with diet, supplement intake, nutrition patterns, contaminants, lifestyle factors, and pre-existing comorbidities that may predispose individuals to PCa is warranted for future research and validation.PMID:39580963 | DOI:10.1016/j.tranon.2024.102196

iPSCs-derived iMSCs prevent osteoporotic bone loss and affect bone metabolites in ovariectomized mice

Sun, 24/11/2024 - 12:00
J Cell Mol Med. 2024 Nov;28(22):e70200. doi: 10.1111/jcmm.70200.ABSTRACTOsteoporosis is a metabolic bone disease that seriously jeopardizes the health of middle-aged and elderly people. Mesenchymal stem cell-based transplantation for osteoporosis is a promising new therapeutic strategy. Induced mesenchymal stem cells (iMSCs) are a new option for stem cell transplantation therapy. Acquired mouse skin fibroblasts were transduced and reprogrammed into induced pluripotent cells and further induced to differentiate into iMSCs. The iMSCs were tested for pluripotency markers, trilineage differentiation ability, cell surface molecular marker tests, and gene expression patterns. The iMSCs were injected into the tail vein of mice by tail vein injection, and the distribution of cells in various organs was observed. The effect of iMSCs on the bone mass of mice was detected after injection into the mouse osteoporosis model. The effects of iMSCs infusion on metabolites in femoral tissue and peripheral blood plasma were detected based on LC-MS untargeted metabolomics. iMSCs have similar morphology, immunophenotype, in vitro differentiation potential, and gene expression patterns as mesenchymal stem cells. The iMSCs were heavily distributed in the lungs after infusion and gradually decreased over time. The iMSCs in the femoral bone marrow cavity gradually increased with time. iMSCs infusion significantly avoided bone loss due to oophorectomy. The results of untargeted metabolomics suggest that amino acid and lipid metabolic pathways are key factors involved in iMSCs bone protection and prevention of osteoporosis formation. iMSCs obtained by reprogramming-induced differentiation had cellular properties similar to those of bone marrow mesenchymal stem cells. The iMSCs could promote the remodelling of bone structure in ovariectomy-induced osteoporotic mice and affect the changes of several key metabolites in bone and peripheral blood. Some of these metabolites can serve as potential biomarkers and therapeutic targets for iMSCs intervention in osteoporosis. Investigating the effects of iMSCs on osteoporosis and the influence of metabolic pathways will provide new ideas and methods for the clinical treatment of osteoporosis.PMID:39580790 | DOI:10.1111/jcmm.70200

Non-invasive diagnosis of papillary thyroid microcarcinoma using a novel metabolomics analysis of urine

Sun, 24/11/2024 - 12:00
Endocrine. 2024 Nov 24. doi: 10.1007/s12020-024-04105-7. Online ahead of print.ABSTRACTBACKGROUND: The severity of thyroid cancer is judged on the basis of histologic and clinical features. A limited number of studies have considered urinary metabolite signatures for its diagnosis, and no reliable urinary metabolite biomarkers have been proposed. This diagnostic method would be particularly valuable because of its non-invasive nature.METHOD: A nuclear magnetic resonance (NMR)-based metabolomics approach was used as the analytical platform to study the urine samples of patients with PTMC. Urine samples collected from 41 PTMC patients, 52 healthy subjects, and 13 patients with benign tumors were analyzed using 1H-NMR spectroscopy to identify metabolic changes. PLS-DA, or partial least squares discriminant analysis, was used to analyze the NMR spectra. A double cross-validation method and randomization tests were used to validate PLS-DA models.RESULTS: Clear discriminations between PTMC patients and healthy controls, as well as between PTMC patients and patients with benign tumors were obtained. Collectively, pi-methyhistidine, trimethylamine, myo-inositol, acetate, suberate, azelate, mannitol, tau-methylhistine, ascorbate, 3-aminoisobutyric acid, 2-oxoglutarate, and methanol contributed to the discrimination. Apart from myo-inositol and methanol, all of these metabolites exhibited increased levels in the urine samples of PTMC patients as compared to that of patients with benign tumors.CONCLUSIONS: The application of this NMR-based metabolomics approach allowed the detection of anomalous metabolic traits directly connected PTMC, potentially yielding a more sensitive and comprehensive diagnostic results for PTMC.PMID:39580767 | DOI:10.1007/s12020-024-04105-7

UGT8 mediated sulfatide synthesis modulates BAX localization and dictates apoptosis sensitivity of colorectal cancer

