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COVID-19 and the gastrointestinal tract:Source of infection or merely a target of the inflammatory process following SARS-CoV-2 infection?

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World Journal of Gastroenterology 2021年第14期27卷 1406-1418页

作者： Jacopo Troisi Giorgia Venutolo Meritxell Pujolassos Tanyà Matteo Delli Carri Annamaria Landolfi Alessio Fasano metabolomics section Theoreo srl-Spin-off Company of the University of SalernoMontecorvino Pugliano 84090SAItaly Department of Chemistry and Biology“A.Zambelli” University of SalernoFisciano 84084SAItaly European Biomedical Research Institute of Salerno Salerno 84125SAItaly Department of Medicine Surgery and Dentistry“Scuola Medica Salernitana”University of SalernoBaronissi 84081SAItaly Mucosal Immunology and Biology Research Center and Center for Celiac Research Harvard Medical SchoolMassachusetts Gen Hosp ChildrenMucosal Immunology and Biology Research CenterBostonMA 02114United States

Gastrointestinal(GI)symptoms have been described in a conspicuous percentage of coronavirus disease 2019(COVID-19)*** clinical evidence is supported by the detection of viral RNA in stool,which also supports the hypothesis of a possible fecal-oral transmission *** involvement of GI tract in severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection is corroborated by the theoretical assumption that angiotensin converting enzyme 2,which is a SARS-CoV-2 target receptor,is present along the GI *** have pointed out that gut dysbiosis may occur in COVID-19 patients,with a possible correlation with disease severity and with complications such as multisystem inflammatory syndrome in ***,the question to be addressed is whether dysbiosis is a consequence or a contributing cause of SARS-CoV-2 *** such a scenario,pharmacological therapies aimed at decreasing GI permeability may be beneficial for COVID-19 *** the possibility of a fecal-oral transmission route,water and environmental sanitation play a crucial role for COVID-19 containment,especially in developing countries.

关键词： COVID-19 SARS-CoV-2 Gastrointestinal symptoms Gut microbiome Dysbiosis Zonulin Fecal-oral transmission

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To metabolomics and beyond:a technological portfolio to investigate cancer metabolism

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Signal Transduction and Targeted Therapy 2023年第4期8卷 1721-1742页

作者： Federica Danzi Raffaella Pacchiana Andrea Mafficini Maria TScupoli Aldo Scarpa Massimo Donadelli Alessandra Fiore Department of Neurosciences Biomedicine and Movement SciencesSection of BiochemistryUniversity of VeronaVeronaItaly Department of Diagnostics and Public Health University of VeronaVeronaItaly Department of Neurosciences Biomedicine and Movement SciencesBiology and Genetics SectionUniversity of VeronaVeronaItaly ARC-NET Research Centre University and Hospital Trust of VeronaVeronaItaly

Tumour cells have exquisite flexibility in reprogramming their metabolism in order to support tumour initiation, progression,metastasis and resistance to therapies. These reprogrammed activities include a complete rewiring of the bioenergetic, biosyntheticand redox status to sustain the increased energetic demand of the cells. Over the last decades, the cancer metabolism field hasseen an explosion of new biochemical technologies giving more tools than ever before to navigate this complexity. Within a cell ora tissue, the metabolites constitute the direct signature of the molecular phenotype and thus their profiling has concrete clinicalapplications in oncology. metabolomics and fluxomics, are key technological approaches that mainly revolutionized the fieldenabling researchers to have both a qualitative and mechanistic model of the biochemical activities in cancer. Furthermore, theupgrade from bulk to single-cell analysis technologies provided unprecedented opportunity to investigate cancer biology at cellularresolution allowing an in depth quantitative analysis of complex and heterogenous diseases. More recently, the advent offunctional genomic screening allowed the identification of molecular pathways, cellular processes, biomarkers and noveltherapeutic targets that in concert with other technologies allow patient stratification and identification of new treatmentregimens. This review is intended to be a guide for researchers to cancer metabolism, highlighting current and emergingtechnologies, emphasizing advantages, disadvantages and applications with the potential of leading the development ofinnovative anti-cancer therapies.

