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Distribution of per-and polyfluoroalkyl substances in blood,serum,and Urine of patients with liver cancer and associations with liver function biomarkers

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Journal of Environmental Sciences 2024年第5期139卷 418-427页

作者： Cao Dai Lin Peng Yanjie Li Zhendong Li Da Chen Fei Wang Nan Lin Department of Hepatobiliary Surgery The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China School of Environment Guangdong Key Laboratory of Environmental Pollution and HealthJinan UniversityGuangzhou 510632China State Key Laboratory of Environmental and Biological Analysis Department of ChemistryHong Kong Baptist UniversityHong Kong 999077China South China Institute of Environmental Sciences MEEGuangzhou 510655China

Studies have shown that per-and polyfluoroalkyl substances(PFASs)may be hepatotoxic in animals or humans.However,data on clinical epidemiology are very limited.In this study,21PFASs were determined in patients with liver diseases,with the highest median concentrations detected in the serum sample(26.7 ng/mL),followed by blood(10.7 ng/mL)and Urine(5.02 ng/mL).Higher total PFAS concentrations were found in hepatocellular carcinoma(HCC)patients compared to non-HCC patients,with significant discrepancies in serum and blood samples.Besides,significant correlations were also found among PFAS concentrations and age,gender,body mass index(BMI),and liver function biomarkers levels.For example,PFAS concentrations are significantly higher in males than in females;Several serum PFASs concentrations increase with age and BMI,while the serum perfluorohexane sulfonic acid(PFHxS)concentrations are negatively correlated with age.In addition,multiple regression models adjusted for age,gender and BMI found that increased serum perfluorobutane sulfonic acid(PFBS),perfluoroheptane sulfonic acid(PFHpS)and perfluorohexylphosphonic acid(PFHxPA)conentrations are correlated with elevated alkaline phosphatase(ALP),aspartate aminotransferase(AST),and alpha-fetoprotein(AFP)(p<0.05).Our results provide epidemiological support for the future study on the potential clinical hepatotoxicity of PFAS.

关键词： Per-and polyfluoroalkyl substances(PFASs) Liver cancer Serum Blood Urine Liver function biomarkers

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Development of an analytical method based on solid-phase extraction and LC-MS/MS for the monitoring of current-use pesticides and their metabolites in human Urine

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Journal of Environmental Sciences 2022年第1期34卷 153-163页

作者： Beibei Gao Giulia Poma Govindan Malarvannan Catalina Dumitrascu Michiel Bastiaensen Minghua Wang Adrian Covaci Toxicological Centre University of AntwerpWilrijk 2610Belgium Department of Pesticide Science College of Plant ProtectionState and Local Joint Engineering Research Center of Green Pesticide Invention and ApplicationNanjing Agricultural UniversityNanjing 210095China

Pyrethroids,organophosphorus pesticides and fipronil have been listed as priority chemicals in human biomonitoring studies because of their wide use and potential health effects in humans.The determination of 13 pesticides,including pyrethroids(deltamethrin,cypermethrin,permethrin,cyfluthrin,bifenthrin),organophosphorus(chlorpyrifos,chlorpyrifosmethyl,and malathion),fipronil,neonicotinoids(imidacloprid,acetamiprid and thiacloprid)and triazole(prothioconazole),together with 13 corresponding metabolites in human Urine samples was achieved by solid-phase extraction and analysis by liquid chromatography coupled to tandem mass spectrometry.All targeted compounds,except malathion dicarboxylic acid,were measured with a mean within-accuracy(n=5)of 71%–114%(RSD:1%–14%)and between-run(n=15)accuracy of 80%–118%(RSD:2%–14%).Limits of quantitation of the targeted analytes ranged from 0.1 to 16 pg/m L.The detection result of Urine samples from 25 volunteers indicated that the detection frequencies of 3,5,6-trichloro-2-pyridinol(median:448 pg/m L),6-chloropyridine-3-carboxylic acid(median:193 pg/m L),2-methyl-3-phenylbenzoic acid(median:181 pg/m L),3-phenoxybenzoic acid(median:99 pg/m L),2-isopropyl-6-methyl-4-pyrimidinol(median:77 pg/m L),cyfluthrin(median:59 pg/m L),cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid(cis-DCCA,median:53 pg/m L),trans-DCCA(median:25 pg/m L),prothioconazole(median:21 pg/m L),imidacloprid(median:7 pg/m L),and prothioconazole-desthio(median:1 pg/m L)were>50%.The obtained results show that the validated method is suitable for the human biomonitoring of these currentuse pesticides and their metabolites.

