To explore the potential utilization of Elaeagnus mollis,we conducted a comprehensive assessment of its phytochemical composition,antioxidant properties,cholinesterase inhibition,and anti-HepG2 cell proliferation acti...To explore the potential utilization of Elaeagnus mollis,we conducted a comprehensive assessment of its phytochemical composition,antioxidant properties,cholinesterase inhibition,and anti-HepG2 cell proliferation activity across different plant parts(branch wood,branch bark,and pericarp)using various solvents(water,methanol,ethanol,and n-hexane).Our findings revealed that water extracts displayed superior antioxidant activities in ABTS and RP assays,while methanol extracts exhibited better performance in DPPH and FRAP assays.Moreover,methanol extracts demonstrated the highest effectiveness against anti-HepG2 cell proliferation,whereas n-hexane extracts showed greater efficiency in cholinesterase inhibition.Notably,branch bark extracts exhibited the highest levels of phytochemical compounds,with both branch bark and pericarp extracts demonstrating significant effects in cholinesterase inhibition and anti-HepG2 cell proliferation.Correlation analysis indicated that phytochemical compounds were primarily responsible for the observed biological activities.Overall,extracts from the branch bark and pericarp of E.mollis showed promising potential for antioxidant and anticancer activities,suggesting their suitability for applications in the pharmaceutical industry as health-promoting products.展开更多
Alzheimer’s disease(AD)poses one of the most urgent medical challenges in the 21st century as it affects millions of people.Unfortunately,the etiopathogenesis of AD is not yet fully understood and the current pharmac...Alzheimer’s disease(AD)poses one of the most urgent medical challenges in the 21st century as it affects millions of people.Unfortunately,the etiopathogenesis of AD is not yet fully understood and the current pharmacotherapy options are somewhat limited.Here,we report a novel inhibitor,Compound 44,for targeting cholinesterases,amyloid-β(Aβ)aggregation,and glycogen synthase kinase 3β(GSK-3β)simultaneously with the aim of achieving symptomatic relief and disease modification in AD therapy.We found that Compound 44 had good inhibitory effects on all intended targets with IC_(50)s of submicromolar or better,significant neuroprotective effects in cell models,and beneficial improvement of cognitive deficits in the triple transgenic AD(3×Tg AD)mouse model.Moreover,we showed that Compound 44 acts as an autophagy regulator by inducing nuclear translocation of transcription factor EB through GSK-3βinhibition,enhancing the biogenesis of lysosomes and elevating autophagic flux,thus ameliorating the amyloid burden and tauopathy,as well as mitigating the disease phenotype.Our results suggest that triple-target inhibition via Compound 44 could be a promising strategy that may lead to the development of effective therapeutic approaches for AD.展开更多
Due to their significant value in both economy and ecology,Daphnia had long been employed to investigate in vivo response of cholinesterase(ChE) in anticholinesterase exposures,whereas the type constitution and proper...Due to their significant value in both economy and ecology,Daphnia had long been employed to investigate in vivo response of cholinesterase(ChE) in anticholinesterase exposures,whereas the type constitution and property of the enzyme remained unclear.A type of ChE was purified from Daphnia magna using a three-step procedure,i.e.,Triton X-100 extraction,ammonium sulfate precipitation,and diethylaminoethyl(DEAE)-Sepharose Fast-Flow chromatography.According to sodium dodecyl sulfate polyacrylamide gel electrophoresis(SDS-PAGE),molecular mass of the purified ChE was estimated to be 84 kDa.Based on substrate studies,the purified enzyme preferred butyrylthiocholine iodide(BTCh) [with maximum velocity(Vmax)/Michaelis constant(Km)=8.428 L/(min·mg protein)] to acetylthiocholine iodide(ATCh) [with V max /Km =5.346 L/(min·mg protein)] as its substrate.Activity of the purified enzyme was suppressed by high concentrations of either ATCh or BTCh.Inhibitor studies showed that the purified enzyme was more sensitive towards inhibition by tetraisopropylpyrophosphoramide(iso-OMPA) than by 1,5-bis(4-allyldimethylammoniumphenyl) pentan-3-one dibromide(BW284C51).Result of the study suggested that the purified ChE was more like a type of pseudocholinesterase,and it also suggested that Daphnia magna contained multiple types of ChE in their bodies.展开更多
Acetylcholine is an essential neurotransmitter found throughout the nervous system. Its action on postsynaptic receptors is regulated through hydrolysis by various carboxylesterases, especially cholinesterases (ChEs)....Acetylcholine is an essential neurotransmitter found throughout the nervous system. Its action on postsynaptic receptors is regulated through hydrolysis by various carboxylesterases, especially cholinesterases (ChEs). The acute toxicity of organophosphate (OP) compounds is directly linked to their action as inhibitors of ChE. One widely used assay for evaluating ChE activity is a spectrophotometric method developed by Ellman et al. When the enzyme source is from tissues or, in particular, blood, hemoglobin displays a spectrophotometric peak at the same wave-length used to analyze cholinergic activity. This creates a substantial background that interferes with the Ellman’s assay and must be overcome in order to accurately monitor cholinesterase activity. Herein, we directly compare blood processing methods: classical method (1.67 ± 0.30 U/mL) and HemogloBindTM treatment (1.51 ± 0.17 U/mL), and clearly demonstrate that pretreatment of blood samples with HemoglobindTM is both a sufficient and rapid sample preparation method for the assessment of ChE activity using the Ellman’s method.展开更多
To determine the predictive performance of cholinesterase compared to existing prognostic models in evaluating liver function in patients with chronic hepatitis D. METHODSIn an observational, cross-sectional and retro...To determine the predictive performance of cholinesterase compared to existing prognostic models in evaluating liver function in patients with chronic hepatitis D. METHODSIn an observational, cross-sectional and retrospective study, consecutive patients with hepatitis D cirrhosis were evaluated. Demographic, clinical and laboratory parameters were recorded. Serum cholinesterase levels were correlated with existing scoring models for chronic liver disease and Liver function tests. Receiver operating characteristic (ROC) curves were constructed to find an optimal cholinesterase level predicting ascites, Child Turcotte Pugh (CTP) score ≥ 10, model for end stage liver disease (MELD) score ≥ 15, baseline-event-anticipation (BEA) score for hepatitis D ≥ 5 and the aspartate transaminase to Platelet Ratio Index (APRI) ≥ 1.5. RESULTSThis study investigated 233 patients with chronic liver disease due to hepatitis D; 192 were male, median age 42 (16-69 years). Fifty patients had ascites and 15 had encephalopathy. One hundred and sixty-seven (71.7%) were in Child class A, 52 (22.3%) in Child class B and 14 (5.0%) in class C. A MELD score of 15 or more was seen in 24 patients. Cholinesterase levels correlated well with the INR, albumin, CTP score, MELD, MELD sodium, BEA and APRI scores (P < 0.001 each). Area under the ROC curve for ascites, CTP ≥ 10, MELD ≥ 15, BEA ≥ 5, APRI ≥ 1.5 was 0.836, 0.966, 0.913, 0.871 and 0.825 respectively (P < 0.001 each). Cut off values of cholinesterase (IU/L) for predicting ascites, CTP ≥ 10, MELD ≥ 15, BEA ≥ 5 and APRI ≥ 1.5 were < 3812, < 2853, < 2829, < 4719 and < 3954 with a sensitivity of 80%, 100%, 91.67%, 82.50%, 58.0% and specificity of 81.97%, 84.79%, 87.56%, 77.06% and 55.64% respectively. CONCLUSIONSerum cholinesterase demonstrates promising correlations with serum albumin, INR and CTP, MELD, BEA and APRI scores and is predictive of liver reserves in hepatitis D cirrhosis.展开更多
The results confirmed that diazepam inhibits the cholinesterase in rat serum,red cell,corpus striatum and diaphragm in vitro,that the higher the diazepam concentration,the stronger the cholinesterase inhibition,and th...The results confirmed that diazepam inhibits the cholinesterase in rat serum,red cell,corpus striatum and diaphragm in vitro,that the higher the diazepam concentration,the stronger the cholinesterase inhibition,and that diazepam is a reversible inhibitor to acetylcholinesterase and diazepam has a stabilizing action on red cell membranes.The role of these effects of diazepam in the treatment of organic phosphate poisoning is discussed展开更多
AIM: To understand the correlation of serum cholinesterase (CHE) activity with gastric cancer and to assess their clinical significance.METHODS: The velocity method was adopted to detect the activity of serum CHE in p...AIM: To understand the correlation of serum cholinesterase (CHE) activity with gastric cancer and to assess their clinical significance.METHODS: The velocity method was adopted to detect the activity of serum CHE in patients with gastric cancer and in patients with non-malignant tumor as controls.RESULTS: The serum CHE activity in the treatment group was significantly lower than that in the control group with a very significant difference between the two groups (83.3:113.1,P = 0.0003). Age was significantly associated with the incidence of gastric caner.CONCLUSION: Serum CHE activity has a close relation with the incidence of gastric cancer.展开更多
