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1Washed microbiota transplantation vs.manual fecal microbiota transplantation:clinical findings,animal studies and in vitro screening显示文摘Fecal microbiota transplantation(FMT)by manual preparation has been applied to treat diseases for thousands of years.However,this method still endures safety risks and challenges the psychological endurance and acceptance of doctors,patients and donors.Population evidence showed the washed microbiota preparation with microfiltration based on an automatic purification system followed by repeated centrifugation plus suspension for three times significantly reduced FMT-related adverse events.This washing preparation makes delivering a precise dose of the enriched microbiota feasible,instead of using the weight of stool.Intraperitoneal injection in mice with the fecal microbiota supernatant obtained after repeated centrifugation plus suspension for three times induced less toxic reaction than that by the first centrifugation following the microfiltration.The toxic reactions that include death,the change in the level of peripheral white blood cells,and the proliferation of germinal center in secondary lymphoid follicles in spleen were noted.The metagenomic next-generation sequencing(NGS)indicated the increasing types and amount of viruses could be washed out during the washing process.Metabolomics analysis indicated metabolites with pro-inflammatory effects in the fecal microbiota supernatant such as leukotriene B4,corticosterone,and prostaglandin G2 could be removed by repeated washing.Near-infrared absorption spectroscopy could be served as a rapid detection method to control the quality of the washingprocess.In conclusion,this study for the first time provides evidence linking clinical findings and animal experiments to support that washed microbiota transplantation(WMT)is safer,more precise and more quality-controllable than the crude FMT by manual.Ting Zhang Gaochen Lu Zhe Zhao Yafei Liu Quan Shen Pan Li Yaoyao Chen Haoran Yin Huiquan Wang Cicilia Marcella Bota Cui Lei Cheng Guozhong Ji Faming Zhang 2020Protein & Cell2020,11,4:44
2Chinmedomics: A Powerful Approach Integrating Metabolomics with Serum Pharmacochemistry to Evaluate the Efficacy of Traditional Chinese Medicine显示文摘Evaluation of the efficacy of traditional Chinese medicines (TCMs) is an important prerequisite for discovering effective substances, lead compounds, and quality markers (Q markers). At present, there is an urgent need to develop a biological language that can act as abridge for the scientific elaboration of the efficacy of TCMs, and to further highlight the significant value of TCM. Chinese medicinal syndromes and formulae are two essential parts of TCM that directly relate to its efficacy. Syndromes and formulae have been taken as the research objects. The serum pharmacochemistry of the TCM approach with metabolomics were integrated to establish an innovative chinmedomics strategy, which is able to explore syndrome biomarkers and evaluate TCM efficacy in order to discover effective substances from TCMs. A great deal of concrete work in chinmedomics has already performed to bridge the gap between Chinese and Western medicine, and to provide a powerful approach to enhance the scientific value of TCM theory and clinical practice. This article summarizes the application of chinmedomics in identifying the candidate biomarkers of a syndrome and revealing the efficacy of the related formula. We also highlight the discovery of lead compounds and Q markers from TCMs.Ai-Hua Zhang Hui Sun Guang-Li Yan Ying Han Qi-Qi Zhao Xi-Jun Wang 2019Engineering2019,5,1:30
3Metabolomics and its application in the treatment of coronary heart disease with traditional Chinese medicine显示文摘Traditional Chinese Medicine(TCM) is the treasure of Chinese Nation and gained the gradual acceptance of the international community. However, the methods and theories of TCM understanding of diseases are lack of appropriate modern scientific characterization systems. Moreover, traditional risk factors cannot promote to detection and prevent those patients with coronary artery disease(CAD) who have not developed acute myocardial infarction(MI) in time. To sum up, there is still no objective systematic evaluation system for the therapeutic mechanism of TCM in the prevention and cure of cardiovascular disease.Thus, new ideas and technologies are needed. The development of omics technology, especially metabolomics, can be used to predict the level of metabolites in vivo and diagnose the physiological state of the body in time to guide the corresponding intervention.In particular, metabolomics is also a very powerful tool to promote the modernization of TCM and the development of TCM in personalized medicine. This article summarized the application of metabolomics in the early diagnosis, the discovery of biomarkers and the treatment of TCM in CAD.WU Gao-Song LI Hou-Kai ZHANG Wei-Dong 2019Chinese Journal of Natural Medicines2019,17,5:28