关键词： Pyrethroids Organophosphorus Fipronil Neonicotinoids Urine Biomonitoring

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An accurate diagnostic approach for urothelial carcinomas based on novel dual methylated DNA markers in small-volume Urine

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Chinese Medical Journal 2024年第2期137卷 232-234页

作者： Yucai Wu Di Cai Jian Fan Chang Meng Shiming He Zhihua Li Lianghao Zhang Kunlin Yang Aixiang Wang Xinfei Li Yicong Du Shengwei Xiong Mancheng Xia Tingting Li Lanlan Dong YanqingGong Liqun Zhou Xuesong Li Department of Urology Peking University First HospitalBeijing 100034China Institute of Urology Peking UniversityBeijing 100034China National Urological Cancer Center Beijing 100034China Urogenital Diseases(Male)Molecular Diagnosis and Treatment Center Peking UniversityBeijing 100034China Wuhan Ammunition Life-tech Company Ltd.WuhanHubei 430200China

Diagnostic methods for urothelial carcinomas(UCs)are often invasive or have suboptimal accuracy.Methylation of exfoliated cell DNA or cell-free DNA in Urine has shown great promise in the diagnosis of UCs.However,most current studies have focused on bladder cancer(BCa),and only a few high-plex methylated DNA panels based on large-volume Urine have been reported to exhibit both high sensitivity and specificity.[1,2]The purpose of this study was to identify universal biomarkers for BCa and upper tract urothelial carcinoma(UTUC)using a small volume of Urine.We developed a dual-target diagnostic panel comprising the novel marker AL021918.2 and the well-known BCa biomarker Vimentin(VIM).This panel can accurately detect UCs using only 1.8 mL of full-voided Urine.

关键词： Urine bladder diagnosis

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Survival outcomes in older patients with different stages of acute kidney injury defined by the addition of Urine output criteria

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Chinese Medical Journal 2023年第9期136卷 1129-1131页

作者： Jiebin Hou Yabin Zhang Jie Zhang Yang Liu Xiaohua Wang Zhen Wu Jiayu Guo Xiaoli Sun Qingli Cheng Qiangguo Ao Department of Nephrology The Second Medical Centre&National Clinical Research Center for Geriatric DiseasesChinese PLA General HospitalBeijing 100853China Department of Nephrology National Clinical Research Center for Geriatric DiseasesChinese PLA General HospitalBeijing 100853China Department of Nephrology The Second Medical CentreChinese PLA General HospitalBeijing 100853China Department of Gastroenterology The Second Medical CentreChinese PLA General HospitalBeijing 100853China

To the Editor:Globally,acute kidney injury(AKI)is a common life-threatening condition.AKI is more prevalent in elderly patients,with increasing mortality rates.Compared with younger patients,older patients with AKI have a higher risk of persistent injury and poorer prognoses.[1]Older individuals often have comorbidities,increasing their susceptibility to AKI.Kidney Disease:Improving Global Outcomes(KDIGO)criteria define and stage AKI based on the higher stage of AKI defined by either serum creatinine(SCr)level or Urine output(UO).[2]However,the record of UO is difficult to access in clinic,the data on the value of UO combined with SCr for AKI diagnosis or prognosis in elderly patients are lacking.Therefore,the objectives of this study were to investigate whether UO would influence the classification of AKI and improve the accuracy of prediction of the clinical prognosis in elderly patients.

关键词： patients Urine Survival

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Graphene as adsorbent for highly efficient extraction of modified nucleosides in Urine prior to liquid chromatography-tandem mass spectrometry analysis

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Chinese Chemical Letters 2024年第4期35卷 490-495页

作者： Cheng Guo Xiaoxiao Zhang Xiujuan Hong Yiqiu Hu Lingna Mao Kezhi Jiang Cancer Institute(Key Laboratory of Cancer Prevention and Intervention China National Ministry of Education)The Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China Cancer Center Zhejiang UniversityHangzhou 310058China Key Laboratory of Organosilicon Chemistry and Material Technology College of Material Chemistry and Chemical EngineeringHangzhou Normal UniversityHangzhou 311121China Department of General Practice The Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China

