PubMed

Front Plant Sci. 2023 Apr 12;14:1103413. doi: 10.3389/fpls.2023.1103413. eCollection 2023.ABSTRACTPlant-microbe interactions are a phenomenal display of symbiotic/parasitic relationships between living organisms. Plant growth-promoting rhizobacteria (PGPR) are some of the most widely investigated plant-beneficial microbes due to their capabilities in stimulating plant growth and development and conferring protection to plants against biotic and abiotic stresses. As such, PGPR-mediated plant priming/induced systemic resistance (ISR) has become a hot topic among researchers, particularly with prospects of applications in sustainable agriculture. The current study applies untargeted ultra-high performance liquid chromatography-high-definition mass spectrometry (UHPLC-HDMS) to investigate PGPR-based metabolic reconfigurations in the metabolome of primed wheat plants against Puccinia striiformis f. sp. tricti (Pst). A seed bio-priming approach was adopted, where seeds were coated with two PGPR strains namely Bacillus subtilis and Paenibacillus alvei (T22) and grown under controlled conditions in a glasshouse. The plants were infected with Pst one-week post-germination, followed by weekly harvesting of leaf material. Subsequent metabolite extraction was carried out for analysis on a UHPLC-HDMS system for data acquisition. The data was chemometrically processed to reveal the underlying trends and data structures as well as potential signatory biomarkers for priming against Pst. Results showed notable metabolic reprogramming in primary and secondary metabolism, where the amino acid and organic acid content of primed-control, primed-challenged and non-primed-challenged plants were differentially reprogrammed. Similar trends were observed from the secondary metabolism, in which primed plants (particularly primed-challenged) showed an up-regulation of phenolic compounds (flavonoids, hydroxycinnamic acids-HCAs- and HCA amides) compared to the non-primed plants. The metabolomics-based semi-quantitative and qualitative assessment of the plant metabolomes revealed a time-dependent metabolic reprogramming in primed-challenged and primed-unchallenged plants, indicating the metabolic adaptations of the plants to stripe rust infection over time.PMID:37123830 | PMC:PMC10132142 | DOI:10.3389/fpls.2023.1103413

Front Plant Sci. 2023 Apr 14;14:1131735. doi: 10.3389/fpls.2023.1131735. eCollection 2023.ABSTRACTCucumber is one of the most important vegetable crops, which is widely planted all over the world. Cucumber always suffers from high-temperature stress in South China in summer. In this study, liquid chromatography-mass spectrometry (LC-MS) analysis was used to study the differential metabolites of cucumber anther between high-temperature (HT) stress and normal condition (CK). After HT, the pollen fertility was significantly reduced, and abnormal anther structures were observed by the paraffin section. In addition, the metabolomics analysis results showed that a total of 125 differential metabolites were identified after HT, consisting of 99 significantly upregulated and 26 significantly downregulated metabolites. Among these differential metabolites, a total of 26 related metabolic pathways were found, and four pathways showed significant differences, namely, porphyrin and chlorophyll metabolism; plant hormone signal transduction; amino sugar and nucleotide sugar metabolism; and glycine, serine, and threonine metabolism. In addition, pollen fertility was decreased by altering the metabolites of plant hormone signal transduction and amino acid and sugar metabolism pathway under HT. These results provide a comprehensive understanding of the metabolic changes in cucumber anther under HT.PMID:37123826 | PMC:PMC10140443 | DOI:10.3389/fpls.2023.1131735

iScience. 2023 Apr 1;26(4):106556. doi: 10.1016/j.isci.2023.106556. eCollection 2023 Apr 21.ABSTRACTThe bZIP transcription factors are well-known transcriptional regulators that are essential for regulating resistance to biotic and abiotic stresses in plants. In this study, a total of 56 putative bZIP members were identified in passion fruit (Passiflora edulis). An integrative analysis was performed using bioinformatics. Transcriptome analysis revealed that most PebZIPs respond to drought, salt, cold and heat stress. By combining the transcriptome results of two different resistant genotypes, four representative members were finally selected for differential expression validation in different tissues and cultivars. Furthermore, transcriptome and metabolome association analysis revealed consistent expression trends of PeZIP20 and PeZIP21, with only one difference at 63aa, with different metabolites including flavonoids, lipids and amino acids. This work will contribute to further studies of the functions of bZIPs and their resistance properties, as well as to the development of novel germplasm.PMID:37123220 | PMC:PMC10130921 | DOI:10.1016/j.isci.2023.106556