4Application of metagenomics in the human gut microbiome显示文摘There are more than 1000 microbial species living in the complex human intestine.The gut microbial community plays an important role in protecting the host against pathogenic microbes,modulating immunity,regulating metabolic processes,and is even regarded as an endocrine organ.However,traditional culture methods are very limited for identifying microbes.With the application of molecular biologic technology in the field of the intestinal microbiome,especially metagenomic sequencing of the next-generation sequencing technology,progress has been made in the study of the human intestinal microbiome.Metagenomics can be used to study intestinal microbiome diversity and dysbiosis,as well as its relationship to health and disease.Moreover,functional metagenomics can identify novel functional genes,microbial pathways,antibiotic resistance genes,functional dysbiosis of the intestinal microbiome,and determine interactions and co-evolution between microbiota and host,though there are still some limitations.Metatranscriptomics,metaproteomics and metabolomics represent enormous complements to the understanding of the human gut microbiome.This review aims to demonstrate that metagenomics can be a powerful tool in studying the human gut microbiome with encouraging prospects.The limitations of metagenomics to be overcome are also discussed.Metatranscriptomics,metaproteomics and metabolomics in relation to the study of the human gut microbiome are also briefly discussed.Wei-Lin Wang Shao-Yan Xu Zhi-Gang Ren Liang Tao Jian-Wen Jiang Shu-Sen Zheng 2015World Journal of Gastroenterology2015,21,3:26
5Metabolomic studies of human gastric cancer:Review显示文摘Metabolomics is a field of study in systems biology that involves the identification and quantification of metabolites present in a biological system. Analyzing metabolic differences between unperturbed and perturbed networks, such as cancerous and noncancerous samples, can provide insight into underlying disease pathology, disease prognosis and diagnosis. Despite the large number of review articles concerning metabolomics and its application in cancer research, biomarker and drug discovery, these reviews do not focus on a specific type of cancer. Metabolomics may provide biomarkers useful for identification of early stage gastric cancer, potentially addressing an important clinical need. Here, we present a short review on metabolomics as a tool for biomarker discovery in human gastric cancer, with a primary focus on its use as a predictor of anticancer drug chemosensitivity, diagnosis, prognosis, and metastasis.Naresh Doni Jayavelu Nadav S Bar 2014World Journal of Gastroenterology2014,20,25:19
6Glucose metabolism in gastric cancer:The cutting-edge显示文摘Glucose metabolism in gastric cancer cells differs from that of normal epithelial cells. Upregulated aerobic glycolysis(Warburg effect) in gastric cancer meeting the demands of cell proliferation is associated with genetic mutations, epigenetic modification and proteomic alteration. Understanding the mechanisms of aerobic glycolysis may contribute to our knowledge of gastric carcinogenesis. Metabolomic studies offer novel, convenient and practical tools in the search for new biomarkers for early detection, diagnosis, prognosis, and chemosensitivity prediction of gastric cancer. Interfering with the process of glycolysis in cancer cells may provide a new and promising therapeutic strategy for gastric cancer. In this article, we present a brief review of recent studies of glucose metabolism in gastric cancer, with primary focus on the clinical applications of new biomarkers and their potential therapeutic role in gastric cancer.Lian-Wen Yuan Hiroharu Yamashita Yasuyuki Seto 2016World Journal of Gastroenterology2016,22,6:18
