Liu Q

References (128)

Title : Santacruzamate A Alleviates Pain and Pain-Related Adverse Emotions through the Inhibition of Microglial Activation in the Anterior Cingulate Cortex - Qin_2024_ACS.Pharmacol.Transl.Sci_7_1002
Author(s) : Qin Y , Liu Q , Wang S , Wang Q , Du Y , Yao J , Chen Y , Yang Q , Wu Y , Liu S , Zhao M , Wei G , Yang L
Ref : ACS Pharmacol Transl Sci , 7 :1002 , 2024
Abstract : Chronic pain is a complex disease. It seriously affects patients' quality of life and imposes a significant economic burden on society. Santacruzamate A (SCA) is a natural product isolated from marine cyanobacteria in Panama. In this study, we first demonstrated that SCA could alleviate chronic inflammatory pain, pain-related anxiety, and depression emotions induced by complete Freund's adjuvant in mice while inhibiting microglial activation in the anterior cingulate cortex. Moreover, SCA treatment attenuated lipopolysaccharide (LPS)-induced inflammatory response by downregulating interleukin 1beta and 6 (IL-1beta and IL-6) and tumor necrosis factor-alpha (TNF-alpha) levels in BV2 cells. Furthermore, we found that SCA could bind to soluble epoxide hydrolase (sEH) through molecular docking technology, and the thermal stability of sEH was enhanced after binding of SCA to the sEH protein. Meanwhile, we identified that SCA could reduce the sEH enzyme activity and inhibit sEH protein overexpression in the LPS stimulation model. The results indicated that SCA could alleviate the development of inflammation by inhibiting the enzyme activity and expression of sEH to further reduce chronic inflammatory pain. Our study suggested that SCA could be a potential drug for treating chronic inflammatory pain.
ESTHER : Qin_2024_ACS.Pharmacol.Transl.Sci_7_1002
PubMedSearch : Qin_2024_ACS.Pharmacol.Transl.Sci_7_1002
PubMedID: 38633586

Title : Two Fluorescent Probes for Recognition of Acetylcholinesterase: Design, Synthesis, and Comparative Evaluation - Lin_2024_Molecules_29_
Author(s) : Lin X , Yi Q , Qing B , Lan W , Jiang F , Lai Z , Huang J , Liu Q , Jiang J , Wang M , Zou L , Huang X , Wang J
Ref : Molecules , 29 : , 2024
Abstract : In this study, two "on-off" probes (BF(2)-cur-Ben and BF(2)-cur-But) recognizing acetylcholinesterase (AChE) were designed and synthesized. The obtained probes can achieve recognition of AChE with good selectivity and pH-independence with a linear range of 0.5~7 U/mL and 0.5~25 U/mL respectively. BF(2)-cur-Ben has a lower limit of detection (LOD) (0.031 U/mL), higher enzyme affinity (K(m) = 16 +/- 1.6 microM), and higher inhibitor sensitivity. A responsive mechanism of the probes for AChE was proposed based on HPLC and mass spectra (MS) experiments, as well as calculations. In molecular simulation, BF(2)-cur-Ben forms more hydrogen bonds (seven, while BF(2)-cur-But has only four) and thus has a more stable enzyme affinity, which is mirrored by the results of the comparison of K(m) values. These two probes could enable recognition of intracellular AChE and probe BF(2)-cur-Ben has superior cell membrane penetration due to its higher log p value. These probes can monitor the overexpression of AChE during apoptosis of lung cancer cells. The ability of BF(2)-cur-Ben to monitor AChE in vivo was confirmed by a zebrafish experiment.
ESTHER : Lin_2024_Molecules_29_
PubMedSearch : Lin_2024_Molecules_29_
PubMedID: 38731452

Title : Carboxylesterase-activated near-infrared fluorescence probe for highly sensitive imaging of liver tumors - Jiang_2024_J.Mater.Chem.B__
Author(s) : Jiang R , Xia Y , Liu Q , Zhang H , Yang X , He L , Cheng D
Ref : J Mater Chem B , : , 2024
Abstract : Carboxylesterases (CESs) are critical for metabolizing ester-containing biomolecules and are specifically important in liver metabolic disorders. The modulation of CESs is also an important issue in pharmacology and clinical applications. Herein, we present a near-infrared (NIR) CES fluorescent probe (NCES) based on the protection-deprotection of the hydroxyl group for monitoring CES levels in living systems. The NCES probe has good selectivity and sensitivity for CESs with a limit of detection (LOD) of 5.24 mU mL(-1), which allows for tracing the fluctuation of cellular CES after treatment with anticancer drugs and under inflammation and apoptosis states. Furthermore, NCES can be successfully applied for guiding liver cancer surgery with high-contrast in vivo imaging and detecting clinical serum samples from liver cancer patients. This work showed that the NCES probe has great potential in drug development, imaging applications for medical diagnosis, and early-stage detection for clinical liver diseases.
ESTHER : Jiang_2024_J.Mater.Chem.B__
PubMedSearch : Jiang_2024_J.Mater.Chem.B__
PubMedID: 38251432