Sat, 23/11/2024 - 12:00
Cell Death Differ. 2024 Nov 23. doi: 10.1038/s41418-024-01418-y. Online ahead of print.ABSTRACTElevated de novo lipid synthesis is a remarkable adaptation of cancer cells that can be exploited for therapy. However, the role of altered lipid metabolism in the regulation of apoptosis is still poorly understood. Using thermal proteome profiling, we identified Manidipine-2HCl, targeting UGT8, a key enzyme in the synthesis of sulfatides. In agreement, lipidomic analysis indicated that sulfatides are strongly reduced in colorectal cancer cells upon treatment with Manidipine-2HCl. Intriguingly, this reduction led to severe mitochondrial swelling and a strong synergism with BH3 mimetics targeting BCL-XL, leading to the activation of mitochondria-dependent apoptosis. Mechanistically, Manidipine-2HCl enhanced mitochondrial BAX localization in a sulfatide-dependent fashion, facilitating its activation by BH3 mimetics. In conclusion, our data indicates that UGT8 mediated synthesis of sulfatides controls mitochondrial homeostasis and BAX localization, dictating apoptosis sensitivity of colorectal cancer cells.PMID:39580596 | DOI:10.1038/s41418-024-01418-y

Altered amino acid levels in young hypopituitarism: impact of NAFLD and insulin resistance

Sat, 23/11/2024 - 12:00
Amino Acids. 2024 Nov 23;56(1):65. doi: 10.1007/s00726-024-03429-y.ABSTRACTElevated concentrations of amino acids (AAs) are commonly observed in patients with nonalcoholic fatty liver disease (NAFLD). Individuals with hypopituitarism (HP) are at a heightened risk of developing NAFLD due to factors such as visceral obesity, increased insulin resistance (IR), and disturbances in lipid metabolism. However, the changes in AAs concentrations associated with HP remain poorly understood. Therefore, our study aimed to investigate whether individuals with HP, who were not receiving growth hormone replacement therapy (GHRT), exhibited altered AAs compared to controls (CTs), and whether these AAs were associated with IR, the presence of NAFLD, and the Metabolic Syndrome (MetS) score. The AAs profiles of 133 young males with HP (age: 24.5 ± 5.9; 57 with NAFLD and 76 without NAFLD) and 90 age and BMI-matched CTs were analyzed using untargeted metabolomics. The results revealed that most AAs were found to be elevated in subjects with HPs compared to CTs. Glutamate, glutamine, norleucine, and branched-chain amino acids (BCAAs) (leucine and valine) were correlated with the homeostasis model assessment of insulin resistance (HOMA-IR), with glutamate and norleucine showing independent linkage. Glutamate and proline levels were specifically associated with MetS score, while alanine and proline linked to NAFLD. Given that elevated glutamate and BCAAs levels have higher prevalence of NAFLD, we hypothesized that the changes in AAs observed in HPs may be attributed to the impact of NAFLD and IR.PMID:39580591 | DOI:10.1007/s00726-024-03429-y

Network structure and fluctuation data improve inference of metabolic interaction strengths with the inverse Jacobian

Sat, 23/11/2024 - 12:00
NPJ Syst Biol Appl. 2024 Nov 23;10(1):137. doi: 10.1038/s41540-024-00457-y.ABSTRACTBased on high-throughput metabolomics data, the recently introduced inverse differential Jacobian algorithm can infer regulatory factors and molecular causality within metabolic networks close to steady-state. However, these studies assumed perturbations acting independently on each metabolite, corresponding to metabolic system fluctuations. In contrast, emerging evidence puts forward internal network fluctuations, particularly from gene expression fluctuations, leading to correlated perturbations on metabolites. Here, we propose a novel approach that exploits these correlations to quantify relevant metabolic interactions. By integrating enzyme-related fluctuations in the construction of an appropriate fluctuation matrix, we are able to exploit the underlying reaction network structure for the inverse Jacobian algorithm. We applied this approach to a model-based artificial dataset for validation, and to an experimental breast cancer dataset with two different cell lines. By highlighting metabolic interactions with significantly changed interaction strengths, the inverse Jacobian approach identified critical dynamic regulation points which are confirming previous breast cancer studies.PMID:39580513 | DOI:10.1038/s41540-024-00457-y

Ethanol extracts of Cinnamomum migao H.W. Li attenuates neuroinflammation in cerebral ischemia-reperfusion injury via regulating TLR4-PI3K-Akt-NF-κB pathways

