PubMed

Biomed Pharmacother. 2023 Dec 8;170:116000. doi: 10.1016/j.biopha.2023.116000. Online ahead of print.ABSTRACTFormononetin, an isoflavone compound, has been extensively researched due to its various biological activities, including a potent protective effect on the cardiovascular system. However, the impact of formononetin on cardiac fibrosis has not been investigated. In this study, C57BL/6 mice were used to establish cardiac fibrosis animal models by subcutaneous injecting of isoproterenol (ISO) and formononetin was orally administrated. The results showed that formononetin reversed ISO-induced heart stiffness revealed by early-to-atrial wave ratio (E/A ratio). Masson staining, western blot, immunohistochemistry and real-time PCR exhibited that the cardiac fibrosis and fibrosis-related proteins (collage III, fibronectin, TGF-β1, α-SMA, and vimentin) and genes (Col1a1, Col3a1, Acta2 and Tgfb1) induced by ISO were significantly suppressed by formononetin. Furthermore, by combining metabolomics and network pharmacology, we found three important targets (ALDH2, HADH, and MAOB), which are associated with mitochondrial function, were involved in the beneficial effect of formononetin. Further validation revealed that these three genes were more abundance in cardiomyocyte than in cardiac fibroblast. The mRNA expression of ALDH2 and HADH were decreased, while MOAB was increased in cardiomyocyte upon ISO treatment and these phenomena were reversed by formononetin. In addition, we investigated mitochondrial membrane potential and ROS production in cardiomyocytes, the results showed that formononetin effectively improved mitochondrial dysfunction induced by ISO. In summary, we demonstrated that formononetin via regulating the expressions of ALDH2, HADH, and MAOB in cardiomyocyte to improve mitochondrial dysfunction and alleviate β-adrenergic activation cardiac fibrosis.PMID:38070245 | DOI:10.1016/j.biopha.2023.116000

Cell Rep. 2023 Dec 8;42(12):113521. doi: 10.1016/j.celrep.2023.113521. Online ahead of print.ABSTRACTThe gut microbiome modulates seizure susceptibility and the anti-seizure effects of the ketogenic diet (KD) in animal models, but whether these relationships translate to KD therapies for human epilepsy is unclear. We find that the clinical KD alters gut microbial function in children with refractory epilepsy. Colonizing mice with KD-associated microbes promotes seizure resistance relative to matched pre-treatment controls. Select metagenomic and metabolomic features, including those related to anaplerosis, fatty acid β-oxidation, and amino acid metabolism, are seen with human KD therapy and preserved upon microbiome transfer to mice. Mice colonized with KD-associated gut microbes exhibit altered hippocampal transcriptomes, including pathways related to ATP synthesis, glutathione metabolism, and oxidative phosphorylation, and are linked to susceptibility genes identified in human epilepsy. Our findings reveal key microbial functions that are altered by KD therapies for pediatric epilepsy and linked to microbiome-induced alterations in brain gene expression and seizure protection in mice.PMID:38070135 | DOI:10.1016/j.celrep.2023.113521

FASEB J. 2024 Jan;38(1):e23349. doi: 10.1096/fj.202301344R.ABSTRACTIn this study, the transcriptional repressor REST (Repressor Element 1 Silencing Transcription factor) was ablated in the mouse placenta to investigate molecular and cellular impacts on the offspring brain at different life stages. Ablation of placental REST deregulated several brain metabolites, including glucose and lactate that fuel brain energy, vitamin C (ascorbic acid) that functions in the epigenetic programming of the brain during postnatal development, and glutamate and creatine that help the brain to respond to stress conditions during adult life. Bulk RNA-seq analysis showed that a lack of placental REST persistently altered multiple transport genes, including those related to oxygen transportation in the offspring brain. While metabolic genes were impacted in the postnatal brain, different stress response genes were activated in the adult brain. DNA methylation was also impacted in the adult brain due to the loss of placental REST, but in a sex-biased manner. Single-nuclei RNA-seq analysis showed that specific cell types of the brain, particularly those of the choroid plexus and ependyma, which play critical roles in producing cerebrospinal fluid and maintaining metabolic homeostasis, were significantly impacted due to the loss of placental REST. These cells showed significant differential expression of genes associated with the metabotropic (G coupled protein) and ionotropic (ligand-gated ion channel) glutamate receptors, suggesting an impact of ablation of placental REST on the glutamatergic signaling of the offspring brain. The study expands our understanding of placental influences on the offspring brain.PMID:38069914 | DOI:10.1096/fj.202301344R