Title : Combination of omics, bioinformatics, molecular docking, and experimental validation to elucidate the hepatoprotective effects, mechanisms, and active compounds of Shandougen - Zhang_2024_Biomed.Chromatogr__e5887
Author(s) : Zhang SN , Liu Q , Li XZ
Ref : Biomedical Chromatography , :e5887 , 2024
Abstract : Omics, bioinformatics, molecular docking, and experimental validation were used to elucidate the hepatoprotective effects, mechanisms, and active compounds of Shandougen (SDG) based on the biolabel-led research pattern. Integrated omics were used to explore the biolabels of SDG intervention in liver tissue. Subsequently, bioinformatics and molecular docking were applied to topologically analyze its therapeutic effects, mechanisms, and active compounds based on biolabels. Finally, an animal model was used to verify the biolabel analysis results. Omics, bioinformatics, and molecular docking revealed that SDG may exert therapeutic effects on liver diseases in the multicompound and multitarget synergistic modes, especially liver cirrhosis. In the validation experiment, SDG and its active compounds (betulinic acid and gallic acid) significantly improved the liver histopathological damage in the CCl(4)-induced liver cirrhosis model. Meanwhile, they also produced significant inhibitory effects on the focal adhesion pathway (integrin alpha-1, myosin regulatory light chain 2, laminin subunit gamma-1, etc.) and alleviated the associated pathological processes: focal adhesion (focal adhesion kinase 1)-extracellular matrix (collagen alpha-1(IV) chain, collagen alpha-1(VI) chain, and collagen alpha-2(VI) chain) dysfunction, carcinogenesis (alpha-fetoprotein, NH(3), and acetylcholinesterase), inflammation (tumor necrosis factor alpha, interleukin-1 [IL-1], IL-6, and IL-10), and oxidative stress (reactive oxygen species, malonaldehyde, and superoxide dismutase). This study provides new evidence and insights for the hepatoprotective effects, mechanisms, and active compounds of SDG.
ESTHER : Zhang_2024_Biomed.Chromatogr__e5887
PubMedSearch : Zhang_2024_Biomed.Chromatogr__e5887
PubMedID: 38751131

Title : Adipose triglyceride lipase suppresses noncanonical inflammasome by hydrolyzing LPS - Li_2024_Nat.Chem.Biol__
Author(s) : Li W , Liu Q , Qian Y , Wang C , Kong C , Sun L , Liu H , Zhang Y , Jiang D , Jiang C , Wang S , Xia P
Ref : Nat Chemical Biology , : , 2024
Abstract : Intracellular recognition of lipopolysaccharide (LPS) by mouse caspase-11 or human caspase-4 is a vital event for the activation of the noncanonical inflammasome. Whether negative regulators are involved in intracellular LPS sensing is still elusive. Here we show that adipose triglyceride lipase (ATGL) is a negative regulator of the noncanonical inflammasome. Through screening for genes participating in the noncanonical inflammasome, ATGL is identified as a negative player for intracellular LPS signaling. ATGL binds LPS and catalyzes the removal of the acylated side chains that contain ester bonds. LPS with under-acylated side chains no longer activates the inflammatory caspases. Cells with ATGL deficiency exhibit enhanced immune responses when encountering intracellular LPS, including an elevated secretion of interleukin-1beta, decreased cell viability and increased cell cytotoxicity. Moreover, ATGL-deficient mice show exacerbated responses to endotoxin challenges. Our results uncover that ATGL degrades cytosolic LPS to suppress noncanonical inflammasome activation.
ESTHER : Li_2024_Nat.Chem.Biol__
PubMedSearch : Li_2024_Nat.Chem.Biol__
PubMedID: 38413746

Title : Didepside Formation by the Nonreducing Polyketide Synthase Preu6 of Preussia isomera Requires Interaction of Starter Acyl Transferase and Thioesterase Domains - Liu_2023_Angew.Chem.Int.Ed.Engl_62_e202214379
Author(s) : Liu Q , Zhang D , Gao S , Cai X , Yao M , Xu Y , Gong Y , Zheng K , Mao Y , Yang L , Yang D , Molnar I , Yang X
Ref : Angew Chem Int Ed Engl , 62 :e202214379 , 2023
Abstract : Orsellinic acid (OA) derivatives are produced by filamentous fungi using nonreducing polyketide synthases (nrPKSs). The chain-releasing thioesterase (TE) domains of such nrPKSs were proposed to also catalyze dimerization to yield didepsides, such as lecanoric acid. Here, we use combinatorial domain exchanges, domain dissections and reconstitutions to reveal that the TE domain of the lecanoric acid synthase Preu6 of Preussia isomera must collaborate with the starter acyl transferase (SAT) domain from the same nrPKS. We show that artificial SAT-TE fusion proteins are highly effective catalysts and reprogram the ketide homologation chassis to form didepsides. We also demonstrate that dissected SAT and TE domains of Preu6 physically interact, and SAT and TE domains of OA-synthesizing nrPKSs may co-evolve. Our work highlights an unexpected domain-domain interaction in nrPKSs that must be considered for the combinatorial biosynthesis of unnatural didepsides, depsidones, and diphenyl ethers.
ESTHER : Liu_2023_Angew.Chem.Int.Ed.Engl_62_e202214379
PubMedSearch : Liu_2023_Angew.Chem.Int.Ed.Engl_62_e202214379
PubMedID: 36484777
Gene_locus related to this paper: preis-preu6

