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This review presents advances in the implementation of high - throughput se quencing and its application to the knowledge of medicinal plants. We conducted a bibliographic search of papers published in PubMed, Science Direct, Google Scholar, Scopus, and Web of Science databases and analyzed the obtained data using VOSviewer (versi on 1.6.19). Given that medicinal plants are a source of specialized metabolites with immense therapeutic values and important pharmacological properties, plant researchers around the world have turned their attention toward them and have begun to examine t hem widely. Recent advances in sequencing technologies have reduced cost and time demands and accelerated medicinal plant research. Such research leverages full genome sequencing, as well as RNA (ribonucleic acid) sequencing and the analysis of the transcr iptome, to identify molecular markers of species and functional genes that control key biological traits, as well as to understand the biosynthetic pathways of bioactive metabolites and regulatory mechanisms of environmental responses. As such, the omics ( e.g., transcriptomics, metabolomics, proteomics, and genomics, among others) have been widely applied within the study of medicinal plants, although their usage in Colombia is still few and, in some areas, scarce. (185)
El extracto de cloroformo (CE) y las fracciones obtenidas de las raíces de Aldama arenaria se evaluaron para determinar su actividad antiproliferativa in vitro contra 10 líneas ce lulares tumorales humanas [leucemia (K - 562), mama (MCF - 7), ovario que expresa un fenotipo resistente a múltiples fármacos (NCI/ADR - RES), melanoma (UACC - 62), pulmón (NCI - H460), próstata (PC - 3), colon (HT29), ovario (OVCAR - 3), glioma (U251) y riñón (786 - 0)]. CE presentó actividad antiproliferativa débil a moderada (log GI 50 medio 1.07), mientras que las fracciones 3 y 4, enriquecidas con diterpenos de tipo pimarane [ent - pimara - 8 (14), ácido 15 - dien - 19 - oico y ent - 8(14),15 - pimaradien - 3 ß - ol], presentaron activid ad moderada a potente para la mayoría de las líneas celulares, con un log GI 50 medio de 0.62 y 0.59, respectivamente. Los resultados mostraron una acción antiproliferativa in vitro prometedora de las muestras obtenidas de A. arenaria , con los mejores resul tados para NCI/ADR - RES, HT29 y OVCAR - 3, y valores de TGI que van desde 5.95 a 28.71 µg.mL - 1, demostrando que los compuestos de esta clase pueden ser prototipos potenciales para el descubrimiento de nuevos agentes terapéuticos
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Plants, Medicinal , Colombia , MultiomicsABSTRACT
ABSTRACT Objective: To identify the salivary metabolites profile of Mucopolysaccharidosis (MPS) types I, II, IV, and VI patients. Material and Methods: The participants were asked to refrain from eating and drinking for one hour before sampling, performed between 7:30 and 9:00 a.m. Samples were centrifuged at 10.000 × g for 60 min at 4°C, and the supernatants (500µl) were stored at −80°C until NMR analysis. The salivary proton nuclear magnetic resonance (1H-NMR) spectra were acquired in a 500 MHz spectrometer, and TOCSY experiments were used to confirm and assign metabolites. Data were analyzed descriptively. Results: Differences in salivary metabolites were found among MPS types and the control, such as lactate, propionate, alanine, and N-acetyl sugar. Understanding these metabolite changes may contribute to precision medicine and early detection of mucopolysaccharidosis and its monitoring. Conclusion: The composition of low molecular weight salivary metabolites of mucopolysaccharidosis subjects may present specific features compared to healthy controls.
Subject(s)
Humans , Male , Female , Saliva , Magnetic Resonance Spectroscopy/instrumentation , Mucopolysaccharidoses/pathology , Metabolomics , Proton Magnetic Resonance Spectroscopy/instrumentation , Cross-Sectional Studies/methodsABSTRACT
ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry（UPLC-Q-TOF-MS）， to evaluate the establishment of a mouse model of liver Yin deficiency by thyroid tablet suspension combined with 10% carbon tetrachloride（CCl4） from the perspective of non-targeted metabolomics， in order to lay the foundation for the establishment of a traditional Chinese medicine（TCM） syndrome model. MethodA total of 24 mice were randomly divided into blank group and model group. The model group was given thyroid tablet suspension（0.003 2 g·kg-1） by gavage for 14 consecutive days， and 10% CCl4（5 mL·kg-1） was intraperitoneally injected once a week to establish a liver Yin deficiency model， while the blank group was injected with an equal amount of olive oil intraperitoneally and gavaged with an equal amount of distilled water， and was fed with normal feed. After the modeling was completed， 6 mice in each group were randomly selected， the levels of alanine aminotransferase（ALT）， aspartate aminotransferase（AST）， cyclic adenosine monophosphate（cAMP）， cyclic guanosine monophosphate（cGMP）， interleukin（IL）-6， IL-10， tumor necrosis factor-α（TNF-α）were measured in the mice serum， and malondialdehyde（MDA）， superoxide dismutase（SOD）， total protein（TP）， hydroxyproline（HYP） and other indicators were measured in the mice liver. Liver tissue sections were taken