Zhou W

References (55)

Title : Efficient enzymatic synthesis of chiral 2,3-dihydro-1,4-benzodioxane motif using engineered Candida antarctica lipase B - Wu_2023_RSC.Adv_13_18953
Author(s) : Wu Z , Shi W , Jin M , Zhou W
Ref : RSC Adv , 13 :18953 , 2023
Abstract : Chiral motifs of 2,3-dihydro-1,4 benzodioxane are extensively utilized in diverse medicinal substances and bioactive natural compounds, exhibiting significant biological activities. Notable examples of such therapeutic agents include prosympal, dibozane, piperoxan, and doxazosin. In this work, using 1,4-benzodioxane-2-carboxylic acid methyl ester as the substrate, after screening 38 CALB covariant residues, we found that mutants A225F and A225F/T103A can catalyze the kinetic resolution of the substrate. The effect of temperature, cosolvent, and cosolvent concentration on kinetic resolution was investigated, revealing that the best results were achieved at 30 degreesC with 20% n-butanol as a cosolvent, resulting in an optimal resolution (e.e.(s) 97%, E = 278) at 50 mM substrate concentration. Structure analysis showed that mutation sites 225 and 103 are not among the sites that interact directly with the substrate, which means that covariant amino acids that interact remotely with the substrate also regulate enzyme catalysis. This research may provide us with a new strategy for enzyme evolution.
ESTHER : Wu_2023_RSC.Adv_13_18953
PubMedSearch : Wu_2023_RSC.Adv_13_18953
PubMedID: 37350861

Title : Effects of monitoring exercise rehabilitation with target intensity on the patient with twice PCI: A case report - Liu_2023_Medicine.(Baltimore)_102_e33583
Author(s) : Liu X , Chen Y , Chen J , Li A , Zhong M , Zhou W , Tang L
Ref : Medicine (Baltimore) , 102 :e33583 , 2023
Abstract : RATIONALE: As the core of cardiac rehabilitation (CR), early exercise rehabilitation is beneficial for patients with coronary heart disease (CHD), and center-based CR with target intensity is superior to home-based CR. However, there was no research to observe the effects of exercise rehabilitation on cardiopulmonary exercise capacity, oxygen uptake efficiency slope, endothelial function evaluated as flow-mediated vasodilation (FMD), and blood plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) in CHD patients undergone percutaneous coronary intervention (PCI) for 3 months. PATIENT CONCERNS: A 57-year-old woman had been identified with triple vessel disease and undergone twice PCI for complete revascularization, however, there was no improvement in Lp-PLA2, FMD, and related indicators of cardiopulmonary exercise testing. DIAGNOSIS: Coronary angiography showed an 85% stenosis in the middle left anterior descending artery, an 85% stenosis in the proximity of a thick first-diagonal branch, a long 75 to 85% stenosis in the middle left circumflex artery, and a 90 to 95% stenosis in the proximal. The case was diagnosed as CHD. INTERVENTIONS: The patient obtained optimal medical therapy comprising therapeutic lifestyle changes, and began monitoring exercise rehabilitation with target intensity 3 months after the second PCI in the CR center. OUTCOMES: There were changes in cardiopulmonary exercise capacity, oxygen uptake efficiency slope, FMD, and Lp-PLA2 in the patient with 3 apparent stenotic coronary arteries who was done PCI twice, without or with postoperative exercise rehabilitation, respectively. LESSONS: We proved that monitoring exercise rehabilitation training with target intensity could improve the prognosis of chronic coronary syndrome patients, and it was never too late to do regular exercise rehabilitation.
ESTHER : Liu_2023_Medicine.(Baltimore)_102_e33583
PubMedSearch : Liu_2023_Medicine.(Baltimore)_102_e33583
PubMedID: 37083775

Title : Cognitive Enhancer Donepezil Attenuates Heroin-Seeking Behavior Induced by Cues in Rats - Mei_2023_J.Integr.Neurosci_22_76
Author(s) : Mei D , Wang F , Yuan B , Lai M , Zhou Y , Cui W , Liu H , Zhou W
Ref : J Integr Neurosci , 22 :76 , 2023
Abstract : PURPOSE: Opioid use disorder is a significant global problem. Chronic heroin use is associated with impairment of cognitive function and conscious control ability. The cholinergic system can be disrupted following heroin administration, indicating that activation of the cholinergic system may prevent chronic heroin misuse. Donepezil as an inhibitor of cholinesterase has been reported to clinically improve cognition and attention. In this study, the inhibition of heroin self-administration and heroin-seeking behaviours by donepezil were evaluated in rats. METHODS: Rats were trained to self-administer heroin every four hours for 14 consecutive days under a fixed ratio 1 (FR1) reinforcement schedule, then underwent withdrawal for two weeks. A progressive ratio schedule was then used to evaluate the relative motivational value of heroin reinforcement. After withdrawal, a conditioned cue was introduced for the reinstatement of heroin-seeking behaviour. Donepezil (0.3-3 mg/kg, i.p.) was used during both the FR1 heroin self-administration and progressive ratio schedules. Immunohistochemistry was used to investigate the mechanism of action of donepezil in the rat brain. RESULTS: Pre-treatment with high dose donepezil (3 mg/kg) but not low doses (0.3-1 mg/kg) significantly inhibited heroin self-administration under the FR1 schedule. Donepezil decreased motivation values under the progressive ratio schedule in a dose-dependent manner. All doses of donepezil (1-3 mg/kg) decreased the reinstatement of heroin seeking induced by cues. Correlation analysis indicated that the inhibition of donepezil on heroin-seeking behaviour was positively correlated with an increased expression of dopamine receptor 1 (D1R) and dopamine receptor 2 (D2R) in the nucleus accumbens (NAc) and increased expression of choline acetyltransferase (ChAT) in the ventral tegmental area (VTA). CONCLUSIONS: The present study demonstrated that donepezil could inhibit heroin intake and heroin-seeking behaviour. Further, donepezil could regulate dopamine receptors in the NAc via an increase of acetylcholine. These results suggested that donepezil could be developed as a potential approach for the treatment of heroin misuse.
ESTHER : Mei_2023_J.Integr.Neurosci_22_76
PubMedSearch : Mei_2023_J.Integr.Neurosci_22_76
PubMedID: 37258429

Title : Inhibition of Th17 cells by donepezil ameliorates experimental lung fibrosis and pulmonary hypertension - Guo_2023_Theranostics_13_1826
Author(s) : Guo Y , He Z , Chen Z , Chen F , Wang C , Zhou W , Liu J , Liu H , Shi R
Ref : Theranostics , 13 :1826 , 2023
Abstract : Rationale: Pulmonary hypertension (PH) secondary to lung fibrosis belongs to WHO Group III, one of the most common subgroups of PH; however, it lacks effective treatment options. Cholinesterase inhibitor donepezil (DON) has been shown to effectively improve Group I PH. However, its effects on Group III PH are unknown. Methods: A lung fibrosis-induced PH mouse model was constructed using a single intratracheal instillation of bleomycin (BLM), after which DON was administered daily. Pulmonary artery and right ventricle (RV) remodeling were evaluated at the end of the study. Lung tissue in each group was analyzed using RNA sequencing, and the results were further verified with datasets from patients with PH. The mechanisms underlying DON-induced effects on PH were verified both in vivo and in vitro. Results: DON effectively improved pulmonary artery and RV remodeling in the BLM-induced mouse model. Transcriptomic profiles of lung tissue indicated that the expression of inflammatory and fibrotic genes was significantly changed in this process. In the animal model and patients with PH, T helper 17 lymphocytes (Th17) were the most common inflammatory cells infiltrating the lung tissue. DON significantly inhibited lung fibroblast activation; thus, preventing lung fibrosis and reducing the inflammatory response and Th17 cell infiltration in the BLM-induced lung tissue. In addition, Th17 cells could activate lung fibroblasts by secreting IL17A, and DON-mediated inhibition of Th17 cell differentiation was found to depend on the alpha7nAchR-JAK2-STAT3 pathway. Conclusion: DON can alleviate lung fibrosis and PH in an experimental mouse model. It inhibited pro-inflammatory Th17 cell differentiation, which is dependent on a cholinergic receptor pathway, thereby regulating fibroblast activation.
ESTHER : Guo_2023_Theranostics_13_1826
PubMedSearch : Guo_2023_Theranostics_13_1826
PubMedID: 37064881

Title : Small molecular fluorescent probes for Alzheimer's disease associated active species - Tang_2023_Chemistry__e202300592
Author(s) : Tang F , Wang K , Liu X , Zhang X , Zhou W , Mu Z , Zhang T , Shu W , Liu Y , Xiao H
Ref : Chemistry , :e202300592 , 2023
Abstract : Alzheimer's disease (AD) is a progressive neurodegenerative disorder and is the main cause of dementia worldwide. As the pathogenesis of AD is quite complicated, there is continuous attention to AD-associated active species, such as amyloid-beta plaques, neurofibrillary tangles, metal ions, reactive oxygen/nitrogen/sulphurspecies, cholinesterase, viscosity, formaldehyde and so on. To this end, a series of small molecular fluorescent probes for these active species have been explored for early diagnosis and even remedy of AD. Herein, we systematacially summarize the versatile fluorescent probes mainly in recent three years, including the relationship between the structure and properties as well as the targeted diagnosis and imaging application of all these fluorescent probes. Moreover, the challenges and perspectives of the AD-related fluorescent probes are briefly explicated. We firmly expect this review may provide guidance for constructing new AD-relevant fluorescent probes and promote the clinical study of AD.
ESTHER : Tang_2023_Chemistry__e202300592
PubMedSearch : Tang_2023_Chemistry__e202300592
PubMedID: 37078523

Title : A Scd1-mediated metabolic alteration participates in liver responses to low-dose bavachin - Shen_2023_J.Pharm.Anal_13_806
Author(s) : Shen P , Bai ZJ , Zhou L , Wang NN , Ni ZX , Sun DZ , Huang CS , Hu YY , Xiao CR , Zhou W , Zhang BL , Gao Y
Ref : J Pharm Anal , 13 :806 , 2023
Abstract : Hepatotoxicity induced by bioactive constituents in traditional Chinese medicines or herbs, such as bavachin (BV) in Fructus Psoraleae, has a prolonged latency to overt drug-induced liver injury in the clinic. Several studies have described BV-induced liver damage and underlying toxicity mechanisms, but little attention has been paid to the deciphering of organisms or cellular responses to BV at no-observed-adverse-effect level, and the underlying molecular mechanisms and specific indicators are also lacking during the asymptomatic phase, making it much harder for early recognition of hepatotoxicity. Here, we treated mice with BV for 7 days and did not detect any abnormalities in biochemical tests, but found subtle steatosis in BV-treated hepatocytes. We then profiled the gene expression of hepatocytes and non-parenchymal cells at single-cell resolution and discovered three types of hepatocyte subsets in the BV-treated liver. Among these, the hepa3 subtype suffered from a vast alteration in lipid metabolism, which was characterized by enhanced expression of apolipoproteins, carboxylesterases, and stearoyl-CoA desaturase 1 (Scd1). In particular, increased Scd1 promoted monounsaturated fatty acids (MUFAs) synthesis and was considered to be related to BV-induced steatosis and polyunsaturated fatty acids (PUFAs) generation, which participates in the initiation of ferroptosis. Additionally, we demonstrated that multiple intrinsic transcription factors, including Srebf1 and Hnf4a, and extrinsic signals from niche cells may regulate the above-mentioned molecular events in BV-treated hepatocytes. Collectively, our study deciphered the features of hepatocytes in response to BV insult, decoded the underlying molecular mechanisms, and suggested that Scd1 could be a hub molecule for the prediction of hepatotoxicity at an early stage.
ESTHER : Shen_2023_J.Pharm.Anal_13_806
PubMedSearch : Shen_2023_J.Pharm.Anal_13_806
PubMedID: 37577386

Title : Hippocampal acetylcholine modulates stress-related behaviors independent of specific cholinergic inputs - Mineur_2022_Mol.Psychiatry_27_1829
Author(s) : Mineur YS , Mose TN , Vanopdenbosch L , Etherington IM , Ogbejesi C , Islam A , Pineda CM , Crouse RB , Zhou W , Thompson DC , Bentham MP , Picciotto MR
Ref : Mol Psychiatry , 27 :1829 , 2022
Abstract : Acetylcholine (ACh) levels are elevated in actively depressed subjects. Conversely, antagonism of either nicotinic or muscarinic ACh receptors can have antidepressant effects in humans and decrease stress-relevant behaviors in rodents. Consistent with a role for ACh in mediating maladaptive responses to stress, brain ACh levels increase in response to stressful challenges, whereas systemically blocking acetylcholinesterase (AChE, the primary ACh degradative enzyme) elicits depression-like symptoms in human subjects, and selectively blocking AChE in the hippocampus increases relevant behaviors in rodents. We used an ACh sensor to characterize stress-evoked ACh release, then used chemogenetic, optogenetic and pharmacological approaches to determine whether cholinergic inputs from the medial septum/diagonal bands of Broca (MSDBB) or ChAT-positive neurons intrinsic to the hippocampus mediate stress-relevant behaviors in mice. Chemogenetic inhibition or activation of MSDBB cholinergic neurons did not result in significant behavioral effects, while inhibition attenuated the behavioral effects of physostigmine. In contrast, optogenetic stimulation of septohippocampal terminals or selective chemogenetic activation of ChAT-positive inputs to hippocampus increased stress-related behaviors. Finally, stimulation of sparse ChAT-positive hippocampal neurons increased stress-related behaviors in one ChAT-Cre line, which were attenuated by local infusion of cholinergic antagonists. These studies suggest that ACh signaling results in maladaptive behavioral responses to stress if the balance of signaling is shifted toward increased hippocampal engagement.
ESTHER : Mineur_2022_Mol.Psychiatry_27_1829
PubMedSearch : Mineur_2022_Mol.Psychiatry_27_1829
PubMedID: 34997190

