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CHO cell cytotoxicity and genotoxicity analyses of disinfection by-products： An updated review

Journal of Environmental Sciences 2017年第8期29卷 64-76页

作者： elizabeth d.wagner Michael J.Plewa Safe Global Water Institute University of Illinois at Urbana-Champaign 1101 W Peabody Dr. Urbana IL 61801 United States department of Crop Sciences University of Illinois at Urbana-Champaign 1101 W Peabody Dr. Urbana IL 61801 United States

The disinfection of drinking water is an important public health service that generates high quality, safe and palatable tap water. The disinfection of drinking water to reduce waterborne disease was an outstanding public health achievement of the 20 th *** unintended consequence is the reaction of disinfectants with natural organic matter,anthropogenic contaminants and bromide/iodide to form disinfection by-products（dBPs）.A large number of dBPs are cytotoxic, neurotoxic, mutagenic, genotoxic, carcinogenic and teratogenic. Epidemiological studies demonstrated low but significant associations between disinfected drinking water and adverse health effects. The distribution of dBPs in disinfected waters has been well defined by advances in high precision analytical chemistry. Progress in the analytical biology and toxicology of dBPs has been *** objective of this review was to provide a detailed presentation of the methodology for the quantitative, comparative analyses on the induction of cytotoxicity and genotoxicity of103 dBPs using an identical analytical biological platform and endpoints. A single Chinese hamster ovary cell line was employed in the assays. The data presented are derived from papers published in the literature as well as additional new data and represent the largest direct quantitative comparison on the toxic potency of both regulated and emerging *** data may form the foundation of novel research to define the major forcing agents of dBP-mediated toxicity in disinfected water and may play an important role in achieving the goal of making safe drinking water better.

关键词： dBPs Mammalian cell cytotoxicity Mammalian cell genotoxicity

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TIC-Tox: A preliminary discussion on identifying the forcing agents of dBP-mediated toxicity of disinfected water

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Journal of Environmental Sciences 2017年第8期29卷 208-216页

作者： Michael J.Plewa elizabeth d.wagner Susan d.Richardson Safe Global Water Institute and the Department of Crop Sciences University of Illinois at Urbana-Champaign department of Chemistry and Biochemistry University of South Carolina

The disinfection of drinking water is a major public health achievement; however, an unintended consequence of disinfection is the generation of disinfection by-products（dBPs）. Many of the identified dBPs exhibit in vitro and in vivo toxicity, generate a diversity of adverse biological effects, and may be hazards to the public health and the *** a few dBPs are regulated by several national and international agencies and it is not clear if these regulated dBPs are the forcing agents that drive the observed toxicity and their associated health effects. In this study, we combine analytical chemical and biological data to resolve the forcing agents associated with mammalian cell cytotoxicity of drinking water samples from three cities. These data suggest that the trihalomethanes（THMs） and haloacetic acids may be a small component of the overall cytotoxicity of the organic material isolated from disinfected drinking water. Chemical classes of nitrogen-containing dBPs, such as the haloacetonitriles and haloacetamides, appear to be the major forcing agents of toxicity in these samples. These findings may have important implications for the design of epidemiological studies that primarily rely on the levels of THMs to define dBP exposure among populations. The TIC-Tox approach constitutes a beginning step in the process of identifying the forcing agents of toxicity in disinfected water.

关键词： dBPs CHO cell cytotoxicity Toxicity Additivity

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Monohalogenated acetamide-induced cellular stress and genotoxicity are related to electrophilic softness and thiol/thiolate reactivity

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Journal of Environmental Sciences 2017年第8期29卷 224-230页

作者： Justin A.Pals elizabeth d.wagner Michael J.Plewa Menghang Xia Matias S.Attene-Ramos department of Crop Sciences University of Illinois at Urbana-Champaign Urbana IL United States department of Environmental and Occupational Health Milken Institute School of Public Health George Washington University Washington DC United States Safe Global Water Institute University of Illinois at Urbana-Champaign Urbana IL United States National Center for Advancing Translational Sciences National Institutes of Health (NIH) Department of Health and Human Services (DHHS) Bethesda MD United States

