Shao X

References (23)

Title : Mechanism and biomass association of glucuronoyl esterase: an alpha\/beta hydrolase with potential in biomass conversion - Zong_2022_Nat.Commun_13_1449
Author(s) : Zong Z , Mazurkewich S , Pereira CS , Fu H , Cai W , Shao X , Skaf MS , Larsbrink J , Lo Leggio L
Ref : Nat Commun , 13 :1449 , 2022
Abstract : Glucuronoyl esterases (GEs) are alpha/beta serine hydrolases and a relatively new addition in the toolbox to reduce the recalcitrance of lignocellulose, the biggest obstacle in cost-effective utilization of this important renewable resource. While biochemical and structural characterization of GEs have progressed greatly recently, there have yet been no mechanistic studies shedding light onto the rate-limiting steps relevant for biomass conversion. The bacterial GE OtCE15A possesses a classical yet distinctive catalytic machinery, with easily identifiable catalytic Ser/His completed by two acidic residues (Glu and Asp) rather than one as in the classical triad, and an Arg side chain participating in the oxyanion hole. By QM/MM calculations, we identified deacylation as the decisive step in catalysis, and quantified the role of Asp, Glu and Arg, showing the latter to be particularly important. The results agree well with experimental and structural data. We further calculated the free-energy barrier of post-catalysis dissociation from a complex natural substrate, suggesting that in industrial settings non-catalytic processes may constitute the rate-limiting step, and pointing to future directions for enzyme engineering in biomass utilization.
ESTHER : Zong_2022_Nat.Commun_13_1449
PubMedSearch : Zong_2022_Nat.Commun_13_1449
PubMedID: 35304453
Gene_locus related to this paper: opitp-b1zmf4

Title : Serum Cholinesterases, a Novel Marker of Clinical Activity in Inflammatory Bowel Disease: A Retrospective Case-Control Study - Shao_2020_Mediators.Inflamm_2020_4694090
Author(s) : Shao X , Yang L , Hu K , Shen R , Ye Q , Yuan X , Zhao Q , Shen J
Ref : Mediators Inflamm , 2020 :4694090 , 2020
Abstract : BACKGROUND: The aim of our study was to investigate whether serum cholinesterase (ChE) levels were associated with inflammatory bowel disease (IBD). MATERIALS AND METHODS: We conducted a retrospective case-control study to clarify the relationship between serum ChE levels and IBD that included 142 patients with ulcerative colitis (UC), 60 patients with Crohn's disease (CD), and 264 healthy controls (HCs). We used ROC curves to evaluate the diagnostic value of serum ChE levels for IBD. RESULTS: Substantially lower serum ChE levels were detected in patients with UC than in HCs (6376 U/L versus 8418 U/L, P < 0.001) and in patients with CD than in HCs (5181 U/L versus 8418 U/L, P < 0.001). Additionally, patients with CD displayed significantly lower serum ChE levels than patients with UC (5181 U/L versus 6376 U/L, P < 0.01). We also found that there was a negative association between serum ChE levels and the Crohn's Disease Activity Index (CDAI) score of patients with CD (P = 0.011) and the Simple Clinical Colitis Activity Index (SCCAI) score of patients with UC (P = 0.018). The area under the curve (AUC) for serum ChE for the diagnosis of IBD was 0.826, and the AUCs of serum ChE for the diagnosis of CD and UC were 0.890 and 0.800, respectively. CONCLUSIONS: Serum ChE levels have important clinical significance in the diagnosis and assessment of clinical activity in patients with IBD, and the cholinergic anti-inflammatory pathway may provide new ideas for targeted treatment of IBD.
ESTHER : Shao_2020_Mediators.Inflamm_2020_4694090
PubMedSearch : Shao_2020_Mediators.Inflamm_2020_4694090
PubMedID: 32733165

Title : Immobilized lipase in bio-based metal-organic frameworks constructed by biomimetic mineralization: A sustainable biocatalyst for biodiesel synthesis - Li_2020_Colloids.Surf.B.Biointerfaces_188_110812
Author(s) : Li Q , Chen Y , Bai S , Shao X , Jiang L
Ref : Colloids Surf B Biointerfaces , 188 :110812 , 2020
Abstract : Herein, thermophilic lipase QLM from Alcaligenes sp. has been successfully immobilized in bio-based metal-organic frameworks (MOFs) through biomimetic mineralization, using zinc acetate and adenine as metal ion and organic ligand, respectively. The morphology and structure of lipase@Bio-MOF was systematically characterized by scanning electron microcopy (SEM), transmission electron microcopy (TEM), powder X-ray diffraction (PXRD) and Fourier transform infrared spectra (FT-IR). The enzyme loading in immobilized enzyme was measured to be 15.9 % by thermogravimetric analysis (TGA). Further, it was demonstrated to possess favorable catalytic activity and stability under high temperature and alkaline conditions and in the presence of metal ions, using the hydrolysis of p-nitrophenyl caprylate as a model. Finally, the immobilized enzyme was successfully applied in the preparation of biodiesel through the trans-esterification of sunflower oil with methanol, obtaining a conversion of >60 % at a high oil/methanol ratio of 8:1. Meanwhile, it showed excellent recyclability during the biodiesel production, and no changes of morphology and crystal structure were observed after being used for 3 cycles. Overall, the immobilized lipase in bio-based MOFs provided an economically and environmentally viable biocatalyst for the synthesis of biodiesel.
ESTHER : Li_2020_Colloids.Surf.B.Biointerfaces_188_110812
PubMedSearch : Li_2020_Colloids.Surf.B.Biointerfaces_188_110812
PubMedID: 31981814

