PubMed

J Pharm Biomed Anal. 2023 Dec 30;240:115957. doi: 10.1016/j.jpba.2023.115957. Online ahead of print.ABSTRACTEpimedium is a Chinese herbal medicine commonly used in clinical practice to reinforce yang. Previous studies have shown that Epimedium fried with suet oil based has the best effect on warming kidney and promoting yang. Evidence suggests a relationship between kidney yang deficiency syndrome (KYDS) and metabolic disorders of the intestinal microflora. However, the specific interaction between KYDS and the intestinal microbiome, as well as the internal regulatory mechanism of the KYDS intestinal microbiome regulated by Epimedium fried with suet oil, remain unclear. The purpose of this study was to investigate the regulatory effects of different processed products of Epimedium on intestinal microflora and metabolites in rats with kidney yang deficiency, and to reveal the processing mechanism of Epimedium fried with suet oil warming kidney and helping yang. 16 S rRNA and LC-MS/MS technology were used to detect fecal samples. Combined with multivariate statistical analysis, differential intestinal flora and metabolites were screened. Then the content of differential bacteria was then quantified using quantitative real-time fluorescence PCR. Furthermore, the correlation between differential bacterial flora and metabolites was analyzed using Spearman's method. The study found that the composition of intestinal flora in rats with kidney yang deficiency changed compared to healthy rats. Epimedium fried with suet oil could increase the levels of beneficial bacteria, while significantly reducing the levels of harmful bacteria. Real-time quantitative PCR results were consistent with 16 S rRNA gene sequencing analysis. Fecal metabolomics revealed that KYDS was associated with 30 different metabolites, involving metabolic pathways steroid hormone biosynthesis etc. Moreover, differential bacteria were closely correlated with potential biomarkers. Epimedium could improve metabolic disorders associated with KYDS by acting on the intestinal flora, with Epimedium fried with suet oil demonstrating the most effective regulatory effect. Its potential mechanism may involve the regulation of abnormal metabolism and the impact on the diversity and structure of the intestinal flora.PMID:38181555 | DOI:10.1016/j.jpba.2023.115957

Mol Genet Metab. 2023 Dec 15;141(1):108115. doi: 10.1016/j.ymgme.2023.108115. Online ahead of print.ABSTRACTInborn errors of metabolism (IEMs) encompass a diverse group of disorders that can be difficult to classify due to heterogenous clinical, molecular, and biochemical manifestations. Untargeted metabolomics platforms have become a popular approach to analyze IEM patient samples because of their ability to detect many metabolites at once, accelerating discovery of novel biomarkers, and metabolic mechanisms of disease. However, there are concerns about the reproducibility of untargeted metabolomics research due to the absence of uniform reporting practices, data analyses, and experimental design guidelines. Therefore, we critically evaluated published untargeted metabolomic platforms used to characterize IEMs to summarize the strengths and areas for improvement of this technology as it progresses towards the clinical laboratory. A total of 96 distinct IEMs were collectively evaluated by the included studies. However, most of these IEMs were evaluated by a single untargeted metabolomic method, in a single study, with a limited cohort size (55/96, 57%). The goals of the included studies generally fell into two, often overlapping, categories: detecting known biomarkers from many biochemically distinct IEMs using a single platform, and detecting novel metabolites or metabolic pathways. There was notable diversity in the design of the untargeted metabolomic platforms. Importantly, the majority of studies reported adherence to quality metrics, including the use of quality control samples and internal standards in their experiments, as well as confirmation of at least some of their feature annotations with commercial reference standards. Future applications of untargeted metabolomics platforms to the study of IEMs should move beyond single-subject analyses, and evaluate reproducibility using a prospective, or validation cohort.PMID:38181458 | DOI:10.1016/j.ymgme.2023.108115