7Integration of lipidomics and metabolomics for in-depth understanding of cellular mechanism and disease progression显示文摘Mass spectrometry(MS)-based omics technologies are now widely used to profile small molecules in multiple matrices to confer comprehensive snapshots of cellular metabolic phenotypes.The metabolomes of cells,tissues,and organisms comprise a variety of molecules including lipids,amino acids,sugars,organic acids,and so on.Metabolomics mainly focus on the hydrophilic classes,while lipidomics has emerged as an independent omics owing to the complexities of the organismal lipidomes.The potential roles of lipids and small metabolites in disease pathogenesis have been widely investigated in various human diseases,but system-level understanding is largely lacking,which could be partly attributed to the insufficiency in terms of metabolite coverage and quantitation accuracy in current analytical technologies.While scientists are continuously striving to develop high-coverage omics approaches,integration of metabolomics and lipidomics is becoming an emerging approach to mechanistic investigation.Integration of metabolome and lipidome offers a complete atlas of the metabolic landscape,enabling comprehensive network analysis to identify critical metabolic drivers in disease pathology,facilitating the study of interconnection between lipids and other metabolites in disease progression.In this review,we summarize omics-based findings on the roles of lipids and metabolites in the pathogenesis of selected major diseases threatening public health.We also discuss the advantages of integrating lipidomics and metabolomics for in-depth understanding of molecular mechanism in disease pathogenesis.Raoxu Wang Bowen Li Sin Man Lam Guanghou Shui 2020Journal of Genetics and Genomics2020,47,2:15
8Serum and urine metabolomic fingerprinting in diagnostics of inflammatory bowel diseases显示文摘AIM:To evaluate the utility of serum and urine metabolomic analysis in diagnosing and monitoring of inflammatory bowel diseases(IBD).METHODS:Serum and urine samples were collected from 24 patients with ulcerative colitis(UC),19 patients with the Crohn’s disease(CD)and 17 healthy controls.The activity of UC was assessed with the Simple Clinical Colitis Activity Index,while the activity of CD was determined using the Harvey-Bradshaw Index.The analysis of serum and urine samples was performed using proton nuclear magnetic resonance(NMR)spectroscopy.All spectra were exported to Matlab for preprocessing which resulted in two data matrixes for serum and urine.Prior to the chemometric analysis,both data sets were unit variance scaled.The differences in metabolite fingerprints were assessed using partial least-squaresdiscriminant analysis(PLS-DA).Receiver operating characteristic curves and area under curves were used to evaluate the quality and prediction performance of the obtained PLS-DA models.Metabolites responsible for separation in models were tested using STATISTICA10 with the Mann-Whitney-Wilcoxon test and the Student’s t test(α=0.05).RESULTS:The comparison between the group of patients with active IBD and the group with IBD in remission provided good PLS-DA models(P value 0.002for serum and 0.003 for urine).The metabolites that allowed to distinguish these groups were:N-acetylated compounds and phenylalanine(up-regulated in serum),low-density lipoproteins and very low-density lipoproteins(decreased in serum)as well as glycine(increased in urine)and acetoacetate(decreased in urine).The significant differences in metabolomic profiles were also found between the group of patients with active IBD and healthy control subjects providing the PLS-DA models with a very good separation(P value<0.001 for serum and 0.003 for urine).The metabolites that were found to be the strongest biomarkers included in this case:leucine,isoleucine,3-hydroxybutyric acid,N-acetylated compounds,acetoacetate,glycine,phenylalanine and lactate(increased in serum),creatine,dimethyl sulfone,histidine,choline and its derivatives(decreased in serum),as well as citrate,hippurate,trigonelline,taurine,succinate and 2-hydroxyisobutyrate(decreased in urine).No clear separation in PLS-DA models was found between CD and UC patients based on the analysis of serum and urine samples,although one metabolite(formate)in univariate statistical analysis was significantly lower in serum of patients with active CD,and two metabolites(alanine and N-acetylated compounds)were significantly higher in serum of patients with CD when comparing jointly patients in the remission and active phase of the diseases.Contrary to the results obtained from the serum samples,the analysis of urine samples allowed to distinguish patients with IBD in remission from healthy control subjects.The metabolites of importance included in this case up-regulated acetoacetate and down-regulated citrate,hippurate,taurine,succinate,glycine,alanine and formate.CONCLUSION:NMR-based metabolomic fingerprinting of serum and urine has the potential to be a useful tool in distinguishing patients with active IBD from those in remission.Tomasz Dawiskiba Stanislaw Deja Agata Mulak Adam Zabek Ewa Jawień Dorota Pawelka Miroslaw Banasik Agnieszka Mastalerz-Migas Waldemar Balcerzak Krzysztof Kaliszewski Jan Skóra Piotr Bar Krzysztof Korta Kornel Pormańczuk Przemyslaw Szyber Adam Litarski Piotr Mlynarz 2014World Journal of Gastroenterology2014,20,1:15