Objective： The aim of the present study was to examine dynamic changes in serum cholinesterase （ChE） activity during early-stage severe trauma and the clinical significance of these changes. Methods： This prospect...Objective： The aim of the present study was to examine dynamic changes in serum cholinesterase （ChE） activity during early-stage severe trauma and the clinical significance of these changes. Methods： This prospective, observational study included 81 patients with severe trauma who were treated between October 2011 and April 2013 in the emergency intensive care unit （EICU） of a university-affiliated, tertiary-care, grade A general hospital in China. Serum ChE activity was measured on Days 1, 3, and 7 post-injury. The correlation of dynamic changes in serum ChE activity with trauma severity and prognosis was assessed. Correlations between changes in serum ChE activity after injury and albumin （ALB）, prealbumin （PAB）, transferrin （TRF）, and C-reactive protein （CRP） levels were also analyzed Results： Serum ChE activity in trauma patients was 42.3%-50.2% lower on Days 1, 3, and 7 compared with the control （P〈0.001 for all time points）, and it continued to decrease after Day 7 in both the survival and death subgroups. In the subgroup with an injury severity score （ISS） of 〈25, serum ChE activity initially decreased, but eventually increased. However, activity decreased continuously in the ISS〉25 subgroup. ChE activity was significantly lower in both the death and the ISS〉25 subgroups than in the survival and ISS〈25 subgroups on Days 1, 3, and 7 after injury. Activity was negatively correlated with ISS and acute physiology and chronic health evaluation Ill （APACHE III） at all time points. When comparing the receiver operating characteristic （ROC） curves for predicting prognosis, the area under the curve （AUC） in the dot of serum ChE was similar to the AUCs in plots of ISS and APACHE Ⅲ, but significantly smaller than the AUC in the plot of the trauma and injury severity score （TRISS）. Serum ChE activity was positively correlated with ALB, PAB, and TRF at all time points post-injury. Activity was not significantly correlated with CRP on Day 1, but was significantly and negatively correlated with CRP on Days 3 and 7. Conclusions： There is a significant decrease in serum ChE activity after severe trauma. Serum ChE may be regarded as a negative acute phase protein （APP） and the dynamic changes in serum ChE may be useful as an auxiliary indicator for evaluating trauma severity and predicting prognosis.展开更多
AIM To examine whether nizatidine stimulates duodenal HCO_3^- secretion in rats by inhibiting AChE activity. METHODS Under pentobarbital anesthesia,a proximal duodenal loop was perfused with saline,and the HCO_3 secre...AIM To examine whether nizatidine stimulates duodenal HCO_3^- secretion in rats by inhibiting AChE activity. METHODS Under pentobarbital anesthesia,a proximal duodenal loop was perfused with saline,and the HCO_3 secretion was measured at pH 7.0 using a pH-stat method and by adding 10mM HCI.Nizatidine,neostigmine,carbachol or famotidine was administered i.v.as a single injection. RESULTS Intravenous administration of nizatidine(3-30 mg/kg)dose-dependently increased duodenal HCO_3^- secretion,and the effect at 10mg/kg was equivalent to that obtained by carbachol at 0.01 mg/kg.This nizatidine action was observed at the same dose range that inhibited acid secretion and enhanced gastric motility,mimicked by i.v.injection of neostigmine(0.03 mg/kg),and significantly attenuated by bilateral vagotomy and prior s.c. administration of atropine but not by indomethacin,a cyclooxygenase inhibitor,or N^G-nitro-L-arginine methyl ester,a NO synthase inhibitor.The HCO_3^- secretory response to acetylcholine(0.001 mg/kg)was significantly potentiated by the concurrent administration of nizatidine(3mg/kg,i.v.).The IC_(50)of nizatidine for AChE of rat erythrocytes was 1.4×10^(-6)M,about 12 times higher than that of neostigmine.Neither famotidine(>10^(-3)M, 30mg/kg,i.v.)nor cisapride(> 10^(-3)M, 3mg/kg,i.v.)had any influence on AChE activity or duodenal HCO_3^- secretion.Duodenal damage induced by acid perfusion(100 mM HCI for 4 h)in the presence of indomethacin was significantly prevented by nizatidine and neostigmine,at the doses that increased the HCO_3^- secretion. CONCLUSION Nizatidine stimulates duodenal HCO_3^- secretion,in both vagal-dependent and atropine-sensitive manners,and the action is associated with the anti-AChE activity of this agent.展开更多
Thiosemicarbazones of 2-amino-5-chlorobenzophenone and 3-aminobenzophenone （L1-La） have been synthesized and their Cu（II） complexes （1-4） were afforded via coordination with cupric chloride. All these compounds ...Thiosemicarbazones of 2-amino-5-chlorobenzophenone and 3-aminobenzophenone （L1-La） have been synthesized and their Cu（II） complexes （1-4） were afforded via coordination with cupric chloride. All these compounds were characterized by UV-vis and lR spectroscopy together with CHN elemental analysis. NMR spectroscopy was also applied to characterize the ligands. In vitro cholinesterase inhibitory assays for the complexes （1-4） showed ICso values less than 10 ~molJL, with complex 1 exhibiting the most activity, ICso = 2.15 ~molJL and 2.16 i^molJL for AChE and BuChE, respectively. Molecular modeling simulation revealed the binding interaction template for complex I with the AChE and BuChE receptors. In DPPH assay, the complexes also showed more in vitro antioxidant activities in comt）arison tn their narent li^ands.展开更多
Objective:To explore cholinesterase inhibitory and antioxidant effect of six coniferous trees(Abies bornmulleriana,Picea pungens,Juniperus communis,Cedrus libani,Taxus baccata,and Cupressus sempervirens var.horizantal...Objective:To explore cholinesterase inhibitory and antioxidant effect of six coniferous trees(Abies bornmulleriana,Picea pungens,Juniperus communis,Cedrus libani,Taxus baccata,and Cupressus sempervirens var.horizantalis).Methods:Acetone(Ace),ethyl acetate(EtOAc),and ethanol(EtOH)extracts prepared from the needles and shoots of the six coniferous trees were screened for their acetylcholinesterase(AChE)and butyrylcholinesterasc(BChE)inhibitory activity at 100μg/mL.Antioxidant activity of the extracts was tested using 2,2-diphenyl-1-picrylhydrazyl(DPPH)and N,N-dimethyl-p-phenylendiamine(DMPD)radical scavenging,nietal-chelation capacity,ferric-(FRAP)and phosphomolibdenum-reducing antioxidant power(PRAP)assays.All of the assays were performed in ELISA microplate reader.Total phenol and flavonoid amounts in the extracts were determined spectrophotometrically.Results:Among thirty-six extracts in total,the shoot-Ace extract of Cupressus sempervirens var.horizantalis exerted the highest inhibition against AChE[(54.84±2.51)%],while the needle-Ace extract of Cedrus libani was the most effective in inhibiting BChE[(67.54±0.30)%].The highest DPPH radical scavenging effect,FRAP and PRAP was observed in the shoot-Ace and EtOAc extracts from Taxus baccata.whereas all the extracts showed a variable degree of scavenging effect against DPMD radical.The shoot-EtOAc extract of Cedrus libani had the highest metalchelation capacity[(58.04±0.70)%].The shoot extracts of Taxus baccata were determined to have the richest total phenol content,which may contribute to its marked antioxidant activity.Conclusions:The conifer species screened in this study may contain cholinesterase-inhibiting and antioxidant properties,which might be useful against Alzheimer's disease.展开更多
To yield cholinesterase（ChE） from prokaryotic expression, the ChE gene that belongs to Daphnia magna was amplified by reverse transcription-polymerase chain reaction（RT-PCR） using forward primer 5＇-CCCYGGNGCSAT G...To yield cholinesterase（ChE） from prokaryotic expression, the ChE gene that belongs to Daphnia magna was amplified by reverse transcription-polymerase chain reaction（RT-PCR） using forward primer 5＇-CCCYGGNGCSAT GATGTG-3＇ and reverse primer 5＇-GYAAGTTRGCCCAATATCT-3＇. To express the gene, one sequence of the amplified DNA, which was able to encode a putative protein containing two conserved carboxylesterase domains, was connected to the prokaryotic expression vector PET-29a（＋）. The recombinant vector was transformed into Escherichia coil BL21（DE3）. Protein expression was induced by isopropy-D-thiogalactoside. The expressed ChE was used as an immunogen to immunize BALB/c mice. The obtained antibodies were tested for their specificity towards crude enzymes from species such as Alona milleri, Macrobrachium nipponense, Bombyx mori, Chironomus kiiensis, Apis mellifera, Eisenia foetida, Brachydanio rerio, and Xenopus laevis. Results indicated that the antibodies had specificity suitable for detecting ChE in Daphnia magna. A type of indirect and non-competitive enzyme-linked immunosorbent assay（IN-ELISA） was used to test the immunoreactive content of ChE（ChE-IR） in Daphina magna. The detection limit of the IN-ELISA was found to be 14.5 ng/ml at an antiserum dilution of 1：22 000. Results from tests on Daphnia magna exposed to sublethal concentrations of triazophos indicated a maximal induction of 57.2% in terms of ChE-IR on the second day after the animals were exposed to a concentration of 2.10 μg/L triazophos. Testing on animals acclimatized to a temperature of 16 °C indicated that ChE-IR was induced by 16.9% compared with the ChE-IR content detected at 21 °C, and the rate of induction was 25.6% at 10 °C. The IN-ELISA was also used to test the stability of ChE-IR in collected samples. Repeated freezing and thawing had no influence on the outcome of the test. All these results suggest that the polyclonal antibodies developed against the recombinant ChE are as efficient as those developed against the native ChE in detecting ChE content in Daphnia magna.展开更多