Title : The GPIHBP1-LPL complex and its role in plasma triglyceride metabolism: Insights into chylomicronemia - Jiang_2023_Biomed.Pharmacother_169_115874
Author(s) : Jiang S , Ren Z , Yang Y , Liu Q , Zhou S , Xiao Y
Ref : Biomed Pharmacother , 169 :115874 , 2023
Abstract : GPIHBP1 is a protein found in the endothelial cells of capillaries that is anchored by glycosylphosphatidylinositol and binds to high-density lipoproteins. GPIHBP1 attaches to lipoprotein lipase (LPL), subsequently carrying the enzyme and anchoring it to the capillary lumen. Enabling lipid metabolism is essential for the marginalization of lipoproteins alongside capillaries. Studies underscore the significance of GPIHBP1 in transporting, stabilizing, and aiding in the marginalization of LPL. The intricate interplay between GPIHBP1 and LPL has provided novel insights into chylomicronemia in recent years. Mutations hindering the formation or reducing the efficiency of the GPIHBP1-LPL complex are central to the onset of chylomicronemia. This review delves into the structural nuances of the GPIHBP1-LPL interaction, the consequences of mutations in the complex leading to chylomicronemia, and cutting-edge advancements in chylomicronemia treatment.
ESTHER : Jiang_2023_Biomed.Pharmacother_169_115874
PubMedSearch : Jiang_2023_Biomed.Pharmacother_169_115874
PubMedID: 37951027

Title : Transcriptomics and Selection Pressure Analysis Reveals the Influence Mechanism of PLIN1 Protein on the Development of Small Size in Min Pigs - Liu_2023_Int.J.Mol.Sci_24_
Author(s) : Liu Q , Yu L , Zhang Z , Chang Y , Liu Z , Xu C
Ref : Int J Mol Sci , 24 : , 2023
Abstract : Body size is an important biological phenotypic trait that has attracted substantial attention. Small domestic pigs can serve as excellent animal models for biomedicine and also help meet sacrificial culture needs in human societies. Although the mechanisms underlying vertebral development regulating body size variation in domestic pigs during the embryonic period have been well described, few studies have examined the genetic basis of body size variation in post embryonic developmental stages. In this study, seven candidate genes-PLIN1, LIPE, PNPLA1, SCD, FABP5, KRT10 and IVL-significantly associated with body size were identified in Min pigs, on the basis of weighted gene co-expression network analysis (WGCNA), and most of their functions were found to be associated with lipid deposition. Six candidate genes except for IVL were found to have been subjected to purifying selection. PLIN1 had the lowest omega value (0.139) and showed heterogeneous selective pressure among domestic pig lineages with different body sizes (p < 0.05). These results suggested that PLIN1 is an important genetic factor regulating lipid deposition and consequently affecting body size variation in pigs. The culture of whole pig sacrifice in Manchu during the Qing Dynasty in China might have contributed to the strong artificial domestication and selection of Hebao pigs.
ESTHER : Liu_2023_Int.J.Mol.Sci_24_
PubMedSearch : Liu_2023_Int.J.Mol.Sci_24_
PubMedID: 36835359

Title : Plants of the genus Mahonia as a Potential Traditional Chinese Medicine for the Prevention and Treatment of Alzheimer's Disease - Yang_2023_Curr.Top.Med.Chem__
Author(s) : Yang S , Shao H , Chen X , Liu Q , Huang S , Huang Y
Ref : Curr Top Med Chem , : , 2023
Abstract : Alzheimer's disease (AD), a prevalent multiple neurodegenerative disease, has gained attention, particularly in the aging population. However, presently available therapies merely focus on alleviating the symptoms of AD and fail to slow disease progression significantly. Traditional Chinese medicine (TCM) has been used to ameliorate symptoms or interfere with the pathogenesis of aging-associated diseases for many years based on disease-modifying in multiple pathological roles with multi-targets, multi-systems and multi-aspects. Mahonia species as a TCM present potential for anti-inflammatory activity, antioxidant activity, anti-acetylcholinesterase activity, and anti-amyloid-beta activity that was briefly discussed in this review. They are regarded as promising drug candidates for AD therapy. The findings in this review support the use of Mahonia species as an alternative therapy source for treating AD.
ESTHER : Yang_2023_Curr.Top.Med.Chem__
PubMedSearch : Yang_2023_Curr.Top.Med.Chem__
PubMedID: 37005525