J Agric Food Chem. 2024 Jan 5. doi: 10.1021/acs.jafc.3c06846. Online ahead of print.ABSTRACTIt is widely accepted that prevéraison application of naphthaleneacetic acid (NAA) can delay the ripening of grapes and improve their quality. However, how NAA impacts grape aroma compound concentrations remains unclear. This study incorporated the analyses of aroma metabolome, phytohormones, and transcriptome of Vitis vinifera L. cv. Cabernet Sauvignon grapes cultivated in continental arid/semiarid regions of western China. The analyses demonstrated that NAA application increased β-damascenone and 1,1,6-trimethyl-1,2-dihydronaphthalene (TDN) in the harvested grapes by delaying véraison and upregulating VvPSY1 and VvCCD4b expressions. Additionally, NAA treatment decreased 2-isobutyl-3-methoxypyrazine (IBMP) at the same phenological stage. Notably, abscisic acid (ABA) levels increased in NAA-treated grapes during véraison, which triggered further changes in norisoprenoid metabolisms. The ABA-responsive factor VvABF2 was potentially involved in VvPSY1 positive modulation, while the auxin response factor VvARF10 may play a role in VvCCD4b upregulation and VvOMT2 downregulation during NAA induction. VvARF10 possibly acts as a crosstalk node between the ABA and auxin signaling pathways following NAA treatment in regulating aroma biosynthesis.PMID:38181223 | DOI:10.1021/acs.jafc.3c06846

J Agric Food Chem. 2024 Jan 5. doi: 10.1021/acs.jafc.3c06616. Online ahead of print.ABSTRACTCannabis is widely used for medicinal and recreational purposes. As a result, there is increased interest in its chemical components and their physiological effects. However, current information on cannabis chemistry is often outdated or scattered across many books and journals. To address this issue, we used modern metabolomics techniques and modern bioinformatics techniques to compile a comprehensive list of >6000 chemical constituents in commercial cannabis. The metabolomics methods included a combination of high- and low-resolution liquid chromatography-mass spectrometry (MS), gas chromatography-MS, and inductively coupled plasma-MS. The bioinformatics methods included computer-aided text mining and computational genome-scale metabolic inference. This information, along with detailed compound descriptions, physicochemical data, known physiological effects, protein targets, and referential compound spectra, has been made available through a publicly accessible database called the Cannabis Compound Database (https://cannabisdatabase.ca). Such a centralized, open-access resource should prove to be quite useful for the cannabis community.PMID:38181219 | DOI:10.1021/acs.jafc.3c06616

Chem Res Toxicol. 2024 Jan 5. doi: 10.1021/acs.chemrestox.3c00344. Online ahead of print.ABSTRACTThe reaction of 1,2-aminothiol groups with aldehyde residues in aqueous solution generates thiazolidine products, and this process has been developed as a catalyst-free click reaction for bioconjugation. The work reported here characterized reactions of the biologically relevant 1,2-aminothiols including cysteamine, cysteine methyl ester, and peptides containing N-terminal cysteine residues with the aldehyde residue of apurinic/apyrimidinic (AP) sites in DNA oligomers. These 1,2-aminothiol-containing compounds rapidly generated adducts with AP sites in single-stranded and double-stranded DNA. NMR and MALDI-TOF-MS analyses provided evidence that the reaction generated a thiazolidine product. Conversion of an AP site to a thiazolidine-AP adduct protected against the rapid cleavage normally induced at AP sites by the endonuclease action of the enzyme APE1 and the AP-lyase activity of the biogenic amine spermine. In the presence of excess 1,2-aminothiols, the thiazolidine-AP adducts underwent slow strand cleavage via a β-lyase reaction that generated products with 1,2-aminothiol-modified sugar residues on the 3'-end of the strand break. In the absence of excess 1,2-aminothiols, the thiazolidine-AP adducts dissociated to release the parent AP-containing oligonucleotide. The properties of the thiazolidine-AP adducts described here mirror critical properties of SRAP proteins HMCES and YedK that capture AP sites in single-stranded regions of cellular DNA and protect them from cleavage.PMID:38181204 | DOI:10.1021/acs.chemrestox.3c00344

