PubMed
Integrated metabolomics and transcriptomics reveal metabolites difference between wild and cultivated Ophiocordyceps sinensis
Food Res Int. 2023 Jan;163:112275. doi: 10.1016/j.foodres.2022.112275. Epub 2022 Nov 29.ABSTRACTOphiocordyceps sinensis is a traditional medicinal fungus endemic to the alpine and high-altitude areas of the Qinghai-Tibet plateau. The scarcity of the wild resource has led to increased attention to artificially cultivated O. sinensis. However, little is known about the metabolic differences and the regulatory mechanisms between cultivated and wild O. sinensis. This study exploited untargeted metabolomics and transcriptomics to uncover the differences in accumulated metabolites and expressed genes between wild and cultivated O. sinensis. Metabolomics results revealed that 368 differentially accumulated metabolites were mainly enriched in biosynthesis of amino acids, biosynthesis of plant secondary metabolites and purine nucleotide metabolism. Cultivated O. sinensis contained more amino acids and derivatives, carbohydrates and derivatives, and phenolic acids than wild O. sinensis, whereas the contents of most nucleosides and nucleotides in wild O. sinensis were significantly higher than in cultivated O. sinensis. Transcriptome analysis indicated that 4430 annotated differentially expressed genes were identified between two types. Integrated metabolomics and transcriptomics analyses suggested that IMPDH, AK, ADSS, guaA and GUK genes might be related to the synthesis of purine nucleotides and nucleosides. Our findings will provide a new insight into the molecular basis of metabolic variations of this medicinal fungus.PMID:36596185 | DOI:10.1016/j.foodres.2022.112275
Nontargeted metabolomic analysis of four different parts of Actinidia arguta by UPLC-Q-TOF-MS<sup>E</sup>
Food Res Int. 2023 Jan;163:112228. doi: 10.1016/j.foodres.2022.112228. Epub 2022 Dec 5.ABSTRACTActinidia arguta, an edible berry plant with high nutritional values, has been widely used in Asian countries as a food and traditional medicinal herb. The well-recognized health-promoting properties of A. arguta were associated with its bioactive components in its different botanical parts. To rapidly screen and identify chemical components and simultaneously determine the potential metabolites from different parts of A. arguta, UPLC-Q-TOF-MSE coupled with UNIFI platform and multivariate statistical analysis approach was established in this study. As a result, a total of 107 components were identified from the four different parts of A. arguta, in which 31 characteristic chemical markers were discovered among them, including 12, 8, 6, and 5 compounds from the fruits, leaves, roots, and stems, respectively. These results suggested that the combination of UPLC-Q-TOF-MSE and metabolomic analysis is a powerful method to rapidly screen characteristic markers for the quality control of A. arguta.PMID:36596158 | DOI:10.1016/j.foodres.2022.112228
Preharvest application of selenite enhances the quality of Chinese flowering cabbage during storage via regulating the ascorbate-glutathione cycle and phenylpropanoid metabolisms
Food Res Int. 2023 Jan;163:112229. doi: 10.1016/j.foodres.2022.112229. Epub 2022 Nov 24.ABSTRACTChinese flowering cabbage (Brassica campestris L. ssp. chinensis var. utilis Tsen et Lee) is a candidate of selenium (Se) accumulator, but it is not clear whether and how preharvest Se treatment affects its quality after harvest. Here, we showed that preharvest application of 100 μmol/L selenite to roots enhanced storage quality of Chinese flowering cabbage. It increased antioxidant capacity and reduced weight loss, leaf yellowing, and protein degradation after harvest. Furthermore, it increased the activities of antioxidant enzymes such as POD, CAT, GSH-Px, and GR, as well as contents of AsA, GSH, phenolics, and flavonoids during storage. Metabolome analysis revealed that phenolic acids including p-Coumaric acid, caffeic acid, and ferulic acid; flavonoids such as naringenin, eriodictyol, apigenin, quercetin, kaempferol, and their derivatives were notably increased by preharvest selenite treatment. Consistently, the total antioxidant capacity, evaluated by DPPH, ABTS, and FRAP methods, were all markedly enhanced in selenite-treated cabbage compared to the control. Transcriptomics analysis showed that the DEGs induced by selenite were significantly enriched in AsA-GSH metabolisms and phenylpropanoids biosynthesis pathways. Moreover, preharvest selenite treatment significantly up-regulated the expressions of BrGST, BrGSH-Px, BrAPX, BrASO, BrC4H, BrCOMT, BrCHS, and BrFLS during storage. These results suggest that preharvest selenite treatment enhanced quality of cabbage not only by increasing Se biological accumulation, but also through regulating AsA-GSH cycle and increasing phenolics and flavonoids synthesis after harvest. This study provides a novel insight into the effects of preharvest Se treatment on quality of Chinese flowering cabbage during storage.PMID:36596157 | DOI:10.1016/j.foodres.2022.112229