Livers. 2022 Dec;2(4):243-257. doi: 10.3390/livers2040020. Epub 2022 Oct 4.ABSTRACTOne carbon metabolism (1CM) can be defined as the transfer of a carbon unit from one metabolite to another and its replenishment by different sources of labile methyl-group nutrients: primarily choline, methionine, betaine, and serine. This flow of carbon units allows the biosynthesis of nucleotides, amino acids, formylated methionyl-tRNA, polyamines, glutathione, phospholipids, detoxification reactions, maintenance of the redox status and the concentration of NAD, and methylation reactions including epigenetic modifications. That is, 1CM functions as a nutrient sensor and integrator of cellular metabolism. A critical process in 1CM is the synthesis of S-adenosylmethionine (SAMe), the source of essentially all the hundreds of millions of daily methyl transfer reactions in a cell. This versatility of SAMe imposes a tight control in its synthesis and catabolism. Much of our knowledge concerning 1CM has been gained from studies in the production and prevention of nonalcoholic fatty liver disease (NAFLD). Here, we discuss in detail the function of the most important enzymes for their quantitative contribution to maintaining the flux of carbon units through 1CM in the liver and discuss how alterations in their enzymatic activity contribute to the development of NAFLD. Next, we discuss NAFLD subtypes based on serum lipidomic profiles with different risk of cardiovascular disease. Among the latter, we highlight the so-called subtype A for its serum lipidomic profile phenocopying that of mice deficient in SAMe synthesis and because its high frequency (about 50% of the NAFLD patients).PMID:37123053 | PMC:PMC10137169 | DOI:10.3390/livers2040020

Front Immunol. 2023 Apr 14;14:1114586. doi: 10.3389/fimmu.2023.1114586. eCollection 2023.ABSTRACTBACKGROUND: Gut dysbiosis and gut microbiome-derived metabolites have been implicated in both disease onset and treatment response, but this has been rarely demonstrated in pemphigus vulgaris (PV). Here, we aim to systematically characterize the gut microbiome to assess the specific microbial species and metabolites associated with PV.METHODS: We enrolled 60 PV patients and 19 matched healthy family members, and collected 100 fecal samples (60 treatment-naïve, 21 matched post-treatment, and 19 controls). Metagenomic shotgun sequencing and subsequent quality control/alignment/annotation were performed to assess the composition and microbial species, in order to establish the association between gut microbiome with PV onset and treatment response. In addition, we evaluated short-chain fatty acids (SCFAs) in PV patients through targeted metabolomics analysis.RESULTS: The diversity of the gut microbiome in PV patients deviates from the healthy family members but not between responder and non-responder, or before and after glucocorticoid treatment. However, the relative abundance of several microbial species, including the pathogenic bacteria (e.g., Escherichia coli) and some SCFA-producing probiotics (e.g., Eubacterium ventriosum), consistently differed between the two groups in each comparison. Escherichia coli was enriched in PV patients and significantly decreased after treatment in responders. In contrast, Eubacterium ventriosum was enriched in healthy family members and significantly increased particularly in responders after treatment. Consistently, several gut microbiome-derived SCFAs were enriched in healthy family members and significantly increased after treatment (e.g., butyric acid and valeric acid).CONCLUSIONS: This study supports the association between the gut microbiome and PV onset, possibly through disrupting the balance of gut pathogenic bacteria and probiotics and influencing the level of gut microbiome-derived SCFAs. Furthermore, we revealed the potential relationship between specific microbial species and glucocorticoid treatment.PMID:37122759 | PMC:PMC10140300 | DOI:10.3389/fimmu.2023.1114586