J Agric Food Chem. 2024 Jan 5. doi: 10.1021/acs.jafc.3c06301. Online ahead of print.ABSTRACTTocotrienols and tocopherols (vitamin E) are potent antioxidants that are synthesized in green plants. Unlike ubiquitous tocopherols, tocotrienols predominantly accumulate in the endosperm of monocot grains, catalyzed by homogentiate geranylgeranyl transferase (HGGT). Previously, we generated a tocotrienol-deficient hvhggt mutant with shrunken barley grains. However, the relationship between tocotrienols and grain development remains unclear. Here, we found that the hvhggt lines displayed hollow endosperms with defective transfer cells and reduced aleurone layers. The carbohydrate and starch contents of the hvhggt endosperm decreased by approximately 20 and 23%, respectively. Weighted gene coexpression network analyses identified a critical gene module containing HvHGGT, which was strongly associated with the hvhggt mutation and enriched with gene functions in starch and sucrose metabolism. Metabolome measurements revealed an elevated soluble sugar content in the hvhggt endosperm, which was significantly associated with the identified gene modules. The hvhggt endosperm had significantly higher NAD(H) and NADP(H) contents and lower levels of ADPGlc (regulated by redox balance) than the wild-type, consistent with the absence of tocotrienols. Interestingly, exogenous α-tocotrienol spraying on developing hvhggt spikes partially rescued starch accumulation and endosperm defects. Our study supports a potential novel function of tocotrienols in grain starch accumulation and endosperm development in monocot crops.PMID:38181192 | DOI:10.1021/acs.jafc.3c06301

Cancer Biother Radiopharm. 2024 Jan 5. doi: 10.1089/cbr.2023.0116. Online ahead of print.ABSTRACTWith the development of the social economy and the deepening understanding of cancer, cancer has become a significant cause of death, threatening human health. Although researchers have made rapid progress in cancer treatment strategies in recent years, the overall survival of cancer patients is still not optimistic. Therefore, it is essential to reveal the spatial pattern of gene expression, spatial heterogeneity of cell populations, microenvironment interactions, and other aspects of cancer. Spatiotemporal transcriptomics can help analyze the mechanism of cancer occurrence and development, greatly help precise cancer treatment, and improve clinical prognosis. Here, we review the integration strategies of single-cell RNA sequencing and spatial transcriptomics data, summarize the recent advances in spatiotemporal transcriptomics in cancer studies, and discuss the combined application of spatial multiomics, which provides new directions and strategies for the precise treatment and clinical prognosis of cancer.PMID:38181185 | DOI:10.1089/cbr.2023.0116

Int J Surg. 2024 Jan 4. doi: 10.1097/JS9.0000000000001033. Online ahead of print.ABSTRACTOBJECTIVES: Prostate cancer (PCa) is one of the most common malignancies in men worldwide and has caused increasing clinical morbidity and mortality, making timely diagnosis and accurate staging crucial. We introduced a novel approach based on mass spectrometry (MS) for precise diagnosis and stratification of PCa to facilitate clinical decision-making.METHODS: Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) MS analysis of trace blood samples was combined with machine learning algorithms to construct diagnostic and stratification models. A total of 367 subjects, comprising 181 with PCa and 186 with non-PCa were enrolled. Additional 60 subjects, comprising 30 with PCa and 30 with non-PCa were enrolled as an external cohort for validation. Subsequent metabolomic analysis was carried out using Autoflex MALDI-TOF, and the mass spectra were introduced into various algorithms to construct different models.RESULTS: Serum metabolic fingerprints were successfully obtained from 181 patients with PCa and 186 patients with non-PCa. The diagnostic model based on the eight signals demonstrated a remarkable area under curve (AUC) of 100% and was validated in the external cohort with the AUC of 87.3%. Fifteen signals were selected for enrichment analysis, revealing the potential metabolic pathways that facilitate tumorigenesis. Furthermore, the stage prediction model with an overall accuracy of 85.9% precisely classified subjects with localized disease and those with metastasis. The risk stratification model, with an overall accuracy of 89.6%, precisely classified the subjects as low-risk and high-risk.CONCLUSIONS: Our study facilitated the timely diagnosis and risk stratification of PCa and provided new insights into the underlying mechanisms of metabolic alterations in PCa.PMID:38181121 | DOI:10.1097/JS9.0000000000001033