The density functional theory at the B3LYP/6-311G（d, p） level was applied to exploring the inhibition mechanism of cholinesterases by carbamate. The results indicate that the inhibition reactions with or without the...The density functional theory at the B3LYP/6-311G（d, p） level was applied to exploring the inhibition mechanism of cholinesterases by carbamate. The results indicate that the inhibition reactions with or without the catalytic effect of the catalytic triad in eholinesterases underwent a two-step addition-elimination mechanism, which is in good agreement with the proposed mechanism. The solvent has a strong effect on the inhibition reactions and the reaction with the catalytic triad in the solvent phase is close to the real reaction under biological condition.展开更多
Objective:To investigate the effect of Cannabis sativa resin and/or tramadol,two commonly drugs of abuse on acetylcholinesterase and butyrylcholinesterase activities as a possible cholinergic biomarkers of neurotoxici...Objective:To investigate the effect of Cannabis sativa resin and/or tramadol,two commonly drugs of abuse on acetylcholinesterase and butyrylcholinesterase activities as a possible cholinergic biomarkers of neurotoxicity induced by these agents.Methods:rats were treated with cannabis resin(5,10 or 20 mg/kg)(equivalent to the active constituent A'-tetrahydrocannabinol),tramadol(5,10 and 20 mg/kg) or tramadol(10 mg/kg)combined with cannabis resin(5,10 and 20 mg/kg) subcutaneously daily for 6 weeks.Acetylcholinesterase(AChE) and butyrylcholinesterase(BChE) activities were measured in brain and serum.We also measured the activity of paraoxonase-1(PONl) in serum of rats treated with these agents.Results:(i) AChE activity in brain increased after 10-20 mg/kg cannabis resin(by 16.3%-36.5%).AChE activity in brain did not change after treatment with 5-20 mg/kg tramadol.The administration of both cannabis resin(5,10 or 20 mg/kg) and tramadol(10 mg/kg) resulted in decreased brain AChE activity by 14.1%,12.9%and 13.6%,respectively;(ii) BChE activity in serum was markedly and dose-dependenlly inhibited by cannabis resin(by 60.9%-76.9%).BChE activity also decreased by 17.6%-36.5%by 10-20mg/kg tramadol and by 57.2%-63.9%by the cannabis resin/tramadol combined treatment;(iii)Cannabis resin at dose of 20 mg/kg increased serum PONl activity by 25.7%.In contrast,tramadol given at 5,10 and 20 mg/kg resulted in a dose-dependent decrease in serum PON1 activity by 19%,36.7%,and 46.1%,respectively.Meanwhile,treatment with cannabis resin plus tramadol resulted in 40.2%,35.8%,30.7%inhibition of PONl activity compared to the saline group.Conclusions:these data suggest that cannabis resin exerts different effects on AChE and BChE activities which could contribute to the memory problems and the decline in cognitive function in chronic users.展开更多
Introduction: Dementia is frequently associated with Parkinson’s disease, especially in later stages. Efficacy of cholinesterase inhibitors (ChI) in Alzheimer’s dementia is well established. However, treatment with ...Introduction: Dementia is frequently associated with Parkinson’s disease, especially in later stages. Efficacy of cholinesterase inhibitors (ChI) in Alzheimer’s dementia is well established. However, treatment with ChI in Parkinson’s disease dementia (PDD) remains controversial. The objective of this systematic review and meta-analysis was to assess the effects of ChI in PDD. Methods: A comprehensive literature search was performed in MEDLINE, EMBASE and Cochrane library up to March 2014 using the descriptors “Parkinson’s disease”, “dementia in Parkinson’s disease”, “cognition”, “acetylcholinesterase inhibitors”, “cholinesterase inhibitors”, “anticholinesterase agents”, “rivastigmine”, “donepezil” and “galantamine” (Pubmed search strategy). All randomized, doubleblinded, placebo-controlled trials that met the eligibility criteria and assessed the effects of ChI in PDD were considered for analysis. There were no restrictions regarding paper language. Summary effect-sizes were presented as standardized mean differences (SMD) and the pooled analysis was performed with a fixed-effects model. Outcomes considered for analysis were the Mini Mental Status Exam (MMSE) score and the cognition scale for evaluation of dementia ADAS-Cog. The degree of heterogeneity between included studies was assessed through the I2 test. Results: After a comprehensive search, 175 references were retrieved. From these, five randomized trials involving 946PDD subjects were included in the review. Four studies used donepezil and only one study used rivastigmine. The pooled analysis of five studies that assessed the effects of ChI in MMSE total score showed a SMD of 0.24 (CI 95% 0.11 - 0.38). Three studies considered the effects of ChI on Adas-Cog and the pooled results showed a SMD of 0.21 (CI 95% 0.07 - 0.35). There was no significant heterogeneity between the studies. Conclusions: The results of this systematic review and meta- analysis suggest that ChI improves cognitive impairment in PDD subjects. Despite statistically significant, the translation of these results into relevant clinical improvement should be taken with caution, as the studies did not address what would be considered a clinically significant result.展开更多
Cholinergic dysfunction is common to Alzheimer’s dementia and Schizophrenia. The objective of this study is to undertake a systematic review and meta-analysis of the literature on the cognitive and clinical effects o...Cholinergic dysfunction is common to Alzheimer’s dementia and Schizophrenia. The objective of this study is to undertake a systematic review and meta-analysis of the literature on the cognitive and clinical effects of cholinesterase inhibitors administered to patients with schizophrenia and co-morbid Alzheimer’s disease dementia. A literature search of the MEDLINE, CINAHL, PubMed, PsycINFO, EMBASE, AMED, BNI, HMIC and Health Business Elite databases has been performed (up to January 2013) to investigate the use of cholinesterase inhibitors in patients with schizophrenia and dementia. The terms “schizophrenia”, “dementia”, “rivastigmine”, “donepezil”, “galantamine” and “cognitive deficit” have been searched, with a restriction for English language. Five published studies including 1 RCT have been included for the qualitative review. Treatments include Donepezil 5 mg and 10 mg as well as Rivastigmine 9 mg. The numbers of participants vary from 2 incase report to20 inthe RCT. Only 1 study qualifies for meta-analysis. There is a very limited evidence on the efficacy and safety of using acetylcholinesterase inhibitors in the management of dementia co-morbid with schizophrenia. The only randomised controlled study shows lack of evidence in terms of efficacy in using cholinesterase inhibitors in the management of dementia with schizophrenia. Future research projects will have to look at an adequate sample size to explore treatment on various cognitive and noncognitive domains and the sample should be selected by using definitive and internationally acceptable diagnostic criteria.展开更多
Two novel naphthol derivatives（1 and 2） were synthesized and characterized via IR,~1H NMR,and HRMS.The structure of compound 2 was verified by single-crystal X-ray crystallography.It crystallizes in monoclinic,space...Two novel naphthol derivatives（1 and 2） were synthesized and characterized via IR,~1H NMR,and HRMS.The structure of compound 2 was verified by single-crystal X-ray crystallography.It crystallizes in monoclinic,space group C2/c with a = 21.6725（9）,b = 6.0127（3）,c = 25.5405（14） A,β = 94.716（5）o,V = 3316.9（3） A^3,Z = 8,F（000） = 1384,D_c = 1.511 Mg/m^3,M_r = 377.22 and μ = 2.487 mm^-1.In addition,their cholinesterase inhibitory activities in vitro toward Electrophorus electricus acetylcholinesterase（eel ACh E） and horse serum butyrylcholinesterase（eq BCh E） were further determined.The results showed that compound 1 as a new acetylcholinesterase（ACh E） inhibitor displayed higher ACh E inhibitory activity（IC_（50） = 1.4 μM）,which could be considered for Alzheimer＇s disease therapeutics.展开更多
