Toxicity Attenuation Mechanism on Processing Method for Aconiti Lateralis Radix Praeparata in Guilingji Based on Urine Metabolomics / 中国实验方剂学杂志

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.

Metabolomics-based study on the improvement mechanism of the Mongolian drug Sugemule-4 on insomnia rats / 中国药房

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.

Exploring Central Regulatory Effect of Chaishao Liujuntang on Chronic Atrophic Gastritis Rats with Liver Depression and Spleen Deficiency Syndrome Based on Metabolomics / 中国实验方剂学杂志

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.

Amino acid metabolism characteristics of Banxia Baizhu Tianma Decoction in realizing drug withdrawal based on transcriptomic analysis / 中国中药杂志

This study aimed to demonstrate the effect of Banxia Baizhu Tianma Decoction(BBTD) on realizing withdrawal of anti-epileptic drugs and explore the relationship between BBTD and the amino acid metabolism by transcriptomic analysis in the rat model of epilepsy induced by lithium chloride-pilocarpine. The rats with epilepsy were divided into a control group(Ctrl), an epilepsy group(Ep), a BBTD & antiepileptic drug integrative group(BADIG), and an antiepileptic drug withdrawal group(ADWG). The Ctrl and Ep were given ultrapure water by gavage for 12 weeks. The BADIG was given BBTD extract and carbamazepine solution by gavage for 12 weeks. The ADWG was given carbamazepine solution and BBTD extract by gavage for the former 6 weeks, and then only given BBTD extract for the latter 6 weeks. The therapeutic effect was evaluated by behavioral observation, electroencephalogram(EEG), and hippocampal neuronal morphological changes. High-throughput sequencing was used to obtain amino acid metabolism-related differen-tial genes in the hippocampus, and the mRNA expression in the hippocampus of each group was verified by real-time quantitative polymerase chain reaction(RT-qPCR). The hub genes were screened out through protein-protein interaction(PPI) network, and Gene Ontology(GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed. Two ceRNA networks, namely circRNA-miRNA-mRNA and lncRNA-miRNA-mRNA, were constructed for ADWG vs BADIG. The experimental results showed that compared with those in Ep, rats in ADWG were significantly improved in the behavioral observation, EEG, and hippocampal neuronal impairment. Thirty-four amino acid metabolism-related differential genes were obtained by transcriptomic analysis, and the sequencing results were confirmed by RT-qPCR. Eight hub genes were obtained through PPI network, involving several biological processes, molecular functions, and signal pathways related to amino acid metabolism. Finally, the circRNA-miRNA-mRNA ternary transcription network of 17 circRNA, 5 miRNA, and 2 mRNA, and a lncRNA-miRNA-mRNA ternary network of 10 lncRNA, 5 miRNA, and 2 mRNA were constructed in ADWG vs BADIG. In conclusion, BBTD can effectively achieve the withdrawal of antiepileptic drugs, which may be related to the transcriptomic regulation of amino acid metabolism.

Effect of Polysaccharides and n-Butanol Fractions of Atractylodis Rhizoma Stir-fried with Bran on Metabonomics in Rats with Spleen Deficiency / 中国实验方剂学杂志

