PubMed

Int J Mol Sci. 2024 Feb 28;25(5):2814. doi: 10.3390/ijms25052814.ABSTRACTThe pathophysiology of nonketotic hyperglycinemia (NKH), a rare neuro-metabolic disorder associated with severe brain malformations and life-threatening neurological manifestations, remains incompletely understood. Therefore, a valid human neural model is essential. We aimed to investigate the impact of GLDC gene variants, which cause NKH, on cellular fitness during the differentiation process of human induced pluripotent stem cells (iPSCs) into iPSC-derived astrocytes and to identify sustainable mechanisms capable of overcoming GLDC deficiency. We developed the GLDC27-FiPS4F-1 line and performed metabolomic, mRNA abundance, and protein analyses. This study showed that although GLDC27-FiPS4F-1 maintained the parental genetic profile, it underwent a metabolic switch to an altered serine-glycine-one-carbon metabolism with a coordinated cell growth and cell cycle proliferation response. We then differentiated the iPSCs into neural progenitor cells (NPCs) and astrocyte-lineage cells. Our analysis showed that GLDC-deficient NPCs had shifted towards a more heterogeneous astrocyte lineage with increased expression of the radial glial markers GFAP and GLAST and the neuronal markers MAP2 and NeuN. In addition, we detected changes in other genes related to serine and glycine metabolism and transport, all consistent with the need to maintain glycine at physiological levels. These findings improve our understanding of the pathology of nonketotic hyperglycinemia and offer new perspectives for therapeutic options.PMID:38474060 | DOI:10.3390/ijms25052814

Int J Mol Sci. 2024 Feb 26;25(5):2705. doi: 10.3390/ijms25052705.ABSTRACTPlant growth exhibits rhythmic characteristics, and gibberellins (GAs) are involved in regulating cell growth, but it is still unclear how GAs crosstalk with circadian rhythm to regulate cell elongation. The study analyzed growth characteristics of wild-type (WT), zmga3ox and zmga3ox with GA3 seedlings. We integrated metabolomes and transcriptomes to study the interaction between GAs and circadian rhythm in mediating leaf elongation. The rates of leaf growth were higher in WT than zmga3ox, and zmga3ox cell length was shorter when proliferated in darkness than light, and GA3 restored zmga3ox leaf growth. The differentially expressed genes (DEGs) between WT and zmga3ox were mainly enriched in hormone signaling and cell wall synthesis, while DEGs in zmga3ox were restored to WT by GA3. Moreover, the number of circadian DEGs that reached the peak expression in darkness was more than light, and the upregulated circadian DEGs were mainly enriched in cell wall synthesis. The differentially accumulated metabolites (DAMs) were mainly attributed to flavonoids and phenolic acid. Twenty-two DAMs showed rhythmic accumulation, especially enriched in lignin synthesis. The circadian DEGs ZmMYBr41/87 and ZmHB34/70 were identified as regulators of ZmHCT8 and ZmBM1, which were enzymes in lignin synthesis. Furthermore, GAs regulated ZmMYBr41/87 and ZmHB34/70 to modulate lignin biosynthesis for mediating leaf rhythmic growth.PMID:38473951 | DOI:10.3390/ijms25052705

Int J Mol Sci. 2024 Feb 26;25(5):2702. doi: 10.3390/ijms25052702.ABSTRACTEctopic fat accumulation in non-adipose tissues is closely related to diabetes-related myocardial dysfunction. Nevertheless, the complete picture of the lipid metabolites involved in the metabolic-related myocardial alterations is not fully characterized. The aim of this study was to characterize the specific lipid profile in hearts in an animal model of obesity/insulin resistance induced by a high-fat diet (HFD). The cardiac lipidome profiles were assessed via liquid chromatography-mass spectrometry (LC-MS)/MS-MS and laser desorption/ionization-mass spectrometry (LDI-MS) tissue imaging in hearts from C57BL/6J mice fed with an HFD or standard-diet (STD) for 12 weeks. Targeted lipidome analysis identified a total of 63 lipids (i.e., 48 triacylglycerols (TG), 5 diacylglycerols (DG), 1 sphingomyelin (SM), 3 phosphatidylcholines (PC), 1 DihydroPC, and 5 carnitines) modified in hearts from HFD-fed mice compared to animals fed with STD. Whereas most of the TG were up-regulated in hearts from animals fed with an HFD, most of the carnitines were down-regulated, thereby suggesting a reduction in the mitochondrial β-oxidation. Roughly 30% of the identified metabolites were oxidated, pointing to an increase in lipid peroxidation. Cardiac lipidome was associated with a specific biochemical profile and a specific liver TG pattern. Overall, our study reveals a specific cardiac lipid fingerprint associated with metabolic alterations induced by HFD.PMID:38473949 | DOI:10.3390/ijms25052702