Title : Immobilization of thermophilic lipase in inorganic hybrid nanoflower through biomimetic mineralization - Liu_2020_Colloids.Surf.B.Biointerfaces_197_111450
Author(s) : Liu Y , Shao X , Kong D , Li G , Li Q
Ref : Colloids Surf B Biointerfaces , 197 :111450 , 2020
Abstract : Thermophilic lipase QLM from Alcaligenes sp. was successfully immobilized in Cu(3)(PO(4))(2)-based inorganic hybrid nanoflower through biomimetic mineralization. The morphology, structure and element composition of immobilized enzyme were systemically characterized to elucidate the successful loading of enzyme molecules. The optimal temperature (65 degreeC) and pH (8.0) of immobilized enzyme were then determined by monitoring the hydrolysis of p-nitrophenyl caprylate. Moreover, compared with free enzyme, immobilized enzyme in inorganic hybrid nanoflower exhibited enhanced stability against thermal, pH and metal ions, attributing to the protective effect of nanoflower shell. Additionally, the immobilized enzyme possessed excellent reusability and long-term storage stability, with slightly decreased activity after being repeatedly used for 8 cycles or stored in water at room temperature for 4 weeks. Overall, the immobilization in inorganic hybrid nanoflower provided a facile and effective approach for the preparation of immobilized enzymes with favorable activity, stability and reusability, and thus the strategy showed great potential in developing ideal catalysts for future biocatalytic applications.
ESTHER : Liu_2020_Colloids.Surf.B.Biointerfaces_197_111450
PubMedSearch : Liu_2020_Colloids.Surf.B.Biointerfaces_197_111450
PubMedID: 33181387

Title : Neurotoxicity of perfluorooctanoic acid and post-exposure recovery due to blueberry anthocyanins in the planarians Dugesia japonica - Zhang_2020_Environ.Pollut_263_114471
Author(s) : Zhang J , Shao X , Zhao B , Zhai L , Liu N , Gong F , Ma X , Pan X , Yuan Z , Zhang X
Ref : Environ Pollut , 263 :114471 , 2020
Abstract : Perfluorooctanoic acid (PFOA) is a widely used synthetic industrial chemical which accumulates in ecosystems and organisms. Our study have investigated the neurobehavioral effects of PFOA and the alleviation effects of PFOA-induced neurotoxicity by blueberry anthocyanins (ANT) in Dugesia japonica. The planarians were exposed to PFOA and ANT for ten days. Researchs showed that exposure to PFOA affected locomotor behavior and ANT significantly alleviated the reduction in locomotion induced by PFOA. The regeneration of eyespots and auricles was suppressed by PFOA and was promoted by ANT. Following exposure to PFOA, acetylcholinesterase activity continually decreased and was unaffected in the ANT group, but was elevated after combined administration of PFOA and ANT. Oxidative DNA damage was found in planarians exposed to PFOA and was attenuated after administration of ANT by the alkaline comet assay. Concentrations of three neurotransmitters increased following exposure to PFOA and decreased after administration of ANT. Furthermore, ANT promoted and PFOA inhibited neuronal regeneration. DjotxA, DjotxB, DjFoxG, DjFoxD and Djnlg associated with neural processes were up-regulated following exposure to PFOA. Our findings indicate that PFOA is a neurotoxicant while ANT can attenuate these detrimental effects.
ESTHER : Zhang_2020_Environ.Pollut_263_114471
PubMedSearch : Zhang_2020_Environ.Pollut_263_114471
PubMedID: 32268227