Chimia (Aarau). 2022 Nov 30;76(11):954-963. doi: 10.2533/chimia.2022.954.ABSTRACTMetabolomics is playing an increasingly prominent role in chemical ecology and in the discovery of bioactive natural products (NPs). The identification of metabolites is a common/central objective in both research fields. NPs have significant biological properties and play roles in multiple chemical-ecological interactions. Classically, in pharmacognosy, their chemical structure is determined after a complex process of isolating and interpreting spectroscopic data. With the advent of powerful analytical techniques such as liquid chromatography-mass spectrometry (LC-MS) the annotation process of the specialised metabolome of plants and microorganisms has improved considerably. In this article, we summarise the possibilities opened by these advances and illustrate how we harnessed them in our own research to automate annotations of NPs and target the isolation of key compounds. In addition, we are also discussing the analytical and computational challenges associated with these emerging approaches and their perspective.PMID:38069791 | DOI:10.2533/chimia.2022.954

Chimia (Aarau). 2022 Nov 30;76(11):922-927. doi: 10.2533/chimia.2022.922.ABSTRACTIt has been estimated that between 40 and 60 % of the assimilated carbon is diverted to the roots and released in the rhizosphere in form of root exudates. Root exudates thus define a complex mixture of low and high molecular weight compounds, including carbohydrates, amino acids, organic, and proteins, but also a broad spectrum of specialized molecules, such as flavonoids, glucosinolates, terpenoids, or alkaloids. Root exudates favour soil mineral nutrition, can bind to soil aggregate and in turn modify soil physico-chemical properties, but also mediate plant-plant, plant-microbe, and plant-animal interactions belowground. With this review, we aim to highlight how chemical ecologists have approached the study of root exudates-mediated interactions between plants and their biotic and abiotic surroundings. We do so by presenting a series of study cases for, on one hand, showcasing different methodologies that have been developed to test the activity of different root exudates, and, on the other hand, to show the broad array of interactions mediated by root exudates. Ultimately, we aim to spur further research and collaborations between chemists and ecologists studying belowground chemically-mediated interactions, so as to tackle essential challenges in terms of food security and climate change in the near future.PMID:38069787 | DOI:10.2533/chimia.2022.922

Chimia (Aarau). 2022 Feb 23;76(1-2):90-100. doi: 10.2533/chimia.2022.90.ABSTRACTUntargeted metabolomics is now widely recognized as a useful tool for exploring metabolic changes taking place in biological systems under different conditions. In this article, we aim to provide a short overview of the liquid-phase separation methods hyphenated to MS to perform untargeted metabolomics of biological samples. Each approach is complemented by up-to-date literature to guide readers, as well as practical information for avoiding or fixing some of the most frequently encountered pitfalls. This article covers mainly data acquisition, but a short discussion is provided regarding signal processing and data treatment, as well as data analysis and its biological interpretation in the context of metabolomic studies.PMID:38069754 | DOI:10.2533/chimia.2022.90