Proc Natl Acad Sci U S A. 2024 Jan 9;121(2):e2321437121. doi: 10.1073/pnas.2321437121. Epub 2024 Jan 5.NO ABSTRACTPMID:38181059 | DOI:10.1073/pnas.2321437121

J Infect Dis. 2024 Jan 5:jiad611. doi: 10.1093/infdis/jiad611. Online ahead of print.ABSTRACTBACKGROUND: Avian influenza viruses pose significant risk to human health. Vaccines targeting the hemagglutinin of these viruses are poorly immunogenic without the use of adjuvants.METHODS: Twenty healthy men and women (18-49 years of age) were randomized to receive two doses of inactivated influenza A/H5N1 vaccine alone (IIV) or with AS03 adjuvant (IIV-AS03) one month apart. Urine and serum samples were collected on day 0 and on days 1, 3, and 7 following first vaccination and subjected to metabolomics analyses to identify metabolites, metabolic pathways, and metabolite clusters associated with immunization.RESULTS: Seventy-three differentially abundant (DA) serum and 88 urine metabolites were identified for any post-vaccination day comparison. Pathway analysis revealed enrichment of tryptophan, tyrosine and nicotinate metabolism in urine and serum among IIV-AS03 recipients. Increased urine abundance of 4-vinylphenol sulfate on Day 1 was associated with serologic response based on hemagglutination inhibition responses. In addition, 9 DA urine metabolites were identified in participants with malaise compared to those without.CONCLUSIONS: Our findings suggest that tryptophan, tyrosine, and nicotinate metabolism are upregulated among IIV-AS03 recipients compared with IIV alone. Metabolites within these pathways may serve as measures of immunogenicity and may provide mechanistic insights for adjuvanted vaccines.PMID:38181048 | DOI:10.1093/infdis/jiad611

Metabolomics. 2024 Jan 5;20(1):13. doi: 10.1007/s11306-023-02081-z.ABSTRACTINTRODUCTION: The burden of stroke in patients with hypertension is very high, and its prediction is critical.OBJECTIVES: We aimed to use plasma lipidomics profiling to identify lipid biomarkers for predicting incident stroke in patients with hypertension.METHODS: This was a nested case-control study. Baseline plasma samples were collected from 30 hypertensive patients with newly developed stroke, 30 matched patients with hypertension, 30 matched patients at high risk of stroke, and 30 matched healthy controls. Lipidomics analysis was performed by ultrahigh-performance liquid chromatography-tandem mass spectrometry, and differential lipid metabolites were screened using multivariate and univariate statistical methods. Machine learning methods (least absolute shrinkage and selection operator, random forest) were used to identify candidate biomarkers for predicting stroke in patients with hypertension.RESULTS: Co-expression network analysis revealed that the key molecular alterations of the lipid network in stroke implicate glycerophospholipid metabolism and choline metabolism. Six lipid metabolites were identified as candidate biomarkers by multivariate statistical and machine learning methods, namely phosphatidyl choline(40:3p)(rep), cholesteryl ester(20:5), monoglyceride(29:5), triglyceride(18:0p/18:1/18:1), triglyceride(18:1/18:2/21:0) and coenzyme(q9). The combination of these six lipid biomarkers exhibited good diagnostic and predictive ability, as it could indicate a risk of stroke at an early stage in patients with hypertension (area under the curve = 0.870; 95% confidence interval: 0.783-0.957).CONCLUSIONS: We determined lipidomic signatures associated with future stroke development and identified new lipid biomarkers for predicting stroke in patients with hypertension. The biomarkers have translational potential and thus may serve as blood-based biomarkers for predicting hypertensive stroke.PMID:38180633 | DOI:10.1007/s11306-023-02081-z