Title : Insecticidal effect of aconitine on the rice brown planthoppers - Wei_2019_PLoS.One_14_e0221090
Author(s) : Wei S , Zhang H , Li B , Ji J , Shao X
Ref : PLoS ONE , 14 :e0221090 , 2019
Abstract : The brown planthopper, Nilaparvata lugens (Stal), severely damages rice production and develops high level resistance to several classes of insecticides. To find potential insecticidal resources is always important. As an environmentally friendly compound, aconitine exhibits potential pesticide features. In the present study, the pesticide and knockdown effects of aconitine were first tested on the brown planthopper. The results showed that the knockdown rates for an aconitine concentration of 200 ppm was 83.6%. The insecticidal LD50 was 22.68 ng/pest (95% CI, 17.75-28.99). The molecular mechanisms responding to aconitine application were analyzed through transcriptional sequencing. Compared to that of the knockdown nymphs of the brown planthoppers, the enzymes CYP3A4, UDP-glucuronosyltransferase (UGT), GST, carboxylesterase (EC3.1.1.1), and GABAergic synapse were up-regulated. We inferred that aconitine might be neurotoxic to the brown planthoppers, and the conscious nymphs resist the drug neurotoxicity through the upregulation of CYP3A4, UGT, and GABA receptor mutation. Although aconitine is not safe for mammals, it may be a leading compound to develop novel insecticides.
ESTHER : Wei_2019_PLoS.One_14_e0221090
PubMedSearch : Wei_2019_PLoS.One_14_e0221090
PubMedID: 31426056

Title : Perfluorooctane sulfonate induced neurotoxicity responses associated with neural genes expression, neurotransmitter levels and acetylcholinesterase activity in planarians Dugesia japonica - Yuan_2018_Chemosphere_206_150
Author(s) : Yuan Z , Shao X , Miao Z , Zhao B , Zheng Z , Zhang J
Ref : Chemosphere , 206 :150 , 2018
Abstract : As a persistent and widespread toxic organic pollutant in the environment, perfluorooctane sulfonate (PFOS) has the potential to cause great harm to wildlife. In our study, the effects of PFOS on neurodevelopment gene expression, neurotransmitter content, neuronal morphology, acetylcholinesterase (AChE) activity were examined, and the potential neurotoxicity mechanisms of PFOS were also investigated in planarians, Dugesia japonica. Using quantitative real-time PCR analysis, five neurodevelopmental related genes were measured, among which, DjotxA, DjotxB, DjFoxD, and DjFoxG were found to be down-regulated, while Djnlg was found to be up-regulated, following exposure to PFOS for 10 days compared with control groups. In addition, the neurotransmitters including dopamine, serotonin, and gamma-aminobutyricacid as well as the acitivity of AChE were altered by PFOS exposure. Furthermore, PFOS exposure altered brain morphology as well as smaller cephalic ganglia which displayed reduced nerve fiber density decreased brain branches compared to controls. Our results demonstrate that neurotransmission was disturbed after exposure to PFOS and that exposure to this pollutant can cause neurotoxic defects. Results from this study provide valuable information regarding the neuro- and ecological toxicity of PFOS in aquatic animals and aquatic environments.
ESTHER : Yuan_2018_Chemosphere_206_150
PubMedSearch : Yuan_2018_Chemosphere_206_150
PubMedID: 29738904

Title : Independent Prognostic Factors for Acute Organophosphorus Pesticide Poisoning - Tang_2016_Respir.Care_61_965
Author(s) : Tang W , Ruan F , Chen Q , Chen S , Shao X , Gao J , Zhang M
Ref : Respir Care , 61 :965 , 2016
Abstract : BACKGROUND: Acute organophosphorus pesticide poisoning (AOPP) is becoming a significant problem and a potential cause of human mortality because of the abuse of organophosphate compounds. This study aims to determine the independent prognostic factors of AOPP by using multivariate logistic regression analysis.
METHODS: The clinical data for 71 subjects with AOPP admitted to our hospital were retrospectively analyzed. This information included the Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, 6-h post-admission blood lactate levels, post-admission 6-h lactate clearance rates, admission blood cholinesterase levels, 6-h post-admission blood cholinesterase levels, cholinesterase activity, blood pH, and other factors. Univariate analysis and multivariate logistic regression analyses were conducted to identify all prognostic factors and independent prognostic factors, respectively. A receiver operating characteristic curve was plotted to analyze the testing power of independent prognostic factors.
RESULTS: Twelve of 71 subjects died. Admission blood lactate levels, 6-h post-admission blood lactate levels, post-admission 6-h lactate clearance rates, blood pH, and APACHE II scores were identified as prognostic factors for AOPP according to the univariate analysis, whereas only 6-h post-admission blood lactate levels, post-admission 6-h lactate clearance rates, and blood pH were independent prognostic factors identified by multivariate logistic regression analysis. The receiver operating characteristic analysis suggested that post-admission 6-h lactate clearance rates were of moderate diagnostic value.
CONCLUSIONS: High 6-h post-admission blood lactate levels, low blood pH, and low post-admission 6-h lactate clearance rates were independent prognostic factors identified by multivariate logistic regression analysis.
ESTHER : Tang_2016_Respir.Care_61_965
PubMedSearch : Tang_2016_Respir.Care_61_965
PubMedID: 27048625

