PubMed

Technol Cancer Res Treat. 2023 Jan-Dec;22:15330338221145994. doi: 10.1177/15330338221145994.ABSTRACTObjectives: Serine metabolism is essential for tumor cells. Endogenous serine arises from de novo synthesis pathways. As the rate-limiting enzyme of this pathway, PHGDH is highly expressed in a variety of tumors including colon cancer. Therefore, targeted inhibition of PHGDH is an important strategy for anti-tumor therapy research. However, the specific gene expression and metabolic pathways regulated by PHGDH in colon cancer are still unclear. Our study was aimed to clarified the role of PHGDH in serine metabolism in colon cancer to provide new knowledge for in-depth understanding of serine metabolism and PHGDH function in colon cancer. Methods: In this study, we analyzed the gene expression and metabolic remodeling process of colon cancer cells (SW620) after targeted inhibition of PHGDH by gene transcriptomics and metabolomics. LC-MS analysis was performed in 293T cells to PHGDH gene transcription and protein post-translational modification under depriving exogenous serine. Results: We found that amino acid transporters, amino acid metabolism, lipid synthesis related pathways compensation and other processes are involved in the response process after PHGDH inhibition. And ATF4 mediated the transcriptional expression of PHGDH under exogenous serine deficiency conditions. While LC-MS analysis of post-translational modification revealed that PHGDH produced changes in acetylation sites after serine deprivation that the K289 site was lost, and a new acetylation site K21was produced. Conclusion: Our study performed transcriptomic and metabolomic analysis by inhibiting PHGDH, thus clarifying the role of PHGDH in gene transcription and metabolism in colon cancer cells. The mechanism of high PHGDH expression in colon cancer cells and the acetylation modification that occurs in PHGDH protein were also clarified by serine deprivation. In our study, the role of PHGDH in serine metabolism in colon cancer was clarified by multi-omics analysis to provide new knowledge for in-depth understanding of serine metabolism and PHGDH function in colon cancer.PMID:36707056 | DOI:10.1177/15330338221145994

Sci Total Environ. 2023 Jan 24:161794. doi: 10.1016/j.scitotenv.2023.161794. Online ahead of print.ABSTRACTThe toxic effects of imidacloprid are attracting increased concern because of its widespread use in agriculture and its persistence in the aquatic environment. Imidacloprid bioaccumulates and triggers various morphological and behavioral responses in amphibians, but the toxic effects and mechanism of imidacloprid in amphibians remain uncertain. In this study, the acute toxicity and chronic effects of imidacloprid on Xenopus laevis were studied. Acute toxicity for 96 h revealed that imidacloprid had an LC50 value of 74.18 mg/L. After exposure for 28 d under 1/10 and 1/100 LC50, liver samples from X. laevis were employed for biochemical analyses, pathological studies, and nontargeted metabolomics to systematically assess the toxic effects and mechanism of imidacloprid. The results showed that oxidative stress and hepatic tissue morphology changes were observed in treated X. laevis liver. Twelve metabolites involved in metabolic pathway were altered between the control and high exposure groups and twenty-one metabolites were altered between the control and low exposure group. Eight metabolic pathways exposed to high levels and nine metabolic pathways exposed to low level of imidacloprid were disturbed. These pathways were primarily related to amino acid metabolism, lipid metabolism, and nucleotide metabolism. Our research provides essential information to evaluate the potential toxicity of imidacloprid to nontarget aquatic organisms.PMID:36707007 | DOI:10.1016/j.scitotenv.2023.161794