ObjectiveTo explore the regulatory effect of polysaccharides and n-butanol fractions of Atractylodis Rhizoma stir-fried with bran on the plasma metabolites of spleen-deficient rats， and then to elucidate their mechanisms of spleen-enhancing effects. MethodForty male SD rats were randomly divided into the blank group， model group， polysaccharide group （FD group， 0.075 6 g·mL-1·d-1）， n-butanol fractions group （FZ group， 0.012 1 g·mL-1·d-1）， with 10 rats in each group. Except the blank group， the other three groups used the compound factors of overwork， dietary disorders and intragastric administration of Sennae Folium decoction to replicate the rat model of spleen deficiency. After the end of modeling， the FD group and FZ group were given the corresponding medicinal solution by gavage for 7 d， meanwhile， the blank group and model group were given an equal volume of saline. The plasma samples from rats in the blank， model， FZ and FD groups were analyzed by ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry （UHPLC-Q-Orbitrap-MS）， multivariate statistical methods were used to process the data and screen differential metabolites， and metabolic pathway enrichment analysis of the screened differential metabolites was performed using the Kyoto Encyclopedia of Genes and Genomes （KEGG)）database and MetaboAnalyst 5.0. ResultThe results of multivariate statistical analysis showed that there were significant differences in plasma metabolites between the model group and blank group， FZ group and model group， FD group and model group. There were 380 differential metabolites between the blank group and the model group， of which 78 and 57 were called back by polysaccharides and n-butanol fractions of Atractylodis Rhizoma stir-fried with bran， respectively. Metabolic pathway enrichment results showed that the n-butanol fractions mainly affected glycine， serine and threonine metabolism， alanine， aspartate and glutamate metabolism， D-arginine and D-ornithine metabolism， which were summarized as amino acid metabolism， while the polysaccharides mainly affected glycine， serine and threonine metabolism， alanine， aspartate and glutamate metabolism， tricarboxylic acid cycle， biotin metabolism and thiamine metabolism. ConclusionBoth of polysaccharides and n-butanol fractions of Atractylodis Rhizoma stir-fried with bran have significant regulating effects on the metabolic abnormalities in spleen-deficient rats， in which the n-butanol fractions is mainly involved in amino acid metabolism， and the polysaccharides are involved in energy metabolism and cofactor and vitamin metabolism in addition to regulating amino acid metabolism.

Mechanism study of rhubarb-peach kernel regulation of feces metabolic profile in mice with adenomyosis / 药学学报

This paper aims to investigate the regulatory mechanism of blood-activating and stasis-dissipating drugs on fecal metabolic characteristics of rhubarb-peach kernel in mice with adenomyosis (AM) using fecal metabolome method. Adenomyosis was modeled by pituitary transplantation, and after the end of modeling administration, fecal samples were collected from mice. Non-targeted metabolomics studies were performed using liquid chromatography-mass spectrometry (LC-MS) to compare the metabolic characteristics of the feces of mice in each group and to find intestinal differential metabolites and potential differential metabolic pathways. The results showed that compared with the normal group, 5-hydroxy-L-tryptophan, histidine, L-acetylcarnitine, 16-hydroxy hexadecanoic acid, thromboxane B2, etc. were significantly up-regulated, L-urobilin and prostaglandin D3 were down-regulated in the feces of the model group, and were reversed after treatment with the rhubarb-peach kernel. The results of metabolic pathway enrichment analysis showed that tryptophan metabolism and histidine metabolism were the main intervention pathways of the rhubarb-peach kernel on AM intestinal metabolism. This study found that the underlying mechanism of the rhubarb-peach kernel in the treatment of AM is related to the intervention of intestinal metabolism of tryptophan, histidine, bile acid, choline and arachidonic acid, and the regulation of pro-inflammatory microenvironment and fatty acid metabolic homeostasis. This study has been approved by the Experimental Animal Ethics Committee of China Three Gorges University (No. 20190801).

Usher syndrome with methylmalonic acidemia and homocysteine in an infant / 中华围产医学杂志

A case of Usher syndrome with methylmalonic acidemia and homocysteine is reported. The patient was a two-month-old and small for gestational age male infant hospitalized for "feeding difficulties" during the neonatal period. The baby boy presented hypotonia, microcephaly, and hearing loss after birth. Genetic test found compound heterozygous mutations of c.482G>A and c.567dup in MMACHC, and both were pathogenic mutations inherited from his parents. Moreover, the patient also had compound heterozygous variants at c.2802T>G and c.14017T>C of USH2A gene. The former was suspected to be pathogenic, and the latter was of unknown clinical significance. Both were from the parents. Usher syndrome and methylmalonic acidemia with homocysteine were clinically diagnosed. Followed up to the age of two, the child was found with moderate mental retardation, while the physical development was comparable to that of the same age group.