Title : Serum alkaline phosphatase was independently associated with depression in patients with cerebrovascular disease - Tao_2023_Front.Psychiatry_14_1184673
Author(s) : Tao X , Yang C , He J , Liu Q , Wu S , Tang W , Wang J
Ref : Front Psychiatry , 14 :1184673 , 2023
Abstract : BACKGROUND AND PURPOSE: Blood markers have important value in the diagnosis of depressive disorders. Serum alkaline phosphatase (ALP) not only predicts stroke recurrence and poor functional prognosis in cerebrovascular disease (CVD) patients but also increases significantly in middle-aged women with depression. Thus, it has not been reported whether serum ALP is associated with the development of depression and/or vascular depression (VDe) in CVD patients. METHODS: This was a cross-sectional study of 353 CVD patients (stroke patients, n = 291; cerebral small vessel disease (CSVD) patients, n = 62). Baseline demographic information, fasting blood markers (such as blood counts, liver function, kidney function and lipids), and brain CT/MRI scans were collected. CVD patients were divided into non-depression, suspected vascular depression (SVD), and positive vascular depression (PVD) groups according to their Hamilton Rating Scale for Depression (HAMD) scores. Univariate analysis of baseline data, blood markers, and the prevalence of lesions (> 1.5 cm) was performed. Subsequently, the diagnostic performance of the univariate and combined variables for SVD and PVD was analyzed using binary logistic regression. The diagnostic value of the multivariate model for VDe was analyzed by ordinal logistic regression. RESULTS: (1) Serum ALP (p = 0.003) and hypersensitive C-reactive protein (hs-CRP, p = 0.001) concentrations increased as HAMD scores increased, and the prevalence of brain atrophy (p = 0.016) and lesions in the basal ganglia (p = 0.001) and parietal (p = 0.001), temporal (p = 0.002), and frontal lobes (p = 0.003) also increased, whereas the concentrations of hemoglobin (Hb, p = 0.003), cholinesterase (ChE, p = 0.001), and high-density lipoprotein cholesterol (HDL-C, p = 0.005) declined. Among these variables, hs-CRP (r = 0.218, p < 0.001) had a weak positively association with HAMD scores, and ChE (r = -0.226, p < 0.001) had a weak negative association. (2) The combination of Hb, hs-CRP, ChE, ALP, and HDL-C improved diagnostic performance for VDe [AUC = 0.775, 95% CI (0.706, 0.844), p < 0.001]. (3) Hb (OR = 0.986, p = 0.049), ChE (OR = 0.999, p = 0.020), ALP (OR = 1.017, p = 0.003), and basal ganglia lesions (OR = 2.197, p < 0.001) were important factors impacting VDe development. After adjusting for Hb, hs-CRP, ChE, HDL-C, lesions in the above mentioned four locations, sex, age and the prevalence of CSVD and brain atrophy, ALP [OR = 1.016, 95% CI (1.005, 1.027), p = 0.004] was independently associated with VDe. CONCLUSION: Hb, hs-CRP, ChE, ALP, and HDL-C concentrations are potential blood markers of depression in CVD patients and, when combined, may improve diagnostic performance for VDe. Serum ALP was independently associated with VDe in patients with CVD.
ESTHER : Tao_2023_Front.Psychiatry_14_1184673
PubMedSearch : Tao_2023_Front.Psychiatry_14_1184673
PubMedID: 37469359

Title : Serum Cholinesterase, C-reactive Protein, Interleukin 6, and Procalcitonin Levels as Predictors of Mortality in Patients in the Intensive Care Unit - Liu_2023_Turk.J.Anaesthesiol.Reanim_51_408
Author(s) : Liu Q , Fan X , Cui W , Wang X , Zhang Z , Wang N , Qiao L
Ref : Turk J Anaesthesiol Reanim , 51 :408 , 2023
Abstract : OBJECTIVE: The prognostic utility of inflammatory markers in survival has been suggested in patients with cancer; however, evidence on their prognostic value in severely ill patients is very limited. We aimed to explore the prognostic value of cholinesterase (ChE), C-reactive protein (CRP), interleukin-6 (IL-6), and procalcitonin (PCT) in predicting mortality in patients from the intensive care unit (ICU). METHODS: Serum levels of ChE, CRP, IL-6 and PCT were measured in ICU patients from December 13(th), 2019 to June 28(th), 2022. We assessed the predictive power of ChE, CRP, IL-6, and PCT using the receiver operating characteristic (ROC) curves. Furthermore, we evaluated their diagnostic accuracy by comparing the areas under the ROC curve (AUCs) along with their corresponding 95% confidence intervals (CIs). The cut-off values were determined to dichotomise these biomarkers, which were then included in multivariable logistic regression models to examine their relationship with ICU mortality. RESULTS: Among 253 ICU patients included in the study, 66 (26%) died during the ICU stay. The AUCs to predict ICU mortality were 0.643 (95% CI, 0.566-0.719), 0.648 (95% CI, 0.633-0.735), 0.643 (95% CI, 0.563-0.723) and 0.735 (95% CI, 0.664-0.807) for ChE, CRP, IL-6 and PCT, respectively. After adjusting for age, sex and disease severity, lower ChE level (<3.668 x 10(3) U L(-1)) and higher levels of CRP (>10.546 mg dL(-1)), IL-6 (>986.245 pg mL(-1)) and PCT (>0.505 microg L(-1)) were associated with higher mortality risk, with odd ratios of 2.70 (95% CI, 1.32-5.54), 4.99 (95% CI, 2.41-10.38), 3.24 (95% CI, 1.54-6.78) and 3.67 (95% CI, 1.45-9.95), respectively. CONCLUSION: ChE, CRP, IL-6 and PCT were independent ICU mortality risk factors in severely ill patients. Elevated PCT levels exhibited better predictive value than the other three biomarkers that were evaluated.
ESTHER : Liu_2023_Turk.J.Anaesthesiol.Reanim_51_408
PubMedSearch : Liu_2023_Turk.J.Anaesthesiol.Reanim_51_408
PubMedID: 37876167