Front Immunol. 2023 Apr 14;14:1139249. doi: 10.3389/fimmu.2023.1139249. eCollection 2023.ABSTRACTINTRODUCTION: The present study assessed whether asinine milk supplementation improved the immune and behavioral responses of piglets during an early life weaning stress event as a model for its future use in humans.METHODS: For this, 48 piglets from 4 different litters were used. At 20 days of age, piglets were weighed and allocated with their litter and dam into group pens until 28 days of age. Four piglets from each litter were then randomly assigned to either (1) asinine milk supplementation (n = 16) (2), skimmed cow milk supplementation (n = 16) or (3) no supplementation (n = 16; control group). The supplementations were voluntarily administered for 3 days preweaning and 3 days postweaning using a baby bottle. The effects on the weaning stress response were assessed through salivary cortisol measurements; behavioral tests such as the open field, novel object end elevated plus maze tests; and gene expression of HSD11B1, NR3C1 and IL1B in PBMCs, which was determined by RT-qPCR and normalized to GAPDH and UBB. To test the effect of the supplementations on weight, milk intake, gene expression, and behavior, a randomized block design was used with repeated measurements over time by the PROC MIXED procedure.RESULTS AND DISCUSSION: The effects on salivary cortisol were determined using the ratio between the morning and afternoon concentrations, considering the time before and after the weaning event. Principal component analysis (PCA) and Fisher's test were performed to evaluate the behavior test data. When comparing salivary cortisol concentrations between the pre- and postweaning periods, there was a difference (p < 0.05) between the supplementation groups in the afternoon period, suggesting that piglets fed asinine milk had lower afternoon cortisol concentrations postweaning than their counterparts. For the behavioral tests, the supplementations had no measurable effects. No difference was between groups pre- and postweaning for the expression of HSD11B2, which codes for an enzyme that breaks down cortisol. However, the expression of NR3C1, which encodes the glucocorticoid receptor, was significantly upregulated in piglets supplemented with cow milk (mean 1.245; p < 0.05).CONCLUSION: Asinine milk downregulated 1L1B gene expression, which codes for an inflammatory cytokine. In conclusion, these results suggest that supplementation with asinine milk may represent a strategy to diminish the damage associated with an early life event by modulating IL1B expression and reducing salivary cortisol levels in piglets undergoing weaning stress. Further transcriptomic and metabolomic studies may improve our understanding of the molecular pathways that mediate this systemic immune-mediated response.PMID:37122716 | PMC:PMC10140756 | DOI:10.3389/fimmu.2023.1139249

Front Immunol. 2023 Apr 5;14:1146443. doi: 10.3389/fimmu.2023.1146443. eCollection 2023.ABSTRACTBACKGROUND: The cross-protective nature of Bacillus Calmette-Guerin (BCG) vaccine against SARS-CoV-2 virus was previously suggested, however its effect in COVID-19 patients with type 2 diabetes (T2D) and the underlying metabolic pathways has not been addressed. This study aims to investigate the difference in the metabolomic patterns of type 2 diabetic patients with BCG vaccination showing different severity levels of COVID-19 infection.METHODS: Sixty-seven COVID-19 patients were categorized into diabetic and non-diabetic individuals who had been previously vaccinated or not with BCG vaccination. Targeted metabolomics were performed from serum samples from all patients using tandem mass spectrometry. Statistical analysis included multivariate and univariate models.RESULTS: Data suggested that while BCG vaccination may provide protection for individuals who do not have diabetes, it appears to be linked to more severe COVID-19 symptoms in T2D patients (p = 0.02). Comparing the metabolic signature of BCG vaccinated T2D individuals to non-vaccinated counterparts revealed that amino acid (sarcosine), cholesterol esters (CE 20:0, 20:1, 22:2), carboxylic acid (Aconitic acid) were enriched in BCG vaccinated T2D patients, whereas spermidine, glycosylceramides (Hex3Cer(d18:1_22:0), Hex2Cer(d18:1/22:0), HexCer(d18:1/26:1), Hex2Cer(d18:1/24:0), HexCer(d18:1/22:0) were higher in BCG vaccinated non- T2D patients. Furthermore, data indicated a decrease in sarcosine synthesis from glycine and choline and increase in spermidine synthesis in the BCG vaccinated cohort in T2D and non-T2D groups, respectively.CONCLUSION: This pilot study suggests increased severity of COVID-19 in BCG vaccinated T2D patients, which was marked by decreased sarcosine synthesis, perhaps via lower sarcosine-mediated removal of viral antigens.PMID:37122708 | PMC:PMC10131282 | DOI:10.3389/fimmu.2023.1146443