for hematoxylin-eosin（HE） staining and observing pathological changes. The remaining 6 mice in each group were subjected to UPLC-Q-TOF-MS combined with principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were used to screen differential metabolites in the liver Yin deficiency mouse model， Kyoto Encyclopedia of Genes and Genomes（KEGG） database was used to analyze the corresponding metabolic pathways of differential metabolites. ResultCompared with the blank group， mice in the model group showed liver Yin deficiency manifestations such as reduced body weight， fatigue and sleepiness， disheveled and lusterless hair， irritability. The levels of ALT， cAMP/cGMP， IL-6， AST， MDA， cAMP， TNF-α significantly increased（P<0.05， P<0.01）， while the levels of SOD， IL-10 and cGMP significantly decreased（P<0.05， P<0.01）， and the changes of HYP and TP were not statistically significant. Hepatic steatosis and distortion of the radial arrangement of the liver plate cells were seen in the section images of the model group， endogenous substances were clearly separated， and 252 differential metabolites were identified in the serum samples， which were mainly involved in the metabolic pathways of purine metabolism， steroid hormone biosynthesis and pyrimidine metabolism. A total of 229 differential metabolites were identified in the liver samples， mainly involving nucleotide metabolism， purine metabolism， steroid hormone biosynthesis， pyrimidine metabolism， antifolate resistance， insulin resistance， primary bile acid biosynthesis， prostate cancer， sulfur relay system， arachidonic acid metabolism and other metabolic pathways. ConclusionThe successful establishment of liver Yin deficiency model in mice by CCl4 combined with thyroid hormone is evaluated through the investigation of serum and liver metabolomics， combined with biochemical indicators， which provides a biological basis and experimental foundation for the Yin deficiency syndrome model of TCM.
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ObjectiveMetabolomics was used to reveal the mechanism of Aconiti Lateralis Radix Praeparata（ALRP） in attenuating toxicity by processing from the aspects of amino acid metabolism， oxidative stress and energy metabolism by analyzing multiple metabolic pathways. MethodTwenty-four rats were randomly divided into control group， raw group and processed group， 8 rats in each group. The raw and processed group were given with 0.64 g·kg-1 of raw ALRP and processed ALRP respectively every day， the control group was given with an equal amount of normal saline once a day. After continuous administration for 7 days， the urine， serum and heart tissue of rats were collected. Pathological examination of the heart was carried out using hematoxylin-eosin（HE） staining， and the activities of lactate dehydrogenase（LDH） and creatine kinase-MB（CK-MB） in serum and cardiac tissues were detected by microplate assay and immunoinhibition assay. The effects of ALRP on rat heart before and after processing were compared and analyzed. Ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） was used to perform urine metabolomics analysis， and multivariate statistical analysis was used to screen for differential metabolites related to ALRP in attenuating toxicity by processing， and pathway enrichment analysis was carried out to explore the processing mechanism. ResultHE staining showed that no obvious pathological changes were observed in the heart tissue of the control group， while obvious infiltration of inflammatory cells such as plasma cells and granulocytes was observed in the heart tissue of the raw group， indicating that the raw ALRP had strong cardiotoxicity. There was no significant difference in HE staining of heart tissue between the processed group and the control group， indicating that the toxicity of ALRP was significantly reduced after processing. Compared with the control group， the activities of LDH and CK-MB were significantly increased in serum and heart tissue of the raw group， and those were significantly decreased in serum and heart tissue of the processed group， suggesting that the myocardial toxicity of processed ALRP was reduced. A total of 108 endogenous differential metabolites associated with the raw ALRP were screened using multivariate statistical analysis in positive and negative modes， of which 51 differential metabolites were back-regulated by the processed ALRP. Biological analysis of the key regulatory pathways and associated network changes showed that the pathways related to toxicity of ALRP mainly included tryptophan metabolism， arginine and proline metabolism， phenylalanine metabolism， aminoacyl-tRNA biosynthesis， alanine， aspartate and glutamate metabolism， etc. The metabolic pathways related to the attenuation of processed ALRP mainly included aminoacyl-tRNA biosynthesis， tryptophan metabolism， phenylalanine， tyrosine and tryptophan biosynthesis， phenylalanine metabolism and caffeine metabolism. ConclusionThe processing technology of ALRP in Guilingji can significantly attenuate the cardiotoxicity of raw products， the mechanism mainly involves amino acid metabolism， oxidative stress and energy metabolism， which can provide experimental bases for the research related to the mechanism of toxicity reduction of ALRP by processing and its clinical safety applications.