Int J Mol Sci. 2024 Feb 24;25(5):2659. doi: 10.3390/ijms25052659.ABSTRACTMany metastatic cancers with poor prognoses correlate to downregulated CD82, but exceptions exist. Understanding the context of this correlation is essential to CD82 as a prognostic biomarker and therapeutic target. Oral squamous cell carcinoma (OSCC) constitutes over 90% of oral cancer. We aimed to uncover the function and mechanism of CD82 in OSCC. We investigated CD82 in human OSCC cell lines, tissues, and healthy controls using the CRISPR-Cas9 gene knockout, transcriptomics, proteomics, etc. CD82 expression is elevated in CAL 27 cells. Knockout CD82 altered over 300 genes and proteins and inhibited cell migration. Furthermore, CD82 expression correlates with S100 proteins in CAL 27, CD82KO, SCC-25, and S-G cells and some OSCC tissues. The 37-50 kDa CD82 protein in CAL 27 cells is upregulated, glycosylated, and truncated. CD82 correlates with S100 proteins and may regulate their expression and cell migration. The truncated CD82 explains the invasive metastasis and poor outcome of the CAL 27 donor. OSCC with upregulated truncated CD82 and S100A7 may represent a distinct subtype with a poor prognosis. Differing alternatives from wild-type CD82 may elucidate the contradictory functions and pave the way for CD82 as a prognostic biomarker and therapeutic target.PMID:38473906 | DOI:10.3390/ijms25052659

Int J Mol Sci. 2024 Feb 23;25(5):2630. doi: 10.3390/ijms25052630.ABSTRACTMetastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease due to the absence of effective therapies. A more comprehensive understanding of molecular events, encompassing the dysregulation of microRNAs (miRs) and metabolic reprogramming, holds the potential to unveil precise mechanisms underlying mCRPC. This study aims to assess the expression of selected serum exosomal miRs (miR-15a, miR-16, miR-19a-3p, miR-21, and miR-141a-3p) alongside serum metabolomic profiling and their correlation in patients with mCRPC and benign prostate hyperplasia (BPH). Blood serum samples from mCRPC patients (n = 51) and BPH patients (n = 48) underwent metabolome analysis through 1H-NMR spectroscopy. The expression levels of serum exosomal miRs in mCRPC and BPH patients were evaluated using a quantitative real-time polymerase chain reaction (qRT-PCR). The 1H-NMR metabolomics analysis revealed significant alterations in lactate, acetate, citrate, 3-hydroxybutyrate, and branched-chain amino acids (BCAAs, including valine, leucine, and isoleucine) in mCRPC patients compared to BPH patients. MiR-15a, miR-16, miR-19a-3p, and miR-21 exhibited a downregulation of more than twofold in the mCRPC group. Significant correlations were predominantly observed between lactate, citrate, acetate, and miR-15a, miR-16, miR-19a-3p, and miR-21. The importance of integrating metabolome analysis of serum with selected serum exosomal miRs in mCRPC patients has been confirmed, suggesting their potential utility for distinguishing of mCRPC from BPH.PMID:38473877 | DOI:10.3390/ijms25052630