Sat, 23/11/2024 - 12:00
J Ethnopharmacol. 2024 Nov 21:119150. doi: 10.1016/j.jep.2024.119150. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Cinnamomum migao H.W. Li, commonly known as migao (MG), is used in the Miao region of China for treating cardiovascular and cerebrovascular diseases, attributed to its detoxifying (Jiedu in Chinese), blood-activating (Huoxue in Chinese), and Qi-promoting (Tongqi in Chinese) effects. However, the therapeutic potential of MG for ischemic stroke (IS) has yet to be explored. Therefore, this study was to explore the protective effect of MG against cerebral ischemia-reperfusion injury caused by IS.AIM OF THE STUDY: The aim of this study was to investigate whether ethanol extract of MG (EEMG) attenuates cerebral ischemia-reperfusion injury, and explored the underlying mechanisms.MATERIALS AND METHODS: Middle cerebral artery occlusion and reperfusion (MCAO/R) was established, and the efficacy of EEMG was evaluated using triphenyltetrazolium chloride (TTC), immunofluorescence, hematoxylin-eosin staining (HE) staining, and real-time quantitative PCR (qRT-PCR). Qualitative analysis of EEMG was analyzed for chemical composition by liquid chromatography-mass spectrometry (LC-MS). The molecular mechanism of EEMG was explored by metabolomics, network pharmacology, immunoblotting, immunofluorescence staining, gene knockdown, and agonist treatment.RESULTS: The results showed that EEMG can alleviate ischemic injury in MCAO/R-operated rats and neuronal damage of OGD/R-treated SH-SY5Y cells. Specifically, EEHGT inhibited the release of inflammatory factors and reversed serum metabolic profile disorders of MCAO/R rats. Network pharmacology analysis showed that the PI3K-Akt and NF-κB signaling pathways maybe involved in EEMG-mediated neuroprotective effects on ischemic injury and inhibition of inflammatory response. As we expected, EEMG can activate PI3K-AKT and suppress NF-kB signaling pathways both in MCAO/R-operated rats and OGD/R-treated BV2 cells. The results showed that knockdown of TLR4 abolished the EEMG-mediated inhibition on neuroinflammation in OGD/R-treated BV2 cells. After treating BV2 cells with the TLR4 agonist neoseptin 3, EEMG showed a trend toward inhibiting neuroinflammation but with no significant difference. Additionally, EEMG was found to improve liver injury caused by cerebral ischemia-reperfusion and associated with NF-κB signaling pathway in this study.CONCLUSIONS: Collectively, this study demonstrated that EEMG attenuates neuroinflammation in cerebral ischemia-reperfusion injury via regulating TLR4-PI3K-Akt-NF-κB pathways.PMID:39580135 | DOI:10.1016/j.jep.2024.119150

Schwann Cells Exposed to Articaine Display Distinct Toxic Pathways Compared to Lidocaine

Sat, 23/11/2024 - 12:00
Chem Biol Interact. 2024 Nov 21:111315. doi: 10.1016/j.cbi.2024.111315. Online ahead of print.ABSTRACTArticaine (ATC) has emerged as one of the most popular local anesthetics (LA) in dental clinics, despite its relatively recent introduction to the market. As a member of the amino-amide class of LA, ATC possesses unique features, including a thiophene ring and an ester group, which allow for its use at higher clinical concentrations. However, reports have indicated a higher incidence of paresthesia associated with ATC, though the underlying cause of this effect remains unclear. To investigate this further, we conducted an extracellular metabolic flux analysis and an NMR-based metabolomics study of ATC effects on Schwann cells - a type of glial cell found in the peripheral nervous system - in comparison to lidocaine (LDC), the "gold standard" LA in dentistry. The results showed that ATC had a more significant impact on Schwann cell oxygen consumption compared to LDC. Metabolomics profiling of Schwann cells revealed distinct metabolic alterations between the two treatments. Notably, ATC triggered elevated intracellular levels of various amino acids, including leucine, isoleucine, valine, phenylalanine, methionine, histidine, tyrosine, and glycine, which were not observed in LDC-treated Schwann cells. This was consistent with signs of endoplasmic reticulum stress and apoptosis in ATC-treated cells, as detected by protein expression analysis. These findings offer insights into the metabolic and cellular responses elicited by the two anesthetics in Schwann cells, that may help explain the differential toxicity and higher incidence of paresthesia associated with ATC.PMID:39580065 | DOI:10.1016/j.cbi.2024.111315

Integration of transcriptomics and metabolomics reveal cytotoxic mechanisms of Polyethylene terephthalate microplastics in BEAS-2B cells