Fungal Genet Biol. 2023 Jan 24:103779. doi: 10.1016/j.fgb.2023.103779. Online ahead of print.ABSTRACTSesquiterpenes (STs) are secondary metabolites, which mediate biotic interactions between different organisms. Predicting the species-specific ST repertoires can contribute to deciphering the language of communication between organisms of the same or different species. High biochemical plasticity and catalytic promiscuity of sesquiterpene synthases (STSs), however, challenge the homology-based prediction of the STS functions. Using integrated analyses of genomic, transcriptomic, volatilomic, and metabolomic data, we predict product profiles for 116 out of 146 putative STS genes identified in the genomes of 30 fungal species from different trophic groups. Our prediction method is based on the observation that STSs encoded by genes closely related phylogenetically are likely to share the initial enzymatic reactions of the ST biosynthesis pathways and, therefore, produce STs via the same reaction route. The classification by reaction routes allows to assign STs known to be emitted by a particular species to the putative STS genes from this species. Gene expression information helps to further specify these ST-to-STS assignments. Validation of the computational predictions of the STS functions using both in silico and experimental approaches shows that integrated multiomic analyses are able to correctly link cyclic STs of non-cadalane type to genes. In the process of the experimental validation, we characterized catalytic properties of several putative STS genes from the mycorrhizal fungus Laccaria bicolor. We show that the STSs encoded by the L.bicolor mycorrhiza-induced genes emit either nerolidol or α-cuprenene and α-cuparene, and discuss the possible roles of these STs in the mycorrhiza formation.PMID:36706978 | DOI:10.1016/j.fgb.2023.103779

Toxicol Appl Pharmacol. 2023 Jan 24:116401. doi: 10.1016/j.taap.2023.116401. Online ahead of print.ABSTRACTChlorophenols (CPs) are widespread pollutants in nature. CPs have raised significant concern due to their potential hepatotoxic effects on humans. This research aimed to ascertain the inhibitory potential of eleven CPs (2-CP, 3-CP, 4-CP, 2,4-DCP, 2,3,4-TCP, 2,4,5-TCP, 2,4,6-TCP, 2,3,4,5-TeCP, 2,3,4,6-TeCP, 2,3,5,6-TeCP, and PCP) on nine human CYP isoforms (CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4). The CPs that inhibit the activity of CYP isoforms were detected with human liver microsomes (HLM) using a cocktail approach in vitro. The results demonstrated that trichlorophenols, tetrachlorophenols, and PCP strongly inhibited CYP2C8 and CYP2C9. The half inhibition concentration (IC50) value of 2,3,4,6-TeCP and PCP for CYP2C8 inhibition was 27.3 μM and 12.3 μM, respectively. The IC50 for the inhibition of 2,4,6-TCP, 2,3,4,6-TeCP and PCP towards CYP2C9 were calculated to be 30.3 μM, 5.8 μM and 2.2 μM, respectively. 2,3,4,6-TeCP, and PCP exhibited non-competitive inhibition towards CYP2C8. 2,4,6-TCP, 2,3,4,6-TeCP, and PCP exhibited competitive inhibition towards CYP2C9. The inhibition kinetics parameters (Ki) were 51.51 μM, 22.28 μM, 37.86 μM, 7.27 μM, 0.68 μM for 2,3,4,6-TeCP-CYP2C8, PCP-CYP2C8, 2,4,6-TCP-CYP2C9, 2,3,4,6-TeCP-CYP2C9, PCP-CYP2C9, respectively. This study also defined clear structure-activity relationships (SAR) of CPs on CYP2C8, supported by molecular docking studies. Overall, CPs were found to cause inhibitory effects on CYP isoforms in vitro, and this finding may provide a basis for CPs focused on CYP isoforms inhibition endpoints.PMID:36706924 | DOI:10.1016/j.taap.2023.116401

Comp Biochem Physiol Part D Genomics Proteomics. 2023 Jan 20;45:101059. doi: 10.1016/j.cbd.2023.101059. Online ahead of print.ABSTRACTHigh-latitude fish are subjected to sustained and diel-cycling hypoxia. Oxygen deficiency could pose a serious threat to fish, but little information is available regarding the response mechanisms employed by high-latitude fish to sustained and diel-cycling hypoxia. In this study, a combination of transcriptomics and metabolomics were used to examine the molecular response mechanisms actioned by sustained and diel-cycling hypoxia in the high-latitude fish, Phoxinus lagowskii. P. lagowskii was divided into normoxic control (6.0-7.0 mg/L dissolved oxygen), sustained (1.5 mg/L dissolved oxygen), and diel-cycling hypoxic treatment (6.0-7.0 mg/L between 07:00-21:00, and 3.0-4.0 mg/L between 21:00-07:00) tanks for 28 days. Differentially expressed genes (DEGs) and significantly different metabolites (DMs) related to digestive proteases, lipid metabolism, estrogen signaling pathway, steroid hormone biosynthesis, glutathione metabolism, and tryptophan metabolism were identified from comparative metabolomic and transcriptomic data expression profiles within the liver. The current study found that P. lagowskii had significantly different responses between sustained and diel-cycling hypoxia. P. lagowskii faced with sustained hypoxia may enhance their tolerance capacity through phospholipid and glutathione metabolism. Our data provide new insights into the high latitude fish coping with changes in hypoxia and warrants further investigation into these potentially important genes and metabolites.PMID:36706598 | DOI:10.1016/j.cbd.2023.101059