RNA modifications have been involved in numerous biological processes, and aberrations of these modifications are tightly associated with various diseases including cancer. Herein, we developed graphenebased solid-phase extraction and robust ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) combined with stable isotope-dilution for simultaneous enrichment and accurate determination of 17 modified nucleosides in human Urine. We found graphene could effectively adsorb various modified nucleosides in human Urine samples. With this method, we identified and quantified these modified nucleosides in Urine samples collected from lung cancer patients and healthy controls.We revealed that the levels of 12 modified nucleosides were all diminished in Urine from lung cancer patients, compared with healthy controls. It is worth noting that we demonstrated, for the first time, the presence of 5,2-O-dimethyluridine(m~5U_m) in human Urine. Together, we established a robust analytical method for simultaneous determinations of 17 modified nucleosides in human Urine, and our results revealed a close correlation between the concentrations of urinary modified nucleosides and the occurrence of lung cancer, implying the potential applications of these modified nucleosides as noninvasive biomarkers for the early detection of lung cancer. Moreover, this study will stimulate future investigations on the regulatory roles of RNA modifications in the initiation and progression of lung cancer.

关键词： Mass spectrometry RNA modification Modified nucleosides Graphene Biomarker Urine

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A novel in vitro prognostic model of bladder cancer based on Urine-derived living tumor cells

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Genes & Diseases 2023年第6期10卷 2586-2596页

作者： Jiaqi Wang Jiying Zhu Junchi Hu Ziruoyu Wang Xiaobo Wang Jianbo Pan Yiwei Chu Zengxia Li Wei Jiang Chunmin Liang Jun Hou Jianming Guo Yongjun Dang Shuai Jiang Key Laboratory of Metabolism and Molecular Medicine Ministry of Education and Department of Biochemistry and Molecular BiologySchool of Basic Medical SciencesFudan UniversityShanghai 200032China Department of Immunology School of Basic Medical SciencesFudan UniversityShanghai 200032China Laboratory of Tumor Immunology Department of AnatomyHistologyand EmbryologySchool of Basic Medical SciencesFudan UniversityShanghai 200032China Center for Novel Target and Therapeutic Intervention Chongqing Medical UniversityChongqing 400016China Department of Pathology Zhongshan HospitalFudan UniversityShanghai 200032China Department of Urology Zhongshan HospitalFudan UniversityShanghai 200032China Department of Urology Zhongshan Hospital Wusong BranchFudan UniversityShanghai 200940China

Bladder cancer(BLCA)remains a difficult malignancy to manage because of its high recurrence,intense follow-up,and invasive diagnostic and treatment techniques.Immune checkpoint inhibitors(ICIs)have forged a new direction for the treatment of BLCA,but it is currently challenging to predict whether an individual patient will be sensitive to ICIs.We collected 43 Urine/tumor samples from BLCA patients for primary bladder cancer cells(BCCs)culturing using our previously reported BCC culture platform.We used flow cytometry(FCM)to measure the expression levels of Programmed Death-Ligand 1(PD-L1)on BCCs before and after interferon-gamma(IFN-γ)treatment and found that PD-L1 expression and the sensitivities to IFN-γvaried among patients.RNA-sequencing,western blotting,and programmed death-1(PD-1)binding assays confirmed that the BCC FCM-based PD-L1 detection platform(BC-PD-L1)was reliable and was not hindered by the glycosylation of PD-L1.In the subsequent retrospective study,we found that IFN-γ-stimulated PD-L1(sPD-L1)expression on BCCs detected by BC-PD-L1 could predict the prognosis of BLCA patients.Importantly,the prognostic value was similar or even better in Urine-derived BC-PD-L1(UBC-PD-L1).Transcriptome analysis showed that BCCs with high sPD-L1 tended to enrich genes associated with the collagen-containing extracellular matrix,cell–cell adhesion,and positive regulation of the immune system.In addition,the UBC-PD-L1 also exhibited predictive value for ICI response in BLCA patients.In conclusion,as a novel personalized Urine-detection method,UBC-PD-L1 may provide a rapid,accurate,and non-invasive tool for monitoring tumor progression,predicting therapeutic responses,and helping improve BLCA clinical treatment in future.