J Exp Bot. 2023 Dec 9:erad456. doi: 10.1093/jxb/erad456. Online ahead of print.ABSTRACTSphingolipids are membrane lipids and play critical roles in signal transduction. Ceramides, central components of sphingolipid metabolism, are involved in cell death. However, the mechanism of ceramides regulating cell death in plants remains unclear. Here, we found ceramides accumulated in mitochondria of accelerated cell death 5 mutant (acd5), and expression of mitochondrion-localized ceramide kinase (ACD5) suppressed mitochondrial ceramides accumulation and the acd5 cell death phenotype. We applied immuno-electron microscopy and observed ceramide-hyperaccumulation in acer acd5 double mutants which are characterized by mutations in both ACER (alkaline ceramidase) and ACD5 genes. The results confirmed that, plants with specific ceramide accumulation exhibited localization of ceramides to mitochondria, resulting in an increase of mitochondrial reactive oxygen species. Interestingly, when compared to the wild type, autophagy deficient mutants showed stronger resistance to ceramide-induced cell death. Lipid profiling analysis demonstrated that plants with ceramide accumulation exhibited a significant increase in phosphatidylethanolamine levels. Further, we found that ceramide treatment or endogenous ceramide accumulation induces autophagy. When exposed to exogenous ceramides, we found an increase in the level of ATG8e associated with mitochondria, where it bound to ceramides directly. Taken together, we proposed that the accumulation of ceramides in mitochondria can induce cell death by regulating autophagy.PMID:38069660 | DOI:10.1093/jxb/erad456

Phytochem Anal. 2023 Dec 8. doi: 10.1002/pca.3300. Online ahead of print.ABSTRACTINTRODUCTION: The genus Clusia L. is mostly recognised for the production of prenylated benzophenones and tocotrienol derivatives.OBJECTIVES: The objective of this study was to map metabolome variation within Clusia minor organs at different developmental stages.MATERIAL AND METHODS: In total 15 organs/stages (leaf, flower, fruit, and seed) were analysed by UPLC-MS and 1 H- and heteronuclear multiple-bond correlation (HMBC)-NMR-based metabolomics.RESULTS: This work led to the assignment of 46 metabolites, belonging to organic acids(1), sugars(2) phenolic acids(1), flavonoids(3) prenylated xanthones(1) benzophenones(4) and tocotrienols(2). Multivariate data analyses explained the variability and classification of samples, highlighting chemical markers that discriminate each organ/stage. Leaves were found to be rich in 5-hydroxy-8-methyltocotrienol (8.5 μg/mg f.w.), while flowers were abundant in the polyprenylated benzophenone nemorosone with maximum level detected in the fully mature flower bud (43 μg/mg f.w.). Nemorosone and 5-hydroxy tocotrienoloic acid were isolated from FL6 for full structural characterisation. This is the first report of the NMR assignments of 5-hydroxy tocotrienoloic acid, and its maximum level was detected in the mature fruit at 50 μg/mg f.w. Seeds as typical storage organ were rich in sugars and omega-6 fatty acids.CONCLUSION: To the best of our knowledge, this is the first report on a comparative 1D-/2D-NMR approach to assess compositional differences in ontogeny studies compared with LC-MS exemplified by Clusia organs. Results derived from this study provide better understanding of the stages at which maximal production of natural compounds occur and elucidate in which developmental stages the enzymes responsible for the production of such metabolites are preferentially expressed.PMID:38069552 | DOI:10.1002/pca.3300

Int J Mol Sci. 2023 Dec 1;24(23):17046. doi: 10.3390/ijms242317046.ABSTRACTLung cancer is a malignant tumor with one of the highest morbidity and mortality rates in the world. Approximately 80-85% of lung cancer is diagnosed as non-small lung cancer (NSCLC), and its 5-year survival rate is only 21%. Cisplatin is a commonly used chemotherapy drug for the treatment of NSCLC. Its efficacy is often limited by the development of drug resistance after long-term treatment. Therefore, determining how to overcome cisplatin resistance, enhancing the sensitivity of cancer cells to cisplatin, and developing new therapeutic strategies are urgent clinical problems. Z-ligustilide is the main active ingredient of the Chinese medicine Angelica sinensis, and has anti-tumor activity. In the present study, we investigated the effect of the combination of Z-ligustilide and cisplatin (Z-ligustilide+cisplatin) on the resistance of cisplatin-resistant lung cancer cells and its mechanism of action. We found that Z-ligustilide+cisplatin decreased the cell viability, induced cell cycle arrest, and promoted the cell apoptosis of cisplatin-resistant lung cancer cells. Metabolomics combined with transcriptomics revealed that Z-ligustilide+cisplatin inhibited phospholipid synthesis by upregulating the expression of phospholipid phosphatase 1 (PLPP1). A further study showed that PLPP1 expression was positively correlated with good prognosis, whereas the knockdown of PLPP1 abolished the effects of Z-ligustilide+cisplatin on cell cycle and apoptosis. Specifically, Z-ligustilide+cisplatin inhibited the activation of protein kinase B (AKT) by reducing the levels of phosphatidylinositol 3,4,5-trisphosphate (PIP3). Z-ligustilide+cisplatin induced cell cycle arrest and promoted the cell apoptosis of cisplatin-resistant lung cancer cells by inhibiting PLPP1-mediated phospholipid synthesis. Our findings demonstrate that the combination of Z-Ligustilide and cisplatin is a promising approach to the chemotherapy of malignant tumors that are resistant to cisplatin.PMID:38069368 | DOI:10.3390/ijms242317046