Title : Circadian Rhythm and Neurotransmitters Are Potential Pathways through Which Ocean Acidification and Warming Affect the Metabolism of Thick-Shell Mussels - Tang_2022_Environ.Sci.Technol__
Author(s) : Tang Y , Du X , Sun S , Shi W , Han Y , Zhou W , Zhang J , Teng S , Ren P , Liu G
Ref : Environ Sci Technol , : , 2022
Abstract : Although the impacts of ocean acidification and warming on marine organisms have been increasingly documented, little is known about the affecting mechanism underpinning their interactive impacts on physiological processes such as metabolism. Therefore, the effects of these two stressors on metabolism were investigated in thick-shell mussel Mytilus coruscus in this study. In addition, because metabolism is primarily regulated by circadian rhythm and neurotransmitters, the impacts of acidification and warming on these two regulatory processes were also analyzed. The data obtained demonstrated that the metabolism of mussels (indicated by the clearance rate, oxygen consumption rate, ammonia excretion rate, O:N ratio, ATP content, activity of pyruvate kinase, and expression of metabolism-related genes) were significantly affected by acidification and warming, resulting in a shortage of energy supply (indicated by the in vivo content of ATP). In addition, exposure to acidification and warming led to evident disruption in circadian rhythm (indicated by the heartrate and the expression rhythm of Per2, Cry, and BMAL1) and neurotransmitters (indicated by the activity of acetyl cholinesterase and in vivo contents of ACh, GABA, and DA). These findings suggest that circadian rhythms and neurotransmitters might be potential routes through which acidification and warming interactively affect the metabolism of mussels.
ESTHER : Tang_2022_Environ.Sci.Technol__
PubMedSearch : Tang_2022_Environ.Sci.Technol__
PubMedID: 35293730

Title : The benefit of exercise rehabilitation guided by 6-minute walk test on lipoprotein-associated phospholipase A2 in patients with coronary heart disease undergoing percutaneous coronary intervention: a prospective randomized controlled study - Liu_2022_BMC.Cardiovasc.Disord_22_177
Author(s) : Liu X , Zhou W , Fan W , Li A , Pang J , Chen Z , Li X , Hu X , Zeng Y , Tang L
Ref : BMC Cardiovasc Disord , 22 :177 , 2022
Abstract : BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) has been taken as a biomarker of inflammation in patients with acute coronary diseases. Regular exercise rehabilitation could attenuate inflammation and promote the rehabilitation of coronary heart disease (CHD). The level of Lp-PLA2 is negatively correlated with 6-min walk test (6-MWT). The exercise prescription of appropriate intensity is the basis of exercise rehabilitation. 6-MWT is associated with maximal oxygen consumption, and can be used to determine the intensity of exercise prescription guiding patients how to do exercise rehabilitation. The aim of this study was to observe the benefit of 6-MWT guided exercise rehabilitation on the level of Lp-PLA2 in patients with CHD undergoing percutaneous coronary intervention (PCI). METHODS: We prospectively, consecutively enrolled 100 patients between Dec 2018 and Dec 2020 in the fourth ward of the Department of Cardiology, Yuebei People's Hospital Affiliated to Shantou University. Eligible patients were 1:1 divided into Group A, with no exercise rehabilitation, and Group B, with regular exercise rehabilitation, using random number table method of simple randomization allocation. Clinical data such as general information, the profile of lipids and the level of Lp-PLA2 were collected at baseline and at 12-week follow-up. RESULTS: There were no statistically significant differences of the percentages of gender, hypertension, type-2 diabetes mellitus (T2DM), the profile of lipids and level of Lp-PLA2 between the groups at baseline (P > 0.05). The level of Lp-PLA2 decreased at 12-week follow-up, moreover, the decline of the Lp-PLA2 level in Group B was more significant than that in Group A (t = 2.875, P = 0.005). Multivariate linear regression analysis indicated that exercise rehabilitation was independently correlated with the level of Lp-PLA2 (beta' = - 0.258, t = - 2.542, P = 0.013). CONCLUSION: Exercise rehabilitation for 12 weeks guided by 6-MWT can further reduce the level of LP-PLA2 in patients with CHD undergoing PCI. Trial registration This trial was registered on the Chinese Clinical Trial Registry: ChiCTR2100048124, registered 3 July 2021- Retrospectively registered. The study protocol adheres to the CONSORT guidelines.
ESTHER : Liu_2022_BMC.Cardiovasc.Disord_22_177
PubMedSearch : Liu_2022_BMC.Cardiovasc.Disord_22_177
PubMedID: 35430800

Title : Accelerated Solvent Extraction of Antioxidant Compounds from Gardeniae Fructus and Its Acetylcholinesterase Inhibitory and PC12 Cell Protective Activities - Fan_2021_Foods_10_
Author(s) : Fan Y , Li X , Ding L , Zhou W , Xu G , Wang Y , Zhang Y , Ni Q
Ref : Foods , 10 : , 2021
Abstract : Gardeniae fructus is a common neuroprotective medicinal food in China, however the extraction efficiency and mixture activities are rarely mentioned. In this study, accelerated solvent extraction (ASE) parameters were optimized by a response surface methodology to extract antioxidants from Gardeniae fructus. Neuroprotective activity was evaluated using H(2)O(2) and amyloid-beta(25-35) peptide-treated PC12 cells. By comparing with three other extract methods (i.e., heated refluxing extraction (HRE), ultrasound-assisted extraction (UAE), microwave-assisted extraction (MAE)), it was found that the yield (35.10%), total iridoids (27.69%), total flavonoid (6.12%) content, antioxidant activities (IC(50) on DPPH, 164.46 microg/mL; FRAP value 4703.54 micromol/L), and acetylcholinesterase inhibitory ability (IC(50) 92.58 microg/mL) of ASE extract under the optimal condition (150 degreesC temperature, 10 min static time, 60% ethanol, 2 extract cycles) were significantly higher than other extract methods. The strongest ability to protect PC12 cells from damage was also present in ASE extract, as evidenced by decreasing lactate dehydrogenase and malondialdehyde levels, elevating superoxide dismutase and glutathioneperoxidase activities. Compositional analysis indicated that the extremely high crocetin level in ASE extract (1.30 microg/mg) may offer great potential. Our results indicated that ASE is a proper extraction method that could offer great potential for finding the neuroprotective ability of Gardeniae fructus for the treatment of AD.
ESTHER : Fan_2021_Foods_10_
PubMedSearch : Fan_2021_Foods_10_
PubMedID: 34829086

Title : Toxicity of gabapentin-lactam on the early developmental stage of zebrafish (Danio rerio) - He_2021_Environ.Pollut_287_117649
Author(s) : He Y , Jia D , Du S , Zhu R , Zhou W , Pan S , Zhang Y
Ref : Environ Pollut , 287 :117649 , 2021
Abstract : Gabapentin-lactam (GBP-L) is a transformation product (TP) of gabapentin (GBP), a widely used anti-epileptic pharmaceutical. Due to its high persistence, GBP-L has been frequently detected in the surface water. However, the effects of GBP-L on aquatic organisms have not been thoroughly investigated. In the present study, zebrafish (Danio rerio) embryos as a model organism were used to study the impacts of GBP-L in terms of embryos LC(50), spontaneous movement at 24 hpf (hours post fertilization), heartbeat rates at 48 hpf, and body length at 72 hpf, with the concentrations of GBP-L down to 0.01 microg/L, covering its environmental concentrations. Various biomarkers from nervous, antioxidant and immune systems of zebrafish larvae were analyzed, including acetylcholinesterase, acetylcholine, dopamine, gamma-aminobutyric acid, superoxide dismutase, catalase, glutathione S-transferase, C reactive protein, and lysozyme, to assess its toxicity on these systems. RT-qPCR was then used to further verify the results and explain the toxicological mechanism at the gene level. The results demonstrated that GBP-L is much more toxic than its parent compound, and could lead to adverse impacts on the aquatic organisms even at every low concentrations.
ESTHER : He_2021_Environ.Pollut_287_117649
PubMedSearch : He_2021_Environ.Pollut_287_117649
PubMedID: 34182397

Title : Design, synthesis, and biological evaluation of novel xanthone-alkylbenzylamine hybrids as multifunctional agents for the treatment of Alzheimer's disease - Zhang_2021_Eur.J.Med.Chem_213_113154
Author(s) : Zhang Z , Guo J , Cheng M , Zhou W , Wan Y , Wang R , Fang Y , Jin Y , Liu J , Xie SS
Ref : Eur Journal of Medicinal Chemistry , 213 :113154 , 2021
Abstract : In this study, a series of multifunctional hybrids against Alzheimer's disease were designed and obtained by conjugating the pharmacophores of xanthone and alkylbenzylamine through the alkyl linker. Biological activity results demonstrated that compound 4j was the most potent and balanced dual ChEs inhibitor with IC(50) values 0.85 microM and 0.59 microM for eeAChE and eqBuChE, respectively. Kinetic analysis and docking study indicated that compound 4j was a mixed-type inhibitor for both AChE and BuChE. Additionally, it exhibited good abilities to penetrate BBB, scavenge free radicals (4.6 trolox equivalent) and selectively chelate with Cu(2+) and Al(3+) at a 1:1.4 ligand/metal molar ratio. Importantly, after assessments of cytotoxic and acute toxicity, we found compound 4j could improve memory function of scopolamine-induced amnesia mice. Hence, the compound 4j can be considered as a promising lead compound for further investigation in the treatment of AD.
ESTHER : Zhang_2021_Eur.J.Med.Chem_213_113154
PubMedSearch : Zhang_2021_Eur.J.Med.Chem_213_113154
PubMedID: 33476932

Title : Study on Hepatotoxicity of Rhubarb Based on Metabolomics and Network Pharmacology - Li_2021_Drug.Des.Devel.Ther_15_1883
Author(s) : Li S , Wang Y , Li C , Yang N , Yu H , Zhou W , Chen S , Yang S , Li Y
Ref : Drug Des Devel Ther , 15 :1883 , 2021
Abstract : BACKGROUND: Rhubarb, as a traditional Chinese medicine, is the preferred drug for the treatment of stagnation and constipation in clinical practice. It has been reported that rhubarb possesses hepatotoxicity, but its mechanism in vivo is still unclear. METHODS: In this study, the chemical components in rhubarb were identified based on UPLC-Q-TOF/MS combined with data postprocessing technology. The metabolic biomarkers obtained through metabolomics technology were related to rhubarb-induced hepatotoxicity. Furthermore, the potential targets of rhubarb-induced hepatotoxicity were obtained by network pharmacology involving the above components and metabolites. Meanwhile, GO gene enrichment analysis and KEGG pathway analysis were performed on the common targets. RESULTS: Twenty-eight components in rhubarb were identified based on UPLC-Q-TOF/MS, and 242 targets related to rhubarb ingredients were predicted. Nine metabolic biomarkers obtained through metabolomics technology were closely related to rhubarb-induced hepatotoxicity, and 282 targets of metabolites were predicted. Among them, the levels of 4 metabolites, namely dynorphin B (10-13), cervonoyl ethanolamide, lysoPE (18:2), and 3-hydroxyphenyl 2-hydroxybenzoate, significantly increased, while the levels of 5 metabolites, namely dopamine, biopterin, choline, coenzyme Q9 and P1, P4-bis (5'-uridyl) tetraphosphate significantly decreased. In addition, 166 potential targets of rhubarb-induced hepatotoxicity were obtained by network pharmacology. The KEGG pathway analysis was performed on the common targets to obtain 46 associated signaling pathways. CONCLUSION: These data suggested that rhubarb may cause liver toxicity due to its action on dopamine D1 receptor (DRD1), dopamine D2 receptor (DRD2), phosphodiesterase 4B (PDE4B), vanilloid receptor (TRPV1); transient receptor potential cation channel subfamily M member 8 (TRPM8), prostanoid EP2 receptor (PTGER2), acetylcholinesterase (ACHE), muscarinic acetylcholine receptor M3 (CHRM3) through the cAMP signaling pathway, cholinergic synapses, and inflammatory mediators to regulate TRP channels. Metabolomics technology and network pharmacology were integrated to explore rhubarb hepatotoxicity to promote the reasonable clinical application of rhubarb.
ESTHER : Li_2021_Drug.Des.Devel.Ther_15_1883
PubMedSearch : Li_2021_Drug.Des.Devel.Ther_15_1883
PubMedID: 33976539

Title : Capsulation of AuNCs with AIE Effect into Metal-Organic Framework for the Marriage of a Fluorescence and Colorimetric Biosensor to Detect Organophosphorus Pesticides - Cai_2021_Anal.Chem__
Author(s) : Cai Y , Zhu H , Zhou W , Qiu Z , Chen C , Qileng A , Li K , Liu Y
Ref : Analytical Chemistry , : , 2021
Abstract : Organophosphorus pesticides (OPs) can inhibit the activity of acetylcholinesterase (AChE) to induce neurological diseases. It is significant to exploit a rapid and sensitive strategy to monitor OPs. Here, a metal-organic framework (MOF) acted as a carrier to encapsulate AuNCs, which can limit the molecular motion of AuNCs, trigger the aggregation-induced emission (AIE) effect, and exhibit a strong fluorescence with a fluorescence lifetime and quantum yield of 6.83 micros and 4.63%, respectively. Then, the marriage of fluorescence and colorimetric signals was realized on the basis of the dual function of the enzymolysis product from AChE and choline oxidase (CHO) on AuNCs@ZIF-8. First, it can decompose ZIF-8 to weaken the restraint on AuNCs, and thus the fluorescence receded. Second, it can be used as a substrate for the peroxidase mimics of the released AuNCs to oxidize 3,3',5,5'-tetramethylbenzidine (TMB) and a visible blue appeared. Thus, on the basis of the inhibition of AChE activity by OPs, a fluorescence-colorimetric dual-signal biosensor was established. In addition, colorimetric paper strips were exploited to realize a visual semiquantitative detection, and a smartphone APP was developed to make the visualization results more precise and realize real-time supervision of pesticide contamination.
ESTHER : Cai_2021_Anal.Chem__
PubMedSearch : Cai_2021_Anal.Chem__
PubMedID: 33957044