Effect of acupuncture combined with rehabilitation training on cognitive function and amino acid metabolism in children with cerebral palsy / 中国针灸

OBJECTIVE@#To observe the effect of acupuncture combined with rehabilitation training on cognitive function and amino acid metabolism in children with cerebral palsy.@*METHODS@#Twenty children with cerebral palsy (cerebral palsy group) were randomly divided into an acupuncture and rehabilitation group (11 cases) and a rehabilitation group (9 cases), and 10 healthy children were included as the normal group. The rehabilitation group was treated with rehabilitation training, 30 min each time; on the basis of rehabilitation training, the acupuncture and rehabilitation group was treated with acupuncture at Sishenzhen, Zhisanzhen, Naosanzhen, Niesanzhen, Dazhui (GV 14), Shenzhu (GV 12), Mingmen (GV 4), etc. The Sishenzhen (left and right points) and the ipsilateral Niesanzhen were respectively connected with a group of electrodes, intermittent wave, frequency of 2 Hz for 30 min. Both groups were treated once every other day, three times a week, totaling for 3 months. The Gesell developmental diagnostic scale (GESELL) was used to evaluate the developmental quotient (DQ) scores before and after treatment, and the blood samples of children with cerebral palsy before and after treatment and normal children were collected for amino acid metabolomics.@*RESULTS@#Compared before treatment, the DQ scores of adaptation, fine motor and social in the acupuncture and rehabilitation group was increased after treatment (@*CONCLUSION@#Acupuncture combined with rehabilitation training could improve cognitive function in children with cerebral palsy, and the effect may be related to the down-regulation of L-histidine and L-citrulline metabolism.

Study on active constituents of Astragalus polysaccharides for injection to regulate metabolism of macrophages based on LC-MS metabolomics / 中草药

Objective: To study the phagocytosis of mouse monocyte-macrophage Raw 264.7 by the active constituents of Astragalus polysaccharides for injection based on LC-MS metabolomics. Methods: Neutral red method was used to detect the phagocytosis of Raw 264.7 by different molecular weight fractions of Astragalus polysaccharides for injection. The active components were selected, and the cell culture supernatant and cell lysate were analyzed by LC-MS. Combined with multivariate statistical analysis and metabolism pathway analysis, the mechanism of action was studied. Results: The small molecular weight fraction of Astragalus polysaccharides for injection significantly promoted the phagocytosis of Raw 264.7 at a concentration of 30 μg/mL. Compared with the control group, after the active part of the injection of Astragalus polysaccharides was applied to Raw 264.7, 41 differential metabolites were found in and out of the cells, mainly related to amino acid metabolism, energy metabolism and antioxidant effects. Conclusion: The small molecular weight fraction of Astragalus polysaccharides for injection can increase the phagocytosis of Raw 264.7, and its mechanism may be closely related to amino acid metabolism, energy metabolism and antioxidant effects.

Cellular metabolism and homeostasis in pluripotency regulation

Pluripotent stem cells (PSCs) can immortally self-renew in culture with a high proliferation rate, and they possess unique metabolic characteristics that facilitate pluripotency regulation. Here, we review recent progress in understanding the mechanisms that link cellular metabolism and homeostasis to pluripotency regulation, with particular emphasis on pathways involving amino acid metabolism, lipid metabolism, the ubiquitin-proteasome system and autophagy. Metabolism of amino acids and lipids is tightly coupled to epigenetic modification, organelle remodeling and cell signaling pathways for pluripotency regulation. PSCs harness enhanced proteasome and autophagy activity to meet the material and energy requirements for cellular homeostasis. These regulatory events reflect a fine balance between the intrinsic cellular requirements and the extrinsic environment. A more complete understanding of this balance will pave new ways to manipulate PSC fate.

Cellular metabolism and homeostasis in pluripotency regulation

Pluripotent stem cells (PSCs) can immortally self-renew in culture with a high proliferation rate, and they possess unique metabolic characteristics that facilitate pluripotency regulation. Here, we review recent progress in understanding the mechanisms that link cellular metabolism and homeostasis to pluripotency regulation, with particular emphasis on pathways involving amino acid metabolism, lipid metabolism, the ubiquitin-proteasome system and autophagy. Metabolism of amino acids and lipids is tightly coupled to epigenetic modification, organelle remodeling and cell signaling pathways for pluripotency regulation. PSCs harness enhanced proteasome and autophagy activity to meet the material and energy requirements for cellular homeostasis. These regulatory events reflect a fine balance between the intrinsic cellular requirements and the extrinsic environment. A more complete understanding of this balance will pave new ways to manipulate PSC fate.