Front Mol Neurosci. 2023 Apr 14;16:1168695. doi: 10.3389/fnmol.2023.1168695. eCollection 2023.ABSTRACTMicroRNA (miRNA) dysregulation is well-documented in psychiatric disease, but miRNA dynamics remain poorly understood during adolescent and early adult brain maturation, when symptoms often first appear. Here, we use RNA sequencing to examine miRNAs and their mRNA targets in cortex and hippocampus from early-, mid-, and late-adolescent and adult mice. Furthermore, we use quantitative proteomics by tandem mass tag mass spectrometry (TMT-MS) to examine protein dynamics in cortex from the same subjects. We found that ~25% of miRNAs' 3' ends shorten with age due to increased 3' trimming and decreased U tailing. Particularly, shorter but functionally competent isoforms (isomiRs) of miR-338-3p increase up to 10-fold during adolescence and only in brain. MiRNAs that undergo 3' shortening exhibit stronger negative correlations with targets that decrease with age and stronger positive correlations with targets that increase with age, than miRNAs with stable 3' ends. Increased 3' shortening with age was also observed in available mouse and human miRNA-seq data sets, and stronger correlations between miRNAs that undergo shortening and their mRNA targets were observed in two of the three available data sets. We conclude that age-associated miRNA 3' shortening is a well-conserved feature of postnatal brain maturation.PMID:37122627 | PMC:PMC10140418 | DOI:10.3389/fnmol.2023.1168695

Front Mol Biosci. 2023 Apr 14;10:1166333. doi: 10.3389/fmolb.2023.1166333. eCollection 2023.ABSTRACTObesity is associated with various adverse health outcomes. Body fat (BF) distribution is recognized as an important factor of negative health consequences of obesity. Although metabolomics studies, mainly focused on body mass index (BMI) and waist circumference, have explored the biological mechanisms involved in the development of obesity, these proxy composite measures are not accurate and cannot reflect BF distribution, and thus may hinder accurate assessment of metabolic alterations and differential risk of metabolic disorders among individuals presenting adiposity differently throughout the body. Thus, the exact relations between metabolites and BF remain to be elucidated. Here, we aim to examine the associations of metabolites and metabolic pathways with BF traits which reflect BF distribution. We performed systematic untargeted serum metabolite profiling and dual-energy X-ray absorptiometry (DXA) whole body fat scan for 517 Chinese women. We jointly analyzed DXA-derived four BF phenotypes to detect cross-phenotype metabolite associations and to prioritize important metabolomic factors. Topology-based pathway analysis was used to identify important BF-related biological processes. Finally, we explored the relationships of the identified BF-related candidate metabolites with BF traits in different sex and ethnicity through two independent cohorts. Acetylglycine, the top distinguished finding, was validated for its obesity resistance effect through in vivo studies of various diet-induced obese (DIO) mice. Eighteen metabolites and fourteen pathways were discovered to be associated with BF phenotypes. Six of the metabolites were validated in varying sex and ethnicity. The obesity-resistant effects of acetylglycine were observed to be highly robust and generalizable in both human and DIO mice. These findings demonstrate the importance of metabolites associated with BF distribution patterns and several biological pathways that may contribute to obesity and obesity-related disease etiology, prevention, and intervention. Acetylglycine is highlighted as a potential therapeutic candidate for preventing excessive adiposity in future studies.PMID:37122566 | PMC:PMC10141311 | DOI:10.3389/fmolb.2023.1166333

