PubMed
New evidence for gut-muscle axis: Lactic acid bacteria-induced gut microbiota regulates duck meat flavor
Food Chem. 2024 Apr 13;450:139354. doi: 10.1016/j.foodchem.2024.139354. Online ahead of print.ABSTRACTThe interaction between gut microbiota and muscles through the gut-muscle axis has received increasing attention. This study attempted to address existing research gaps by investigating the effects of gut microbiota on meat flavor. Specifically, lactic acid bacteria were administered to ducks, and the results of e-nose and e-tongue showed significantly enhanced meat flavor in the treatment group. Further analyses using GC-MS revealed an increase in 6 characteristic volatile flavor compounds, including pentanal, hexanal, heptanal, 1-octen-3-ol, 2,3-octanedione, and 2-pentylfuran. Linoleic acid was identified as the key fatty acid that influences meat flavor. Metagenomic and transcriptomic results further confirmed that cecal microbiota affects the duck meat flavor by regulating the metabolic pathways of fatty acids and amino acids, especially ACACB was related to fatty acid biosynthesis and ACAT2, ALDH1A1 with fatty acid degradation. This study sheds light on a novel approach to improving the flavor of animal-derived food.PMID:38636385 | DOI:10.1016/j.foodchem.2024.139354
Widely targeted metabolomic and KEGG analyses of natural deep eutectic solvent-based saponins extraction from Camellia oleifera Abel.: Effects on composition
Food Chem. 2024 Apr 12;450:139333. doi: 10.1016/j.foodchem.2024.139333. Online ahead of print.ABSTRACTCamellia saponins are important by-products of Camellia Oleifer Abel. processing. In this study, an eco-friendly method based on natural deep eutectic solvents (NaDESs, proline and glycerol at a molar ratio of 2:5) was established to extract saponins from C.oleifera cakes. The content of saponin (702.22 ± 1.28 mg/g) obtained using NaDES was higher than those extracted using water or methanol. UPLC-Q-TOF MS analysis of chemical structure showed that the difference in the extraction technique alter individual saponins. A widely targeted metabolomic approach and KEGG metabolic pathway analysis showed that the upregulated metabolites in the NaDES-based extract mainly included flavonoids, alkaloids, and phenolic acids; and they were involved in arginine and proline metabolism, metabolic pathways, phenylpropanoid biosynthesis, biosynthesis of secondary metabolites, and flavonoid biosynthesis. The present study proposes a selective substitute for use in the extraction of camellia saponins with composition analysis.PMID:38636384 | DOI:10.1016/j.foodchem.2024.139333
Metabolic signatures of two scleractinian corals from the northern South China sea in response to extreme high temperature events
Mar Environ Res. 2024 Apr 16;198:106490. doi: 10.1016/j.marenvres.2024.106490. Online ahead of print.ABSTRACTCoral bleaching events are becoming increasingly common worldwide, causing widespread coral mortality. However, not all colonies within the same coral taxa show sensitivity to bleaching events, and the current understanding of the metabolic mechanisms underlying thermal bleaching in corals remains limited. We used untargeted metabolomics to analyze the biochemical processes involved in the survival of two bleaching phenotypes of the common corals Pavona decussata and Acropora pruinosa, during a severe bleaching event in the northern South China Sea in 2020. During thermal bleaching, P. decussata and A. pruinosa significantly accumulated energy products such as succinate and EPA, antioxidants and inflammatory markers, and reduced energy storage substances like glutamate and thymidine. KEGG analysis revealed enrichment of energy production pathways such as ABC transporters, nucleotide metabolism and lipid metabolism, suggesting the occurrence of oxidative stress and energy metabolism disorders in bleached corals. Notably, heat stress exerted distinct effects on metabolic pathways in the two coral species, e.g., P. decussata activating carbohydrate metabolism pathways like glycolysis and the TCA cycle, along with amino acid metabolism pathways, whereas A. pruinosa significantly altered the content of multiple small peptides affected amino acid metabolism. Furthermore, the osmoregulatory potential of corals correlates with their ability to survive in heat-stress environments in the wild. This study provides valuable insights into the metabolic mechanisms linked to thermal tolerance in reef-building corals, contributes to the understanding of corals' adaptive potential to heat stress induced by global warming and lays the foundation for developing targeted conservation strategies in the future.PMID:38636276 | DOI:10.1016/j.marenvres.2024.106490