关键词： Bladder cancer Immune checkpoint inhibitors Predictive model Primary cells Urine

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Plasmonic Gold Chip for Multiplexed Detection of Ovarian Cancer Biomarker in Urine

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Chemical Research in Chinese Universities 2022年第4期38卷 935-940页

作者： CHEN Minwen LIAO Tao ZENG Linsheng ZENG Zhongyi YANG Qinglai WANG Guoxin WWHS Biotech.Inc. Shenzhen518000P.R.China Center for Molecular Imaging Probe Hunan Province Key Laboratory of Tumor Cellular and Molecular PathologyCancer Research InstituteSchool of Preclinical MedicineHengyang Medical SchoolUniversity of South ChinaHengyang421001P.R.China Shenzhen Traditional Chinese Medicine Hospital Shenzhen518033P.R.China

Human epididymal protein 4(HE4),carbohydrate antigen 125(CA125)and osteopontin(OPN)are three key biomarkers in detecting ovarian cancer.To explore the diagnosis value of combined detection of these three biomarkers for ovarian cancer,we developed a multiplexed assay on a plasmonic gold(pGOLD)platform for measuring HE4,CA125 and OPN in Urine.The receiver operator characteristic(ROC)curve was drawn,and the diagnosis values of each biomarker alone or in combination for ovarian cancer were evaluated.In the analysis to distinguish ovarian cancer from other gynecological cancers,ovarian cysts and healthy people,the sensitivities of HE4,CA125 and OPN were 72.55%,52.82%and 68.63%,the specificity values were 95.06%,87.65%and 90.12%,while the areas under the curve(AUC)were 0.85,0.75 and 0.77,respectively.The sensitivity and specificity for combination detection of the three markers were 90.20%and 80.25%.The detection methods of HE4,CA125 and OPN based on plasma fluorescence enhanced chip showed good analytic and diagnostic performance,and provided a non-invasive method for the diagnosis of ovarian cancer.

关键词： Plasmonic gold chip Urine Ovarian cancer Multiplexed detection

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A sandwich ELISA kit reveals marked elevation of titin N-terminal fragment levels in the Urine of mdx mice

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Animal Models and Experimental Medicine 2022年第1期5卷 48-55页

作者： Taku Shirakawa Ayumu Ikushima Nobuhiro Maruyama Yoshinori Nambu Hiroyuki Awano Kayo Osawa Kei Nirasawa Yoichi Negishi Hisahide Nishio Shoji Fukushima Masafumi Matsuo Research Center for Locomotion Biology Kobe Gakuin UniversityKobeJapan KNC Department of Nucleic Acid Drug Discovery Faculty of RehabilitationKobe Gakuin UniversityKobeJapan Department of Pharmaceutics Faculty of Pharmaceutical SciencesKobe Gakuin UniversityKobeJapan Diagnostic&Research Reagents Division Immuno-Biological Laboratories Co.LtdFujiokaJapan Department of Pediatrics Kobe University Graduate School of MedicineKobeJapan Department of Medical Technology Faculty of Health SciencesKobe Tokiwa UniversityKobeJapan Department of Drug Delivery and Molecular Biopharmaceutics School of PharmacyTokyo University of Pharmacy and Life SciencesTokyoJapan

The mdx mouse is a model of Duchenne muscular dystrophy(DMD),a fatal progressive muscle wasting disease caused by dystrophin deficiency,and is used most widely in preclinical studies.Mice with dystrophin deficiency,however,show milder muscle strength phenotypes than humans.In human,the introduction of a sandwich enzyme-linked immunosorbent assay(ELISA)kit revealed a more than 700-fold increase in titin N-terminal fragment levels in the Urine of pediatric patients with DMD.Notably,the urinary titin level declines with aging,reflecting progression of muscle wasting.In mouse,development of a highly sensitive ELISA kit has been awaited.Here,a sandwich ELISA kit to measure titin N-terminal fragment levels in mouse Urine was developed.The developed kit showed good linearity,recovery,and repeatability in measuring recombinant or natural mouse titin N-terminal fragment levels.The titin N-terminal fragment concentration in the Urine of mdx mice was more than 500-fold higher than that of normal mice.Urinary titin was further analyzed by extending the collection of Urine samples to both young(3-11 weeks old)and aged(56-58 weeks old)mdx mice.The concentration in the young group was significantly higher than that in the aged group.It was concluded that muscle protein breakdown is active and persistent in mdx mice even though the muscle phenotype is mild.Our results provide an opportunity to develop DMD treatments that aim to alleviate muscle protein breakdown by monitoring urinary titin levels.