Int J Mol Sci. 2023 Dec 1;24(23):17035. doi: 10.3390/ijms242317035.ABSTRACTMarrubium species have been used since ancient times as food additives and curative treatments. Their phytochemical composition and various pharmacological activities were the focus of a number of scientific investigations but no comprehensive metabolome profiling to identify the numerous primary and secondary metabolites has been performed so far. This study aimed to generate a comprehensive picture of the total metabolite content of two Marrubium species-M. peregrinum and M. friwaldskyanum-to provide detailed information about the main primary and secondary metabolites. In addition, the elemental composition was also evaluated. For this purpose, non-targeted metabolomic analyses were conducted using GC-MS, UPLC-MS/MS and ICP-MS approaches. Nearly 500 compounds and 12 elements were detected and described. The results showed a strong presence of phenolic acids, flavonoids and their glucosides, which are generally of great interest due to their various pharmacological activities. Furthermore, tissue-specific analyses for M. friwaldskyanum stem, leaves and flowers were carried out in order to outline the sources of potentially important bioactive molecules. The results generated from this study depict the Marrubium metabolome and reveal its dual scientific importance-from one side, providing information about the metabolites that is fundamental and vital for the survival of these species, and from the other side, defining the large diversity of secondary substances that are a potential source of phytotherapeutic agents.PMID:38069358 | DOI:10.3390/ijms242317035

Int J Mol Sci. 2023 Dec 1;24(23):17025. doi: 10.3390/ijms242317025.ABSTRACTTorreya grandis is native Chinese tree species of economic significance, renowned for its long lifespan and the rich nutritional value of its nuts. In this study, we analyzed the morphological characteristics, metabolites, associated gene expressions, and regulatory mechanism in nuts from young (10 years old) and old (1000 years old) T. grandis trees. We observed that the length, width, and weight of nuts from older trees were considerably greater than those from younger trees. Metabolomic analysis revealed that the concentrations of 18 amino acids and derivatives (including histidine and serine) in nuts from older trees were markedly higher than those in nuts from younger trees. Transcriptome and metabolomic correlation analysis identified 16 genes, including TgPK (pyruvate kinase), TgGAPDH (glyceraldehyde 3-phosphate dehydrogenase), and others, which exhibit higher expression levels in older trees compared to younger trees, as confirmed by qRT-PCR. These genes are associated with the biosynthesis of histidine, glutamic acid, tryptophan, and serine. Transient expression of TgPK in tobacco led to increased pyruvate kinase activity and amino acid content (histidine, tryptophan, and serine). Additionally, dual-luciferase assays and yeast one-hybrid results demonstrated that TgWRKY21 positively regulates TgPK expression by directly binding to the TgPK promoter. These findings not only demonstrate the nutritional differences between nuts from young and old trees but also offer fresh insights into the development of nutritional sources and functional components based on nuts from old trees, enriching our understanding of the potential benefits of utilizing nuts from older trees.PMID:38069348 | DOI:10.3390/ijms242317025