Int J Mol Sci. 2024 Feb 23;25(5):2577. doi: 10.3390/ijms25052577.ABSTRACTFlower color is an important trait for the ornamental value of colored rapeseed (Brassica napus L.), as the plant is becoming more popular. However, the color fading of red petals of rapeseed is a problem for its utilization. Unfortunately, the mechanism for the process of color fading in rapeseed is unknown. In the current study, a red flower line, Zhehuhong, was used as plant material to analyze the alterations in its morphological and physiological characteristics, including pigment and phytohormone content, 2 d before flowering (T1), at flowering (T2), and 2 d after flowering (T3). Further, metabolomics and transcriptomics analyses were also performed to reveal the molecular regulation of petal fading. The results show that epidermal cells changed from spherical and tightly arranged to totally collapsed from T1 to T3, according to both paraffin section and scanning electron microscope observation. The pH value and all pigment content except flavonoids decreased significantly during petal fading. The anthocyanin content was reduced by 60.3% at T3 compared to T1. The content of three phytohormones, 1-aminocyclopropanecarboxylic acid, melatonin, and salicylic acid, increased significantly by 2.2, 1.1, and 30.3 times, respectively, from T1 to T3. However, auxin, abscisic acid, and jasmonic acid content decreased from T1 to T3. The result of metabolomics analysis shows that the content of six detected anthocyanin components (cyanidin, peonidin, pelargonidin, delphinidin, petunidin, and malvidin) and their derivatives mainly exhibited a decreasing trend, which was in accordance with the trend of decreasing anthocyanin. Transcriptomics analysis showed downregulation of genes involved in flavonol, flavonoid, and anthocyanin biosynthesis. Furthermore, genes regulating anthocyanin biosynthesis were preferentially expressed at early stages, indicating that the degradation of anthocyanin is the main issue during color fading. The corresponding gene-encoding phytohormone biosynthesis and signaling, JASMONATE-ZIM-DOMAIN PROTEIN, was deactivated to repress anthocyanin biosynthesis, resulting in fading petal color. The results clearly suggest that anthocyanin degradation and phytohormone regulation play essential roles in petal color fading in rapeseed, which is a useful insight for the breeding of colored rapeseed.PMID:38473825 | DOI:10.3390/ijms25052577

Int J Mol Sci. 2024 Feb 21;25(5):2521. doi: 10.3390/ijms25052521.ABSTRACTDrip irrigation with brackish water increases the risk of soil salinization while alleviating water shortage in arid areas. In order to alleviate soil salinity stress on crops, polymer soil amendments are increasingly used. But the regulation mechanism of a polymer soil amendment composed of polyacrylamide polyvinyl alcohol, and manganese sulfate (PPM) on rapeseed photosynthesis under drip irrigation with different types of brackish water is still unclear. In this field study, PPM was applied to study the responses of the rapeseed (Brassica napus L.) phenotype, photosynthetic physiology, transcriptomics, and metabolomics at the peak flowering stage under drip irrigation with water containing 6 g·L-1 NaCl (S) and Na2CO3 (A). The results showed that the inhibitory effect of the A treatment on rapeseed photosynthesis was greater than that of the S treatment, which was reflected in the higher Na+ content (73.30%) and lower photosynthetic-fluorescence parameters (6.30-61.54%) and antioxidant enzyme activity (53.13-77.10%) of the A-treated plants. The application of PPM increased the biomass (63.03-75.91%), photosynthetic parameters (10.55-34.06%), chlorophyll fluorescence parameters (33.83-62.52%), leaf pigment content (10.30-187.73%), and antioxidant enzyme activity (28.37-198.57%) under S and A treatments. However, the difference is that under the S treatment, PPM regulated the sulfur metabolism, carbon fixation and carbon metabolism pathways in rapeseed leaves. And it also regulated the photosynthesis-, oxidative phosphorylation-, and TCA cycle-related metabolic pathways in rapeseed leaves under A treatment. This study will provide new insights for the application of polymer materials to tackle the salinity stress on crops caused by drip irrigation with brackish water, and solve the difficulty in brackish water utilization.PMID:38473771 | DOI:10.3390/ijms25052521