关键词： metabolism qualitative beyond

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Measurement of very low-molecular weight metabolites by traveling wave ion mobility and its use in human urine samples

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Journal of Pharmaceutical Analysis 2024年第5期14卷 733-743页

作者： Alongkorn Kurilung Suphitcha Limjiasahapong Khwanta Kaewnarin Pattipong Wisanpitayakorn Narumol Jariyasopit Kwanjeera Wanichthanarak Sitanan Sartyoungkul Stephen Choong Chee Wong Nuankanya Sathirapongsasuti Chagriya Kitiyakara Yongyut Sirivatanauksorn Sakda Khoomrung Siriraj Center of Research Excellent in metabolomics and Systems Biology(SiCORE-MSB) Faculty of Medicine Siriraj HospitalMahidol UniversityBangkok10700Thailand Siriraj metabolomics and Phenomics Center Faculty of Medicine Siriraj HospitalMahidol UniversityBangkok10700Thailand Department of Biomedical Informatics University of Arkansas for Medical SciencesLittle RockAR72205USA SingHealth Duke-NUS Institute of Biodiversity Medicine National Cancer Centre Singapore168583Singapore Waters Pacific Pte. Ltd.Singapore117528Singapore Program in Translational Medicine Faculty of Medicine Ramathibodi HospitalMahidol UniversityBangkok10400Thailand Chakri Naruebodindra Medical Institute Faculty of Medicine Ramathibodi HospitalMahidol UniversitySamut Prakan10540Thailand Department of Medicine Ramathibodi HospitalMahidol UniversityBangkok10400Thailand Department of Biochemistry Faculty of Medicine Siriraj HospitalMahidol UniversityBangkok10700Thailand Center of Excellence for Innovation in Chemistry(PERCH-CIC) Faculty of ScienceMahidol UniversityBangkok10400Thailand

The collision cross-sections(CCS)measurement using ion mobility spectrometry(IMS)in combination with mass spectrometry(MS)offers a great opportunity to increase confidence in metabolite ***,owing to the lack of sensitivity and resolution,IMS has an analytical challenge in studying the CCS values of very low-molecular-weight metabolites(VLMs250 Da).Here,we describe an analytical method using ultrahigh-performance liquid chromatography(UPLC)coupled to a traveling wave ion mobility-quadrupole-time-of-flight mass spectrometer optimized for the measurement of VLMs in human urine *** experimental CCS values,along with mass spectral properties,were reported for the 174 *** experimental data included the mass-to-charge ratio(m/z),retention time(RT),tandem MS(MS/MS)spectra,and CCS *** the studied metabolites,263 traveling wave ion mobility spectrometry(TWIMS)-derived CCS values(TWCCSN2)were reported for the first time,and more than 70%of these were CCS values of *** TWCCSN2 values were highly repeatable,with inter-day variations ofmetabolomics Standards Initiative,55 urinary metabolites were identified with a confidence level of *** these 55 metabolites,53(96%)were *** larger number of confirmed compounds found in this study was a result of the addition of TWCCSN2 values,which clearly increased metabolite identification confidence.

关键词： Very low-molecular-weight metabolites Traveling wave ion mobility Collision cross-section Human urine

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Disease monitoring of hepatocellular carcinoma through metabolomics

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World Journal of Hepatology 2017年第1期9卷 1-17页

作者： Asem I Fitian Roniel Cabrera School of Medicine Virginia Commonwealth University Department of Medicine Division of Gastroen- terology Hepatology and Nutrition Section of Hepatobiliary Diseases University of Florida

We elucidate major pathways of hepatocarcinogenesis and accurate diagnostic metabolomic biomarkers of hepatocellular carcinoma (HCC) identified by contemporary HCC metabolomics studies, and delineate a model HCC metabolomics study design. A literature search was carried out on Pubmed for HCC metabolomics articles published in English. All relevant articles were accessed in full text. Major search terms included “HCC”, “metabolomics”, “metabolomics”, “metabonomic” and “biomarkers”. We extracted clinical and demographic data on all patients and consolidated the lead candidate biomarkers, pathways, and diagnostic performance of metabolomic expression patterns reported by all studies in tables. Where reported, we also extracted and summarized the metabolites and pathways most highly associated with the development of cirrhosis in table format. Pathways of lysophospholipid, sphingolipid, bile acid, amino acid, and reactive oxygen species metabolism were most consistently associated with HCC in the cited works. Several studies also elucidate metabolic alterations strongly associated with cirrhosis, with γ-glutamyl peptides, bile acids, and dicarboxylic acids exhibiting the highest capacity for stratifying cirrhosis patients from appropriately matched controls. Collectively, global metabolomic profiles of the referenced works exhibit a promising diagnostic capacity for HCC at a capacity greater than that of conventional diagnostic biomarker alpha-fetoprotein. metabolomics is a powerful strategy for identifying global metabolic signatures that exhibit potential to be leveraged toward the screening, diagnosis, and management of HCC. A streamlined study design and patient matching methodology may improve concordance among metabolomic datasets in future works.