Flavor production in fermented chayote inoculated with lactic acid bacteria strains: Genomics and metabolomics based analysis
Food Res Int. 2023 Jan;163:112224. doi: 10.1016/j.foodres.2022.112224. Epub 2022 Nov 24.ABSTRACTIn this study, genomics and metabolomics were combined to reveal possible bio-synthetic pathways of core flavor compounds in pickled chayote via lactic acid bacteria (LAB) fermentation. The Lactiplantibacillus plantarum, Levilactobacillus brevis, and Lacticaseibacillus paracasei were selected as core LAB strains with better flavor-producing ability for chayote fermentation. The genomic results showed L. plantarum contained the largest number of metabolism annotated genes, while L. brevis had the fewest. Besides, the largest number of volatile compounds was detected in chayote fermented by L. plantarum, followed by L. brevis and L. paracasei. Some unique odor-active compounds (aldehydes, esters, and alcohols) and taste-active compounds (amino acids and dipeptides) were produced by different LAB strains. Accordingly, phenylalanine metabolic pathway (M00360), amino acid metabolic decomposition pathway (the Ehrlich pathway) and the anabolic pathway (the Harris pathway), and fatty acid biosynthesis pathway (M00061) were the main biosynthesis pathway involved in the flavor formation via LAB fermentation.PMID:36596153 | DOI:10.1016/j.foodres.2022.112224
Seaweed metabolomics: A review on its nutrients, bioactive compounds and changes in climate change
Food Res Int. 2023 Jan;163:112221. doi: 10.1016/j.foodres.2022.112221. Epub 2022 Nov 24.ABSTRACTSeaweed, an important food resource in several Asian countries, contains various metabolites, including sugars, organic acids, and amino acids; however, their content is affected by prevailing environmental conditions. This review discusses seaweed metabolomics, especially the distribution of primary and functional secondary metabolites (e.g., carotenoids, polyphenols) in seaweed. Additionally, the effects of global warming on seaweed metabolite profile changes are discussed. For example, high temperatures can increase amino acid levels in seaweeds. Overall, understanding the effects of global warming on seaweed metabolite profiles can be useful for evaluating the nutritional composition of seaweeds as food. This review provides an overview of recent applications of metabolomics in seaweed research as well as a perspective on the nutrient content and cultivation of seaweeds under climate change scenarios.PMID:36596150 | DOI:10.1016/j.foodres.2022.112221
Transcriptome and metabolome reveal the effects of three canopy types on the flavonoids and phenolic acids in 'Merlot' (Vitis vinifera L.) berry pericarp
Food Res Int. 2023 Jan;163:112196. doi: 10.1016/j.foodres.2022.112196. Epub 2022 Nov 19.ABSTRACTThe flavonoids and phenolic acids in grape berries greatly influence the quality of wine. Various methods are used to shape and prune grapevines, but their effects on the flavonoids and phenolic acids remain unclear. The flavonoids and phenolic acids in the berry pericarps from grapevines pruned using three types of leaf canopy, namely, V-shaped, T-shaped, and vertical shoot-positioned (VSP) canopies, were compared in this study. Results showed that the V-shaped canopy was more favorable for the accumulation of flavonoids and phenolic acids. Transcriptome and metabolome analyses revealed that the differentially expressed genes (DEGs) and differentially regulated metabolites (DRMs) were significantly enriched in the flavonoid and phenylpropanoid biosynthesis pathways. A total of 96 flavonoids and 32 phenolic acids were detected among the DRMs. Their contents were higher in the V-shaped canopy than in the T-shaped and VSP canopies. Conjoint analysis of transcriptome and metabolome showed that nine DEGs (e.g., cytochrome P450 98A9 and 98A2) were