Cellular metabolism and homeostasis in pluripotency regulation

Pluripotent stem cells (PSCs) can immortally self-renew in culture with a high proliferation rate, and they possess unique metabolic characteristics that facilitate pluripotency regulation. Here, we review recent progress in understanding the mechanisms that link cellular metabolism and homeostasis to pluripotency regulation, with particular emphasis on pathways involving amino acid metabolism, lipid metabolism, the ubiquitin-proteasome system and autophagy. Metabolism of amino acids and lipids is tightly coupled to epigenetic modification, organelle remodeling and cell signaling pathways for pluripotency regulation. PSCs harness enhanced proteasome and autophagy activity to meet the material and energy requirements for cellular homeostasis. These regulatory events reflect a fine balance between the intrinsic cellular requirements and the extrinsic environment. A more complete understanding of this balance will pave new ways to manipulate PSC fate.

Bacterial stress response, physiological metabolism and antimicrobial tolerance and the control strategies / 生物工程学报

Overuse of antibiotics in medical care and animal husbandry has led to the development of bacterial antimicrobial resistance, causing increasingly more health concern. In addition to genetic mutations and the formation of resistance, the various stresses bacteria encountered in the natural environment trigger their stress responses, which not only protect them from these stresses, but also change their tolerance to antimicrobials. The emergence of antimicrobial tolerance will inevitably affect the physiological metabolism of bacteria. However, bacteria can restore their sensitivity to drugs by regulating their own metabolism. This article reviews recent studies on the relationship between bacterial stress responses or the physiological metabolism and antimicrobial tolerance, intending to take more effective measures to control the occurrence and spread of antimicrobial resistance.

Hematology and serum biochemistry of broilers at the initial and growth stages submitted to different levels of digestible sulfur amino acids / Hematologia e bioquímica sérica de frangos de corte submetidos a diferentes níveis de aminoácidos sulfurados digestíveis

ABSTRACT: The objective of this study was to evaluate the effect of digestible methionine and cystine (Met + Cys) levels on the hematological and serum biochemical parameters of broiler chickens during the initial and growth stages. For this, 1,800 male chicks of the Coob 500 strain were used, with 900 chicks in the initial phase (1 to 21 days old) and 900 chicks in the growth phase (22 to 42 days old), distributed in a completely randomized design of five treatments with six replicates of 30 birds. The treatments consisted of 0.545, 0.616, 0.711, 0.782, and 0.853%; and 0.514, 0.571, 0.647, 0.704, and 0.761% digestible Met + Cys for "1 to 21" and "22 to 42" days of breeding, respectively. Results showed that digestible Met + Cys levels in broiler feed altered some hematological parameters (erythrocyte, hematocrit hemoglobin, total leukocytes, heterophile: lymphocyte) and serum biochemistry (uric acid, PST, total LDL, and TG). The digestible Met + Cys levels in the diet of broilers affected the hematological parameters and serum biochemistry, especially at higher levels. From the inclusion level 0.761 of Met + Cist in the broiler diet, red blood cells, hemoglobin and hematocrit changes begin to appear.

RESUMO: Teve-se como objetivos neste estudo avaliar o efeito dos níveis de metionina + cistina (Met+Cis) digestível na dieta sobre os parâmetros hematológicos e bioquímicos séricos de frangos de corte na fase inicial e de crescimento. Para isso, utilizou-se 1.800 pintos, machos, da linhagem Coob 500, sendo 900 pintos para a fase inicial (1 a 21 dias de idade) e mais 900 pintos para a fase de crescimento (22 a 42 dias de idade), distribuídos em delineamento inteiramente casualizado composto de cinco tratamentos, com seis repetições de 30 aves. Os tratamentos consistiram em 0,545; 0,616; 0,711; 0,782 e 0,853% e 0,514; 0,571; 0,647; 0,704 e 0,761% de Met+Cis digestíveis para a fase inicial e de crescimento, respectivamente. Os resultados demonstraram que níveis de Met+Cis digestível na alimentação de frango de corte, acarretam alterações em parâmetros hematológicos como: hemácia, hematócrito, hemoglobina, leucócitos totais, relação heterófilo: linfócito; e bioquímico sérico como: ácido úrico, albumina, colesterol total, proteínas séricas totais (PST), lipoproteína de baixa densidade (LDL) e triglicerídeos (TG). Os níveis digestíveis de Met + Cys na dieta de frangos de corte afetam os parâmetros hematológicos e a bioquímica sérica, principalmente em níveis mais elevados. A partir do nível de inclusão 0.761 de Met + Cist na dieta de frangos de corte, começam a aparecer alterações nos glóbulos vermelhos, hemoglobina e hematócrito.