Title : Conotoxin alphaD-GeXXA utilizes a novel strategy to antagonize nicotinic acetylcholine receptors - Xu_2015_Sci.Rep_5_14261
Author(s) : Xu S , Zhang T , Kompella SN , Yan M , Lu A , Wang Y , Shao X , Chi C , Adams DJ , Ding J , Wang C
Ref : Sci Rep , 5 :14261 , 2015
Abstract : Nicotinic acetylcholine receptors (nAChRs) play essential roles in transmitting acetylcholine-mediated neural signals across synapses and neuromuscular junctions, and are also closely linked to various diseases and clinical conditions. Therefore, novel nAChR-specific compounds have great potential for both neuroscience research and clinical applications. Conotoxins, the peptide neurotoxins produced by cone snails, are a rich reservoir of novel ligands that target receptors, ion channels and transporters in the nervous system. From the venom of Conus generalis, we identified a novel dimeric nAChR-inhibiting alphaD-conotoxin GeXXA. By solving the crystal structure and performing structure-guided dissection of this toxin, we demonstrated that the monomeric C-terminal domain of alphaD-GeXXA, GeXXA-CTD, retains inhibitory activity against the alpha9alpha10 nAChR subtype. Furthermore, we identified that His7 of the rat alpha10 nAChR subunit determines the species preference of alphaD-GeXXA, and is probably part of the binding site of this toxin. These results together suggest that alphaD-GeXXA cooperatively binds to two inter-subunit interfaces on the top surface of nAChR, thus allosterically disturbing the opening of the receptor. The novel antagonistic mechanism of alphaD-GeXXA via a new binding site on nAChRs provides a valuable basis for the rational design of new nAChR-targeting compounds.
ESTHER : Xu_2015_Sci.Rep_5_14261
PubMedSearch : Xu_2015_Sci.Rep_5_14261
PubMedID: 26395518

Title : Intranasal H102 Peptide-Loaded Liposomes for Brain Delivery to Treat Alzheimer's Disease - Zheng_2015_Pharm.Res_32_3837
Author(s) : Zheng X , Shao X , Zhang C , Tan Y , Liu Q , Wan X , Zhang Q , Xu S , Jiang X
Ref : Pharm Res , 32 :3837 , 2015
Abstract : PURPOSE: H102, a novel beta-sheet breaker peptide, was encapsulated into liposomes to reduce its degradation and increase its brain penetration through intranasal administration for the treatment of Alzheimer's disease (AD).
METHODS: The H102 liposomes were prepared using a modified thin film hydration method, and their transport characteristics were tested on Calu-3 cell monolayers. The pharmacokinetics in rats' blood and brains were also investigated. Behavioral experiments were performed to evaluate the improvements on AD rats' spatial memory impairment. The neuroprotective effects were tested by detecting acetylcholinesterase (AchE), choline acetyltransferase (ChAT) and insulin degrading enzyme (IDE) activity and conducting histological assays. The safety was evaluated on rats' nasal mucosa and cilia.
RESULTS: The liposomes prepared could penetrate Calu-3 cell monolayers consistently. After intranasal administration, H102 could be effectively delivered to the brain, and the AUC of H102 liposomes in the hippocampus was 2.92-fold larger than that of solution group. H102 liposomes could excellently ameliorate spatial memory impairment of AD model rats, increase the activities of ChAT and IDE and inhibit plaque deposition, even in a lower dosage compared with H102 intranasal solution. H102 nasal formulations showed no toxicity on nasal mucosa.
CONCLUSIONS: The H102-loaded liposome prepared in this study for nasal administration is stable, effective and safe, which has great potential for AD treatment.
ESTHER : Zheng_2015_Pharm.Res_32_3837
PubMedSearch : Zheng_2015_Pharm.Res_32_3837
PubMedID: 26113236

Title : Insect nicotinic receptor interactions in vivo with neonicotinoid, organophosphorus, and methylcarbamate insecticides and a synergist - Shao_2013_Proc.Natl.Acad.Sci.U.S.A_110_17273
Author(s) : Shao X , Xia S , Durkin KA , Casida JE
Ref : Proc Natl Acad Sci U S A , 110 :17273 , 2013
Abstract : The nicotinic acetylcholine (ACh) receptor (nAChR) is the principal insecticide target. Nearly half of the insecticides by number and world market value are neonicotinoids acting as nAChR agonists or organophosphorus (OP) and methylcarbamate (MC) acetylcholinesterase (AChE) inhibitors. There was no previous evidence for in vivo interactions of the nAChR agonists and AChE inhibitors. The nitromethyleneimidazole (NMI) analog of imidacloprid, a highly potent neonicotinoid, was used here as a radioligand, uniquely allowing for direct measurements of house fly (Musca domestica) head nAChR in vivo interactions with various nicotinic agents. Nine neonicotinoids inhibited house fly brain nAChR [(3)H]NMI binding in vivo, corresponding to their in vitro potency and the poisoning signs or toxicity they produced in intrathoracically treated house flies. Interestingly, nine topically applied OP or MC insecticides or analogs also gave similar results relative to in vivo nAChR binding inhibition and toxicity, but now also correlating with in vivo brain AChE inhibition, indicating that ACh is the ultimate OP- or MC-induced nAChR active agent. These findings on [(3)H]NMI binding in house fly brain membranes validate the nAChR in vivo target for the neonicotinoids, OPs and MCs. As an exception, the remarkably potent OP neonicotinoid synergist, O-propyl O-(2-propynyl) phenylphosphonate, inhibited nAChR in vivo without the corresponding AChE inhibition, possibly via a reactive ketene metabolite reacting with a critical nucleophile in the cytochrome P450 active site and the nAChR NMI binding site.
ESTHER : Shao_2013_Proc.Natl.Acad.Sci.U.S.A_110_17273
PubMedSearch : Shao_2013_Proc.Natl.Acad.Sci.U.S.A_110_17273
PubMedID: 24108354