RSC Med Chem. 2023 Mar 1;14(4):710-714. doi: 10.1039/d3md00049d. eCollection 2023 Apr 26.ABSTRACTA concise semi-synthesis of the Aspidosperma alkaloids, (-)-jerantinine A and (-)-melodinine P, and derivatives thereof, is reported. The novel compounds were shown to have potent activity against MDA-MB-231 triple-negative breast cancer cells. Furthermore, unbiased metabolomics and live cell reporter assays reveal (-)-jerantinine A alters cellular redox metabolism and induces oxidative stress that coincides with cell cycle arrest.PMID:37122543 | PMC:PMC10131581 | DOI:10.1039/d3md00049d

Front Neurol. 2023 Apr 14;14:1153193. doi: 10.3389/fneur.2023.1153193. eCollection 2023.ABSTRACTBACKGROUND: The pathophysiological processes linked to an acute ischemic stroke (IS) can be reflected in the circulating metabolome. Amino acids (AAs) have been demonstrated to be one of the most significant metabolites that can undergo significant alteration after a stroke.METHODS: We sought to identify the potential biomarkers for the early detection of IS using an extensive targeted technique for reliable quantification of 27 different AAs based on ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). A cohort with 216 participants was enrolled, including 70 mild to moderate ischemic stroke patients (National Institutes of Health Stroke Scale < 15, MB group), 76 stroke mimics (MM group) and 70 healthy controls (NC group).RESULTS: It was found that upon comparing MB and MM to control patients, AAs shifts were detected via partial least squares discrimination analysis (PLS-DA) and pathway analysis. Interestingly, MB and MM exhibited similar AAs pattern. Moreover, ornithine, asparagine, valine, citrulline, and cysteine were identified for inclusion in a biomarker panel for early-stage stroke detection based upon an AUC of 0.968 (95% CI 0.924-0.998). Levels of ornithine were positively associated with infract volume, 3 months mRS score, and National Institutes of Health Stroke Scale (NIHSS) score in MB. In addition, a metabolites biomarker panel, including ornithine, taurine, phenylalanine, citrulline, cysteine, yielded an AUC of 0.99 (95% CI 0.966-1) which can be employed to effectively discriminate MM patients from control.CONCLUSION: Overall, alternations in serum AAs are characteristic metabolic features of MB and MM. AAs could serve as promising biomarkers for the early diagnosis of MB patients since mild to moderate IS patients were enrolled in the study. The metabolism of AAs can be considered as a key indicator for both the prevention and treatment of IS.PMID:37122289 | PMC:PMC10140586 | DOI:10.3389/fneur.2023.1153193

Gut Microbes. 2023 Jan-Dec;15(1):2201160. doi: 10.1080/19490976.2023.2201160.ABSTRACTGut microbiome maturation in infants born prematurely is uniquely influenced by the physiological, clinical, and environmental factors surrounding preterm birth and early life, leading to altered patterns of microbial succession relative to term infants during the first months of life. These differences in microbiome composition are implicated in acute clinical conditions that disproportionately affect preterm infants, including necrotizing enterocolitis (NEC) and late-onset sepsis (LOS). Probiotic supplementation initiated early in life is an effective prophylactic measure for preventing NEC, LOS, and other clinical concerns relevant to preterm infants. In parallel, reported benefits of probiotics on the preterm gut microbiome, metabolome, and immune function are beginning to emerge. This review summarizes the current literature on the influence of probiotics on the gut microbiome of preterm infants, outlines potential mechanisms by which these effects are exerted, and highlights important clinical considerations for determining the best practices for probiotic use in premature infants.PMID:37122152 | DOI:10.1080/19490976.2023.2201160

Environ Microbiol. 2023 Apr 30. doi: 10.1111/1462-2920.16390. Online ahead of print.ABSTRACTMarine Bacteroidetes that degrade polysaccharides contribute to carbon cycling in the ocean. Organic matter, including glycans from terrestrial plants, might enter the oceans through rivers. Whether marine bacteria degrade structurally related glycans from diverse sources including terrestrial plants and marine algae was previously unknown. We show that the marine bacterium Flavimarina sp. Hel_I_48 encodes two polysaccharide utilization loci (PULs) which degrade xylans from terrestrial plants and marine algae. Biochemical experiments revealed activity and specificity of the encoded xylanases and associated enzymes of these PULs. Proteomics indicated that these genomic regions respond to glucuronoxylans and arabinoxylans. Substrate specificities of key enzymes suggest dedicated metabolic pathways for xylan utilization. Some of the xylanases were active on different xylans with the conserved β-1,4-linked xylose main chain. Enzyme activity was consistent with growth curves showing Flavimarina sp. Hel_I_48 uses structurally different xylans. The observed abundance of related xylan-degrading enzyme repertoires in genomes of other marine Bacteroidetes indicates similar activities are common in the ocean. The here presented data show that certain marine bacteria are genetically and biochemically variable enough to access parts of structurally diverse xylans from terrestrial plants as well as from marine algal sources.PMID:37121608 | DOI:10.1111/1462-2920.16390