Title : Physiological and transcriptomic changes of zebrafish (Danio rerio) embryos-larvae in response to 2-MIB exposure - Zhou_2021_J.Hazard.Mater_416_126142
Author(s) : Zhou W , Li X , Wang Y , Wang J , Zhang J , Wei H , Peng C , Wang Z , Li G , Li D
Ref : J Hazard Mater , 416 :126142 , 2021
Abstract : 2-Methylisoborneol (2-MIB), a natural odorous substance, is widely distributed in water environment, but there is a paucity of information concerning its systemic toxicity. Herein, we investigated the effects of 2-MIB exposure on developmental parameters, locomotive behavior, oxidative stress, apoptosis and transcriptome of zebrafish. Zebrafish embryos exposed to different concentrations (0, 0.5, 5 and 42.8 microg/L) of 2-MIB showed no changes in mortality, hatchability, and malformation rate, but the body length of zebrafish larvae was significantly increased in a dose-dependent manner, and accompanied by the changes of growth hormone/insulin-like growth factor (GH/IGF) axis and the hypothalamic-pituitary-thyroid (HPT) axis genes. Moreover, the swimming activity of zebrafish larvae increased, which may be due to the increase of acetylcholinesterase (AChE) activity. Meanwhile, 2-MIB caused oxidative stress and apoptosis in zebrafish larvae by altering the NF-E2-related factor 2 (Nrf2) and mitochondrial signaling pathways, respectively. Transcriptome sequencing assay showed that the phototransduction signaling pathway was significantly enriched, and most of the genes in this pathway exhibited enhanced expression after exposure to 2-MIB. These findings provide an important reference for risk assessment and early warning to 2-MIB exposure.
ESTHER : Zhou_2021_J.Hazard.Mater_416_126142
PubMedSearch : Zhou_2021_J.Hazard.Mater_416_126142
PubMedID: 34492931

Title : Huperzine A inhibits heroin-seeking behaviors induced by cue or heroin priming in rats - Ma_2020_Neuroreport_31_819
Author(s) : Ma B , Cai Y , Zhang X , Wang F , Zhuang D , Liu H , Liu Y , Zhou W
Ref : Neuroreport , 31 :819 , 2020
Abstract : Cholinergic systems modulate dopaminergic function in brain pathways are thought to mediate heroin addiction. This study investigated whether huperzine A, an acetylcholinesterase inhibitor, has beneficial effects on heroin reward and heroin-seeking behavior. Rats were trained to self-administer heroin (50microg/kg/infusion) under the fixed ratio 1 schedule for 14days and then drug-seeking was extinguished for 10days, after which reinstatement of drug-seeking was induced by conditioned cues or heroin priming. Acute treatment with huperzine A at dose from 0.05 to 0.2mg/kg potently and dose-dependently suppressed the cue- and heroin-induced reinstatement of heroin-seeking behavior following extinction. Huperzine A at these doses failed to alter either heroin rewarding effect or spontaneous locomotion activity. The study demonstrated that acute treatment with huperzine A inhibited heroin-seeking behavior, suggesting that huperzine A may be used as an adjuvant treatment for heroin relapse and addiction.
ESTHER : Ma_2020_Neuroreport_31_819
PubMedSearch : Ma_2020_Neuroreport_31_819
PubMedID: 32576772

Title : First maternal uniparental disomy for chromosome 2 with PREPL novel frameshift mutation of congenital myasthenic syndrome 22 in an infant - Zhang_2020_Mol.Genet.Genomic.Med_8_e1144
Author(s) : Zhang P , Wu B , Lu Y , Ni Q , Liu R , Zhou W , Wang H
Ref : Mol Genet Genomic Med , 8 :e1144 , 2020
Abstract : BACKGROUND: Congenital myasthenic syndrome 22 (CMS22) is a rare autosomal recessive disorder due to isolated PREPL deficiency and characterized by neonatal hypotonia, muscular weakness, and feeding difficulties. Eight such cases have already been reported, while maternal uniparental disomy with a PREPL pathogenic mutation has never been involved. METHODS: Trio whole-exome sequencing (WES), comparative genomic hybridization microarray (arry-CGH), and Sanger sequencing were performed on a 6-month-old girl with severe neonatal hypotonia and feeding difficulties. Also, the phenotype and genotype of reported CMS22 patients were reviewed. RESULTS: In this female infant, we identified a novel homozygous frameshift mutation in PREPL (c.1282_1285delTTTG, p.Phe428Argfs*18) by trio-WES. Sanger sequencing confirmed that her mother was heterozygous and her father was normal. Trio-WES data showed that 96.70% (1668/1725) variants on chromosome 2 were homozygous and maternally inherited, suggesting maternal uniparental disomy of chromosome 2 [UPD(2)mat]. Array-CGH did not show copy number variants (CNVs) but revealed complete UPD(2). CONCLUSION: To date, nine patients with CMS22 have been reported including our patient, and we report the youngest and the first UPD(2)mat with PREPL novel homozygous pathogenic mutation case, which expand the mutation spectrum of PREPL gene.
ESTHER : Zhang_2020_Mol.Genet.Genomic.Med_8_e1144
PubMedSearch : Zhang_2020_Mol.Genet.Genomic.Med_8_e1144
PubMedID: 31985178
Gene_locus related to this paper: human-PREPL

Title : Surface functionalization of graphene oxide by amino acids for Thermomyces lanuginosus lipase adsorption - Zhou_2019_J.Colloid.Interface.Sci_546_211
Author(s) : Zhou W , Zhuang W , Ge L , Wang Z , Wu J , Niu H , Liu D , Zhu C , Chen Y , Ying H
Ref : J Colloid Interface Sci , 546 :211 , 2019
Abstract : Graphene oxide (GO) with oxygen containing functional groups can be selectively modified by small biomolecules to achieve heterogeneous surface properties. To achieve a hyper-enzymatic activity, the surface functionality of GO should be tailored to the orientation adsorption of the Thermomyces lanuginosus (TL) lipase, and the active center can be covered by a relatively hydrophobic helical lid for protection. In this work, amino acids were used to interact with GO through reduction reaction, hydrophobic forces, electrostatic forces, or hydrogen bonding to alter the surface hydrophobicity and charge density. Characterization of the structure and surface properties confirmed that the GO samples decorated with phenylalanine (Phe) and glutamic acid (Glu) exhibited superior hydrophobicity than other modifications, whereas tryptophan (Trp) and cysteine (Cys) provided weaker reduction effects on GO. Moreover, the zeta potential of the samples modified by amino acids of lysine (Lys) and arginine (Arg) is higher than other modified samples. The adsorption amount of lipase on Glu-GO reached 172mg/g and the relative enzymatic activity reached up to 200%. The thermodynamic data and the Freundlich isotherm model fitting showed that the lipase adsorption process on modified samples was spontaneous, endothermic and entropy increase.
ESTHER : Zhou_2019_J.Colloid.Interface.Sci_546_211
PubMedSearch : Zhou_2019_J.Colloid.Interface.Sci_546_211
PubMedID: 30921675

Title : Characterization of a Lipase From the Silkworm Intestinal Bacterium Bacillus pumilus With Antiviral Activity Against Bombyx mori (Lepidoptera: Bombycidae) Nucleopolyhedrovirus In Vitro - Liu_2018_J.Insect.Sci_18_
Author(s) : Liu R , Wang W , Liu X , Lu Y , Xiang T , Zhou W , Wan Y
Ref : J Insect Sci , 18 : , 2018
Abstract : To investigate whether Bombyx mori Linnaeus (Lepidoptera: Bombycidae) intestinal microorganism play a role in the host defence system against viral pathogens, a lipase gene from the silkworm intestinal bacterium Bacillus pumilus SW41 was characterized, and antiviral activity of its protein against B. mori nucleopolyhedrovirus (BmNPV) was tested. The lipase gene has an open-reading frame of 648 bp, which encodes a 215-amino-acid enzyme with a 34-amino-acid signal peptide. The recombinant lipase (without signal peptide) was expressed and purified by using an Escherichia coli BL21 (DE3) expression system. The total enzyme activity of this recombinant lipase reached 277.40 U/mg at the optimum temperature of 25 degrees C and optimum pH value of 8.0. The antiviral test showed that a relative high concentration of the recombinant lipase reduced BmNPV infectivity in vitro, which resulted in decreased viral DNA abundance and viral occlusion bodies. Besides, the preincubation method also suggested that the lipase probably directly acting on the budded virions. The results suggest that the lipase from intestinal bacterium B. pumilus SW41 is a potential antiviral factor for silkworm against BmNPV.
ESTHER : Liu_2018_J.Insect.Sci_18_
PubMedSearch : Liu_2018_J.Insect.Sci_18_
PubMedID: 30395292

Title : Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity - Turcot_2018_Nat.Genet_50_26
Author(s) : Turcot V , Lu Y , Highland HM , Schurmann C , Justice AE , Fine RS , Bradfield JP , Esko T , Giri A , Graff M , Guo X , Hendricks AE , Karaderi T , Lempradl A , Locke AE , Mahajan A , Marouli E , Sivapalaratnam S , Young KL , Alfred T , Feitosa MF , Masca NGD , Manning AK , Medina-Gomez C , Mudgal P , Ng MCY , Reiner AP , Vedantam S , Willems SM , Winkler TW , Abecasis G , Aben KK , Alam DS , Alharthi SE , Allison M , Amouyel P , Asselbergs FW , Auer PL , Balkau B , Bang LE , Barroso I , Bastarache L , Benn M , Bergmann S , Bielak LF , Bluher M , Boehnke M , Boeing H , Boerwinkle E , Boger CA , Bork-Jensen J , Bots ML , Bottinger EP , Bowden DW , Brandslund I , Breen G , Brilliant MH , Broer L , Brumat M , Burt AA , Butterworth AS , Campbell PT , Cappellani S , Carey DJ , Catamo E , Caulfield MJ , Chambers JC , Chasman DI , Chen YI , Chowdhury R , Christensen C , Chu AY , Cocca M , Collins FS , Cook JP , Corley J , Corominas Galbany J , Cox AJ , Crosslin DS , Cuellar-Partida G , D'Eustacchio A , Danesh J , Davies G , Bakker PIW , Groot MCH , Mutsert R , Deary IJ , Dedoussis G , Demerath EW , Heijer M , Hollander AI , Ruijter HM , Dennis JG , Denny JC , Angelantonio E , Drenos F , Du M , Dube MP , Dunning AM , Easton DF , Edwards TL , Ellinghaus D , Ellinor PT , Elliott P , Evangelou E , Farmaki AE , Farooqi IS , Faul JD , Fauser S , Feng S , Ferrannini E , Ferrieres J , Florez JC , Ford I , Fornage M , Franco OH , Franke A , Franks PW , Friedrich N , Frikke-Schmidt R , Galesloot TE , Gan W , Gandin I , Gasparini P , Gibson J , Giedraitis V , Gjesing AP , Gordon-Larsen P , Gorski M , Grabe HJ , Grant SFA , Grarup N , Griffiths HL , Grove ML , Gudnason V , Gustafsson S , Haessler J , Hakonarson H , Hammerschlag AR , Hansen T , Harris KM , Harris TB , Hattersley AT , Have CT , Hayward C , He L , Heard-Costa NL , Heath AC , Heid IM , Helgeland O , Hernesniemi J , Hewitt AW , Holmen OL , Hovingh GK , Howson JMM , Hu Y , Huang PL , Huffman JE , Ikram MA , Ingelsson E , Jackson AU , Jansson JH , Jarvik GP , Jensen GB , Jia Y , Johansson S , Jorgensen ME , Jorgensen T , Jukema JW , Kahali B , Kahn RS , Kahonen M , Kamstrup PR , Kanoni S , Kaprio J , Karaleftheri M , Kardia SLR , Karpe F , Kathiresan S , Kee F , Kiemeney LA , Kim E , Kitajima H , Komulainen P , Kooner JS , Kooperberg C , Korhonen T , Kovacs P , Kuivaniemi H , Kutalik Z , Kuulasmaa K , Kuusisto J , Laakso M , Lakka TA , Lamparter D , Lange EM , Lange LA , Langenberg C , Larson EB , Lee NR , Lehtimaki T , Lewis CE , Li H , Li J , Li-Gao R , Lin H , Lin KH , Lin LA , Lin X , Lind L , Lindstrom J , Linneberg A , Liu CT , Liu DJ , Liu Y , Lo KS , Lophatananon A , Lotery AJ , Loukola A , Luan J , Lubitz SA , Lyytikainen LP , Mannisto S , Marenne G , Mazul AL , McCarthy MI , McKean-Cowdin R , Medland SE , Meidtner K , Milani L , Mistry V , Mitchell P , Mohlke KL , Moilanen L , Moitry M , Montgomery GW , Mook-Kanamori DO , Moore C , Mori TA , Morris AD , Morris AP , Muller-Nurasyid M , Munroe PB , Nalls MA , Narisu N , Nelson CP , Neville M , Nielsen SF , Nikus K , Njolstad PR , Nordestgaard BG , Nyholt DR , O'Connel JR , O'Donoghue ML , Olde Loohuis LM , Ophoff RA , Owen KR , Packard CJ , Padmanabhan S , Palmer CNA , Palmer ND , Pasterkamp G , Patel AP , Pattie A , Pedersen O , Peissig PL , Peloso GM , Pennell CE , Perola M , Perry JA , Perry JRB , Pers TH , Person TN , Peters A , Petersen ERB , Peyser PA , Pirie A , Polasek O , Polderman TJ , Puolijoki H , Raitakari OT , Rasheed A , Rauramaa R , Reilly DF , Renstrom F , Rheinberger M , Ridker PM , Rioux JD , Rivas MA , Roberts DJ , Robertson NR , Robino A , Rolandsson O , Rudan I , Ruth KS , Saleheen D , Salomaa V , Samani NJ , Sapkota Y , Sattar N , Schoen RE , Schreiner PJ , Schulze MB , Scott RA , Segura-Lepe MP , Shah SH , Sheu WH , Sim X , Slater AJ , Small KS , Smith AV , Southam L , Spector TD , Speliotes EK , Starr JM , Stefansson K , Steinthorsdottir V , Stirrups KE , Strauch K , Stringham HM , Stumvoll M , Sun L , Surendran P , Swift AJ , Tada H , Tansey KE , Tardif JC , Taylor KD , Teumer A , Thompson DJ , Thorleifsson G , Thorsteinsdottir U , Thuesen BH , Tonjes A , Tromp G , Trompet S , Tsafantakis E , Tuomilehto J , Tybjaerg-Hansen A , Tyrer JP , Uher R , Uitterlinden AG , Uusitupa M , Laan SW , Duijn CM , Leeuwen N , van Setten J , Vanhala M , Varbo A , Varga TV , Varma R , Velez Edwards DR , Vermeulen SH , Veronesi G , Vestergaard H , Vitart V , Vogt TF , Volker U , Vuckovic D , Wagenknecht LE , Walker M , Wallentin L , Wang F , Wang CA , Wang S , Wang Y , Ware EB , Wareham NJ , Warren HR , Waterworth DM , Wessel J , White HD , Willer CJ , Wilson JG , Witte DR , Wood AR , Wu Y , Yaghootkar H , Yao J , Yao P , Yerges-Armstrong LM , Young R , Zeggini E , Zhan X , Zhang W , Zhao JH , Zhao W , Zhou W , Zondervan KT , Rotter JI , Pospisilik JA , Rivadeneira F , Borecki IB , Deloukas P , Frayling TM , Lettre G , North KE , Lindgren CM , Hirschhorn JN , Loos RJF
Ref : Nat Genet , 50 :26 , 2018
Abstract : Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are ~10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed ~7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
ESTHER : Turcot_2018_Nat.Genet_50_26
PubMedSearch : Turcot_2018_Nat.Genet_50_26
PubMedID: 29273807