9A novel approach based on metabolomics coupled with network pharmacology to explain the effect mechanisms of Danggui Buxue Tang in anaemia显示文摘Danggui Buxue Tang(DBT) is a famous Chinese medicinal decoction. Mechanism of DBT action is wide ranging and unclear. Exploring new ways of treatment with DBT is useful. Sprague–Dawley(SD) rats were randomly divided into 3 groups including control(NC, Saline), the DBT(at a dose of 8.10 g?kg–1), and blood deficiency(BD)(Cyclophosphamide(APH)-and Cyclophosphamide(CTX)-induced anaemia). A metabolomics approach using Liquid Chromatography-Quadrupole-Time-of-Flight/Mass Spectrometry(LC/Q-TOFMS) was developed to perform the plasma metabolic profiling analysis and differential metabolites were screened according to the multivariate statistical analysis comparing the NC and BD groups, and the hub metabolites were outliers with high scores of the centrality indices. Anaemia disease-related protein target and compound of DBT databases were constructed. The TCMSP, Chem Mapper and STITCH databases were used to predict the protein targets of DBT. Using the Cytoscape 3.2.1 to establish a phytochemical component–target protein interaction network and establish a component, protein and hub metabolite protein–protein interaction(PPI) network and merging the three PPI networks basing on BisoGenet. The gene enrichment analysis was used to analyse the relationship between proteins based on the relevant genetic similarity by ClueGO. The results shown DBT effectively treated anaemia in vivo. 11 metabolic pathways are involved in the therapeutic effect of DBT in vivo; S-adenosyl-L-methionine, glycine, L-cysteine, arachidonic acid(AA) and phosphatidylcholine(PC) were screened as hub metabolites in APH-and CTX-induced anaemia. A total of 288 targets were identified as major candidates for anaemia progression. The gene-set enrichment analysis revealed that the targets are involved in iron ion binding, haemopoiesis, reactive oxygen species production, inflammation and apoptosis. The results also showed that these targets were associated with iron ion binding, haemopoiesis, ROS production, apoptosis, inflammation and related signalling pathways. DBT can promote iron ion binding and haemopoiesis activities, restrain inflammation, production of reactive oxygen, block apoptosis, and contribute significantly to the DBT treat anaemia.HUA Yong-Li MA Qi YUAN Zi-Wen ZHANG Xiao-Song YAO Wan-Ling JI Peng HU Jun-Jie WEI Yan-Ming 2019Chinese Journal of Natural Medicines2019,17,4:14
10Effect of Tong Xie Yao Fang on endogenous metabolites in urine of irritable bowel syndrome model rats显示文摘BACKGROUND Tong Xie Yao Fang is a representative traditional Chinese prescription for the treatment of liver and spleen deficiency,abdominal pain and diarrhea.It has a unique function in the treatment of gastrointestinal dysfunction including irritable bowel syndrome(IBS),is a common functional bowel disease.Its main symptoms are recurrent abdominal pain,diarrhea,constipation or alternations between diarrhea and constipation.There are obvious differences in metabolites between TCM syndromes.By comparing the body fluid metabolism maps of model animals,metabolomics can discover disease biomarkers,analyze the differences in metabolic pathways and understand the pathological process and the metabolic pathways of substances in the body.Thus,the evaluation of animal models tends to be comprehensive and objective.This may provide further understanding between the interaction between Tong Xie Yao Fang and the IBS model.AIM To evaluate the effect of Tong Xie Yao Fang on IBS rats by using metabolomics method.METHODS Wistar rats were used to establish IBS models,and then randomly divided into four groups:A model control group and three Tong Xie Yao Fang treatment groups(high,medium and low doses).A normal,non-IBS group was established.The rats were treated for 2 wk.On days 0 and 14 of the experimental model,urine was collected for 12 h and was analyzed by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry.Nine potential biomarkers were identified,and six major metabolic pathways were found to be related to IBS.RESULTS In the study of metabonomics,nine potential biomarkers including L-serine,4-methylgallic acid,L-threonine,succinylacetone,prolyl-hydroxyproline,valylserine,acetyl citrate,marmesin rutinoside and 5-hydroxy-L-tryptophan were identified in urine,which were assigned to amino acids,organic acids,succinyl and glycosides.Furthermore,the metabolic pathway of L-serine,L-threonine and 5-hydroxy-L-tryptophan was found in the Kyoto Encyclopedia of Genes and Genomes,which mainly involved the metabolism of cysteine and methionine,vitamin B6 metabolism,serotonin synapse,tryptophan metabolism,sphingolipid metabolism,digestion,absorption of protein and amino acid metabolism.These pathways are related to intestinal dysfunction,inflammatory syndrome,nervous system dysfunction and other diseases.CONCLUSION Tong Xie Yao Fang has pharmacological effects on IBS,and its mechanism may be related to the metabolism of the nine potential biomarkers identified above in urine.Xue-Ying Zhao Jian-Wei Wang Yue Yin Kai Li Miao Zhang Fu-Ping Yan 2019World Journal of Gastroenterology2019,25,34:14