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OBJECTIVE To study the effects of the Mongolian medicine Sugemule-4 on the metabolism of insomnia rats， and to preliminarily explore its possible mechanisms for improving insomnia. METHODS The rat model of chronic stress insomnia was established by tail clipping stimulation and intraperitoneal injection of p-chlorophenyl alanine solution. Twenty-four male rats were randomly divided into the normal group， model group， diazepam group （positive control， 0.92 mg/kg）， and Sugemule-4 group （5.2 g/kg）， with 6 rats in each group. Since the 7th day of tail clipping stimulation， the Sugemule-4 group and diazepam group began to be intragastrically administered with relevant medicine； the normal group and model group were intragastrically administered with an equal volume of distilled water， once a day， for 14 consecutive days. The learning and memory abilities of rats were tested using a water maze experiment， and the non-invasive sleep activity monitoring system was used to monitor the 24- hour sleep time of rats. A metabolomics study was conducted on rat serum and hippocampal tissue by using ultra-high-performance liquid chromatography-tandem mass spectrometry. The multivariate statistical analysis method was adopted to analyze the differential metabolites in serum and hippocampal tissue of rats， and screen for differential metabolites and metabolic pathways among those groups. RESULTS Compared with the normal group， the escape latency of rats in the model group was significantly increased， the times of crossing platforms were significantly reduced， and the percentage of average 24-hour sleep time was significantly reduced （P＜0.05）. Compared with the model group， the levels of the above indicators were significantly reversed in the diazepam group and Sugemule-4 group （P＜0.05）. Metabolomics studies found that a total of 9 differential metabolites were identified in rat serum and hippocampal tissue， including 5-hydroxyindoleacetic acid， canine urate， canine urinary quinolinic acid， 5-hydroxytryptamine， phenol sulfate， 1-carboxyethyltyrosine， 3-（4-hydroxyphenyl） lactate， N-acetyl tyrosine， tyrosine and phenol sulfate， mainly involving 2 metabolic pathways of tryptophan and tyrosine.CONCLUSIONS Sugemule-4 can improve the sleep time and behavioral performance of insomnia rats， and its mechanism may be associated with affecting amino acid metabolic pathways such as tryptophan and tyrosine.
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ObjectiveBased on ultra performance liquid chromatography-mass spectrometry（UPLC-MS） and non-targeted metabolomics technology to discuss the central regulatory effect of Chaishao Liujuntang on chronic atrophic gastritis（CAG） rats with liver-depression and spleen-deficiency， and to look for the correlation between cerebral cortex， hypothalamus and metabolic status of gastric tissues. MethodA CAG rat model with liver-depression and spleen-deficiency was established by chemical induction， hunger and satiety disorders， chronic restraint and tail clamping stimulation， lasting for 16 weeks. Twenty-eight Wistar rats were randomly divided into a blank group of 8 rats and a model group of 20 rats. After the completion of modeling， 4 rats in the model group were taken to observe the pathological changes of gastric mucosa. The remaining model rats were randomly divided into a model group of 8 rats and a Chaishao Liujuntang group of 8 rats. Chaishao Liujuntang group rats were given 5.1 g·kg-1 by gavage， and the remaining rats were given equal volume sterilized water by gavage for 4 weeks. Macroscopic characteristics， behavioral indicators and histopathological changes of the gastric mucosa of rats in each group were observed and compared. UPLC-MS non-targeted metabolomics was used to explore the metabolic regulation effect of Chaishao Liujuntang on the cerebral cortex， hypothalamus and stomach tissues of CAG rats with liver-depression and spleen-deficiency. Pearson correlation coefficient method was used to analyze the correlation between different tissue metabolites. ResultCompared with the model group， the macroscopic characteristics of rats in Chaishao Liujuntang group were improved， such as hair color， mental state and stool properties， and the number of times of crossing and standing in the open field experiment was significantly increased， and the static time of forced swimming was significantly reduced（P<0.01）， and the gastric mucosa atrophy was reduced. The metabolic data from the cerebral cortex of rats in each group identified a total of 3 common potential biomarkers， but not enriched in pathways， 26 common potential biomarkers were identified in the hypothalamus， and the key metabolic pathways involved were mainly enriched in purine metabolism， glycerol phospholipid metabolism， D-glutamine and D-glutamic acid metabolism. Seventeen common potential biomarkers were identified in the stomach， and the key metabolic pathways involved were mainly enriched in thiamine metabolism， valine， leucine and isoleucine biosynthesis， and taurine and taurine metabolism. Correlation analysis of metabolites in different tissues revealed that multiple amino acids and their derivatives mediated metabolic connections between the cerebral cortex， hypothalamus and stomach of rats. ConclusionThe metabolic disorders in the cerebral cortex， hypothalamus and stomach of CAG rats with liver-depression and spleen-deficiency have their own characteristics， mainly manifested by changes in the content of glycerol phospholipids， fatty acids and bile acid metabolites. Moreover， Chaishao Liujuntang may play a central regulatory role in CAG rats with liver-depression and spleen-deficiency by correcting the metabolic disorders of amino acids.