A new strategy to intervene tumor metabolism: regulatory targets for amino acid metabolism and advances in drug research / 药学学报

Reprogramming of metabolism is one of the most critical features in tumorigenesis and tumor growth. Many types of cancer show an increased demand for specific amino acids, rely on exogenous supplies, or alter amino acid metabolic pathways, leading to changes in corresponding amino acid levels to meet the need of tumorigenesis. Therefore, if the level of tumor growth-dependent amino acids can be effectively controlled, a new treatment strategy can be developed from the perspective of cell metabolism. At present, remarkable progress has been made in this field. This paper outlines the amino acid metabolic pathways closely related to tumorigenesis and tumor growth, and summarizes the corresponding regulatory mechanisms and active molecules. Finally, the direction of the field is discussed and prospected for future development.

Metabolomic Analysis Identifies Alterations of Amino Acid Metabolome Signatures in the Postmortem Brain of Alzheimer's Disease

Despite significant advances in neuroscience research over the past several decades, the exact cause of AD has not yet fully understood. The metabolic hypothesis as well as the amyloid and tau hypotheses have been proposed to be associated with AD pathogenesis. In order to identify metabolome signatures from the postmortem brains of sporadic AD patients and control subjects, we performed ultra performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometer (UPLC-LTQ–Orbitrap-MS). Not only our study identified new metabolome signatures but also verified previously known metabolome profiles in the brain. Statistical modeling of the analytical data and validation of the structural assignments discovered metabolic biomarkers associated with the AD pathogenesis. Interestingly, hypotaurin, myo-inositol and oxo-proline levels were markedly elevated in AD while lutamate and N-acetyl-aspartate were decreased in the postmortem brain tissue of AD patients. In addition, neurosteroid level such as cortisol was significantly increased in AD. Together, our data indicate that impaired amino acid metabolism is associated with AD pathogenesis and the altered amino acid signatures can be useful diagnostic biomarkers of AD. Thus, modulation of amino acid metabolism may be a possible therapeutic approach to treat AD.

Effect of Liuwei Dihuangwan on Blood Metabolism During Growth and Development of Rats / 中国实验方剂学杂志

Objective: The effect of Liuwei Dihuangwan on blood metabolism during growth and development of rats was investigated by taking the overall metabolic profile and biomarkers of metabolomics as indexes. Method: Ultra performance liquid chromatography-high definition mass spectrometry(UPLC-HDMS) was employed to establish a blood metabolomics study method for characterizing the blood metabolic profile of rats at different time before and after administration. The pattern recognition method was used to integrate and analyze the metabolic profiles, and the differential metabolic markers related to drug action were searched. Based on metabolomics pathway analysis(MetPA) and Kyoto encyclopedia of genes and genomes(KEGG) and other databases, the metabolic pathways related to differential markers were analyzed to study the effect of Liuwei Dihuangwan on blood metabolism during growth and development of rats. Result: Liuwei Dihuangwan significantly affect the blood metabolism profiles during growth and development of rats by regulating 30 blood metabolic markers and 12 related target metabolic pathways, and 8 key metabolic markers were delineated. Conclusion: Liuwei Dihuangwan can significantly regulate the blood metabolic network during the growth and development of rats, thereby affecting the growth and development of rats.

Analysis of Mechanism of Artesunate in Treatment of Liver Cancer Based on Metabolomics / 中国实验方剂学杂志

Objective: To study on the antitumor mechanism of artesunate in the treatment of liver cancer based on gas chromatography-mass spectrometry (GC-MS). Method: CellTiter-Glo® Luminescent Cell Viability Assay was used to detect activity of artesunate with different concentrations (0, 12.5, 25, 50, 100 μmol·L-1) on human liver cancer Huh7, SMMC-7721 cells for 24, 48, 72 h. GC-MS was employed to analyze the changes of metabolites of artesunate in two kinds of hepatoma cells (Huh7, SMMC-7721) for 24 h. The data was preprocessed by Postrun Analysis 4.41 workstation. Partial least squares-discriminant analysis (PLS-DA) was used to analyze two sets of differential metabolites and to analyze metabolic pathways of differential metabolites based on MetaboAnalyst 3.0 software. Result: Compared with the normal group, after two kinds of liver cancer cells was treated by artesunate, a total of 39 identical metabolites in the cells have undergone significant changes, which were mainly related to five metabolic pathways,including biosynthesis of aminoacyl-transfer RNA (tRNA), metabolism of alanine, aspartic acid and glutamic acid, metabolism of glycine, serine and threonine, metabolism of arginine and proline, metabolism of glutathione. Conclusion: Artesunate (12.5-100 μmol·L-1) can inhibit the growth of liver cancer cells (Huh7, SMMC-7721), it mainly involves five metabolic pathways, which may be the pathway of artesunate against liver cancer.