Int J Mol Sci. 2023 Nov 30;24(23):17002. doi: 10.3390/ijms242317002.ABSTRACTAs a medicinal tree species, ginkgo (Ginkgo biloba L.) and terpene trilactones (TTLs) extracted from its leaves are the main pharmacologic activity constituents and important economic indicators of its value. The accumulation of TTLs is known to be affected by environmental stress, while the regulatory mechanism of environmental response mediated by microRNAs (miRNAs) at the post-transcriptional levels remains unclear. Here, we focused on grafted ginkgo grown in northwestern, southwestern, and eastern-central China and integrally analyzed RNA-seq and small RNA-seq high-throughput sequencing data as well as metabolomics data from leaf samples of ginkgo clones grown in natural environments. The content of bilobalide was highest among detected TTLs, and there was more than a twofold variation in the accumulation of bilobalide between growth conditions. Meanwhile, transcriptome analysis found significant differences in the expression of 19 TTL-related genes among ginkgo leaves from different environments. Small RNA sequencing and analysis showed that 62 of the 521 miRNAs identified were differentially expressed among different samples, especially the expression of miRN50, miR169h/i, and miR169e was susceptible to environmental changes. Further, we found that transcription factors (ERF, MYB, C3H, HD-ZIP, HSF, and NAC) and miRNAs (miR319e/f, miRN2, miRN54, miR157, miR185, and miRN188) could activate or inhibit the expression of TTL-related genes to participate in the regulation of terpene trilactones biosynthesis in ginkgo leaves by weighted gene co-regulatory network analysis. Our findings provide new insights into the understanding of the regulatory mechanism of TTL biosynthesis but also lay the foundation for ginkgo leaves' medicinal value improvement under global change.PMID:38069325 | DOI:10.3390/ijms242317002

Int J Mol Sci. 2023 Nov 30;24(23):16992. doi: 10.3390/ijms242316992.ABSTRACTThe apricot (Prunus armeniaca L.) is a fruit that belongs to the Rosaceae family; it has a unique flavor and is of important economic and nutritional value. The composition and content of soluble sugars and organic acids in fruit are key factors in determining the flavor quality. However, the molecular mechanism of sugar and acid accumulation in apricots remains unclear. We measured sucrose, fructose, glucose, sorbitol, starch, malate, citric acid, titratable acid, and pH, and investigated the transcriptome profiles of three apricots (the high-sugar cultivar 'Shushanggan', common-sugar cultivar 'Sungold', and low-sugar cultivar 'F43') at three distinct developmental phases. The findings indicated that 'Shushanggan' accumulates a greater amount of sucrose, glucose, fructose, and sorbitol, and less citric acid and titratable acid, resulting in a better flavor; 'Sungold' mainly accumulates more sucrose and less citric acid and starch for the second flavor; and 'F43' mainly accumulates more titratable acid, citric acid, and starch for a lesser degree of sweetness. We investigated the DEGs associated with the starch and sucrose metabolism pathways, citrate cycle pathway, glycolysis pathway, and a handful of sugar transporter proteins, which were considered to be important regulators of sugar and acid accumulation. Additionally, an analysis of the co-expression network of weighted genes unveiled a robust correlation between the brown module and sucrose, glucose, and fructose, with VIP being identified as a hub gene that interacted with four sugar transporter proteins (SLC35B3, SLC32A, SLC2A8, and SLC2A13), as well as three structural genes for sugar and acid metabolism (MUR3, E3.2.1.67, and CSLD). Furthermore, we found some lncRNAs and miRNAs that regulate these genes. Our findings provide clues to the functional genes related to sugar metabolism, and lay the foundation for the selection and cultivation of high-sugar apricots in the future.PMID:38069317 | DOI:10.3390/ijms242316992