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ObjectiveTo investigate the effects of Jiaohong pills （JHP） and its prescription， Pericarpium Zanthoxyli （PZ） and Rehmanniae Radix （RR） cognitive dysfunction in scopolamine-induced Alzheimer's disease （AD） mice and its mechanism through pharmacodynamic and metabolomics study. MethodThe animal model of AD induced by scopolamine was established and treated with PZ， RG and JHP， respectively. The effects of JHP and its formulations were investigated by open field test， water maze test， object recognition test， avoidance test， cholinergic system and oxidative stress related biochemical test. Untargeted metabolomics analysis of cerebral cortex was performed by ultra-performance liquid chromatography-Quadrupole/Orbitrap high resolution mass spectrometry （UPLC Q-Exactive Orbitrap MS）. ResultThe behavioral data showed that， compared with the model group， the discrimination indexes of the high dose of JHP， PZ and RR groups was significantly increased （P<0.05）. The staging rate of Morris water maze test in the PZ， RR， high and low dose groups of JHP was significantly increased （P<0.05， P<0.01）， the crossing numbers in the PZ， JHP high and low dose groups were significantly increased （P<0.05， P<0.01）； the number of errors in the avoidance test were significantly reduced in the PZ and high-dose JHP groups （P<0.01）， and the error latencies were significantly increased in the JHP and its prescription drug groups （P<0.01）. Compared with the model group， the activities of acetylcholinesterase in the cerebral cortex of the two doses of JHP group and the PZ group were significantly increased （P<0.05， P<0.01）， and the activity of acetylcholinesterase in the high-dose JHP group was significantly decreased （P<0.05）， and the level of acetylcholine was significantly increased （P<0.01）. At the same time， the contents of malondialdehyde in the serum of the two dose groups of JHP decreased significantly （P<0.05， P<0.01）. The results of metabolomics study of cerebral cortex showed that 149 differential metabolites were identified between the JHP group and the model group， which were involved in neurotransmitter metabolism， energy metabolism， oxidative stress and amino acid metabolism. ConclusionJHP and its prescription can antagonize scopolamine-induced cognitive dysfunction， regulate cholinergic system， and reduce oxidative stress damage. The mechanism of its therapeutic effect on AD is related to the regulation of neurotransmitter， energy， amino acid metabolism， and improvement of oxidative stress.
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Resumen Las novedades en el campo de los errores innatos del metabolismo (EIM) son espectaculares. Se han descrito nuevos EIM, se conoce mejor sus bases fisiopatológicas y las implicaciones para el organismo. Con la llegada de las nuevas técnicas de metabolómica, lípidomica y genómica se han multiplicado los avances en el diag nóstico y permiten explorar nuevas opciones terapéu ticas. Se ha establecido una nueva clasificación de los EIM en base a los más de 1.450 EIM identificados. Está irrumpiendo una nueva especialidad, que es la medici na metabólica. El cribado neonatal se estáempezando a universalizar y nos permite hoy en día, con tándem masas, el diagnóstico de más de 20 enfermedades me tabólicas del período neonatal que tienen opciones de tratamiento. Se están creando unidades de EIM para adultos para seguir niños con EIM que sobreviven a la enfermedad y con cada vez mejor calidad de vida y se diagnostican EIM que debutan en la adolescencia o laedad adulta. Aparecen las terapias personalizadas y las guías de práctica clínica para muchos EIM. Finalmente están emergiendo cada vez nuevas opciones terapéuticas que permiten una mayor supervivencia y mejor calidad de vida. La terapia génica convencional ya se está aplicando en algunos EIM.Sin embargo, las estrategias de edición de genes con terapias de ARN pueden permitir corregir la mutación genética mini mizando los problemas asociados con la terapia génica de compensación convencional.
Abstract The advances in the field of inborn errors of metabo lism (IEM) are spectacular. New IEM have been described, their pathophysiological bases and implications for the organism are better known. With the advent of new metabolomics, lipidomics and genomics techniques, advances in diagnosis have multiplied and allow new therapeutic options to be explored. A new IEM classi fication has been established based on the more than 1.450 IEM identified. A new specialty is emerging, which is metabolic medicine. Neonatal screening is becom ing universal and allows us today, with tandem mass, to diagnose more than 20 metabolic diseases of the neonatal period, with treatment options. IEM units for adults are being created to follow-up children with IEM who survive the disease and with an increasingly better quality of life, and some IEM that start in adolescence or adulthood are diagnosed. Personalized therapies and clinical practice guidelines appear for any IEM. Finally, new therapeutic options are emerging day to day that allow a longer survival and better quality of life. Con ventional gene therapy is already being applied in some IEM. However, gene editing strategies with RNA thera pies may allow the correction of the genetic mutation, minimizing the problems associated with conventional compensation gene therapy.
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With the advancements in analytical and molecular techniques, Dried Blood Spots (DBS) are re-emerging as attractive and cost-effective alternatives for global health surveillance. The use of DBS has been well-characterized in the neonatal screening of metabolic diseases, therapeutic screening as well as in epidemiological studies for biomonitoring. Malaria is one such infectious disease where DBS use can expedite molecular surveillance for assessing drug resistance and for refining drug usage policies. In India, malaria cases have reduced significantly over the past decade but to achieve malaria elimination by 2030, country-wide DBS-based screening should be conducted to identify the presence of molecular markers of artemisinin resistance and to study parasite reservoirs in asymptomatic populations. DBS has wide applications in genomics, proteomics, and metabolomic studies concerning both host and pathogen factors. Hence, it is a comprehensive tool for malaria surveillance that can capture both host and parasite information. In this review, we elucidate the current and prospective role of DBS in malaria surveillance and its applications in studies ranging from genetic epidemiology, parasite and vector surveillance, drug development and polymorphisms to ultimately how they can pave the roadmap for countries aiming malaria elimination
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L-theanine has been shown to have a therapeutic effect on depression.However,whether L-theanine has an excellent preventive effect on depression in children and adolescents and what its mechanism is have not been well explained.Given the complexity of the pathogenesis of depression,this study investigated the preventive effect and mechanism of L-theanine on depression in juvenile rats by combining serum and hippocampal metabolomic strategies.Behavioral tests,hippocampal tissue sections,and serum and hippocampal biochemical indexes were studied,and the results confirmed the preventive effect of L-theanine.Untargeted reversed-phase liquid chromatography-quadrupole-time-of-flight mass spec-trometry and targeted hydrophilic interaction liquid chromatography-triple quadrupole mass spec-trometry were developed to analyze the metabolism changes in the serum and hippocampus to screen for potential biomarkers related to L-theanine treatment.The results suggested that 28 abnormal me-tabolites in the serum and hippocampus that were considered as potential biomarkers returned to near-normal levels after L-theanine administration.These biomarkers were involved in various metabolic pathways,mainly including amino acid metabolism and lipid metabolism.The levels of amino acids and neurotransmitters in the phenylalanine,tryptophan,and glutamic acid pathways were significantly reduced after L-theanine administration compared with chronic unpredictable mild stress-induced rats.In summary,L-theanine had a significant preventive effect on depression and achieved its preventive results on depression by regulating various aspects of the body,such as amino acids,lipids,and inflammation.This research systematically analyzed the mechanism of L-theanine in preventing depression and laid the foundation for applying L-theanine to prevent depression in children and adolescents.