significantly correlated to nine phenolic acids (e.g., gentisic acid and neochlorogenic acid) and three genes (i.e., chalcone isomerase, UDP-glycosyltransferase 88A1, and caffeoyl-CoA O-methyltransferase) significantly correlated to 15 flavonoids (e.g., baimaside and tricin-7-O-rutinoside). These genes may be involved in the regulation of various flavonoids and phenolic acids in grape berries, but their functions need validation. This study provides novel insights into the effects of leaf canopy on flavonoids and phenolic acids in the skin of grape berries and reveals the potential regulatory networks involved in this phenomenon.PMID:36596135 | DOI:10.1016/j.foodres.2022.112196
Metabolomics during the spontaneous fermentation in cocoa (Theobroma cacao L.): An exploraty review
Food Res Int. 2023 Jan;163:112190. doi: 10.1016/j.foodres.2022.112190. Epub 2022 Nov 19.ABSTRACTSpontaneous fermentation is a process that depends on substrates' physical characteristics, crop variety, and postharvest practices; it induces variations in the metabolites that are responsible for the taste, aroma, and quality. Metabolomics makes it possible to detect key metabolites using chemometrics and makes it possible to establish patterns or identify biomarker behaviors under certain conditions at a given time. Therefore, sensitive and highly efficient analytical techniques allow for studying the metabolomic fingerprint changes during fermentation; which identify and quantify metabolites related to taste and aroma formation of an adequate processing time. This review shows that studying metabolomics in spontaneous fermentation permits the characterization of spontaneous fermentation in different stages. Also, it demonstrates the possibility of modulating the quality of cocoa by improving the spontaneous fermentation time (because of volatile aromatic compounds formation), thus standardizing the process to obtain attributes and quality that will later impact the chocolate quality.PMID:36596129 | DOI:10.1016/j.foodres.2022.112190
UHPLC-QTOF-MS-based untargeted metabolomics and mineral element analysis insight into the geographical differences of Chrysanthemum morifolium Ramat cv. "Hangbaiju" from different origins
Food Res Int. 2023 Jan;163:112186. doi: 10.1016/j.foodres.2022.112186. Epub 2022 Nov 18.ABSTRACTChrysanthemum morifolium Ramat cv. "Hangbaiju" (HBJ), known as one of the "eight flavors of Zhejiang", is commonly used as a classical tea material for both food and medicine over three thousand years in China. The quality of HBJ is closely related to its geographical origins. However, the mechanism underlying the geographical differences of HBJ remains to be elucidated. In this study, an untargeted metabolomic strategy based on UHPLC-QTOF-MS was established to discover the differential metabolites in HBJ samples from four different origins and explore the possible relationship with mineral elements in planting soils by chemometric analysis. Eight compounds were screened and identified as the key differential metabolites in HBJ samples from different origins. Among them, four important pharmacodynamic compounds including L-arginine, rutin, chlorogenic acid and apigenin-7-O-glucoside are the most abundant in HBJ samples from Tongxiang region, which suggests that HBJ planted in Tongxiang has higher medicinal values. Pearson correlation analysis revealed that the contents of soil mineral elements are positively correlated with those of chlorogenic acid, rutin, apigenin-7-O-glucoside in HBJ samples. Furthermore, an interrelationship model based on random forest algorithm was established to successfully predict the contents of differential metabolites in HBJ samples by soil mineral elements. All these results indicated that the contents of differential metabolites in HBJ samples seemed to be affected by soil mineral elements and therefore resulted in the geographical differences of HBJ.PMID:36596127 | DOI:10.1016/j.foodres.2022.112186
Diet-rich in wheat bran modulates tryptophan metabolism and AhR/IL-22 signalling mediated metabolic health and gut dysbacteriosis: A novel prebiotic-like activity of wheat bran