Sat, 23/11/2024 - 12:00
Food Chem Toxicol. 2024 Nov 21:115125. doi: 10.1016/j.fct.2024.115125. Online ahead of print.ABSTRACTPolyethylene terephthalate microplastics (PET-MPs) have emerged as significant environmental pollutants with potential health risks. This study investigates the cytotoxic effects of PET-MPs on BEAS-2B lung epithelial cells through integrated transcriptomic and metabolomic analyses. The results of the CCK8 assay showed a reduction in the viability of BEAS-2B cells following continuous exposure to PET-MPs. Transcriptomic analysis identified 1,412 differentially expressed genes (DEGs) mainly enriched in apoptosis and extracellular matrix organization processes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that these DEGs are predominantly involved in the PI3K-Akt, TNF, and MAPK signaling pathways. Metabolomic analysis identified 2,869 differentially expressed metabolites (DEMs), mainly associated with pyrimidine, arginine, proline, and β-alanine metabolism pathways. Multi-omics analysis indicated that PET-MPs primarily disrupt lipid metabolism, which may lead to an increased risk of apoptosis. We hypothesize that PET-MPs affect lipid metabolism by up-regulating the ANGPTL4 gene, thereby promoting cellular apoptosis. This study reveals the mechanisms of PET-MPs toxicity, emphasizing the potential risks they pose to human health.PMID:39580014 | DOI:10.1016/j.fct.2024.115125

Unveiling the impacts of biodegradable microplastics on cadmium toxicity, translocation, transformation, and metabolome in lettuce

Sat, 23/11/2024 - 12:00
Sci Total Environ. 2024 Nov 21:177669. doi: 10.1016/j.scitotenv.2024.177669. Online ahead of print.ABSTRACTBiodegradable microplastics (BMPs) may impact the environmental fate and ecotoxicity of Cd, but the effect mechanism in soil-plant system remain poorly understood. This study investigated the impact of BMPs (poly(lactic acid) (PLA) and poly(butylene adipate terephthalate) (PBAT) microplastics) on the Cd toxicity, translocation, transformation, and metabolome in lettuce (Lactuca sativa L.) by pot experiments. The results show that co-exposure to BMPs and Cd synergistically inhibited the shoot growth. 0.2 % PLA MPs enhanced but 2.5 % PLA MPs inhibited the photosynthesis; however, the dose of PBAT MPs was negatively correlated with the content of chlorophyll a. Moreover, the presence of 2.5 % PBAT MPs increased the nitrate content of leaves by 9.5 % compared to single Cd exposure. The partial least squares path model (PLS-PM) indicates that BMPs exacerbated the inhibitory effects of Cd on lettuce growth. PLA MPs enhanced K, Ca, Cu, and Zn accumulation in root stele, whereas PBAT MPs promoted Fe and Mn enrichment in epidermis. Furthermore, co-exposure resulted in higher inorganic and water-soluble Cd proportions in shoots. PLA MPs elevated Cd contents in cell wall fractions of both roots and shoots, while PBAT MPs increased Cd contents in shoot cell walls and root cells and soluble Cd ratio in shoots. BMPs enhanced Cd toxicity and bioaccumulation by downregulating the expression of ABC transporters and phenylpropanoid biosynthesis pathways, and the relative abundance of related metabolites.PMID:39579896 | DOI:10.1016/j.scitotenv.2024.177669

Effect of particles from wind turbine blades erosion on blue mussels Mytilus edulis

Sat, 23/11/2024 - 12:00
Sci Total Environ. 2024 Nov 21:177509. doi: 10.1016/j.scitotenv.2024.177509. Online ahead of print.ABSTRACTOffshore wind farms (OWFs) pose new anthropogenic pressures on the marine environment as the erosion of turbine blades release organic and inorganic substances with potential consequences for marine life. In the present study, possible effects of the released particles and their chemical constituents on the metabolic profile of the blue mussel, Mytilus edulis, were investigated, utilizing 1H NMR spectroscopy. In the lab, mussels were exposed for 7 and 14 days to different concentrations (10 and 40 mg/L) of microplastic (MP) particles which were derived from cryo-milled rotor blade coatings and core materials (glass fiber polymer, GFP). Raman imaging techniques revealed that 30-40 % of the coating and GFP particles had MP sizes below 5 μm, with the majority (~98 %) being ≤50 μm. Despite the identified enrichment factors (EF) for metals and metalloids from the rotor blade materials, especially Ba, Cu, Cd, Cr and Ni with EFs between 0.93 and 6.1, untargeted metabolic profiling of the entire soft body tissues of M. edulis showed no significant metabolic disruption, regardless of the particle concentration. Observed trends in elevated concentrations of metabolites may indicate a possible short-term effect on mussels' neuroendocrine system and a possible long-term effect on energy metabolism. Experimental worst-case scenario of massive abrasion and the minimal response observed in M. edulis under the conditions tested suggest that erosion caused by wind turbine blades may pose little to no risk to bivalves at this stage. However, it is important to note that this study is only a preliminary step and further studies are needed to obtain a comprehensive overview of the issue before reaching a definite firm conclusion regarding the potential threat of OWFs abrasion to the marine environment, particularly considering the planned future extension of windpark construction in connection with the ongoing EU-wide energy transition.PMID:39579893 | DOI:10.1016/j.scitotenv.2024.177509