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Improved analytical methods for the metabolomic profiling of tissue samples are constantly needed.Currently,conventional sample preparation methods often involve tissue biopsy and/or homogenization,which disrupts the endogenous metabolome.In this study,solid-phase microextraction(SPME)fibers were used to monitor changes in endogenous compounds in homogenized and intact ovine lung tissue.Following SPME,a Biocrates AbsoluteIDQ assay was applied to make a downstream targeted metab-olomics analysis and confirm the advantages of in vivo SPME metabolomics.The AbsoluteIDQ kit enabled the targeted analysis of over 100 metabolites via solid-liquid extraction and SPME.Statistical analysis revealed significant differences between conventional liquid extractions from homogenized tissue and SPME results for both homogenized and intact tissue samples.In addition,principal component analysis revealed separated clustering among all the three sample groups,indicating changes in the metabolome due to tissue homogenization and the chosen sample preparation method.Furthermore,clear differences in free metabolites were observed when extractions were performed on the intact and homogenized tissue using identical SPME procedures.Specifically,a direct comparison showed that 47 statistically distinct metabolites were detected between the homogenized and intact lung tissue samples(P＜0.05)using mixed-mode SPME fibers.These changes were probably due to the disruptive homogenization of the tissue.This study's findings highlight both the importance of sample preparation in tissue-based metabolomics studies and SPME's unique ability to perform minimally invasive extractions without tissue biopsy or homogenization while providing broad metabolite coverage.
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Myopia has become a global public health concern with its increasing prevalence.It is the interaction result of genetic and environmental factors.Exploration of the changes of metabolites in myopia is helpful to know new clues about its pathogenic mechanism.Metabolomics focuses on the integral analysis of all small molecular metabolites (relative molecular mass <1 000) which form a biological system and it is used as an effective tool to discover potential biomarkers.Metabolomic analysis of the myopic population could discover the metabolic changes related to myopia and screen the markers with potential biological significance, which can be used in the early diagnosis and treatment of myopia.It has been found that metabolites related to oxidative stress and inflammation play an important role in the development of myopia.Abnormal energy metabolism and amino acid metabolism are associated with myopic fundus changes.In addition, classical myopia-associated metabolites such as retinoic acid, dopamine and vitamin D, other metabolites such as melatonin, cyclic adenosine monophosphate and 5-hydroxy indole acetic acid, as well as multiple metabolic pathways such as fatty acid metabolism and mitochondrial metabolism are all closely related to myopia.This article systematically reviewed metabolomics researches on myopia, providing clues for better prevention and control of myopia in the future.
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Community-acquired pneumonia(CAP) is one of the leading causes of death in children under 5 years of age.Early identification and clarification of its severity and appropriate therapeutic measures can improve survival, but there are limitations in the existing laboratory indices applied to diagnose CAP.Therefore, it is still necessary to find new and highly specific biomarkers that can identify the etiology and predict the severity of the disease before it worsens in children, and provides a basis for more effective therapeutic measures.Metabolomics provides a new way to search for biomarkers and pathogenesis through qualitative and quantitative analysis of metabolite changes in biological samples.This review summarized the latest research progress on metabolomics in childhood CAP, hoping to provide ideas for the early diagnosis and treatment of childhood CAP.
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Sepsis is a heterogeneous disease with a complex pathogenesis and diverse clinical manifestations.Sepsis leads to disruption of biochemical homeostasis, which strongly promotes changes in metabolites in the body.Initial differences in metabolites may predict the severity of the disease, and changes in metabolites over time may useful in assessing treatment response, predicting progression of disease progression or clinical outcomes.This review focused on the studies related to the application of metabolomics strategy in sepsis, which could help to understand the potential value of sepsis metabolomics in the pathogenesis, diagnosis, prognosis and treatment of sepsis.