Food Res Int. 2023 Jan;163:112179. doi: 10.1016/j.foodres.2022.112179. Epub 2022 Nov 19.ABSTRACTTryptophan metabolism has shown to involve in pathogenesis of various metabolic diseases. Gut microbiota-orientated diets hold great potentials to improve metabolic health via regulating tryptophan metabolism. The present study showed that the 6-week high fat diet (HFD) disturbed tryptophan metabolism accompanied with gut dysbacteriosis, also influenced the dietary tryptophan induced changes in cecum microbiome and serum metabolome in mice. The colonic expressions of aryl hydrocarbon receptor (AhR) and interleukin-22 (IL-22) were significantly reduced in mice fed on HFD. Notably, a diet- rich in wheat bran effectively inhibited transformation of tryptophan to kynurenine-pathway metabolites, while increased melatonin and microbial catabolites, i.e. indole-3-propionic acid, indole-3-acetaldehyde and 5-hydroxy-indole-3-acetic acid. Such regulatory effects were accompanied with reduced fasting glucose and total triglycerides, and promoted AhR and IL-22 levels in HFD mice. Wheat bran increased the abundance of health promoting bacteria (e.g., Akkermansia and Lactobacillus), which were significantly correlated with tryptophan derived indolic metabolites. Additionally, beneficial modulatory effects of wheat bran on indolic metabolites in associations with gut dysbacteriosis from type 2 diabetes patients were confirmed in vitro fecal fermentation experiment. Our study proves the detrimental effects of HFD induced gut dysbacteriosis on tryptophan metabolism that may influence immune modulation, and provides novel insights in the mechanisms by which wheat bran could induce health benefits.PMID:36596122 | DOI:10.1016/j.foodres.2022.112179
Integration of metabolomics and transcriptomics analyses investigates the accumulation of secondary metabolites in maturing seed plumule of sacred lotus (Nelumbo nucifera)
Food Res Int. 2023 Jan;163:112172. doi: 10.1016/j.foodres.2022.112172. Epub 2022 Nov 25.ABSTRACTLotus seed plumule (LP) is rich in a variety of antioxidant and anti-inflammatory secondary metabolites, making it a traditional food and medicine widely used in China. Physiological and histological evidences indicated that LP mainly accumulated metabolites in 15-24 days after pollination (DAP) during their development. To systematically investigate the dynamic accumulation of major secondary metabolites, the UPLC-HRMS-based widely targeted metabolomics analyses were performed on maturing LP at 15, 18, 21, and 24 DAP. In total, 767 metabolites were identified, including many secondary metabolites, e.g., 27 % flavonoids and 8 % alkaloids. Among them, 591 were identified as differentially accumulated metabolites (DAMs). The majority of secondary metabolites showed great accumulation after 18 DAP even at the late stage of LP maturation, such as hesperidin, neohesperidin, orobol, serotonin, and lotus special O-nornuciferine, endowing mature LP with effective pharmaceutical properties. The paralleled transcriptomic analysis identified 11,019 differentially expressed genes (DEGs). Based on the comprehensive data, several systematical metabolic regulation maps were established for different secondary metabolites, and 18 DAP was found as a switching point for LP maturing from active primary metabolism to massive secondary metabolites deposition. This study provides valuable information for understanding the mechanism of secondary metabolite accumulation in maturing LP and facilitates its pharmaceutical application.PMID:36596118 | DOI:10.1016/j.foodres.2022.112172
Landscape of lipidomics in cardiovascular medicine from 2012 to 2021: A systematic bibliometric analysis and literature review
Medicine (Baltimore). 2022 Dec 30;101(52):e32599. doi: 10.1097/MD.0000000000032599.ABSTRACTLipidomics has shaped our knowledge of how lipids play a central role in cardiovascular diseases (CVD), whereas there is a lack of a summary of existing research findings. This study performed a bibliometric analysis of lipidomics research in cardiovascular medicine to reveal the core countries, institutions, key researchers, important references, major journals, research hotspots and frontiers in this field. From 2012 to 2021, a total of 761 articles were obtained from the Web of Science Core Collection database. There is a steady increase of publications yearly. The United States and China are on the top of the list regarding article output. The institutions with the most publications were the Baker Heart and Diabetes Institute, the Chinese Academy of Sciences and Harvard Medical School. Peter J Meikle was both the most published and most co-cited author. The major journal in this field is Journal of lipid research. Keyword co-occurrence analysis indicated that coronary heart disease, mass spectrometry, risk, fatty acid, and insulin resistance have become hot topics in this field and keyword burst detection suggests that metabolomics, activation, liver, low density lipoprotein are the frontiers of research in recent years. Collectively, lipidomics in CVD is still in its infancy with a steady increase yearly. More in-depth studies in this area are warranted in the future.PMID:36596038 | DOI:10.1097/MD.0000000000032599