Cancers (Basel). 2024 Feb 26;16(5):942. doi: 10.3390/cancers16050942.ABSTRACTThymomas (THs) are a unique group of heterogeneous tumors of the thymic epithelium. In particular, the subtypes B2 and B3 tend to be aggressive and metastatic. Radical tumor resection remains the only curative option for localized tumors, while more advanced THs require multimodal treatment. Deep sequencing analyses have failed to identify known oncogenic driver mutations in TH, with the notable exception of the GTF2I mutation, which occurs predominantly in type A and AB THs. However, there are multiple alternative non-mutational mechanisms (e.g., perturbed thymic developmental programs, metabolism, non-coding RNA networks) that control cellular behavior and tumorigenesis through the deregulation of critical molecular pathways. Here, we attempted to show how the results of studies investigating such alternative mechanisms could be integrated into a current model of TH biology. This model could be used to focus ongoing research and therapeutic strategies.PMID:38473304 | DOI:10.3390/cancers16050942

Cancers (Basel). 2024 Feb 23;16(5):913. doi: 10.3390/cancers16050913.ABSTRACTMelanoma progression is a multistep evolution from a common melanocytic nevus through a radial superficial growth phase, the invasive vertical growth phase finally leading to metastatic dissemination into distant organs. Melanoma aggressiveness largely depends on the propensity to metastasize, which means the capacity to escape from the physiological microenvironment since tissue damage due to primary melanoma lesions is generally modest. Physiologically, epidermal melanocytes are attached to the basement membrane, and their adhesion/migration is under the control of surrounding keratinocytes. Thus, the epidermal compartment represents the first microenvironment responsible for melanoma spread. This complex process involves cell-cell contact and a broad range of secreted bioactive molecules. Invasion, or at the beginning of the microinvasion, implies the breakdown of the dermo-epidermal basement membrane followed by the migration of neoplastic melanocytic cells in the superficial papillary dermis. Correspondingly, several experimental evidences documented the structural and functional rearrangement of the entire tissue surrounding neoplasm that in some way reflects the atypia of tumor cells. Lastly, the microenvironment must support the proliferation and survival of melanocytes outside the normal epidermal-melanin units. This task presumably is mostly delegated to fibroblasts and ultimately to the self-autonomous capacity of melanoma cells. This review will discuss remodeling that occurs in the epidermis during melanoma formation as well as skin changes that occur independently of melanocytic hyperproliferation having possible pro-tumoral features.PMID:38473275 | DOI:10.3390/cancers16050913

Animals (Basel). 2024 Mar 2;14(5):788. doi: 10.3390/ani14050788.ABSTRACTThe gut microbiota is highly symbiotic with the host, and the microbiota and its metabolites are essential for regulating host health and physiological functions. Astragalus, as a feed additive, can improve animal immunity. However, the effects of Astragalus root powder on the rumen microbiota and their metabolites in lambs are not apparent. In this study, thirty healthy Hu sheep lambs with similar body weights (17.42 ± 2.02 kg) were randomly selected for the feeding experiment. Lambs were fed diets supplemented with 0.3% Astragalus root powder, and the rumen microbiota density and metabolome were measured to determine the effects of Astragalus on the health of lambs in the rumen. The results showed that the relative abundance of Butyrivibrio fibrisolvens (Bf), Ruminococcus flavefaciens (Rf), Succiniclasticum (Su), and Prevotella (Pr) in the rumen was increased in the Astragalus group (p < 0.01), and metabolic profiling showed that the metabolites, such as L-lyrosine and L-leucine, were upregulated in the Astragalus group (p < 0.01). KEGG functional annotation revealed that upregulated metabolites were mainly enriched in the pathways of amino acid metabolism, lipid metabolism, fatty acid biosynthesis, and bile secretion in the Astragalus group, and downregulated metabolites were enriched in the pathways of methane metabolism and other pathways. Correlation analysis revealed that butyric acid was positively correlated with Roseburia and Blautia (p < 0.05) and negatively correlated with Desulfovibrio (p < 0.05). Thus, by analyzing the interactions of Astragalus root powder with the density of rumen microorganisms and their metabolites in lambs, it was shown that Astragalus root powder could improve the structure of rumen microbiota and their metabolites and then participate in the regulation of amino acid metabolism, lipid metabolism, immune metabolism, and other pathways to improve the efficiency of energy absorption of the lambs.PMID:38473173 | DOI:10.3390/ani14050788