Antidiabetic action of the Chinese formula Shouhuitongbian and the underlying mechanism associated with alteration of gut microbiota
Phytomedicine. 2024 Apr 4;129:155575. doi: 10.1016/j.phymed.2024.155575. Online ahead of print.ABSTRACTBACKGROUND: The prevalence and incidence of type 2 diabetes mellitus (T2DM) have dramatically increased. The intestinal flora and its derived metabolites are demonstrated to play vital roles in the etiology and onset of T2DM. Shouhuitongbian (SHTB) is a traditional Chinese formula to treat constipation. SHTB is composed of seven herbs and components of Colla corii asini (CCA) that are obtained from the hide of Equus asinus L.. Some of herbs in SHTB such as Aloe vera (L.) Burm.f., Cassia obtusifolia L., fruits of Lycium barbarum L., and Citrus aurantium L. have shown to improve insulin resistance (IR) and T2DM in early reports. We hypothesized that SHTB composed of these herbs has antidiabetic effects. The antidiabetic efficacy and mechanism of action of SHTB have not been previously reported.HYPOTHESIS/PURPOSE: To demonstrate the antidiabetic effect and elucidate the underlying mechanisms of SHTB from the perspective of gut microbiota.STUDY DESIGN: The main compounds were identified and quantified by high-performance liquid chromatography (HPLC)-mass spectrometry analysis. High fat diet (HFD)-fed mice and db/db mice were used to assess the antidiabetic effects and the mechanism of SHTB. The underlying mechanisms were evaluated by enzyme-linked immunosorbent assay (ELISA), western blot analysis, quantitative real time polymerase chain reaction (qPCR) analysis, 16S rRNA high-throughput sequencing, and targeted metabolome analysis.METHODS: HFD-fed mice and db/db mice were orally treated with the standard positive drug metformin (100 mg/kg/d) and with SHTB (200 and 100 mg/kg/d), which was chemically characterized according to the European Medicine Agency (EMA) guidelines. The beneficial effects of SHTB were studied by homeostasis model assessment of insulin resistance (HOMA-IR) index, oral glucose tolerance test (OGTT), insulin tolerance test (ITT), total cholesterol (T-CHO), triglyceride (TG), and inflammation. Subsequently, 16S rDNA-based high-throughput pyrosequencing and GC-MS-based targeted metabolomics profiling were performed to analyze the gut microbiota composition and metabolites profile in the gut, respectively. Moreover, the mammalian target of rapamycin complex 1 (mTORC1) / insulin receptor substrate 1 (IRS-1) / phosphoinositide 3-kinase (PI3K) / protein kinase B (AKT) pathway was evaluated via qPCR and western blot.RESULTS: Chemically characterized SHTB, in which six markers were quantified, effectively alleviated glucose intolerance and IR, ameliorated lipid metabolism dysfunction, and reduced inflammation. In addition, 16S rDNA sequencing found that SHTB reshaped the composition of intestinal flora, as indicated by the enrichment of Akkermansia and Parabacteroides in both HFD-fed and db/db mice. Moreover, SHTB enhanced the intestinal production of short-chain fatty acids (SCFAs) and branched short-chain fatty acids (BSCFAs), and reduced the levels of the fecal and circulating branched-chain amino acids (BCAAs). The IRS-1/PI3K/AKT signaling pathway was upregulated after treatment with SHTB.CONCLUSION: Orally administration of SHTB effectively improved IR and reduced hyperglycemia in mice. Treatment with SHTB regulated the gut BCAAs-mTORC1/IRS-1/PI3K/AKT axis by enhancing the BCAAs catabolism in the gut, which attenuated the deleterious effect of BCAAs on the IRS-1 signaling pathway.PMID:38636179 | DOI:10.1016/j.phymed.2024.155575
Chemoselectivity Strategy Based on B-Label Integrated with Tailored COF for Targeted Metabolomic Analysis of Short-Chain Fatty Acids by UHPLC-MS/MS
Anal Chem. 2024 Apr 18. doi: 10.1021/acs.analchem.3c05590. Online ahead of print.ABSTRACTChemoselective extraction strategy is an emerging and powerful means for targeted metabolomics analysis, which allows for the selective identification of biomarkers. Short-chain fatty acids (SCFAs) as functional metabolites for many diseases pose challenges in qualitative and quantitative analyses due to their high polarity and uneven abundance. In our study, we proposed the B-labeled method for the derivatization of SCFAs using easily available 3-aminobenzeneboronic acid as the derivatization reagent, which enables the introduction of recognition unit (boric acid groups). To analyze the B-labeled targeted metabolites accurately, cis-diol-based covalent organic framework (COF) was designed to