Unknown Metabolite Identification Using Machine Learning Collision Cross-Section Prediction and Tandem Mass Spectrometry
Anal Chem. 2023 Jan 3. doi: 10.1021/acs.analchem.2c03749. Online ahead of print.ABSTRACTIon mobility (IM) spectrometry provides semiorthogonal data to mass spectrometry (MS), showing promise for identifying unknown metabolites in complex non-targeted metabolomics data sets. While current literature has showcased IM-MS for identifying unknowns under near ideal circumstances, less work has been conducted to evaluate the performance of this approach in metabolomics studies involving highly complex samples with difficult matrices. Here, we present a workflow incorporating de novo molecular formula annotation and MS/MS structure elucidation using SIRIUS 4 with experimental IM collision cross-section (CCS) measurements and machine learning CCS predictions to identify differential unknown metabolites in mutant strains of Caenorhabditis elegans. For many of those ion features, this workflow enabled the successful filtering of candidate structures generated by in silico MS/MS predictions, though in some cases, annotations were challenged by significant hurdles in instrumentation performance and data analysis. While for 37% of differential features we were able to successfully collect both MS/MS and CCS data, fewer than half of these features benefited from a reduction in the number of possible candidate structures using CCS filtering due to poor matching of the machine learning training sets, limited accuracy of experimental and predicted CCS values, and lack of candidate structures resulting from the MS/MS data. When using a CCS error cutoff of ±3%, on average, 28% of candidate structures could be successfully filtered. Herein, we identify and describe the bottlenecks and limitations associated with the identification of unknowns in non-targeted metabolomics using IM-MS to focus and provide insights into areas requiring further improvement.PMID:36595469 | DOI:10.1021/acs.analchem.2c03749
From 'Omics to Multi-omics Technologies: the Discovery of Novel Causal Mediators
Curr Atheroscler Rep. 2023 Jan 3. doi: 10.1007/s11883-022-01078-8. Online ahead of print.ABSTRACTPURPOSE OF REVIEW: 'Omics studies provide a comprehensive characterisation of a biological entity, such as the genome, epigenome, transcriptome, proteome, metabolome, or microbiome. This review covers the unique properties of these types of 'omics and their roles as causal mediators in cardiovascular disease. Moreover, applications and challenges of integrating multiple types of 'omics data to increase predictive power, improve causal inference, and elucidate biological mechanisms are discussed.RECENT FINDINGS: Multi-omics approaches are growing in adoption as they provide orthogonal evidence and overcome the limitations of individual types of 'omics data. Studies with multiple types of 'omics data have improved the diagnosis and prediction of disease states and afforded a deeper understanding of underlying pathophysiological mechanisms, beyond any single type of 'omics data. For instance, disease-associated loci in the genome can be supplemented with other 'omics to prioritise causal genes and understand the function of non-coding variants. Alternatively, techniques, such as Mendelian randomisation, can leverage genetics to provide evidence supporting a causal role for disease-associated molecules, and elucidate their role in disease pathogenesis. As technologies improve, costs for 'omics studies will continue to fall and datasets will become increasingly accessible to researchers. The intrinsically unbiased nature of 'omics data is well-suited to exploratory analyses that discover causal mediators of disease, and multi-omics is an emerging discipline that leverages the strengths of each type of 'omics data to provide insights greater than the sum of its parts.PMID:36595202 | DOI:10.1007/s11883-022-01078-8
