Chemical cocktails in the environment can cause adverse impacts on ecosystems and human health even at low concentrations.Effect-directed analysis(EDA)has proven to be very valuable in identifying key toxic substances...Chemical cocktails in the environment can cause adverse impacts on ecosystems and human health even at low concentrations.Effect-directed analysis(EDA)has proven to be very valuable in identifying key toxic substances in environmental mixtures.For this,it is important to carefully select accurate bioassays from a wide range of tests for EDA when applying it to actual environmental samples.This article reviews studies published from2014 to 2023 that have applied EDA and summarizes the bioassays and their corresponding biological effects.A total of 127 studies were selected from 591 publications evaluating the toxic effects of environmental samples,including wastewater,surface water,and sediments.Here,bioassays used in EDA are summarized,including the assays that measure specific receptormediated modes of action(MOA),induction of xenobiotic metabolism pathways,and induction of adaptive stress response pathways using either in vitro or in vivo bioassays.Also,the identified substances using EDA are discussed based on their MOA.The importance of EDA in establishing a comprehensive approach for the detection of environmental contaminants using bioanalytical methods is emphasized.The current limitations and benefits of using EDA in practical applications are outlined and strategies for moving forward are proposed.展开更多
Background Sleep-disordered breathing （SDB） is known to occur frequently in and may predict worsening progression of patients with congestive heart failure （CHF）. SDB is also known to play an important role in the...Background Sleep-disordered breathing （SDB） is known to occur frequently in and may predict worsening progression of patients with congestive heart failure （CHF）. SDB is also known to play an important role in the development of idiopathic pulmonary arterial hyper- tension （PAH） via inducing endothelial dysfunction and vascular remodeling, a pathological process that can be significantly influenced by factors such as osteoprotegerin （OPG） and endothelial progenitor cells （EPCs）. The objective of this study is to determine if CHF with SDB is associated with changes in OPG, EPCs, and PAIl. Methods EPCs were isolated, cultured, and quantified from CHF patients with SDB （n = 52）, or without SDB （n - 68）. OPG and N-terminal pro-brain natriuretic peptide （NT-proBNP） from each group was analyzed and cor- related with EPCs and the mean pulmonary artery pressure （mPAP） measured by right heart catheterization. Results A significant decrease in circulating EPCs （29.30 ± 9.01 vs. 45.17 ± 10.51 EPCs/x 200 field; P 〈 0.05） was found in CHF patients with SDB compared to those without SDB. Both OPG （789.83 ±89.38 vs. 551.29 ± 42.12 pg/mL; P 〈 0.05） and NT-proBNP （5946.50 ± 1434.50 vs. 3028.60 ± 811.90 ng/mL; P 〈 0.05） were also significantly elevated in SDB CHF patients who also had significantly elevated mPAP （50.2 ± 9.5 vs. 36.4 ± 4.1 mm Hg; P 〈 0.05）. EPC numbers correlated inversely with the episodes of apnea and hypopnea per hour （RDI, r = -0.45, P = 0.037） and blood level of OPG （r =-0.53, P = 0.011）. Although NT-proBNP was also increased significantly in patients with SDB, it had no correlation with either EPCs or RD1. Conclusions SDBdue to hypoxemia from decompensated CHF is associated with （1） OPG elevation, （2） EPC depletion, and （3） mPAP elevation. The inverse relationship of circulating OPG with EPCs suggests a likely mechanism for hypoxemia and OPG in the development of pulmonary vascular dysfunction via depleting EPCs, thus worsening prognosis of CHF.展开更多
基金supported by the National Natural Science Foundation of China(Nos.22106157 and U20A20133)the National Key Research and Development Program of China(No.2022YFF0606700)+1 种基金the CIRP Open Fund of Radiation Protection Laboratories(No.ZFYHHJMN-2023003)the Fundamental Research Funds for the Provincial Universities of Zhejiang,China.
文摘Chemical cocktails in the environment can cause adverse impacts on ecosystems and human health even at low concentrations.Effect-directed analysis(EDA)has proven to be very valuable in identifying key toxic substances in environmental mixtures.For this,it is important to carefully select accurate bioassays from a wide range of tests for EDA when applying it to actual environmental samples.This article reviews studies published from2014 to 2023 that have applied EDA and summarizes the bioassays and their corresponding biological effects.A total of 127 studies were selected from 591 publications evaluating the toxic effects of environmental samples,including wastewater,surface water,and sediments.Here,bioassays used in EDA are summarized,including the assays that measure specific receptormediated modes of action(MOA),induction of xenobiotic metabolism pathways,and induction of adaptive stress response pathways using either in vitro or in vivo bioassays.Also,the identified substances using EDA are discussed based on their MOA.The importance of EDA in establishing a comprehensive approach for the detection of environmental contaminants using bioanalytical methods is emphasized.The current limitations and benefits of using EDA in practical applications are outlined and strategies for moving forward are proposed.
文摘Background Sleep-disordered breathing （SDB） is known to occur frequently in and may predict worsening progression of patients with congestive heart failure （CHF）. SDB is also known to play an important role in the development of idiopathic pulmonary arterial hyper- tension （PAH） via inducing endothelial dysfunction and vascular remodeling, a pathological process that can be significantly influenced by factors such as osteoprotegerin （OPG） and endothelial progenitor cells （EPCs）. The objective of this study is to determine if CHF with SDB is associated with changes in OPG, EPCs, and PAIl. Methods EPCs were isolated, cultured, and quantified from CHF patients with SDB （n = 52）, or without SDB （n - 68）. OPG and N-terminal pro-brain natriuretic peptide （NT-proBNP） from each group was analyzed and cor- related with EPCs and the mean pulmonary artery pressure （mPAP） measured by right heart catheterization. Results A significant decrease in circulating EPCs （29.30 ± 9.01 vs. 45.17 ± 10.51 EPCs/x 200 field; P 〈 0.05） was found in CHF patients with SDB compared to those without SDB. Both OPG （789.83 ±89.38 vs. 551.29 ± 42.12 pg/mL; P 〈 0.05） and NT-proBNP （5946.50 ± 1434.50 vs. 3028.60 ± 811.90 ng/mL; P 〈 0.05） were also significantly elevated in SDB CHF patients who also had significantly elevated mPAP （50.2 ± 9.5 vs. 36.4 ± 4.1 mm Hg; P 〈 0.05）. EPC numbers correlated inversely with the episodes of apnea and hypopnea per hour （RDI, r = -0.45, P = 0.037） and blood level of OPG （r =-0.53, P = 0.011）. Although NT-proBNP was also increased significantly in patients with SDB, it had no correlation with either EPCs or RD1. Conclusions SDBdue to hypoxemia from decompensated CHF is associated with （1） OPG elevation, （2） EPC depletion, and （3） mPAP elevation. The inverse relationship of circulating OPG with EPCs suggests a likely mechanism for hypoxemia and OPG in the development of pulmonary vascular dysfunction via depleting EPCs, thus worsening prognosis of CHF.