specifically capture and release target compounds by pH-response borate affinity principle. The COF synthesized by the one-step Schiff base reaction possessed a large surface area (215.77 m2/g), excellent adsorption capacity (774.9 μmol/g), good selectivity, and strong regeneration ability (20 times). Combined with ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis, our results indicated that the detection sensitivities of SCFAs increased by 1.2-2500 folds compared with unlabeled method, and the retention time and isomer separation were improved. Using this strategy, we determined twenty-six SCFAs in the serum and urine of rats in four groups about osteoporosis and identified important biomarkers related to the tricarboxylic acid cycle and fatty acid metabolism pathways. In summary, UHPLC-MS/MS based on B-labeled derivatization with tailored COF strategy shows its high selectivity, excellent sensitivity, and good chromatographic behavior and has remarkable application prospect in targeted metabolomics study of biospecimens.PMID:38637908 | DOI:10.1021/acs.analchem.3c05590
Comprehensive mapping of saliva by multiomics in children with idiopathic nephrotic syndrome
Nephrology (Carlton). 2024 Apr 18. doi: 10.1111/nep.14308. Online ahead of print.ABSTRACTAIM: Saliva can reflect an individual's physiological status or susceptibility to systemic disease. However, little attention has been given to salivary analysis in children with idiopathic nephrotic syndrome (INS). We aimed to perform a comprehensive analysis of saliva from INS children.METHODS: A total of 18 children (9 children with INS and 9 normal controls) were recruited. Saliva was collected from each INS patient in the acute and remission phases. 16S rRNA gene sequencing, widely targeted metabolomics, and 4D-DIA proteomics were performed.RESULTS: Actinobacteria and Firmicutes were significantly enriched in the pretreatment group compared with the normal control group, while Bacteroidota and Proteobacteria were significantly decreased. A total of 146 metabolites were identified as significantly different between INS children before treatment and normal controls, which covers 17 of 23 categories. KEGG enrichment analysis revealed three significantly enriched pathways, including ascorbate and aldarate metabolism, pentose and glucuronate interconversions, and terpenoid backbone biosynthesis (P < 0.05). A total of 389 differentially expressed proteins were selected between INS children before treatment and normal controls. According to the KEGG and GO enrichment analyses of the KOGs, abnormal ribosome structure and function and humoral immune disorders were the most prominent differences between INS patients and normal controls in the proteomic analysis.CONCLUSION: Oral microbiota dysbiosis may modulate the metabolic profile of saliva in children with INS. It is hypothesized that children with INS might have "abnormal ribosome structure and function" and "humoral immune disorders".PMID:38637907 | DOI:10.1111/nep.14308
Analysis of plasma metabolomes from 11 309 subjects in five population-based cohorts
Sci Rep. 2024 Apr 18;14(1):8933. doi: 10.1038/s41598-024-59388-7.ABSTRACTPlasma metabolomics holds potential for precision medicine, but limited information is available to compare the performance of such methods across multiple cohorts. We compared plasma metabolite profiles after an overnight fast in 11,309 participants of five population-based Swedish cohorts (50-80 years, 52% women). Metabolite profiles were uniformly generated at a core laboratory (Metabolon Inc.) with untargeted liquid chromatography mass spectrometry and a comprehensive reference library. Analysis of a second sample obtained one year later was conducted in a subset. Of 1629 detected metabolites, 1074 (66%) were detected in all cohorts while only 10% were unique to one cohort, most of which were xenobiotics or uncharacterized. The major classes were lipids (28%), xenobiotics (22%), amino acids (14%), and uncharacterized (19%). The most abundant plasma metabolome components were the major dietary fatty acids and amino acids, glucose, lactate and creatinine. Most metabolites displayed a log-normal distribution. Temporal variability was generally similar to clinical chemistry analytes but more pronounced for xenobiotics. Extensive metabolite-metabolite correlations were observed but mainly restricted to within each class. Metabolites were broadly associated with clinical factors, particularly body mass index, sex and renal function. Collectively, our findings inform the conduct and interpretation of metabolite association and precision medicine studies.PMID:38637659 | DOI:10.1038/s41598-024-59388-7