Int J Mol Sci. 2023 Nov 30;24(23):16989. doi: 10.3390/ijms242316989.ABSTRACTOne of the most productive ecosystems in the world, mangroves are susceptible to cold stress. However, there is currently insufficient knowledge of the adaptation mechanisms of mangrove plants in response to chilling stress. This study conducted a comparative analysis of transcriptomics and metabolomics to investigate the adaptive responses of Kandelia obovata (chilling-tolerant) and Avicennia marina (chilling-sensitive) to 5 °C. The transcriptomics results revealed that differentially expressed genes (DEGs) were mostly enriched in signal transduction, photosynthesis-related pathways, and phenylpropanoid biosynthesis. The expression pattern of genes involved in photosynthesis-related pathways in A. marina presented a downregulation of most DEGs, which correlated with the decrease in total chlorophyll content. In the susceptible A. marina, all DEGs encoding mitogen-activated protein kinase were upregulated. Phenylpropanoid-related genes were observed to be highly induced in K. obovata. Additionally, several metabolites, such as 4-aminobutyric acid, exhibited higher levels in K. obovata than in A. marina, suggesting that chilling-tolerant varieties regulated more metabolites in response to chilling. The investigation defined the inherent distinctions between K. obovata and A. marina in terms of signal transduction gene expression, as well as phenylpropanoid and flavonoid biosynthesis, during exposure to low temperatures.PMID:38069316 | DOI:10.3390/ijms242316989

Int J Mol Sci. 2023 Nov 30;24(23):16995. doi: 10.3390/ijms242316995.ABSTRACTOral mucositis (OM) is a common and clinically impactful side effect of cytotoxic cancer treatment, particularly in patients with head and neck squamous cell carcinoma (HNSCC) who undergo radiotherapy with or without concomitant chemotherapy. The etiology and pathogenic mechanisms of OM are complex, multifaceted and elicit both direct and indirect damage to the mucosa. In this narrative review, we describe studies that use various omics methodologies (genomics, transcriptomics, microbiomics and metabolomics) in attempts to elucidate the biological pathways associated with the development or severity of OM. Integrating different omics into multi-omics approaches carries the potential to discover links among host factors (genomics), host responses (transcriptomics, metabolomics), and the local environment (microbiomics).PMID:38069314 | DOI:10.3390/ijms242316995

Int J Mol Sci. 2023 Nov 30;24(23):16966. doi: 10.3390/ijms242316966.ABSTRACTCrohn's disease (CD) is characterized by a chronic, progressive inflammation of the gastrointestinal tract often leading to complications, such as strictures and fistulae. Currently, there are no validated tools anticipating short- and long-term outcomes at an early stage. This investigation aims to elucidate variations in protein abundance across distinct CD phenotypes with the objective of uncovering potential biomarkers implicated in disease advancement. Serum samples collected from 30 CD patients and 15 healthy age-matched controls (HC) were subjected to depletion of highly abundant proteins and to a label-free mass spectrometry analysis. Twenty-four proteins were shown to be significantly different when comparing CD with HC. Of these, WD repeat-containing protein 31 (WDR31), and proteins involved in the acute inflammatory response, leucine-rich alpha-2-glycoprotein (LRG1) and serum amyloid A1 (SAA1), were more abundant in the aggressive subgroup. Against standard biomarkers, a positive correlation between SAA1 and WDR31 and C-reactive protein (CRP) was found. In this study, a unique serum biomarker panel for aggressive CD was identified, which could aid in predicting the disease course.PMID:38069288 | DOI:10.3390/ijms242316966

Int J Mol Sci. 2023 Nov 29;24(23):16913. doi: 10.3390/ijms242316913.ABSTRACTThe technological advances of recent years have significantly enhanced medical discoveries [...].PMID:38069240 | DOI:10.3390/ijms242316913

Int J Mol Sci. 2023 Nov 28;24(23):16871. doi: 10.3390/ijms242316871.ABSTRACTSkin color is an important trait that is mainly determined by the content and composition of anthocyanins in apples. In this study, a new bud mutant (RM) from 'Oregon Spur II' (OS) of Red Delicious apple was obtained to reveal the mechanism underlying red color formation. Results showed that the total anthocyanin content in RM was significantly higher than that in OS with the development of fruit. Through widely-targeted metabolomics, we found that cyanidin-3-O-galactoside was significantly accumulated in the fruit skin of RM. Transcriptome analysis revealed that the structural gene MdF3H and MdMYB66 transcription factor were significantly up-regulated in the mutant. Overexpression of MdMYB66 in apple fruit and apple callus significantly promoted anthocyanin accumulation and significantly increased the expression level of MdMYB66 and structural genes related to anthocyanin synthesis. Y1H and LUC analysis verified that MdMYB66 could specifically bind to the promoter of MdF3H. The results of the double luciferase activity test showed that MdMYB66 activated MdF3H 3.8 times, which led to increased anthocyanin contents. This might explain the phenotype of red color in RM at the early stage. Taken together, these results suggested that MdMYB66 was involved in regulating the anthocyanin metabolic pathways through precise regulation of gene expression. The functional characterization of MdMYB66 provides insight into the biosynthesis and regulation of anthocyanins.PMID:38069191 | DOI:10.3390/ijms242316871