Haloacetamides（HAMs） are cytotoxic, genotoxic, and mutagenic byproducts of drinking water disinfection. They are soft electrophilic compounds that form covalent bonds with the free thiol/thiolate in cysteine residues through an S_N2 reaction *** of the monohalogenated HAMs（iodoacetamide, IAM; bromoacetamide, BAM;or chloroacetamide, CAM） varied depending on the halogen substituent. The aim of this research was to investigate how the halogen atom affects the reactivity and toxicological properties of HAMs, measured as induction of oxidative/electrophilic stress response and genotoxicity. Additionally, we wanted to determine how well in silico estimates of electrophilic softness matched thiol/thiolate reactivity and in vitro toxicological *** of the HAMs significantly induced nuclear Rad51 accumulation and ARE signaling activity compared to a negative control. The rank order of effect was IAM 〉 BAM 〉 CAM for Rad51, and BAM ≈ IAM 〉 CAM for ARE. In general, electrophilic softness and in chemico thiol/thiolate reactivity provided a qualitative indicator of toxicity, as the softer electrophiles IAM and BAM were more thiol/thiolate reactive and were more toxic than CAM.

关键词： drinking water disinfection byproducts Haloacetamide Toxicity Soft electrophile Oxidative stress dNA damage

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Chloramination of wastewater effluent: Toxicity and formation of disinfection byproducts

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Journal of Environmental Sciences 2017年第8期29卷 135-145页

作者： Julien Le Roux Michael J.Plewa elizabeth d.wagner Maolida Nihemaiti Azra dad Jean-Philippe Croué LEESU(UMR MA 102) Université Paris-Est–AgroParisTech department of Crop Sciences the Global Safe Water InstituteUniversity of Illinois at Urbana-Champaign Curtin Water Quality Research Centre Department of ChemistryCurtin University US Food and drug Administration National Center for Toxicological Research

The reclamation and disinfection of waters impacted by human activities（e.g., wastewater effluent discharges） are of growing interest for various applications but has been associated with the formation of toxic nitrogenous disinfection byproducts（N-dBPs）. Monochloramine used as an alternative disinfectant to chlorine can be an additional source of nitrogen in the formation of N-dBPs. Individual toxicity assays have been performed on many dBPs, but few studies have been conducted with complex mixtures such as wastewater effluents. In this work, we compared the cytotoxicity and genotoxicity of wastewater effluent organic matter（Ef OM） before and after chloramination. The toxicity of chloraminated Ef OM was significantly higher than the toxicity of raw Ef OM, and the more hydrophobic fraction（HPO）isolated on XAd-8 resin was more toxic than the fraction isolated on XAd-4 *** dBPs were also isolated on the XAd-8 resin. N-dBPs（i.e., haloacetonitriles or haloacetamides） were responsible for the majority of the cytotoxicity estimated from dBP concentrations measured in the XAd-8 and XAd-4 fractions（99.4% and 78.5%, respectively）.Measured dBPs accounted for minor proportions of total brominated and chlorinated products, which means that many unknown halogenated compounds were formed and can be responsible for a significant part of the toxicity. Other non-halogenated byproducts（e.g.,nitrosamines） may contribute to the toxicity of chloraminated effluents as well.

关键词： disinfection byproducts Chloramination Toxicity Wastewater XAd resins Haloacetonitriles Haloacetamides

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The impact of iodinated X-ray contrast agents on formation and toxicity of disinfection by-products in drinking water

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Journal of Environmental Sciences 2017年第8期29卷 173-182页

作者： Clara H.Jeong Edward J.Machek Morteza Shakeri Stephen E.duirk Thomas A.Ternes Susan d.Richardson elizabeth d.wagner Michael J.Plewa Molecular and Environmental Toxicology Center School of Medicine and Public Health University of Wisconsin-Madison Madison WI USA department of Civil Engineering University of Akron Akron OH USA department of Water Chemistry Federal Institute of Hydrology Koblenz Germany department of Chemistry and Biochemistry University of South Carolina Columbia SC USA department of Crop Sciences and the Safe Global Water Institute University of Illinois at Urbana-Champaign Urbana IL USA