<strong>Objective:</strong> To evaluate early prediction value of IPS<span> </span><span><span style="font-family:Verdana;">combined with SchE and D-dimer detection for in...<strong>Objective:</strong> To evaluate early prediction value of IPS<span> </span><span><span style="font-family:Verdana;">combined with SchE and D-dimer detection for infection and survival in critically ill patients. </span><b><span style="font-family:Verdana;">Methods:</span></b></span><b><span> </span></b><span style="font-family:Verdana;">199 critically ill patients admitted to the emergency intensive care unit (EICU) of our hospital from December 2018 to December 2019 were retrospectively analyzed, including 110 infection patients (infection group) and 89 non-infection</span><span> </span><span style="font-family:Verdana;">patients (non-infection group).</span><span> </span><span><span style="font-family:Verdana;">According to the survival, the infection group was divided into death group (68 cases) and survival group (42 cases). The IPS, APACHE II, SOFA and SchE, D-dimer expression levels were detected and compared;Univariate and logistic regression analysis were used to evaluate the independent prognostic factors. </span><b><span style="font-family:Verdana;">Results: </span></b><span style="font-family:Verdana;">The IPS and APACHE II of patients in the infected group were higher than those in the non-infected group, the level of SchE was lower than that in the non-infected group, and the level of D-dimer was higher than that in the non-infected group (</span><i><span style="font-family:Verdana;">P</span></i></span><i><span> </span></i><span style="font-family:Verdana;"><</span><span> </span><span style="font-family:Verdana;">0.001). IPS, SOFA, APACHE</span><span style="font-family:Verdana;"> II</span><span style="font-family:Verdana;">, SchE, D-dimer, invasive mechanical ventilation, septic shock, and ICU length</span><span style="font-family:Verdana;"> of stay had significant influence on the prognosis of critically ill patients</span><span> </span><span><span style="font-family:Verdana;">(</span><i><span style="font-family:Verdana;">P</span></i></span><i><span> </span></i><span style="font-family:Verdana;"><</span><span> </span><span><span style="font-family:Verdana;">0.001). Logistic regression analysis showed that IPS (</span><i><span style="font-family:Verdana;">OR</span></i><span style="font-family:Verdana;"> = 2.821, </span><span><span style="font-family:Verdana;">95%</span><i><span style="font-family:Verdana;"> CI</span></i></span><span style="font-family:Verdana;"> 1.501</span></span><span style="font-family:Verdana;"> - </span><span><span style="font-family:Verdana;">5.227), SOFA (</span><i><span style="font-family:Verdana;">OR</span></i><span style="font-family:Verdana;"> = 5.078, </span><span><span style="font-family:Verdana;">95% </span><i><span style="font-family:Verdana;">CI</span></i></span><span style="font-family:Verdana;"> 3.327 </span></span><span style="font-family:Verdana;">-</span><span><span style="font-family:Verdana;"> 7.690), APACHE II (</span><i><span style="font-family:Verdana;">OR</span></i><span style="font-family:Verdana;"> = 14.308, </span><span><span style="font-family:Verdana;">95% </span><i><span style="font-family:Verdana;">CI</span></i></span><span style="font-family:Verdana;"> 8.901 </span></span><span style="font-family:Verdana;">-</span><span><span style="font-family:Verdana;"> 21.893), SchE (</span><i><span style="font-family:Verdana;">OR</span></i><span style="font-family:Verdana;"> = 0.223, </span><span><span style="font-family:Verdana;">95%</span><i><span style="font-family:Verdana;"> CI</span></i></span><span style="font-family:Verdana;"> 0.165 </span></span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;"> 0.291), D-dimer</span><span style="font-family:Verdana;"> (</span><i><span style="font-family:Verdana;">OR</span></i><i><span> </span></i><span style="font-family:Verdana;">=</span><span> </span><span style="font-family:Verdana;">2.10</span><span style="font-family:Verdana;">, </span><span style="font-family:Verdana;">95%</span><i><span> </span></i><i><span style="font-family:Verdana;">CI</span></i><i><span> </span></i><span style="font-family:Verdana;">1.55</span><span style="font-family:Verdana;"> - </span><span style="font-family:Verdana;">2.85</span><span style="font-family:Verdana;">)</span><span><span style="font-family:Verdana;">, septic shock (</span><i><span style="font-family:Verdana;">OR</span></i><span style="font-family:Verdana;"> = 9.948,</span></span><span> </span><span style="font-family:Verdana;">95%</span><span> </span><i><span style="font-family:Verdana;">CI</span></i><span style="font-family:Verdana;"> 7.012</span><span style="font-family:Verdana;"> - </span><span style="font-family:Verdana;">17.012)</span><span> </span><span style="font-family:Verdana;">were independent factors affecting the prognosis of critically ill patients with infection</span><span style="font-family:Verdana;"> (</span><i><span style="font-family:Verdana;">P</span></i><span> </span><span style="font-family:Verdana;"><</span><span> </span><span style="font-family:Verdana;">0.001</span><span style="font-family:Verdana;">)</span><span style="font-family:Verdana;">.</span><span> </span><b><span style="font-family:Verdana;">Conclusion:</span></b><b><span> </span></b><span style="font-family:Verdana;">IPS and D-dimer expression level in infected patients were increased and SchE decreased significantly compared with those in non-infected patients, and they significantly correlated with</span><span> </span><span style="font-family:Verdana;">disease severity of infected</span><span> </span><span style="font-family:Verdana;">patients</span><span> </span><span style="font-family:Verdana;">and could be early prediction</span><span> </span><span style="font-family:Verdana;">for prognosis.</span>展开更多
Objective: To study the changes of serum pancreatic stone protein (PSP) and cholinesterase (ChE) contents in children with sepsis and their correlation with systemic inflammatory response and target organ damage. Meth...Objective: To study the changes of serum pancreatic stone protein (PSP) and cholinesterase (ChE) contents in children with sepsis and their correlation with systemic inflammatory response and target organ damage. Methods: A total of 64 children with sepsis who were treated in the hospital between January 2015 and January 2017 were selected as observation group, and 50 healthy children who received vaccination in the hospital during the same period were selected as normal control group. The contents of PSP, ChE, inflammatory factors as well as liver and kidney function indexes in the two groups were detected. Pearson test was used to assess the correlation of serum PSP and ChE contents with systemic inflammatory response and target organ damage in children with sepsis. Results: Serum PSP content of observation group was higher than that of control group while ChE content was lower than that of control group;serum inflammatory factors PCT, CRP, IL-1, IL-6 and IL-10 contents of observation group were higher than those of normal control group;liver function indexes TBIL, ALT and AST contents were higher than those of normal control group;kidney function indexes Scr and BUN contents were higher than those of normal control group. Pearson test showed that the serum PSP and ChE contents in children with sepsis were directly correlated with the systemic inflammatory response as well as liver and renal function injury. Conclusion: Serum PSP content significantly increases while ChE content significantly decreases in children with sepsis and the specific change is directly correlated with the overall disease severity.展开更多
Objective:To investigate effects of hemoperfusion and hemofiltration combination on treating patients with acute organophosphours pesticide poisoning (AOPP) and influence of it on cholinesterase, dopamine and inflamma...Objective:To investigate effects of hemoperfusion and hemofiltration combination on treating patients with acute organophosphours pesticide poisoning (AOPP) and influence of it on cholinesterase, dopamine and inflammatory factors.Methods:A total of 82 cases of AOPP patients treated in our hospital from Sep 2012 to Jul 2016 were selected as subjects. They were randomly divided to be the observation group and the control group, 41 cases for each. For patients in observation group, combined therapy of hemoperfusion (HP) and hemofiltration (HF) were provided. For patients in control group, combined therapy of HP and hemodialysis (HD) were provided. Effects on the two groups of patients were compared. Meanwhile, cholinesterase, dopamine and inflammatory factors levels in different times before and after treatment were compared.Results:Consciousness improvement times and hospitalization times in observation group were significantly lower than in control group. No significant difference showed on fatality rates between the two groups. Before treatment, no significant difference showed on CHE and DE levels between two groups of patients;6 h and 12 h after treatment, CHE average levels in two groups were significantly higher than before treatment in the same group, and levels in observation group at the same phase were significantly higher than in control group;6 h and 12 h after treatment, DA levels in observation group were significantly lower than the same group before treatment, and significantly lower than control group, while 12 h after treatment, DA levels in control group were significantly lower than the same group before treatment. Before treatment, no significant difference showed on serum TGF-β1, TNF-α, IL-6, IL-8 between two groups of patients. After treatment, each index levels in two groups were significantly lower than the same group before treatment, and levels in observation group at the same phase were significantly lower than control group. Conclusion:Effects of blood purification therapy on treating AOPP were worth approving, but effects of HP and HF combined therapy were more significant. In addition, improvement of HP+HF on CHE, DA and inflammatory factors were better than HP+HD.展开更多
基金National Natural Science Foundation of China(Grant No.31600549).
