Cui Y

References (51)

Title : Enzymatic Preparation, In-Depth Molecular Analysis, and In Vitro Digestion Simulation of Palmitoleic Acid (-7)-Enriched Fish Oil Triacylglycerols - Ge_2024_J.Agric.Food.Chem__
Author(s) : Ge L , Cheng K , Lu W , Cui Y , Yin X , Jiang J , Li Y , Yao H , Liao J , Xue J , Shen Q
Ref : Journal of Agricultural and Food Chemistry , : , 2024
Abstract : In this study, an enzymatic reaction was developed for synthesizing pure triacylglycerols (TAG) with a high content of palmitoleic acid (POA) using fish byproduct oil. The characteristics of synthesized structural TAGs rich in POA (POA-TAG) were analyzed in detail through ultrahigh-performance liquid chromatography Q Exactive orbitrap mass spectrometry. Optimal conditions were thoroughly investigated and determined for reaction systems, including the use of Lipozyme TL IM and Novozym 435, 15 wt % lipase loading, substrate mass ratio of 1:3, and water content of 2.5 and 0.5 wt %, respectively, resulting in yields of 67.50 and 67.45% for POA-TAG, respectively. Multivariate statistical analysis revealed that TAG 16:1/16:1/20:4, TAG 16:1/16:1/16:1, TAG 16:1/16:1/18:1, and TAG 16:0/16:1/18:1 were the main variables in Lipozyme TL IM and Novozym 435 enzyme-catalyzed products under different water content conditions. Finally, the fate of POA-TAG across the gastrointestinal tract was simulated using an in vitro digestion model. The results showed that the maximum release of free fatty acids and apparent rate constants were 71.44% and 0.0347 s(-1), respectively, for POA-TAG lipids, and the physical and structural characteristics during digestion depended on their microenvironments. These findings provide a theoretical basis for studying the rational design of POA-structural lipids and exploring the nutritional and functional benefits of POA products.
ESTHER : Ge_2024_J.Agric.Food.Chem__
PubMedSearch : Ge_2024_J.Agric.Food.Chem__
PubMedID: 38564481

Title : Ameliorative Effect of Natural Sesquiterpene Alcohol Cedrol Against Cerebral Ischemia Infarction-In Vitro and In Vivo Studies - Hu_2024_Appl.Biochem.Biotechnol__
Author(s) : Hu X , Han M , Liu J , Li F , Cui Y
Ref : Appl Biochem Biotechnol , : , 2024
Abstract : Cedrol is a major bioactive compound present in the Cedrus atlantica with numerous biological properties. In this study, we elucidated the neuroprotective properties of cedrol against ischemic infarction in animal and in vitro studies. A cerebral ischemic/reperfusion model was induced in adult Wistar rats, and oxygen-glucose deprivation/reperfusion was induced in SH-SY5Y neuronal cells and treated with different concentrations of cedrol. The percentage of water content, cerebral infarct, and neurological deficit score was assessed in experimental rats. The acetylcholinesterase activity and inflammatory cytokines were quantified to analyze the anti-inflammatory potency of cedrol. Oxidative stress marker malondialdehyde and antioxidants were quantified to evaluate the antioxidant potency of cedrol in an ischemic condition. The neuroprotective potency of cedrol was confirmed by histopathological analysis of the brain tissue of cedrol-treated I/R-induced rats. In in vitro studies, the MTT and LDH assays were performed in cedrol-treated OGD/R SH-SY5Y cells to analyze the cytoprotective effect of cedrol. The anti-inflammatory property of cedrol was confirmed by quantifying the pro-inflammatory cytokine levels in OGD/R-induced cedrol-treated SH-SY5Y cells. The results obtained prove that cedrol significantly prevents brain edema, neurological deficits, acetylcholinesterase activity, and oxidative damage in ischemic-induced rats. It inhibited neuroinflammation in ischemic-induced rats and also in in vitro models. The neuroprotective effect of cedrol during an ischemic condition was authentically established with histological analysis in an animal model and cell survival assays in an in vitro model. Overall, our results confirm that cedrol is a potent alternative drug to treat cerebral ischemia in the future.
ESTHER : Hu_2024_Appl.Biochem.Biotechnol__
PubMedSearch : Hu_2024_Appl.Biochem.Biotechnol__
PubMedID: 38668841

Title : Design, synthesis, and activity evaluation of novel multitargeted l-tryptophan derivatives with powerful antioxidant activity against Alzheimer's disease - Zeng_2024_Arch.Pharm.(Weinheim)__e2300603
Author(s) : Zeng X , Cheng S , Li H , Yu H , Cui Y , Fang Y , Yang S , Feng Y
Ref : Arch Pharm (Weinheim) , :e2300603 , 2024
Abstract : Alzheimer's disease (AD) is a multifactorial neurological disease, and the multitarget directed ligand (MTDL) strategy may be an effective approach to delay its progression. Based on this strategy, 27 derivatives of l-tryptophan, 3a-1-3d-1, were designed, synthesized, and evaluated for their biological activity. Among them, IC(50) (inhibitor concentration resulting in 50% inhibitory activity) values of compounds 3a-18 and 3b-1 were 0.58 and 0.44 microM for human serum butyrylcholinesterase (hBuChE), respectively, and both of them exhibited more than 30-fold selectivity for human serum acetylcholinesterase. Enzyme kinetics studies showed that these two compounds were mixed inhibitors of hBuChE. In addition, these two derivatives possessed extraordinary antioxidant activity in OH radical scavenging and oxygen radical absorption capacity fluorescein assays. Meanwhile, these compounds could also prevent beta-amyloid (Abeta) self-aggregation and possessed low toxicity on PC12 and AML12 cells. Molecular modeling studies revealed that these two compounds could interact with the choline binding site, acetyl binding site, and peripheral anionic site to exert submicromolar BuChE inhibitory activity. In the vitro blood-brain barrier permeation assay, compounds 3a-18 and 3b-1 showed enough blood-brain barrier permeability. In drug-likeness prediction, compounds 3a-18 and 3b-1 showed good gastrointestinal absorption and a low risk of human ether-a-go-go-related gene toxicity. Therefore, compounds 3a-18 and 3b-1 are potential multitarget anti-AD lead compounds, which could work as powerful antioxidants with submicromolar selective inhibitory activity for hBuChE as well as prevent Abeta self-aggregation.
ESTHER : Zeng_2024_Arch.Pharm.(Weinheim)__e2300603
PubMedSearch : Zeng_2024_Arch.Pharm.(Weinheim)__e2300603
PubMedID: 38290060

Title : PGC 1alpha-Mediates Mitochondrial Damage in the Liver by Inhibiting the Mitochondrial Respiratory Chain as a Non-cholinergic Mechanism of Repeated Low-Level Soman Exposure - Jin_2023_Biol.Pharm.Bull_46_563
Author(s) : Jin Q , Zhang Y , Cui Y , Shi M , Shi J , Zhu S , Shi T , Zhang R , Chen X , Zong X , Wang C , Li L
Ref : Biol Pharm Bull , 46 :563 , 2023
Abstract : This work aimed to assess whether mitochondrial damage in the liver induced by subacute soman exposure is caused by peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1alpha) and whether PGC-1alpha regulates mitochondrial respiratory chain damage. Toxicity mechanism research may provide theoretical support for developing anti-toxic drugs in the future. First, a soman animal model was established in male Sprague-Dawley (SD) rats by subcutaneous soman injection. Then, liver damage was biochemically evaluated, and acetylcholinesterase (AChE) activity was also determined. Transmission electron microscopy (TEM) was performed to examine liver mitochondrial damage, and high-resolution respirometry was carried out for assessing mitochondrial respiration function. In addition, complex I-IV levels were quantitatively evaluated in isolated liver mitochondria by enzyme-linked immunosorbent assay (ELISA). PGC-1alpha levels were detected with a Jess capillary-based immunoassay device. Finally, oxidative stress was analyzed by quantifying superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), oxidized glutathione (GSSG), and reactive oxygen species (ROS) levels. Repeated low-level soman exposure did not alter AChE activity, while increasing morphological damage of liver mitochondria and liver enzyme levels in rat homogenates. Complex I, II and I + II activities were 2.33, 4.95, and 5.22 times lower after treatment compared with the control group, respectively. Among complexes I-IV, I-III decreased significantly (p < 0.05), and PGC-1alpha levels were 1.82 times lower after soman exposure than in the control group. Subacute soman exposure significantly increased mitochondrial ROS production, which may cause oxidate stress. These findings indicated dysregulated mitochondrial energy metabolism involves PGC-1alpha protein expression imbalance, revealing non-cholinergic mechanisms for soman toxicity.
ESTHER : Jin_2023_Biol.Pharm.Bull_46_563
PubMedSearch : Jin_2023_Biol.Pharm.Bull_46_563
PubMedID: 37005300

Title : Study of Huperzine A derivatives with extended protection against soman intoxication - Cui_2023_Toxicol.Appl.Pharmacol__116646
Author(s) : Cui Y , Chen X , Shi J , Jin Q , Zhang R , Shi T , Wang C , Li L
Ref : Toxicol Appl Pharmacol , :116646 , 2023
Abstract : Pre-administration of huperzine A (Hup A) was validated to prevent poisoning from exposure to nerve agents (NAs) by reversibly inhibiting acetylcholinesterase (AChE). However, like the currently commonly used reversible inhibitors, Hup A has a short half-life and is unable to produce a long-term preventative effect. To extend the protective time of Hup A against NAs, 42 derivatives with a CN bond were designed based on the structure of Hup A in this study. All designed derivatives showed good binding capability with AChE via molecular docking. Six compounds (H3, H4, H11, H14, H16, and H25) with representative structures were selected for synthesis by Schiff base reaction, and their structures were stable. The modified Ellman's method showed the six compounds concentration-dependently inhibited AChE, and the half maximal inhibitory concentration (IC(50)) were higher than that of Hup A. Pretreatment of AChE with the derivatives significantly increased the IC(50) of soman. In vivo experiments demonstrated H3, H4, H14, H16, and H25 had longer protective capacities against 1 x LD(95) soman-induced death in mice than Hup A. The 12 h protective index showed that the protective ratios of H3, H4, H14 and H16 were 2.31, 1.85, 2.23 and 1.99 respectively, better than that of Hup A. The extended protection of the derivatives against soman may be explained by their transformation to Hup A in vivo. Furthermore, all six compounds showed lower acute oral toxicity than Hup A. Overall, our study provided an optional strategy to acquire pretreatment agents for NAs with extended action and low toxicity.
ESTHER : Cui_2023_Toxicol.Appl.Pharmacol__116646
PubMedSearch : Cui_2023_Toxicol.Appl.Pharmacol__116646
PubMedID: 37517785

Title : Molecular Basis of the Reinforced Effect of Berberine against Cutinase from Colletotrichum capsisi by Supplying Sodium Stearate as Dispersant - Li_2022_ACS.Appl.Bio.Mater__
Author(s) : Li Y , He R , Cui Y , Ge X
Ref : ACS Appl Bio Mater , : , 2022
Abstract : Berberine (BBR) is a promising botanical pesticide that can reduce the enzyme activity of secreted cutinase from fungal pathogens. However, only less than 15% of total activity was prohibited. Herein we researched BBR's self-aggregation in water via molecular dynamics simulations, and further investigated the effect of dispersant on blocking the aggregation together with the impact on cutinase. Strong hydrophobic interactions were found between adjacent BBR molecules, and these molecules formed clustered conformations at different BBR concentrations. Interestingly, one of the tested dispersants, sodium stearate (ST), is able to insert into BBR clusters and form stable interaction until the end of simulation, resulting in decreased hydrophobic strength in the BBR-ST cluster. More importantly, supply of ST with BBR resulted in BBR's reinforced hydrophobic interactions between BBR and the catalytic center of cutinase, which led to the inactivated mode of cutinase. Finally, wet experiments demonstrated that combined application of BBR and ST indeed resulted in a synergy-like effect on reducing the activity of cutinase. Overall, our findings revealed the mechanism of the reinforced effect of BBR against cutinase when supplying ST as dispersant, suggesting an undiscovered role of ST in enhancing the efficiency of this botanical pesticide.
ESTHER : Li_2022_ACS.Appl.Bio.Mater__
PubMedSearch : Li_2022_ACS.Appl.Bio.Mater__
PubMedID: 35114082