Foods. 2024 Feb 27;13(5):724. doi: 10.3390/foods13050724.ABSTRACTAs a biological alternative to the antimicrobial action of SO2, bioprotection has been proposed to winemakers as a means to limit or prevent grape musts microbial alteration. Competition for nitrogenous nutrients and for oxygen are often cited as potential explanations for the effectiveness of bioprotection. This study analyses the effect of a bioprotective M. pulcherrima strain on the growth of one H. valbyensis strain and one H. uvarum strain. Bioprotection efficiency was observed only against H. valbyensis inoculated at the two lowest concentrations. These results indicate a potential species-dependent efficiency of the bioprotective strain and a strong impact of the initial ratio between bioprotective and apiculate yeasts. The analysis of the consumption of nitrogen compounds revealed that leucine, isoleucine, lysine and tryptophan were consumed preferentially by all three strains. The weaker assimilation percentages of these amino acids observed in H. valbyensis at 24 h growth suggest competition with M. pulcherrima that could negatively affects the growth of the apiculate yeast in co-cultures. The slowest rate of O2 consumption of H. valbyensis strain, in comparison with M. pulcherrima, was probably not involved in the bioprotective effect. Non-targeted metabolomic analyses of M. pulcherrima and H. valbyensis co-culture indicate that the interaction between both strains particularly impact lysin and tryptophan metabolisms.PMID:38472837 | DOI:10.3390/foods13050724

Foods. 2024 Feb 26;13(5):701. doi: 10.3390/foods13050701.ABSTRACTThis study investigated the immunoprotective effects of the extract of Vanilla planifolia Andrew (EVPA) on cyclophosphamide (Cy)-induced immunosuppression in mice. The results show that EVPA administration significantly alleviated the immune damage induced by Cy, as evidenced by an improved body weight, organ index, and colonic injury. A further analysis of microbial diversity revealed that the EVPA primarily increased the abundance of the beneficial bacteria Verrucomicrobiota, Lactobacillaceae, and Lactobacillus while decreasing Akkermansiaceae, Akkermansia, Romboutsia, and Lactococcus, thereby ameliorating the microbial dysbiosis caused by Cy. A metabolomic analysis revealed significant alterations in the microbial metabolite levels after EVPA treatment, including urobilinogen, formamidopyrimidine nucleoside triphosphate, Cer (d18:1/18:0), pantetheine, and LysoPC (15:0/0:0). These altered metabolites are associated with pathways related to sphingolipid metabolism, carbapenem biosynthesis, pantothenate and CoA biosynthesis, glycerophospholipid metabolism, and porphyrin metabolism. Furthermore, significant correlations were observed between certain microbial groups and the differential metabolites. These findings provide new insights into the immunomodulatory effects of EVPA on the intestinal microbiota and metabolism, laying the foundation for more extensive utilization.PMID:38472814 | DOI:10.3390/foods13050701