Title : Cycloxaprid insecticide: nicotinic acetylcholine receptor binding site and metabolism - Shao_2013_J.Agric.Food.Chem_61_7883
Author(s) : Shao X , Swenson TL , Casida JE
Ref : Journal of Agricultural and Food Chemistry , 61 :7883 , 2013
Abstract : Cycloxaprid (CYC) is a novel neonicotinoid prepared from the (nitromethylene)imidazole (NMI) analogue of imidacloprid. In this study we consider whether CYC is active per se or only as a proinsecticide for NMI. The IC50 values (nM) for displacing [(3)H]NMI binding are 43-49 for CYC and 2.3-3.2 for NMI in house fly and honeybee head membranes and 302 and 7.2, respectively, in mouse brain membranes, potency relationships interpreted as partial conversion of some CYC to NMI under the assay conditions. The 6-8-fold difference in toxicity of injected CYC and NMI to house flies is consistent with their relative potencies as in vivo nicotinic acetylcholine receptor (nAChR) inhibitors in brain measured with [(3)H]NMI binding assays. CYC metabolism in mice largely involves cytochrome P450 pathways without NMI as a major intermediate. Metabolites of CYC tentatively assigned are five monohydroxy derivatives and one each of dihydroxy, nitroso, and amino modifications. CYC appears be a proinsecticide, serving as a slow-release reservoir for NMI with selective activity for insect versus mammalian nAChRs.
ESTHER : Shao_2013_J.Agric.Food.Chem_61_7883
PubMedSearch : Shao_2013_J.Agric.Food.Chem_61_7883
PubMedID: 23889077

Title : Poster: Novel strategy of blocking nAChR revealed by dissecting a dimeric conotoxin alphaD-GeXXA -
Author(s) : Kompella SN , Xu S , Zhang T , Yan M , Shao X , Chi C , Ding J , Wang C , Adams DJ
Ref : Biochemical Pharmacology , 86 :1229 , 2013

Title : Effects of Di-n-butyl Phthalate and Diethyl Phthalate on Acetylcholinesterase Activity and Neurotoxicity Related Gene Expression in Embryonic Zebrafish - Xu_2013_Bull.Environ.Contam.Toxicol_91_635
Author(s) : Xu H , Shao X , Zhang Z , Zou Y , Chen Y , Han S , Wang S , Wu X , Yang L , Chen Z
Ref : Bulletin of Environmental Contamination & Toxicology , 91 :635 , 2013
Abstract : In the present study, zebrafish embryos were used to assess the neurotoxicity of di-n-butyl phthalate (DBP), diethyl phthalate (DEP) and their mixture. Four-hour post-fertilization (hpf) zebrafish embryos were exposed to various concentrations of DBP, DEP and their mixture (DBP-DEP) until 96 hpf. The transcriptions levels of selected neuron-related genes reported as neurotoxicity biomarkers were analyzed. The results showed that transcripts of growth associated protein 43 (gap43), embryonic lethal abnormal vision-like 3 (elavl3), glial fibrillary acidic protein (gfap), myelin basic protein (mbp), alpha1-tubulin and neurogenin1 (ngn1) were significantly up-regulated after DBP, DEP and DBP-DEP mixture exposure. In addition, acetylcholinesterase activity was significantly inhibited in the embryos. These results indicate that DBP and DEP have the potential neurotoxicity in zebrafish embryos.
ESTHER : Xu_2013_Bull.Environ.Contam.Toxicol_91_635
PubMedSearch : Xu_2013_Bull.Environ.Contam.Toxicol_91_635
PubMedID: 24042840
Gene_locus related to this paper: danre-ACHE