Title : Multi-Protection of DL0410 in Ameliorating Cognitive Defects in D-Galactose Induced Aging Mice - Lian_2017_Front.Aging.Neurosci_9_409
Author(s) : Lian W , Jia H , Xu L , Zhou W , Kang , Liu A , Du G
Ref : Front Aging Neurosci , 9 :409 , 2017
Abstract : D-galactose has been reported to accelerate senescence in rodents, accompanied by a decline in learning and memory. We used a model of D-galactose-induced amnesia for the efficacy evaluation and pharmacologic studies of active compounds against Alzheimer's disease (AD). DL0410 is a potent inhibitor against acetylcholinesterase (AChE) and, in the present study, the effect of DL0410 was evaluated in this model. We found that DL0410 could significantly improve the learning and memory of D-galactose induced aging mice in a series of behavioral tests: novel-object recognition test, nest-building test, Morris water maze test and step-through test. Pharmacologic studies were conducted from several aspects: the cholinergic system, mitochondrial respiration, oxidative stress, neuroinflammation, apoptosis and synaptic loss. The acetylcholine level and AChE activity were not altered by D-galactose but were slightly affected by DL0410 in the brain. DL0410 could significantly improve decreased mitochondrial respiration in the NADH chain and FADH2 chain, and protect mitochondrial ultrastructure. DL0410 reduced the accumulation of advanced glycation end products (AGEs) and malondialdehyde (MDA) and increase the total antioxidant capability of the brain via an increase in activity of catalase, glutathione peroxidase (GPx) and superoxide dismutase (SOD). RAGE expression was inhibited by DL0410, followed by the decreased activation of astrocytes and microglia. Subsequent phosphorylation of NF-kappaB was also reversed by DL0410, with lower expression of cyclooxygenase-2 (COX2) and iNOS. With respect to apoptosis, the activation of caspase 3 and cleavage of PARP were downregulated significantly by DL0410, after the inhibition of phosphorylation of JNK induced by inflammation and oxidative stress. Synaptic protection by DL0410 was also demonstrated. These data suggest that mitochondrial protection has a primary role in the ameliorating effect of DL0410 on the impaired learning and memory, oxidative stress, inflammation, apoptosis and synaptic loss induced by D-galactose. DL0410 is a promising candidate for the treatment of aging-related AD, and this study lays an important foundation for its further research and development.
ESTHER : Lian_2017_Front.Aging.Neurosci_9_409
PubMedSearch : Lian_2017_Front.Aging.Neurosci_9_409
PubMedID: 29276489

Title : Nucleos(t)ide analogs improve long-term prognosis in patients with chronic hepatitis B-associated liver failure - Hu_2017_Hepatol.Res_47_347
Author(s) : Hu T , Yao L , Hu A , Jiang S , Ying H , Deng Q , Hu Y , Zhou W , Xiong T
Ref : Hepatol Res , 47 :347 , 2017
Abstract : AIM: Chronic hepatitis B-associated liver failure (CHB-LF) is associated with high mortality. Antiviral therapy with nucleoside and nucleotide analogs (NUCs) has been reported to improve the short-term prognosis of patients with CHB-LF. However, the long-term effects of the therapy remain unclear. We undertook a cohort study to investigate the long-term effect of NUC-based antiviral therapy in patients with CHB-LF.
METHODS: A total of 976 patients with CHB-LF were enrolled between January 2001 and December 2009 at the Liver Disease Center of Ningbo No. 2 Hospital (Ningbo, China). The patients were divided into the NUC treatment group (n = 412) and control group (n = 564). The propensity score matching method was used to match the patients between the two groups to equilibrate the covariates. Survival analysis was carried out using the matched samples. The Cox proportional hazard model was used for the analysis of prognostic factors.
RESULTS: After propensity matching, 262 pairs were successfully matched. No statistically significant difference was observed in the baseline characteristics of the matching pairs (P > 0.05). The long-term survival rate and survival duration of the NUC treatment group were higher than that of the control group (P < 0.05). Gender, age, Model for End-stage Liver Disease values, cholinesterase levels, white blood cell counts, hepatic encephalopathy, concomitant infection, and treatment with NUCs were found to be the independent factors associated with long-term prognosis. CONCLUSION: Antiviral therapy with NUCs may reduce the mortality rate and improve the long-term prognosis of patients with CHB-LF.
ESTHER : Hu_2017_Hepatol.Res_47_347
PubMedSearch : Hu_2017_Hepatol.Res_47_347
PubMedID: 27283374

Title : DL0410 Ameliorates Memory and Cognitive Impairments Induced by Scopolamine via Increasing Cholinergic Neurotransmission in Mice - Lian_2017_Molecules_22_
Author(s) : Lian W , Fang J , Xu L , Zhou W , Kang , Xiong W , Jia H , Liu AL , Du GH
Ref : Molecules , 22 : , 2017
Abstract : Deficiency of the cholinergic system is thought to play a vital role in cognitive impairment of dementia. DL0410 was discovered as a dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinestease (BuChE), with potent efficiency in in-vitro experiments, but its in vivo effect on the cholinergic model has not been evaluated, and its action mechanism has also not been illustrated. In the present study, the capability of DL0410 in ameliorating the amnesia induced by scopolamine was investigated, and its effect on the cholinergic system in the hippocampus and its binding mode in the active site of AChE was also explored. Mice were administrated DL0410 (3 mg/kg, 10 mg/kg, and 30 mg/kg), and mice treated with donepezil were used as a positive control. The Morris water maze, escape learning task, and passive avoidance task were used as behavioral tests. The test results indicated that DL0410 could significantly improve the learning and memory impairments induced by scopolamine, with 10 mg/kg performing best. Further, DL0410 inhibited the AChE activity and increased acetylcholine (ACh) levels in a dose-dependent manner, and interacted with the active site of AChE in a similar manner as donepezil. However, no difference in the activity of BuChE was found in this study. All of the evidence indicated that its AChE inhibition is an important mechanism in the anti-amnesia effect. In conclusion, DL0410 could be an effective therapeutic drug for the treatment of dementia, especially Alzheimer's disease.
ESTHER : Lian_2017_Molecules_22_
PubMedSearch : Lian_2017_Molecules_22_
PubMedID: 28272324

Title : Delayed recovery from paralysis associated with plasma cholinesterase deficiency - Zhou_2016_Springerplus_5_1887
Author(s) : Zhou W , Lv S
Ref : Springerplus , 5 :1887 , 2016
Abstract : INTRODUCTION: This case was to describe a patient presented a 6 h length of apnea associated with low cholinesterase activity. CASE DESCRIPTION: A 32 years old female patient (body weight 50 kg, height 160 cm) was admitted to the hospital for laparoscopy combined with hysteroscopy exploration. The preoperative interrogation revealed no significant personal or family history of adverse reaction to anesthetics. The patient was healthy, with no chronic or systemic disease. ASA classification is I. We performed a general anesthesia with intubation to the patient. Succinylcholine 100 mg was administered in anesthesia induction. After intubation, cisatracurium 3 mg and 3% sevoflurane were used for anesthesia maintenance. The patient had been mostly unresponsive to external stimuli for 10 min since the end of the operation. Six hours after operation, the patient had totally recovered from paralysis and tracheal tube was extubated. The plasma cholinesterase test showed 291 U/L, significantly below normal (4650-10,440 U/L). Three days after operation, the patient was discharged from hospital with no special discomfort. DISCUSSION AND EVALUATION: Reduced plasma cholinesterase activity may occur as a result of inherited, acquired defects or iatrogenic causes. If the acquired defects are excluded, low BChE activity is usually considered to be caused by mutations in butyrylcholinesterase gene (BCHE). 80% of the patients experiencing prolonged neuromuscular blockade following mivacurium have butyrylcholinesteraseen enzyme (BChE) deficiency of genetic origin. The novel mutation of BChE gene is usually associated with the ethnic of the patients. There is no specific treatment for butyrylcholinesterase deficiency and the mainstream is to maintain ventilatory support until succinlcholine is metabolized out of the myoneural junction and neuromuscular function recovers. Transfusion of fresh frozen plasma is also viable.
CONCLUSIONS: Plasma cholinesterase deficiency is a genetic or acquired condition. The most obvious feature of this genetic variants is prolonged recovery from paralysis in which administrated with succinylcholine or mivacurium. Once this is suspected, a laboratory test is important. There is no specific treatment for plasma cholinesterase deficiency. The best and safest way is to let the patient recover spontaneously. Mechanical ventilation support is important.
ESTHER : Zhou_2016_Springerplus_5_1887
PubMedSearch : Zhou_2016_Springerplus_5_1887
PubMedID: 27843744

Title : Fibroblast Activation Protein Cleaves and Inactivates Fibroblast Growth Factor 21 - Dunshee_2016_J.Biol.Chem_291_5986
Author(s) : Dunshee DR , Bainbridge TW , Kljavin NM , Zavala-Solorio J , Schroeder AC , Chan R , Corpuz R , Wong M , Zhou W , Deshmukh G , Ly J , Sutherlin DP , Ernst JA , Sonoda J
Ref : Journal of Biological Chemistry , 291 :5986 , 2016
Abstract : FGF21 is a stress-induced hormone with potent anti-obesity, insulin-sensitizing, and hepatoprotective properties. Although proteolytic cleavage of recombinant human FGF21 in preclinical species has been observed previously, the regulation of endogenously produced FGF21 is not well understood. Here we identify fibroblast activation protein (FAP) as the enzyme that cleaves and inactivates human FGF21. A selective chemical inhibitor, immunodepletion, or genetic deletion of Fap stabilized recombinant human FGF21 in serum. In addition, administration of a selective FAP inhibitor acutely increased circulating intact FGF21 levels in cynomolgus monkeys. On the basis of our findings, we propose selective FAP inhibition as a potential therapeutic approach to increase endogenous FGF21 activity for the treatment of obesity, type 2 diabetes, non-alcoholic steatohepatitis, and related metabolic disorders.
ESTHER : Dunshee_2016_J.Biol.Chem_291_5986
PubMedSearch : Dunshee_2016_J.Biol.Chem_291_5986
PubMedID: 26797127

Title : Sunitinib, a Clinically Used Anticancer Drug, Is a Potent AChE Inhibitor and Attenuates Cognitive Impairments in Mice - Huang_2016_ACS.Chem.Neurosci_7_1047
Author(s) : Huang L , Lin J , Xiang S , Zhao K , Yu J , Zheng J , Xu D , Mak SH , Hu S , Nirasha S , Wang C , Chen X , Zhang J , Xu S , Wei X , Zhang Z , Zhou D , Zhou W , Cui W , Han YF , Hu Z , Wang Q
Ref : ACS Chem Neurosci , 7 :1047 , 2016
Abstract : Sunitinib, a tyrosine kinase inhibitor, is clinically used for the treatment of cancer. In this study, we found for the first time that sunitinib inhibits acetylcholinesterase (AChE) at submicromolar concentrations in vitro. In addition, sunitinib dramatically decreased the hippocampal and cortical activity of AChE in a time-dependent manner in mice. Molecular docking analysis further demonstrates that sunitinib might interact with both the catalytic anion and peripheral anionic sites within AChE, which is in accordance with enzymatic activity results showing that sunitinib inhibits AChE in a mixed pattern. Most importantly, we evaluated the effects of sunitinib on scopolamine-induced cognitive impairments in mice by using novel object recognition and Morris water maze tests. Surprisingly, sunitinib could attenuate cognitive impairments to a similar extent as donepezil, a marketed AChE inhibitor used for the treatment of Alzheimer's disease. In summary, our results have shown that sunitinib could potently inhibit AChE and attenuate cognitive impairments in mice.
ESTHER : Huang_2016_ACS.Chem.Neurosci_7_1047
PubMedSearch : Huang_2016_ACS.Chem.Neurosci_7_1047
PubMedID: 27046396