Title : Comparative efficacy and acceptability of cholinesterase inhibitors and memantine based on dosage in patients with vascular cognitive impairment: a network meta-analysis - Shi_2022_Curr.Alzheimer.Res__
Author(s) : Shi X , Ren G , Cui Y , Xu Z
Ref : Curr Alzheimer Res , : , 2022
Abstract : BACKGROUND: Considering the lack of direct comparison between cholinesterase inhibitors and memantine in patients with vascular cognitive impairment (VCI), determining how to choose the best treatment plan remains inconclusive. Hence, we conducted the network meta-analysis to compare the efficacy and acceptability of these drugs. METHODS: PubMed, the Cochrane Central Register of Controlled Trials, Embase and Web of Science were searched for double-blind randomized controlled trials (RCTs) for the treatment of VCI, which involved donepezil, galantamine, rivastigmine, and memantine, from database inception to January 1, 2020. Then, a network meta-analysis based on the frequency method was conducted. RESULTS: Eleven RCTs were included. Compared with the placebo, in terms of efficacy donepezil 5 mg (standardized mean difference = -1.11, 95% confidence interval = -1.88 to -0.34), donepezil 10 mg (-1.44, -2.31 to -0.56), galantamine 24 mg (-1.99, -3.03 to -0.95), and memantine 20 mg (-1.89, -2.93 to -0.86) were more effective on the cognition of ADAS-cog; and donepezil 5 mg (0.46, 0.12 to 0.81), donepezil 10 mg (0.76, 0.34 to 1.17), and rivastigmine 12mg (0.60, 0.10 to 1.10) exhibited superior benefits on the cognition of MMSE. Donepezil 10 mg (-0.25, -0.44 to -0.06; -1.47, -2.79 to -0.15) exhibited improvements on CDR-SB and EXIT25, respectively. In terms of acceptability, the memantine behaved as the best. CONCLUSIONS: Donepezil 5 mg, donepezil 10 mg, galantamine 24 mg, memantine 20 mg, and rivastigmine 12 mg have beneficial effects on cognition, and donepezil 10mg provides beneficial effects on executive function and global status. Based on the network meta-analysis, donepezil 10 mg might be the best choice, considering the benefits on cognition function, executive function and global status, but dose-related adverse reactions need to be noted. In the meantime, memantine is a better comprehensive choice, in terms of efficacy and safety acceptability.
ESTHER : Shi_2022_Curr.Alzheimer.Res__
PubMedSearch : Shi_2022_Curr.Alzheimer.Res__
PubMedID: 35048806

Title : Millions of microplastics released from a biodegradable polymer during biodegradation\/enzymatic hydrolysis - Wei_2022_Water.Res_211_118068
Author(s) : Wei XF , Capezza AJ , Cui Y , Li L , Hakonen A , Liu B , Hedenqvist MS
Ref : Water Res , 211 :118068 , 2022
Abstract : In this article, we show that enzymatic hydrolysis of a biodegradable polyester (poly(sigma-caprolactone)) by Amano Lipase PS in an aqueous (buffer) environment yielded rapidly an excessive number of microplastic particles; merely 0.1 g of poly(sigma-caprolactone) film was demonstrated to yield millions of particles. There were also indications of non-enzymatic hydrolysis at the same conditions, but this did not yield any particles within the time frame of the experiment (up to 6 days). Microplastic particles formed had irregular shapes with an average size of around 10 microm, with only a few reaching 60 microm. The formation of microplastic particles resulted from the uneven hydrolysis/erosion rate across the polymer film surface, which led to a rough and undulating surface with ridge, branch, and rod-shaped micro-protruding structures. The consequent detachment and fragmentation of these micro-sized protruding structures resulted in the release of microplastics to the surroundings. Together with microplastics, hydrolysis products such as acidic monomers and oligomers were also released during the enzymatic hydrolysis process, causing a pH decrease in the surrounding liquid. The results suggest that the risk of microplastic pollution from biodegradable plastics is notable despite their biodegradation. Special attention needs to be paid when using and disposing of biodegradable plastics, considering the enormous impact of the paradigm shift towards more biodegradable products on the environment.
ESTHER : Wei_2022_Water.Res_211_118068
PubMedSearch : Wei_2022_Water.Res_211_118068
PubMedID: 35066257

Title : Repeated low-dose exposures to sarin disrupted the homeostasis of phospholipid and sphingolipid metabolism in guinea pig hippocampus - Shi_2021_Toxicol.Lett_338_32
Author(s) : Shi M , Deng S , Cui Y , Chen X , Shi T , Song L , Zhang R , Zhang Y , Xu J , Shi J , Wang C , Li L
Ref : Toxicol Lett , 338 :32 , 2021
Abstract : Repeated low-level exposure to sarin results to hippocampus dysfunction. Metabonomics involves a holistic analysis of a set of metabolites in an organism in the search for a relationship between these metabolites and physiological or pathological changes. The objective of the present study was to evaluate the effects of repeated exposure to low-level sarin on the metabonomics in hippocampus of a guinea pig model. Guinea pigs were divided randomly into control and sarin treated groups (n = 14). Guinea pigs in the control group received saline; while the sarin-treated group received 0.4xLD(50) (16.8 microg/kg) sarin. Daily injections (a total of 14 days) were administered sc between the shoulder blades in a volume of 1.0 ml/kg body weight. At the end of the final injection, 6 animals in each group were chosen for Morris water maze test. The rest guinea pigs (n = 8 for each group) were sacrificed by decapitation, and hippocampus were dissected for analysis. Compared with the control-group, the escape latency in sarin-group was significantly (p < 0.05) longer while the crossing times were significantly decreased in the Morris water task (p < 0.05). Sarin inhibited activities of acetylcholinesterase (AChE) and neuropathy target esterase (NTE) in hippocampus. The AChE activity of hippocampus from sarin-treated groups is equivalent to 59.9 +/- 6.4 %, and the NTE activity of hippocampus from sarin-groups is equivalent to 78.1 +/- 8.3 % of that from control-group. Metabolites were identified and validated. A total of 14 variables were selected as potential biomarkers. Phospholipids [phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidic acid (PA), phosphatidylglycerol (PG), phosphatidylinositol (PI), Lysophosphatidylethanolamine (LysoPE or LPE)] and sphingolipids (SPs) [sphinganine (SA), phytosphingosine (PSO) and sphinganine-1-phosphate (SA1P)] were clearly modified. In conclusion, repeated low-dose exposures to sarin disrupted the homeostasis of phospholipid and sphingolipid metabolism in guinea pig hippocampus and may lead to a neuronal-specific function disorders. Identified metabolites such as SA1P need to be studied more deeply on their biological function that against sarin lesions. In future research, we should pay more attention to characterize the physiological roles of lipid metabolism enzymes as well as their involvement in pathologies induced by repeated low-level sarin exposure.
ESTHER : Shi_2021_Toxicol.Lett_338_32
PubMedSearch : Shi_2021_Toxicol.Lett_338_32
PubMedID: 33253782

Title : Computational redesign of a PETase for plastic biodegradation under ambient condition by the GRAPE strategy - Cui_2021_ACS.Catal_11_1340
Author(s) : Cui Y , Chen Y , Liu X , Dong S , Tian Y , Qiao Y , Mitra R , Han J , Li C , Han X
Ref : ACS Catal , 11 :1340 , 2021
Abstract : Nature has provided a fantastic array of enzymes that are responsible for essential biochemical functions but not usually suitable for technological applications. Not content with the natural repertoire, protein engineering holds promise to extend the applications of improved enzymes with tailored properties. However, engineering of robust proteins remains a difficult task since the positive mutation library may not cooperate to reach the target function in most cases owing to the ubiquity of epistatic effects. The main demand lies in identifying an efficient path of accumulated mutations. Herein, we devised a computational strategy (greedy accumulated strategy for protein engineering, GRAPE) to improve the robustness of a PETase from Ideonella sakaiensis. A systematic clustering analysis combined with greedy accumulation of beneficial mutations in a computationally derived library enabled the redesign of a variant, DuraPETase, which exhibits an apparent melting temperature that is drastically elevated by 31 C and a strikingly enhanced degradation toward semicrystalline poly(ethylene terephthalate) (PET) films (30%) at mild temperatures (over 300-fold). Complete biodegradation of 2 g/L microplastics to water-soluble products under mild conditions is also achieved, opening up opportunities to steer the biological degradation of uncollectable PET waste and further conversion of the resulting monomers to high-value molecules. The crystal structure revealed the individual mutation match with the design model. Concurrently, synergistic effects are captured, while epistatic interactions are alleviated during the accumulation process. We anticipate that our design strategy will provide a broadly applicable strategy for global optimization of enzyme performance.
ESTHER : Cui_2021_ACS.Catal_11_1340
PubMedSearch : Cui_2021_ACS.Catal_11_1340
Gene_locus related to this paper: idesa-peth

Title : GRAPE, a greedy accumulated strategy for computational protein engineering - Sun_2021_Methods.Enzymol_648_207
Author(s) : Sun J , Cui Y , Wu B
Ref : Methods Enzymol , 648 :207 , 2021
Abstract : Nature harbors fascinating enzymatic catalysts with high efficiency, chemo-, regio- and stereoselectivity. However, the insufficient stability of the enzymes often prevents their widespread utilization for industrial processes. Not content with the finite repertoire of naturally occurring enzymes, protein engineering holds promises to extend the applications of the improved enzymes with desired physical and catalytic properties. Herein, we devised a computational strategy (greedy accumulated strategy for protein engineering, GRAPE) to enhance the thermostability of enzymes. Through scanning of all point mutations of the structural and evolutionary consensus analysis, a library containing fewer than 100 mutations was established for characterization. After preliminary experimental verification, effective mutations are clustered in a multidimensional physical property space and then accumulated via the greedy algorithm to produce the final designed enzyme. Using the recently reported IsPETase from Ideonella sakaiensis that decomposes PET under ambient temperatures as a starting point, we adopted the GRAPE strategy to come up with a DuraPETase (T(M)=77 degreesC, raised by 31 degreesC) which showed drastically enhanced degradation performance (300-fold) on semicrystalline PET films at 40 degreesC.
ESTHER : Sun_2021_Methods.Enzymol_648_207
PubMedSearch : Sun_2021_Methods.Enzymol_648_207
PubMedID: 33579404
Gene_locus related to this paper: idesa-peth

Title : Inverting the Enantiopreference of Nitrilase-Catalyzed Desymmetric Hydrolysis of Prochiral Dinitriles by Reshaping the Binding Pocket with a Mirror-Image Strategy - Yu_2021_Angew.Chem.Int.Ed.Engl_60_3679
Author(s) : Yu S , Li J , Yao P , Feng J , Cui Y , Liu X , Wu Q , Lin J , Zhu D
Ref : Angew Chem Int Ed Engl , 60 :3679 , 2021
Abstract : A mirror-image strategy, that is, symmetry analysis of the substrate-binding pocket, was applied to identify two key amino acid residues W170 and V198 that possibly modulate the enantiopreference of a nitrilase from Synechocystis sp. PCC6803 towards 3-isobutyl glutaronitrile (1a). Exchange of these two residues resulted in the enantiopreference inversion (S, 90% ee to R, 47% ee). By further reshaping the substrate-binding pocket via routine site-saturation and combinatorial mutagenesis, variant E8 with higher activity and stereoselectivity (99% ee, R) was obtained. The mutant enzyme was applied in the preparation of optically pure (R)-3-isobutyl-4-cyanobutanoic acid ((R)-2a) and showed similar stereopreference inversion towards a series of 3-substituted glutaronitriles. This study may offer a general strategy to switch the stereopreference of other nitrilases and other enzymes toward the desymmetric reactions of prochiral substrates with two identical reactive functional groups.
ESTHER : Yu_2021_Angew.Chem.Int.Ed.Engl_60_3679
PubMedSearch : Yu_2021_Angew.Chem.Int.Ed.Engl_60_3679
PubMedID: 33141478

Title : Monolayer platform using human biopsy-derived duodenal organoids for pharmaceutical research - Yamashita_2021_Mol.Ther.Methods.Clin.Dev_22_263
Author(s) : Yamashita T , Inui T , Yokota J , Kawakami K , Morinaga G , Takatani M , Hirayama D , Nomoto R , Ito K , Cui Y , Ruez S , Harada K , Kishimoto W , Nakase H , Mizuguchi H
Ref : Mol Ther Methods Clin Dev , 22 :263 , 2021
Abstract : The human small intestine is the key organ for absorption, metabolism, and excretion of orally administered drugs. To preclinically predict these reactions in drug discovery research, a cell model that can precisely recapitulate the in vivo human intestinal monolayer is desired. In this study, we developed a monolayer platform using human biopsy-derived duodenal organoids for application to pharmacokinetic studies. The human duodenal organoid-derived monolayer was prepared by a simple method in 3-8 days. It consisted of polarized absorptive cells and had tight junctions. It showed much higher cytochrome P450 (CYP)3A4 and carboxylesterase (CES)2 activities than did the existing models (Caco-2 cells). It also showed efflux activity of P-glycoprotein (P-gp) and inducibility of CYP3A4. Finally, its gene expression profile was closer to the adult human duodenum, compared to the profile of Caco-2 cells. Based on these findings, this monolayer assay system using biopsy-derived human intestinal organoids is likely to be widely adopted.
ESTHER : Yamashita_2021_Mol.Ther.Methods.Clin.Dev_22_263
PubMedSearch : Yamashita_2021_Mol.Ther.Methods.Clin.Dev_22_263
PubMedID: 34485610