Title : Enhancement of nose-to-brain delivery of basic fibroblast growth factor for improving rat memory impairments induced by co-injection of beta-amyloid and ibotenic acid into the bilateral hippocampus - Feng_2012_Int.J.Pharm_423_226
Author(s) : Feng C , Zhang C , Shao X , Liu Q , Qian Y , Feng L , Chen J , Zha Y , Zhang Q , Jiang X
Ref : Int J Pharm , 423 :226 , 2012
Abstract : Basic fibroblast growth factor (bFGF) delivery to the brain of animals appears to be an emerging potential therapeutic approach to neurodegenerative diseases, such as Alzheimer's disease (AD). The intranasal route of administration could provide an alternative to intracerebroventricular infusion. A nasal spray of bFGF had been developed previously and the objective of the present study was to investigate whether bFGF nasal spray could enhance brain uptake of bFGF and ameliorate memory impairment induced by co-injection of beta-amyloid(25-35) and ibotenic acid into bilateral hippocampus of rats. The results of brain uptake study showed that the AUC(0-12h) of bFGF nasal spray in olfactory bulb, cerebrum, cerebellum and hippocampus was respectively 2.47, 2.38, 2.56 and 2.19 times that of intravenous bFGF solution, and 1.11, 1.95, 1.40 and 1.93 times that of intranasal bFGF solution, indicating that intranasal administration of bFGF nasal spray was an effective means of delivering bFGF to the brain, especially to cerebrum and hippocampus. In Morris water maze tasks, intravenous administration of bFGF solution at high dose (40 mug/kg) showed little improvement on spatial memory impairment. In contrast, bFGF solution of the same dose following intranasal administration could significantly ameliorate spatial memory impairment. bFGF nasal spray obviously improved spatial memory impairment even at a dose half (20 mug/kg) of bFGF solution, recovered their acetylcholinesterase and choline acetyltransferase activity to the sham control level, and alleviated neuronal degeneration in rat hippocampus, indicating neuroprotective effects on the central nerve system. In a word, bFGF nasal spray may be a new formulation of great potential for treating AD.
ESTHER : Feng_2012_Int.J.Pharm_423_226
PubMedSearch : Feng_2012_Int.J.Pharm_423_226
PubMedID: 22193058

Title : In vivo toxicity and immunogenicity of wheat germ agglutinin conjugated poly(ethylene glycol)-poly(lactic acid) nanoparticles for intranasal delivery to the brain - Liu_2011_Toxicol.Appl.Pharmacol_251_79
Author(s) : Liu Q , Shao X , Chen J , Shen Y , Feng C , Gao X , Zhao Y , Li J , Zhang Q , Jiang X
Ref : Toxicol Appl Pharmacol , 251 :79 , 2011
Abstract : Biodegradable polymer-based nanoparticles have been widely studied to deliver therapeutic agents to the brain after intranasal administration. However, knowledge as to the side effects of nanoparticle delivery system to the brain is limited. The aim of this study was to investigate the in vivo toxicity and immunogenicity of wheat germ agglutinin (WGA) conjugated poly(ethylene glycol)-poly(lactic acid) nanoparticles (WGA-NP) after intranasal instillation. Sprague-Dawley rats were intranasally given WGA-NP for 7 continuous days. Amino acid neurotransmitters, lactate dehydrogenase (LDH) activity, reduced glutathione (GSH), acetylcholine, acetylcholinesterase activity, tumor necrosis factor alpha (TNF-alpha) and interleukin-8 (IL-8) in rat olfactory bulb (OB) and brain were measured to estimate the in vivo toxicity of WGA-NP. Balb/C mice were intranasally immunized by WGA-NP and then WGA-specific antibodies in serum and nasal wash were detected by indirect ELISA. WGA-NP showed slight toxicity to brain tissue, as evidenced by increased glutamate level in rat brain and enhanced LDH activity in rat OB. No significant changes in acetylcholine level, acetylcholinesterase activity, GSH level, TNF-alpha level and IL-8 level were observed in rat OB and brain for the WGA-NP group. WGA-specific antibodies in mice serum and nasal wash were not increased after two intranasal immunizations of WGA-NP. These results demonstrate that WGA-NP is a safe carrier system for intranasal delivery of therapeutic agents to the brain.
ESTHER : Liu_2011_Toxicol.Appl.Pharmacol_251_79
PubMedSearch : Liu_2011_Toxicol.Appl.Pharmacol_251_79
PubMedID: 21163285

Title : Complete genome sequence of Bacillus thuringiensis subsp. chinensis strain CT-43 - He_2011_J.Bacteriol_193_3407
Author(s) : He J , Wang J , Yin W , Shao X , Zheng H , Li M , Zhao Y , Sun M , Wang S , Yu Z
Ref : Journal of Bacteriology , 193 :3407 , 2011
Abstract : Bacillus thuringiensis has been widely used as an agricultural biopesticide for a long time. As a producing strain, B. thuringiensis subsp. chinensis strain CT-43 is highly toxic to lepidopterous and dipterous insects. It can form various parasporal crystals consisting of Cry1Aa3, Cry1Ba1, Cry1Ia14, Cry2Aa9, and Cry2Ab1. During fermentation, it simultaneously generates vegetative insecticidal protein Vip3Aa10 and the insecticidal nucleotide analogue thuringiensin. Here, we report the finished, annotated genome sequence of B. thuringiensis strain CT-43.
ESTHER : He_2011_J.Bacteriol_193_3407
PubMedSearch : He_2011_J.Bacteriol_193_3407
PubMedID: 21551307
Gene_locus related to this paper: bacan-BA3703 , bacan-BA5009 , bacan-DHBF , bacce-BC0192 , bacce-BC0968 , bacce-BC1788 , bacce-BC2141 , bacce-BC4854 , bacce-BC4862 , bacce-PHAC , baccr-pepx