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Objective:To explore the effect of breast feeding versus mixed feeding on fecal metabolites of infants delivered by cesarean section.Methods:This was a cross-sectional study.Fecal samples were collected from 23 healthy 1-month-old infants delivered by cesarean section from autumn 2021 and winter 2022 in two maternal and infant care facilities in the North and South of Xi′an city.The samples were divided into the breast feeding group (11 cases) and mixed feeding group (12 cases). Fecal metabolites were analyzed by the non-targeted metabolomic approach and gas chromatography-mass spectrometry coupling, and differentially expressed fecal metabolites between groups were screened using the non-parametric Mann- Whitney U test.Metabolic pathways enriched in them were further analyzed. Results:A total of 155 metabolites were characterized, including 57 sugars and sugar derivatives, 34 fatty acids, 25 organic acids, 22 amino acids, 8 esters, 4 nucleosides, 3 vitamins and 2 other substances.The relative contents of the differentially expressed fecal metabolites were measured, and it was found that some types of sugars and sugar derivatives were highly expressed in the fecal samples of breast feeding group, while amino acids, organic acids and fatty acids were highly expressed in those of the mixed feeding group.A total of 28 metabolic pathways enriched in differentially expressed fecal metabolites were obtained.Among them, alanine, aspartic acid and glutamic acid metabolism, valine, leucine and isoleucine metabolism, arginine metabolism and the tricarboxylic acid (TCA) cycle influenced infant health.Conclusions:Feeding methods have an effect on the fecal metabolites in infants delivered by cesarean section born infants, and mixed feeding may speed up the process of TCA cycle and amino acid metabolism in the intestine of infants delivered by cesarean section to a certain extent.
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ObjectiveTo investigate the changes of endogenous metabolites in serum of ovariectomized rats and the effect of Erxiantang on them based on liquid chromatography-mass spectrometry（LC-MS）. MethodTwenty-four healthy female SD rats were randomly divided into sham-operated group， model group and Erxiantang group（7.5 g·kg-1）， with 8 rats in each group. Bilateral ovarian tissues were excised in the model and Erxiantang groups， and small pieces of adipose tissues were excised in the abdominal cavity of the sham-operated group bilaterally， and gastric administration was started 2 weeks after surgery， and equal volumes of distilled water were gavaged in the sham-operated and model groups. After 12 weeks of administration， blood was collected from abdominal aorta， and non-targeted metabonomics was performed on rat serum by LC-MS， and orthogonal partial least squares-discriminant analysis（OPLS-DA） was used to screen differential metabolites. Metabolic pathway analysis was performed based on Kyoto Encyclopedia of Genes and Genomes（KEGG）， and the levels of key enzymes of metabolic pathways were verified by enzyme-linked immunosorbent assay（ELISA）. ResultThe results of metabonomics showed that 82 differential metabolites between the model group and the sham-operated group were glycerophospholipids， fatty acyls， steroids and steroid derivatives， of which the most significant difference was glycerophospholipids. At the same time， Erxiantang could call back 65 out of 82 differential metabolites， of which 11 were statistically significant， mainly phosphatidylcholine（PC） and lysophosphatidylcholine（LysoPC） in glycerophospholipids， followed by corticosterone and 11-deoxycortisol in steroids and steroid derivatives. Metabolic pathway analysis showed that the pathways of glycerophospholipid metabolism and steroid hormone biosynthesis in model group were changed， and were recovered after the administration of Erxiantang. ELISA results showed that compared with the sham-operated group， serum levels of cholinephosphate cytidylytransferase（CCT）， secretory phospholipase A2（sPLA2） and lysophosphatidylcholine acyltransferase（LPCAT）， which were the key metabolic enzymes of glycerophospholipid metabolite PC and LysoPC， were significantly decreased in the model group（P<0.05， P<0.01）， and choline phosphotransferase 1（CPT1） levels decreased but the difference was not statistically significant， compared with the model group， the levels of CCT， sPLA2 and CPT1 were significantly increased in Erxiantang group（P<0.01）. In addition， compared with the sham-operated group， the levels of cholesterol（TC）， triglyceride（TG） and low density lipoprotein cholesterol（LDL-C） were significantly increased in the model group（P<0.01）， the high density lipoprotein cholesterol（HDL-C） level was decreased（P<0.05）， compared with the model group， the levels of TC， TG and LDL-C were significantly decreased and the level of HDL-C was significantly increased in Erxiantang group（P<0.01）. ConclusionEndogenous metabolites and related metabolic pathways in ovariectomized rats were altered， and Erxiantang can reverse some of the different metabolites and related pathways， such as regulating glycerophospholipid metabolism by regulating metabolic enzymes CCT， sPLA2 and CPT1 to increase the levels of PC and LysoPC， and then improve the pathological changes such as lipid metabolism disorder in ovariectomized rats.