关键词： biomarker Duchenne muscular dystrophy ELISA mdx mouse titin Urine

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Probing the degradation of pharmaceuticals in Urine using MFC and studying their removal efficiency by UPLC-MS/MS

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Journal of Pharmaceutical Analysis 2021年第3期11卷 320-329页

作者： Priya Sharma Devendra Kumar Srikanth Mutnuri Applied Environmental Biotechnology Laboratory Birla Institute of Technology&Science(BITS)Pilani403726ZuarinagarIndia Central Sophisticated Instrumentation Facility Birla Institute of Technology&Science(BITS)Pilani403726ZuarinagarIndia Department of Pharmaceutical Sciences College of PharmacyUniversity of Nebraska Medical CenterOmahaNE68198-602USA

Nutrient recovery from source-separated human Urine has attracted interest as it is rich in nitrogen and phosphorus that can be utilized as fertilizer.However,Urine also contains pharmaceuticals,steroid hormones,etc.and their removal is crucial as they have detrimental effects on the environment and human health.The current study focuses on investigating the degradation of pharmaceuticals using a double-chamber microbial fuel cell(MFC).Urine was spiked with four pharmaceuticals(trimethoprim,lamivudine,levofloxacin,and estrone)at a concentration of 2 mg/mL.The MFC was operated for 7 months in batch mode with this spiked Urine as feed.The degradation efficiency of the MFC was studied,for which a selective liquid chromatography-tandem mass-spectrometric method was developed for the quantitation of compounds used in the spiking experiments and was validated with a lower limit of quantification of 0.39 ng/mL.The maximum removal rate achieved was 96%±2%.The degradation mechanism involved processes like sorption and anoxic biodegradation.The voltage curve obtained showed that the presence of pharmaceuticals had an initial negative impact on power generation along with increased organic content;however,after the reactor acclimatization,increased power output was achieved with maximum organics removal at 30 h of retention time.This work opens a new perspective for the anoxic biodegradation of pharmaceuticals and can be useful in future bioremediation studies.

关键词： Pharmaceuticals Urine MFC Biodegradation Liquid chromatography mass spectroscopy

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Urine Metabonomic Analysis of Interventions Effect of Soy Isoflavones on Rats Exposed to Di-(2-ethylhexyl) Phthalate

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Biomedical and Environmental Sciences 2020年第2期33卷 77-88页

作者： DONG Xin Wen YAO San Qiao WU Hao Yu ZHANG Yun Bo WANG Cheng NA Xiao Lin WU Wei Dong Department of Environmental and Occupational Health School of Public HealthXinxiang Medical UniversityXinxiang 453003HenanChina Department of Environmental Hygiene Public Health CollegeHarbin Medical UniversityHarbin 150086HeilongjiangChina

Objective Di-(2-ethylhexyl) phthalate(DEHP) is a ubiquitous environmental contaminant.As an endocrine disruptor,it seriously threatens human health and ecological environmental safety.This study examines the impact of intervention with soybean isoflavones(SIF) on DEHP-induced toxicity using a metabonomics approach.Methods Rats were randomly divided into control(H),SIF-treated(A,86 mg/kg body weight),DEHP-treated(B,68 mg/kg),and SIF plus DEHP-treated(D) groups.Rats were given SIF and DEHP daily through diet and gavage,respectively.After 30 d of treatment,rat Urine was tested using UPLC/MS with multivariate analysis.Metabolic changes were also evaluated using biochemical assays.Results Metabolomics analyses revealed that p-cresol glucuronide,methyl hippuric acid,N1-methyl-2-pyridone-5-carboxamide,lysophosphatidycholine [18:2(9 Z,12 Z)] {lyso PC [18:2(9 Z,12 Z)]},lyso PC(16:0),xanthosine,undecanedioic acid,and N6-acetyl-l-lysine were present at significantly different levels in control and treatment groups.Conclusion SIF supplementation partially protects rats from DEHP-induced metabolic abnormalities by regulating fatty acid metabolism,antioxidant defense system,amino acid metabolism,and is also involved in the protection of mitochondria.

关键词： Di-(2-ethylhexyl) phthalate Soy isoflavones Metabonomics UPLC-QTOF-MS/MS Urine

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