Effect of Wuzhuyu Decoction on urine metabolic spectrum in rats with deficiency cold and vomit based on UHPLC-MS / 中草药

Objective: To observe the changes of urine metabolic profile of Wuzhuyu Decoction in rats with deficiency cold and vomit, and explore its possible mechanism of treatment of deficiency cold and vomit syndrome. Methods: A rat model of deficiency cold and vomit was prepared by a composite method (rhucax + cisplatin). Rats were randomly divided into control group, model group, and Wuzhuyu Decoction group. UPLC-MS/MS combined with principal component analysis and partial least squares analysis were used to analyze urine data and identify potential biomarkers. Diversified ROC curves were used to validate differential metabolites; Pathway Analysis database was used for topological analysis of differential metabolites; R and Cytoscape were used for correlation analysis and modular analysis of metabolites. Results: The urine metabolic spectrum of control group and model group were completely separated. Wuzhuyu Decoction group was close to the control group, indicating that the model was successfully replicated; And Wuzhuyu Decoction can interfere with the symptoms of deficiency cold and vomit in rats, suggesting that the rat body had a tendency to return to normal state. Through modular analysis of 34 urine differential metabolites, the deficiency cold and vomit treatment was revealed to affect biosynthesis of valine, leucine and isoleucine, phenylalanine, tyrosine and tryptophan biosynthesis, arginine and proline metabolism, tryptophan metabolism, tyrosine metabolism, arachidonic acid metabolism, citric acid cycle (TCA cycle) pathways. Modularity analysis revealed that there was close relationship between 10 modules; Alanine, leucine, tyrosine, tryptophan, isoleucine, succinic acid, alanine, fumaric acid, malic acid, isocitrate, and other biological targets can thus be used as markers of deficiency cold and vomit. Conclusion: Wuzhuyu Decoction can improve the physiological characteristics of the model of deficiency cold and vomit. The mechanism may be related to the regulation of amino acid metabolism, energy metabolism and lipid metabolism in rats.

Effects of Huanbei Zhike Recipe on cough variant asthma model guinea pig based on 1H-NMR metabolomics / 中草药

Objective To investigate the mechanism of action of Huanbei Zhike Recipe on the cough variant asthma model (CVA) of guinea pigs by 1H-NMR metabolomics methods. Methods The CVA model was induced by ip 4% OVA and ip 2% Al(OH)3 in guinea pigs abdominal cavity, and the effects of Huanbei Zhike Recipe (5, 10, and 20 g/kg) on the cough induced by capsaicine was investigated. After the administration, the lung of right middle lobe in guinea pigs were taken out and determinated by 1H-NMR, and multivariate statistical analysis was used to investigate the intervention effects of Huanbei Zhike Recipe on CVA. Results The cough latency of guinea pigs can be significantly prolonged and the frequency of cough were reduced (P < 0.01), and the inflammatory factors in lung lavage fluid were obviously reduced (P < 0.05). Compared with the blank group, the levels of leucine, isoleucine, valine, alanine, α-glucose, acetic acid, glutamic acid, methionine, pyruvic acid, succinic acid, 3-hydroxybutyrate (3-HB), GSSG, creatine, ethanolamine, cholic acid, glycine, glycerophosphoryl choline (GPC), glutamine, betaine, phosphorylethanolamine (PE), β-glucose, and arginine were increased, while the levels of lactate and methyl-phosphate were decreased. These 24 potential metabolites could be reversely regulated in different degree after treatment with Huanbei Zhike Recipe. Conclusion Huanbei Zhike Recipe could prevent CVA diseases likely through the regulation of energy metabolism and amino acid metabolism.