Hum Exp Toxicol. 2023 Jan-Dec;42:9603271231171648. doi: 10.1177/09603271231171648.ABSTRACTBACKGROUND: N-propylparaben (PP), a type of paraben, is commonly used as a preservative or antibacterial agent in daily chemicals, medicine, food, cosmetics, feed, and various industrial preservatives. Although PP promotes the growth of human breast adenocarcinoma (MCF-7) cells by activating the human estrogen receptor (ER), the mechanism responsible for this type of programmed cell proliferation is poorly understood.OBJECTIVE: To clarify the effect of PP on cell metabolic function and the potential molecular mechanism of PP induced MCF-7 cell proliferation from a new perspective.METHODS: To use high-resolution mass spectrometry-based metabolomics combined with bioinformatics analysis to analyze the molecular mechanism.RESULTS: The results illustrated that differential endogenous compounds related to the effects of PP on cell metabolic functions were detected. PP was found to promote glycolysis in MCF-7 cells and enhance the tricarboxylic acid cycle (TCA cycle) in mitochondria, thus improving the energy supply to these tumor cells for metabolic function and promotion of rapid proliferation. Moreover, we found that PP promoted cell proliferation by affecting the mitogen-activated protein kinase (MAPK) signaling pathway of MCF-7 cells.CONCLUSION: Our results revealed the molecular mechanism of low concentration PP promoting MCF-7 cell proliferation by activating ER.PMID:37121592 | DOI:10.1177/09603271231171648

Toxicology. 2023 Apr 28:153530. doi: 10.1016/j.tox.2023.153530. Online ahead of print.ABSTRACTEndemic fluorosis is a global public health problem. Cardiovascular diseases caused by fluoride are closely related to endothelial cell injury. Metabolism disorder of endothelial cells (ECs) are recognized as the key factor of endothelial dysfunction which has been a hot topic in recent years. However, the toxic effect of fluoride on vascular endothelium has not been elucidated. The aim of this study was to explore the alteration of endothelial cell metabolites in Human Umbilical Vein Endothelial Cells (HUVECs) exposed to NaF using LC-MS/MS technique. The screening conditions were Variable Importance for the Projection (VIP) > 1 and P < 0.05. It was found that the expression of the metabolites Lumichrome and S-Methyl-5'-thioadenosine was upregulated and of the other metabolites, such as Creatine, L-Glutamate, Stearic acid was downregulated. Differential metabolites were found to be primarily related to FoxO、PI3K/Akt and apoptosis signaling pathways by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. From the perspective of metabolism, this study explored the possible mechanism of fluoride induced endothelial cell injury which providing theories and clues for subsequent studies.PMID:37121536 | DOI:10.1016/j.tox.2023.153530