Title : The cholinergic system, intelligence, and dental fluorosis in school-aged children with low-to-moderate fluoride exposure - Wang_2021_Ecotoxicol.Environ.Saf_228_112959
Author(s) : Wang S , Zhao Q , Li G , Wang M , Liu H , Yu X , Chen J , Li P , Dong L , Zhou G , Cui Y , Liu L , Wang A
Ref : Ecotoxicology & Environmental Safety , 228 :112959 , 2021
Abstract : Disruption of cholinergic neurotransmission can affect cognition, but little is known about whether low-to-moderate fluoride exposure affects cholinergic system and its effect on the prevalence of dental fluorosis (DF) and intelligence quotient (IQ). A cross-sectional study was conducted to explore the associations of moderate fluoride exposure and cholinergic system in relation to children's DF and IQ. We recruited 709 resident children in Tianjin, China. Ion selective electrode method was used to detect fluoride concentrations in water and urine. Cholinergic system was assessed by the detection of choline acetyltransferase (ChAT), acetylcholinesterase (AChE) and acetylcholine (ACh) levels in serum. Compared with children in the first quartile, those in fourth quartile the risk of either developing DF or IQ < 120 increased by 19% and 20% for water and urinary fluoride. The risk of having both increased by 58% and 62% in third and fourth quartile for water fluoride, 52% and 65% for urinary fluoride. Water fluoride concentrations were positively associated with AChE and negatively associated with ChAT and ACh, trends were same for urinary fluoride except for ACh. The risk of either developing DF or having non-high intelligence rose by 22% (95%CI: 1.07%, 1.38%) for the fourth quartile than those in the first quartile of AChE, for having the both, the risk was 1.27 (95%CI: 1.07, 1.50), 1.37 (95%CI: 1.17, 1.62) and 1.44 (95%CI: 1.23, 1.68) in second, third and fourth quartiles. The mediation proportion by AChE between water fluoride and either developing DF or IQ < 120 was 15.7%. For both to exist, the proportion was 6.7% and 7.2% for water and urinary fluoride. Our findings suggest low-to-moderate fluoride exposure was associated with dysfunction of cholinergic system for children. AChE may partly mediate the prevalence of DF and lower probability of having superior and above intelligence.
ESTHER : Wang_2021_Ecotoxicol.Environ.Saf_228_112959
PubMedSearch : Wang_2021_Ecotoxicol.Environ.Saf_228_112959
PubMedID: 34808511

Title : MLL5alpha activates AR\/NDRG1 signaling to suppress prostate cancer progression - Quan_2020_Am.J.Cancer.Res_10_1608
Author(s) : Quan Y , Cui Y , Wahafu W , Liu Y , Ping H , Zhang X
Ref : Am J Cancer Research , 10 :1608 , 2020
Abstract : Prostate cancer (PCa) is one of the most prevalent malignancies in men. However, the molecular mechanism controlling the transformation of androgen-dependent PCa (ADPC) to castration-resistant PCa (CRPC) is largely unknown. Androgen receptor (AR) signaling has been reported to play a key role in this process; thus, searching for the novel AR co-activator is important for identifying the mechanism underlying PCa progression. In this study, we focused on the function of mixed lineage leukemia-5alpha (MLL5alpha), an epigenetic regulator that exhibits aberrant expression in PCa. MLL5alpha was the primary expressed form of MLL5 protein in PCa cells and it significantly suppressed proliferation, invasion, and migration in PCa cell lines. Upon stimulation with dihydrotestosterone (DHT), knockdown of MLL5alpha significantly suppressed N-myc downstream regulated gene 1 (NDRG1) and Kallikrein-related peptidase 3 (KLK3) expression. MLL5alpha directly bound with AR on the androgen response elements (AREs) and recruited H3K4me3 to the promoters of NDRG1 and KLK3. Downregulation of NDRG1 partially restored the cell invasion and migration suppressed by MLL5alpha. As evaluated by the proliferation of PCa cells, overexpression of MLL5alpha synergistically promoted sensitivity to enzalutamide (ENZ) treatment. In PCa patients, MLL5alpha expression was lower in the high Gleason score (GS) (GS > 7) group than in the low GS (GS < 7) group. In conclusion, suppression of AR/NDRG1 signaling via androgen deprivation therapy (ADT) may be a potential mechanism of CRPC progression. MLL5alpha significantly suppressed PCa progression by promoting AR/NDRG1 signaling, indicating that regulating MLL5alpha expression may be a potential treatment approach for patients with advanced PCa.
ESTHER : Quan_2020_Am.J.Cancer.Res_10_1608
PubMedSearch : Quan_2020_Am.J.Cancer.Res_10_1608
PubMedID: 32509400

Title : In-Depth Characterization of EpiIntestinal Microtissue as a Model for Intestinal Drug Absorption and Metabolism in Human - Cui_2020_Pharmaceutics_12_
Author(s) : Cui Y , Claus S , Schnell D , Runge F , MacLean C
Ref : Pharmaceutics , 12 : , 2020
Abstract : The Caco-2 model is a well-accepted in vitro model for the estimation of fraction absorbed in human intestine. Due to the lack of cytochrome P450 3A4 (CYP3A4) activities, Caco-2 model is not suitable for the investigation of intestinal first-pass metabolism. The purpose of this study is to evaluate a new human intestine model, EpiIntestinal microtissues, as a tool for the prediction of oral absorption and metabolism of drugs in human intestine. The activities of relevant drug transporters and drug metabolizing enzymes, including MDR1 P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), CYP3A4, CYP2J2, UDP-glucuronosyltransferases (UGT), carboxylesterases (CES), etc., were detected in functional assays with selective substrates and inhibitors. Compared to Caco-2, EpiIntestinal microtissues proved to be a more holistic model for the investigation of drug absorption and metabolism in human gastrointestinal tract.
ESTHER : Cui_2020_Pharmaceutics_12_
PubMedSearch : Cui_2020_Pharmaceutics_12_
PubMedID: 32354111

Title : Rv3091, An Extracellular Patatin-Like Phospholipase in Mycobacterium tuberculosis, Prolongs Intracellular Survival of Recombinant Mycolicibacterium smegmatis by Mediating Phagosomal Escape - Cui_2020_Front.Microbiol_11_2204
Author(s) : Cui Z , Dang G , Song N , Cui Y , Li Z , Zang X , Liu H , Wang Z , Liu S
Ref : Front Microbiol , 11 :2204 , 2020
Abstract : Patatin-like phospholipases (PLPs) are important virulence factors of many pathogens. However, there are no prevailing studies regarding PLPs as a virulence factor of Mycobacterium tuberculosis (Mtb). Analysis of Rv3091, a putative protein of Mtb, shows that it belongs to the PLPs family. Here, we cloned and expressed the rv3091 gene in Mycobacterium smegmatis and, subsequently, conducted protein purification and characterization. We show that it possesses phospholipase A(1), phospholipase A(2), and lipase activity. We confirm the putative active site residues, namely, Ser214 and Asp407, using site directed mutagenesis. The Rv3091 is an extracellular protein that alters the colony morphology of M. smegmatis. The presence of Rv3091 enhances the intracellular survival capability of M. smegmatis in murine peritoneal macrophages. Additionally, it promotes M. smegmatis phagosomal escape from macrophages. Moreover, Rv3091 significantly increased the survival of M. smegmatis and aggravated lesions in C57BL/6 J murine lungs in vivo. Taken together, our results indicate that Rv3091 as an extracellular PLP that is critical to the pathogenicity of mycobacterium as it allows mycobacterium to utilize phospholipids for its growth and provides resistance to phagosome killing, resulting in its enhanced intracellular survival.
ESTHER : Cui_2020_Front.Microbiol_11_2204
PubMedSearch : Cui_2020_Front.Microbiol_11_2204
PubMedID: 33042041

Title : Patatin primary structural properties and effects on lipid metabolism - Wu_2020_Food.Chem__128661
Author(s) : Wu J , Wu Q , Yang D , Zhou M , Xu J , Wen Q , Cui Y , Bai Y , Xu S , Wang Z , Wang S
Ref : Food Chem , :128661 , 2020
Abstract : Patatin, the major protein found in potatoes, was purified and shows several isoforms. The essential amino acid content of patatin was ashighas 76%, indicating that it is a valuable protein source. Patatin was an O-linked glycoprotein that contained fucose monosaccharides, as well as mannose, rhamnose, glucose, galactose, xylose, and arabinose. Patatin had a fucosylated glycan structural feature, which strongly bound AAL (Aleuria aurantia Leukoagglutinin), a known fucose binding lectin. Moreover, thelipid metabolism regulatory effects of patatin on the fat catabolism, fat absorption, and inhibition of lipase activity were measured after high-fat feeding of zebrafish larvae. Results revealed that 37.0 g/mL patatin promoted 23% lipid decomposition metabolism. Meanwhile patatin could inhibite lipase activity and fat absorption, whose effects accounted for half that of a positive control drug. Our findings suggest that patatin, a fucosylated glycoprotein, could potentially be used as a naturalactiveconstituent with anti-obesity effects.
ESTHER : Wu_2020_Food.Chem__128661
PubMedSearch : Wu_2020_Food.Chem__128661
PubMedID: 33272761

Title : Development of a Highly Sensitive Enzyme-Linked Immunosorbent Assay for Mouse Soluble Epoxide Hydrolase Detection by Combining a Polyclonal Capture Antibody with a Nanobody Tracer - Li_2020_Anal.Chem_92_11654
Author(s) : Li D , Cui Y , Morisseau C , Wagner KM , Cho YS , Hammock BD
Ref : Analytical Chemistry , 92 :11654 , 2020
Abstract : Enzyme-linked immunosorbent assays (ELISA) for the detection of soluble epoxide hydrolase (sEH), a key enzyme in the metabolism of fatty acids and a biomarker, may increasingly represent an important diagnostic tool. However, there is a lack of ELISAs for mouse sEH quantification, thus resulting in a bottleneck in understanding the pathogenesis of many diseases related to sEH based on mouse models. In this work, nanobodies recognizing mouse sEH were obtained through rebiopanning against mouse sEH in the previous phage display library of human sEH. Later, we developed four ELISAs involving a combination of anti-mouse sEH polyclonal antibodies (pAbs) and nanobodies. It was found that the double antibodies worked as dual filters and had a huge impact on both the sensitivity and selectivity of sandwich immunoassays. The switch from anti-human sEH pAbs to anti-mouse sEH pAbs led to over a 100-fold increase in the sensitivity and a dramatic decrease of the limit of detection to a picogram per milliliter range in format B (pAb/biotin-VHH/streptavidin-poly-horseradish peroxidase). Moreover, we found that the four sandwich ELISAs might demonstrate excellent selectivities to mouse sEH, despite the antibodies alone showing significant cross-reactivity to the matrix, indicating the enhanced selectivity of double antibodies as dual filters. Eventually, for the first time, the ELISA (format B) was successfully used to measure the mouse sEH level in cancer cells with ultralow abundances. The ELISAs proposed here represent a sensitive tool for tracking sEH in various biological processes and also provide deep insights into developing sandwich immunoassays against various targets in terms of both the sensitivity and selectivity.
ESTHER : Li_2020_Anal.Chem_92_11654
PubMedSearch : Li_2020_Anal.Chem_92_11654
PubMedID: 32786492

Title : Electrostatic Effect of Functional Surfaces on the Activity of Adsorbed Enzymes: Simulations and Experiments - Zheng_2020_ACS.Appl.Mater.Interfaces_12_35676
Author(s) : Zheng H , Yang SJ , Zheng YC , Cui Y , Zhang Z , Zhong JY , Zhou J
Ref : ACS Appl Mater Interfaces , 12 :35676 , 2020
Abstract : The efficient immobilization of haloalkane dehalogenase (DhaA) on carriers with retaining of its catalytic activity is essential for its application in environmental remediation. In this work, adsorption orientation and conformation of DhaA on different functional surfaces were investigated by computer simulations; meanwhile, the mechanism of varying the catalytic activity was also probed. The corresponding experiments were then carried out to verify the simulation results. (The simulations of DhaA on SAMs provided parallel insights into DhaA adsorption in carriers. Then, the theory-guided experiments were carried out to screen the best surface functional groups for DhaA immobilization.) The electrostatic interaction was considered as the main impact factor for the regulation of enzyme orientation, conformation, and enzyme bioactivity during DhaA adsorption. The synergy of overall conformation, enzyme substrate tunnel structural parameters, and distance between catalytic active sites and surfaces codetermined the catalytic activity of DhaA. Specifically, it was found that the positively charged surface with suitable surface charge density was helpful for the adsorption of DhaA and retaining its conformation and catalytic activity and was favorable for higher enzymatic catalysis efficiency in haloalkane decomposition and environmental remediation. The neutral, negatively charged surfaces and positively charged surfaces with high surface charge density always caused relatively larger DhaA conformation change and decreased catalytic activity. This study develops a strategy using a combination of simulation and experiment, which can be essential for guiding the rational design of the functionalization of carriers for enzyme adsorption, and provides a practical tool to rationally screen functional groups for the optimization of adsorbed enzyme functions on carriers. More importantly, the strategy is general and can be applied to control behaviors of different enzymes on functional carrier materials.
ESTHER : Zheng_2020_ACS.Appl.Mater.Interfaces_12_35676
PubMedSearch : Zheng_2020_ACS.Appl.Mater.Interfaces_12_35676
PubMedID: 32649833