Title : DL0410, a novel dual cholinesterase inhibitor, protects mouse brains against Abeta-induced neuronal damage via the Akt\/JNK signaling pathway - Zhou_2016_Acta.Pharmacol.Sin_37_1401
Author(s) : Zhou D , Zhou W , Song JK , Feng ZY , Yang RY , Wu S , Wang L , Liu AL , Du GH
Ref : Acta Pharmacol Sin , 37 :1401 , 2016
Abstract : AIM: 1,1'-([1,1'-Biphenyl]-4,4'-diyl)bis(3-(piperidin-1-yl)propan-1-one)dihydrochlorid e (DL0410) is a novel synthetic dual acetylcholinesterase (AChE)/butyrocholinesterase (BuChE) inhibitor, which has shown a potential therapeutic effect on Alzheimer's disease (AD). In this study we examined whether DL0410 produced neuroprotective effects in an AD cellular model and an Abeta1-42-induced amnesia mouse model.
METHODS: The in vitro inhibitory activities against AChE and BuChE were estimated using Ellman's assay. Copper-induced toxicity in APPsw-SY5Y cells was used as AD cellular model, the cell viability was assessed using MTS assay, and cell apoptosis was evaluated based on mitochondrial membrane potential detection. Abeta1-42-induced amnesia mouse model was made in male mice by injecting aggregated Abeta1-42 (2 mug in 2 muL 0.1% DMSO) into the right cerebral ventricle. Before and after Abeta1-42 injection, the mice were orally administered DL0410 (1, 3, 9 mg.kg-1.d-1) or rivastigmine (2 mg.kg-1.d-1) for 3 and 11 d, respectively. Memory impairments were examined using Morris water maze (MWM) test and passive avoidance test. The expression levels of APP, CREB, BDNF, JNK and Akt in the mouse brains were measured with either immunohistochemistry or Western blotting.
RESULTS: DL0410 exhibited in vitro inhibitory abilities against AChE and BuChE with IC50 values of 0.286+/-0.004 and 3.962+/-0.099 mumol/L, respectively, which were comparable to those of donepezil and rivastigmine. In APPsw-SY5Y cells, pretreatment with DL0410 (1, 3, and 10 mumol/L) decreased the phosphorylation of JNK and increased the phosphorylation of Akt, markedly decreased copper-stimulated Abeta1-42 production, reversed the loss of mitochondrial membrane potential, and dose-dependently increased the cell viability. In Abeta1-42-treated mice, DL0410 administration significantly ameliorated learning and memory deficits in MWM test and passive avoidance test. Furthermore, DL0410 administration markedly decreased Abeta1-40/42 deposits in mouse cerebral cortices, and significantly up-regulated neurotrophic CREB/BDNF. Meanwhile, Akt/JNK signaling pathway may play a key role in the neuroprotective effect of DL0410. CONCLUSION: DL0410 ameliorates cognitive deficit and exerts neuronal protection in AD models, implicating this compound as a candidate drug for the prevention and therapy of AD.
ESTHER : Zhou_2016_Acta.Pharmacol.Sin_37_1401
PubMedSearch : Zhou_2016_Acta.Pharmacol.Sin_37_1401
PubMedID: 27498773

Title : Characterization of large structural genetic mosaicism in human autosomes - Machiela_2015_Am.J.Hum.Genet_96_487
Author(s) : Machiela MJ , Zhou W , Sampson JN , Dean MC , Jacobs KB , Black A , Brinton LA , Chang IS , Chen C , Chen K , Cook LS , Crous Bou M , De Vivo I , Doherty J , Friedenreich CM , Gaudet MM , Haiman CA , Hankinson SE , Hartge P , Henderson BE , Hong YC , Hosgood HD, 3rd , Hsiung CA , Hu W , Hunter DJ , Jessop L , Kim HN , Kim YH , Kim YT , Klein R , Kraft P , Lan Q , Lin D , Liu J , Le Marchand L , Liang X , Lissowska J , Lu L , Magliocco AM , Matsuo K , Olson SH , Orlow I , Park JY , Pooler L , Prescott J , Rastogi R , Risch HA , Schumacher F , Seow A , Setiawan VW , Shen H , Sheng X , Shin MH , Shu XO , VanDen Berg D , Wang JC , Wentzensen N , Wong MP , Wu C , Wu T , Wu YL , Xia L , Yang HP , Yang PC , Zheng W , Zhou B , Abnet CC , Albanes D , Aldrich MC , Amos C , Amundadottir LT , Berndt SI , Blot WJ , Bock CH , Bracci PM , Burdett L , Buring JE , Butler MA , Carreon T , Chatterjee N , Chung CC , Cook MB , Cullen M , Davis FG , Ding T , Duell EJ , Epstein CG , Fan JH , Figueroa JD , Fraumeni JF, Jr. , Freedman ND , Fuchs CS , Gao YT , Gapstur SM , Patino-Garcia A , Garcia-Closas M , Gaziano JM , Giles GG , Gillanders EM , Giovannucci EL , Goldin L , Goldstein AM , Greene MH , Hallmans G , Harris CC , Henriksson R , Holly EA , Hoover RN , Hu N , Hutchinson A , Jenab M , Johansen C , Khaw KT , Koh WP , Kolonel LN , Kooperberg C , Krogh V , Kurtz RC , Lacroix A , Landgren A , Landi MT , Li D , Liao LM , Malats N , McGlynn KA , McNeill LH , McWilliams RR , Melin BS , Mirabello L , Peplonska B , Peters U , Petersen GM , Prokunina-Olsson L , Purdue M , Qiao YL , Rabe KG , Rajaraman P , Real FX , Riboli E , Rodriguez-Santiago B , Rothman N , Ruder AM , Savage SA , Schwartz AG , Schwartz KL , Sesso HD , Severi G , Silverman DT , Spitz MR , Stevens VL , Stolzenberg-Solomon R , Stram D , Tang ZZ , Taylor PR , Teras LR , Tobias GS , Viswanathan K , Wacholder S , Wang Z , Weinstein SJ , Wheeler W , White E , Wiencke JK , Wolpin BM , Wu X , Wunder JS , Yu K , Zanetti KA , Zeleniuch-Jacquotte A , Ziegler RG , de Andrade M , Barnes KC , Beaty TH , Bierut LJ , Desch KC , Doheny KF , Feenstra B , Ginsburg D , Heit JA , Kang JH , Laurie CA , Li JZ , Lowe WL , Marazita ML , Melbye M , Mirel DB , Murray JC , Nelson SC , Pasquale LR , Rice K , Wiggs JL , Wise A , Tucker M , Perez-Jurado LA , Laurie CC , Caporaso NE , Yeager M , Chanock SJ
Ref : American Journal of Human Genetics , 96 :487 , 2015
Abstract : Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 x 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population.
ESTHER : Machiela_2015_Am.J.Hum.Genet_96_487
PubMedSearch : Machiela_2015_Am.J.Hum.Genet_96_487
PubMedID: 25748358

Title : Sulfonamides as multifunctional agents for Alzheimer's disease - Bag_2015_Bioorg.Med.Chem.Lett_25_626
Author(s) : Bag S , Tulsan R , Sood A , Cho H , Redjeb H , Zhou W , LeVine H, 3rd , Torok B , Torok M
Ref : Bioorganic & Medicinal Chemistry Lett , 25 :626 , 2015
Abstract : Sulfonamide linker-based inhibitors with extended linear structure were designed and synthesized with the aim of producing multifunctional agents against several processes involved in the pathology of Alzheimer's disease (AD). The potency of the compounds were assessed in the inhibition of Abeta self-assembly (fibril and oligomer formation), in modulating cholinesterase (AChE, BCHE) activity, and scavenging free radicals. Several compounds exhibited promising Abeta self-assembly and cholinesterase inhibition and in parallel, showed good free radical scavenging properties. The investigation of the scaffold described in this study resulted in the identification of three compounds (14, 19 and 26) as promising leads for the further design of multifunctional drug candidates for AD.
ESTHER : Bag_2015_Bioorg.Med.Chem.Lett_25_626
PubMedSearch : Bag_2015_Bioorg.Med.Chem.Lett_25_626
PubMedID: 25537270

Title : mAChRs activation induces epithelial-mesenchymal transition on lung epithelial cells - Yang_2014_BMC.Pulm.Med_14_53
Author(s) : Yang K , Song Y , Tang YB , Xu ZP , Zhou W , Hou LN , Zhu L , Yu ZH , Chen HZ , Cui YY
Ref : BMC Pulm Med , 14 :53 , 2014
Abstract : BACKGROUND: Epithelial-mesenchymal transition (EMT) has been proposed as a mechanism in the progression of airway diseases and cancer. Here, we explored the role of acetylcholine (ACh) and the pathway involved in the process of EMT, as well as the effects of mAChRs antagonist.
METHODS: Human lung epithelial cells were stimulated with carbachol, an analogue of ACh, and epithelial and mesenchymal marker proteins were evaluated usingwestern blot and immunofluorescence analyses.
RESULTS: Decreased E-cadherin expression and increased vimentin and alpha-SMA expression induced by TGF-beta1 in alveolar epithelial cell (A549) were significantly abrogated by the non-selective mAChR antagonist atropine and enhanced by the acetylcholinesterase inhibitor physostigmine. An EMT event also occurred in response to physostigmine alone. Furthermore, ChAT express and ACh release by A549 cells were enhanced by TGF-beta1. Interestingly, ACh analogue carbachol also induced EMT in A549 cells as well as in bronchial epithelial cells (16HBE) in a time- and concentration-dependent manner, the induction of carbachol was abrogated by selective antagonist of M1 (pirenzepine) and M3 (4-DAMP) mAChRs, but not by M2 (methoctramine) antagonist. Moreover, carbachol induced TGF-beta1 production from A549 cells concomitantly with the EMT process. Carbachol-induced EMT occurred through phosphorylation of Smad2/3 and ERK, which was inhibited by pirenzepine and 4-DAMP.
CONCLUSIONS: Our findings for the first time indicated that mAChR activation, perhaps via M1 and M3 mAChR, induced lung epithelial cells to undergo EMT and provided insights into novel therapeutic strategies for airway diseases in which lung remodeling occurs.
ESTHER : Yang_2014_BMC.Pulm.Med_14_53
PubMedSearch : Yang_2014_BMC.Pulm.Med_14_53
PubMedID: 24678619

Title : Blood transcriptomic biomarkers of Alzheimer's disease patients treated with EHT 0202 - Desire_2013_J.Alzheimers.Dis_34_469
Author(s) : Desire L , Blondiaux E , Carriere J , Haddad R , Sol O , Fehlbaum-Beurdeley P , Einstein R , Zhou W , Pando MP
Ref : J Alzheimers Dis , 34 :469 , 2013
Abstract : Monitoring the genomic expression of patients in clinical trials for Alzheimer's disease (AD) can assist trial design and treatment response analysis. Here, we report on the identification in AD patients of blood-based transcriptomic signatures associated with treatment response of EHT 0202, a new compound with potential disease-modifying and symptomatic properties, in a 3-month, placebo-controlled, Phase IIA study aimed at determining the clinical safety, tolerability, and exploratory efficacy of EHT 0202 (40 and 80 mg bid) as adjunctive therapy to one cholinesterase inhibitor in mild to moderate AD patients. Genome-wide transcriptomic profiling was performed on blood samples taken prior to treatment and at study completion in a subpopulation of 60 AD patients selected as either the 10 worst disease decliners or the 10 best improvers of each treatment group, using ADAS-Cog scores as measure of disease severity. In the patients responding to EHT 0202, a pre-treatment (baseline) transcriptomic signature showed activation of pathways related to AD, CNS disorders, diabetes, inflammation, and autoimmunity, while a post-treatment signature indicated reduced activation of these pathways with induced metabolic and transcription stimulation. This pilot study demonstrates the utility of blood transcriptomic signatures used as biomarkers for predicting patient response or monitoring efficacy, for an administered therapeutic drug in a complex disease such as AD. For EHT 0202 or other AD drugs, such biomarkers may help to improve strategies to better identify appropriate patient populations for treatment, understand the drug mechanism of efficacy, and/or clarify the inherent subjectivity in most clinical endpoints used in this disease.
ESTHER : Desire_2013_J.Alzheimers.Dis_34_469
PubMedSearch : Desire_2013_J.Alzheimers.Dis_34_469
PubMedID: 23234880

Title : Draft Genome Sequence of Streptomyces bottropensis ATCC 25435, a Bottromycin-Producing Actinomycete - Zhang_2013_Genome.Announc_1_e0001913
Author(s) : Zhang H , Zhou W , Zhuang Y , Liang X , Liu T
Ref : Genome Announc , 1 :e0001913 , 2013
Abstract : A series of bottromycin antibiotics have been isolated and identified from Streptomyces bottropensis strain ATCC 25435. Here, a draft genome sequence of S. bottropensis ATCC 25435 is presented. The genome carries an intact biosynthetic gene cluster for bottromycin antibiotics, which provides insight into the combinatorial biosynthesis of bottromycin antibiotics.
ESTHER : Zhang_2013_Genome.Announc_1_e0001913
PubMedSearch : Zhang_2013_Genome.Announc_1_e0001913
PubMedID: 23516178
Gene_locus related to this paper: 9actn-k0p1p9 , 9actn-m3fsi6 , 9actn-m3dmy7