Quantifying maternal investment in mammals using allometry
Commun Biol. 2024 Apr 18;7(1):475. doi: 10.1038/s42003-024-06165-x.ABSTRACTMaternal investment influences the survival and reproduction of both mothers and their progeny and plays a crucial role in understanding individuals' life-history and population ecology. To reveal the complex mechanisms associated with reproduction and investment, it is necessary to examine variations in maternal investment across species. Comparisons across species call for a standardised method to quantify maternal investment, which remained to be developed. This paper addresses this limitation by introducing the maternal investment metric - MI - for mammalian species, established through the allometric scaling of the litter mass at weaning age by the adult mass and investment duration (i.e. gestation + lactation duration) of a species. Using a database encompassing hundreds of mammalian species, we show that the metric is not highly sensitive to the regression method used to fit the allometric relationship or to the proxy used for adult body mass. The comparison of the maternal investment metric between mammalian subclasses and orders reveals strong differences across taxa. For example, our metric confirms that Eutheria have a higher maternal investment than Metatheria. We discuss how further research could use the maternal investment metric as a valuable tool to understand variation in reproductive strategies.PMID:38637653 | DOI:10.1038/s42003-024-06165-x
Intake of different types of seafood and meat and risk of type 2 diabetes in women: a prospective study supported by a dietary intervention in mice
Sci Rep. 2024 Apr 18;14(1):8950. doi: 10.1038/s41598-024-59491-9.ABSTRACTDetailed knowledge regarding the associations between intake of different types of seafood and meat and the risk of type 2 diabetes (T2D), and insight into possible mechanisms are warranted. In this study we aimed to evaluate the associations between intake of different types of seafood and meat and the subsequent risk of T2D using the Norwegian Mother, Father, and Child Cohort Study (MoBa), and furthermore, by using a mouse model to gain further insight into possible molecular mechanisms contributing to the associated metabolic changes. Women in MoBa who were free of pharmacologically treated diabetes at baseline (n = 60,777) were prospectively evaluated for incident T2D, identified on the basis of medication usages > 90 days after delivery, ascertained by the Norwegian Prescription Database. Dietary intake was obtained with a validated 255-item food frequency questionnaire which assessed habitual diet during the first 4-5 months of pregnancy. Metabolic phenotypes and plasma metabolome were investigated in female mice fed isocaloric diets with different types of seafood and meat mimicking the dietary intake in the human cohort. During maximum 10-year and mean (SD) 7.2 (1.6) years follow-up time, 681 (1.1%) women developed pharmacologically treated T2D. All statistical models identified a higher risk of T2D with increased shellfish intake, whereas no associations were observed for total seafood, fatty fish, total meat and red meat in the adjusted models. In mice, the shellfish-based western diet induced reduced glucose tolerance and insulin secretion compared to the diet based on lean fish, and we identified a number of metabolites elevated in plasma from shellfish-fed mice that correlated with glucose intolerance. Mice fed a western diet based on meat also exhibited reduced glucose tolerance in comparison to lean fish fed mice, whereas mice fed fatty fish, total seafood or red meat did not differ from lean fish fed mice. We observed a diet-specific metabolic signature in plasma demonstrating five distinct metabolite profiles in mice fed shellfish, fatty fish, total seafood/lean fish, a mixed diet and meat. In conclusion, these findings demonstrate that different types of seafood have different outcome on T2D risk. In women, intake of shellfish was associated with higher risk of T2D. In female mice, a shellfish enriched diet reduced glucose tolerance and altered the abundance of several distinct plasma metabolites correlating with glucose tolerance.PMID:38637574 | DOI:10.1038/s41598-024-59491-9
Relationship between gut microbiota and its metabolite dysregulation and postoperative cognitive dysfunction in elderly male C57BL/6J mice after laparotomy exploration