Psychiatry Res. 2023 Jan 24;321:115070. doi: 10.1016/j.psychres.2023.115070. Online ahead of print.ABSTRACTSchizophrenia (SCZ) is a severe mental disorder. Using liquid chromatography mass spectrometry, we performed comprehensive metabolomics analyses of plasma samples from healthy controls (HC) and first episode SCZ patients before and after an acute period of medication. Ten lipid metabolites and 27 soluble small molecules were identified as potential biomarkers associated with the diagnosis and treatment of SCZ. These metabolites were significantly reduced in SCZ, and lipids and sulfate were significantly increased after treatment. Of the metabolites identified, four showed significant correlations with the Positive and Negative Syndrome Scale total scores. A biomarker panel composed of alpha-dimorphecolic, Phosphatidylcholine (PC) (16:0/18:1(11Z)), 1-methylnicotinamide, Phosphatidylethanolamine (PE) (20:2(11Z,14Z)/18:2(9Z,12Z)), sulfate, and L-tryptophan was selected to distinguish SCZ from HC; this provided the maximum classification performance with an AUC of 0.972. A biomarker panel including C16 sphinganine, gamma-linolenic acid, linoleic acid, PC(16:0/18:1(11Z)), PE(20:2(11Z,14Z)/18:2(9Z,12Z)), and sulfate, was selected for discrimination between SCZ before and after medication, and produced the optimal classification performance with an AUC of 0.905. Disturbances in lipid metabolism, sulfation modification, tryptophan metabolism, anti-inflammatory and antioxidant systems, and unsaturated fatty acids metabolism, were identified in SCZ. Our findings could facilitate the development of objective diagnostic or drug treatment monitoring tools for schizophrenia.PMID:36706560 | DOI:10.1016/j.psychres.2023.115070

J Pharm Biomed Anal. 2023 Jan 21;226:115266. doi: 10.1016/j.jpba.2023.115266. Online ahead of print.ABSTRACTLab-on-a-chip (LOC) or micro total analysis system is one of the microfluidic technologies defined as the adaptation, miniaturization, integration, and automation of analytical laboratory procedures into a single instrument or "chip". In this article, we review developments over the past five years in the application of LOC biosensors for the detection of different types of cancer. Microfluidics encompasses chemistry and biotechnology skills and has revolutionized healthcare diagnosis. Superior to traditional cell culture or animal models, microfluidic technology has made it possible to reconstruct functional units of organs on chips to study human diseases such as cancer. LOCs have found numerous biomedical applications over the past five years, including integrated bioassays, cell analysis, metabolomics, drug discovery and delivery systems, tissue and organ physiology and disease modeling, and personalized medicine. This review provides an overview of the latest developments in microfluidic-based cancer research, with pros, cons, and prospects.PMID:36706542 | DOI:10.1016/j.jpba.2023.115266