Metabolomics. 2024 Jan 5;20(1):12. doi: 10.1007/s11306-023-02078-8.ABSTRACTINTRODUCTION: Alzheimer's Disease (AD) is complex and novel approaches are urgently needed to aid in diagnosis. Blood is frequently used as a source for biomarkers; however, its complexity prevents proper detection. The analytical power of metabolomics, coupled with statistical tools, can assist in reducing this complexity.OBJECTIVES: Thus, we sought to validate a previously proposed panel of metabolic blood-based biomarkers for AD and expand our understanding of the pathological mechanisms involved in AD that are reflected in the blood.METHODS: In the validation cohort serum and plasma were collected from 25 AD patients and 25 healthy controls. Serum was analysed for metabolites using nuclear magnetic resonance (NMR) spectroscopy, while plasma was tested for markers of neuronal damage and AD hallmark proteins using single molecule array (SIMOA).RESULTS: The diagnostic performance of the metabolite biomarker panel was confirmed using sparse-partial least squares discriminant analysis (sPLS-DA) with an area under the curve (AUC) of 0.73 (95% confidence interval: 0.59-0.87). Pyruvic acid and valine were consistently reduced in the discovery and validation cohorts. Pathway analysis of significantly altered metabolites in the validation set revealed that they are involved in branched-chain amino acids (BCAAs) and energy metabolism (glycolysis and gluconeogenesis). Additionally, strong positive correlations were observed for valine and isoleucine between cerebrospinal fluid p-tau and t-tau.CONCLUSIONS: Our proposed panel of metabolites was successfully validated using a combined approach of NMR and sPLS-DA. It was discovered that cognitive-impairment-related metabolites belong to BCAAs and are involved in energy metabolism.PMID:38180611 | DOI:10.1007/s11306-023-02078-8

Endocr Connect. 2024 Jan 1:EC-23-0384. doi: 10.1530/EC-23-0384. Online ahead of print.ABSTRACTDiabetic cardiomyopathy (DCM) is a serious complication of type 2 diabetes mellitus (T2DM) that contributes to cardiovascular morbidity and mortality. However, the metabolic alterations and specific biomarkers associated with DCM in T2DM remain unclear. In this study, we conducted a comprehensive metabolomic analysis using liquid chromatography-mass spectrometry (LC-MS) to investigate the plasma metabolite profiles of T2DM patients with and without DCM. We identified significant differences in metabolite levels between the groups, highlighting the dysregulation of various metabolic pathways, including starch and sucrose metabolism, steroid hormone biosynthesis, tryptophan metabolism, purine metabolism, and pyrimidine metabolism. Although several metabolites showed altered abundance in DCM, they were also shared characteristics of DCM and T2DM rather than specific to DCM. Additionally, through biomarker analyses, we identified potential biomarkers for DCM, such as cytidine triphosphate, 11-ketoetiocholanolone, saccharopine, nervonic acid, and erucic acid. These biomarkers demonstrated distinct patterns and associations with metabolic pathways related to DCM. Our findings provide insights into the metabolic changes associated with DCM in T2DM patients and highlight potential biomarkers for further validation and clinical application. Further research is needed to elucidate the underlying mechanisms and validate the diagnostic and prognostic value of these biomarkers in larger cohorts.PMID:38180052 | DOI:10.1530/EC-23-0384

