Peng T

References (7)

Title : Biotransformation of HBCDs by the microbial communities enriched from mangrove sediments - Yu_2024_J.Hazard.Mater_469_134036
Author(s) : Yu F , Zhang B , Liu Y , Luo W , Chen H , Gao J , Ye X , Li J , Xie Q , Peng T , Wang H , Huang T , Hu Z
Ref : J Hazard Mater , 469 :134036 , 2024
Abstract : 1,2,5,6,9,10-Hexabromocyclododecanes (HBCDs) are a sort of persistent organic pollutants (POPs). This research investigated 12 microbial communities enriched from sediments of four mangroves in China to transform HBCDs. Six microbial communities gained high transformation rates (27.5-97.7%) after 12 generations of serial transfer. Bacteria were the main contributors to transform HBCDs rather than fungi. Analyses on the bacterial compositions and binning genomes showed that Alcanivorax (55.246-84.942%) harboring haloalkane dehalogenase genes dadAH and dadBH dominated the microbial communities with high transformation rates. Moreover, expressions of dadAH and dadBH in the microbial communities and Alcanivorax isolate could be induced by HBCDs. Further, it was found that purified proteins DadAH and DadBH showed high conversion rates on HBCDs in 36 h (91.9 +/- 7.4 and 101.0 +/- 1.8%, respectively). The engineered Escherichia coli BL21 strains harbored two genes could convert 5.7 +/- 0.4 and 35.1 +/- 0.1% HBCDs, respectively, lower than their cell-free crude extracts (61.2 +/- 5.2 and 56.5 +/- 8.7%, respectively). The diastereoisomer-specific transforming trend by both microbial communities and enzymes were gamma- > alpha- > beta-HBCD, differed from alpha- > beta- > gamma-HBCD by the Alcanivorax isolate. The identified transformation products indicated that HBCDs were dehalogenated via HBr elimination (dehydrobromination), hydrolytic and reductive debromination pathways in the enriched cultures. Two enzymes converted HBCDs via hydrolytic debromination. The present research provided theoretical bases for the biotransformation of HBCDs by microbial community and the bioremediation of HBCDs contamination in the environment.
ESTHER : Yu_2024_J.Hazard.Mater_469_134036
PubMedSearch : Yu_2024_J.Hazard.Mater_469_134036
PubMedID: 38493623

Title : Kinetics-Driven Drug Design Strategy for Next-Generation Acetylcholinesterase Inhibitors to Clinical Candidate - Zhou_2021_J.Med.Chem_64_1844
Author(s) : Zhou Y , Fu Y , Yin W , Li J , Wang W , Bai F , Xu S , Gong Q , Peng T , Hong Y , Zhang D , Liu Q , Xu Y , Xu HE , Zhang H , Jiang H , Liu H
Ref : Journal of Medicinal Chemistry , 64 :1844 , 2021
Abstract : The acetylcholinesterase (AChE) inhibitors remain key therapeutic drugs for the treatment of Alzheimer's disease (AD). However, the low-safety window limits their maximum therapeutic benefits. Here, a novel kinetics-driven drug design strategy was employed to discover new-generation AChE inhibitors that possess a longer drug-target residence time and exhibit a larger safety window. After detailed investigations, compound 12 was identified as a highly potent, highly selective, orally bioavailable, and brain preferentially distributed AChE inhibitor. Moreover, it significantly ameliorated cognitive impairments in different mouse models with a lower effective dose than donepezil. The X-ray structure of the cocrystal complex provided a precise binding mode between 12 and AChE. Besides, the data from the phase I trials demonstrated that 12 had good safety, tolerance, and pharmacokinetic profiles at all preset doses in healthy volunteers, providing a solid basis for its further investigation in phase II trials for the treatment of AD.
ESTHER : Zhou_2021_J.Med.Chem_64_1844
PubMedSearch : Zhou_2021_J.Med.Chem_64_1844
PubMedID: 33570950
Gene_locus related to this paper: human-ACHE