Ecotoxicol Environ Saf. 2023 Jan 25;252:114580. doi: 10.1016/j.ecoenv.2023.114580. Online ahead of print.ABSTRACTSilicosis is one of the most frequent, rapidly developing, and lethal types of pneumoconiosis. However, our understanding of the underlying mechanisms of its pathogenesis and progress remains unclear. We investigated the fundamental processes of silicosis incidence and progression using a combination of lung function testing, histopathology, 16 S rRNA, untargeted metabolomics, and cytokine chips at different exposure times (4 or 8 weeks). The results show that silica exposure damages lung tissue reduces lung function, and increases with time. Cytokines with time-specific properties were found in lung lavage fluid: IFN-γ (4 weeks; P＜0.05), TNF-α, M-CSF, GM-CSF (8 weeks; P＜0.01). In addition, silica exposure for different periods interferes to varying degrees with the metabolism of lipids. The composition of the intestinal microbiota changed with increasing exposure time and there were time-specific: Allobaculum, Turicibacter、Jeotgalicoccu、Coprococcus 1 (4 weeks; P＜0.05), Ruminococcaceae NK4A214 group、Ruminiclostridium 5 (8 weeks; P＜0.05). We found strong associations between cytokines, gut microbiota changes, and metabolic disturbances at different exposure times. These results suggest that time-specific changes in crosstalk among cytokines, the gut microbiota, and metabolites may be a potential mechanism for silica-induced lung injury.PMID:36706523 | DOI:10.1016/j.ecoenv.2023.114580

Food Chem. 2023 Jan 24;412:135549. doi: 10.1016/j.foodchem.2023.135549. Online ahead of print.ABSTRACTPolyphenols are multifaceted bioactive compounds, but little is known about their real impact on human health after consumption. In this work, the phenolic profiling of quebracho, yellow maize, and violet rice extracts was comprehensively investigated, together with the impact of in vitro digestion and colonic fermentation on the bioaccessibility and bioavailability of these phytochemicals. The different matrices showed distinct profiles, potentially influencing in vitro starch digestion under cooking conditions. Furthermore, after the extracts underwent in vitro gastrointestinal digestion and faecal fermentation, phenolics exhibited a differential bioaccessibility trend at every digestion level, with matrix-dependent behaviour. The bioavailability results suggest that polyphenols are metabolised during colonic fermentation, mainly into tyrosols, phenolic acids, and lignans, which are partially absorbed by Caco-2 cells. By combining metabolomics with in vitro cellular methods, this research provides new insights into the fate of these phytochemicals in the gut, yielding comprehensive data on their consumption in food matrices.PMID:36706508 | DOI:10.1016/j.foodchem.2023.135549

Food Chem. 2023 Jan 21;412:135542. doi: 10.1016/j.foodchem.2023.135542. Online ahead of print.ABSTRACTChinese cabbage is a nutrients-rich vegetable with diverse leaf colors. Here, we used widely-targeted metabolomics technology to study the metabolic responses of three Chinese cabbage varieties with representative leaf colors after blue light treatment. The inner leaf color of orange varieties 20S530 and 15S1094 changed from yellow to golden yellow, while no visible color change occurred in the common variety 14S23 after the treatment. A total of 844 metabolites were measured from the leaf samples of these three varieties in a time course study after short term blue light treatment, with kaempferol-4'-O-glucoside, isoquercitrin, hyperin, arbutin, sulforaphane as enriched nutritional metabolites. Orange Chinese cabbage varieties showed additional nutrition enhancement after the treatment. This study is the first to explore the global metabolic responses of Chinese cabbage after blue light treatment, and our findings provided valuable insights on how to effectively use lighting conditions to enhance specific groups of nutrients in vegetables.PMID:36706505 | DOI:10.1016/j.foodchem.2023.135542

J Agric Food Chem. 2023 Jan 27. doi: 10.1021/acs.jafc.2c07539. Online ahead of print.ABSTRACTControlling cucumber Fusarium wilt caused by Fusarium oxysporum f. sp. cucumerinum (FOC) with Bacillus strains is a hot research topic. However, the molecular mechanism of Bacillus underlying the biocontrol of cucumber wilt is rarely reported. In this study, B. subtilis strain Z-14 showed significant antagonistic activity against FOC, and the control effect reached 88.46% via pot experiment. Microscopic observations showed that strain Z-14 induced the expansion and breakage of FOC hyphae. The cell wall thickness was uneven, and the organelle structure was degraded. The combined analysis of metabolome and transcriptome showed that strain Z-14 inhibited the FOC infection by inhibiting the synthesis of cell wall and cell membrane, energy metabolism, and amino acid synthesis of FOC mycelium, inhibiting the clearance of reactive oxygen species (ROS) and the secretion of cell wall-degrading enzymes (CWDEs), thereby affecting mitogen-activated protein kinase (MAPK) signal transduction and inhibiting the transport function.PMID:36706360 | DOI:10.1021/acs.jafc.2c07539