文摘To explore the potential utilization of Elaeagnus mollis,we conducted a comprehensive assessment of its phytochemical composition,antioxidant properties,cholinesterase inhibition,and anti-HepG2 cell proliferation activity across different plant parts(branch wood,branch bark,and pericarp)using various solvents(water,methanol,ethanol,and n-hexane).Our findings revealed that water extracts displayed superior antioxidant activities in ABTS and RP assays,while methanol extracts exhibited better performance in DPPH and FRAP assays.Moreover,methanol extracts demonstrated the highest effectiveness against anti-HepG2 cell proliferation,whereas n-hexane extracts showed greater efficiency in cholinesterase inhibition.Notably,branch bark extracts exhibited the highest levels of phytochemical compounds,with both branch bark and pericarp extracts demonstrating significant effects in cholinesterase inhibition and anti-HepG2 cell proliferation.Correlation analysis indicated that phytochemical compounds were primarily responsible for the observed biological activities.Overall,extracts from the branch bark and pericarp of E.mollis showed promising potential for antioxidant and anticancer activities,suggesting their suitability for applications in the pharmaceutical industry as health-promoting products.
基金supported by the Science and Technology Development Fund,Macao SAR(File no.0062/2021/A)the University of Macao(MYRG2022-00171-FHS).
文摘Alzheimer’s disease(AD)poses one of the most urgent medical challenges in the 21st century as it affects millions of people.Unfortunately,the etiopathogenesis of AD is not yet fully understood and the current pharmacotherapy options are somewhat limited.Here,we report a novel inhibitor,Compound 44,for targeting cholinesterases,amyloid-β(Aβ)aggregation,and glycogen synthase kinase 3β(GSK-3β)simultaneously with the aim of achieving symptomatic relief and disease modification in AD therapy.We found that Compound 44 had good inhibitory effects on all intended targets with IC_(50)s of submicromolar or better,significant neuroprotective effects in cell models,and beneficial improvement of cognitive deficits in the triple transgenic AD(3×Tg AD)mouse model.Moreover,we showed that Compound 44 acts as an autophagy regulator by inducing nuclear translocation of transcription factor EB through GSK-3βinhibition,enhancing the biogenesis of lysosomes and elevating autophagic flux,thus ameliorating the amyloid burden and tauopathy,as well as mitigating the disease phenotype.Our results suggest that triple-target inhibition via Compound 44 could be a promising strategy that may lead to the development of effective therapeutic approaches for AD.
基金Project supported by the Zhejiang Provincial Natural Science Foundation of China(No.LY12B07008)the Department of Education of Zhejiang Province,China(No.20070138)
文摘Due to their significant value in both economy and ecology,Daphnia had long been employed to investigate in vivo response of cholinesterase(ChE) in anticholinesterase exposures,whereas the type constitution and property of the enzyme remained unclear.A type of ChE was purified from Daphnia magna using a three-step procedure,i.e.,Triton X-100 extraction,ammonium sulfate precipitation,and diethylaminoethyl(DEAE)-Sepharose Fast-Flow chromatography.According to sodium dodecyl sulfate polyacrylamide gel electrophoresis(SDS-PAGE),molecular mass of the purified ChE was estimated to be 84 kDa.Based on substrate studies,the purified enzyme preferred butyrylthiocholine iodide(BTCh) [with maximum velocity(Vmax)/Michaelis constant(Km)=8.428 L/(min·mg protein)] to acetylthiocholine iodide(ATCh) [with V max /Km =5.346 L/(min·mg protein)] as its substrate.Activity of the purified enzyme was suppressed by high concentrations of either ATCh or BTCh.Inhibitor studies showed that the purified enzyme was more sensitive towards inhibition by tetraisopropylpyrophosphoramide(iso-OMPA) than by 1,5-bis(4-allyldimethylammoniumphenyl) pentan-3-one dibromide(BW284C51).Result of the study suggested that the purified ChE was more like a type of pseudocholinesterase,and it also suggested that Daphnia magna contained multiple types of ChE in their bodies.
文摘Acetylcholine is an essential neurotransmitter found throughout the nervous system. Its action on postsynaptic receptors is regulated through hydrolysis by various carboxylesterases, especially cholinesterases (ChEs). The acute toxicity of organophosphate (OP) compounds is directly linked to their action as inhibitors of ChE. One widely used assay for evaluating ChE activity is a spectrophotometric method developed by Ellman et al. When the enzyme source is from tissues or, in particular, blood, hemoglobin displays a spectrophotometric peak at the same wave-length used to analyze cholinergic activity. This creates a substantial background that interferes with the Ellman’s assay and must be overcome in order to accurately monitor cholinesterase activity. Herein, we directly compare blood processing methods: classical method (1.67 ± 0.30 U/mL) and HemogloBindTM treatment (1.51 ± 0.17 U/mL), and clearly demonstrate that pretreatment of blood samples with HemoglobindTM is both a sufficient and rapid sample preparation method for the assessment of ChE activity using the Ellman’s method.
文摘To determine the predictive performance of cholinesterase compared to existing prognostic models in evaluating liver function in patients with chronic hepatitis D. METHODSIn an observational, cross-sectional and retrospective study, consecutive patients with hepatitis D cirrhosis were evaluated. Demographic, clinical and laboratory parameters were recorded. Serum cholinesterase levels were correlated with existing scoring models for chronic liver disease and Liver function tests. Receiver operating characteristic (ROC) curves were constructed to find an optimal cholinesterase level predicting ascites, Child Turcotte Pugh (CTP) score ≥ 10, model for end stage liver disease (MELD) score ≥ 15, baseline-event-anticipation (BEA) score for hepatitis D ≥ 5 and the aspartate transaminase to Platelet Ratio Index (APRI) ≥ 1.5. RESULTSThis study investigated 233 patients with chronic liver disease due to hepatitis D; 192 were male, median age 42 (16-69 years). Fifty patients had ascites and 15 had encephalopathy. One hundred and sixty-seven (71.7%) were in Child class A, 52 (22.3%) in Child class B and 14 (5.0%) in class C. A MELD score of 15 or more was seen in 24 patients. Cholinesterase levels correlated well with the INR, albumin, CTP score, MELD, MELD sodium, BEA and APRI scores (P < 0.001 each). Area under the ROC curve for ascites, CTP ≥ 10, MELD ≥ 15, BEA ≥ 5, APRI ≥ 1.5 was 0.836, 0.966, 0.913, 0.871 and 0.825 respectively (P < 0.001 each). Cut off values of cholinesterase (IU/L) for predicting ascites, CTP ≥ 10, MELD ≥ 15, BEA ≥ 5 and APRI ≥ 1.5 were < 3812, < 2853, < 2829, < 4719 and < 3954 with a sensitivity of 80%, 100%, 91.67%, 82.50%, 58.0% and specificity of 81.97%, 84.79%, 87.56%, 77.06% and 55.64% respectively. CONCLUSIONSerum cholinesterase demonstrates promising correlations with serum albumin, INR and CTP, MELD, BEA and APRI scores and is predictive of liver reserves in hepatitis D cirrhosis.