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ObjectiveIn this study， based on ultra-high performance liquid chromatography-mass spectrometry（UHPLC-MS/MS） and high-throughput transcriptome sequencing technology（RNA-seq）， we investigated the mechanism of Yishen Huashi granules in regulating serum metabolites and renal messenger ribonucleic acid（mRNA） expression to improve diabetic kidney disease（DKD）. MethodSD rats were randomly divided into normal group ， model group and Yishen Huashi granules group， with 8 rats in each group. The rat model of DKD was established by intraperitoneal injection of streptozotocin. Yishen Huashi granules group was given 5.54 g·kg-1·d-1 of Yishen Huashi granules by gavage， and the normal group and the model group were given the same amount of normal saline for 6 weeks. During the experiment， the body weight and blood glucose of rats were monitored， and the rats were anesthetized 24 hours after the last administration， blood was collected from the inferior vena cava， serum was separated， and renal function， blood lipid， and inflammatory indicators were detected. Kidney tissue of rats was fixed in neutral paraformaldehyde， and stained with hematoxylin-eosin（HE）， Masson and periodic acid-Schiff（PAS） to observe the renal pathological changes. UHPLC-MS/MS and RNA-seq were used to identify the changes of serum metabolism and the differences of renal mRNA expression， and real time fluorescence quantitative polymerase chain reaction（Real-time PCR） and Western blot were used to detect the differential mRNA and protein expression in renal tissue to explore the common expression mechanism. ResultCompared with the normal group， rats in the model group showed a decrease in body weight， a significant increase in blood glucose， urinary microalbumin to urinary creatinine ratio（UACR）， blood urea nitrogen（BUN）， cystatin-C（Cys-C）， β2-microglobulin（β2-MG）， interleukin-6（IL-6）， triglyceride（TG） and total cholesterol（TC）， and a significant decrease in total superoxide dismutase（T-SOD）（P<0.01）. After the intervention of Yishen Huashi granules， all the indexes were improved to different degrees in rats（P<0.05， P<0.01）. Compared with the normal group， the model group showed renal mesangial stromal hyperplasia， fibrous tissue hyperplasia and tubular vacuolar degeneration. Compared with the model group， the renal pathology of rats in Yishen Huashi granules group was improved to a certain extent. A total of 14 target metabolites and 96 target mRNAs were identified， the target metabolites were mainly enriched in 20 metabolic pathways， including sphingolipid metabolism， glycerophospholipid metabolism， and the biosynthesis of phenylalanine， tyrosine and tryptophan. The target mRNAs were enriched to obtain a total of 21 differential mRNAs involved in the TOP20 pathways closely related to glycolipid metabolism. A total of 6 pathways， glycerophospholipid metabolism， arachidonic acid metabolism， purine metabolism， primary bile acid biosynthesis， ascorbic acid and uronic acid metabolism， and galactose metabolism， were enriched by serum differential metabolites and renal differential mRNAs， among them， there were 7 differential metabolites such as phosphatidylethanolamine（PE） and 7 differential mRNAs such as recombinant adenylate cyclase 3（ADCY3）. Seven differential metabolites had high predictive accuracy as verified by receiver operating characteristic（ROC） curve， and the results of Real-time PCR and Western blot were highly consistent with the sequencing results. ConclusionYishen Huashi granules can reduce UACR， BUN and other biochemical indexes， correct the disorder of glucose and lipid metabolism， and improve renal function of DKD rats. And its mechanism may be related to the regulation of the level of PE and other blood metabolites， and expression of Phospho1 and other mRNAs in the kidney， of which six pathways， including glycerophospholipid metabolism， may play an important role.
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@#【Objective】 To investigate the correlations between intestinal flora, plasma metabolites, and blood stasis syndrome in coronary heart disease (CHD), and the mechanisms of Yangxin Tongmai Formula (养心通脉方, YXTMF) for blood stasis syndrome in CHD rats. 【Methods】 A total of 18 specific pathogen free (SPF) male Sqrague-Dawley (SD) rats were used to establish CHD rat models with blood stasis syndrome, which were then randomized into model, YXTMF, and atorvastatin calcium (AVT) groups, with six rats in each group, and were intervened through gavage for two weeks. Subsequently, additional six rats that received normal diet were included as normal group. The pathological changes in the CHD rat models were identified by hematoxylin-eosin (HE) staining. The electrocardiogram, hemodynamics, and lipid profiles of the rats were detected as well. The untargeted plasma metabolomics of rats were analyzed by liquid chromotography-tandem mass spectrometry (LC-MS/MS), their ileal mucosal flora by 16S rRNA sequencing, and the correlation between the two results were also analyzed. 【Results】 The whole blood viscosity, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) of rats in the model group increased compared with those in the control group (P < 0.05). In the model group, the proliferation of endothelial cells in the coronary artery of rats was damaged, with quite a few vacuolated pathological changes observed. However, the endothelial lesions in the coronary artery of rats were alleviated in the intervention groups (YXTMF and AVT groups). With the use of LC-MS/MS, a total of 33 potential endogenous metabolites were identified in plasma, among which 1-methylhistidine, N-acetylhistamine, progesterone, and deoxycorticosterone were expected to be the differential metabolites in CHD rats with blood stasis syndrome. The 16S rRNA sequencing results showed that improved diversity and abundance of intestinal flora were observed in the YXTMF group. The correlation analysis suggested that Hydrogenophaga, Limnohabitans, and Polaromonas, which were highly related to the formation of blood stasis syndrome in CHD patients, were positively correlated with plasma metabolites such as 5-hydroxyindole, N-acetylhistamine, and progesterone (P < 0.01), but were negatively correlated with plasma metabolites such as L-arginine, homoarginine, and Boc-beta-cyano-L-alanine (P < 0.01). After YXTMF intervention, Lactobacillus, Corynebacterium, and Candidatus Nitrososphaera were positively correlated with plasma metabolites such as Boc-β-cyano-L-alanine, stachydrine, and naringenin (P < 0.05), while negatively correlated with 5-hydroxyindole, N-acetylhistamine, and oleoylethanolamide (P < 0.05). 【Conclusion】 YXTMF could alleviate blood stasis syndrome in CHD rats through improving their plasma metabolisms achieved by regulating the intestinal flora.