关键词： metabolomics Hepatocellular carcinoma Biomarkers Metabolic profiling Chromatography/mass spectrometry Noninvasive biomarkers Cirrhosis

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4-Aminoazobenzene:A novel negative ion matrix for enhanced MALDI tissue imaging of metabolites

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Chinese Chemical Letters 2024年第11期35卷 273-277页

作者： Ran Wu Dongxu Jiang Hao Hu Chenyu Yang Liang Qin Lulu Chen Zehui Hu Hualei Xu Jinrong Li Haiqiang Liu Hua Guo Jinxiang Fu Qichen Hao Yijun Zhou Jinchao Feng Qiang Wang Xiaodong Wang Key Laboratory of Mass Spectrometry Imaging and metabolomics(Minzu University of China) State Ethnic Affairs CommissionBeijing 100081China College of Life and Environmental Sciences Centre for Imaging&Systems BiologyMinzu University of ChinaBeijing 100081China College of Biological Sciences and Biotechnology Beijing Forestry UniversityBeijing 100083China Department of Orthopaedic Surgery Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310016China Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province Hangzhou 310016China

Endogenous metabolites play key functions in many important physiological and biochemical *** comprehensive in situ detection and direct imaging of metabolites in bio-tissues by matrix-assisted laser desorption/ionization mass spectrometry imaging(MALDI-MSI)is very important for understanding complex and diverse biological processes and has become an essential aspect of spatial *** this work,4-aminoazobenzene(AAB)was successfully screened and optimized as a new negative ion(-)MALDI matrix to enhance the in situ detection and imaging of metabolites in tissues using ***,AAB exhibited superior properties in terms of ultraviolet absorption,background ion interference,matrix morphology,and metabolite ionization *** was used for in situ detection and imaging of metabolites in rat brain and germinating Chinese yew seed tissue sections,where 264and 339 metabolite ion signals were successfully detected and imaged using(-)MALDI-MS,*** addition,high-resolution imaging of mouse eyeball section using MALDI-tims TOF MSI with spatial resolution of up to 10μm was successfully carried out,showing that AAB is an efficient(-)MALDI matrix for capturing high-resolution images of metabolites in biological tissue sections.

关键词： MALDI-MSI 4-Aminoazobenzene Metabolites In situ detection Tissue imaging

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The dilemmas of liver cancer heterogeneity

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Cancer Biology & Medicine 2018年第S1期15卷 14-14页

作者： Xinwei Wang The Liver Carcinogenesis section Laboratory of Human CarcinogenesisCenter for Cancer ResearchNational Cancer InstituteBethesdaMarylandUSA

Genomic analyses of most solid tumors reveal a complex mutational landscape with vast inter-tumor and intratumor *** histological tumor type and the tumor cells within each tumor type display striking molecular and biological *** molecular heterogeneity in tumors is a major obstacle for early diagnosis and effective *** is especially relevant to hepatocellular carcinoma(HCC)and intrahepatic cholangiocarcinoma(iCCA)where the etiological factors elicit different molecular mechanisms to initiate carcinogenesis leading to distinct molecular subtypes and complex tumor cell *** heterogeneity poses a major challenge in exploring the factors responsible for early stage hepatocarcinogenesis,development of diagnostic tools,and defining effective treatment strategies for HCC and *** obstacles emphasize the importance of developing new strategies to change the current dire *** establishment of patient populations with associated wellannotated biobanks and molecularly well-characterized samples are essential to define unique tumor ***,understanding the molecular features of tumor cells at a single cell level might provide a better understanding of tumor cell communities and help define the key drivers responsible for tumor initiation and ***-based technologies such as integrated genomics,transcriptomics,and metabolomics aid in a better way to distinguish tumor subtypes allowing the stratification of patients with greater homogeneity and assist in molecular *** genome-based signatures might serve to delineate the critical gatekeepers of cancer initiation and progression which further helps to identify the druggable targets by integrated genomics and to explore the functionally linked networks in HCC and *** these available backgrounds,we might effectively identify biomarkers and potential targets for early liver cancer intervention.