11Novel chinmedomics strategy for discovering effective constituents from ShenQiWan acting on ShenYangXu syndrome显示文摘Elucidation of the efficacy of traditional Chinese medicine(TCM) is of importance for scientists of modern medicine to understand the value of TCM clinical experience, and it is necessary to have a biological language to scientifically describe the efficacy of TCM. With this background,Chinmedomics has been proposed by our team, which includes integrating serum pharmacochemistry and metabolomics technology, defining theory and research methods for expressing the efficacy of TCMs based on the biomarkers discovery of TCM syndrome and elucidating the efficacy of TCM formulae, discovering effective constituents, and finally elucidating the scientific value of TCM. In the present study, the innovative chinmedomics strategy was conducted to evaluate the therapeutic effects of Shen Qi Wan(SQW) acting on Shen Yang Xu(kidney-yang deficiency syndrome, KYDS). We analyzed the urine metabolic trajectory between the model and control groups, and identified the biomarkers by the multivariate analysis. We found that SQW caused significant restoration of abnormal metabolism of KYDs. Using the method of metabolomics, 17 potential urine biomarkers were analyzed through 4 repeated tests in our serial studies on SQW and KYDS. Under the premise of therapeutic efficacy, a total of 56 peaks were tentatively characterized in vivo by the use of serum pharmacochemistry. Correlation analysis between marker metabolites and in vivo constituents of SQW showed that 28 compositions had a close relationship with urine biomarkers of therapeutic effects, whichmight play a key role in the therapeutic effect of SQW. These compounds were imported into an online database to predict their targets. Twenty-three important potential targets were identified, which were related to the metabolism of steroid hormone, tryptophan utilization, and thyroid hormone. In conclusion, chinmedomics is a useful strategy for discovery of potentially effective constituents from complex TCM formulae.ZHOU Xiao-Hang ZHANG Ai-Hua WANG Liang TAN Yun-Long GUAN Yu HAN Ying SUN Hui WANG Xi-Jun 2016Chinese Journal of Natural Medicines2016,14,8:13
12Altered oral microbiota in chronic hepatitis B patients with different tongue coatings显示文摘AIM To elucidate tongue coating microbiota and metabolic differences in chronic hepatitis B(CHB) patients with yellow or white tongue coatings.METHODS Tongue coating samples were collected from 53 CHBpatients(28 CHB yellow tongue coating patients and 25 CHB white tongue coating patients) and 22 healthy controls.Microbial DNA was extracted from the tongue samples,and the bacterial 16 S ribosomal RNA gene V3 region was amplified from all samples and sequenced with the Ion Torrent PGM^(TM)sequencing platform according to the standard protocols.The metabolites in the tongue coatings were evaluated using a liquid chromatographymass spectrometry(LC-MS) platform.Statistical analyses were then performed.RESULTS The relative compositions of the tongue coating microbiotas and metabolites in the CHB patients were significantly different from those of the healthy controls,but the tongue coating microbiota abundances and diversity levels were not significantly different.Compared with the CHB white tongue coating patients,the CHB yellow tongue coating patients had higher hepatitis B viral DNA(HBV-DNA) titers(median 21210 vs 500,respectively,P = 0.03) and a significantly lower level of Bacteroidetes(20.14% vs 27.93%,respectively,P = 0.013) and higher level of Proteobacteria(25.99% vs 18.17%,respectively,P = 0.045) in the microbial compositions at the phylum level.The inferred metagenomic pathways enriched in the CHB yellow tongue coating patients were mainly those involved in amino acid metabolism,which was consistent with the metabolic disorder.The abundances of bacteria from Bacteroidales at the order level were higher in the CHB white tongue coating patients(19.2% vs 27.22%,respectively,P = 0.011),whereas Neisseriales were enriched in the yellow tongue coating patients(21.85% vs 13.83%,respectively,P = 0.029).At the family level,the abundance of Neisseriaceae in the yellow tongue patients was positively correlated with the HBV-DNA level but negatively correlated with the S-adenosyl-L-methionine level.CONCLUSION This research illustrates specific clinical features and bacterial structures in CHB patients with different tongue coatings,which facilitates understanding of the traditional tongue diagnosis.Yu Zhao Yu-Feng Mao Yi-Shuang Tang Ming-Zhu Ni Qiao-Hong Liu Yan Wang Qin Feng Jing-Hua Peng Yi-Yang Hu 2018World Journal of Gastroenterology2018,24,30:13