Zhonghua Yi Xue Za Zhi. 2024 Apr 16;104(15):1316-1322. doi: 10.3760/cma.j.cn112137-20230810-00199.ABSTRACTObjective: To explore the relationship between gut microbiota and its metabolite dysregulation and postoperative cognitive dysfunction in elderly male C57BL/6J mice after laparotomy exploration. Methods: A total of 48 specific pathogen-free (SPF) male C57BL/6J mice, aged 16-17 months, were divided into two groups by random number table method: control group (n=24) and operation group (n=24). Mice in the operation group were induced with 1.4% isoflurane for 15 minutes, followed by a 10 minutes exploratory laparotomy anesthetized with 1.4% isoflurane and 100% oxygen, and anesthesia continued for 2 hours after surgery. Mice in control group were put in 100% oxygen for 2 hours. Feces and venous blood samples of both groups were collected 48 hours after surgery. Changes in the abundance and diversity of intestinal bacteria in the feces were detected by 16S rDNA gene sequencing. Functional changes of fecal metabolic profiles were detected by liquid chromatography tandem mass spectrometry (LC/MS) metabolomics and differential metabolite functions were analyzed. The serum level of interleukin (IL)-6, IL-1β and tumor necrosis factor-α (TNF-α) were detected by Enzyme-linked immunosorbent assay (ELISA). The cognitive function of the mice was detected by Morris water maze test 3 days after operation. Results: The postoperative escape latency of mice in control group and operation group was (22.0±4.9) and (35.0±5.1) s, and the target quadrant residence time was (26.0±3.7) and (16.0±2.9) s, respectively. Compared with the control group, the postoperative escape latency of mice in the operation group was prolonged (P=0.035), and the residence time in the target quadrant was reduced (P=0.006). The difference of intestinal flora between the two groups was comparable. The expression levels of Escherichia coli, shigella and clostridium in the operation group were up-regulated, while the expression levels of rumen bacteria and butyricobacteria were down-regulated. Fecal metabolic profiles of mice in control group and operation group were obtained by LC/MS, and 14 and 21 different metabolites were screened in positive and negative ion modes, respectively. The different metabolites in positive ion mode were glutamic acid, 2-indoleic acid, kynuuric acid and glyceraldehyde. The negative ion pattern differential metabolites are methionine, aspartic acid, L-threonine, tyrosyl-threonine and 5-hydroxyindole-3-acetic acid. The identified differential metabolite pathways are mainly involved in amino acid, fatty acid and tryptophan metabolism and nucleotide synthesis. There were no significant differences in serum levels of IL-1β, IL-6 and TNF-α between the two groups (all P>0.05). Conclusion: The dysregulated changes of gut microbiota and its metabolites are correlated with the occurrence of postoperative cognitive dysfunction in elderly male C57BL/6J mice. Anesthesia and surgery alter the structure of mice intestinal bacteria on the level of abundance, and change the metabolic balance and feces metabolomic phenotype.PMID:38637168 | DOI:10.3760/cma.j.cn112137-20230810-00199
Correction to: Metabolomic Profiles of Human Glioma Inform Patient Survival, by Scott et al. Antioxid Redox Signal 2023;39(13-15):942-956; doi: 10.1089/ars.2022.0085
Antioxid Redox Signal. 2024 Apr 18. doi: 10.1089/ars.2022.0085.correx. Online ahead of print.NO ABSTRACTPMID:38635956 | DOI:10.1089/ars.2022.0085.correx
Nanomedomics
ACS Nano. 2024 Apr 18. doi: 10.1021/acsnano.3c11154. Online ahead of print.ABSTRACTNanomaterials have attractive physicochemical properties. A variety of nanomaterials such as inorganic, lipid, polymers, and protein nanoparticles have been widely developed for nanomedicine via chemical conjugation or physical encapsulation of bioactive molecules. Superior to traditional drugs, nanomedicines offer high biocompatibility, good water solubility, long blood circulation times, and tumor-targeting properties. Capitalizing on this, several nanoformulations have already been clinically approved and many others are currently being studied in clinical trials. Despite their undoubtful success, the molecular mechanism of action of the vast majority of nanomedicines remains poorly understood. To tackle this limitation, herein, this review critically discusses the strategy of applying multiomics analysis to study the mechanism of action of nanomedicines, named nanomedomics, including advantages, applications, and future directions. A comprehensive understanding of the molecular mechanism could provide valuable insight and therefore foster the development and clinical translation of nanomedicines.PMID:38635910 | DOI:10.1021/acsnano.3c11154
State of open science in cancer research