The serine palmitoyltransferase core subunit StLcb2 regulates sphingolipid metabolism and promotes Setosphaeria turcica pathogenicity by modulating appressorium development

Sat, 23/11/2024 - 12:00
Int J Biol Macromol. 2024 Nov 21:137928. doi: 10.1016/j.ijbiomac.2024.137928. Online ahead of print.ABSTRACTThe fungal pathogen Setosphaeria turcica (S. turcica) causes northern corn leaf blight (NCLB), resulting in significant yield and economic losses in maize. To elucidate the metabolic pathways essential for its pathogenicity, we investigated the metabolome of S. turcica during appressorium development, a critical stage for host infection. Our analysis indicated a substantial enrichment of sphingosine and related compounds during this phase. The application of chemical inhibitors to disrupt sphingolipid metabolism confirmed their pivotal role in appressorium formation and pathogenicity. Additionally, silencing of the serine palmitoyl transferase (Spt) core subunit gene StLCB2 led to significant alterations in fungal morphology and growth, accompanied by changes in cell membrane integrity, surface hydrophobicity, melanin, and sphingosine synthesis. These findings underscore the importance of sphingolipids in the pathogenicity of S. turcica and suggest that targeting specific components of the sphingolipid pathway could aid in developing novel fungicides or genetically engineered maize varieties with increased resistance to NCLB.PMID:39579824 | DOI:10.1016/j.ijbiomac.2024.137928

Integrated transcriptomic and metabolomic analyses reveal that MsSPHK1 - A sphingosine kinase gene negatively regulates drought tolerance in alfalfa (Medicago sativa L.)

Sat, 23/11/2024 - 12:00
Plant Physiol Biochem. 2024 Nov 19;218:109302. doi: 10.1016/j.plaphy.2024.109302. Online ahead of print.ABSTRACTAlfalfa is a valuable forage crop but voluntarily affected by drought. Understanding the mechanisms of drought resistance in alfalfa is crucial for improving resilient cultivars. In our study, we used four distinct alfalfa accessions two drought-tolerance (DT) and two drought-sensitive (DS) and identified transcriptional modules and candidate genes associated with the drought tolerance in the DS from transcriptomic analyses. Our metabolic profiling of 520 metabolites revealed significant variations between the DS and DT groups, particularly in the levels of flavonoids and nucleotides and their derivatives. The integrated analysis of transcriptome and metabolome analysis revealed that the glycine, serine, and threonine metabolism and the sphingolipid metabolism are associated with the drought resistance. When drought stress occurs, MsSRR (MsG 0180002649.01) and MsSPHK1 (MsG 0280006618.01) are significantly up-regulated, L-serine and dihydrosphingosine (DHS) significantly down-regulated in DS. By silencing the MsSPHK1 gene we found the drought resistance was significantly improved. This was evidenced by a significant increase in the activity of antioxidant enzymes such as SOD, POD, and CAT, compared to the control group. Additionally, the photosynthetic rate, stomatal conductance, and efficiency of photosystem II measured by Fv/Fm, phi2 and qL, were significantly higher in the silenced plants than in the control group. In conclusion, our results suggest that the increased level of dihydrosphingosine improves alfalfa resistance to drought stress. Moreover, the negative regulatory role of MsSPHK1 in drought tolerance provides a promising target for genetic manipulation to enhance the resilience of alfalfa to drought stress.PMID:39579717 | DOI:10.1016/j.plaphy.2024.109302

Honey-fried licorice in the treatment of arrhythmia: Structure elucidation and the mechanism of antiarrhythmic activity