The presence of iodinated X-ray contrast media（ICM） in source waters is of high concern to public health because of their potential to generate highly toxic disinfection by-products（dBPs）. The objective of this study was to determine the impact of ICM in source waters and the type of disinfectant on the overall toxicity of dBP mixtures and to determine which ICM and reaction conditions give rise to toxic by-products. Source waters collected from Akron,OH were treated with five different ICMs, including iopamidol, iopromide, iohexol,diatrizoate and iomeprol, with or without chlorine or chloramine disinfection. The reaction product mixtures were concentrated with XAd resins and the mammalian cell cytotoxicity and genotoxicity of the reaction mixture concentrates was measured. Water containing iopamidol generated an enhanced level of mammalian cell cytotoxicity and genotoxicity after disinfection. While chlorine disinfection with iopamidol resulted in the highest cytotoxicity overall, the relative iopamidol-mediated increase in toxicity was greater when chloramine was used as the disinfectant compared with chlorine. Four other ICMs（iopromide, iohexol, diatrizoate, and iomeprol） expressed some cytotoxicity over the control without any disinfection, and induced higher cytotoxicity when chlorinated. Only iohexol enhanced genotoxicity compared to the chlorinated source water.

关键词： disinfection by-products Iodo-dBPs Iodinated X-ray contrast media

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Efficacy of Yisui granule(益髓颗粒)on myelodysplastic syndromes in SKM-1 mouse xenograft model through suppressing Wnt/β-catenin signaling pathway

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Journal of Traditional Chinese Medicine 2024年第1期44卷 78-87页

作者： WU Jieya HOU Li ZHANG Xiaoyuan elizabeth Gullen GAO Chong WANG Jing department of Oncology and Hematology Dongzhimen HospitalBeijing University of Chinese MedicineBeijing 100700China department of Pharmacology Yale Medical SchoolNew HavenCT 06510USA department of Oncology Beijing Hospital of Traditional Chinese MedicineCapital Medical UniversityBeijing 100010China

OBJECTIVE:To unmask the underlying mechanisms of Yisui granule(益髓颗粒,YSG)for the treatment of Myelodysplastic syndromes(MdS).METHOdS:Our study used an SKM-1 mouse xenograft model of MdS to explore the anti-tumor potential of YSG and its safety,assess its effect on overall survival(OS),and evaluate whether its mechanism is associated with the demethylation of the secreted frizzled related protein 5(s FRP5)gene and suppressing Wnt/β-catenin *** amplicon sequencing was applied to detect the level of methylation of the s FRP5 gene;western blotting,immunofluorescence staining,and real-time Polymerase Chain Reaction were performed to detect dNA methyltransferase 1(dNMT1),s FRP5,and other Wnt/β-catenin pathway-related m RNA and protein ***:The results showed that high-dosage YSG exerted an anti-tumor effect similar to that of decitabine,improved OS,and reduced long-term adverse effects in the long ***,YSG reduced the expression of dNMT1 methyltransferase,decreased the methylation,and increased the expression of the Wnt/β-catenin pathway antagonist-s ***,components of the Wnt/β-catenin pathway,including Wnt3a,β-catenin,c-Myc,and cyclin d1,were down-regulated in response to YSG,suggesting that YSG could treat MdS by demethylating the s FRP5 gene and suppressing the Wnt/β-catenin ***:Our findings demonstrated that YSG could be used alone or in combination with decitabine to improve outcomes in the MdS animal model,providing an alternative solution for treating MdS.