Title : Let-7f Regulates the Hypoxic Response in Cerebral Ischemia by Targeting NDRG3 - Yao_2017_Neurochem.Res_42_446
Author(s) : Yao Y , Wang W , Jing L , Wang Y , Li M , Hou X , Wang J , Peng T , Teng J , Jia Y
Ref : Neurochem Res , 42 :446 , 2017
Abstract : microRNAs are a class of non-coding RNAs including approximately 22 nucleotides in length and play a pivotal role in post-transcriptional gene regulation. Currently, the role of miRNAs in the pathophysiology of ischemic stroke has been the subject of recent investigations. In particular, antagomirs to microRNA (miRNA) let-7f have been found to be neuroprotective in vivo, although the detailed function of let-7f during cerebral ischemia has not been fully illustrated. NDRG3 is an N-myc downstream-regulated gene (NDRG) family member that has been observed in the nuclei in most brain cells. Recently, a NDRG3-mediated lactate signaling, in which stabilized NDRG3 protein can promote angiogenesis and cell growth by activating the Raf-ERK pathway in hypoxia was discovered. In this study, we preliminarily explored the change in the expression of the NDRG3 protein which indicated that NDRG3 protein is an oxygen-regulated protein in neurons in rat cerebral ischemia in vivo and in vitro. We further identified let-7f as an upstream regulator of NDRG3 by the lentiviral transfection of rat cortical neurons and the dual luciferase analysis of human genes. In addition, a dual-color fluorescence in situ hybridization assay showed that when the expression of let-7f was elevated, the expression of NDRG3 mRNA was accordingly reduced in rat cerebral ischemia. Taken together, our results identify a new regulatory mechanism of let-7f on NDRG3 expression in the hypoxic response of cerebral ischemia and raise the possibility that the let-7f/NDRG3 pathway may serve as a potential target for the treatment of ischemic stroke.
ESTHER : Yao_2017_Neurochem.Res_42_446
PubMedSearch : Yao_2017_Neurochem.Res_42_446
PubMedID: 27812761

Title : Developmental exposure of zebrafish larvae to organophosphate flame retardants causes neurotoxicity - Sun_2016_Neurotoxicol.Teratol_55_16
Author(s) : Sun L , Xu W , Peng T , Chen H , Ren L , Tan H , Xiao D , Qian H , Fu Z
Ref : Neurotoxicology & Teratology , 55 :16 , 2016
Abstract : With the gradual ban on brominated flame retardants (FRs), the application of organophosphate flame retardants (OPFRs) has increased remarkably. Considering the structural similarity between OPFRs and organophosphate pesticides, hypotheses that OPFRs may interfere with neurodevelopment as organophosphate pesticides are reasonable. In this study, the neurotoxicity of three OPFRs, including tri-n-butyl phosphate (TNBP), tris (2-butoxyethyl) phosphate (TBOEP) and tris (2-chloroethyl) phosphate (TCEP), was evaluated in zebrafish larvae and then compared with the neurotoxicity of organophosphate pesticide chlorpyrifos (CPF). The results showed that similar to CPF, exposure to OPFRs for 5days resulted in significant changes in locomotor behavior, either in free swimming or in photomotor response. However, given the transcriptional changes that occur in nervous system genes in response to OPFRs and CPF, as well as the altered enzyme activity of AChE and its mRNA level, the underlying mechanisms for neurotoxicity among these organophosphate chemicals might be varied. In summary, the results confirm the potential neurodevelopmental toxicity of OPFRs and underscore the importance of identifying the mechanistic targets of the OPFRs with specific moieties. Furthermore, as the neurobehavioral responses are well conserved among vertebrates and the exposure of children to OPFRs is significant, a thorough assessment of the risk of OPFRs exposure during early development should be highly emphasized in future studies.
ESTHER : Sun_2016_Neurotoxicol.Teratol_55_16
PubMedSearch : Sun_2016_Neurotoxicol.Teratol_55_16
PubMedID: 27018022

Title : Developmental neurotoxicity of organophosphate flame retardants in early life stages of Japanese medaka (Oryzias latipes) - Sun_2016_Environ.Toxicol.Chem_35_2931
Author(s) : Sun L , Tan H , Peng T , Wang S , Xu W , Qian H , Jin Y , Fu Z
Ref : Environ Toxicol Chem , 35 :2931 , 2016
Abstract : Because brominated flame retardants are being banned or phased out worldwide, organophosphate flame retardants have been used as alternatives on a large scale and have thus become ubiquitous environmental contaminants; this raises great concerns about their environmental health risk and toxicity. Considering that previous research has identified the nervous system as a sensitive target, Japanese medaka were used as an aquatic organism model to evaluate the developmental neurotoxicity of 4 organophosphate flame retardants: triphenyl phosphate, tri-n-butyl phosphate, tris(2-butoxyethyl) phosphate, and tris(2-chloroethyl) phosphate (TCEP). The embryo toxicity test showed that organophosphate flame retardant exposure could decrease hatchability, delay time to hatching, increase the occurrence of malformations, reduce body length, and slow heart rate. Regarding locomotor behavior, exposure to the tested organophosphate flame retardants (except TCEP) for 96 h resulted in hypoactivity for medaka larvae in both the free-swimming and the dark-to-light photoperiod stimulation test. Changes of acetylcholinesterase activity and transcriptional responses of genes related to the nervous system likely provide a reasonable explanation for the neurobehavioral disruption. Overall, the present study clearly demonstrates the developmental neurotoxicity of various organophosphate flame retardants with very different potency and contribute to the determination of which organophosphate flame retardants are appropriate substitutes, as well as the consideration of whether regulations are reasonable and required. Environ Toxicol Chem 2016;35:2931-2940. (c) 2016 SETAC.
ESTHER : Sun_2016_Environ.Toxicol.Chem_35_2931
PubMedSearch : Sun_2016_Environ.Toxicol.Chem_35_2931
PubMedID: 27146889