关键词： dilemmas liver cancer heterogeneity

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Changes in the Non-targeted Metabolomic Profile of Three-year-old Toddlers with Elevated Exposure to Polycyclic Aromatic Hydrocarbons

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Biomedical and Environmental Sciences 2024年第5期37卷 479-493页

作者： LI Yang LIN Dan ZHANG Xiu Qin JU Guang Xiu SU Ya ZHANG Qian DUAN Hai Ping YU Wei Sen WANG Bing Ling PANG Shu Tao Department of Epidemiology and Health Statistics School of Public HealthQingdao UniversityQingdao 266021ShandongChina Department of Environmental Health Qingdao Municipal Center for Disease Control and PreventionQingdao Institute of Preventive MedicineQingdao 266033ShandongChina Physicochemical Laboratory Qingdao Municipal Center for Disease Control and PreventionQingdao Institute of Preventive MedicineQingdao 266033ShandongChina section of Child Health Care Huangdao Maternity and Child Health Care Hospital of QingdaoQingdao 266499ShandongChina Qingdao Blood Center Qingdao 266071ShandongChina

Objective To investigate changes in the urinary metabolite profiles of children exposed to polycyclic aromatic hydrocarbons(PAHs)during critical brain development and explore their potential link with the intestinal *** Liquid chromatography-tandem mass spectrometry was used to determine ten hydroxyl metabolites of PAHs(OH-PAHs)in 36-month-old ***,37 children were categorized into low-and high-exposure groups based on the sum of the ten ***-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to identify non-targeted metabolites in the urine ***,fecal flora abundance was assessed by 16S rRNA gene sequencing using Illumina *** The concentrations of 21 metabolites were significantly higher in the high exposure group than in the low exposure group(variable importance for projection>1,P<0.05).Most of these metabolites were positively correlated with the hydroxyl metabolites of naphthalene,fluorine,and phenanthrene(r=0.336–0.531).The identified differential metabolites primarily belonged to pathways associated with inflammation or proinflammatory states,including amino acid,lipid,and nucleotide ***,these distinct metabolites were significantly associated with specific intestinal flora abundances(r=0.34–0.55),which were mainly involved in *** Higher PAH exposure in young children affected metabolic homeostasis,particularly that of certain gut microbiota-derived *** investigation is needed to explore the potential influence of PAHs on the gut microbiota and their possible association with neurodevelopmental outcomes.

关键词： Child Gut microbiota Non-targeted metabolomics Polycyclic aromatic hydrocarbons Urinary metabolite profile

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Global tissue and serum metabolomics reveals altered tumor biochemical activity in molecular subtypes of hepatocellular carcinoma and cholangiocarcinoma

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Cancer Biology & Medicine 2018年第S1期15卷 13-14页

作者： Xinwei Wang Thaniya Mathuros Ruchirawat Anuradha Budhu Yotsawat Pomyen Jittiporn Chaisaingmongkoll Hien Dang Siritida Rabibhadana Benjarath Pupacdi Marshonna Forgues Vajarabhongsa Bhudhisawasdi Nirush Lertprasertsuke Anon Chotirosniramit Chawalit Pairojkul Chirayu Auewarakul Thaniya Sricharunrat Kannika Phornphutkul Suleeporn Sangrajrang Chulabhorn Mahidol The Liver Carcinogenesis section Laboratory of Human CarcinogenesisCenter for Cancer ResearchNational Cancer InstituteBethesdaMDUSA Chulabhorn Research Institute BangkokThailand Khon Kaen University Khon KaenThailand Chiang Mai University Chiang MaiThailand Chulabhorn Hospital BangkokThailand Rajavej Hospital and Lampang Cancer Center Chiang MaiThailand

Objective:Cancer metabolite profiling(or cancer metabolomics),the global view of the biochemical end products of cellular processes,is a promising approach to identify biomarkers and tumor subgroups,and to understand ... 详细信息

关键词： Global tissue metabolomics

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Exhaled Breath Condensates as a Source for Biomarkers for Characterization of Inflammatory Lung Diseases

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Journal of Analytical Sciences, Methods and Instrumentation 2013年第1期3卷 17-29页

作者： Puneet Bajaj Faoud T. Ishmael Department of Biochemistry and Molecular Biology College of Medicine The Pennsylvania State University Hershey USA Department of Medicine Division of Pulmonary Allergy and Critical Care Medicine Section of Allergy and Immunology Milton S. Hershey Medical Center The Pennsylvania State University Hershey USA