Title : Genetic association of lipids and lipid-lowering drug target genes with non-alcoholic fatty liver disease - Li_2023_EBioMedicine_90_104543
Author(s) : Li Z , Zhang B , Liu Q , Tao Z , Ding L , Guo B , Zhang E , Zhang H , Meng Z , Guo S , Chen Y , Peng J , Li J , Wang C , Huang Y , Xu H , Wu Y
Ref : EBioMedicine , 90 :104543 , 2023
Abstract : BACKGROUND: Some observational studies found that dyslipidaemia is a risk factor for non-alcoholic fatty liver disease (NAFLD), and lipid-lowering drugs may lower NAFLD risk. However, it remains unclear whether dyslipidaemia is causative for NAFLD. This Mendelian randomisation (MR) study aimed to explore the causal role of lipid traits in NAFLD and evaluate the potential effect of lipid-lowering drug targets on NAFLD. METHODS: Genetic variants associated with lipid traits and variants of genes encoding lipid-lowering drug targets were extracted from the Global Lipids Genetics Consortium genome-wide association study (GWAS). Summary statistics for NAFLD were obtained from two independent GWAS datasets. Lipid-lowering drug targets that reached significance were further tested using expression quantitative trait loci data in relevant tissues. Colocalisation and mediation analyses were performed to validate the robustness of the results and explore potential mediators. FINDINGS: No significant effect of lipid traits and eight lipid-lowering drug targets on NAFLD risk was found. Genetic mimicry of lipoprotein lipase (LPL) enhancement was associated with lower NAFLD risks in two independent datasets (OR(1) = 0.60 [95% CI 0.50-0.72], p(1) = 2.07 x 10(-8); OR(2) = 0.57 [95% CI 0.39-0.82], p(2) = 3.00 x 10(-3)). A significant MR association (OR = 0.71 [95% CI, 0.58-0.87], p = 1.20 x 10(-3)) and strong colocalisation association (PP.H(4) = 0.85) with NAFLD were observed for LPL expression in subcutaneous adipose tissue. Fasting insulin and type 2 diabetes mediated 7.40% and 9.15%, respectively, of the total effect of LPL on NAFLD risk. INTERPRETATION: Our findings do not support dyslipidaemia as a causal factor for NAFLD. Among nine lipid-lowering drug targets, LPL is a promising candidate drug target in NAFLD. The mechanism of action of LPL in NAFLD may be independent of its lipid-lowering effects. FUNDING: Capital's Funds for Health Improvement and Research (2022-4-4037). CAMS Innovation Fund for Medical Sciences (CIFMS, grant number: 2021-I2M-C&T-A-010).
ESTHER : Li_2023_EBioMedicine_90_104543
PubMedSearch : Li_2023_EBioMedicine_90_104543
PubMedID: 37002989

Title : Personalised treatment for cognitive impairment in dementia: development and validation of an artificial intelligence model - Liu_2022_BMC.Med_20_45
Author(s) : Liu Q , Vaci N , Koychev I , Kormilitzin A , Li Z , Cipriani A , Nevado-Holgado A
Ref : BMC Med , 20 :45 , 2022
Abstract : BACKGROUND: Donepezil, galantamine, rivastigmine and memantine are potentially effective interventions for cognitive impairment in dementia, but the use of these drugs has not been personalised to individual patients yet. We examined whether artificial intelligence-based recommendations can identify the best treatment using routinely collected patient-level information. METHODS: Six thousand eight hundred four patients aged 59-102 years with a diagnosis of dementia from two National Health Service (NHS) Foundation Trusts in the UK were used for model training/internal validation and external validation, respectively. A personalised prescription model based on the Recurrent Neural Network machine learning architecture was developed to predict the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores post-drug initiation. The drug that resulted in the smallest decline in cognitive scores between prescription and the next visit was selected as the treatment of choice. Change of cognitive scores up to 2 years after treatment initiation was compared for model evaluation. RESULTS: Overall, 1343 patients with MMSE scores were identified for internal validation and 285 [21.22%] took the drug recommended. After 2 years, the reduction of mean [standard deviation] MMSE score in this group was significantly smaller than the remaining 1058 [78.78%] patients (0.60 [0.26] vs 2.80 [0.28]; P = 0.02). In the external validation cohort (N = 1772), 222 [12.53%] patients took the drug recommended and reported a smaller MMSE reduction compared to the 1550 [87.47%] patients who did not (1.01 [0.49] vs 4.23 [0.60]; P = 0.01). A similar performance gap was seen when testing the model on patients prescribed with AChEIs only. CONCLUSIONS: It was possible to identify the most effective drug for the real-world treatment of cognitive impairment in dementia at an individual patient level. Routine care patients whose prescribed medications were the best fit according to the model had better cognitive performance after 2 years.
ESTHER : Liu_2022_BMC.Med_20_45
PubMedSearch : Liu_2022_BMC.Med_20_45
PubMedID: 35101059

Title : The Chemical Composition Characteristics and Health Risk Assessment of Cooking Fume Condensates from Residential Kitchens in Different Regions of China - Liu_2022_Foods_12_
Author(s) : Liu Q , Zhang X , Yang Y , Tang Q , Zheng L , Lou H , Chen H , Yang Q
Ref : Foods , 12 : , 2022
Abstract : The aim of this study was to explore the similarities and differences of volatile organic pollutants (VOCs) in cooking fumes (COF) of residential buildings in different regions of China, as well as to evaluate their potential health risks. COF condensates were collected from 10 representative cities in China and analyzed by a GC-MS method. Their effects on alpha-glucosidase, acetylcholinesterase (AchE), and lactate dehydrogenase (LDH) activities were then detected to evaluate potential health risks. A total of 174 kinds of VOCs, including aldehydes, esters, hydrocarbons, alcohols, and carboxylic acid, were identified. There were 59 identical compounds in the northern and southern regions, and 56 common compounds in spicy and non-spicy regions. Health risk assessment results showed that COF condensate could inhibit the activity of alpha-glucosidase to varying degrees (61.73-129.25%), suggesting that it had a potential risk of causing hypoglycemia. Daily and 3 and 6 month intakes of COF in minors, adults, and the elderly had both activated and inhibited effects on AchE. The activated effect in the southern and spicy areas was higher than that in northern and non-spicy areas, revealing that different regions and dietary habits had different effects on the risk of neurological diseases caused by changes in AchE activity. For minors, adults, and the elderly, COF had different degrees of activation of LDH at different exposure times and regions. Activation in the northern and non-spicy areas was higher than that in southern and spicy areas, suggesting that the health risks caused by changes in LDH activity levels were significantly increased.
ESTHER : Liu_2022_Foods_12_
PubMedSearch : Liu_2022_Foods_12_
PubMedID: 36613322