文摘The results confirmed that diazepam inhibits the cholinesterase in rat serum,red cell,corpus striatum and diaphragm in vitro,that the higher the diazepam concentration,the stronger the cholinesterase inhibition,and that diazepam is a reversible inhibitor to acetylcholinesterase and diazepam has a stabilizing action on red cell membranes.The role of these effects of diazepam in the treatment of organic phosphate poisoning is discussed
文摘AIM: To understand the correlation of serum cholinesterase (CHE) activity with gastric cancer and to assess their clinical significance.METHODS: The velocity method was adopted to detect the activity of serum CHE in patients with gastric cancer and in patients with non-malignant tumor as controls.RESULTS: The serum CHE activity in the treatment group was significantly lower than that in the control group with a very significant difference between the two groups (83.3:113.1,P = 0.0003). Age was significantly associated with the incidence of gastric caner.CONCLUSION: Serum CHE activity has a close relation with the incidence of gastric cancer.
基金Project supported by the Zhejiang Medical and Health Research Project(No.2012KYB092)the Education Department of Zhejiang Province(No.Y201018337)the Science and Technology Department of Zhejiang Province(No.2012C33124),China
文摘Objective： The aim of the present study was to examine dynamic changes in serum cholinesterase （ChE） activity during early-stage severe trauma and the clinical significance of these changes. Methods： This prospective, observational study included 81 patients with severe trauma who were treated between October 2011 and April 2013 in the emergency intensive care unit （EICU） of a university-affiliated, tertiary-care, grade A general hospital in China. Serum ChE activity was measured on Days 1, 3, and 7 post-injury. The correlation of dynamic changes in serum ChE activity with trauma severity and prognosis was assessed. Correlations between changes in serum ChE activity after injury and albumin （ALB）, prealbumin （PAB）, transferrin （TRF）, and C-reactive protein （CRP） levels were also analyzed Results： Serum ChE activity in trauma patients was 42.3%-50.2% lower on Days 1, 3, and 7 compared with the control （P〈0.001 for all time points）, and it continued to decrease after Day 7 in both the survival and death subgroups. In the subgroup with an injury severity score （ISS） of 〈25, serum ChE activity initially decreased, but eventually increased. However, activity decreased continuously in the ISS〉25 subgroup. ChE activity was significantly lower in both the death and the ISS〉25 subgroups than in the survival and ISS〈25 subgroups on Days 1, 3, and 7 after injury. Activity was negatively correlated with ISS and acute physiology and chronic health evaluation Ill （APACHE III） at all time points. When comparing the receiver operating characteristic （ROC） curves for predicting prognosis, the area under the curve （AUC） in the dot of serum ChE was similar to the AUCs in plots of ISS and APACHE Ⅲ, but significantly smaller than the AUC in the plot of the trauma and injury severity score （TRISS）. Serum ChE activity was positively correlated with ALB, PAB, and TRF at all time points post-injury. Activity was not significantly correlated with CRP on Day 1, but was significantly and negatively correlated with CRP on Days 3 and 7. Conclusions： There is a significant decrease in serum ChE activity after severe trauma. Serum ChE may be regarded as a negative acute phase protein （APP） and the dynamic changes in serum ChE may be useful as an auxiliary indicator for evaluating trauma severity and predicting prognosis.
文摘AIM To examine whether nizatidine stimulates duodenal HCO_3^- secretion in rats by inhibiting AChE activity. METHODS Under pentobarbital anesthesia,a proximal duodenal loop was perfused with saline,and the HCO_3 secretion was measured at pH 7.0 using a pH-stat method and by adding 10mM HCI.Nizatidine,neostigmine,carbachol or famotidine was administered i.v.as a single injection. RESULTS Intravenous administration of nizatidine(3-30 mg/kg)dose-dependently increased duodenal HCO_3^- secretion,and the effect at 10mg/kg was equivalent to that obtained by carbachol at 0.01 mg/kg.This nizatidine action was observed at the same dose range that inhibited acid secretion and enhanced gastric motility,mimicked by i.v.injection of neostigmine(0.03 mg/kg),and significantly attenuated by bilateral vagotomy and prior s.c. administration of atropine but not by indomethacin,a cyclooxygenase inhibitor,or N^G-nitro-L-arginine methyl ester,a NO synthase inhibitor.The HCO_3^- secretory response to acetylcholine(0.001 mg/kg)was significantly potentiated by the concurrent administration of nizatidine(3mg/kg,i.v.).The IC_(50)of nizatidine for AChE of rat erythrocytes was 1.4×10^(-6)M,about 12 times higher than that of neostigmine.Neither famotidine(>10^(-3)M, 30mg/kg,i.v.)nor cisapride(> 10^(-3)M, 3mg/kg,i.v.)had any influence on AChE activity or duodenal HCO_3^- secretion.Duodenal damage induced by acid perfusion(100 mM HCI for 4 h)in the presence of indomethacin was significantly prevented by nizatidine and neostigmine,at the doses that increased the HCO_3^- secretion. CONCLUSION Nizatidine stimulates duodenal HCO_3^- secretion,in both vagal-dependent and atropine-sensitive manners,and the action is associated with the anti-AChE activity of this agent.
基金Universiti Sains Malaysia -Science Fund Grant No.1001/PK1M1A/823003 and RU Grant No. 1001/PKIMIA/811196 for the financial support of this work
文摘Thiosemicarbazones of 2-amino-5-chlorobenzophenone and 3-aminobenzophenone （L1-La） have been synthesized and their Cu（II） complexes （1-4） were afforded via coordination with cupric chloride. All these compounds were characterized by UV-vis and lR spectroscopy together with CHN elemental analysis. NMR spectroscopy was also applied to characterize the ligands. In vitro cholinesterase inhibitory assays for the complexes （1-4） showed ICso values less than 10 ~molJL, with complex 1 exhibiting the most activity, ICso = 2.15 ~molJL and 2.16 i^molJL for AChE and BuChE, respectively. Molecular modeling simulation revealed the binding interaction template for complex I with the AChE and BuChE receptors. In DPPH assay, the complexes also showed more in vitro antioxidant activities in comt）arison tn their narent li^ands.
基金the Scientific and Technological Research Council of Turkey(TUBITAK)for the scholarship provided her for Ph.D.program
文摘Objective:To explore cholinesterase inhibitory and antioxidant effect of six coniferous trees(Abies bornmulleriana,Picea pungens,Juniperus communis,Cedrus libani,Taxus baccata,and Cupressus sempervirens var.horizantalis).Methods:Acetone(Ace),ethyl acetate(EtOAc),and ethanol(EtOH)extracts prepared from the needles and shoots of the six coniferous trees were screened for their acetylcholinesterase(AChE)and butyrylcholinesterasc(BChE)inhibitory activity at 100μg/mL.Antioxidant activity of the extracts was tested using 2,2-diphenyl-1-picrylhydrazyl(DPPH)and N,N-dimethyl-p-phenylendiamine(DMPD)radical scavenging,nietal-chelation capacity,ferric-(FRAP)and phosphomolibdenum-reducing antioxidant power(PRAP)assays.All of the assays were performed in ELISA microplate reader.Total phenol and flavonoid amounts in the extracts were determined spectrophotometrically.Results:Among thirty-six extracts in total,the shoot-Ace extract of Cupressus sempervirens var.horizantalis exerted the highest inhibition against AChE[(54.84±2.51)%],while the needle-Ace extract of Cedrus libani was the most effective in inhibiting BChE[(67.54±0.30)%].The highest DPPH radical scavenging effect,FRAP and PRAP was observed in the shoot-Ace and EtOAc extracts from Taxus baccata.whereas all the extracts showed a variable degree of scavenging effect against DPMD radical.The shoot-EtOAc extract of Cedrus libani had the highest metalchelation capacity[(58.04±0.70)%].The shoot extracts of Taxus baccata were determined to have the richest total phenol content,which may contribute to its marked antioxidant activity.Conclusions:The conifer species screened in this study may contain cholinesterase-inhibiting and antioxidant properties,which might be useful against Alzheimer's disease.