13The aldose reductase inhibitor epalrestat exerts nephritic protection on diabetic nephropathy in db/db mice through metabolic modulation显示文摘Epalrestat is an inhibitor of aldose reductase in the polyol pathway and is used for the management of diabetic neuropathy clinically.Our pilot experiments and accumulated evidences showed that epalrestat inhibited polyol pathway and reduced sorbitol production,and suggested the potential renal protection effects of epalrestat on diabetic nephropathy (DN).To evaluate the protective effect of epalrestat,the db/db mice were used and exposed to epalrestat for 8 weeks,both the physiopathological condition and function of kidney were examined.For the first time,we showed that epalrestatmarkedlyreduced albuminuria and alleviated the podocyte foot process fusion and interstitial fibrosis of db/db mice.Metabolomics was employed,and metabolites in the plasma,renal cortex,and urine were profiled using a gas chromatography-mass spectrometry (GC/MS)-based metabolomic platform.We observed an elevation of sorbitol and fructose,and a decrease of myo-inositol in the renal cortex of db/db mice. Epalrestat reversed the renal accumulation of the polyol pathway metabolites of sorbitol and fructose,and increased myo-inositol level.Moreover,the upregulation of aldose reductase,fibronectin,collagen Ⅲ,and TGF-β1 in renal cortex of db/db mice was downregulated by epalrestat.The data suggested that epalrestat has protective effects on DN,and the inhibition ofaldose reductas and the modulation of polyol pathway in nephritic cells be a potentially therapeutic strategy for DN.Jun He Hao-xue Gao Na Yang Xiao-dong Zhu Run-bin Sun Yuan Xie Cai-hong Zeng Jing-wei Zhang Jian-kun Wang Fei Ding Ji-ye Aa Guang-ji Wang 2019Acta Pharmacologica Sinica2019,40,1:13
14Metabolomics analysis and rapid identification of changes in chemical ingredients in crude and processed Astragali Radix by UPLC-QTOF-MS combined with novel informatics UNIFI platform显示文摘Astragali Radix, the root of Astragalus membranaceus(Fisch.) Bge. var. mongholicus(Bge.) Hsiao or Astragalus membranaceus(Fisch.) Bge., is widely used as a tonic decoction pieces in the clinic of traditional Chinese medicine(TCM). Astragali Radix has various processed products with varying pharmacological actions. There is no modern scientific evidence to explain the differences in pharmacological activities and related mechanisms. In the present study, we explore the changes in chemical components in Astragali Radix after processing, by ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry(UPLC-QTOF-MS) combined with novel informatics UNIFI platform and multivariate statistical analysis. Our results showed that the crude and various processed products could be clearly separated in PCA scores plot and 15 significant markers could be used to distinguish crude and various processed products by OPLS-DA in UNIFI platform. In conclusion, the present study provided a basis of chemical components for revealing connotation of different processing techniques on Astragali Radix.LIU Peng-Peng SHAN Guo-Shun ZHANG Fan CHEN Jiang-Ning JIA Tian-Zhu 2018Chinese Journal of Natural Medicines2018,16,9:12
15New strategies for colorectal cancer screening显示文摘Colorectal cancer (CRC) is still one of the leading causes of cancer-related death in Western countries, despite major improvements in its treatment. The dramatically high social and economic impact of CRC on human health makes the identification of a reliable screening tool of paramount importance. Current screening methods, such as the fecal occult blood test and colonoscopy do not adequately meet the ideal requisites of a screening test because, even if they are effective, they are limited first by too low specificity and sensitivity, or second by high invasiveness, costs and risk. Nowadays extended efforts are made by researchers to look for more reliable and effective screening tests based on a systems biology approach, using biological samples easily available, such as urine, breath, serum and feces. The effectiveness and reliability of several new attempts to screen these patients by non-invasive analysis of their biological samples using genomic (genetic and epigenetic alteration), transcriptomic (miRNA), proteomic (cancer-related antigens, new antibodies against tumor-associated antigens, mutated proteins) and metabolomic (volatile organic metabolites) methods are discussed in this review. Among the most interesting new screening tools, fecal fluorescent long-DNA, fecal miRNA and metabolomic evaluation in breath and/ or serum seem to be most promising.Maria Di Lena Elisabetta Travaglio Donato F Altomare 2013World Journal of Gastroenterology2013,19,12:12