Biomark Med. 2024 Jan 5. doi: 10.2217/bmm-2023-0420. Online ahead of print.ABSTRACTAsthma, chronic obstructive pulmonary disease (COPD) and asthma-COPD overlap are the third leading cause of mortality around the world. They share some common features, which can lead to misdiagnosis. To properly manage these conditions, reliable markers for early and accurate diagnosis are needed. Over the past 20 years, many molecules have been investigated in the exhaled breath condensate to better understand inflammation pathways and mechanisms related to these disorders. Recently, more advanced techniques, such as sensitive metabolomic and proteomic profiling, have been used to obtain a more comprehensive understanding. This article reviews the use of targeted and untargeted metabolomic methodology to study asthma, COPD and asthma-COPD overlap.PMID:38179966 | DOI:10.2217/bmm-2023-0420

Anal Chem. 2024 Jan 5. doi: 10.1021/acs.analchem.3c03660. Online ahead of print.ABSTRACTThe implementation of quality control strategies is crucial to ensure the reproducibility, accuracy, and meaningfulness of metabolomics data. However, this pivotal step is often overlooked within the metabolomics workflow and frequently relies on the use of nonstandardized and poorly reported protocols. To address current limitations in this respect, we have developed QComics, a robust, easily implementable and reportable method for monitoring and controlling data quality. The protocol operates in various sequential steps aimed to (i) correct for background noise and carryover, (ii) detect signal drifts and "out-of-control" observations, (iii) deal with missing data, (iv) remove outliers, (v) monitor quality markers to identify samples affected by improper collection, preprocessing, or storage, and (vi) assess overall data quality in terms of precision and accuracy. Notably, this tool considers important issues often neglected along quality control, such as the need of separately handling missing values and truly absent data to avoid losing relevant biological information, as well as the large impact that preanalytical factors may elicit on metabolomics results. Altogether, the guidelines compiled in QComics might contribute to establishing gold standard recommendations and best practices for quality control within the metabolomics community.PMID:38179935 | DOI:10.1021/acs.analchem.3c03660

Circ Heart Fail. 2024 Jan 5:e010813. doi: 10.1161/CIRCHEARTFAILURE.123.010813. Online ahead of print.ABSTRACTBACKGROUND: Metabolomics has become a valuable tool for identifying potential new biomarkers and metabolic profiles. It has the potential to improve the diagnosis and prognosis of different phenotypes of heart failure. To generate a distinctive metabolic profile, we assessed and compared the metabolic phenotypes of patients with acute decompensated heart failure (ADHF), patients with chronic heart failure (CHF), and healthy controls.METHODS: Plasma metabolites were analyzed by liquid-chromatography mass spectrometry/mass spectrometry and the MxP Quant 500 kit in 15 patients with ADHF, 50 patients with CHF (25 with dilated cardiomyopathy, 25 with ischemic cardiomyopathy), and 13 controls.RESULTS: Of all metabolites identified to be significantly altered, 3-indolepropionic acid and 1-methyl histidine showed the highest concentration differences in ADHF and CHF compared with control. Area under the curve-receiver operating characteristic analysis showed an area under the curve ≥0.8 for 3-indolepropionic acid and 1-methyl histidine, displaying good discrimination capabilities between control and patient cohorts. Additionally, symmetrical dimethylarginine (mean, 1.97±0.61 [SD]; P=0.01) was identified as a suitable biomarker candidate for ADHF and kynurenine (mean, 1.69±0.39 [SD]; P=0.009) for CHF when compared with control, both demonstrating an area under the curve ≥0.85.CONCLUSIONS: Our study provides novel insights into the metabolic differences between ADHF and CHF and healthy controls. We here identify new metabolites for potential diagnostic and prognostic purposes.PMID:38179791 | DOI:10.1161/CIRCHEARTFAILURE.123.010813