J Ethnopharmacol. 2023 Apr 28:116546. doi: 10.1016/j.jep.2023.116546. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: P. lobata and P. thomsonii are medicinal plants with similar pharmacological functions but different therapeutic effects. A novel method is presented herein to investigate metabolites in terms of their distribution and qualification, quantification is necessary to elucidate the different therapeutic effects of the two Puerariae species.AIM OF THE STUDY: The aim of the present study was to perform spatially resolved metabolomics combined with bioactivity analyses to systematically compare the metabolite differences in P. lobata and P. thomsonii by distribution, qualification, quantification, and biological activity to evaluate their pharmacological properties.MATERIALS AND METHODS: Air flow-assisted desorption electrospray ionization-mass spectrometry imaging (AFADESI-MSI) was performed to characterize the differences in the metabolite distributions of P. lobata and P. thomsonii. Further qualitative and quantitative analyses of the differential metabolites were performed using liquid chromatography-mass spectrometry (LC-MS). Biological activities correlated with the differences in the metabolites were validated by MTT assays.RESULTS: Some metabolites showed complementary distributions of the phloem and xylem in the two species, saccharide, vitamin, and inosine levels were higher in the phloem of P. thomsonii but higher in the xylem of P. lobata. The 3'-hydroxyl puerarin level was higher in the xylem of P. thomsonii but higher in the phloem of P. lobata. Qualitative and quantitative analyses of the metabolites revealed a total of 52 key differential metabolites. MTT assays showed that daidzein, daidzin, puerarin, ononin, genistin, formononetin, 3'-hydroxy puerarin, 3'-methoxy puerarin, mirificin, and 3'-methoxy daidzin exerted protective effects on H9c2 cells against hypoxia/reoxygenation injury. P. lobata extracts exhibited a significantly better protective efficacy than P. thomsonii extracts.CONCLUSIONS: In this study, AFADESI-MSI combined with LC-MS and biological activities comprehensively elucidated metabolite differences in the distribution, qualification, quantification, and pharmacological properties of P. lobata and P. thomsonii. The results of this study could provide a novel strategy for species identification and quality assessment of similar Chinese herbal medicines.PMID:37121451 | DOI:10.1016/j.jep.2023.116546

Anal Chem. 2023 Apr 25. doi: 10.1021/acs.analchem.3c00369. Online ahead of print.ABSTRACTUrine is a preferred object for noninvasive diagnostic strategies. Urinary metabolic analysis is speculatively regarded as an ideal tool for screening diseases closely related to the genitourinary system in view of the intimate relationship between metabolomics and phenotype. Herein, we propose a urinary metabolic fingerprint-based noninvasive diagnostic strategy by designing hollow core-shell metal oxide heterojunctions (denoted as MOHs). With outstanding light absorption and electron-hole separation ability, MOHs aid in the extraction of high-performance urine metabolic fingerprints. Coupled with optimized machine learning algorithms, we establish a metabolic marker panel for accurate diagnosis of prostate cancer (PCa), which is the most common malignant tumor of the male genitourinary system, achieving accuracies of 84.72 and 83.33% in the discovery and validation sets, respectively. Furthermore, metabolite variations and related pathway analyses confirm the credibility and change correlation of key metabolic features in PCa. This work tends to advance the noninvasive diagnostic strategy toward clinical realities.PMID:37121232 | DOI:10.1021/acs.analchem.3c00369

J Hazard Mater. 2023 Apr 28;454:131532. doi: 10.1016/j.jhazmat.2023.131532. Online ahead of print.ABSTRACTTriclosan (TCS) is an antiseptic incorporated in consumer goods and personal care products that can be absorbed via the skin, raising public health concerns for its continuous detection in human biofluids and tissues. Epidemiology has associated TCS exposure with thyroid function disturbances and decreasing serum thyroid hormone (TH) levels, but the underlying mechanism remains unclear. In this study, we revealed hypothyroidism and histological alternation in the thyroid of mice with chronic percutaneous exposure to TCS, indicating a TCS-caused thyroid impairment. Subsequently, multi-omics approaches were performed to investigate the molecular mechanism of the thyroid in response to long-term dermal TCS exposure. We discovered that TCS interfered with the TH synthesis as indicated by the changes in the levels of the synthetic materials for TH (iodide, Tg, and H2O2) and affected TH release by the downregulation of lysosomal enzymes. The upregulation of glycolysis, tricarboxylic acid cycle, fatty acid, amino acid metabolism, and adenine salvage in the thyroid was also observed after TCS exposure. All these changes led to the elevation of ATP, serving as a rescue for the decreasing thyroid functions. Together, our study demonstrated TCS-induced thyroid damage and identified the interrupted pathways, providing meaningful insight into the molecular mechanisms underpinning the potential health influence of TCS in humans.PMID:37121033 | DOI:10.1016/j.jhazmat.2023.131532