Title : An effective immobilized haloalkane dehalogenase DhaA from Rhodococcus rhodochrous by adsorption, crosslink and PEGylation on meso-cellular foam - Zheng_2019_Int.J.Biol.Macromol_125_1016
Author(s) : Zheng H , Yu WL , Guo X , Zhao YZ , Cui Y , Hu T , Zhong JY
Ref : Int J Biol Macromol , 125 :1016 , 2019
Abstract : Haloalkane dehalogenase DhaA catalyzes the hydrolysis of halogenated compounds by cleavage of the carbon-halogen bond. However, DhaA suffers from poor environmental stability and difficult recovery, which significantly increase the cost of DhaA. Here, an effective enzyme immobilization strategy was developed to overcome the disadvantages of DhaA. DhaA was physically absorbed with amine-functionalized meso-cellular foam (MCF). The MCF-absorbed DhaA (MD) was intermolecularly crosslinked with 8-arm PEG Nhydroxysuccinimide ester and then PEGylated by maleimide-thiol chemistry. DhaA from Rhodococcus rhodochrous was absorbed at a loading capacity of 100mg/g in MD. The bulk crystallinity and morphology of MCF were largely maintained. The immobilized DhaA (MD-P1-P2) showed a lower Michaelis constant (Km, 0.588mM) than DhaA (0.905mM), along with an extremely low leaching ratio of DhaA (1.1%) from MCF. MD-P1-P2 exhibited a high stability in the extreme environmental conditions, as reflected by the remaining activity of 99.8% in 40% (v/v) DMSO for 5h, 87.3% in 3M urea solution for 1h, 25.9% at pH3.0, and 51.8% at room temperature for 30days. Thus, our study was expected to develop an effective immobilized DhaA for practical application.
ESTHER : Zheng_2019_Int.J.Biol.Macromol_125_1016
PubMedSearch : Zheng_2019_Int.J.Biol.Macromol_125_1016
PubMedID: 30576728

Title : The removal of cyhalofop-butyl in soil by surplus Rhodopseudanonas palustris in wastewater purification - Wu_2019_J.Environ.Manage_245_168
Author(s) : Wu P , Mo W , Chen Z , Wang Y , Cui Y , Zhang Y , Song Y , Jin L , Hou Y , Zhu F , Cao B , Li N
Ref : J Environ Manage , 245 :168 , 2019
Abstract : The biorestoration of cyhalofop-butyl and fertility in soil using Rhodopseudanonas palustris (R. palustris) in the treated wastewater were investigated in this research. Cyhalofop-butyl was not degraded under control group. The treated wastewater containing R. palustris degraded cyhalofop-butyl and remediated fertility. Interestingly, the cyhalofop-butyl-hydrolyzing carboxylesterase gene was expressed after inoculation 24h. Subsequently, the cyhalofop-butyl-hydrolyzing carboxylesterase were synthesized to degrade cyhalofop-butyl. The cyhalofop-butyl started to be degraded after inoculation 24h. The cyhalofop-butyl as stimulus signal induced cyhalofop-butyl-hydrolyzing carboxylesterase gene expression through signal transduction pathway. This process took 24h for R. palustris as they were ancient bacteria. The residual organics in the wastewater provided sufficient carbon sources and energy for R. palustris under three dosage groups. The new method completed the remediation of cyhalofop-butyl pollution, the improvement of soil fertility and soybean processing wastewater treatment simultaneously, and realized the resource reutilization of wastewater and R. palustris as sludge.
ESTHER : Wu_2019_J.Environ.Manage_245_168
PubMedSearch : Wu_2019_J.Environ.Manage_245_168
PubMedID: 31152960

Title : A new prognostic factor of breast cancer: High carboxyl ester lipase expression related to poor survival - Cui_2019_Cancer.Genet_239_54
Author(s) : Cui Y , Jiao Y , Wang K , He M , Yang Z
Ref : Cancer Genet , 239 :54 , 2019
Abstract : OBJECTIVE: The enzyme carboxyl ester lipase (CEL), known as bile salt-dependent lipase (BSDL) or bile salt-stimulated lipase (BSSL), is mainly expressed in pancreatic acinar cells and lactating mammary glands. To investigate the link between CEL expression of breast cancer (BC) tissues and the survival of BC patients by analyzing The Cancer Genome Atlas Breast Carcinoma (TCGA-BRCA) level 3 data. METHODS: The clinical information and RNA-sequencing (RNA-Seq) expression data were downloaded from TCGA. Patients were divided into a high CEL expression group and a low CEL expression group using the optimal cutoff value (5.611) identified from the ROC curve. Chi-square test and Fisher exact test were used to find the correlation between the expression of CEL and clinicopathologic features. To assess the diagnostic capability, the receiver operating characteristic (ROC) curve of CEL was drawn. The survival differences between high and low CEL expression groups were compared by Cox regression analysis. Log-rank test was applied to the calculation of p values and the comparison of the Kaplan-Meier curves. Furthermore, Gene Expression Omnibus (GEO) datasets were used for external data validation. RESULTS: Analysis of 1104 cases of tumor data showed that CEL was over-expressed in breast cancer. There were relationships between high CEL expression and clinicopathologic features. The high CEL expression group had a lower survival. By analyzing the area under the ROC curve (AUC) of CEL, it was found to have a limited diagnostic capability. CEL expression may be an independent prognostic factor for breast cancer survival through the multivariate analysis. The validation in GEO datasets also showed that CEL expression was higher in breast tumor tissues than in normal breast tissues. High CEL expression was associated with the poor overall survival of breast cancer. CONCLUSIONS: High CEL expression may be an independent prognostic factor for the poor survival of breast cancer.
ESTHER : Cui_2019_Cancer.Genet_239_54
PubMedSearch : Cui_2019_Cancer.Genet_239_54
PubMedID: 31561066

Title : Intestinal damage, neurotoxicity and biochemical responses caused by tris (2-chloroethyl) phosphate and tricresyl phosphate on earthworm - Yang_2018_Ecotoxicol.Environ.Saf_158_78
Author(s) : Yang Y , Xiao Y , Chang Y , Cui Y , Klobucar G , Li M
Ref : Ecotoxicology & Environmental Safety , 158 :78 , 2018
Abstract : Organophosphate esters (OPEs) draw growing concern about characterizing the potential risk on environmental health due to its wide usage and distribution. Two typical types of organophosphate esters (OPEs): tris (2-chloroethyl) phosphate (TCEP) and tricresyl phosphate (TCP) were selected to evaluate toxicity of OPEs to the soil organism like earthworm (Eisenia fetida). Histopathological examination (H&E), oxidative stress, DNA damage and RT-qPCR was used to identify the effects and potential mechanism of their toxicity. Hameatoxylin and eosin (H&E) demonstrated that intestinal cells suffered serious damage, and the observed up-regulation of chitinase and cathepsin L in mRNA levels confirmed it. Both TCEP and TCP significantly increased the DNA damage when the concentrations exceeded 1mg/kg (p<0.01), and a dose-response relationship was observed. In addition, TCEP and TCP also changed the acetylcholinesterase (AChE) activity and expression of genes associated with neurotoxic effects in earthworms even under exposure to low OPEs concentration (0.1mg/kg). Moreover, genes associated with nicotinic acetylcholine receptors (nAChR) and carrier protein further demonstrated that highest concentration of TCEP (10mg/kg) may have an overloading impact on the cholinergic system of E. fetida. Integrated Biological Response index (IBRv2) showed that TCEP exerted stronger toxicity than TCP under the same concentrations. We deduced that the observed intestinal damage, oxidative stress and neurotoxic effect might be the primary mechanisms of TCEP and TCP toxicity. This study provides insight into the toxicological effects of OPEs on earthworm model, and may be useful for risk assessment of OPEs on soil ecosystems.
ESTHER : Yang_2018_Ecotoxicol.Environ.Saf_158_78
PubMedSearch : Yang_2018_Ecotoxicol.Environ.Saf_158_78
PubMedID: 29660616

Title : Extensive intraspecific gene order and gene structural variations between Mo17 and other maize genomes - Sun_2018_Nat.Genet_50_1289
Author(s) : Sun S , Zhou Y , Chen J , Shi J , Zhao H , Song W , Zhang M , Cui Y , Dong X , Liu H , Ma X , Jiao Y , Wang B , Wei X , Stein JC , Glaubitz JC , Lu F , Yu G , Liang C , Fengler K , Li B , Rafalski A , Schnable PS , Ware DH , Buckler ES , Lai J
Ref : Nat Genet , 50 :1289 , 2018
Abstract : Maize is an important crop with a high level of genome diversity and heterosis. The genome sequence of a typical female line, B73, was previously released. Here, we report a de novo genome assembly of a corresponding male representative line, Mo17. More than 96.4% of the 2,183 Mb assembled genome can be accounted for by 362 scaffolds in ten pseudochromosomes with 38,620 annotated protein-coding genes. Comparative analysis revealed large gene-order and gene structural variations: approximately 10% of the annotated genes were mutually nonsyntenic, and more than 20% of the predicted genes had either large-effect mutations or large structural variations, which might cause considerable protein divergence between the two inbred lines. Our study provides a high-quality reference-genome sequence of an important maize germplasm, and the intraspecific gene order and gene structural variations identified should have implications for heterosis and genome evolution.
ESTHER : Sun_2018_Nat.Genet_50_1289
PubMedSearch : Sun_2018_Nat.Genet_50_1289
PubMedID: 30061735
Gene_locus related to this paper: maize-a0a1d6kqc9 , maize-k7v3i9 , maize-b6u9v9 , maize-a0a3l6e780 , maize-b4fv80 , maize-a0a3l6d913

Title : Pretreatment serum pseudocholinesterase level as a novel prognostic biomarker for upper tract urothelial carcinoma - Zhang_2016_Int.Urol.Nephrol_48_1993
Author(s) : Zhang B , Shen C , Jin J , Song Y , Zhao Z , Zhang X , Wang G , Fan Y , Mi Y , Hu S , Cui Y , Zhou L , He Z , Yu W , Han W
Ref : International Urology & Nephrology , 48 :1993 , 2016
Abstract : PURPOSE: Pretreatment serum pseudocholinesterase (PChE) has been reported to be a prognostic predictor in several cancers. However, the prognostic significance of serum PChE level in patients with upper tract urothelial carcinoma (UTUC) remains unknown.
METHODS: A total of 180 patients who underwent radical nephroureterectomy (RNU) for UTUC were included in this retrospective analysis. The associations of pretreatment serum PChE levels with clinicopathological characteristics and clinical outcomes were assessed.
RESULTS: The median (IQR) pretreatment serum PChE level was 6385 (5449-7260) IU/L, and an optimal cutoff value of 5336 IU/L was set according to ROC analysis. Decreased pretreatment serum PChE levels were significantly correlated with older patient age, higher preoperative chronic kidney disease (CKD) stage and pT stage (all P < 0.05). On multivariate analysis, adjusting for preoperative variables, decreased pretreatment serum PChE levels independently predicted higher pT stage (P = 0.011). Moreover, Kaplan-Meier curves suggested that patients with PChE levels <5336 IU/L were predicted to have a shorter overall survival (OS) and cancer-specific survival (CSS) than those with PChE levels >/=5336 IU/L (both P < 0.001). On multivariate analysis, decreased pretreatment serum PChE levels were significantly associated with shorter OS (HR 0.553; 95 %CI 0.322-0.951; P = 0.032) and CSS (HR 0.484; 95 %CI 0.269-0.870; P = 0.015).
CONCLUSIONS: Decreased pretreatment serum PChE level is an independent predictor for higher pT stage, shorter OS and CSS in patients with UTUC. Pretreatment serum PChE levels may act as a simple and effective parameter to predict prognosis for UTUC patients after RNU.
ESTHER : Zhang_2016_Int.Urol.Nephrol_48_1993
PubMedSearch : Zhang_2016_Int.Urol.Nephrol_48_1993
PubMedID: 27554671