Foods. 2024 Feb 21;13(5):657. doi: 10.3390/foods13050657.ABSTRACTPostharvest ripening is correlated to the quality and shelf life of European pear fruit. In this study, the effects of peppermint extract on fruit phenotype, related physiological activities, and aroma components during postharvest ripening of the European pear variety 'Packham's Triumph' were examined. Fruit treated with 2.0 g L-1 peppermint extract for 12 h showed delayed softening by 4 d compared with that of the untreated control group. The peak values of ethylene and respiratory rate in fruit were reduced to a certain extent after peppermint extract treatment; however, the peppermint extract did not delay the occurrence of the respiratory climacteric peak. Peppermint extract treatment also did not significantly increase the content of the characteristic peppermint aroma in pear fruit. Further, widely targeted metabolome analysis revealed 298 significantly different metabolites, with flavonoids (40%) and lipid compounds (15%) accounting for the highest proportion on the first day after treatment. The Kyoto Encyclopedia of Genes and Genomes pathway result showed significant enrichment in the metabolic pathways of biosynthesis of flavonoid, isoflavonoid, flavone and flavonol, linoleic acid, and alpha-linolenic acid metabolism following peppermint extract treatment. The combined analysis of transcriptome and metabolome data showed significant enrichment in linoleic acid metabolism and alpha-linolenic acid metabolism on the first, third, and fifth days after peppermint extract treatment. This study indicates that peppermint extract mainly affects the pear fruit softening process in the early stage after treatment.PMID:38472770 | DOI:10.3390/foods13050657

Plant Cell Rep. 2024 Mar 12;43(4):94. doi: 10.1007/s00299-024-03169-z.ABSTRACTTaxadiene synthase, taxadiene-5α-hydroxylase, and taxane 13α-hydroxylase genes were introduced into Nicotiana benthamiana, and the improved resistance to lepidoptera pest fall armyworm was reported. Fall armyworm (FAW) is a serious agricultural pest. Genetic engineering techniques have been used to create pest-resistant plant varieties for reducing pest damage. Paclitaxel is a diterpenoid natural metabolite with antineoplastic effects in medicine. However, the effects of taxanes on the growth and development of lepidoptera pests, such as the FAW, are unknown. Here, selected paclitaxel precursor biosynthesis pathway genes, taxadiene synthase, taxane 5α-hydroxylase, and taxane 13α-hydroxylase, were engineered in the heterologous host Nicotiana benthamiana plants. Bioassay experiments showed that the transgenic N. benthamiana plants displayed improved resistance to FAW infestation, with degeneration of gut tissues and induced expression of apoptosis-related genes. Cytotoxicity experiment showed that the paclitaxel precursor, 10-deacetylbaccatin III, is cytotoxic to Sf9 cells, causing cell cycle arrest at the G2/M phase and disorder of the cytoskeleton. Metabolome analysis showed that heterologous expression of taxane genes in N. benthamiana affected the digestive system, steroid hormone and purine metabolism pathways of FAW larvae. In summary, this study provides a candidate approach for FAW control.PMID:38472660 | DOI:10.1007/s00299-024-03169-z

Clin Chem. 2024 Mar 13:hvae007. doi: 10.1093/clinchem/hvae007. Online ahead of print.ABSTRACTBACKGROUND: Premature coronary heart disease (CHD) is a major cause of death in women. We aimed to characterize biomarker profiles of women who developed CHD before and after age 65 years.METHODS: In the Women's Health Study (median follow-up 21.5 years), women were grouped by age and timing of incident CHD: baseline age <65 years with premature CHD by age 65 years (25 042 women; 447 events) and baseline age ≥65 years with nonpremature CHD (2982 women; 351 events). Associations of 44 baseline plasma biomarkers measured using standard assays and a nuclear magnetic resonance (NMR)-metabolomics assay were analyzed using Cox models adjusted for clinical risk factors.RESULTS: Twelve biomarkers showed associations only with premature CHD and included lipoprotein(a), which was associated with premature CHD [adjusted hazard ratio (HR) per SD: 1.29 (95% CI 1.17-1.42)] but not with nonpremature CHD [1.09(0.98-1.22)](Pinteraction = 0.02). NMR-measured lipoprotein insulin resistance was associated with the highest risk of premature CHD [1.92 (1.52-2.42)] but was not associated with nonpremature CHD (Pinteraction <0.001). Eleven biomarkers showed stronger associations with premature vs nonpremature CHD, including apolipoprotein B. Nine NMR biomarkers showed no association with premature or nonpremature CHD, whereas 12 biomarkers showed similar significant associations with premature and nonpremature CHD, respectively, including low-density lipoprotein (LDL) cholesterol [1.30(1.20-1.45) and 1.22(1.10-1.35)] and C-reactive protein [1.34(1.19-1.50) and 1.25(1.08-1.44)].CONCLUSIONS: In women, a profile of 12 biomarkers was selectively associated with premature CHD, driven by lipoprotein(a) and insulin-resistant atherogenic dyslipoproteinemia. This has implications for the development of biomarker panels to screen for premature CHD.PMID:38472127 | DOI:10.1093/clinchem/hvae007