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OBJECTIVE To explore the mechanism of Kuaisong yin in the prevention and treatment of constipation. METHODS Slow transit constipation （STC） model was established with Compound difenoxylate tablet in mice and rats. Two batches of mice were divided into blank group， model group， positive control group （Maren soft capsule， 0.64 g/kg）， Kuaisong yin low-dose， medium-dose and high-dose groups （3.2， 6.4， 12.8 g/kg）， with 10 mice in each group. The effect of Kuaisong yin on constipation in mice was evaluated by intestinal propulsion experiment and defecation experiment. Rats were divided into blank group， model group， positive control group （Maren soft capsule，0.36 g/kg）， Kuaisong yin low-dose and high-dose groups （2.4， 4.8 g/kg）， with 7 or 8 rats in each group. They were given relevant medicine once a day for 1 week. The metabonomics of serum and urine of rats were analyzed by UPLC-Q-TOF-MS/MS technology. RESULTS Compared with model group， the ink propulsion rate and 5 h defecation volume of mice in Kuaisong yin high-dose group were significantly increased （P＜0.05）； the first defecation time of mice in Kuaisong yin medium-dose and high-dose groups was significantly shortened， and the quality of defecation was significantly reduced within 5 h （P＜0.05 or P＜0.01）. Serum metabonomics screened 16 compounds （such as proline， propionylcarnitine， hemolytic phosphatidylcholine， etc.） and 6 metabolic pathways （such as sphingomyelin metabolism， arginine and proline metabolism， sphingolipid biosynthesis-lactose and neolactone series）. Urine metabonomics screened 20 different metabolites （such as prostaglandin A2， L-valine， phosphatidylcholine， sphingomyelin， etc.） and 8 metabolic pathways （such as valine， leucine and isoleucine biosynthesis， sphingomyelin metabolism， pyruvate metabolism， etc.）. CONCLUSIONS Kuaisong yin can play a role in improving constipation by regulating different metabolites such as hemolytic phosphatidylcholine， phosphatidylcholine， prostaglandin A2， L-valine， proline， and regulating metabolic pathways such as multiple amino acid metabolism， sphingomyelin metabolism， etc.
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ObjectiveUsing multi-omics technology， we conducted the present study to determine whether dexamethasone has therapeutic effect on pneumonia rats through the regulation of intestinal flora and metabolites. MethodsTotally 18 Sprague-Dawley rats were randomly divided into 3 groups （n = 6 each）： Control group， Model group and Dexamethasone （Dex） group. Lipopolysaccharide （LPS） was continuously injected intraperitoneally into rats at a dose of 4 mg/kg for 7 days to induce pneumonia except the Control group. Then the Dex group was given Dex at a dose of 2 mg/kg via oral gavage for 12 days， and both the other two groups received continuously equal volume of sterile PBS buffer for 12 days. On the 19th day， lung， plasma， feces and intestinal contents of rat were collected. Hematoxylin-eosin （H&E） staining and Bio-plex suspension chip system were applied to evaluate the effect of Dex on pneumonia. Furthermore， metagenomic sequencing and UPLC-Q-TOF-MS/MS technology were employed to determine the intestinal flora and metabolites of rats， respectively. ResultsH&E staining results showed that the lung tissue of the Model group was infiltrated with inflammatory cells， the alveolar septum was increased， alveolar hemorrhage， and histological lesions were less severe in Dex group than in the model group. The levels of 3 inflammatory cytokines including TNF-α （P < 0.000 1）， IL-1α （P = 0.009 6） and IL-6 （P < 0.000 1） in the Model group were increased compared with the Control group， while Dex treatment reduced the levels of the three inflammatory factors. Taken together， Dex treatment effectively reversed the features of pneumonia in rats. Metagenomic analysis revealed that the intestinal flora structure of the three groups of rats was changed. In contrast with the Model group， an increasing level of the Firmicutes and an elevated proportion of Firmicutes/Bacteroidetes were observed after Dex treatment. Dex-treated rats possessed notably enrichment of Bifidobacterium， Lachnospiraceae and Lactobacillus. Multivariate statistical analysis showed a great separation between Model group and Dex group， indicating metabolic profile changes. In addition， 69 metabolites （P < 0.05） were screened， including 38 up-regulated in the Model group and 31 elevated in the Dex group， all of which were mainly involved in 3 metabolic pathways： linoleic acid metabolism， tryptophan metabolism and primary bile acid biosynthesis. ConclusionsIn summary， we demonstrate the beneficial effects of Dex on the symptoms of pneumonia. Meanwhile， integrated microbiome-metabolome analysis reveals that Dex improves LPS-induced pneumonia in rats through regulating intestinal flora and host metabolites. This study may provide new insights into the mechanism of Dex treatment of pneumonia in rats.