Title : Metabolic Profile of 3-Acetyl-11-Keto-beta-Boswellic Acid and 11-Keto-beta-Boswellic Acid in Human Preparations In Vitro, Species Differences, and Bioactivity Variation - Cui_2016_AAPS.J_18_1273
Author(s) : Cui Y , Tian X , Ning J , Wang C , Yu Z , Wang Y , Huo X , Jin L , Deng S , Zhang B , Ma X
Ref : AAPS J , 18 :1273 , 2016
Abstract : 3-Acetyl-11-keto-beta-boswellic acid (AKBA) and 11-keto-beta-boswellic acid (KBA) are widely used in the clinic as anti-inflammatory drugs. However, these drugs have the poor bioavailability, which may be caused by their extensive metabolism. In this study, we systemically characterized both phase I and II metabolism of AKBA and KBA in vitro. In total, four major metabolites were firstly biosynthesized and identified using 1D and 2D NMR spectroscopy. Among them, three metabolites were novel. The kinetic parameters (K m , V max , CL int, and K i ) were also analyzed systematically in various biological samples. Finally, the deacetylation of AKBA and hydroxylation of KBA were confirmed to be the major metabolic pathways based on their large CL int and the high amounts of KBA (46.7%) and hydroxylated KBA (50.8%) along with a low amount of AKBA (2.50%) in human primary hepatocytes. Carboxylesterase 2 (CE2) selectively catalyzed the deacetylation of AKBA to form KBA. Although CYP3A4, CYP3A5, and CYP3A7 catalyzed the metabolism of KBA, CYP3A4 played a predominant role in the hydroxylation reaction of KBA in human. Notably, deacetylation and regioselective hydroxylation exhibited considerable species differences. Deacetylation was only observed in human liver microsomes and primary human hepatocytes; 21- and 20-mono-hydroxylation of KBA were primarily observed in human, monkey, and dog; and 16- and 30-mono-hydroxylation were observed in other species. More importantly, all four mono-hydroxylation metabolites exhibited a moderate anti-inflammatory activity. The 21- and 20-hydroxylation metabolites inhibited the expression of iNOS, the LPS-induced activation of IkBalpha and p65 phosphorylation, and suppressed p65 nuclear translocation in RAW264.7 cells.
ESTHER : Cui_2016_AAPS.J_18_1273
PubMedSearch : Cui_2016_AAPS.J_18_1273
PubMedID: 27329304

Title : Expression, Purification and Characterisation of Secreted Esterase Rv2525c from Mycobacterium tuberculosis - Dang_2015_Appl.Biochem.Biotechnol_176_1
Author(s) : Dang G , Chen L , Li Z , Deng X , Cui Y , Cao J , Yu S , Pang H , Liu S
Ref : Appl Biochem Biotechnol , 176 :1 , 2015
Abstract : Rv2525c from Mycobacterium tuberculosis belongs to the domain of unknown function (DUF) 1906 superfamily, but it also contains the motif G-X-S-X-G, the consensus active site sequence of the ester/lipid family. Biochemical analysis indicated that the mature Rv2525c protein is secreted. The discovery and characterisation of novel enzymes secreted by M. tuberculosis are vital for understanding the pathogenesis of the most important human bacterial pathogen. The proteome of M. tuberculosis contains over 400 potentially secreted proteins, of which the majority remain uncharacterised. In this study, we cloned and expressed the rv2525c gene in Escherichia coli and purified the recombinant protein using a three-step process (affinity chromatography, ion exchange chromatography, gel filtration chromatography), obtaining more than 99% pure protein. Mass spectrometry was performed to confirm that the purified protein was Rv2525c. Circular dichroism spectroscopy results showed that its conformation was stable at pH ranging from 6.0 to 8.0 and at temperatures <= 40 degrees C. Moreover, we tested the esterase activity using p-nitrophenyl esters (C2, C4, C6, C8, C12, C14, C16). This enzyme exhibited broad substrate acceptance, preferentially hydrolysing p-nitrophenyl butyrate (C4) at pH 7.0 and 37 degrees C. The dynamic activity test demonstrated that the optimal conditions were pH 8.0 and 38 degrees C. Site-directed mutagenesis studies revealed that Gly 113, Ser 115 and Gly 117 residues play catalytic roles in Rv2525c.
ESTHER : Dang_2015_Appl.Biochem.Biotechnol_176_1
PubMedSearch : Dang_2015_Appl.Biochem.Biotechnol_176_1
PubMedID: 25869294

Title : Heavy chain single-domain antibodies to detect native human soluble epoxide hydrolase - Cui_2015_Anal.Bioanal.Chem_407_7275
Author(s) : Cui Y , Li D , Morisseau C , Dong JX , Yang J , Wan D , Rossotti MA , Gee SJ , Gonzalez-Sapienza GG , Hammock BD
Ref : Anal Bioanal Chem , 407 :7275 , 2015
Abstract : The soluble epoxide hydrolase (sEH) is a potential pharmacological target for treating hypertension, vascular inflammation, pain, cancer, and other diseases. However, there is not a simple, inexpensive, and reliable method to estimate levels of active sEH in tissues. Toward developing such an assay, a polyclonal variable domain of heavy chain antibody (VHH) sandwich immunoassay was developed. Ten VHHs, which are highly selective for native human sEH, were isolated from a phage-displayed library. The ten VHHs have no significant cross-reactivity with human microsomal epoxide hydrolase, rat and mouse sEH, and denatured human sEH. There is a high correlation between protein levels of the sEH determined by the enzyme-linked immunosorbent assay (ELISA) and the catalytic activity of the enzyme in S9 fractions of human tissues (liver, kidney, and lung). The VHH-based ELISA appears to be a new reliable method for monitoring the sEH and may be useful as a diagnostic tool for diseases influenced by sEH. This study also demonstrates the broad utility of VHH in biochemical and pharmacological research.
ESTHER : Cui_2015_Anal.Bioanal.Chem_407_7275
PubMedSearch : Cui_2015_Anal.Bioanal.Chem_407_7275
PubMedID: 26229025

Title : Expanding the biotechnology potential of lactobacilli through comparative genomics of 213 strains and associated genera - Sun_2015_Nat.Commun_6_8322
Author(s) : Sun Z , Harris HM , McCann A , Guo C , Argimon S , Zhang W , Yang X , Jeffery IB , Cooney JC , Kagawa TF , Liu W , Song Y , Salvetti E , Wrobel A , Rasinkangas P , Parkhill J , Rea MC , O'Sullivan O , Ritari J , Douillard FP , Paul Ross R , Yang R , Briner AE , Felis GE , de Vos WM , Barrangou R , Klaenhammer TR , Caufield PW , Cui Y , Zhang H , O'Toole PW
Ref : Nat Commun , 6 :8322 , 2015
Abstract : Lactobacilli are a diverse group of species that occupy diverse nutrient-rich niches associated with humans, animals, plants and food. They are used widely in biotechnology and food preservation, and are being explored as therapeutics. Exploiting lactobacilli has been complicated by metabolic diversity, unclear species identity and uncertain relationships between them and other commercially important lactic acid bacteria. The capacity for biotransformations catalysed by lactobacilli is an untapped biotechnology resource. Here we report the genome sequences of 213 Lactobacillus strains and associated genera, and their encoded genetic catalogue for modifying carbohydrates and proteins. In addition, we describe broad and diverse presence of novel CRISPR-Cas immune systems in lactobacilli that may be exploited for genome editing. We rationalize the phylogenomic distribution of host interaction factors and bacteriocins that affect their natural and industrial environments, and mechanisms to withstand stress during technological processes. We present a robust phylogenomic framework of existing species and for classifying new species.
ESTHER : Sun_2015_Nat.Commun_6_8322
PubMedSearch : Sun_2015_Nat.Commun_6_8322
PubMedID: 26415554
Gene_locus related to this paper: 9laco-a0a0r1hz65 , 9laco-a0a0r1j1t4 , 9laco-a0a0r1j3p0 , 9laco-a0a0r1k3i0 , 9laco-a0a0r1k563 , 9laco-a0a0r1kgb3 , 9laco-a0a0r1kji2 , 9laco-a0a0r1kwq5 , 9laco-a0a0r1l700 , 9laco-a0a0r1p6l8 , 9laco-a0a0r1q939 , 9laco-a0a0r1qv39 , 9laco-a0a0r1wj75 , laccl-a0a0r2bne3 , 9laco-a0a0r2dnk9 , 9laco-a0a0r2ds70 , 9laco-a0a0r2k127 , 9laco-a0a0r2lee7 , 9laco-a0a0r2lqt2 , 9laco-a0a0r2m354 , 9laco-a0a0r2n9f2 , 9laco-a0a0r2nrk2 , lacze-a0a0r1ekw6 , 9laco-a0a0r1ju11 , 9laco-a0a0r1k516 , 9laco-a0a0r1leq9 , 9laco-a0a0r1lul8 , 9laco-a0a0r1lzg4 , 9laco-a0a0r1mhp8 , 9laco-a0a0r1mjt1 , 9laco-a0a0r1nv21 , 9laco-a0a0r1q1p6 , 9laco-a0a0r1qm41 , 9laco-a0a0r1qs58 , 9laco-a0a0r1rgu0 , 9laco-a0a0r1tg12 , 9laco-a0a0r1u777 , 9laco-a0a0r1ufv3 , 9laco-a0a0r1ul77 , 9laco-a0a0r1vad0 , 9laco-a0a0r1w3f4 , 9laco-a0a0r1w9r8 , 9laco-a0a0r1wpq2 , 9laco-a0a0r1x2g3 , 9laco-a0a0r2abe6 , 9laco-a0a0r2b6w1 , 9laco-a0a0r2b8g1 , 9laco-a0a0r2ch10 , 9laco-a0a0r2cld6 , 9laco-a0a0r2cv38 , 9laco-a0a0r2d3x3 , 9laco-a0a0r2dct2 , 9laco-a0a0r2flt3 , 9laco-a0a0r2frk5 , 9laco-a0a0r2guq4 , 9firm-a0a0r2h5m0 , weivi-a0a0r2h8r4 , 9lact-a0a0r2hnx4 , 9lact-a0a0r2jkt6 , 9lact-a0a0r2jmz1 , 9laco-a0a0r2jwg5 , 9laco-a0a0r2jxu0 , 9laco-a0a0r2jxw0 , lacam-a0a0r2kgt3 , 9laco-a0a0r2kx86 , 9laco-a0a0r2mxi6 , 9laco-a0a0r1vln2 , 9laco-a0a0r2ca25 , 9laco-a0a0r1zjs2 , weipa-c5rbw8

Title : Role of Neurexin-1beta and Neuroligin-1 in Cognitive Dysfunction After Subarachnoid Hemorrhage in Rats - Shen_2015_Stroke_46_2607
Author(s) : Shen H , Chen Z , Wang Y , Gao A , Li H , Cui Y , Zhang L , Xu X , Wang Z , Chen G
Ref : Stroke , 46 :2607 , 2015
Abstract : BACKGROUND AND PURPOSE: Neurexin-1beta and neuroligin-1 play an important role in the formation, maintenance, and regulation of synaptic structures. This study is to estimate the potential role of neurexin-1beta and neuroligin-1 in subarachnoid hemorrhage (SAH)-induced cognitive dysfunction.
METHODS: In vivo, 228 Sprague-Dawley rats were used. An experimental SAH model was induced by single blood injection to prechiasmatic cistern. Primary cultured hippocampal neurons were exposed to oxyhemoglobin to mimic SAH in vitro. Specific small interfering RNAs and expression plasmids for neurexin-1beta and neuroligin-1 were exploited both in vivo and in vitro. Western blot, immunofluorescence, immunoprecipitation, neurological scoring, and Morris water maze were performed to evaluate the mechanism of neurexin-1beta and neuroligin-1, as well as neurological outcome.
RESULTS: Both in vivo and in vitro experiments showed SAH-induced decrease in the expressions of neurexin-1beta and neuroligin-1 and the interaction between neurexin-1beta and neuroligin-1 in neurons. In addition, the interaction between neurexin-1beta and neuroligin-1 was reduced by their knockdown and increased by their overexpression. The formation of excitatory synapses was inhibited by oxyhemoglobin treatment, which was significantly ameliorated by overexpression of neurexin-1beta and neuroligin-1 and aggravated by the knockdown of neurexin-1beta and neuroligin-1. More importantly, neurexin-1beta and neuroligin-1 overexpression ameliorated SAH-induced cognitive dysfunction, whereas neurexin-1beta and neuroligin-1 knockdown induced an opposite effect.
CONCLUSIONS: Enhancing the expressions of neurexin-1beta and neuroligin-1 could promote the interaction between them and the formation of excitatory synapses, which is helpful to improve cognitive dysfunction after SAH. Neurexin-1beta and neuroligin-1 might be good targets for improving cognitive function after SAH.
ESTHER : Shen_2015_Stroke_46_2607
PubMedSearch : Shen_2015_Stroke_46_2607
PubMedID: 26219651