Title : Whole-genome sequencing of Oryza brachyantha reveals mechanisms underlying Oryza genome evolution - Chen_2013_Nat.Commun_4_1595
Author(s) : Chen J , Huang Q , Gao D , Wang J , Lang Y , Liu T , Li B , Bai Z , Luis Goicoechea J , Liang C , Chen C , Zhang W , Sun S , Liao Y , Zhang X , Yang L , Song C , Wang M , Shi J , Liu G , Liu J , Zhou H , Zhou W , Yu Q , An N , Chen Y , Cai Q , Wang B , Liu B , Min J , Huang Y , Wu H , Li Z , Zhang Y , Yin Y , Song W , Jiang J , Jackson SA , Wing RA , Chen M
Ref : Nat Commun , 4 :1595 , 2013
Abstract : The wild species of the genus Oryza contain a largely untapped reservoir of agronomically important genes for rice improvement. Here we report the 261-Mb de novo assembled genome sequence of Oryza brachyantha. Low activity of long-terminal repeat retrotransposons and massive internal deletions of ancient long-terminal repeat elements lead to the compact genome of Oryza brachyantha. We model 32,038 protein-coding genes in the Oryza brachyantha genome, of which only 70% are located in collinear positions in comparison with the rice genome. Analysing breakpoints of non-collinear genes suggests that double-strand break repair through non-homologous end joining has an important role in gene movement and erosion of collinearity in the Oryza genomes. Transition of euchromatin to heterochromatin in the rice genome is accompanied by segmental and tandem duplications, further expanded by transposable element insertions. The high-quality reference genome sequence of Oryza brachyantha provides an important resource for functional and evolutionary studies in the genus Oryza.
ESTHER : Chen_2013_Nat.Commun_4_1595
PubMedSearch : Chen_2013_Nat.Commun_4_1595
PubMedID: 23481403
Gene_locus related to this paper: orysa-Q6ZDG3 , orysa-q6h415 , orysj-q6yse8 , orysa-q33aq0 , orybr-j3l7k2 , orybr-j3m138 , orybr-j3l6m8 , orybr-j3m3b3 , orybr-j3l8d1 , orybr-j3kza5 , orybr-j3mnb5 , orybr-j3n4p4 , orybr-j3lg73 , orybr-j3l342 , orybr-j3msi2 , orybr-j3nb83 , orybr-j3mpc5

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 : [Multivariate analysis of hepatic encephalopathy occurrence in patients with liver failure] - Pan_2012_Zhonghua.Gan.Zang.Bing.Za.Zhi_20_434
Author(s) : Pan C , Xu LJ , Zhou R , Zhou W , Huang JR
Ref : Zhonghua Gan Zang Bing Za Zhi , 20 :434 , 2012
Abstract : To investigate the risk factors of hepatic encephalopathy in patients with liver failure. Nine-hundred-and-seventy-six hepatitis B virus (HBV) patients with liver failure were retrospectively analyzed. Clinical data (sex, age, family history, liver cirrhosis, diabetes, celiac infection, pulmonary infection, liver kidney syndrome, upper gastrointestinal hemorrhage) and laboratory findings (albumin, globulin, total bilirubin, direct bilirubin, alanine aminotransferase, aspartate aminotransferase (AST), gamma-glutamyl transferase, alkaline phosphatase, cholesterol, cholinesterase, K+, Na+, creatinine, international normalized ratio (INR), alpha-fetoprotein, HBV DNA, white blood cell, hemoglobin, platelet) were collected and used to screen the risk factors for hepatic encephalopathy by univariate and multiple regress analyses. Multiple logistic regression analysis indicated that upper gastrointestinal hemorrhage [risk (R) = 0.993, relative hazard (RH) = 2.699, 95% confidence interval (CI): 1.567-4.651], pulmonary infection [R = 1.043, RH = 2.839, 95% CI: 1.680-4.797], INR [R = 0.257, RH = 1.293, 95% CI: 1.220-1.370], AST level [R = 0.001, RH = 1.001, 95% CI: 1.000-1.001], and cirrhosis [R = 0.569, RH = 1.815, 95% CI: 1.112-2.965] were closely correlated with hepatic encephalopathy. HBV-infected patients presenting with upper gastrointestinal haemorrhage, pulmonary infection, prolonged INR, elevated AST, or liver cirrhosis should be carefully monitored for indications of hepatic encephalopathy to initiate timely therapeutic interventions.
ESTHER : Pan_2012_Zhonghua.Gan.Zang.Bing.Za.Zhi_20_434
PubMedSearch : Pan_2012_Zhonghua.Gan.Zang.Bing.Za.Zhi_20_434
PubMedID: 23044200

Title : Erythrocyte damage of crucian carp (Carassius auratus) caused by microcystin-LR: in vitro study - Zhou_2012_Fish.Physiol.Biochem_38_849
Author(s) : Zhou W , Liang H , Zhang X
Ref : Fish Physiol Biochem , 38 :849 , 2012
Abstract : Fish suffer from anemia and hypovolemic hypotensive shock after in vivo exposure with microcystins.However except for in vivo causes for anemia and hypotension an in vitro study of fish erythrocytes exposed to MC is necessary For a better understanding of hematology toxicity of MC the main aim of the present study was to investigate the toxic effects of microcystin on fish erythrocytes in vitro Crucian carp erythrocytes were incubated in vitro with microcystin-LR MC-LR at doses of 0 1 10 100 and 1,000 nM.The level of lipid peroxidate significantly increased in MC-LR treatment groups Glutathione decreased after exposure to MC-LR The activities of antioxidative enzymes including superoxide dismutase catalase,glutathione peroxidase and glutathione-S-transferase,were significantly increased after exposure with MC-LR.The hemolysis was significantly increased while the activities of acetylcholinesterase Na-K-ATPase and Ca2+-Mg2+-ATPase were significantly decreased In addition pathological alterations in agglomerated and jagged erythrocytes were observed in blood smears The findings indicate that damages to erythrocytes should also be responsible for anemia and hypotensive shock or even death.
ESTHER : Zhou_2012_Fish.Physiol.Biochem_38_849
PubMedSearch : Zhou_2012_Fish.Physiol.Biochem_38_849
PubMedID: 22286870

Title : TNF-alpha-induced CXCL8 production by A549 cells: Involvement of the non-neuronal cholinergic system - Xu_2012_Pharmacol.Res_68_16
Author(s) : Xu ZP , Devillier P , Xu GN , Qi H , Zhu L , Zhou W , Hou LN , Tang YB , Yang K , Yu ZH , Chen HZ , Cui YY
Ref : Pharmacol Res , 68 :16 , 2012
Abstract : It was recently suggested that the non-neuronal cholinergic system has a regulatory role in pulmonary inflammation. We investigated this system's involvement in the control of cytokine production by the A549 human alveolar epithelial cell line. CXCL8 and acetylcholine (ACh) concentrations were measured using ELISA and LC-MS/MS, respectively. The mRNA expression of muscarinic receptor (MR) subtypes was determined using RT-PCR. In A549 cells, TNF-alpha increased the release of CXCL8 and ACh and the expression of the subtype 3 MR (M3R). Furthermore, TNF-alpha-induced CXCL8 secretion was (i) inhibited by the MR antagonist tiotropium and the M3R antagonist 4-DAMP and (ii) enhanced by the M1/M3R agonist pilocarpine and the cholinesterase inhibitor physostigmine. Taken as a whole, these results suggest that ACh release by A549 cells enhances TNF-alpha-induced CXCL8 secretion through activation of the M3R. Western blot analysis revealed that pilocarpine and physostigmine enhanced the TNF-alpha-induced phosphorylation of ERK1/2 and p38 MAPK and the degradation of IkappaBalpha. Inhibition of these pathways with specific inhibitors abrogated the pilocarpine-induced CXCL8 release. Our results suggest that the TNF-alpha-induced secretion of CXCL8 in A549 cells is regulated by the release of ACh, the latter's binding to the M3R and the downstream activation of NF-kappaB and the ERK1/2 and p38 MAPK signaling pathways. Our findings suggest that MR antagonists may have anti-inflammatory effects by preventing pro-inflammatory events driven by endogenous, non-neuronal ACh.
ESTHER : Xu_2012_Pharmacol.Res_68_16
PubMedSearch : Xu_2012_Pharmacol.Res_68_16
PubMedID: 23142559

Title : Galantamine attenuates the heroin seeking behaviors induced by cues after prolonged withdrawal in rats - Liu_2012_Neuropharmacol_62_2515
Author(s) : Liu H , Lai M , Zhou X , Zhu H , Liu Y , Sun A , Ma B , Zhang F , Zhou W
Ref : Neuropharmacology , 62 :2515 , 2012
Abstract : BACKGROUND AND OBJECTIVE: Evidence shows that acetylcholinergic transmission in the ventral tegmental area (VTA) or nucleus accumbens (NAc) plays an important role in heroin-seeking induced by cues. Cholinergic modulation of VTA neurons arises from the lateral dorsal tegmental nucleus (LDT). The present studies investigated the effect of systemic or intra- LDT administration of galantamine, an inhibitor of acetylcholinesterase, on heroin-seeking induced by cues. METHODS: Rats were trained to self-administer heroin for 12 days, underwent extinction training for 12 days followed by two weeks in their home cages. Then the conditioned cues were introduced for the reinstatement of heroin-seeking. RESULTS: The reinstatement of heroin-seeking induced by cues was attenuated by the administration of galantamine (0, 0.3, 1 or 3mg/kg, i.p.) in a dose-dependent manner. In contrast, galantamine only at the dose of 3mg/kg could inhibit the reinstatement of sucrose-seeking. Galantamine at those doses failed to alter the locomotor activity in heroin-withdrawn rats. The inhibition of drug-seeking by galantamine was reversed by pretreatment with scopolamine (0.5mg/kg) but not with mecamylamine (3mg/kg) or scopolamine methobromide (1mg/kg). Moreover, the microinjection of galantamine into the LDT blocked cue-induced heroin-seeking, while the microinjection of scopolamine into the LDT reversed the inhibitory effect of galantamine on drug-seeking behavior. CONCLUSION: The results suggest that cholinergic transmission in the LDT may play a critical role in heroin-seeking behavior induced by cues and that galantamine may have the beneficial effect of blocking heroin-seeking behavior, which is mediated through its actions on the muscarinic receptors.
ESTHER : Liu_2012_Neuropharmacol_62_2515
PubMedSearch : Liu_2012_Neuropharmacol_62_2515
PubMedID: 22342742

Title : Isolation and characterization of lipase-producing bacteria in the intestine of the silkworm, Bombyx mori, reared on different forage - Feng_2011_J.Insect.Sci_11_135
Author(s) : Feng W , Wang XQ , Zhou W , Liu GY , Wan YJ
Ref : J Insect Sci , 11 :135 , 2011
Abstract : The silkworm, Bombyx mori L. (Lepidoptera: Bombycidae), an oligophagous insect that mainly feeds on mulberry leaves, is susceptible to entomopathogen infection when reared with tricuspid cudrania leaves. A total of 56 dominant bacterial strains, classified into 12 phylotypes based on bacteriological properties and analysis of 16S rRNA genes, were isolated from the intestine of the fourth and fifth instar silkworm larvae. Ten and seven phylotypes exist in the intestine of the silkworm larvae reared with mulberry leaves and tricuspid cudrania leaves, respectively. Four of them are common in the intestine of the two treatment groups. By screening their lipolytic ability on a Rhodamine B agar plate, nine lipase-producing bacterial strains were obtained and classified into six genera, including Bacillus, Brevibacterium, Corynebacterium, Staphylococcus, Klebsiella, and Stenotrophomonas. Except for Stenotrophomonas, which is common in both, the other genera only exist in the intestine of the silkworm larvae fed with mulberry leaves. In addition, by culture and fermentation in vitro, the maximum cell density and lipase activity of lipase-producing bacteria were examined at about 48 hours. The results indicate that diet has a significant impact on the gut bacterial community, especially lipase-producing bacteria. We suggest that the difference of lipase-producing bacterial diversity might be related to disease resistance of the silkworm.
ESTHER : Feng_2011_J.Insect.Sci_11_135
PubMedSearch : Feng_2011_J.Insect.Sci_11_135
PubMedID: 22243438

Title : Complete genome sequence of the bacterium Methylovorus sp. strain MP688, a high-level producer of pyrroloquinolone quinone - Xiong_2011_J.Bacteriol_193_1012
Author(s) : Xiong XH , Zhi JJ , Yang L , Wang JH , Zhao Y , Wang X , Cui YJ , Dong F , Li MX , Yang YX , Wei N , An JJ , Du BH , Liang L , Zhang JS , Zhou W , Cheng SF , He T , Wang L , Chen HP , Liu DS , Zhang WC
Ref : Journal of Bacteriology , 193 :1012 , 2011
Abstract : Methylotrophic bacteria are widespread microbes which can use one carbon compound as their only carbon and energy sources. Here we report the finished, annotated genome sequence of the methylotrophic bacterium Methylovorus sp. strain MP688, which was isolated from soil for high-level production of pyrroloquinolone quinone (PQQ) in our lab.
ESTHER : Xiong_2011_J.Bacteriol_193_1012
PubMedSearch : Xiong_2011_J.Bacteriol_193_1012
PubMedID: 21148725
Gene_locus related to this paper: mets6-e4qna9 , mets6-e4qnd9 , metsd-c6xa50

Title : Effects of pyrethroids on neuronal excitability of adult honeybees Apis mellifera - Zhou_2011_Pestic.Biochem.Physiol_100_35
Author(s) : Zhou T , Zhou W , Wang Q , Dai P-L , Liu F , Zhang Y-L , Sun J-H
Ref : Pesticide Biochemistry and Physiology , 100 :35 , 2011
Abstract : Pyrethroids act on the nervous system as a primary target organ and exert their neurotoxic effects primarily by altering the conductance of sodium channel, leading to hyperexcitation. However, few studies investigated the effects of pyrethroids on neuronal excitability of honeybee brain neurons. In this study, a whole-cell patch-clamp technique was used to record current threshold, the minimum current to induce an action potential, and peak sodium current in the dissociated honeybee brain neurons treated with bifenthrin, deltamethrin and fluvalinate in vitro & in vivo. The study showed that these pyrethroids greatly suppressed the neuronal excitability as revealed by increasing current injected and inhibited the peak sodium current in honeybees. The three pyrethroids also inhibited steady-state inactivation in addition to reduction of sodium peak current.
ESTHER : Zhou_2011_Pestic.Biochem.Physiol_100_35
PubMedSearch : Zhou_2011_Pestic.Biochem.Physiol_100_35
PubMedID:

Title : Genomic and proteomic analyses of the fungus Arthrobotrys oligospora provide insights into nematode-trap formation - Yang_2011_PLoS.Pathog_7_e1002179
Author(s) : Yang J , Wang L , Ji X , Feng Y , Li X , Zou C , Xu J , Ren Y , Mi Q , Wu J , Liu S , Liu Y , Huang X , Wang H , Niu X , Li J , Liang L , Luo Y , Ji K , Zhou W , Yu Z , Li G , Li L , Qiao M , Feng L , Zhang KQ
Ref : PLoS Pathog , 7 :e1002179 , 2011
Abstract : Nematode-trapping fungi are "carnivorous" and attack their hosts using specialized trapping devices. The morphological development of these traps is the key indicator of their switch from saprophytic to predacious lifestyles. Here, the genome of the nematode-trapping fungus Arthrobotrys oligospora Fres. (ATCC24927) was reported. The genome contains 40.07 Mb assembled sequence with 11,479 predicted genes. Comparative analysis showed that A. oligospora shared many more genes with pathogenic fungi than with non-pathogenic fungi. Specifically, compared to several sequenced ascomycete fungi, the A. oligospora genome has a larger number of pathogenicity-related genes in the subtilisin, cellulase, cellobiohydrolase, and pectinesterase gene families. Searching against the pathogen-host interaction gene database identified 398 homologous genes involved in pathogenicity in other fungi. The analysis of repetitive sequences provided evidence for repeat-induced point mutations in A. oligospora. Proteomic and quantitative PCR (qPCR) analyses revealed that 90 genes were significantly up-regulated at the early stage of trap-formation by nematode extracts and most of these genes were involved in translation, amino acid metabolism, carbohydrate metabolism, cell wall and membrane biogenesis. Based on the combined genomic, proteomic and qPCR data, a model for the formation of nematode trapping device in this fungus was proposed. In this model, multiple fungal signal transduction pathways are activated by its nematode prey to further regulate downstream genes associated with diverse cellular processes such as energy metabolism, biosynthesis of the cell wall and adhesive proteins, cell division, glycerol accumulation and peroxisome biogenesis. This study will facilitate the identification of pathogenicity-related genes and provide a broad foundation for understanding the molecular and evolutionary mechanisms underlying fungi-nematodes interactions.
ESTHER : Yang_2011_PLoS.Pathog_7_e1002179
PubMedSearch : Yang_2011_PLoS.Pathog_7_e1002179
PubMedID: 21909256
Gene_locus related to this paper: artoa-g1wyr4 , artoa-g1x1a7 , artoa-g1x3f4 , artoa-g1x3h6 , artoa-g1x9s5 , artoa-g1x9z4 , artoa-g1xcb5 , artoa-g1xhl6 , artoa-g1xjb3 , artoa-g1xjy0 , artoa-g1xkw3 , artoa-g1xnf2 , artoa-g1xnf8 , artoa-g1xqd4 , artoa-g1xqt1 , artoa-g1xte8 , artoa-g1xu91 , artoa-g1xv59 , artoa-g1x382 , artoa-g1x3q3 , artoa-g1wxl5 , artoa-g1xj75 , artoa-g1xd25 , artoa-g1wzu7 , artoa-g1xt42 , artoa-g1xhm8 , artoa-g1wy43

Title : Enhancement of endocannabinoid signaling with JZL184, an inhibitor of the 2-arachidonoylglycerol hydrolyzing enzyme monoacylglycerol lipase, produces anxiolytic effects under conditions of high environmental aversiveness in rats - Sciolino_2011_Pharmacol.Res_64_226
Author(s) : Sciolino NR , Zhou W , Hohmann AG
Ref : Pharmacol Res , 64 :226 , 2011
Abstract : Dysregulation in signaling of the endocannabinoid 2-arachidonoylglycerol (2-AG) is implicated in hyperresponsiveness to stress. We hypothesized that blockade of monoacylglycerol lipase (MGL), the primary enzyme responsible for 2-AG deactivation in vivo, would produce context-dependent anxiolytic effects in rats. Environmental aversiveness was manipulated by varying illumination of an elevated plus maze. Percentage open arm time and numbers of open and closed arm entries were measured in rats receiving a single intraperitoneal (i.p.) injection of either vehicle, the MGL inhibitor JZL184 (1-8mg/kg), the benzodiazepine diazepam (1mg/kg), the cannabinoid CB(1) receptor antagonist rimonabant (1mg/kg), or JZL184 (8mg/kg) coadministered with rimonabant (1mg/kg). JZL184 (8mg/kg) produced anxiolytic-like effects (i.e., increased percentage open arm time and number of open arm entries) under high, but not low, levels of environmental aversiveness. Diazepam produced anxiolytic effects in either context. Rimonabant blocked the anxiolytic-like effects of JZL184, consistent with mediation by CB(1). Anxiolytic effects of JZL184 were preserved following chronic (8mg/kg per dayx6 days) administration. Chronic and acute JZL184 treatment similarly enhanced behavioral sensitivity to an exogenous cannabinoid (WIN55,212-2; 2.5mg/kg i.p.) 24 or 72h following the terminal injection, suggesting a pervasive effect of MGL inhibition on the endocannabinoid system. We attribute our results to alterations in emotion rather than locomotor activity as JZL184 did not alter the number of closed arm entries in the plus maze or produce motor ataxia in the bar test. Our results demonstrate that JZL184 has beneficial, context-dependent effects on anxiety in rats, presumably via inhibition of MGL-mediated hydrolysis of 2-AG. These data warrant further testing of MGL inhibitors to elucidate the functional role of 2-AG in controlling anxiety and stress responsiveness. Our data further implicate a role for 2-AG in the regulation of emotion and validate MGL as a therapeutic target.
ESTHER : Sciolino_2011_Pharmacol.Res_64_226
PubMedSearch : Sciolino_2011_Pharmacol.Res_64_226
PubMedID: 21600985

Title : Drug treatment of Alzheimer's disease patients leads to expression changes in peripheral blood cells - Calciano_2010_Alzheimers.Dement_6_386
Author(s) : Calciano MA , Zhou W , Snyder PJ , Einstein R
Ref : Alzheimers Dement , 6 :386 , 2010
Abstract : BACKGROUND: Increasing cholinergic activity has been the primary mechanism for treating dementia due to Alzheimer's disease. However, the effectiveness of cholinesterase inhibitors (ChEIs) is still widely debated. The identification of specific biomarkers capable of identifying patients more likely to respond to these treatments could potentially provide specific evidence to clearly address this controversy through patient stratification. The goal of this study was to determine the feasibility of discovering biomarkers specific for the treatment of Alzheimer's disease. METHODS: Peripheral blood was collected from a cohort of patients treated with different ChEIs. Total RNA was isolated and profiled on the human Genome-Wide SpliceArray (GWSA) to test the feasibility of discriminating the different treatment subgroups of subjects based on the expression patterns generated from the Genome-Wide SpliceArray. RESULTS: Specific expression differences were identified for the various treatment groups that lead to a clear separation between patients treated with ChEIs versus naive patients when Principal Component Analysis was performed on probe sets selected for differential expression. In addition, specific probe sets were identified to be dependent on the inhibitor used among the treated patients. CONCLUSIONS: Distinct separation between non-treated, galantamine, donepezil, and rivastigmine-treated patients was clearly identified based on small sets of expression probes. The ability to identify drug-specific treatment expression differences strengthens the potential for using peripheral gene signatures for the identification of individuals responding to drug treatment.
ESTHER : Calciano_2010_Alzheimers.Dement_6_386
PubMedSearch : Calciano_2010_Alzheimers.Dement_6_386
PubMedID: 20185375

Title : Identification of the novel protein FAM172A, and its up-regulation by high glucose in human aortic smooth muscle cells - Li_2010_Int.J.Mol.Med_26_483
Author(s) : Li L , Dong X , Leong MC , Zhou W , Yang Z , Chen F , Bao Y , Jia W , Hu R
Ref : Int J Mol Med , 26 :483 , 2010
Abstract : The family with sequence similarity 172, member A (FAM172A) is a hypothetical protein. We recently cloned the FAM172A gene from normal human aortic tissues. In a previous study we also showed that the FAM172A gene was up-regulated by high glucose levels in macrophages. In the present study, we further identified the FAM172A protein at the level of translation and studied the effects of high glucose levels on its expression in human aortic smooth muscle cells. The FAM172A gene was subcloned into the eukaryotic expression vectors, PDC315 and pEGFP-N2. The cloned sequence shows an open reading frame of 1251 nucleotides encoding a protein of 416 amino acids. We further expressed the recombinant FAM172A protein and generated rabbit anti-human FAM172A polyclonal antibodies. The FAM172A protein was identified for the first time at the translation level by Western blot analysis. Western blotting also demonstrated that the FAM172A protein could be detected in human aortic endothelial, human aortic smooth muscle cells and THP-1-derived macrophages, the highest expression being observed in the human aortic smooth muscle cells. By a combination of bioinformatics and confocal laser scanning microscopy, we found that the FAM172A protein in HEK293 cells, was mainly located in the nucleus, and that there was an Arb2 conserved domain in the FAM172A protein sequence. We also presented evidence that the FAM172 protein expression in human aortic smooth muscle cells was up-regulated by high glucose levels in a concentration-dependent and time-course manner. We speculated that as a novel protein, FAM172A could be involved in the pathogenesis of high glucose-induced vascular damage.
ESTHER : Li_2010_Int.J.Mol.Med_26_483
PubMedSearch : Li_2010_Int.J.Mol.Med_26_483
PubMedID: 20818486
Gene_locus related to this paper: human-f172a

Title : RanBPM is an acetylcholinesterase-interacting protein that translocates into the nucleus during apoptosis - Gong_2009_Acta.Biochim.Biophys.Sin.(Shanghai)_41_883
Author(s) : Gong X , Ye W , Zhou H , Ren X , Li Z , Zhou W , Wu J , Gong Y , Ouyang Q , Zhao X , Zhang X
Ref : Acta Biochim Biophys Sin (Shanghai) , 41 :883 , 2009
Abstract : Acetylcholinesterase (AChE) expression may be induced during apoptosis in various cell types. Here, we used the C-terminal of AChE to screen the human fetal brain library and found that it interacted with Ran-binding protein in the microtubule-organizing center (RanBPM). This interaction was further confirmed by coimmunoprecipitation analysis. In HEK293T cells, RanBPM and AChE were heterogeneously expressed in the cisplatin-untreated cytoplasmic extracts and in the cisplatin-treated cytoplasmic or nuclear extracts. Our previous studies performed using morphologic methods have shown that AChE translocates from the cytoplasm to the nucleus during apoptosis. Taken together, these results suggest that RanBPM is an AChE-interacting protein that is translocated from the cytoplasm into the nucleus during apoptosis, similar to the translocation observed in case of AChE.
ESTHER : Gong_2009_Acta.Biochim.Biophys.Sin.(Shanghai)_41_883
PubMedSearch : Gong_2009_Acta.Biochim.Biophys.Sin.(Shanghai)_41_883
PubMedID: 19902122

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 : Bis-(-)-nor-meptazinols as novel nanomolar cholinesterase inhibitors with high inhibitory potency on amyloid-beta aggregation - Xie_2008_J.Med.Chem_51_2027
Author(s) : Xie Q , Wang H , Xia Z , Lu M , Zhang W , Wang X , Fu W , Tang Y , Sheng W , Li W , Zhou W , Zhu X , Qiu Z , Chen H
Ref : Journal of Medicinal Chemistry , 51 :2027 , 2008
Abstract : Bis-(-)-nor-meptazinols (bis-(-)-nor-MEPs) 5 were designed and synthesized by connecting two (-)-nor-MEP monomers with alkylene linkers of different lengths via the secondary amino groups. Their acetylcholinesterase (AChE) inhibitory activities were more greatly influenced by the length of the alkylene chain than butyrylcholinesterase (BChE) inhibition. The most potent nonamethylene-tethered dimer 5h exhibited low-nanomolar IC 50 values for both ChEs, having a 10 000-fold and 1500-fold increase in inhibition of AChE and BChE compared with (-)-MEP. Molecular docking elucidated that 5h simultaneously bound to the catalytic and peripheral sites in AChE via hydrophobic interactions with Trp86 and Trp286. In comparison, it folded in the large aliphatic cavity of BChE because of the absence of peripheral site and the enlargement of the active site. Furthermore, 5h and 5i markedly prevented the AChE-induced Abeta aggregation with IC 50 values of 16.6 and 5.8 microM, similar to that of propidium (IC 50 = 12.8 microM), which suggests promising disease-modifying agents for the treatment of AD patients.
ESTHER : Xie_2008_J.Med.Chem_51_2027
PubMedSearch : Xie_2008_J.Med.Chem_51_2027
PubMedID: 18333606