16Plasma free amino acid profiling of esophageal cancer using high-performance liquid chromatography spectroscopy显示文摘AIM:To perform plasma free amino acid(PFAA)profiling of esophageal squamous cell carcinoma(ESCC)patients at different pathological stages and healthy subjects.METHODS:Plasma samples from ESCC patients(n=51)and healthy control adults(n=60)were analyzed by high-performance liquid chromatography(HPLC).The ESCC patients included moderate/poorly-differentiation(n=24),lymph node metastasis(n=17)and clinical stage>Ib2(n=36).Partial least squares discriminant analysis was performed to demonstrate that the PFAA metabolic patterns enabled discrimination between ESCC patients and controls,and the Student t test was applied to assess significant differences in PFAA concentrations between the two groups.RESULTS:There were significant differences in the PFAA profiles between controls and ESCC patients.Compared with healthy controls,the levels of Asp,Glu,Gly,His,Thr,Tau,Ala,Met,Ile,Leu,and Phe were decreased in ESCC patients,but Cys was increased.There exists a strong correlation between PFAA profiles and clinicopathological characteristics in ESCC patients.The levels of many PFAAs(i.e.,Glu,Asp,Ser,Gly,Tau,Ala,Tyr,Val,Ile,and Leu)were related to pathological grading,lymph node metastasis,and ESCC clinical stage.Very good discrimination between ESCC patients and control subjects was achieved by multivariate modeling of plasma profiles.CONCLUSION:HPLC-based plasma profiling analysis was shown to be an effective approach to differentiate between ESCC patients and controls.PFAA profiles may have potential value for screening or diagnosing ESCC.Hong Ma Ayshamgul Hasim Batur Mamtimin Bin Kong Hai-Ping Zhang Ilyar Sheyhidin 2014World Journal of Gastroenterology2014,20,26:11
17Metabolomics of gastric cancer metastasis detected by gas chromatography and mass spectrometry显示文摘AIM:To elucidate the underlying mechanisms of metastasis and to identify the metabolomic markers of gastric cancer metastasis.METHODS:Gastric tumors from metastatic and nonmetastatic groups were used in this study.Metabolites and different metabolic patterns were analyzed by gas chromatography,mass spectrometry and principal components analysis (PCA),respectively.Differentiation performance was validated by the area under the curve (AUC) of receiver operating characteristic curves.RESULTS:Twenty-nine metabolites were differentially expressed in animal models of human gastric cancer.Of the 29 metabolites,20 were up-regulated and 9 were down-regulated in metastasis group compared to non-metastasis group.PCA models from the metabolite profiles could differentiate the metastatic from the nonmetastatic specimens with an AUC value of 1.0.These metabolites were mainly involved in several metabolic pathways,including glycolysis (lactic acid,alaline),serine metabolism (serine,phosphoserine),proline metabolism (proline),glutamic acid metabolism,tricarboxylic acid cycle (succinate,malic acid),nucleotide metabolism (pyrimidine),fatty acid metabolism (docosanoic acid,and octadecanoic acid),and methylation(glycine).The serine and proline metabolisms were highlighted during the progression of metastasis.CONCLUSION:Proline and serine metabolisms play an important role in metastasis.The metabolic profiling of tumor tissue can provide new biomarkers for the treatment of gastric cancer metastasis.Jin-Lian Chen,Jun-Duo Hu,Jing Fan,Jing Hong,Department of Gastroenterology,Shanghai Sixth People’s Hospital,Shanghai Jiao Tong University,Shanghai 200233,China Hui-Qing Tang,Jian-Zhong Gu,Shanghai Laboratory Animal Center,Chinese Academy of Sciences,Shanghai 201615,China 2010World Journal of Gastroenterology2010,16,46:11