Int J Mol Sci. 2023 Nov 26;24(23):16776. doi: 10.3390/ijms242316776.ABSTRACTThe major goal of this study is to create a venue for further work on the effect of pulsed magnetic fields on plant metabolism. It deals with metabolite synthesis in the aforementioned conditions in microplants of Pyrus communis L. So far, there have been glimpses into the governing factors of plant biochemistry in vivo, and low-frequency pulsed magnestatic fields have been shown to induce additional electric currents in plant tissues, thus perturbing the value of cell membrane potential and causing the biosynthesis of new metabolites. In this study, sixty-seven metabolites synthesized in microplants within 3-72 h after treatment were identified and annotated. In total, thirty-one metabolites were produced. Magnetic-pulse treatment caused an 8.75-fold increase in the concentration of chlorogenic acid (RT = 8.33 ± 0.0197 min) in tissues and the perturbation of phenolic composition. Aucubin, which has antiviral and antistress biological activity, was identified as well. This study sheds light on the effect of magnetic fields on the biochemistry of low-molecular-weight metabolites of pear plants in vitro, thus providing in-depth metabolite analysis under optimized synthetic conditions. This study utilized high-resolution gas chromatography-mass spectrometry, metabolomics methods, stochastic dynamics mass spectrometry, quantum chemistry, and chemometrics, respectively. Stochastic dynamics uses the relationships between measurands and molecular structures of silylated carbohydrates, showing virtually identical mass spectra and comparable chemometrics parameters.PMID:38069098 | DOI:10.3390/ijms242316776

Int J Mol Sci. 2023 Nov 25;24(23):16764. doi: 10.3390/ijms242316764.ABSTRACTInspiratory muscle training (IMT) is known to promote physiological benefits and improve physical performance in endurance sports activities. However, the metabolic adaptations promoted by different IMT prescribing strategies remain unclear. In this work, a longitudinal, randomized, double-blind, sham-controlled, parallel trial was performed to investigate the effects of 11 weeks (3 days·week-1) of IMT at different exercise intensities on the serum metabolomics profile and its main regulated metabolic pathways. Twenty-eight healthy male recreational cyclists (30.4 ± 6.5 years) were randomized into three groups: sham (6 cm·H2O of inspiratory pressure, n = 7), moderate-intensity (MI group, 60% maximal inspiratory pressure (MIP), n = 11) and high-intensity (HI group, 85-90% MIP, n = 10). Blood serum samples were collected before and after 11 weeks of IMT and analyzed by 1H NMR and UHPLC-HRMS/MS. Data were analyzed using linear mixed models and metabolite set enrichment analysis. The 1H NMR and UHPLC-HRMS/MS techniques resulted in 46 and 200 compounds, respectively. These results showed that ketone body metabolism, fatty acid biosynthesis, and aminoacyl-tRNA biosynthesis were upregulated after IMT, while alpha linolenic acid and linoleic acid metabolism as well as biosynthesis of unsaturated fatty acids were downregulated. The MI group presented higher MIP, Tryptophan, and Valine levels but decreased 2-Hydroxybutyrate levels when compared to the other two studied groups. These results suggest an increase in the oxidative metabolic processes after IMT at different intensities with additional evidence for the upregulation of essential amino acid metabolism in the MI group accompanied by greater improvement in respiratory muscle strength.PMID:38069087 | DOI:10.3390/ijms242316764