Title : TARP subtypes differentially and dose-dependently control synaptic AMPA receptor gating - Milstein_2007_Neuron_55_905
Author(s) : Milstein AD , Zhou W , Karimzadegan S , Bredt DS , Nicoll RA
Ref : Neuron , 55 :905 , 2007
Abstract : A family of transmembrane AMPA receptor regulatory proteins (TARPs) profoundly affects the trafficking and gating of AMPA receptors (AMPARs). Although TARP subtypes are differentially expressed throughout the CNS, it is unclear whether this imparts functional diversity to AMPARs in distinct neuronal populations. Here, we examine the effects of each TARP subtype on the kinetics of AMPAR gating in heterologous cells and in neurons. We report a striking heterogeneity in the effects of TARP subtypes on AMPAR deactivation and desensitization, which we demonstrate controls the time course of synaptic transmission. In addition, we find that some TARP subtypes dramatically slow AMPAR activation kinetics. Synaptic AMPAR kinetics also depend on TARP expression level, suggesting a variable TARP/AMPAR stoichiometry. Analysis of quantal synaptic transmission in a TARP gamma-4 knockout (KO) mouse corroborates our expression data and demonstrates that TARP subtype-specific gating of AMPARs contributes to the kinetics of native AMPARs at central synapses.
ESTHER : Milstein_2007_Neuron_55_905
PubMedSearch : Milstein_2007_Neuron_55_905
PubMedID: 17880894

Title : Role of acetylcholine transmission in nucleus accumbens and ventral tegmental area in heroin-seeking induced by conditioned cues - Zhou_2007_Neurosci_144_1209
Author(s) : Zhou W , Liu H , Zhang F , Tang S , Zhu H , Lai M , Kalivas PW
Ref : Neuroscience , 144 :1209 , 2007
Abstract : The involvement of cholinergic transmission in heroin self-administration and the reinstatement of heroin-seeking was examined in rats trained to nose-poke for i.v. heroin. Systemic treatment with physostigmine, an inhibitor of acetylcholinesterase, modestly reduced the acquisition and rate of heroin self-administration, and this suppression of heroin intake was reversed by pretreatment with scopolamine but not by mecamylamine. Following 10-14 days of self-administration, rats were left in the home environment for 14 days. Subsequently, rats were evaluated for extinction of nose-pokes during the first hour after being returned to the self-administration apparatus. One hour later a conditioned stimulus (house light, light in the nose-poke hole, sound of the infusion pump) was presented to initiate cue-induced reinstatement. Physostigmine produced a dose-dependent inhibition of cue-induced reinstatement, but only the dose of 0.5 mg/kg significantly decreased nose-poke responding in the extinction test. Chronic treatment with physostigmine (0.1 mg/kg) did not impair performance during acquisition of heroin self-administration. However, during a subsequent reinstatement test conducted in the absence of physostigmine pretreatment, heroin seeking was significantly below that of rats chronically pretreated with saline. To evaluate brain regions mediating the effects of systemic drug treatment on reinstatement, physostigmine was microinjected into the nucleus accumbens (NAc) or ventral tegmental area (VTA). Microinjection of physostigmine into the NAc prior to presenting conditioned cues inhibited the reinstatement of heroin-seeking, without affecting extinction responding. In contrast, microinjection of physostigmine into the VTA augmented the reinstatement induced by conditioned cues and extinction responding. Inactivation of either NAc or VTA by microinjecting tetrodotoxin blocked both extinction responding and cue-induced reinstatement. These data demonstrate that cholinergic transmission influences heroin self-administration and reinstatement. Moreover, cue-induced reinstatement was inhibited by physostigmine in the NAc and potentiated by cholinergic stimulation in the VTA.
ESTHER : Zhou_2007_Neurosci_144_1209
PubMedSearch : Zhou_2007_Neurosci_144_1209
PubMedID: 17184925

Title : Microsomal epoxide hydrolase, endotoxin, and lung function decline in cotton textile workers - Hang_2005_Am.J.Respir.Crit.Care.Med_171_165
Author(s) : Hang J , Zhou W , Wang X , Zhang H , Sun B , Dai H , Su L , Christiani DC
Ref : American Journal of Respiratory & Critical Care Medicine , 171 :165 , 2005
Abstract : Occupational exposure to endotoxin in organic dust may induce lung function decline. Microsomal epoxide hydrolase (mEH) detoxifies reactive oxygen species generated by endotoxin exposure, and polymorphisms of the mEH gene are associated with altered enzyme activity. We investigated the associations between mEH polymorphisms, endotoxin exposure, and lung function decline in a 20-year prospective study of 265 workers exposed to endotoxin and 234 control subjects. mEH Tyr113His and His139Arg polymorphisms were genotyped by the 5' nuclease assay, and data were analyzed using multivariate linear regression models, adjusting for important covariates. Overall, the annual decline rate of FEV1 was 29.47 ml during the 20-year follow-up. Endotoxin exposure was associated with faster lung function decline among genotypes associated with slower enzyme activity: estimates (SE) of annual FEV1 decline rates for endotoxin exposure were -2.33 (2.07), -2.81 (1.66), and -6.73 (2.83) ml for Tyr/Tyr, Tyr/His, and His/His genotype groups, respectively, for the Tyr113His polymorphism; and -1.82 (2.58) and -4.27 (1.33) ml for Arg/Arg + His/Arg and His/His genotypes, respectively, for the His139Arg polymorphism. We conclude that mEH polymorphisms modify the association between occupational endotoxin exposure and longitudinal lung function decline.
ESTHER : Hang_2005_Am.J.Respir.Crit.Care.Med_171_165
PubMedSearch : Hang_2005_Am.J.Respir.Crit.Care.Med_171_165
PubMedID: 15531751

Title : Oxidative stress and free radical damage in patients with acute dipterex poisoning - Zhou_2004_Biomed.Environ.Sci_17_223
Author(s) : Zhou JF , Zhou W , Zhang SM , Luo YE , Chen HH
Ref : Biomedical & Environmental Sciences , 17 :223 , 2004
Abstract : OBJECTIVE: To investigate whether acute dipterex poisoning (ADP) may cause oxidative stress and free radical damage in the bodies of acute dipterex poisoning patients (ADPPs), and to explore the mechanisms by which ADP may cause oxidative stress and free radical damage.
METHODS: Fifty ADPPs and fifty healthy adult volunteers (HAVs) whose ages, gender and others were matched with the ADPPs were enrolled in a randomized controlled study, in which concentrations of nitric oxide (NO), vitamin C (VC), vitamin E (VE) and beta-carotene (beta-CAR) in plasma as well as concentration of lipoperoxide (LPO), and activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and acetylcholinesterase (AChE) in erythrocytes were determined by spectrophotometric analytical methods.
RESULTS: Compared with the average values of experimental parameters in the HAVs group, the average values of plasma NO and erythrocyte LPO in the ADPPs group were significantly increased (P<0.0001), while those of plasma VC, VE and beta-CAR as well as erythrocyte SOD, CAT, GPX and AChE in the ADPPs group were significantly decreased (P<0.0001). Bivariate correlation analysis and partial correlation analysis suggested that when NO and LPO values were increased, and VC, VE, beta-CAR, SOD, CAT and GPX values were decreased in the ADPPs, AChE value was decreased gradually in the ADPPs (P<0.001-0.0001). Reliability analysis of experimental parameters reflecting oxidative stress and free radical damage in the ADPPs showed that the reliability coefficient (8 items) alpha=0.6909, and the standardized item alpha=0.8574. CONCLUSION: The findings in the present study suggest that ADP can cause oxidative stress and free radical damage, and inhibit markedly erythrocyte acetylcholinesterase activity in ADPPs.
ESTHER : Zhou_2004_Biomed.Environ.Sci_17_223
PubMedSearch : Zhou_2004_Biomed.Environ.Sci_17_223
PubMedID: 15386949

Title : Methyl parathion increases neuronal activities in the rat locus coeruleus - Zhu_2004_J.Biomed.Sci_11_732
Author(s) : Zhu H , Zhou W , Li XR , Ma T , Ho IK , Rockhold RW
Ref : J Biomed Sci , 11 :732 , 2004
Abstract : Exposure to organophosphate insecticides induces undesirable behavioral changes in humans, including anxiety and irritability, depression, cognitive disturbances and sleep disorders. Little information currently exists concerning the neural mechanisms underlying such behavioral changes. The brain stem locus coeruleus (LC) could be a mediator of organophosphate insecticide-induced behavioral toxicities since it contains high levels of acetylcholinesterase and is involved in the regulation of the sleep-wake cycle, attention, arousal, memory, and pathological processes, including anxiety and depression. In the present study, using a multi-wire recording technique, we examined the effects of methyl parathion, a commonly used organophosphate insecticide, on the firing patterns of LC neurons in rats. Systemic administration of a single dose of methyl parathion (1 mg/kg, i.v.) increased the spontaneous firing rates of LC neurons by 240% but did not change the temporal relationships among the activities of multiple LC neurons. This dose of methyl parathion induced a 50% decrease in blood acetylcholinesterase activity and a 48% decrease in LC acetylcholinesterase activity. The methyl parathion-induced excitation of LC neurons was reversed by administration of atropine sulfate, a muscarinic receptor antagonist, indicating an involvement of muscarinic receptors. The methyl parathion-induced increase in LC neuronal activity returned to normal within 30 min while the blood acetylcholinesterase activity remained inhibited for over 1 h. These data indicate that methyl parathion treatment can elicit excitation of LC neurons. Such excitation could contribute to the neuronal basis of organophosphate insecticide-induced behavioral changes in human.
ESTHER : Zhu_2004_J.Biomed.Sci_11_732
PubMedSearch : Zhu_2004_J.Biomed.Sci_11_732
PubMedID: 15591769

Title : Genetic polymorphisms in N-acetyltransferase-2 and microsomal epoxide hydrolase, cumulative cigarette smoking, and lung cancer - Zhou_2002_Cancer.Epidemiol.Biomarkers.Prev_11_15
Author(s) : Zhou W , Liu G , Thurston SW , Xu LL , Miller DP , Wain JC , Lynch TJ , Su L , Christiani DC
Ref : Cancer Epidemiol Biomarkers Prev , 11 :15 , 2002
Abstract : N-acetyltrasferase-2 (NAT2) and microsomal epoxide hydrolase (mEH) are polymorphic genes that metabolize different tobacco carcinogens. Smaller studies found inconsistent relationships between NAT2 or mEH polymorphisms and lung cancer risk. To determine whether there is gene-environment interaction between NAT2 polymorphisms, alone or in combination with mEH polymorphisms, and cumulative smoking exposure in the development of lung cancer, we conducted a case control study of 1115 Caucasian lung cancer patients and 1250 spouse and friend controls. The results were analyzed using generalized additive models and logistic regression, adjusting for relevant covariates. There was no overall relationship between NAT2 genotype and lung cancer risk; the adjusted odds ratio (OR) of the rapid versus slow acetylator genotypes was 0.96 [95% confidence interval (CI), 0.79-1.16]. However, gene-environment interaction analyses revealed that the adjusted ORs increased significantly as pack-years increased. For nonsmokers, the fitted OR was 0.66 (95% CI, 0.44-0.99), whereas for heavy smokers (80 pack-years), the OR increased to 1.22 (95% CI, 0.89-1.67). When comparing the extreme genotype combinations of the NAT2 rapid acetylator, higher mEH activity genotype to the NAT2 slow acetylator, and very low mEH activity genotype, the corresponding ORs at 0 and 80 pack-years were 0.30 (95% CI, 0.14-0.62) and 2.19 (95% CI, 1.26-3.81), respectively. Results were similar with ORs derived from stratified models. In conclusion, NAT2 rapid acetylator genotypes are protective against lung cancer in nonsmokers but are risk factors in heavy smokers. The joint effects of NAT2 and mEH polymorphisms are consistent with an independent, additive effect of these two genes, modified by smoking history.
ESTHER : Zhou_2002_Cancer.Epidemiol.Biomarkers.Prev_11_15
PubMedSearch : Zhou_2002_Cancer.Epidemiol.Biomarkers.Prev_11_15
PubMedID: 11815396

Title : The interaction between microsomal epoxide hydrolase polymorphisms and cumulative cigarette smoking in different histological subtypes of lung cancer - Zhou_2001_Cancer.Epidemiol.Biomarkers.Prev_10_461
Author(s) : Zhou W , Thurston SW , Liu G , Xu LL , Miller DP , Wain JC , Lynch TJ , Su L , Christiani DC
Ref : Cancer Epidemiol Biomarkers Prev , 10 :461 , 2001
Abstract : Microsomal epoxide hydrolase (mEH) is involved in the metabolism of environmental and tobacco carcinogens. Smaller studies found inconsistent results in the relationship between mEH polymorphisms and lung cancer risk. We investigated the two polymorphisms of mEH in 974 Caucasian lung cancer patients and 1142 controls using PCR-RFLP techniques. The results were analyzed using generalized additive models and logistic regression, adjusting for relevant covariates. There was no overall relationship between mEH genotypes and lung cancer risk. The adjusted odds ratio (OR) of the very low activity genotype versus that of other genotypes combined was 1.00 [95% confidence interval (CI), 0.74-1.34]. However, gene-environment interaction analyses revealed that the ORs decreased as cumulative smoking (defined as square root of pack-years) increased. When pack-years = 0, the OR was 1.89 (95% CI, 1.08-3.28). When pack-years = 28.5, the OR was 1.00 (95% CI, 0.76-1.32), and when pack-years = 80, the OR decreased to 0.65 (95% CI, 0.42-1.00). When cases were stratified according to histological subtypes, the interaction between mEH genotype and cumulative smoking was statistically significant (P < 0.01) for the 222 squamous cell carcinoma cases, whereas it was not significant (P = 0.18) for the 432 adenocarcinoma cases. In conclusion, cumulative cigarette smoking plays a pivotal role in the association between mEH polymorphisms and lung cancer risk, altering the direction of risk (in the case of the very low activity genotype) from a risk factor in nonsmokers to a relatively protective factor in heavy smokers.
ESTHER : Zhou_2001_Cancer.Epidemiol.Biomarkers.Prev_10_461
PubMedSearch : Zhou_2001_Cancer.Epidemiol.Biomarkers.Prev_10_461
PubMedID: 11352855