Clin Transl Oncol. 2024 Apr 18. doi: 10.1007/s12094-024-03468-7. Online ahead of print.ABSTRACTPURPOSE: This study has been focused on assessing the Open Science scenario of cancer research during the period 2011-2021, in terms of the derived scientific publications and raw data dissemination.METHODS: A cancer search equation was executed in the Science Citation Index-Expanded, collecting the papers signed by at least one Spanish institution. The same search strategy was performed in the Data Citation Index to describe dataset diffusion.RESULTS: 50,822 papers were recovered, 71% of which belong to first and second quartile journals. 59% of the articles were published in Open Access (OA) journals. The Open Access model and international collaboration positively conditioned the number of citations received. Among the most productive journals stood out Plos One, Cancers, and Clinical and Translational Oncology. 2693 genomics, proteomics and metabolomics datasets were retrieved, being Gene Expression Omnibus the favoured repository.CONCLUSIONS: There has been an increase in oncology publications in Open Access. Most were published in first quartile journals and received higher citations than non-Open Access articles, as well as when oncological investigation was performed between international research teams, being relevant in the context of Open Science. Genetic repositories have been the preferred for sharing oncology datasets. Further investigation of research and data sharing in oncology is needed, supported by stronger Open Science policies, to achieve better data sharing practices among three scientific main pillars: researchers, publishers, and scientific organizations.PMID:38635076 | DOI:10.1007/s12094-024-03468-7
Blood-Based Multiomics-Guided Detection of a Precancerous Pancreatic Tumor
OMICS. 2024 Apr 17. doi: 10.1089/omi.2023.0278. Online ahead of print.ABSTRACTOver a decade ago, longitudinal multiomics analysis was pioneered for early disease detection and individually tailored precision health interventions. However, high sample processing costs, expansive multiomics measurements along with complex data analysis have made this approach to precision/personalized medicine impractical. Here we describe in a case report, a more practical approach that uses fewer measurements, annual sampling, and faster decision making. We also show how this approach offers promise to detect an exceedingly rare and potentially fatal condition before it fully manifests. Specifically, we describe in the present case report how longitudinal multiomics monitoring (LMOM) helped detect a precancerous pancreatic tumor and led to a successful surgical intervention. The patient, enrolled in an annual blood-based LMOM since 2018, had dramatic changes in the June 2021 and 2022 annual metabolomics and proteomics results that prompted further clinical diagnostic testing for pancreatic cancer. Using abdominal magnetic resonance imaging, a 2.6 cm lesion in the tail of the patient's pancreas was detected. The tumor fluid from an aspiration biopsy had 10,000 times that of normal carcinoembryonic antigen levels. After the tumor was surgically resected, histopathological findings confirmed it was a precancerous pancreatic tumor. Postoperative omics testing indicated that most metabolite and protein levels returned to patient's 2018 levels. This case report illustrates the potentials of blood LMOM for precision/personalized medicine, and new ways of thinking medical innovation for a potentially life-saving early diagnosis of pancreatic cancer. Blood LMOM warrants future programmatic translational research with the goals of precision medicine, and individually tailored cancer diagnoses and treatments.PMID:38634790 | DOI:10.1089/omi.2023.0278
Urinary Metabolomic Profiles Uncover Metabolic Pathways in Children with Asthma
J Asthma. 2024 Apr 18:1-11. doi: 10.1080/02770903.2024.2338865. Online ahead of print.ABSTRACTObjective: The prevalence of asthma has gradually increased worldwide in recent years, which has made asthma a global public health problem. However, due to its complexity and heterogeneity, there are a few academic debates on the pathogenic mechanism of asthma. The study of the pathogenesis of asthma through metabolomics has become a new research direction. We aim to uncover the metabolic pathway of children with asthma.Methods: Liquid chromatography (LC)-mass spectrometry (MS)-based metabolomic analysis was conducted to compare urine metabolic profiles between asthmatic children (n = 30) and healthy controls (n = 10).Results: Orthogonal projections to latent structures-discrimination analysis (OPLS-DA) showed that