Title : The toxicity of chlorpyrifos on the early life stage of zebrafish: A survey on the endpoints at development, locomotor behavior, oxidative stress and immunotoxicity - Jin_2015_Fish.Shellfish.Immunol_43_405
Author(s) : Jin Y , Liu Z , Peng T , Fu Z
Ref : Fish Shellfish Immunol , 43 :405 , 2015
Abstract : Chlorpyrifos (CPF) is one of the most toxic pesticides in aquatic ecosystem, but its toxicity mechanisms to fish are still not fully understood. This study examined the toxicity targets of CPF in early life stage of zebrafish on the endpoints at developmental toxicity, neurotoxicity, oxidative stress and immunotoxicity. Firstly, CPF exposure decreased the body length, inhibited the hatchability and heart rate, and resulted in a number of morphological abnormalities, primarily spinal deformities (SD) and pericardial edema (PE), in larval zebrafish. Secondly, the free swimming activities and the swimming behaviors of the larvae in response to the stimulation of light-to-dark photoperiod transition were significantly influenced by the exposure to 100 and 300 mug/L CPF. In addition, the activity of acetylcholinesterase (AChE) and the transcription of some genes related to neurotoxicity were also influenced by CPF exposure. Thirdly, CPF exposure induced oxidative stress in the larval zebrafish. The malondialdehyde (MDA) levels increased and the glutathione (GSH) contents decreased significantly in a concentration-dependent manner after the exposure to CPF for 96 hours post fertilization (hpf). CPF affected not only the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and glutathione S-transferase (GST), but also the transcriptional levels of their respective genes. Finally, the mRNA levels of the main cytokines including tumor necrosis factor alpha (Tnfalpha), interferon (Ifn), interleukin-1 beta (Il-1beta), interleukin 6 (Il6), complement factor 4 (C4) in the larvae increased significantly after the exposure to 100 or 300 mug/L CPF for 96 hpf, suggesting that the innate immune system disturbed by CPF in larvae. Taken together, our results suggested that CPF had the potential to cause developmental toxicity, behavior alterations, oxidative stress and immunotoxicity in the larval zebrafish.
ESTHER : Jin_2015_Fish.Shellfish.Immunol_43_405
PubMedSearch : Jin_2015_Fish.Shellfish.Immunol_43_405
PubMedID: 25634256

Title : Transcriptomic comparison of thiamethoxam-resistance adaptation in resistant and susceptible strains of Aphis gossypii Glover - Pan_2014_Comp.Biochem.Physiol.Part.D.Genomics.Proteomics_13C_10
Author(s) : Pan Y , Peng T , Gao X , Zhang L , Yang C , Xi J , Xin X , Bi R , Shang Q
Ref : Comparative Biochemistry & Physiology Part D Genomics Proteomics , 13C :10 , 2014
Abstract : A thiamethoxam-resistant strain of cotton aphid (ThR) strain displayed a 19.35-fold greater resistance to thiamethoxam compared to a susceptible cotton aphid (SS) strain. Solexa sequencing technology was used to investigate differentially expressed genes (DEGs) in cotton aphids in the context of thiamethoxam resistance. A total of 22,569,311 and 21,317,732 clean reads were obtained from the ThR and SS transcriptomes, respectively, and assembled into 35,222 non-redundant (Nr) consensus sequences. The expression of 620 unigenes changed significantly in the ThR libraries compared to the SS strain; 349 genes were up-regulated, and 271 genes were down-regulated (P<=0.001). Expression levels of ribosomal proteins, ATP synthase, cytochrome c oxidase, ecdysteroid UDP-glucosyltransferase and esterase were up-regulated significantly in the ThR strain compared to the SS strain. The genes of cuticle proteins, salivary proteins, and fibroin heavy chain decreased dramatically. One nicotinic acetylcholine receptor (nAChR) alpha subunit was down-regulated in the ThR strain. The expression levels of 10 differentially expressed unigenes were confirmed using real-time RT-PCR, and the observed trends in gene expression matched the Solexa expression profiles. Specific single-nucleotide polymorphisms (SNPs) in nAChRs that cause amino acid substitution were found from the ThR and SS stains respectively. These data illustrate that genetic changes in nAChR genes and up-regulated ribosomal proteins, ecdysteroid UDP-glucosyltransferase, cytochrome c oxidase, esterase and peroxidase may confer the tolerance of resistant cotton aphids to thiamethoxam.
ESTHER : Pan_2014_Comp.Biochem.Physiol.Part.D.Genomics.Proteomics_13C_10
PubMedSearch : Pan_2014_Comp.Biochem.Physiol.Part.D.Genomics.Proteomics_13C_10
PubMedID: 25528611