Sat, 23/11/2024 - 12:00
Phytomedicine. 2024 Nov 15;136:156259. doi: 10.1016/j.phymed.2024.156259. Online ahead of print.ABSTRACTAIM OF THE STUDY: To evaluate the therapeutic mechanism of Honey-fried licorice on arrhythmia, to explore the distribution of main components of Honey-fried licorice in vivo before and after processing, and to elucidate the active ingredient of Honey-fried licorice on arrhythmia.MATERIALS AND METHODS: UPLC-Q-TOF/MS were used to analyze the common and different components of raw and honey-fried licorice before and after processing. Yin deficiency syndrome was established by continuous irritability and water platform sleep deprivation, and then ventricular arrhythmia model was established by injection of calcium chloride into the tail vein. Applying the electrocardiograph changes in heart rate in rats. Subsequently, ELISA and histopathological examinations were conducted to assess the therapeutic effects of honey-fried licorice on arrhythmia. Metabonomics analysis was employed to predict key regulatory pathways involved in the treatment response. Finally, RT-PCR and enzyme activity assays were utilized to verify the expression and function of key genes and proteins, providing insights into the underlying mechanisms.RESULTS: The heart rate of rats increased after injection of Cacl2 solution into the tail vein. Honey-fried licorice has a certain improvement effect on heart injury and tachycardia, and its mechanism may be through the obvious correction effect on SOD, MDA, LDH, Na+-K+-ATPase, CaM and CAMK2 in the arrhythmia model. Under pathological conditions, Metabonomics revealed that the heart was highly exposed to glycyrrhetic acid 3-O-glucuronide, isoformononetin, araboglycyrrhizin, 18β-glycyrrhetinic acid, liquiritigenin, licoflavonol and isoliquiritigenin are known to have anti-arrhythmic effects through immune regulation and oxidation. Notably, both PCR and ELISA analyses indicated that honey-fried licorice may effectively treat arrhythmia, potentially through the modulation of the arachidonic acid pathway.CONCLUSION: These results suggested that honey-fried licorice could protect against arrhythmia and alleviate oxidative stress and tissue damage caused by arrhythmia. Through correlation analysis and metabolomics, it was found that glycyrrhetic acid 3-O-glucuronide, isoformononetin, araboglycyrrhizin, 18β-glycyrrhetinic acid, liquiritigenin, licoflavonol and isoliquiritigenin can be used as the active ingredient of honey-fried licorice in the treatment of arrhythmia. Moreover, our results suggested that the therapeutic effect of honey-fried licorice on arrhythmia may be linked to the regulation of the arachidonic acid pathway. This study elucidates the mechanisms by which honey-fried licorice treats arrhythmia from a metabolic perspective, highlighting its role in "tonifying the spleen and stomach, supplementing qi, and replenishing the pulse." These findings provide a foundation for the further application of honey-fried licorice and the development of related products.PMID:39579611 | DOI:10.1016/j.phymed.2024.156259

Metabolomics reveals the size effect of microplastics impeding membrane synthesis in rice cells

Sat, 23/11/2024 - 12:00
Ecotoxicol Environ Saf. 2024 Nov 22;288:117378. doi: 10.1016/j.ecoenv.2024.117378. Online ahead of print.ABSTRACTThe global-scale production of plastics has led to a significant accumulation in the environment, and it has become a major stressor to environmental sustainability, agricultural crops, and human health. Here we report the particle size effect of polystyrene (PS, typically microplastic) on the impact on rice suspension cells. This study used PS of different particle sizes (30 nm, 200 nm, and 2 μm) in a three-day co-culture experiment, the results showed that 30 nm, 200 nm, and 2 μm PS at the same concentration (100 μg/mL) caused 4.6 %, 55.8 %, and 66.4 % decrease in rice suspension cell viability, respectively. Furthermore, a substantial reduction in protein content, amounting to 26.53 % and 48.47 %, was observed in cells treated with 200 nm and 2 μm PS, and the DNA and RNA content of rice suspension cells also decreased substantially at 100 μg/mL PS. Non-targeted metabolomics analyses showed that PS disrupted fatty acid biosynthesis with a clear size effect, wherein 2 μm PS caused a decrease of 64.9 % in hexadecanoic acid content. Consequently, this finding provides valuable perspectives on the potential ecotoxicity of microplastics at the single-cell level of rice and will facilitate the formulation of an environmental management program specifically tailored for addressing the challenges posed by microplastics.PMID:39579448 | DOI:10.1016/j.ecoenv.2024.117378

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