Title : Superparamagnetic Polymer Emulsion Particles from a Soap-Free Seeded Emulsion Polymerization and their Application for Lipase Immobilization - Cui_2014_Appl.Biochem.Biotechnol_172_701
Author(s) : Cui Y , Chen X , Li Y , Liu X , Lei L , Zhang Y , Qian J
Ref : Appl Biochem Biotechnol , 172 :701 , 2014
Abstract : Using emulsion copolymer of styrene (St), glycidyl methacrylate (GMA) and 2-hydroxyethyl methacrylate (HEMA) as seed latexes, the superparamagnetic polymer emulsion particles were prepared by seeded emulsion copolymerization of butyl methacrylate (BMA), vinyl acetate (VAc) and ethylene glycol dimethacrylate in the presence of the seed latexes and superparamagnetic Fe3O4/SiOx nanoparticles (or Fe3O4-APTS nanoparticles) through a two-step process, without addition of any emulsifier. The magnetic emulsion particles named P(St-GMA-HEMA)/P(BMA-VAc) were characterized by transmission electron microscope and vibrating sample magnetometry. The results showed that the magnetic emulsion particles held a structure with a thinner shell (around 100 nm) and a bigger cavity (around 200 nm), and possessed a certain level of magnetic response. The resulting magnetic emulsion particles were employed in the immobilization of lipase by two strategies to immobilized lipase onto the resulting magnetic composites directly (S-1) or using glutaraldehyde as a coupling agent (S-2), thus, experimental data showed that the thermal stability and reusability of immobilized lipase based on S-2 were higher than that of S-1.
ESTHER : Cui_2014_Appl.Biochem.Biotechnol_172_701
PubMedSearch : Cui_2014_Appl.Biochem.Biotechnol_172_701
PubMedID: 24114322

Title : Short-term effects of Dechlorane Plus on the earthworm Eisenia fetida determined by a systems biology approach - Zhang_2014_J.Hazard.Mater_273C_239
Author(s) : Zhang L , Ji F , Li M , Cui Y , Wu B
Ref : J Hazard Mater , 273C :239 , 2014
Abstract : Dechlorane Plus (DP), a chlorinated flame retardant, has been widely detected in environmental matrices, especially in sediment and soil. DP has characteristics similar to persistent organic pollutants. However, no toxicity data of DP on terrestrial invertebrate are available. In this study, earthworms Eisenia fetida were exposed to 0.1, 1, 10, and 50mg/kg DP for 14 days. Lethality, oxidative stress and damage, neurotoxicity, and transcriptomic profiles of E. fetida were assessed on day 7 and day 14 of exposure. Results showed that the acute toxicity of DP was very low. However, DP exposure induced an increase in the oxidative stress markers malonaldehyde (MDA) and 8-Hydroxy-2'-deoxyguanosine (8-OHdG), and altered acetylcholinesterase (AChE) activities. High throughput sequencing-based transcriptomic analysis showed that DP exposure significantly altered gene expression and pathways related to antioxidant enzymes, stress responses, neurological dysfunctions, calcium binding, and signal transduction. The results from different toxicological endpoints indicate that DP toxicity on the earthworm is primarily through oxidative damage and neurotoxicity. Based on these results, we deduce that changes in oxidative stress and neurotoxicity might be the primary mechanisms of DP toxicity. This study provides insight into the toxicological effects of DP on earthworm model, and may be useful for risk assessment of DP on soil ecosystems.
ESTHER : Zhang_2014_J.Hazard.Mater_273C_239
PubMedSearch : Zhang_2014_J.Hazard.Mater_273C_239
PubMedID: 24751489

Title : Alpha oscillations in response to affective and cigarette-related stimuli in smokers - Cui_2013_Nicotine.Tob.Res_15_917
Author(s) : Cui Y , Versace F , Engelmann JM , Minnix JA , Robinson JD , Lam CY , Karam-Hage M , Brown VL , Wetter DW , Dani JA , Kosten TR , Cinciripini PM
Ref : Nicotine Tob Res , 15 :917 , 2013
Abstract : INTRODUCTION: The presence of cigarette-related cues has been associated with smoking relapse. These cues are believed to activate brain mechanisms underlying emotion, attention, and memory. Electroencephalography (EEG) alpha desynchronization (i.e., reduction in alpha power) has been suggested to index the engagement of these mechanisms. Analyzing EEG alpha desynchronization in response to affective and smoking cues might improve our understanding of how smokers process these cues, and the potential impact of this processing on relapse.
METHODS: Before the start of a medication-assisted cessation attempt, we recorded EEG from 179 smokers during the presentation of neutral, pleasant, unpleasant, and cigarette-related pictures. Wavelet analysis was used to extract EEG alpha oscillations (8-12 Hz) in response to these pictures. Alpha oscillations were analyzed as a function of picture valence and arousal dimensions.
RESULTS: Emotional and cigarette-related stimuli induced a higher level of alpha desynchronization (i.e., less power in the alpha frequency band) than neutral stimuli. In addition, the level of alpha desynchronization induced by cigarette-related stimuli was similar to that induced by highly arousing stimuli (i.e., erotica and mutilations).
CONCLUSIONS: These results suggest that, for smokers, cigarette-related cues are motivationally significant stimuli that may engage emotional, attentional, and memory-related neural mechanisms at a level comparable to that seen in response to highly arousing stimuli. This finding suggests that activation of emotional, attentional, and memory-related brain mechanisms may be an important contributor to cue-induced smoking relapse.
ESTHER : Cui_2013_Nicotine.Tob.Res_15_917
PubMedSearch : Cui_2013_Nicotine.Tob.Res_15_917
PubMedID: 23060019

Title : Bis(9)-(-)-nor-meptazinol as a novel dual-binding AChEI potently ameliorates scopolamine-induced cognitive deficits in mice - Liu_2013_Pharmacol.Biochem.Behav_104_138
Author(s) : Liu T , Xia Z , Zhang WW , Xu JR , Ge XX , Li J , Cui Y , Qiu ZB , Xu J , Xie Q , Wang H , Chen HZ
Ref : Pharmacol Biochem Behav , 104 :138 , 2013
Abstract : Alzheimer's disease (AD) is a multifaceted neurodegenerative disorder which is characterized by the progressive deterioration of cognition and the emergence of behavioral and psychological symptoms in aging patients. Given that the clinical effectiveness of acetylcholinesterase inhibitors (AChEIs) has still been questioned due to dubious disease-modifying effects, the multi-target directed ligand (MTDL) design has become an emerging strategy for developing new drugs for AD treatment. Bis(9)-(-)-nor-meptazinol (Bis-Mep) was firstly reported by us as a novel MTDL for both potent cholinesterase and amyloid-beta aggregation inhibition. In this study, we further explored its AChE inhibition kinetic features and cognitive amelioration. Bis-Mep was found to be a mixed-type inhibitor on electric eel AChE by enzyme kinetic study. Molecular docking revealed that two "water bridges" located at the two wings of Bis-Mep stabilized its interaction with both catalytic and peripheral anionic sites of AChE. Furthermore, subcutaneous administration of Bis-Mep (10, 100 or 1000ng/kg) significantly reversed the scopolamine-induced memory deficits in a typical bell-shaped dose-response manner. The maximal cognitive amelioration of Bis-Mep was achieved at 100ng/kg, comparable with the effect of a reference drug Huperzine A at 1mg/kg and also the relevant AChE inhibition in brain. These findings suggested that Bis-Mep might be a promising dual-binding AChE inhibitor for potential AD therapeutics.
ESTHER : Liu_2013_Pharmacol.Biochem.Behav_104_138
PubMedSearch : Liu_2013_Pharmacol.Biochem.Behav_104_138
PubMedID: 23262302

Title : Val-boroPro accelerates T cell priming via modulation of dendritic cell trafficking resulting in complete regression of established murine tumors - Walsh_2013_PLoS.One_8_e58860
Author(s) : Walsh MP , Duncan B , Larabee S , Krauss A , Davis JP , Cui Y , Kim SY , Guimond M , Bachovchin W , Fry TJ
Ref : PLoS ONE , 8 :e58860 , 2013
Abstract : Although tumors naturally prime adaptive immune responses, tolerance may limit the capacity to control progression and can compromise effectiveness of immune-based therapies for cancer. Post-proline cleaving enzymes (PPCE) modulate protein function through N-terminal dipeptide cleavage and inhibition of these enzymes has been shown to have anti-tumor activity. We investigated the mechanism by which Val-boroPro, a boronic dipeptide that inhibits post-proline cleaving enzymes, mediates tumor regression and tested whether this agent could serve as a novel immune adjuvant to dendritic cell vaccines in two different murine syngeneic murine tumors. In mice challenged with MB49, which expresses the HY antigen complex, T cell responses primed by the tumor with and without Val-boroPro were measured using interferon gamma ELISPOT. Antibody depletion and gene-deficient mice were used to establish the immune cell subsets required for tumor regression. We demonstrate that Val-boroPro mediates tumor eradication by accelerating the expansion of tumor-specific T cells. Interestingly, T cells primed by tumor during Val-boroPro treatment demonstrate increased capacity to reject tumors following adoptive transfer without further treatment of the recipient. Val-boroPro -mediated tumor regression requires dendritic cells and is associated with enhanced trafficking of dendritic cells to tumor draining lymph nodes. Finally, dendritic cell vaccination combined with Val-boroPro treatment results in complete regression of established tumors. Our findings demonstrate that Val-boroPro has antitumor activity and a novel mechanism of action that involves more robust DC trafficking with earlier priming of T cells. Finally, we show that Val-boroPro has potent adjuvant properties resulting in an effective therapeutic vaccine.
ESTHER : Walsh_2013_PLoS.One_8_e58860
PubMedSearch : Walsh_2013_PLoS.One_8_e58860
PubMedID: 23554941

Title : Molecular mechanism of inflammatory response in mouse liver caused by exposure to CeCl3 - Li_2013_Environ.Toxicol_28_349
Author(s) : Li N , Cheng J , Cheng Z , Hu R , Cai J , Gao G , Cui Y , Wang L , Hong F
Ref : Environ Toxicol , 28 :349 , 2013
Abstract : To investigate the molecular mechanism of inflammatory response in the mouse liver caused by exposure to CeCl3 , we measured the liver indices, and cerium content, evaluated the liver histopathological section, detected serum biochemical parameters of liver function, and the immunoglobulin M (IgM) content, analyzed the liver mRNA and protein expression levels of Toll-like receptor 2, 4 (TLR2, TLR4), and inflammatory cytokines in liver using real-time quantitative reverse transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay. The results showed that exposure to CeCl3 decreased body weight and caused cerium accumulation in the mouse liver and histopathological changes of liver (such as inflammatory cell infiltration). Furthermore, biochemical assays suggested that CeCl3 could promote the activities of alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase, pseudocholinesterase, and leucine aminopeptidase, decrease serum IgM, upregulate the levels of TLR2, TLR4, nuclear factor-kappaB (NF-kappaB), NF-kappaBp52, NF-kappaBp65, NF-kappaB-inducing kinase (NIK), IkappaB kinase alpha (IKK-alpha), IkappaB kinase beta (IKK-beta), and tumor necrosis factor-alpha (TNF-alpha) expression, and suppress NF-kappaB-inhibiting factor (IkappaB) and interleukin-2 (IL-2) expression in liver. Taken together, the inflammation of mice liver caused by exposure to CeCl3 might be closely associated with the alteration of inflammatory cytokine expressions in the mouse liver, the signal-transducing events happening in CeCl3 -induced macrophages of liver sequentially might occur via activation of TLRs-->TNF-alpha-->NIK-->IkappaB kinase (including IKK1, IKK2)-->NF-kappaB (including NF-kappaBP52, NF-kappaBP65)--> inflammation. (c) 2011 Wiley Periodicals, Inc. Environ Toxicol, 2013.
ESTHER : Li_2013_Environ.Toxicol_28_349
PubMedSearch : Li_2013_Environ.Toxicol_28_349
PubMedID: 21656643

Title : Draft genome of the wheat A-genome progenitor Triticum urartu - Ling_2013_Nature_496_87
Author(s) : Ling HQ , Zhao S , Liu D , Wang J , Sun H , Zhang C , Fan H , Li D , Dong L , Tao Y , Gao C , Wu H , Li Y , Cui Y , Guo X , Zheng S , Wang B , Yu K , Liang Q , Yang W , Lou X , Chen J , Feng M , Jian J , Zhang X , Luo G , Jiang Y , Liu J , Wang Z , Sha Y , Zhang B , Tang D , Shen Q , Xue P , Zou S , Wang X , Liu X , Wang F , Yang Y , An X , Dong Z , Zhang K , Luo MC , Dvorak J , Tong Y , Yang H , Li Z , Wang D , Zhang A
Ref : Nature , 496 :87 , 2013
Abstract : Bread wheat (Triticum aestivum, AABBDD) is one of the most widely cultivated and consumed food crops in the world. However, the complex polyploid nature of its genome makes genetic and functional analyses extremely challenging. The A genome, as a basic genome of bread wheat and other polyploid wheats, for example, T. turgidum (AABB), T. timopheevii (AAGG) and T. zhukovskyi (AAGGA(m)A(m)), is central to wheat evolution, domestication and genetic improvement. The progenitor species of the A genome is the diploid wild einkorn wheat T. urartu, which resembles cultivated wheat more extensively than do Aegilops speltoides (the ancestor of the B genome) and Ae. tauschii (the donor of the D genome), especially in the morphology and development of spike and seed. Here we present the generation, assembly and analysis of a whole-genome shotgun draft sequence of the T. urartu genome. We identified protein-coding gene models, performed genome structure analyses and assessed its utility for analysing agronomically important genes and for developing molecular markers. Our T. urartu genome assembly provides a diploid reference for analysis of polyploid wheat genomes and is a valuable resource for the genetic improvement of wheat.
ESTHER : Ling_2013_Nature_496_87
PubMedSearch : Ling_2013_Nature_496_87
PubMedID: 23535596
Gene_locus related to this paper: triua-m8a764 , triua-m8ag96 , triua-m7zp69 , wheat-w5d1z6 , wheat-w5d232 , wheat-w5bnf5 , triua-t1nm05 , wheat-w5cae4 , triua-m7ytf7 , wheat-w5f1j8 , triua-m8ad49 , wheat-a0a077s1q2 , wheat-a0a3b6c2m6 , triua-m7zi26 , wheat-a0a3b6at77 , wheat-a0a3b6atp7