关键词： myelodysplastic syndromes Wnt signaling pathway beta catenin decitabine survival adverse effects sFRP5 gene methylation Yisui granule

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LKB1 depletion-mediated epithelial-mesenchymal transition induces fibroblast activation in lung fibrosis

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Genes & diseases 2024年第3期11卷 417-426页

作者： Zijian Xu elizabeth R.davies Liudi Yao Yilu Zhou Juanjuan Li Aiman Alzetani Ben G.Marshall david Hancock Tim Wallis Julian downward Rob M.Ewing donna E.davies Mark G.Jones Yihua Wang Biological Sciences Faculty of Environmental and Life SciencesUniversity of SouthamptonSouthampton SO171BJUK clinical and Experimental Sciences Faculty of MedicineUniversity of SouthamptonSouthampton SO166YDUK Institute for Life Sciences University of SouthamptonSouthampton SO171BJUK NIHR Southampton Biomedical Research Centre University Hospital SouthamptonSouthampton SO166YDUK University Hospital Southampton Southampton SO166YDUK Oncogene Biology The Francis Crick InstituteLondon NW11ATUK

The factors that determine fibrosis progression or normal tissue repair are largely *** previously demonstrated that autophagy inhibition-mediated epithelial-mesenchymal transition(EMT)in human alveolar epithelial type Il(ATIl)cells augments local myofibroblast differentiation in pulmonary fibrosis by paracrine ***,we report that liver kinase B1(LKB1)inactivation in ATIl cells inhibits autophagy and induces EMT as a *** IPF lungs,this is caused by the down-regulation of CAB39L,a key subunit within the LKB1 complex.3d co-cultures of ATIl cells and MRC5 lung fibroblasts coupled with RNA sequencing(RNA-seq)confirmed that paracrine signaling between LKB1-depleted ATIl cells and fibroblasts augmented myofibroblast ***,these data suggest that reduced autophagy caused by LKB1 inhibition can induce EMT in ATIl cells and contribute to fibrosis via aberrant epithelial-fibroblast crosstalk.

关键词： CAB39L Crosstalk EMT LKB1 Pulmonary fibrosis

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重症监护室护士限制治疗努力的能力:整合性综述

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International Journal of Nursing Sciences 2024年第1期11卷 143-154,I0003页

作者： Elvia R.Lopez-Panza Vanessa C.Pacheco-Roys Kelly J.Fernandez-Ahumada diana C.díaz-Mass María Y.Exposito-Concepcion elizabeth Villarreal-Cantillo Cesar I.Aviles Gonzalez Nursing department Universidad del NorteBarranquillaColombia Nursing Program Faculty of Health SciencesUniversidad Popular del CesarValleduparColombia Clínica Valledupar ValleduparColombia Hospital Universidad del Norte SoledadColombia department of Medical Sciences and Public Health University of CagliariCittadella Universitaria di MonserratoCagliariItaly

目的在重症监护病房(IntensiveCareUnit,ICU),护土难免会遇到需要限制治疗努力(limiting therapeutie efort,LTE)的患者,尽管多数护士还缺乏为这些临终患者及其家庭提供支持的准备。本综述旨在描述ICU护士在LTE中需要具备的能力。方法对... 详细信息

目的在重症监护病房(IntensiveCareUnit,ICU),护土难免会遇到需要限制治疗努力(limiting therapeutie efort,LTE)的患者,尽管多数护士还缺乏为这些临终患者及其家庭提供支持的准备。本综述旨在描述ICU护士在LTE中需要具备的能力。方法对2010年--2023年发表的文献进行综述。系统检索了5个数据库:Medline、Wiley Online Library、SciELO、Sciencedirect和Web of Science。使用关键评估项目工具西班牙语版(Critical Appraisal Skills Programme in Spanish,CASPe)作为评判性阅读工具。使用牛津循证医学中心(Center for Evidence-Based Medicine.,CEBM)评估工具确定证据级别和推荐强度。结果共纳入25篇文献。ICU护士LTE护理的能力包括对患者的直接护理、以家庭为中心的护理以及护士在团队中的作用。该综述确定了3个类别的能力:作为患者、家庭与跨学科团队之间维护者的能力,在LTE方面的决策能力,在患者生命末期治疗和护理干预的能力。结论ICU护士在LTE方面需要具备相应的能力,这对患者的生活质量死亡尊严以及患者家庭应对悲伤的全面支持至关重要。