18A systematic review of metabolomic profiling of gastric cancer and esophageal cancer显示文摘Objective:Upper gastrointestinal(UGI)cancers,predominantly gastric cancer(GC)and esophageal cancer(EC),are malignant tumor types with high morbidity and mortality rates.Accumulating studies have focused on metabolomic profiling of UGI cancers in recent years.In this systematic review,we have provided a collective summary of previous findings on metabolites and metabolomic profiling associated with GC and EC.Methods:A systematic search of three databases(Embase,PubMed,and Web of Science)for molecular epidemiologic studies on the metabolomic profiles of GC and EC was conducted.The Newcastle–Ottawa Scale(NOS)was used to assess the quality of the included articles.Results:A total of 52 original studies were included for review.A number of metabolites were differentially distributed between GC and EC cases and non-cases,including those involved in glycolysis,anaerobic respiration,tricarboxylic acid cycle,and protein and lipid metabolism.Lactic acid,glucose,citrate,and fumaric acid were among the most frequently reported metabolites of cellular respiration while glutamine,glutamate,and valine were among the most commonly reported amino acids.The lipid metabolites identified previously included saturated and unsaturated free fatty acids,aldehydes,and ketones.However,the key findings across studies to date have been inconsistent,potentially due to limited sample sizes and the majority being hospital-based case-control analyses lacking an independent replication group.Conclusions:Studies on metabolomics have thus far provided insights into etiological factors and biomarkers for UGI cancers,supporting the potential of applying metabolomic profiling in cancer prevention and management efforts.Sha Huang Yang Guo Zhexuan Li Yang Zhang Tong Zhou Weicheng You Kaifeng Pan Wenqing Li 2020Cancer Biology & Medicine2020,17,1:11
19Combination of LC/MS and GC/MS based metabolomics to study the hepatotoxic effect of realgar nanoparticles in rats显示文摘Realgar nanoparticles(NPs) are increasingly used as therapeutic agents for their enhanced anti-proliferation effect and cytotoxicity on cancer cells. However, the alteration of particle size may enhance biological reactivity as well as toxicity. A LC/MS and GC/MS based metabolomics approach was employed to explore the mechanism of realgar NPs-induced hepatotoxicity and identify potential biomarkers. Male Sprague-Dawley rats were administrated intragastrically with realgar or realgar NPs at a dose of 1.0 g·kg^(-1)·d^(-1) for 28 days and toxic effects of realgar NPs on liver tissues were examined by biochemical indicator analysis and histopathologic examination. Increased levels of serum enzymes and high hepatic steatosis were discovered in the realgar NPs treated group. Multivariate data analysis revealed that rats with realgar NPs-induced hepatotoxicity could be distinctively differentiated from the animals in the control and realgar treated groups. In addition, 21 and 32 endogenous metabolites were apparently changed in the serum and live extracts, respectively. Realgar NPs might induce free fatty acid and triglyceride accumulation, resulting in hepatotoxicity. In conclusion, the present study represents the first comprehensive LC/MS-and GC/MS-based metabolomics analysis of realgar NPs-induced hepatotoxicity, which may help further research of nanotoxicity.ZHANG Mo-Han CHEN Jia-Qing GUO Hui-Min LI Rui-Ting GAO Yi-Qiao TIAN Yuan ZHANG Zun-Jian HUANG Yin 2017Chinese Journal of Natural Medicines2017,15,9:10
20Potential role of metabolomics in diagnosis and surveillance of gastric cancer显示文摘Gastric cancer is one of the deadliest cancers worldwide, and is especially prevalent in Asian countries. With such high morbidity and mortality, early diagnosis is essential to achieving curative intent treatment and long term survival. Metabolomics is a new field of study that analyzes metabolites from biofluids and tissue samples. While metabolomics is still in its infancy, there are numerous potential applications in oncology, specifically early diagnosis. Only a few studies in the literature have examined metabolomics' role in gastric cancer. Various fatty acid, carbohydrate, nucleic acid, and amino acid metabolites have been identified that distinguish gastric cancer from normal tissue and benign gastric disease. However, findings from these few studies are at times conflicting. Most studies demonstrate some relationship of cancer cells to the Warburg Effect, in that glycolysis predominates with conversion of pyruvate to lactate. This is one of the most consistent findings across the literature. There is less consistency in metabolomic signature with respect to nucleic acids, lipids and amino acids. In spite of this, metabolomics holds some promise for cancer surveillance but further studies are necessary to achieve consistency and validation before it can be widely employed as a clinical tool.Angela W Chan Richdeep S Gill Daniel Schiller Michael B Sawyer 2014World Journal of Gastroenterology2014,20,36:9
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