Title : FumDSB can alleviate the inflammatory response induced by fumonisin B(1) in growing pigs - Liu_2022_Food.Addit.Contam.Part.A.Chem.Anal.Control.Expo.Risk.Assess__
Author(s) : Liu Q , Huang L , Cui Z , Qiao B , Li F , Wang C
Ref : Food Additives & Contaminants Part A Chem Anal Control Expo Risk Assess , :1 , 2022
Abstract : Fumonisin B(1) (FB(1)) has the highest natural contamination rate among all fumonisin analogs and can inhibit food intake and weight gain of pigs. Under laboratory conditions, carboxylesterase FumDSB has a high FB(1) degradation rate and excellent pH and thermal stability. The present study sought to estimate the effects of FumDSB on growing pigs from the perspective of a brain-intestinal axis. Twenty-four growing pigs of similar weight were divided into Control, FB(1) (5mg FB(1)/kg feed), and FumDSB (5mg FB(1)/kg and 0.1% FumDSB in the feed) groups. After 42 days of feeding, hypothalamus and jejunum samples were collected for quantitative real-time fluorescence, western blotting, and immunohistochemistry. The results showed that FB(1) consumption can destruct the tissue structure of hypothalamus and jejunum, affect the expression and distribution of several appetite-related neuropeptides and inflammatory cytokines, thereby inducing neuroinflammatory responses and affecting food intake and weight gain. However, these anorexia effects and inflammatory responses are alleviated when FumDSB is added to the feed. In short, FumDSB can alleviate the inflammatory response induced by FB(1) in growing pigs.
ESTHER : Liu_2022_Food.Addit.Contam.Part.A.Chem.Anal.Control.Expo.Risk.Assess__
PubMedSearch : Liu_2022_Food.Addit.Contam.Part.A.Chem.Anal.Control.Expo.Risk.Assess__
PubMedID: 35858108
Gene_locus related to this paper: sphmc-FumD , 9sphn-a0a101vlk1

Title : Cloning and Functional Characterization of the Polyketide Synthases Based on Genome Mining of Preussia isomera XL-1326 - Liu_2022_Front.Microbiol_13_819086
Author(s) : Liu Q , Zhang D , Xu Y , Gao S , Gong Y , Cai X , Yao M , Yang X
Ref : Front Microbiol , 13 :819086 , 2022
Abstract : Fungal polyketides (PKs) are one of the largest families of structurally diverse bioactive natural products biosynthesized by multidomain megasynthases, in which thioesterase (TE) domains act as nonequivalent decision gates determining both the shape and the yield of the polyketide intermediate. The endophytic fungus Preussia isomera XL-1326 was discovered to have an excellent capacity for secreting diverse bioactive PKs, i.e., the hot enantiomers (+/-)-preuisolactone A with antibacterial activity, the single-spiro minimoidione B with alpha-glucosidase inhibition activity, and the uncommon heptaketide setosol with antifungal activity, which drive us to illustrate how the unique PKs are biosynthesized. In this study, we first reported the genome sequence information of P. isomera. Based on genome mining, we discovered nine transcriptionally active genes encoding polyketide synthases (PKSs), Preu1-Preu9, of which those of Preu3, Preu4, and Preu6 were cloned and functionally characterized due to possessing complete sets of synthetic and release domains. Through heterologous expression in Saccharomyces cerevisiae, Preu3 and Preu6 could release high yields of orsellinic acid (OA) derivatives [3-methylorsellinic acid (3-MOA) and lecanoric acid, respectively]. Correspondingly, we found that Preu3 and Preu6 were clustered into OA derivative synthase groups by phylogenetic analysis. Next, with TE domain swapping, we constructed a novel "non-native" PKS, Preu6-TE(Preu3), which shared a very low identity with OA synthase, OrsA, from Aspergillus nidulans but could produce a large amount of OA. In addition, with the use of Preu6-TE(Preu3), we synthesized methyl 3-methylorsellinate (synthetic oak moss of great economic value) from 3-MOA as the substrate, and interestingly, 3-MOA exhibited remarkable antibacterial activities, while methyl 3-methylorsellinate displayed broad-spectrum antifungal activity. Taken together, we identified two novel PKSs to biosynthesize 3-MOA and lecanoric acid, respectively, with information on such kinds of PKSs rarely reported, and constructed one novel "non-native" PKS to largely biosynthesize OA. This work is our first step to explore the biosynthesis of the PKs in P. isomera, and it also provides a new platform for high-level environment-friendly production of OA derivatives and the development of new antimicrobial agents.
ESTHER : Liu_2022_Front.Microbiol_13_819086
PubMedSearch : Liu_2022_Front.Microbiol_13_819086
PubMedID: 35602042
Gene_locus related to this paper: preis-preu6