Untargeted metabolomics to evaluate antifungal mechanism: a study of Cophinforma mamane and Candida albicans interaction
Nat Prod Bioprospect. 2023 Jan 3;13(1):1. doi: 10.1007/s13659-022-00365-w.ABSTRACTMicrobial interactions between filamentous fungi and yeast are still not fully understood. To evaluate a potential antifungal activity of a filamentous fungus while highlighting metabolomic changes, co-cultures between an endophytic strain of Cophinforma mamane (CM) and Candida albicans (CA) were performed. The liquid cultures were incubated under static conditions and metabolite alterations during the course were investigated by ultra-performance liquid chromatography-tandem mass spectrophotometry (UPLC-MS/MS). Results were analyzed using MS-DIAL, MS-FINDER, METLIN, Xcalibur, SciFinder, and MetaboAnalyst metabolomics platforms. The metabolites associated with catabolic processes, including the metabolism of branched-chain amino acids, carnitine, and phospholipids were upregulated both in the mono and co-cultures, indicating fungal adaptability to environmental stress. Several metabolites, including C20 sphinganine 1-phosphate, myo-inositol, farnesol, gamma-undecalactone, folinic acid, palmitoleic acid, and MG (12:/0:0/0:0) were not produced by CA during co-culture with CM, demonstrating the antifungal mechanism of CM. Our results highlight the crucial roles of metabolomics studies to provide essential information regarding the antifungal mechanism of C. mamane against C. albicans, especially when the lost/undetected metabolites are involved in fungal survival and pathogenicity.PMID:36595109 | DOI:10.1007/s13659-022-00365-w
Asperosaponin VI Protects Against Bone Loss Due to Hindlimb Unloading in Skeletally Growing Mice Through Regulating Microbial Dysbiosis Altering the 5-HT Pathway
Calcif Tissue Int. 2023 Jan 3. doi: 10.1007/s00223-022-01057-w. Online ahead of print.ABSTRACTOsteoporosis is a complex multifactorial disease that can lead to an increased risk of fracture. However, selective and effective osteoporosis drugs are still lacking. We showed that Asperosaponin VI (AVI) has the implications to be further developed as an alternative supplement for the prevention and treatment of bone loss. AVI has been found to have beneficial effects on metabolic diseases such as bone loss, obesity, and atherosclerosis. Our study was designed to determine the effect and mechanism of action of AVI against bone loss through regulating microbial dysbiosis. A hindlimb unloading mouse model was established to determine the effect of AVI on bone microarchitecture, gut microbiota, and serum metabolites. Eighteen female C57BL/6 J mice were divided into three groups: control, hindlimb unloading with vehicle (HLU), and hindlimb unloading treated with AVI (HLU-AVI, 200 mg/kg/day). AVI was administrated orally for 4 weeks. The results demonstrated that AVI improved the bone microstructure by reversing the decrease in bone volume fraction and trabecular number, and the increase in trabecular separation and structure model index of cancellous bone in hindlimb suspension mice. The results of 16sRNA gene sequencing suggested that the therapeutic effect of AVI on bone loss may be achieved through it regulating the gut microbiota, especially certain specific microorganisms. Combined with the analysis of ELISA, immunohistochemistry, and serum metabolome results, it could be speculated that AVI played an important role in adjusting the balance of bone metabolism by influencing specific flora such as Clostridium and its metabolites to regulate the 5-hydroxytryptophan pathway. The study explored the novel mechanism of AVI against osteoporosis, and has implications for the further development of AVI as an alternative supplement for the prevention and treatment of bone loss.PMID:36595050 | DOI:10.1007/s00223-022-01057-w
Lipidomic and Metallomic Alteration of <em>Caenorhabditis elegans</em> after Acute and Chronic Manganese, Iron, and Zinc Exposure with a Link to Neurodegenerative Disorders