基金supported by the Zhejiang Provincial Natural Science Foundation(No.LY12B07008),China
文摘To yield cholinesterase（ChE） from prokaryotic expression, the ChE gene that belongs to Daphnia magna was amplified by reverse transcription-polymerase chain reaction（RT-PCR） using forward primer 5＇-CCCYGGNGCSAT GATGTG-3＇ and reverse primer 5＇-GYAAGTTRGCCCAATATCT-3＇. To express the gene, one sequence of the amplified DNA, which was able to encode a putative protein containing two conserved carboxylesterase domains, was connected to the prokaryotic expression vector PET-29a（＋）. The recombinant vector was transformed into Escherichia coil BL21（DE3）. Protein expression was induced by isopropy-D-thiogalactoside. The expressed ChE was used as an immunogen to immunize BALB/c mice. The obtained antibodies were tested for their specificity towards crude enzymes from species such as Alona milleri, Macrobrachium nipponense, Bombyx mori, Chironomus kiiensis, Apis mellifera, Eisenia foetida, Brachydanio rerio, and Xenopus laevis. Results indicated that the antibodies had specificity suitable for detecting ChE in Daphnia magna. A type of indirect and non-competitive enzyme-linked immunosorbent assay（IN-ELISA） was used to test the immunoreactive content of ChE（ChE-IR） in Daphina magna. The detection limit of the IN-ELISA was found to be 14.5 ng/ml at an antiserum dilution of 1：22 000. Results from tests on Daphnia magna exposed to sublethal concentrations of triazophos indicated a maximal induction of 57.2% in terms of ChE-IR on the second day after the animals were exposed to a concentration of 2.10 μg/L triazophos. Testing on animals acclimatized to a temperature of 16 °C indicated that ChE-IR was induced by 16.9% compared with the ChE-IR content detected at 21 °C, and the rate of induction was 25.6% at 10 °C. The IN-ELISA was also used to test the stability of ChE-IR in collected samples. Repeated freezing and thawing had no influence on the outcome of the test. All these results suggest that the polyclonal antibodies developed against the recombinant ChE are as efficient as those developed against the native ChE in detecting ChE content in Daphnia magna.
基金Supported by the National Natural Science Foundation of China(Nos.20333050 and 20673044), PCSIRT(No.IRT0625) Key Subject of Science and Technology by Jilin Province, China
文摘The density functional theory at the B3LYP/6-311G（d, p） level was applied to exploring the inhibition mechanism of cholinesterases by carbamate. The results indicate that the inhibition reactions with or without the catalytic effect of the catalytic triad in eholinesterases underwent a two-step addition-elimination mechanism, which is in good agreement with the proposed mechanism. The solvent has a strong effect on the inhibition reactions and the reaction with the catalytic triad in the solvent phase is close to the real reaction under biological condition.
文摘Objective:To investigate the effect of Cannabis sativa resin and/or tramadol,two commonly drugs of abuse on acetylcholinesterase and butyrylcholinesterase activities as a possible cholinergic biomarkers of neurotoxicity induced by these agents.Methods:rats were treated with cannabis resin(5,10 or 20 mg/kg)(equivalent to the active constituent A'-tetrahydrocannabinol),tramadol(5,10 and 20 mg/kg) or tramadol(10 mg/kg)combined with cannabis resin(5,10 and 20 mg/kg) subcutaneously daily for 6 weeks.Acetylcholinesterase(AChE) and butyrylcholinesterase(BChE) activities were measured in brain and serum.We also measured the activity of paraoxonase-1(PONl) in serum of rats treated with these agents.Results:(i) AChE activity in brain increased after 10-20 mg/kg cannabis resin(by 16.3%-36.5%).AChE activity in brain did not change after treatment with 5-20 mg/kg tramadol.The administration of both cannabis resin(5,10 or 20 mg/kg) and tramadol(10 mg/kg) resulted in decreased brain AChE activity by 14.1%,12.9%and 13.6%,respectively;(ii) BChE activity in serum was markedly and dose-dependenlly inhibited by cannabis resin(by 60.9%-76.9%).BChE activity also decreased by 17.6%-36.5%by 10-20mg/kg tramadol and by 57.2%-63.9%by the cannabis resin/tramadol combined treatment;(iii)Cannabis resin at dose of 20 mg/kg increased serum PONl activity by 25.7%.In contrast,tramadol given at 5,10 and 20 mg/kg resulted in a dose-dependent decrease in serum PON1 activity by 19%,36.7%,and 46.1%,respectively.Meanwhile,treatment with cannabis resin plus tramadol resulted in 40.2%,35.8%,30.7%inhibition of PONl activity compared to the saline group.Conclusions:these data suggest that cannabis resin exerts different effects on AChE and BChE activities which could contribute to the memory problems and the decline in cognitive function in chronic users.
文摘Introduction: Dementia is frequently associated with Parkinson’s disease, especially in later stages. Efficacy of cholinesterase inhibitors (ChI) in Alzheimer’s dementia is well established. However, treatment with ChI in Parkinson’s disease dementia (PDD) remains controversial. The objective of this systematic review and meta-analysis was to assess the effects of ChI in PDD. Methods: A comprehensive literature search was performed in MEDLINE, EMBASE and Cochrane library up to March 2014 using the descriptors “Parkinson’s disease”, “dementia in Parkinson’s disease”, “cognition”, “acetylcholinesterase inhibitors”, “cholinesterase inhibitors”, “anticholinesterase agents”, “rivastigmine”, “donepezil” and “galantamine” (Pubmed search strategy). All randomized, doubleblinded, placebo-controlled trials that met the eligibility criteria and assessed the effects of ChI in PDD were considered for analysis. There were no restrictions regarding paper language. Summary effect-sizes were presented as standardized mean differences (SMD) and the pooled analysis was performed with a fixed-effects model. Outcomes considered for analysis were the Mini Mental Status Exam (MMSE) score and the cognition scale for evaluation of dementia ADAS-Cog. The degree of heterogeneity between included studies was assessed through the I2 test. Results: After a comprehensive search, 175 references were retrieved. From these, five randomized trials involving 946PDD subjects were included in the review. Four studies used donepezil and only one study used rivastigmine. The pooled analysis of five studies that assessed the effects of ChI in MMSE total score showed a SMD of 0.24 (CI 95% 0.11 - 0.38). Three studies considered the effects of ChI on Adas-Cog and the pooled results showed a SMD of 0.21 (CI 95% 0.07 - 0.35). There was no significant heterogeneity between the studies. Conclusions: The results of this systematic review and meta- analysis suggest that ChI improves cognitive impairment in PDD subjects. Despite statistically significant, the translation of these results into relevant clinical improvement should be taken with caution, as the studies did not address what would be considered a clinically significant result.
文摘Cholinergic dysfunction is common to Alzheimer’s dementia and Schizophrenia. The objective of this study is to undertake a systematic review and meta-analysis of the literature on the cognitive and clinical effects of cholinesterase inhibitors administered to patients with schizophrenia and co-morbid Alzheimer’s disease dementia. A literature search of the MEDLINE, CINAHL, PubMed, PsycINFO, EMBASE, AMED, BNI, HMIC and Health Business Elite databases has been performed (up to January 2013) to investigate the use of cholinesterase inhibitors in patients with schizophrenia and dementia. The terms “schizophrenia”, “dementia”, “rivastigmine”, “donepezil”, “galantamine” and “cognitive deficit” have been searched, with a restriction for English language. Five published studies including 1 RCT have been included for the qualitative review. Treatments include Donepezil 5 mg and 10 mg as well as Rivastigmine 9 mg. The numbers of participants vary from 2 incase report to20 inthe RCT. Only 1 study qualifies for meta-analysis. There is a very limited evidence on the efficacy and safety of using acetylcholinesterase inhibitors in the management of dementia co-morbid with schizophrenia. The only randomised controlled study shows lack of evidence in terms of efficacy in using cholinesterase inhibitors in the management of dementia with schizophrenia. Future research projects will have to look at an adequate sample size to explore treatment on various cognitive and noncognitive domains and the sample should be selected by using definitive and internationally acceptable diagnostic criteria.
文摘Two novel naphthol derivatives（1 and 2） were synthesized and characterized via IR,~1H NMR,and HRMS.The structure of compound 2 was verified by single-crystal X-ray crystallography.It crystallizes in monoclinic,space group C2/c with a = 21.6725（9）,b = 6.0127（3）,c = 25.5405（14） A,β = 94.716（5）o,V = 3316.9（3） A^3,Z = 8,F（000） = 1384,D_c = 1.511 Mg/m^3,M_r = 377.22 and μ = 2.487 mm^-1.In addition,their cholinesterase inhibitory activities in vitro toward Electrophorus electricus acetylcholinesterase（eel ACh E） and horse serum butyrylcholinesterase（eq BCh E） were further determined.The results showed that compound 1 as a new acetylcholinesterase（ACh E） inhibitor displayed higher ACh E inhibitory activity（IC_（50） = 1.4 μM）,which could be considered for Alzheimer＇s disease therapeutics.