there were significant differences in metabolism between the asthma group and the control group with three different metabolites screened out, including traumatic acid, dodecanedioic acid and glucobrassicin, and the levels of traumatic acid and dodecanedioic acid in the urine samples of asthmatic children were lower than those of healthy controls therein. Pathway enrichment analysis of differentially abundant metabolites suggested that alpha-linolenic acid metabolism was an asthma-related pathway.Conclusions: This study suggests that there are significant metabolic differences in the urine of asthmatic children and healthy controls, and alpha-linolenic acid metabolic pathways may be involved in the pathogenesis of asthma.PMID:38634666 | DOI:10.1080/02770903.2024.2338865
AtMYB41 acts as a dual-function transcription factor that regulates the formation of lipids in an organ- and development-dependent manner
Plant Biol (Stuttg). 2024 Apr 18. doi: 10.1111/plb.13650. Online ahead of print.ABSTRACTThe plant cuticle controls non-stomatal water loss and can serve as a barrier against biotic agents, whereas the heteropolymer suberin and its associated waxes are deposited constitutively at specific cell wall locations. While several transcription factors controlling cuticle formation have been identified, those involved in the transcriptional regulation of suberin biosynthesis remain poorly characterized. The major goal of this study was to further analyse the function of the R2R3-Myeloblastosis (MYB) transcription factor AtMYB41 in formation of the cuticle, suberin, and suberin-associated waxes throughout plant development. For functional analysis, the organ-specific expression pattern of AtMYB41 was analysed and Atmyb41ge alleles were generated using the CRISPR/Cas9 system. These were investigated for root growth and water permeability upon stress. In addition, the fatty acid, wax, cutin, and suberin monomer composition of different organs was evaluated by gas chromatography. The characterization of Atmyb41ge mutants revealed that AtMYB41 negatively regulates the production of cuticular lipids and fatty acid biosynthesis in leaves and seeds, respectively. Remarkably, biochemical analyses indicate that AtMYB41 also positively regulates the formation of cuticular waxes in stems of Arabidopsis thaliana. Overall, these results suggest that the AtMYB41 acts as a negative regulator of cuticle and fatty acid biosynthesis in leaves and seeds, respectively, but also as a positive regulator of wax production in A. thaliana stems.PMID:38634447 | DOI:10.1111/plb.13650
Carboxylesterase and Cytochrome P450 Confer Metabolic Resistance Simultaneously to Azoxystrobin and Some Other Fungicides in <em>Botrytis cinerea</em>
J Agric Food Chem. 2024 Apr 18. doi: 10.1021/acs.jafc.4c02409. Online ahead of print.ABSTRACTPlant pathogens have frequently shown multidrug resistance (MDR) in the field, often linked to efflux and sometimes metabolism of fungicides. To investigate the potential role of metabolic resistance in B. cinerea strains showing MDR, the azoxystrobin-sensitive strain B05.10 and -resistant strain Bc242 were treated with azoxystrobin. The degradation half-life of azoxystrobin in Bc242 (9.63 days) was shorter than that in B05.10 (28.88 days). Azoxystrobin acid, identified as a metabolite, exhibited significantly lower inhibition rates on colony and conidia (9.34 and 11.98%, respectively) than azoxystrobin. Bc242 exhibited higher expression levels of 34 cytochrome P450s (P450s) and 11 carboxylesterase genes (CarEs) compared to B05.10 according to RNA-seq analysis. The expression of P450 genes Bcin_02g01260 and Bcin_12g06380, along with the CarEs Bcin_12g06360 in Saccharomyces cerevisiae, resulted in reduced sensitivity to various fungicides, including azoxystrobin, kresoxim-methyl, pyraclostrobin, trifloxystrobin, iprodione, and carbendazim. Thus, the mechanism of B. cinerea MDR is linked to metabolism mediated by the CarE and P450 genes.PMID:38634420 | DOI:10.1021/acs.jafc.4c02409
Multiomics Analysis Revealed Colorectal Cancer Pathogenesis