Huan Jing Ke Xue. 2024 Mar 8;45(3):1859-1868. doi: 10.13227/j.hjkx.202304058.ABSTRACTTo investigate the influences of functional groups on the biological effects caused by microplastics, the accumulation of three polystyrene microplastics (PS, PS-NH2, and PS-COOH) in zebrafish (Danio rerio) embryos were analyzed, and then the responses of metabolic functions and microbial communities in zebrafish larvae were revealed using the combination of the microbiome and metabolome methods. The results showed that all microplastics could accumulate in zebrafish with concentrations ranging from 143 to 175 μg·g-1, and there were no significant differences in the accumulation potentials among different PS treatments. Exposure to plain PS significantly affected the metabolic capacity of aminoglycosides in zebrafish larvae, whereas the metabolic processes of amino acids were affected by PS-NH2. In the PS-COOH treatment, the metabolic pathways of the tricarboxylic acid cycle, amino acids, and glycolysis in zebrafish were markedly altered. The metabolic functions of zebrafish larvae were changed by all PS microplastics, resulting in toxic effects on zebrafish, and the functional group modification of microplastics may have further enhanced these toxicities. Compared to that in the control, exposure to PS-NH2 significantly reduced the diversity of microbial communities in zebrafish larvae and increased the proportion of Proteobacteria in the composition, leading to an imbalance of the bacterial community in zebrafish and thus disrupting the metabolic functions in the fish. Therefore, the functional modifications of microplastics may significantly alter the related stresses on aquatic organisms, leading to unpredictable ecological risks.PMID:38471897 | DOI:10.13227/j.hjkx.202304058

Nucleic Acids Res. 2024 Mar 12:gkae191. doi: 10.1093/nar/gkae191. Online ahead of print.NO ABSTRACTPMID:38471813 | DOI:10.1093/nar/gkae191

J Proteomics. 2024 Mar 10:105154. doi: 10.1016/j.jprot.2024.105154. Online ahead of print.ABSTRACTHigh-grade serous ovarian cancer (HGSOC) has a high death rate and poor prognosis. The main causes of poor prognosis are asymptomatic early disease, no effective screening method at present, and advanced disease. Changes in cellular metabolism are characteristic of cancer, and plasma metabolome analysis can be used to identify biomarkers. In this study, we used Q Exactive liquid chromatography tandem mass spectrometry (LC-MS/MS, QE) to compare the differentiation between plasma samples (22 HGSOC samples and 22 normal samples). In total, we detected 124 metabolites, and an orthogonal partial least-squares-discriminant analysis (OPLS-DA) model was useful to distinguish HGSOC patients from healthy controls. Choline, 25-hydroxyvitamin D2, and sphingomyelin (d18:0/16:1(9Z) (OH))/SM(d18:0/16:1(9Z) (OH)) showed significantly differential plasma levels in HGSOC patients under the conditions of variable importance in projection (VIP) > 1, p < 0.05 using Student's t-test, and fold change (FC) ≥ 1.5 or ≤ 0.667. Metabolic pathway analysis can provide valuable information to enhance the understanding of the underlying pathophysiology of HGSOC. In conclusion, the Q Exactive LC/MS/MS method validation-based plasma metabolomics approach may have potential as a convenient screening method for HGSOC and may be a method to monitor tumor recurrence in patients with HGSOC after surgery SIGNIFICANCE: High-grade serous ovarian cancer (HGSOC) has a high death rate and poor prognosis. The main causes of poor prognosis are asymptomatic early disease, no effective screening method at present, and advanced disease. Changes in cellular metabolism are characteristic of cancer, and plasma metabolome analysis can be used to identify biomarkers. In this study, we used Q Exactive liquid chromatography tandem mass spectrometry (LC-MS/MS, QE) to compare the differentiation between plasma samples (20 HGSOC samples and 20 normal samples). In total, we detected 124 metabolites, and an orthogonal partial least-squares-discriminant analysis (OPLS-DA) model was useful to distinguish HGSOC patients from healthy controls. Choline, 25-hydroxyvitamin D2, and sphingomyelin (d18:0/16:1(9Z) (OH))/SM(d18:0/16:1(9Z) (OH)) showed significantly differential plasma levels in HGSOC patients under the conditions of variable importance in projection (VIP) > 1, p < 0.05 using Student's t-test, and fold change (FC) ≥ 1.5 or ≤ 0.667. Metabolic pathway analysis can provide valuable information to enhance the understanding of the underlying pathophysiology of HGSOC. In conclusion, the Q Exactive LC/MS/MS method validation-based plasma metabolomics approach may have potential as a convenient screening method for HGSOC and may be a method to monitor tumor recurrence in patients with HGSOC after surgery.PMID:38471622 | DOI:10.1016/j.jprot.2024.105154