J Agric Food Chem. 2023 Jan 27. doi: 10.1021/acs.jafc.2c07413. Online ahead of print.ABSTRACTNitrogen (N) application increases wheat yield and protein content and affects the nutritional quality of the grain. Analysis of N use efficiency revealed that N uptake efficiency is a key factor affecting protein content. Two wheat lines with significant differences in protein content were used to investigate the response of differential accumulation of metabolites to N levels and the spatial variation pattern of metabolites related to nutritional quality in wheat grains using widely targeted metabolomics analysis. The results showed that amino acids, nucleic acids, and phytohormones and their derivatives and glycolytic processes are the crucial factors affecting protein content in two wheat lines. Amino acids and derivatives, lipids, and flavonoids are the main contributors to metabolite spatial variation of grains, which were interactively regulated by nitrogen and genotypes. N application significantly increased the relative accumulation of beneficial bioactive substances in the inner layer (P3 to P5), but excessive N application may inhibit this effect and lead to poor nutritional quality.PMID:36706242 | DOI:10.1021/acs.jafc.2c07413

High Alt Med Biol. 2023 Jan 27. doi: 10.1089/ham.2022.0003. Online ahead of print.ABSTRACTXu, Jin, Shenhan Gao, Mingyuan Xin, Wenjie Chen, Kaikun Wang, Wenjing Liu, Xinzong Yan, Sinan Peng, and Yanming Ren. Comparative tandem mass tag-based quantitative proteomics analysis of liver against chronic hypoxia: molecular insights into metabolism in rats. High Alt Med Biol. 00:000-000, 2023. Objective: Using a metabolomic approach, we uncovered key regulators in metabolism from tandem mass tag (TMT)-based proteomic analysis in animals chronically exposed to hypoxia. Methods: Sixteen Sprague-Dawley rats (n = 8 per group) were exposed to chronic normoxia or hypoxia (380 mmHg corresponding to a simulated altitude of 5,500 m) for 35 consecutive days. Hypoxia-induced alterations in metabolic pathways were analyzed from TMT-based proteomic analysis, complemented by western blot validation of key regulators. Results: We profiled biochemical parameters and serum lipids, found that serum alanine aminotransferase and blood glucose were not significantly changed due to chronic hypoxia. However, serum triglycerides, total cholesterol, high-density lipoprotein, and low-density lipoprotein (LDL) were significantly affected by chronic hypoxia. And the levels of LDL nearly doubled (p < 0.05) after hypoxia exposure for 35 days. Through Kyoto Encyclopedia of Genes and Genomes classification, we found several metabolic pathways were enriched, including lipid metabolism, cofactor and vitamin metabolism, amino acids metabolism, carbohydrate metabolism, and energy metabolism. To explore the potential functions of proteins in metabolic pathways that become a coordinated shift under chronic hypoxic conditions, Gene Ontology and pathway analysis were carried out on differentially expressed proteins. As the co-expression network shown in Figure, we identified the most significant differentially expressed proteins after chronic hypoxic changes in the livers of rats. Furthermore, we validated the gene expression profiles at the protein level using western blot. Results of western blot were in accordance with our quantitative polymerase chain reaction findings. The levels of fatty acid synthase and aquaporin 1 were significantly downregulated after 35 days and the levels of ATP citrate lyase, 2'-5'-oligoadenylate synthetase 1A, aldehyde dehydrogenase 2, and Ras-related protein Rap-1A were significantly upregulated after 35 days. Conclusions: Although this study cannot completely account for all the molecular mechanisms in rats, we provide a good analysis of protein expression and profiling of rats under chronic hypoxia conditions.PMID:36706039 | DOI:10.1089/ham.2022.0003