Title : Hepatitis B virus genotype is an independent prognostic factor of telbivudine and tenofovir treatment in hepatitis B surface antigen-positive pregnant women - Zhang_2022_Food.Sci.Nutr_10_3
Author(s) : Zhang B , Yu L , Cheng M , Zhang Q , Wu J , Yang J , Liu Q , Lu S , Zhao X , Deng K , Liu Y , Wang J , Zhao P
Ref : Food Sci Nutr , 10 :3 , 2022
Abstract : To investigate whether HBV genotype influences the effect of tenofovir and telbivudine on HBV DNA and RNA levels in HBsAg-positive pregnant women. This was a retrospective study of 74 HBsAg-positive pregnant women in Guizhou of China. All patients were treated with telbivudine or tenofovir from 12 weeks of pregnancy and HBV infection to the date of delivery. Blood samples were collected at 12-24, 28-32, and 36-40 weeks of pregnancy for the measurement of genotype, HBsAg, hepatitis B e antigen (HBeAg), HBV DNA, HBV RNA, and liver function, including alanine transaminase, aspartate transaminase, total bilirubin, total bile acids, cholinesterase, alkaline phosphatase (ALP), and gamma-glutamyl transferase. All women with HBsAg were followed up. The HBV genotype was B in 64.9% and C in 35.1%. There were 37 patients of telbivudine and tenofovir group respectively. The telbivudine and tenofovir groups showed no differences in demographic and clinical characteristics, including liver function tests, HBsAg, HBeAg, log(10)(HBV DNA), and log(10)(HBV RNA). Compared with baseline (12-24 weeks), telbivudine group showed a significant increase in ALP and significant reductions in HBsAg, HBeAg, log(10)(HBV DNA), and log(10)(HBV RNA) at 36-40 weeks (p < .05). Tenofovir group exhibited a significant increase in ALP and significant reductions in HBeAg, log(10)(HBV DNA), and log(10)(HBV RNA) at 36-40 weeks, compared with baseline (p < .05). HBV genotype (B vs. C) was independently associated with HBV DNA change after therapy (p = .005). In telbivudine group, log(10) (HBV DNA) increased from 3.38 (2.00-7.30) to 7.43 (4.68-8.70). In tenofovir group, log(10) (HBV DNA) decreased from 7.52 (3.32-8.70) to 2.98 (2.00-5.01). HBV genotype was independently associated with HBV DNA change response to telbivudine or tenofovir in pregnant women with hepatitis B. These findings might be helpful for risk assessment regarding vertical transmission of HBV in HBeAg-positive mothers treated with nucleos(t)ide analogues.
ESTHER : Zhang_2022_Food.Sci.Nutr_10_3
PubMedSearch : Zhang_2022_Food.Sci.Nutr_10_3
PubMedID: 35035905

Title : Antifeedant Mechanism of Dodonaea viscosa Saponin A Isolated from the Seeds of Dodonaea viscosa - Yu_2022_Molecules_27_4464
Author(s) : Yu H , Li J , Wu G , Tang Q , Duan X , Liu Q , Lan M , Zhao Y , Hao X , Qin X , Ding X
Ref : Molecules , 27 :4464 , 2022
Abstract : Dodonaea viscosa is a medicinal plant which has been used to treat various diseases in humans. However, the anti-insect activity of extracts from D. viscosa has not been evaluated. Here, we found that the total saponins from D. viscosa (TSDV) had strong antifeedant and growth inhibition activities against 4th-instar larvae of Spodoptera litura. The median antifeeding concentration (AFC(50)) value of TSDV on larvae was 1621.81 microg/mL. TSDV affected the detoxification enzyme system of the larvae and also exerted antifeedant activity possibly through targeting the gamma-aminobutyric acid (GABA) system. The AFC(50) concentration, the carboxylesterase activity, glutathione S-transferases activity, and cytochrome P450 content increased to 258%, 205%, and 215%, respectively, and likewise the glutamate decarboxylase activity and GABA content to 195% and 230%, respectively, in larvae which fed on TSDV. However, D. viscosa saponin A (DVSA) showed better antifeedant activity and growth inhibition activity in larvae, compared to TSDV. DVSA also exerted their antifeedant activity possibly through targeting the GABA system and subsequently affected the detoxification enzyme system. Further, DVSA directly affected the medial sensillum and the lateral sensillum of the 4th-instar larvae. Stimulation of Spodoptera litura. with DVSA elicited clear, consistent, and robust excitatory responses in a single taste cell.
ESTHER : Yu_2022_Molecules_27_4464
PubMedSearch : Yu_2022_Molecules_27_4464
PubMedID: 35889337

Title : Rapid Screening of Lipase Inhibitors from Ophiopogonis Radix Using High-Performance Thin Layer Chromatography by Two Step Gradient Elution Combined with Bioautographic Method - Hua_2022_Molecules_27_
Author(s) : Hua X , Hong HJ , Zhang DY , Liu Q , Leong F , Yang Q , Hu YJ , Chen XJ
Ref : Molecules , 27 : , 2022
Abstract : In this study, a high-performance thin layer chromatography (HPTLC) method by two step gradient elution with two mobile phases was developed for the simultaneous analysis of seven constituents in Ophiopogonis Radix. The chromatography was performed on silica gel 60 F(254) plate with dichloromethane-methanol-ethyl acetate-water (70:25:12:3, v/v/v/v) and dichloromethane-methanol (300:1, v/v) as the mobile phase for two step gradient elution. Then, the HPTLC profiles were observed after derivatization with 10% sulfuric acid in ethanol solution. The obtained HPTLC images were further analyzed by chemometric approaches and the samples could be clustered based on regions and/or growth years, which were two important factors affecting the constituents in Ophiopogonis Radix. Furthermore, five compounds including ophiopogonin D, ophiopojaponin C, ophiopogonin D', ophiopogonin C' and methylophiopogonanone B were screened as potential lipase inhibitors from Ophiopogonis Radix by the HPTLC-bioautographic method. The binding modes and interactions between the five compounds and lipase were further explored by molecular docking analysis. The developed HPTLC method could be used for quality control of Ophiopogonis Radix and screening of the potential lipase inhibitors.
ESTHER : Hua_2022_Molecules_27_
PubMedSearch : Hua_2022_Molecules_27_
PubMedID: 35208944