J Proteome Res. 2024 Apr 18. doi: 10.1021/acs.jproteome.3c00894. Online ahead of print.ABSTRACTGut microbiota-derived microbial compounds may link to the pathogenesis of colorectal cancer (CRC). However, the role of the host-microbiome in the incidence and progression of CRC remains elusive. We performed 16S rRNA sequencing, metabolomics, and proteomic studies on samples from 85 CRC patients who underwent colonoscopy examination and found two distinct changed patterns of microbiome in CRC patients. The relative abundances of Catabacter and Mogibacterium continuously increased from intramucosal carcinoma to advanced stages, whereas Clostridium, Anaerostipes, Vibrio, Flavonifractor, Holdemanella, and Hungatella were significantly altered only in intermediate lesions. Fecal metabolomics analysis exhibited consistent increases in bile acids, indoles, and urobilin as well as a decrease in heme. Serum metabolomics uncovered the highest levels of bilin, glycerides, and nucleosides together with the lowest levels of bile acids and amino acids in the stage of intermediate lesions. Three fecal and one serum dipeptides were elevated in the intermediate lesions. Proteomics analysis of colorectal tissues showed that oxidation and autophagy through the PI3K/Akt-mTOR signaling pathway contribute to the development of CRC. Diagnostic analysis showed multiomics features have good predictive capability, with AUC greater than 0.85. Our overall findings revealed new candidate biomarkers for CRC, with potentially significant diagnostic and prognostic capabilities.PMID:38634357 | DOI:10.1021/acs.jproteome.3c00894
Exploring the impact of polyphenolic compounds on the chromatic characteristics in flowers of Rhododendron arboreum Sm. collected from different altitudinal locations
Phytochem Anal. 2024 Apr 18. doi: 10.1002/pca.3354. Online ahead of print.ABSTRACTINTRODUCTION: Rhododendron arboreum Sm. flowers grow in the Himalayan region and have traditionally been used in beverages and food. These wild edible Himalayan flowers are known for their sweet-sour flavor and beautiful scarlet red color. The primary pigments responsible for the scarlet red color of these flowers are anthocyanins.OBJECTIVE: In the present study, we conducted chemo-profiling and elucidated the chromatic characteristics of R. arboreum flower petals growing in the wild in different altitudinal areas.METHODOLOGY: The content of anthocyanins, phenolics, and other flavonoids was determined in R. arboreum flower petals collected from 38 different locations in two provinces in India (Himachal Pradesh and Uttarakhand) to obtain a distinguishable chemical index. A UHPLC method has also been developed and validated for the quantitative analysis. Besides, the color characteristics of each collected floral sample were also analyzed.RESULTS: Chemometric analysis (principal component analysis [PCA] and heatmap analysis) revealed that floral samples collected from different altitudes exhibited similar chemical diversity, whereas statistical analysis (bivariate linear correlation) revealed a positive correlation between the color parameter a*/b* and cyanidin glycosides. Besides, non-targeted metabolomics analysis was carried out, which resulted in the tentative identification of 150 metabolites.CONCLUSION: The results revealed that there is a direct influence of accumulated anthocyanins to color parameter a*/b* values in the floral samples irrespective of altitude.PMID:38634333 | DOI:10.1002/pca.3354
Metabolome-microbiome insights into therapeutic impact of 8-O-acetylharpagide against breast cancer in a murine model
Biomed Chromatogr. 2024 Apr 17:e5880. doi: 10.1002/bmc.5880. Online ahead of print.ABSTRACTIridoid glycosides extract, which is the main active extract of Ajuga decumbens Thunb, has been proved to have anti-breast cancer activity in previous studies. However, it is still unknown whether 8-O-acetylharpagide, a main active compound in the extract, has anti-breast cancer activity. In this study, 4 T1 breast cancer mice model was first successfully established. Then the anti-breast cancer effect of 8-O-acetylharpagide was systematically investigated. Feces were collected for metabolomics and 16S rRNA analysis to assess the potential mechanism. The results showed that 8-O-acetylharpagide was effective in reducing 4 T1 mouse tumor volume and weight compared with the model group. Metabolome analysis revealed 12 potential metabolite biomarkers in feces, mainly involved in primary bile acid biosynthesis and arachidonic acid metabolism. The 16S rRNA sequencing results demonstrated that 8-O-acetylharpagide modulated the abundance of the intestinal flora in 4 T1 mice. Spearman correlation analysis showed that calcitriol and prostaglandin G2 strongly correlated with Akkermansia, Firmicutes and Muribaculum. Overall, the active compound 8-O-acetylharpagide could inhibit significantly breast cancer growth in 4 T1 breast cancer model mice. The mechanism of the anti-breast cancer effect of 8-O-acetylharpagide may be related to the regulation of primary bile acid biosynthesis and arachidonic acid metabolism and modulation of the abundance of Akkermansia and Firmicutes.PMID:38634147 | DOI:10.1002/bmc.5880