Neurotox Res. 2023 Jan 27. doi: 10.1007/s12640-023-00634-7. Online ahead of print.ABSTRACTEssential trace metals like zinc (Zn), iron (Fe), and copper (Cu) play an important physiological role in the metabolomics and healthy functioning of body organs, including the brain. However, abnormal accumulation of trace metals in the brain and dyshomeostasis in the different regions of the brain have emerged as contributing factors in neuronal degeneration, Aβ aggregation, and Tau formation. The link between these essential trace metal ions and the risk of AD has been widely studied, although the conclusions have been ambiguous. Despite the absence of evidence for any clinical benefit, therapeutic chelation is still hypothesized to be a therapeutic option for AD. Furthermore, the parameters like bioavailability, ability to cross the BBB, and chelation specificity must be taken into consideration while selecting a suitable chelation therapy. The data in this review summarizes that the primary intervention in AD is brain metal homeostasis along with brain metal scavenging. This review evaluates the impact of different trace metals (Cu, Zn, Fe) on normal brain functioning and their association with neurodegeneration in AD. Also, it investigates the therapeutic potential of metal chelators in the management of AD. An extensive literature search was carried out on the "Web of Science, PubMed, Science Direct, and Google Scholar" to investigate the effect of trace elements in neurological impairment and the role of metal chelators in AD. In addition, the current review highlights the advantages and limitations of chelation therapies and the difficulties involved in developing selective metal chelation therapy in AD patients.PMID:36705861 | DOI:10.1007/s12640-023-00634-7

Mol Divers. 2023 Jan 27. doi: 10.1007/s11030-023-10609-7. Online ahead of print.ABSTRACTEarthworms are used to cure wounds in Chinese villages for thousands of years. Recently, scientists realized their extracts could promote wound healing and they have anti-inflammatory, antioxidant, anti-apoptosis, and anti-microbial properties, but its mechanism of promoting wound healing remains unclear. In the presented study, electronic literature databases and LC-MS/MS were used to determine earthworms' ingredients and differential metabolites. Swiss Target Prediction database was used for ingredients' target prediction and wound disease-relevant genes were found from GeneCards, OMIM, and DrugBank databases. Network pharmacology was conducted to demonstrate filtering hub targets, biological functions, and the signaling pathways of earthworms extract against wounds. Molecular docking and metabolism analysis were used to look for core target genes and key bioactive molecules from earthworms. Finally, the investigation shows 5 most important signal pathways, 5 core genes, and 6 bioactive ingredients-related cell-cell adhesion, cell proliferation, and cell migration processes could be affected by earthworms' extract. On 3rd day, the extract could regulate HIF1A and EGFR targets to make the differences of quantities of 4-pyridoxate, tetradecanoic acid, and L-kynurenine. While on 7th day, the regulation refers 6 earthworms' bioactive ingredients, 4 core genes (CTNNB1, EGFR, SRC, and CASP3), and 4 differential metabolites (4-hydoxy-2-quinolinecarboxylic acid, urocanate, deoxyinosine, creatine, and sn-glycerol-3-phosphocholine). on 14th day, 2 core genes (EGFR, SRC) are influenced in the biological processes. Briefly, we found that 6 ingredients from earthworms have most bioactive and 5 core genes play an important role in promoting wound-healing processes. These discovers indicates earthworms could against wound via AGE-RAGE, PI3K-Akt, HIF1A, MAPK, and Axon guidance pathways.PMID:36705857 | DOI:10.1007/s11030-023-10609-7