J Proteome Res. 2023 Jan 3. doi: 10.1021/acs.jproteome.2c00578. Online ahead of print.ABSTRACTParkinson's disease (PD) progresses with the loss of dopaminergic neurons in the substantia nigra pars compacta region of the brain. The superior mechanisms and the cause of this specific localized neurodegeneration is currently unknown. However, experimental evidence indicates a link between PD progression and reactive oxygen species with imbalanced metal homeostasis. Wild-type Caenorhabditis elegans exposed to redox-active metals was used as the model organism to study cellular response to imbalanced metal homeostasis linked to neurodegenerative diseases. Using modern hyphenated techniques such as capillary electrophoresis coupled to inductively coupled plasma mass spectrometry and ultrahigh-performance liquid chromatography mass spectrometry, alterations in the lipidome and metallome were determined in vivo. In contrast to iron, most of the absorbed zinc and manganese were loosely bound. We observed changes in the phospholipid composition for acute iron and manganese exposures, as well as chronic zinc exposure. Furthermore, we focused on the mitochondrial membrane alteration due to its importance in neuronal function. However, significant changes in the inner mitochondrial membrane by determination of cardiolipin species could only be observed for acute iron exposure. These results indicate different intracellular sites of local ROS generation, depending on the redox active metal. Our study combines metallomic and lipidomic alterations as the cause and consequence to enlighten intracellular mechanisms in vivo, associated with PD progression. The mass spectrometry raw data have been deposited to the MassIVE database (https://massive.ucsd.edu) with the identifier MSV000090796 and 10.25345/C51J97C8F.PMID:36594972 | DOI:10.1021/acs.jproteome.2c00578
Mass spectrometry-based quantitation combined with time-dependent metabolomics to discover metabolic features in human neurogenesis using neural constructs generated from neural progenitor cells
Analyst. 2023 Jan 3. doi: 10.1039/d2an01162j. Online ahead of print.ABSTRACTDirect studies focusing on the human brain are difficult to plan and conduct due to ethical and practical reasons. The advent of human pluripotent stem cell (hPSC)-derived neurons has revolutionized the research of the human brain and central nervous system, but relevant analytical techniques have been much less explored. Herein, we have designed a novel bioanalytical strategy to discover the characteristics of human neurogenesis using liquid chromatography-mass spectrometry-based quantitation and time-dependent metabolomics in combination with hPSC-derived neural constructs. To examine the growth of neurons in vitro, a quantitative method for the simultaneous measurement of N-acetylaspartic acid (NAA) and N-acetylglutamic acid (NAG) in a culture medium was established. The analysis of endogenous NAA and NAG concentrations over 28 days of neural cell culture not only illustrated the growth and maturation process of neural progenitors, but also confirmed the successful achievement of human neural constructs. Depending on the quantitative results, day 0, 10, 18, and 28 samples representing different growth phases were selected for further investigation of the global metabolic changes in developing human neurons. A versatile non-targeted, time-dependent metabolomics study identified 17 significantly changed metabolites and revealed the altered metabolic pathways including amino acid metabolism (tryptophan, phenylalanine, aspartate and beta-alanine metabolisms), pantothenate and coenzyme A biosynthesis, fatty acid metabolism, and purine and pyrimidine metabolism. The new metabolite profiles and overall metabolic pathways advance our understanding of human neurodevelopment. Additionally, the bioanalytical approach proposed in this study opens an interesting window for the capture and evaluation of the complex metabolic states of human neural cells, which would potentially be utilized in other in vitro models relevant to pathophysiology and treatment of neurological disorders, benefiting biomarker discovery and metabolic mechanism interpretation.PMID:36594636 | DOI:10.1039/d2an01162j
<em>Bifidobacterium animalis</em> subsp. <em>lactis</em> BL-99 ameliorates colitis-related lung injury in mice by modulating short-chain fatty acid production and inflammatory monocytes/macrophages