Front Biosci (Landmark Ed). 2023 Dec 26;28(12):344. doi: 10.31083/j.fbl2812344.ABSTRACTBACKGROUND: Activating transcription factor 4 (ATF4) is a fundamental basic-leucine zipper transcription factor that plays a pivotal role in numerous stress responses, including endoplasmic reticulum (ER) stress and the integrated stress response. ATF4 regulates adaptive gene expression, thereby triggering stress resistance in cells.METHODS: To characterize the metabolic status of atf4-⁣/- Drosophila larvae, we conducted both metabolomic and microarray analyses.RESULTS: Metabolomic analysis demonstrated an increase in lactate levels in atf4-⁣/- mutants when compared to wild-type flies. However, there was a significant reduction in adenosine triphosphate (ATP) synthesis in the atf4-⁣/- flies, suggesting an abnormal energy metabolism in the mutant larvae. Microarray analysis unveiled that Drosophila ATF4 controls gene expression related to diverse biological processes, including lipase activity, oxidoreductase activity, acyltransferase, immune response, cell death, and transcription factor, particularly under nutrient-restricted conditions. In situ hybridization analysis further demonstrated specific augmentation of CG6283, classified as a gastric lipase, within the gastric caeca of nutrient-restricted flies. Moreover, overexpression of lipases, CG6283 and CG6295, made the flies resistant to starvation.CONCLUSIONS: These findings underscore the role of Drosophila ATF4 in responding to metabolic fluctuations and modulating gene expression associated with metabolism and stress adaptation. Dysregulation of ATF4 may detrimentally impact the development and physiology of Drosophila.PMID:38179767 | DOI:10.31083/j.fbl2812344

Front Biosci (Landmark Ed). 2023 Dec 26;28(12):345. doi: 10.31083/j.fbl2812345.ABSTRACTBACKGROUND: Chinese cabbage (Brassica rapa L. ssp. pekinensis) is one of the most popular vegetables in China because of its taste and health benefits. The area of production has obvious effects on the quality of Chinese cabbage. However, metabolite profiling and variations in different production areas are still unclear.METHODS: Here, widely targeted metabolite analyses based on the ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) approach were performed to study the metabolite profiling of Chinese cabbage planted in the Jiaozhou and Jinan areas.RESULTS: A total of 531 metabolites were detected, of which 529 were present in the Chinese cabbage from both areas, 108 were found to be chemicals related to Chinese traditional medicine, and 79 were found to correspond to at least one disease. Chinese cabbage is rich in nutritious substances such as lipids, phenolic acids, amino acids and derivatives, nucleotides and derivatives, organic acids, flavonoids, glucosinolates, saccharides, alcohols, and vitamins. Comparative analysis showed that the metabolic profiles differed between areas, and 89 differentially altered metabolites (DAMs) were characterized. Of these, 78 DAMs showed higher levels in Jinan Chinese cabbage, whereas 11 had higher levels in Jiaozhou Chinese cabbage. Two metabolites, S-(Methyl)glutathione and nicotinic acid adenine dinucleotide, were unique in Jiaozhou Chinese cabbage. Based on Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, the DAMs were enriched into 23 pathways, of which tryptophan metabolism and thiamine metabolism were the significant enrichment pathways.CONCLUSIONS: This study provides new insights into the metabolite profiles and production areas affecting the metabolite variations of Chinese cabbage, which will be useful for functional Chinese cabbage cultivation.PMID:38179748 | DOI:10.31083/j.fbl2812345