Title : Structure of MERS-CoV spike receptor-binding domain complexed with human receptor DPP4 - Wang_2013_Cell.Res_23_986
Author(s) : Wang N , Shi X , Jiang L , Zhang S , Wang D , Tong P , Guo D , Fu L , Cui Y , Liu X , Arledge KC , Chen YH , Zhang L , Wang X
Ref : Cell Res , 23 :986 , 2013
Abstract : The spike glycoprotein (S) of recently identified Middle East respiratory syndrome coronavirus (MERS-CoV) targets the cellular receptor, dipeptidyl peptidase 4 (DPP4). Sequence comparison and modeling analysis have revealed a putative receptor-binding domain (RBD) on the viral spike, which mediates this interaction. We report the 3.0 A-resolution crystal structure of MERS-CoV RBD bound to the extracellular domain of human DPP4. Our results show that MERS-CoV RBD consists of a core and a receptor-binding subdomain. The receptor-binding subdomain interacts with DPP4 beta-propeller but not its intrinsic hydrolase domain. MERS-CoV RBD and related SARS-CoV RBD share a high degree of structural similarity in their core subdomains, but are notably divergent in the receptor-binding subdomain. Mutagenesis studies have identified several key residues in the receptor-binding subdomain that are critical for viral binding to DPP4 and entry into the target cell. The atomic details at the interface between MERS-CoV RBD and DPP4 provide structural understanding of the virus and receptor interaction, which can guide development of therapeutics and vaccines against MERS-CoV infection.
ESTHER : Wang_2013_Cell.Res_23_986
PubMedSearch : Wang_2013_Cell.Res_23_986
PubMedID: 23835475
Gene_locus related to this paper: human-DPP4

Title : Toxicological effects of multi-walled carbon nanotubes adsorbed with nonylphenol on earthworm Eisenia fetida - Hu_2013_Environ.Sci.Process.Impacts_15_2125
Author(s) : Hu C , Cai Y , Wang W , Cui Y , Li M
Ref : Environ Sci Process Impacts , 15 :2125 , 2013
Abstract : The high surface area of multi-walled carbon nanotubes (MWCNTs) tends to adsorb a large variety of toxic chemicals, which may enhance the toxicity of both MWCNTs and chemicals to organisms. In order to evaluate the combined toxicity of nonylphenol (NP) and MWCNTs to the earthworm Eisenia fetida in soil, artificial soil systems containing distilled water, 0.1 g kg(-1) MWCNTs, 1 g kg(-1) MWCNTs, 1 g kg(-1) MWCNTs absorbed 5 mg kg(-1) NP, and 10 mg kg(-1) NP alone were prepared and exposed to earthworms for 7 days. Antioxidative responses, and activities of cellulase, Na(+), K(+)-ATPase and acetylcholinesterase (TChE) as well as DNA damage were chosen as toxicological endpoints. The results showed that 1 g kg(-1) MWCNTs adsorbed 5 mg kg(-1) NP from the soil which caused much more adverse effects on the earthworms than each chemical alone, evident from the responses of cellulase, Na(+), K(+)-ATPase and comet assay. This study indicated that MWCNTs facilitated the bioavailability of NP to the earthworm and increased the harmful effects of NP.
ESTHER : Hu_2013_Environ.Sci.Process.Impacts_15_2125
PubMedSearch : Hu_2013_Environ.Sci.Process.Impacts_15_2125
PubMedID: 24104387

Title : Differential cigarette-related startle cue reactivity among light, moderate, and heavy smokers - Cui_2012_Addict.Behav_37_885
Author(s) : Cui Y , Robinson JD , Versace F , Lam CY , Minnix JA , Karam-Hage M , Dani JA , Kosten TR , Wetter DW , Brown VL , Cinciripini PM
Ref : Addict Behav , 37 :885 , 2012
Abstract : In this study, we examined the relationship between the level of daily cigarette consumption and the startle response to affective and cigarette-related cues among treatment-seeking smokers. Before receiving any behavioral or pharmacological treatment, 136 smokers attended a baseline laboratory session, during which we recorded their reflexive eyeblink responses to acoustic startle probes while they were viewing pleasant, unpleasant, neutral, and cigarette-related pictures. We found that 1) cigarette-related and pleasant pictures similarly reduced the startle magnitude compared to neutral pictures; 2) the magnitude of startle modulation rendered by pleasant or unpleasant pictures did not differ among light, moderate, and heavy smokers; and 3) startle attenuation by cigarette-related pictures was greater in heavy smokers than in light smokers. These results suggest that similar to pleasant stimuli, cigarette-related cues are motivationally salient for smokers, and that this salience increases with nicotine dependence.
ESTHER : Cui_2012_Addict.Behav_37_885
PubMedSearch : Cui_2012_Addict.Behav_37_885
PubMedID: 22571920

Title : Novel bis-(-)-nor-meptazinol derivatives act as dual binding site AChE inhibitors with metal-complexing property - Zheng_2012_Toxicol.Appl.Pharmacol_264_65
Author(s) : Zheng W , Li J , Qiu Z , Xia Z , Li W , Yu L , Chen H , Chen J , Chen Y , Hu Z , Zhou W , Shao B , Cui Y , Xie Q
Ref : Toxicol Appl Pharmacol , 264 :65 , 2012
Abstract : The strategy of dual binding site acetylcholinesterase (AChE) inhibition along with metal chelation may represent a promising direction for multi-targeted interventions in the pathophysiological processes of Alzheimer's disease (AD). In the present study, two derivatives (ZLA and ZLB) of a potent dual binding site AChE inhibitor bis-(-)-nor-meptazinol (bis-MEP) were designed and synthesized by introducing metal chelating pharmacophores into the middle chain of bis-MEP. They could inhibit human AChE activity with IC(50) values of 9.63uM (for ZLA) and 8.64uM (for ZLB), and prevent AChE-induced amyloid-beta (Abeta) aggregation with IC(50) values of 49.1uM (for ZLA) and 55.3uM (for ZLB). In parallel, molecular docking analysis showed that they are capable of interacting with both the catalytic and peripheral anionic sites of AChE. Furthermore, they exhibited abilities to complex metal ions such as Cu(II) and Zn(II), and inhibit Abeta aggregation triggered by these metals. Collectively, these results suggest that ZLA and ZLB may act as dual binding site AChEIs with metal-chelating potency, and may be potential leads of value for further study on disease-modifying treatment of AD.
ESTHER : Zheng_2012_Toxicol.Appl.Pharmacol_264_65
PubMedSearch : Zheng_2012_Toxicol.Appl.Pharmacol_264_65
PubMedID: 22842334

Title : Muscarinic Acetylcholine Receptor Subtypes as Potential Drug Targets for the Treatment of Schizophrenia, Drug Abuse and Parkinson's Disease - Dencker_2012_ACS.Chem.Neurosci_3_80
Author(s) : Dencker D , Thomsen M , Wortwein G , Weikop P , Cui Y , Jeon J , Wess J , Fink-Jensen A
Ref : ACS Chem Neurosci , 3 :80 , 2012
Abstract : The neurotransmitter dopamine plays important roles in modulating cognitive, affective, and motor functions. Dysregulation of dopaminergic neurotransmission is thought to be involved in the pathophysiology of several psychiatric and neurological disorders, including schizophrenia, Parkinson's disease and drug abuse. Dopaminergic systems are regulated by cholinergic, especially muscarinic, input. Not surprisingly, increasing evidence implicates muscarinic acetylcholine receptor-mediated pathways as potential targets for the treatment of these disorders classically viewed as "dopamine based". There are five known muscarinic receptor subtypes (M(1) to M(5)). Due to their overlapping expression patterns and the lack of receptor subtype-specific ligands, the roles of the individual muscarinic receptors have long remained elusive. During the past decade, studies with knock-out mice lacking specific muscarinic receptor subtypes have greatly advanced our knowledge of the physiological roles of the M(1)-M(5) receptors. Recently, new ligands have been developed that can interact with allosteric sites on different muscarinic receptor subtypes, rather than the conventional (orthosteric) acetylcholine binding site. Such agents may lead to the development of novel classes of drugs useful for the treatment of psychosis, drug abuse and Parkinson's disease. The present review highlights recent studies carried out using muscarinic receptor knock-out mice and new subtype-selective allosteric ligands to assess the roles of M(1), M(4), and M(5) receptors in various central processes that are under strong dopaminergic control. The outcome of these studies opens new perspectives for the use of novel muscarinic drugs for several severe disorders of the CNS.
ESTHER : Dencker_2012_ACS.Chem.Neurosci_3_80
PubMedSearch : Dencker_2012_ACS.Chem.Neurosci_3_80
PubMedID: 22389751

Title : A subpopulation of neuronal M4 muscarinic acetylcholine receptors plays a critical role in modulating dopamine-dependent behaviors - Jeon_2010_J.Neurosci_30_2396
Author(s) : Jeon J , Dencker D , Wortwein G , Woldbye DP , Cui Y , Davis AA , Levey AI , Schutz G , Sager TN , Mork A , Li C , Deng CX , Fink-Jensen A , Wess J
Ref : Journal of Neuroscience , 30 :2396 , 2010
Abstract : Acetylcholine (ACh) regulates many key functions of the CNS by activating cell surface receptors referred to as muscarinic ACh receptors (M(1)-M(5) mAChRs). Like other mAChR subtypes, the M(4) mAChR is widely expressed in different regions of the forebrain. Interestingly, M(4) mAChRs are coexpressed with D(1) dopamine receptors in a specific subset of striatal projection neurons. To investigate the physiological relevance of this M(4) mAChR subpopulation in modulating dopamine-dependent behaviors, we used Cre/loxP technology to generate mutant mice that lack M(4) mAChRs only in D(1) dopamine receptor-expressing cells. The newly generated mutant mice displayed several striking behavioral phenotypes, including enhanced hyperlocomotor activity and increased behavioral sensitization following treatment with psychostimulants. These behavioral changes were accompanied by a lack of muscarinic inhibition of D(1) dopamine receptor-mediated cAMP stimulation in the striatum and an increase in dopamine efflux in the nucleus accumbens. These novel findings demonstrate that a distinct subpopulation of neuronal M(4) mAChRs plays a critical role in modulating several important dopamine-dependent behaviors. Since enhanced central dopaminergic neurotransmission is a hallmark of several severe disorders of the CNS, including schizophrenia and drug addiction, our findings have substantial clinical relevance.
ESTHER : Jeon_2010_J.Neurosci_30_2396
PubMedSearch : Jeon_2010_J.Neurosci_30_2396
PubMedID: 20147565