Food Funct. 2023 Jan 3. doi: 10.1039/d2fo03374g. Online ahead of print.ABSTRACTPulmonary inflammation as one of the extraintestinal manifestations of ulcerative colitis (UC) has attracted extensive attention, and its pathogenesis is closely related to gut dysbiosis. Bifidobacterium animalis subsp. lactis BL-99 (BL-99) can alleviate osteoporosis caused by UC, but less research has been done on other extraintestinal manifestations (EIM) caused by UC. This study aimed to explore the role and potential mechanisms of BL-99 on DSS-induced pulmonary complications in colitis mice. The results showed that BL-99 decreased weight loss, disease activity index score, colonic pathology score, and the production of pro-inflammatory cytokines (e.g., TNF-α, IL-1β, and IL-6) in colitis mice. BL-99 also alleviated DSS-induced lung pathological damage by suppressing the infiltration of pro-inflammatory cytokines, inflammatory monocytes, and macrophages. Furthermore, 16S rRNA gene sequencing showed lower abundances of several potentially pathogenic bacteria (e.g., Burkholderia, Shigella, and Clostridium perfringens) and enrichment in specific beneficial bacteria (e.g., Adlercreutzia and Bifidobacterium animalis) in colitis mice with BL-99 treatment. Targeted metabolomics suggested that BL-99 intervention promoted the production of intestinal acetate and butyrate. Finally, we observed that the pulmonary expression of primary acetate and butyrate receptors, including FFAR2, FFAR3, and, GPR109a, was up-regulated in BL-99-treated mice, which negatively correlated with inflammatory monocytes and macrophages. Altogether, these results suggest that BL-99 might be utilized as a probiotic intervention to prevent the incidence of colitis-related lung injury owing to its ability to shape the intestinal microbiota and suppress inflammation.PMID:36594489 | DOI:10.1039/d2fo03374g
Sex-inducing effects toward planarians widely present among parasitic flatworms
iScience. 2022 Dec 8;26(1):105776. doi: 10.1016/j.isci.2022.105776. eCollection 2023 Jan 20.ABSTRACTVarious parasitic flatworms infect vertebrates for sexual reproduction, often causing devastating diseases in their hosts. Consequently, flatworms are of great socioeconomic and biomedical importance. Although the cessation of parasitic flatworm sexual reproduction is a major target of anti-parasitic drug design, little is known regarding bioactive compounds controlling flatworm sexual maturation. Using the planarian Dugesia ryukyuensis, we observed that sex-inducing substances found in planarians are also widespread in parasitic flatworms, such as monogeneans and flukes (but not in tapeworms). Reverse-phase HPLC analysis revealed the sex-inducing substance(s) eluting around the tryptophan retention time in the fluke Calicophoron calicophorum, consistent with previous studies on the planarian Bipalium nobile, suggesting that the substance(s) is likely conserved among flatworms. Moreover, six of the 18 ovary-inducing substances identified via transcriptome and metabolome analyses are involved in purine metabolism. Our findings provide a basis for understanding and modifying the life cycles of various parasitic flatworms.PMID:36594009 | PMC:PMC9804148 | DOI:10.1016/j.isci.2022.105776
Pre-clinical Investigations of Therapeutic Markers Associated with Acute and Chronic Restraint Stress: A Nuclear Magnetic Resonance Based Contrast Metabolic Approach
Nanotheranostics. 2023 Jan 1;7(1):91-101. doi: 10.7150/ntno.76294. eCollection 2023.ABSTRACTStress can be defined by two parameters, first the psychological sensing of pressure and second is the body's response. However, the exposure time to stress depicts the biological response produced against it. The effect of acute and chronic restraint stress on anxiety and the production of systemic metabolites were investigated in male Sprague-Dawley (SD) rats. Behavioural test was performed on elevated plus maze (EPM) in conjunction with the statistical analysis that exhibited the habituation during long term exposure to stress when compared with the short-term stress. These behaviour-based changes resulted in interpolated concentration of some serum metabolites like carbohydrates, amino acids and lipids as analysed by NMR. Metabolic analysis along with the multivariate analysis demonstrated that the expression of concentration of metabolites including glutamate, proline, succinate, citrate, and tyrosine is higher in the acute stress than the chronic stress, while glucose and lipids i.e., LDL and VLDL changed in the opposite trends. Thus, the aforesaid study provides an analytical strategy for the characterization of perturbed metabolites induced due to the behavioural modifications in an organism. It may further aid in developing potential therapeutic markers at the metabolic levels which may broaden the treatment options for stress and anxiety related disorders.PMID:36593795 | PMC:PMC9760362 | DOI:10.7150/ntno.76294