Appl Biochem Biotechnol. 2023 Jan 27. doi: 10.1007/s12010-023-04325-z. Online ahead of print.ABSTRACTRichness in nutrients with an ample of the myco-bioactive molecules makes Pleurotus osteratus preferential mushroom. In this paper, we conducted a preliminary study on bio-assay-guided fractionation of dichloromethane:ethanol crude extract (1:1, v/v) of P. osteratus (CD) against human breast cancer cell line (MDA-MB-231). Later, CD and its potent hexane (H) and ethyl acetate (EA) fraction were screened against a panel of a human cancer cell lines. H fraction possesses higher cytotoxicity followed by EA and CD. Literature review revealed that polyphenol and ergosterol are the biomarkers found in P. osteratus and could responsible for its cytotoxic potential. Accordingly, hyphenated liquid chromatography with tandem mass spectrometry (LC-MS/MS)-based polyphenol and ergosterol-targeted myco-metabolite profiling of CD, H, and EA fractions were carried out. Despite being significantly rich in polyphenol and ergosterol content, EA fraction showed moderate cytotoxicity. Considering this, liquid chromatography-hybrid quadrupole time-of-flight mass spectrometry (LC-QTOF/MS)-based untargeted myco-metabolite profiling of CD, H and EA fractions was further conducted to identify a new biomarker. Tentatively, 20 myco-metabolites were identified, belonging to the class of steroids, alkaloid, terpenoid, fatty alcohol, and polyketide. The myco-metabolite variabilities among potent samples in correlation to their in vitro anti-cancer activity was explored using the different chemometric tools: principal component analysis (PCA), hierarchical clustering analysis (HCA), and partial least square (PLS). A probable synergistic action among identified myco-metabolites (betulin, solanocapsine, ophiobolin F, linoleoyl ethanolamide, (13R,14R)-7-labdene-13,14,15-triol, asterosterol, cholest-5-ene, (3b,6b,8a,12a)-8,12-epoxy-7(11)-eremophilene-6,8,12-trimethoxy-3-ol, beta-obscurine, myxalamid B, momordol, and avocadyne 4-acetate) may be responsible for the observed cytotoxicity potential of H fraction of P. osteratus.PMID:36705844 | DOI:10.1007/s12010-023-04325-z

Environ Sci Pollut Res Int. 2023 Jan 27. doi: 10.1007/s11356-022-24992-5. Online ahead of print.ABSTRACTAllelochemicals are essential agents for the biological control of harmful blooms. It is crucial to identify efficient algal suppressors and understand their mechanisms. This study reports the inhibition of Microcystis aeruginosa growth by 6 phenolic acids derived from plants' secondary metabolites. The inhibitory effect of phenolic acids was significantly influenced by exposure dose and phenolic acid species. Caffeic acid has the most efficient algal inhibition ability (96 h-EC50 of 5.8 mg/L). In contrast, the other 5 analogs (cinnamic acid, p-coumaric acid, 3-hydroxycinnamic acid, ferulic acid, and isoferulic acid) showed a weak inhibition effect or promotion effect with the exposure dose of 5-100 mg/L. ROS and chlorophyll a content tests combined with metabolomics analysis revealed that caffeic acid could induce the ROS accumulation of M. aeruginosa. They mainly disturbed nucleotide, amino acid, and fatty acid metabolism, leading to the downregulation of most metabolites, including toxins of microcystin LR and cyanopeptolin A, and the precursors of some unpleasant terpenoids. It has been suggested that caffeic acid is an effective agent for controlling M. aeruginosa blooms.PMID:36705822 | DOI:10.1007/s11356-022-24992-5

Anal Bioanal Chem. 2023 Jan 27. doi: 10.1007/s00216-023-04527-8. Online ahead of print.ABSTRACTDespite its critical role in neurodevelopment and brain function, vitamin D (vit-D) homeostasis, metabolism, and kinetics within the central nervous system remain largely undetermined. Thus, it is of critical importance to establish an accurate, highly sensitive, and reproducible method to quantitate vit-D in brain tissue. Here, we present a novel liquid chromatography tandem mass spectrometry (LC-MS/MS) method and for the first time, demonstrate detection of seven major vit-D metabolites in brain tissues of C57BL/6J wild-type mice, namely 1,25(OH)2D3, 3-epi-1,25(OH)2D3, 1,25(OH)2D2, 25(OH)D3, 25(OH)D2, 24,25(OH)2D3, and 24,25(OH)2D2. Chromatographic separation was achieved on a pentaflurophenyl column with 3 mM ammonium formate water/methanol [A] and 3 mM ammonium formate methanol/isopropanol [B] mobile phase components. Detection was by positive ion electrospray tandem mass spectrometry with the EVOQ elite triple quadrupole mass spectrometer with an Advance ultra-high-performance liquid chromatograph and online extraction system. Calibration standards of each metabolite prepared in brain matrices were used to validate the detection range, precision, accuracy, and recovery. Isotopically labelled analogues, 1,25(OH)2D3-d3, 25(OH)D3-c5, and 24,25(OH)2D3-d6, served as the internal standards for the closest molecular-related metabolite in all measurements. Standards between 1 fg/mL and 10 ng/mL were injected with a resulting linear range between 0.001 and 1 ng, with an LLOD and LLOQ of 1 pg/mL and 12.5 pg/mL, respectively. The intra-/inter-day precision and accuracy for measuring brain vit-D metabolites ranged between 0.12-11.53% and 0.28-9.11%, respectively. Recovery in acetonitrile ranged between 99.09 and 106.92% for all metabolites. Collectively, the sensitivity and efficiency of our method supersedes previously reported protocols used to measure vit-D and to our knowledge, the first protocol to reveal the abundance of 25(OH)D2, 1,25(OH)D2, and 24,25(OH)2D2, in brain tissue of any species. This technique may be important in supporting the future advancement of pre-clinical research into the function of vit-D in neurophysiological and neuropsychiatric disorders, and neurodegeneration.PMID:36705732 | DOI:10.1007/s00216-023-04527-8