Title : Complete genome sequence of Bacillus thuringiensis mutant strain BMB171 - He_2010_J.Bacteriol_192_4074
Author(s) : He J , Shao X , Zheng H , Li M , Wang J , Zhang Q , Li L , Liu Z , Sun M , Wang S , Yu Z
Ref : Journal of Bacteriology , 192 :4074 , 2010
Abstract : Bacillus thuringiensis has been widely used as a biopesticide for a long time. Here we report the finished and annotated genome sequence of B. thuringiensis mutant strain BMB171, an acrystalliferous mutant strain with a high transformation frequency obtained and stocked in our laboratory.
ESTHER : He_2010_J.Bacteriol_192_4074
PubMedSearch : He_2010_J.Bacteriol_192_4074
PubMedID: 20525827
Gene_locus related to this paper: bacan-BA3703 , bacan-DHBF , bacce-BC0192 , bacce-BC0968 , bacce-BC1677 , bacce-BC1788 , bacce-BC2141 , bacce-BC2171 , bacce-BC2456 , bacce-BC2458 , bacce-BC3133 , bacce-BC4102 , bacce-BC4854 , bacce-BC4862 , bacce-BC5130 , bacce-PHAC , baccr-pepx

Title : Evaluation of 18F-labeled acetylcholinesterase substrates as PET radiotracers - Shao_2005_Bioorg.Med.Chem_13_869
Author(s) : Shao X , Koeppe RA , Butch ER , Kilbourn MR , Snyder SE
Ref : Bioorganic & Medicinal Chemistry , 13 :869 , 2005
Abstract : Four 18F-labeled acetylcholinesterase (AChE) substrates, (S)-N-[18F]fluoroethyl-2-piperidinemethyl acetate (1), (R)-N-[18F]fluoroethyl-3-pyrrolidinyl acetate (2), N-[18F]fluoroethyl-4-piperidinyl acetate (3), and (R)-N-[18F]fluoroethyl-3-piperidinyl acetate (4), were evaluated for in vivo blood and brain metabolism in mice, brain pharmacokinetics in rats monkeys (M. nemistrina) using PET imaging. All 18F-labeled compounds were compared to N-[11C]methyl-4-piperidinyl propionate (PMP). Compound 1 was completely metabolized within 1 min in mouse blood and brain. This compound had relatively fast regional brain pharmacokinetics and poor discrimination between brain regions with different AChE concentration. Compound 4 showed relatively slower blood metabolism and slower pharmacokinetics than compound 1 but again poor discrimination between brain regions. Both compounds 1 and 4 showed different kinetic profiles than PMP in PET studies. Compound 3 had the slowest blood metabolism and slower pharmacokinetics than PMP. Compound 2 showed highly encouraging characteristics with an in vivo metabolism rate, primate brain uptake, and regional brain pharmacokinetics similar to [11C]PMP. The apparent hydrolysis rate constant k3 in primate cortex was very close to that of [11C]PMP. This compound has potential to be a good PET radiotracer for measuring brain AChE activity. The longer lifetime of 18F would permit longer imaging times and allows preparation of radiotracer batches for multiple patients and delivery of the tracer to other facilities, making the technique more widely available to clinical investigators.
ESTHER : Shao_2005_Bioorg.Med.Chem_13_869
PubMedSearch : Shao_2005_Bioorg.Med.Chem_13_869
PubMedID: 15653352

Title : N-[(18)F]Fluoroethylpiperidinyl, N-[(18)F]fluoroethylpiperidinemethyl and N-[(18)F]fluoroethylpyrrolidinyl esters as radiotracers for acetylcholinesterase - Shao_2003_Nucl.Med.Biol_30_491
Author(s) : Shao X , Butch ER , Kilbourn MR , Snyder SE
Ref : Nucl Med Biol , 30 :491 , 2003
Abstract : A series of N-fluoroethylpiperidinyl (1), N-fluoroethylpiperidinemethyl (2) and N-fluoroethylpyrrolidinyl (3) esters were synthesized and examined as new (18)F-labeled radiotracers for measuring brain cholinesterase activity. The fluoroethyl group, instead of methyl group, results in slower in vitro enzymatic cleavage rates and higher selectivity for AChE. Based on metabolism in mouse blood and PET time-activity curves in rats, two radiotracers were identified as potential candidates for further in vivo evaluation in higher species.
ESTHER : Shao_2003_Nucl.Med.Biol_30_491
PubMedSearch : Shao_2003_Nucl.Med.Biol_30_491
PubMedID: 12831986