Inflammatory lung diseases such as asthma and chronic obstructive pulmonary disease are common and difficult to diagnose and characterize. This is due in large part to difficulty in obtaining samples directly from the inflamed lung. The collection of lung secretions by traditional methods including bronchoalveolar lavage and induced sputum collection are limited by their invasive nature. Exhaled breath condensate (EBC) is a simple and non-invasive technique of collecting fluid samples, which are representative of airway lining fluid. Advances in collection methods and evolving molecular techniques have led to development of more sensitive assays for existing biomarkers and identification of new biomarkers, which can be potentially useful in monitoring lung inflammation. In this review, we present the current understanding of various biomarkers including small molecules (H2O2, pH and nitric oxide related biomarkers), lipid mediators (8-isprostane, leukotrienes and prostaglandins), small proteins (cytokines and chemokines) and nucleic acids (DNA and microRNAs). We also discuss the differential profile of biomarkers in recognizing different patterns of lung inflammation. As the sensitivity of methods of EBC improves, this biofluid will play an increasing role in diagnosis and monitoring of lung diseases.

关键词： Exhaled Breath Condensate Inflammation Biomarkers Hydrogen Peroxide Ph Micrornas Nitric Oxide Leukotrienes Prostaglandins metabolomics

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Metabolic pathway modulation by olanzapine:Multitarget approach for treating violent aggression in patients with schizophrenia

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World Journal of Psychiatry 2025年第1期15卷 37-53页

作者： Yan-Ning Song Shuang Xia Zhi Sun Yong-Chao Chen Lu Jiao Wen-Hua Wan Hong-Wei Zhang Xiao Guo Hua Guo Shou-Feng Jia Xiao-Xin Li Shi-Xian Cao Li-Bin Fu Meng-Meng Liu Tian Zhou Lv-Feng Zhang Qing-Quan Jia Department of Pharmacy The Affiliated Encephalopathy Hospital of Zhengzhou University(Zhumadian Second People's Hospital)Zhumadian 463000Henan ProvinceChina Department of Pharmacy The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina Department of Pharmacy Zhumadian First People's HospitalZhumadian 463000Henan ProvinceChina Scientific Education section The Affiliated Encephalopathy Hospital of Zhengzhou University(Zhumadian Second People's Hospital)Zhumadian 463000Henan ProvinceChina Department of Psychiatry The Affiliated Encephalopathy Hospital of Zhengzhou University(Zhumadian Second People's Hospital)Zhumadian 463000Henan ProvinceChina Clinical Laboratory The Affiliated Encephalopathy Hospital of Zhengzhou University(Zhumadian Second People's Hospital)Zhumadian 463000Henan ProvinceChina Publicity Division The Affiliated Encephalopathy Hospital of Zhengzhou University(Zhumadian Second People's Hospital)Zhumadian 463000Henan ProvinceChina

BACKGROUND The use of network pharmacology and blood metabolomics to study the patho-genesis of violent aggression in patients with schizophrenia and the related drug mechanisms of action provides new directions for reducing the risk of violent aggression and optimizing treatment *** To explore the metabolic regulatory mechanism of olanzapine in treating patients with schizophrenia with a moderate to high risk of violent *** Metabolomic technology was used to screen differentially abundant metabolites in patients with schizophrenia with a moderate to high risk of violent aggression before and after olanzapine treatment,and the related metabolic pathways were *** pharmacology was used to establish protein-protein interaction networks of the core targets of *** Ontology functional analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were subsequently *** Compared with the healthy group,the patients with schizophrenia group presented significant changes in the levels of 24 metabolites related to the disruption of 9 metabolic pathways,among which the key pathways were the alanine,aspartate and glutamate metabolism and arginine biosynthesis *** treatment with olanzapine,the levels of 10 differentially abundant metabolites were significantly reversed in patients with *** effectively regulated six metabolic pathways,among which the key pathways were alanine,aspartate and glutamate metabolism and arginine biosynthesis *** core targets of olanzapine were involved in several key *** The metabolic pathways of alanine,aspartate,and glutamate metabolism and arginine biosynthesis are the key pathways involved in olanzapine treatment for aggressive schizophrenia.

关键词： Schizophrenia Violent aggression Olanzapine metabolomics Network pharmacology

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