关键词：重症监护家庭支持重症监护病房护士的作用安宁疗护专业能力

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The computerized LASSI-BC Test versus the Standard LASSI-L Paper-and-Pencil Version in Community-Based-Samples

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Advances in Alzheimer's disease 2024年第1期13卷 11-25页

作者： Rosie E. Curiel Cid Alexandra Ortega Ubbo Visser Marcela Kitaigorodsky d. diane Zheng diana Hincapie Kirsten Horne Crenshaw Ashleigh Beaulieu Brooke Bosworth Liz Gallardo Emory Neer Sofia Ramirez elizabeth A. Crocco Mike Georgiou Efrosyni Sfakianaki david A. Loewenstein Center for Cognitive Neuroscience and Aging and department of Psychiatry and Behavioral Sciences Miller School of Medicine University of Miami Miami FL USA department of Computer Sciences University of Miami Coral Gables FL USA Nova Southeastern University Fort Lauderdale FL USA department of Radiology and Nuclear Medicine Miller School of Medicine University of Miami Miami FL USA

Proactive Semantic Interference (PSI) and failure to recover from PSI (frPSI), are novel constructs assessed by the LASSI-L. These measures are sensitive to cognitive changes in early Mild Cognitive Impairment (MCI) and preclinical Ad determined by Aβ load using PET. The goal of this study was to compare a new computerized version of the LASSI-L (LASSI-Brief Computerized) to the standard paper-and-pencil version of the test. In this study, we examined 110 cognitively unimpaired (CU) older adults and 79 with amnestic MCI (aMCI) who were administered the paper-and-pencil form of the LASSI-L. Their performance was compared with 62 CU older adults and 52 aMCI participants examined using the LASSI-BC. After adjustment for covariates (degree of initial learning, sex, education, and language of evaluation) both the standard and computerized versions distinguished between aMCI and CU participants. The performance of CU and aMCI groups using either form was relatively commensurate. Importantly, an optimal combination of Cued B2 recall and Cued B1 intrusions on the LASSI-BC yielded an area under the ROC curve of .927, a sensitivity of 92.3% and specificity of 88.1%, relative to an area under the ROC curve of .815, a sensitivity of 72.5%, and a specificity of 79.1% obtained for the paper-and-pencil LASSI-L. Overall, the LASSI-BC was comparable, and in some ways, superior to the paper-and-pencil LASSI-L. Advantages of the LASSI-BC include a more standardized administration, suitability for remote assessment, and an automated scoring mechanism that can be verified by a built-in audio recording of responses.

关键词： Mild Cognitive Impairment Proactive Semantic Interference LASSI-L Computerized Cognitive Assessment

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Aging gracefully: social engagement joins exercise and enrichment as a key lifestyle factor in resistance to age-related cognitive decline

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Neural Regeneration Research 2019年第1期14卷 39-42页

作者： Tyler J.dause elizabeth d.Kirby department of Psychology The Ohio State University department of Neuroscience The Ohio State University Chronic Brain Injury Program The Ohio State University

Cognitive impairment is a consequence of the normal aging process that effects many species, including humans and rodent models. decline in hippocampal memory function is especially prominent with age and often reduces quality of life. As the aging population expands, the need for interventional strategies to prevent cognitive decline has become more pressing. Fortunately, several major lifestyle factors have proven effective at combating hippocampal aging, the most well-known of which are environmental enrichment and exercise. While the evidence supporting the beneficial nature of these factors is substantial, a less well-understood factor may also contribute to healthy cognitive aging: social engagement. We review the evidence supporting the role of social engagement in preserving hippocampal function in old age. In elderly humans, high levels of social engagement correlate with better hippocampal function, yet there is a dearth of work to indicate a causative role. Existing rodent literature is also limited but has begun to provide causative evidence and establish candidate mechanisms. Summed together, while many unanswered questions remain, it is clear that social engagement is a viable lifestyle factor for preserving cognitive function in old age. Social integration across the lifespan warrants more investigation and more appreciation when designing living circumstances for the elderly.

关键词： aging age-related cognitive decline social engagement hippocampus cognitive enrichment exercise memory neurogenesis

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