Plant Cell Rep. 2023 Jan 27. doi: 10.1007/s00299-023-02982-2. Online ahead of print.ABSTRACTBy using the organelle glue technique, we artificially manipulated organelle interactions and controlled the plant metabolome at the pathway level. Plant cell metabolic activity changes with fluctuating environmental conditions, in part via adjustments in the arrangement and interaction of organelles. This hints at the potential for designing plants with desirable metabolic activities for food and pharmaceutical industries by artificially controlling the interaction of organelles through genetic modification. We previously developed a method called the organelle glue technique, in which chloroplast-chloroplast adhesion is induced in plant cells using the multimerization properties of split fluorescent proteins. Here, we generated transgenic Arabidopsis (Arabidopsis thaliana) plants in which chloroplasts adhere to each other and performed metabolome analysis to examine the metabolic changes in these lines. In plant cells expressing a construct encoding the red fluorescent protein mCherry targeted to the chloroplast outer envelope by fusion with a signal sequence (cTP-mCherry), chloroplasts adhered to each other and formed chloroplast aggregations. Mitochondria and peroxisomes were embedded in the aggregates, suggesting that normal interactions between chloroplasts and these organelles were also affected. Metabolome analysis of the cTP-mCherry-expressing Arabidopsis shoots revealed significantly higher levels of glycine, serine, and glycerate compared to control plants. Notably, these are photorespiratory metabolites that are normally transported between chloroplasts, mitochondria, and peroxisomes. Together, our data indicate that chloroplast-chloroplast adhesion alters organellar interactions with mitochondria and peroxisomes and disrupts photorespiratory metabolite transport. These results highlight the possibility of controlling plant metabolism at the pathway level by manipulating organelle interactions.PMID:36705704 | DOI:10.1007/s00299-023-02982-2

Pediatr Allergy Immunol. 2023 Jan;34(1):e13905. doi: 10.1111/pai.13905.ABSTRACTBACKGROUND: Perturbation of gut symbiosis has been linked to childhood allergic diseases. However, the underlying host-microbe interaction connected with specific phenotypes is poorly understood.METHODS: To address this, integrative analyses of stool metagenomic and metabolomic profiles associated with IgE reactions in 56 children with mite-sensitized airway allergies (25 with rhinitis and 31 with asthma) and 28 nonallergic healthy controls were conducted.RESULTS: We noted a decrease in the number and abundance of gut microbiome-encoded carbohydrate-active enzyme (CAZyme) genes, accompanied with a reduction in species richness, in the asthmatic gut microflora but not in that from allergic rhinitis. Such loss of CAZymes was consistent with the observation that a CAZyme-linked decrease in fecal butyrate was found in asthmatics and negatively correlated with mite-specific IgE responses. Different from the CAZymes, we demonstrated an increase in α diversity at the virulome levels in asthmatic gut microbiota and identified phenotype-specific variations of gut virulome. Moreover, use of fecal metagenomic and metabolomic signatures resulted in distinct effects on differentiating rhinitis and asthma from nonallergic healthy controls.CONCLUSION: Overall, our integrative analyses reveal several signatures of systems-level gut microbiome in robust associations with fecal metabolites and disease phenotypes, which may be of etiological and diagnostic implications in childhood airway allergies.PMID:36705037 | DOI:10.1111/pai.13905