Title : Genome sequencing and analysis of the model grass Brachypodium distachyon. -
Author(s) : Vogel JP , Garvin DF , Mockler TC , Schmutz J , Rokhsar D , Bevan MW , Barry K , Lucas S , Harmon-Smith M , Lail K , Tice H , Grimwood J , McKenzie N , Huo N , Gu YQ , Lazo GR , Anderson OD , You FM , Luo MC , Dvorak J , Wright J , Febrer M , Idziak D , Hasterok R , Lindquist E , Wang M , Fox SE , Priest HD , Filichkin SA , Givan SA , Bryant DW , Chang JH , Wu H , Wu W , Hsia AP , Schnable PS , Kalyanaraman A , Barbazuk B , Michael TP , Hazen SP , Bragg JN , Laudencia-Chingcuanco D , Weng Y , Haberer G , Spannagl M , Mayer K , Rattei T , Mitros T , Lee SJ , Rose JK , Mueller LA , York TL , Wicker T , Buchmann JP , Tanskanen J , Schulman AH , Gundlach H , Bevan M , de Oliveira AC , Maia Lda C , Belknap W , Jiang N , Lai J , Zhu L , Ma J , Sun C , Pritham E , Salse J , Murat F , Abrouk M , Bruggmann R , Messing J , Fahlgren N , Sullivan CM , Carrington JC , Chapman EJ , May GD , Zhai J , Ganssmann M , Gurazada SG , German M , Meyers BC , Green PJ , Tyler L , Wu J , Thomson J , Chen S , Scheller HV , Harholt J , Ulvskov P , Kimbrel JA , Bartley LE , Cao P , Jung KH , Sharma MK , Vega-Sanchez M , Ronald P , Dardick CD , De Bodt S , Verelst W , Inz D , Heese M , Schnittger A , Yang X , Kalluri UC , Tuskan GA , Hua Z , Vierstra RD , Cui Y , Ouyang S , Sun Q , Liu Z , Yilmaz A , Grotewold E , Sibout R , Hematy K , Mouille G , Hofte H , Michael T , Pelloux J , O'Connor D , Schnable J , Rowe S , Harmon F , Cass CL , Sedbrook JC , Byrne ME , Walsh S , Higgins J , Li P , Brutnell T , Unver T , Budak H , Belcram H , Charles M , Chalhoub B , Baxter I
Ref : Nature , 463 :763 , 2010
PubMedID: 20148030
Gene_locus related to this paper: bradi-i1grm0 , bradi-i1gx82 , bradi-i1hb80 , bradi-i1hkv6 , bradi-i1hpu6 , bradi-i1i3e4 , bradi-i1i9i0 , bradi-i1i435 , bradi-i1ix93 , bradi-i1gsk6 , bradi-i1hk44 , bradi-i1hk45 , bradi-i1hnk7 , bradi-i1hsd5 , bradi-i1huy4 , bradi-i1huy9 , bradi-i1huz0 , bradi-i1gxx9 , bradi-i1hl25 , bradi-i1hcw7 , bradi-i1hyv6 , bradi-i1hyb5 , bradi-i1hvr8 , bradi-i1hmu2 , bradi-i1hf05 , bradi-i1gry7 , bradi-i1hf06 , bradi-i1i5z8 , bradi-i1icy3 , bradi-i1j1h3 , bradi-i1h1e3 , bradi-i1hvr9 , bradi-a0a0q3r7i7 , bradi-i1i377 , bradi-i1hjg5 , bradi-i1h3i9 , bradi-i1gsg5 , bradi-a0a0q3mph9 , bradi-i1h682 , bradi-a0a0q3lc91 , bradi-i1gx49 , bradi-i1i839 , bradi-a0a2k2dsp5 , bradi-i1gsb5

Title : Clinicopathologic features between multicentric occurence and intrahepatic metastasis of multiple hepatocellular carcinomas related to HBV - Wang_2009_Surg.Oncol_18_25
Author(s) : Wang J , Li Q , Sun Y , Zheng H , Cui Y , Li H , Zhou H , Hao X
Ref : Surg Oncol , 18 :25 , 2009
Abstract : AIMS: To clarify the incidence of multicentric occurrence (MO) and intrahepatic metastasis (IM) for hepatocellular carcinoma (HCC) related to hepatitis B virus (HBV) in China and to identify the differences between them. PATIENTS AND METHODS: Histopathologic features of multiple tumors in 82 cases with HCC were analyzed. The two groups, the origin was determinable as of multicentric occurrence or as of intrahepatic metastasis, were analyzed for their survival rate, disease-free survival and clinicopathologic differences. RESULTS: According to histological findings, 19.5% and 69.5% patients were considered to be MO and IM, respectively. In total 73 cases from the histopathological method were selected and divided into group MO (16 cases) and the group IM (57 cases). Analysis of stepwise regression identified that: Child's stage, cholinesterase (host factors), tumor size, histological grade and positive portal vein invasion (tumor factors) were the most important discriminating factors between MO and IM (p<0.05). As for their prognosis, Kaplan-Meier and Log rank test showed the survival rate in group MO was significantly better than that in the group IM (p=0.003). No statistical significance was found between the disease-free survival in group MO and that in group IM (p=0.141). The analysis of Cox's proportional hazards model showed that tumor type (MO or IM) and Child's stage were the important prognostic factors (p=0.002 and 0.014, respectively). CONCLUSIONS: The incidence of MO in patients with multiple HCCs related to HBV is only about 20%, which is lower than that of Japan. Child's stage, cholinesterase (host factors), tumor size, histological grade and positive portal vein invasion (tumor factors) are the most important discriminating factors between MO and IM. The prognosis of patients with MO compared to IM is significantly better and tumor type (MO or IM) and Child's stage are important prognostic factors.
ESTHER : Wang_2009_Surg.Oncol_18_25
PubMedSearch : Wang_2009_Surg.Oncol_18_25
PubMedID: 18640032

Title : Protection of PMS777, a new AChE inhibitor with PAF antagonism, against amyloid-beta-induced neuronal apoptosis and neuroinflammation - Li_2009_Cell.Mol.Neurobiol_29_589
Author(s) : Li J , Hu J , Shao B , Zhou W , Cui Y , Dong C , Ezoulin JM , Zhu X , Ding W , Heymans F , Chen H
Ref : Cellular Molecular Neurobiology , 29 :589 , 2009
Abstract : Amyloid-beta (Abeta) plays a central role in the neuroinflammation and cholinergic neuronal apoptosis in Alzheimer's disease, and thus has been considered as a main determinant of this disease. In the previous study, we reported that PMS777, a novel bis-interacting ligand for acetylcholinesterase (AChE) inhibition and platelet-activating factor (PAF) receptor antagonism, could significantly attenuate PAF-induced neurotoxicity. Continuing our efforts, we further investigated the protective effect of PMS777 on Abeta-induced neuronal apoptosis in vitro and neuroinflammation in vivo. PMS777 (1-100 microM) was found to inhibit Abeta-induced human neuroblastoma SH-SY5Y cell apoptosis in a concentration-dependent manner. Concurrently, PMS777 increased ratio of bcl-2 to bax mRNA, and inhibited both mRNA expression and activity of caspase-3 in SH-SY5Y cells after the exposure with Abeta. In vivo experimental study demonstrated that PMS777 could attenuate Abeta-induced microglial and astrocytic activation in the rat hippocampus after systemic administration. These results suggest that PMS777 potently protects against Abeta-induced neuronal apoptosis and neuroinflammation, and warrants further investigations in connection with its potential value in the treatment of Alzheimer's disease.
ESTHER : Li_2009_Cell.Mol.Neurobiol_29_589
PubMedSearch : Li_2009_Cell.Mol.Neurobiol_29_589
PubMedID: 19194797

Title : M1-M3 muscarinic acetylcholine receptor-deficient mice: novel phenotypes - Gautam_2006_J.Mol.Neurosci_30_157
Author(s) : Gautam D , Duttaroy A , Cui Y , Han SJ , Deng C , Seeger T , Alzheimer C , Wess J
Ref : Journal of Molecular Neuroscience , 30 :157 , 2006
Abstract : The five muscarinic acetylcholine receptors (M1-M5 mAChRs) mediate a very large number of important physiological functions (Caulfield, 1993; Caulfield and Birdsall, 1998; Wess, 2004). Because of the lack of small molecule ligands endowed with a high degree of receptor subtype selectivity and the fact that most tissues or cell types express two or more mAChR subtypes, identification of the physiological and pathophysiological roles of the individual mAChR subtypes has proved to be a challenging task. To overcome these difficulties, we recently generated mutant mouse lines deficient in each of the five mAChR genes (M1R-/- mice, M2R-/- mice, M3R-/- mice, etc. [Wess, 2004]). Phenotyping studies showed that each of the five mutant mouse lines displayed characteristic physiological, pharmacological, behavioral, biochemical, or neurochemical deficits (Wess, 2004). This chapter summarizes recent findings dealing with the importance of the M2mAChR for cognitive processes and the roles of the M1 and M3 mAChRs in mediating stimulation of glandular secretion.
ESTHER : Gautam_2006_J.Mol.Neurosci_30_157
PubMedSearch : Gautam_2006_J.Mol.Neurosci_30_157
PubMedID: 17192665

Title : Selection of 2'-fluoro-modified RNA aptamers for alleviation of cocaine and MK-801 inhibition of the nicotinic acetylcholine receptor - Cui_2004_J.Membr.Biol_202_137
Author(s) : Cui Y , Ulrich H , Hess GP
Ref : J Membr Biol , 202 :137 , 2004
Abstract : The nicotinic acetylcholine receptor (nAChR) belongs to a group of five structurally related proteins that regulate signal transmission between approximately 10(12) cells of the mammalian nervous system. Many therapeutic agents and abused drugs inhibit the nAChR, including the anti-convulsant MK-801 and the abused drug cocaine. Many attempts have been made to find compounds that prevent inhibition by cocaine. Use of transient kinetic techniques to investigate the inhibition of the receptor by MK-801 and cocaine led to an inhibition mechanism not previously proposed. The mechanism led to the development of combinatorially synthesized RNA ligands that alleviate inhibition of the receptor. However, these ligands are relatively unstable. Here we determined whether much more stable 2'-fluoro-modified RNA ligands can be prepared and used to study the alleviation of receptor inhibition. Two classes of 2'-fluoro-modified RNA ligands were obtained: One class binds with higher affinity to the cocaine-binding site on the closed-channel form and, as predicted by the mechanism, inhibits the receptor. The second class binds with equal or higher affinity to the cocaine-binding site on the open-channel form and, as predicted by the mechanism, does not inhibit the receptor, and does alleviate cocaine and MK-801 inhibition of the nAChR. The stability of these 2'-fluoro-RNAs expands the utility of these ligands.
ESTHER : Cui_2004_J.Membr.Biol_202_137
PubMedSearch : Cui_2004_J.Membr.Biol_202_137
PubMedID: 15798902

Title : Novel insights into M5 muscarinic acetylcholine receptor function by the use of gene targeting technology - Yamada_2003_Life.Sci_74_345
Author(s) : Yamada M , Basile AS , Fedorova I , Zhang W , Duttaroy A , Cui Y , Lamping KG , Faraci FM , Deng CX , Wess J
Ref : Life Sciences , 74 :345 , 2003
Abstract : Until recently, little was known about the possible physiological functions of the M(5) muscarinic acetylcholine receptor subtype, the last member of the muscarinic receptor family (M(1)-M(5)) to be cloned. To learn more about the potential physiological roles of this receptor subtype, we generated and analyzed M(5) receptor-deficient mice (M5 -/- mice). Strikingly, acetylcholine, a potent dilator of most vascular beds, virtually lost the ability to dilate cerebral arteries and arterioles in M5 -/- mice, suggesting that endothelial M(5) receptors mediate this activity in wild-type mice. This effect was specific for cerebral blood vessels, since acetylcholine-mediated dilation of extra-cerebral arteries remained fully intact in M5 -/- mice. In addition, in vitro neurotransmitter release experiments indicated that M(5) receptors located on dopaminergic nerve terminals play a role in facilitating muscarinic agonist-induced dopamine release in the striatum, consistent with the observation that the dopaminergic neurons innervating the striatum almost exclusively express the M(5) receptor subtype. We also found that the rewarding effects of morphine, the prototypical opiate analgesic, were substantially reduced in M5 -/- mice, as measured in the conditioned place preference paradigm. Furthermore, both the somatic and affective components of naloxone-induced morphine withdrawal symptoms were significantly attenuated in M5 -/- mice. It is likely that these behavioral deficits are caused by the lack of mesolimbic M(5) receptors, activation of which is known to stimulate dopamine release in the nucleus accumbens. These results convincingly demonstrate that the M(5) muscarinic receptor is involved in modulating several important pharmacological and behavioral functions. These findings may lead to novel therapeutic strategies for the treatment of drug addiction and certain cerebrovascular disorders.
ESTHER : Yamada_2003_Life.Sci_74_345
PubMedSearch : Yamada_2003_Life.Sci_74_345
PubMedID: 14607263

Title : Deficiency of phosphatidylinositol-linked membrane proteins on erythrocytes of different subpopulations in paroxysmal nocturnal hemoglobinuria - Cui_1993_Chin.Med.J_106_323
Author(s) : Cui Y , Zhang ZN , Liu EK , Pan HZ
Ref : Chinese Medical Journal , 106 :323 , 1993
Abstract : The surface phosphatidylinositol (PI)-linked proteins on membrane of paroxysmal nocturnal hemoglobinuria (PNH) erythrocytes (PNHE) was analysed by a flowcytometer (FACS 420). It was found that the loss of acetylcholinesterase (AchE) and decay accelerating factor (DAF), two PI-linked proteins, from cell membrane of PNHE was not synchronous. The hemolysis rates of DAF (-) and AchE (-) PNHE were much higher than that of mixed population in cobra-venom factor (CoF) lysis test. Intact PNHE remaining after CoF lysis had relatively lower immunofluorescent labeling rate of AchE on membrane in comparison with normal erythrocytes. It implied that this subpopulation, in spite of being insensitive to complement lysis, was still abnormal in terms of the amount of PI-linked protein on cell membrane. When these intact PNHE remaining after CoF lysis were incubated with activated polymorphonuclear leukocytes (PMN) for three hours, immunofluorescent labeling of AchE on PNHE was prominently decreased. This indicated that reactive oxidants released from activated PMN might injure PI-linked proteins.
ESTHER : Cui_1993_Chin.Med.J_106_323
PubMedSearch : Cui_1993_Chin.Med.J_106_323
PubMedID: 7691484