Aquat Toxicol. 2023 Apr 26;259:106547. doi: 10.1016/j.aquatox.2023.106547. Online ahead of print.ABSTRACTSince glass eels are continuously exposed to contamination throughout their migratory journey in estuaries, to a certain extent the fall in the population of this endangered species might be attributed to this exposure, which is especially acute in estuaries under high urban pressure. In this work, metabolomics was used to address the main objective of this study, to evaluate the effects of two pharmaceuticals previously identified as potential concerning chemicals for fish (diazepam and irbesartan) on glass eels. An exposure experiment to diazepam, irbesartan and their mixture was carried out over 7 days followed by 7 days of depuration phase. After exposure, glass eels were individually sacrificed using a lethal bath of anesthesia, and then an unbiased sample extraction method was used to extract separately the polar metabolome and the lipidome. The polar metabolome was submitted to targeted and non-targeted analysis, whereas for the lipidome only the non-targeted analysis was carried out. A combined strategy using partial least squares discriminant analysis and univariate and multivariate statistical analysis (ANOVA, ASCA, t-test, and fold-change analysis) was used to identify the metabolites altered in the exposed groups with respect to the control group. The results of the polar metabolome analysis revealed that glass eels exposed to the diazepam-irbesartan mixture were the most impacted ones, with altered levels for 11 metabolites, some of them belonging to the energetic metabolism, which was confirmed to be sensitive to these contaminants. Additionally, the dysregulation of the levels of twelve lipids, most of them with energetic and structural functions, was also found after exposure to the mixture, which might be related to oxidative stress, inflammation, or alteration of the energetic metabolism.PMID:37120958 | DOI:10.1016/j.aquatox.2023.106547

J Anim Sci Biotechnol. 2023 May 1;14(1):68. doi: 10.1186/s40104-023-00865-w.ABSTRACTBACKGROUND: The mechanism by which Meishan (MS) sows are superior to white crossbred sows in ovarian follicle development remains unclear. Given gut microbiota could regulate female ovarian function and reproductive capacity, this study aimed to determine the role of gut microbiota-ovary axis on follicular development in sows.METHODS: We compared the ovarian follicular development, gut microbiota, plasma metabolome, and follicular fluid metabolome between MS and Landrace × Yorkshire (L × Y) sows. A H2O2-induced cell apoptosis model was used to evaluate the effects of multi-omics identified metabolites on the apoptosis of porcine ovarian granulosa cells in vitro.RESULTS: Compared with L × Y sows, MS sows have greater ovary weight and improved follicular development, including the greater counts of large follicles of diameter ≥ 5 mm, secondary follicles, and antral follicles, but lesser atretic follicles. The ovarian granulosa cells in MS sows had alleviated apoptosis, which was indicated by the increased BCL-2, decreased caspases-3, and decreased cleaved caspases-3 than in L × Y sows. The ovarian follicular fluid of MS sows had higher concentrations of estradiol, progesterone, follicle-stimulating hormone, luteinizing hormone, and insulin like growth factor 1 than L × Y sows. Gut microbiota of MS sows formed a distinct cluster and had improved alpha diversity, including increased Shannon and decreased Simpson than those of L × Y sows. Corresponding to the enhanced function of carbohydrate metabolism and elevated short-chain fatty acids (SCFAs) in feces, the differential metabolites in plasma between MS and L × Y sows are also mainly enriched in pathways of fatty acid metabolism. There were significant correlations among SCFAs with follicular development, ovarian granulosa cells apoptosis, and follicular fluid hormones, respectively. Noteworthily, compared with L × Y sows, MS sows had higher follicular fluid SCFAs concentrations which could ameliorate H2O2-induced porcine granulosa cells apoptosis in vitro.CONCLUSION: MS sows have more secondary and antral follicles, but fewer atretic follicles and apoptotic ovarian granulosa cells, as well as harbored a distinctive gut microbiota than L × Y sows. Gut microbiota may participate in regulating ovarian follicular development via SCFAs affecting granulosa cells apoptosis in sows.PMID:37122038 | DOI:10.1186/s40104-023-00865-w