Sci Total Environ. 2024 Mar 10:171632. doi: 10.1016/j.scitotenv.2024.171632. Online ahead of print.ABSTRACTRegulating photosynthetic machinery is a powerful but challenging strategy for selectively inhibiting bloom-forming cyanobacteria, in which photosynthesis mainly occurs in thylakoids. P-coumaric acid (p-CA) has several biological properties, including free radical scavenging and antibacterial effects, and studies have shown that it can damage bacterial cell membranes, reduce chlorophyll a in cyanobacteria, and effectively inhibit algal growth at concentrations exceeding 0.127 g/L. Allelochemicals typically inhibit cyanobacteria by inhibiting photosynthesis; however, research on inhibiting harmful algae using phenolic acids has focused mainly on their inhibitory and toxic effects and metabolite levels, and the molecular mechanism by which p-CA inhibits photosynthesis remains unclear. Thus, we examined the effect of p-CA on the photosynthesis of Limnothrix sp. in detail. We found that p-CA inhibits algal growth and damages photosynthesis-related proteins in Limnothrix sp., reduces carotenoid and allophycocyanin levels, and diminishes the actual quantum yield of Photosystem II (PSII). Moreover, p-CA significantly altered algal cell membrane protein systems, and PSII loss resulting from p-CA exposure promoted reactive oxygen species production. It significantly altered algae cell membrane protein systems. Finally, p-CA was found to be environmentally nontoxic; 80 % of 48-h-old Daphnia magna larvae survived when exposed to 0.15 g/L p-CA. These findings provide insight into the mechanism of cyanobacterial inhibition by p-CA, providing a more practical approach to controlling harmful algal blooms.PMID:38471589 | DOI:10.1016/j.scitotenv.2024.171632

Cell. 2024 Mar 6:S0092-8674(24)00185-5. doi: 10.1016/j.cell.2024.02.019. Online ahead of print.ABSTRACTThe repertoire of modifications to bile acids and related steroidal lipids by host and microbial metabolism remains incompletely characterized. To address this knowledge gap, we created a reusable resource of tandem mass spectrometry (MS/MS) spectra by filtering 1.2 billion publicly available MS/MS spectra for bile-acid-selective ion patterns. Thousands of modifications are distributed throughout animal and human bodies as well as microbial cultures. We employed this MS/MS library to identify polyamine bile amidates, prevalent in carnivores. They are present in humans, and their levels alter with a diet change from a Mediterranean to a typical American diet. This work highlights the existence of many more bile acid modifications than previously recognized and the value of leveraging public large-scale untargeted metabolomics data to discover metabolites. The availability of a modification-centric bile acid MS/MS library will inform future studies investigating bile acid roles in health and disease.PMID:38471500 | DOI:10.1016/j.cell.2024.02.019