文摘<strong>Objective:</strong> To evaluate early prediction value of IPS<span> </span><span><span style="font-family:Verdana;">combined with SchE and D-dimer detection for infection and survival in critically ill patients. </span><b><span style="font-family:Verdana;">Methods:</span></b></span><b><span> </span></b><span style="font-family:Verdana;">199 critically ill patients admitted to the emergency intensive care unit (EICU) of our hospital from December 2018 to December 2019 were retrospectively analyzed, including 110 infection patients (infection group) and 89 non-infection</span><span> </span><span style="font-family:Verdana;">patients (non-infection group).</span><span> </span><span><span style="font-family:Verdana;">According to the survival, the infection group was divided into death group (68 cases) and survival group (42 cases). The IPS, APACHE II, SOFA and SchE, D-dimer expression levels were detected and compared;Univariate and logistic regression analysis were used to evaluate the independent prognostic factors. </span><b><span style="font-family:Verdana;">Results: </span></b><span style="font-family:Verdana;">The IPS and APACHE II of patients in the infected group were higher than those in the non-infected group, the level of SchE was lower than that in the non-infected group, and the level of D-dimer was higher than that in the non-infected group (</span><i><span style="font-family:Verdana;">P</span></i></span><i><span> </span></i><span style="font-family:Verdana;"><</span><span> </span><span style="font-family:Verdana;">0.001). IPS, SOFA, APACHE</span><span style="font-family:Verdana;"> II</span><span style="font-family:Verdana;">, SchE, D-dimer, invasive mechanical ventilation, septic shock, and ICU length</span><span style="font-family:Verdana;"> of stay had significant influence on the prognosis of critically ill patients</span><span> </span><span><span style="font-family:Verdana;">(</span><i><span style="font-family:Verdana;">P</span></i></span><i><span> </span></i><span style="font-family:Verdana;"><</span><span> </span><span><span style="font-family:Verdana;">0.001). Logistic regression analysis showed that IPS (</span><i><span style="font-family:Verdana;">OR</span></i><span style="font-family:Verdana;"> = 2.821, </span><span><span style="font-family:Verdana;">95%</span><i><span style="font-family:Verdana;"> CI</span></i></span><span style="font-family:Verdana;"> 1.501</span></span><span style="font-family:Verdana;"> - </span><span><span style="font-family:Verdana;">5.227), SOFA (</span><i><span style="font-family:Verdana;">OR</span></i><span style="font-family:Verdana;"> = 5.078, </span><span><span style="font-family:Verdana;">95% </span><i><span style="font-family:Verdana;">CI</span></i></span><span style="font-family:Verdana;"> 3.327 </span></span><span style="font-family:Verdana;">-</span><span><span style="font-family:Verdana;"> 7.690), APACHE II (</span><i><span style="font-family:Verdana;">OR</span></i><span style="font-family:Verdana;"> = 14.308, </span><span><span style="font-family:Verdana;">95% </span><i><span style="font-family:Verdana;">CI</span></i></span><span style="font-family:Verdana;"> 8.901 </span></span><span style="font-family:Verdana;">-</span><span><span style="font-family:Verdana;"> 21.893), SchE (</span><i><span style="font-family:Verdana;">OR</span></i><span style="font-family:Verdana;"> = 0.223, </span><span><span style="font-family:Verdana;">95%</span><i><span style="font-family:Verdana;"> CI</span></i></span><span style="font-family:Verdana;"> 0.165 </span></span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;"> 0.291), D-dimer</span><span style="font-family:Verdana;"> (</span><i><span style="font-family:Verdana;">OR</span></i><i><span> </span></i><span style="font-family:Verdana;">=</span><span> </span><span style="font-family:Verdana;">2.10</span><span style="font-family:Verdana;">, </span><span style="font-family:Verdana;">95%</span><i><span> </span></i><i><span style="font-family:Verdana;">CI</span></i><i><span> </span></i><span style="font-family:Verdana;">1.55</span><span style="font-family:Verdana;"> - </span><span style="font-family:Verdana;">2.85</span><span style="font-family:Verdana;">)</span><span><span style="font-family:Verdana;">, septic shock (</span><i><span style="font-family:Verdana;">OR</span></i><span style="font-family:Verdana;"> = 9.948,</span></span><span> </span><span style="font-family:Verdana;">95%</span><span> </span><i><span style="font-family:Verdana;">CI</span></i><span style="font-family:Verdana;"> 7.012</span><span style="font-family:Verdana;"> - </span><span style="font-family:Verdana;">17.012)</span><span> </span><span style="font-family:Verdana;">were independent factors affecting the prognosis of critically ill patients with infection</span><span style="font-family:Verdana;"> (</span><i><span style="font-family:Verdana;">P</span></i><span> </span><span style="font-family:Verdana;"><</span><span> </span><span style="font-family:Verdana;">0.001</span><span style="font-family:Verdana;">)</span><span style="font-family:Verdana;">.</span><span> </span><b><span style="font-family:Verdana;">Conclusion:</span></b><b><span> </span></b><span style="font-family:Verdana;">IPS and D-dimer expression level in infected patients were increased and SchE decreased significantly compared with those in non-infected patients, and they significantly correlated with</span><span> </span><span style="font-family:Verdana;">disease severity of infected</span><span> </span><span style="font-family:Verdana;">patients</span><span> </span><span style="font-family:Verdana;">and could be early prediction</span><span> </span><span style="font-family:Verdana;">for prognosis.</span>
文摘Objective: To study the changes of serum pancreatic stone protein (PSP) and cholinesterase (ChE) contents in children with sepsis and their correlation with systemic inflammatory response and target organ damage. Methods: A total of 64 children with sepsis who were treated in the hospital between January 2015 and January 2017 were selected as observation group, and 50 healthy children who received vaccination in the hospital during the same period were selected as normal control group. The contents of PSP, ChE, inflammatory factors as well as liver and kidney function indexes in the two groups were detected. Pearson test was used to assess the correlation of serum PSP and ChE contents with systemic inflammatory response and target organ damage in children with sepsis. Results: Serum PSP content of observation group was higher than that of control group while ChE content was lower than that of control group;serum inflammatory factors PCT, CRP, IL-1, IL-6 and IL-10 contents of observation group were higher than those of normal control group;liver function indexes TBIL, ALT and AST contents were higher than those of normal control group;kidney function indexes Scr and BUN contents were higher than those of normal control group. Pearson test showed that the serum PSP and ChE contents in children with sepsis were directly correlated with the systemic inflammatory response as well as liver and renal function injury. Conclusion: Serum PSP content significantly increases while ChE content significantly decreases in children with sepsis and the specific change is directly correlated with the overall disease severity.
文摘Objective:To investigate effects of hemoperfusion and hemofiltration combination on treating patients with acute organophosphours pesticide poisoning (AOPP) and influence of it on cholinesterase, dopamine and inflammatory factors.Methods:A total of 82 cases of AOPP patients treated in our hospital from Sep 2012 to Jul 2016 were selected as subjects. They were randomly divided to be the observation group and the control group, 41 cases for each. For patients in observation group, combined therapy of hemoperfusion (HP) and hemofiltration (HF) were provided. For patients in control group, combined therapy of HP and hemodialysis (HD) were provided. Effects on the two groups of patients were compared. Meanwhile, cholinesterase, dopamine and inflammatory factors levels in different times before and after treatment were compared.Results:Consciousness improvement times and hospitalization times in observation group were significantly lower than in control group. No significant difference showed on fatality rates between the two groups. Before treatment, no significant difference showed on CHE and DE levels between two groups of patients;6 h and 12 h after treatment, CHE average levels in two groups were significantly higher than before treatment in the same group, and levels in observation group at the same phase were significantly higher than in control group;6 h and 12 h after treatment, DA levels in observation group were significantly lower than the same group before treatment, and significantly lower than control group, while 12 h after treatment, DA levels in control group were significantly lower than the same group before treatment. Before treatment, no significant difference showed on serum TGF-β1, TNF-α, IL-6, IL-8 between two groups of patients. After treatment, each index levels in two groups were significantly lower than the same group before treatment, and levels in observation group at the same phase were significantly lower than control group. Conclusion:Effects of blood purification therapy on treating AOPP were worth approving, but effects of HP and HF combined therapy were more significant. In addition, improvement of HP+HF on CHE, DA and inflammatory factors were better than HP+HD.