Technol Cancer Res Treat. 2024 Jan-Dec;23:15330338231223080. doi: 10.1177/15330338231223080.ABSTRACTBACKGROUND: Acute myeloid leukemia (AML) with Fms-like tyrosine kinase 3 gene internal tandem duplication (FLT3-ITD) mutations has a poor prognosis. The combination of arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) has a synergistic killing effect on leukemia cells with FLT3-ITD mutation. However, the mechanism, especially the changes of gene expression and metabolic activity remain unclear. Here we explore the transcriptome and metabolomics changes of FLT3-ITD AML cells treated with ATO/ATRA.METHODS: RNA-seq was used to identify differential expressed genes (DEGs), and ultra-high performance liquid chromatography-quadrupole electrostatic field orbital trap mass spectrometry (UHPLC-QE-MS) nontargeted metabolomics method was used to screen out the differential metabolites in FLT3-ITD mutant cell lines treated with ATRA and ATO. KEGG pathway database was utilized for pathway exploration and Seahorse XF24 was used to detect extracellular acidification rate (ECAR). Metabolic polymerase chain reaction (PCR) array and real-time quantitative PCR (RT-qPCR) were used to detect mRNA levels of key metabolic genes of glycolysis and fatty acid after drug treatment.RESULTS: A total of 3873 DEGs were identified and enriched in 281 Gene Ontology (GO) terms, among which 210 were related to biological processes, 43 were related to cellular components, and 28 were related to molecular functions. Besides, 1794 and 927 differential metabolites were screened in positive and negative ion mode separately, and 59 different metabolic pathways were involved, including alanine-aspartate-glutamate metabolic pathway, arginine, and proline metabolic pathway, glycerophospholipid metabolic pathways, etc. According to KEGG Pathway analysis of transcriptome combined with metabolome, glycolysis/gluconeogenesis pathway and fatty acid metabolism pathway were significantly founded enriched. ATRA + ATO may inhibit the glycolysis of FLT3-ITD AML cells by inhibiting FLT3 and its downstream AKT/HK2-VDAC1 signaling pathway.CONCLUSIONS: The gene transcription profile and metabolites of FLT3-ITD mutant cells changes significantly after treatment, which might be related to the anti-FLT3-ITD AML effect. The screened DEGs, differential metabolites pathway are helpful in studying the mechanism of anti-leukemia effects and drug targets.PMID:38179723 | DOI:10.1177/15330338231223080

Front Plant Sci. 2023 Dec 21;14:1274700. doi: 10.3389/fpls.2023.1274700. eCollection 2023.ABSTRACTFlavonoids are secondary metabolites that have economic value and are essential for health. Poplar is a model perennial woody tree that is often used to study the regulatory mechanisms of flavonoid synthesis. We used a poplar bud mutant, the red leaf poplar variety 2025 (Populus × euramericana 'Zhonghuahongye'), and green leaves as study materials and selected three stages of leaf color changes for evaluation. Phenotypic and biochemical analyses showed that the total flavonoid, polyphenol, and anthocyanin contents of red leaves were higher than those of green leaves in the first stage, and the young and tender leaves of the red leaf variety had higher antioxidant activity. The analyses of widely targeted metabolites identified a total of 273 flavonoid metabolites (114 flavones, 41 flavonols, 34 flavonoids, 25 flavanones, 21 anthocyanins, 18 polyphenols, 15 isoflavones, and 5 proanthocyanidins). The greatest difference among the metabolites was found in the first stage. Most flavonoids accumulated in red leaves, and eight anthocyanin compounds contributed to red leaf coloration. A comprehensive metabolomic analysis based on RNA-seq showed that most genes in the flavonoid and anthocyanin biosynthetic pathways were differentially expressed in the two types of leaves. The flavonoid synthesis genes CHS (chalcone synthase gene), FLS (flavonol synthase gene), ANS (anthocyanidin synthase gene), and proanthocyanidin synthesis gene LAR (leucoanthocyanidin reductase gene) might play key roles in the differences in flavonoid metabolism. A correlation analysis of core metabolites and genes revealed several candidate regulators of flavonoid and anthocyanin biosynthesis, including five MYB (MYB domain), three bHLH (basic helix-loop-helix), and HY5 (elongated hypocotyl 5) transcription factors. This study provides a reference for the identification and utilization of flavonoid bioactive components in red-leaf poplar and improves the understanding of the differences in metabolism and gene expression between red and green leaves at different developmental stages.PMID:38179486 | PMC:PMC10764563 | DOI:10.3389/fpls.2023.1274700