Title : N-methylpiperidinemethyl, N-methylpyrrolidyl and N-methylpyrrolidinemethyl esters as PET radiotracers for acetylcholinesterase activity - Shao_2003_Nucl.Med.Biol_30_293
Author(s) : Shao X , Lisi JM , Butch ER , Kilbourn MR , Snyder SE
Ref : Nucl Med Biol , 30 :293 , 2003
Abstract : The N-[(11)C]methylpiperidinyl esters are used as radiopharmaceuticals for measuring brain cholinesterase activity. We have synthesized a series of N-methylpiperidinemethyl (1), N-methylpyrrolidinyl (2) and N-methylpyrrolidinemethyl (3) esters and examined the effects of sterric constraint and stereochemistry on cholinesterase-mediated cleavage. Acetylcholinesterase exhibited a preference for primary esters 1 and for the R-isomers of both 1 and 2. Biological data for (S)-N-[(11)C]methyl-2-piperidinemethyl acetate (1a) were similar to [(11)C]AMP. These data better define the structure-activity relationships for cholinesterase radiotracers and provide lead compounds for (18)F- labeling.
ESTHER : Shao_2003_Nucl.Med.Biol_30_293
PubMedSearch : Shao_2003_Nucl.Med.Biol_30_293
PubMedID: 12745021

Title : [Study on monitoring and clearing of organophosphate in blood in organophosphate poisoned rats] - Zhang_2002_Zhonghua.Lao.Dong.Wei.Sheng.Zhi.Ye.Bing.Za.Zhi_20_413
Author(s) : Zhang J , Zhao J , Zheng Y , Shao X
Ref : Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi , 20 :413 , 2002
Abstract : OBJECTIVE: To study the new method of monitoring and clearing organophosphate in blood during single or mixed organophosphate(OP) poisoning. METHOD: (1) Mixed equal volumes of blood of OP poisoned rat and healthy rat, then determine whole blood cholinesterase (ChE) activity. The descending range of ChE activity represents the level of residual OP in blood. (2) Poisoned rats by single or mixed OP pesticides were injected with 5% NaHCO3 15 ml/kg intraperitoneally, then the level of OP in blood was detected.
RESULTS: (1) The monitoring results of blood residual OP by gas chromatography were similar to that by "Mixes blood method", which showed significant difference(P < 0.05) from that before OP administration. (2) NaHCO3 injection could not improve the toxic symptoms and whole blood or brain ChE inhibition in 10 CP poisoned rats, blood residual OP level was also not affected, but lung pathological changes by OP such as interstitial inflammation and oedema showed some relief. CONCLUSION: The monitoring of blood ChE by "mixed blood method" may reflect the general level of the blood residual OP within the range of exposure dose. The effect of NaHCO3 was not satisfactory, but it may improve OP-induced lung pathological changes.
ESTHER : Zhang_2002_Zhonghua.Lao.Dong.Wei.Sheng.Zhi.Ye.Bing.Za.Zhi_20_413
PubMedSearch : Zhang_2002_Zhonghua.Lao.Dong.Wei.Sheng.Zhi.Ye.Bing.Za.Zhi_20_413
PubMedID: 14694586

Title : Huperzine A attenuates cognitive deficits and brain injury in neonatal rats after hypoxia-ischemia - Wang_2002_Brain.Res_949_162
Author(s) : Wang L , Zhou J , Shao X , Tang X
Ref : Brain Research , 949 :162 , 2002
Abstract : The protective effects of huperzine A, a novel acetylcholinesterase inhibitor, on hypoxic-ischemic (HI) brain injury were investigated in neonatal rats. A unilateral HI brain injury was produced by the ligation of left common carotid artery followed by 1 h hypoxia with 7.7% oxygen in 7-day-old rat pups. After 5 weeks, HI brain injury in rat pups resulted in working memory impairments shown by increased escape latency in a water maze and reduced time spent in the target quadrant. The combination of common carotid artery ligation and exposure to a hypoxic environment caused the damage in the striatum, cortex, and hippocampus in the ipsilateral hemisphere, and the neuronal loss in the CA1 region. Huperzine A was administrated daily at the dose of 0.05 or 0.1 mg/kg i.p. for 5 weeks after HI injury. The significant protection against HI injury on behavior and neuropathology was produced by huperzine A at the dose of 0.1 mg/kg. These findings suggest that huperzine A might be beneficial in the treatment of hypoxic-ischemic encephalopathy in neonates.
ESTHER : Wang_2002_Brain.Res_949_162
PubMedSearch : Wang_2002_Brain.Res_949_162
PubMedID: 12213312