Title : Neurotoxicity and transcriptome changes in embryonic zebrafish induced by halobenzoquinone exposure - Yang_2022_J.Environ.Sci.(China)_117_129
Author(s) : Yang X , Wang C , Yang L , Zheng Q , Liu Q , Wawryk NJP , Li XF
Ref : J Environ Sci (China) , 117 :129 , 2022
Abstract : Halobenzoquinones (HBQs) are emerging disinfection byproducts (DBPs) with a widespread presence in drinking water that exhibit much higher cytotoxicity than regulated DBPs. However, the developmental neurotoxicity of HBQs has not been studied in vivo. In this work, we studied the neurotoxicity of HBQs on zebrafish embryos, after exposure to varying concentrations (0-8 micromol/L) of three HBQs, 2,5-dichloro-1,4-benzoquinone (2,5-DCBQ), 2,6-dichloro-1,4-benzoquinone (2,6-DCBQ), and 2,5-dibromo-1,4-benzoquinone (2,5-DBBQ) for 4 to 120 hr post fertilization (hpf). HBQ exposure significantly decreased the locomotor activity of larvae, accompanied by significant reduction of neurotransmitters (dopamine and gamma-aminobutyric acid) and acetylcholinesterase activity. Furthermore, the expression of genes involved in neuronal morphogenesis (gfap, alpha1-tubulin, mbp, and syn-2alpha) were downregulated by 4.4-, 5.2-, 3.0-, and 4.5-fold in the 5 micromol/L 2,5-DCBQ group and 2.0-, 1.6-, 2.1-, and 2.3-fold in the 5 micromol/L 2,5-DBBQ group, respectively. Transcriptomic analysis revealed that HBQ exposure affected the signaling pathways of neural development. This study demonstrates the significant neurotoxicity of HBQs in embryonic zebrafish and provides molecular evidence for understanding the potential mechanisms of HBQ neurotoxicity.
ESTHER : Yang_2022_J.Environ.Sci.(China)_117_129
PubMedSearch : Yang_2022_J.Environ.Sci.(China)_117_129
PubMedID: 35725065

Title : The Comparative Analysis of Genomic Diversity and Genes Involved in Carbohydrate Metabolism of Eighty-Eight Bifidobacterium pseudocatenulatum Isolates from Different Niches of China - Lin_2022_Nutrients_14_
Author(s) : Lin G , Liu Q , Wang L , Li H , Zhao J , Zhang H , Wang G , Chen W
Ref : Nutrients , 14 : , 2022
Abstract : Eighty-eight Bifidobacterium pseudocatenulatum strains, which were isolated from human, chicken and cow fecal samples from different niches of China, were compared genomically in this study to evaluate their diversity. It was found that B. pseudocatenulatum displayed a closed pan-genome, including abundant glycoside hydrolase families of the carbohydrate active enzyme (CAZy). A total of 30 kinds of glycoside hydrolases (GHs), 14 kinds of glycosyl transferases (GTs), 13 kinds of carbohydrate-binding modules (CBMs), 6 kinds of carbohydrate-esterases (CEs), and 2 kinds of auxiliary activities (AAs) gene families were identified across the genomes of the 88 B. pseudocatenulatum strains. Specifically, this showed that significant differences were also present in the number of 10 carbohydrate-active enzyme gene families (GT51, GH13_32, GH26, GH42, GH121, GH3, AA3, CBM46, CE2, and CE6) among the strains derived from the hosts of different age groups, particularly between strains from infants and those from other human age groups. Twelve different individuals of B. pseudocatenulatum from four main clusters were selected for further study to reveal the genetic diversity of carbohydrate metabolism-related genes within the same phylogenetics. The animal experiment showed that 3 weeks of oral administration and 1 week after cessation of administration of these strains did not markedly alter the serum routine inflammatory indicators in mice. Furthermore, the administration of these strains did not significantly cause adverse changes in the gut microbiota, as indicated by the alpha- and beta-diversity indexes, relative to the control group (normal diet). Beyond that, FAHBZ9L5 significantly increased the abundance of B. pseudocatenulatum after 3 weeks and significantly increased the abundance of acetic acid and butyric acid in the host's intestinal tract 3 and 4 weeks after the first administration, respectively, compared with the control group. Corresponding to this, comparative genomic analyses of 12 B. pseudocatenulatum suggest that FAHBZ9L5-specific genes were rich in ABC transporters and carbohydrate esterase. Combining the results of comparative genomics analyses and animal experiment, it is suggested that the strains containing certain gene clusters contribute to another competitive growth advantage of B. pseudocatenulatum, which facilitates its intestinal carbohydrate metabolism in a host.
ESTHER : Lin_2022_Nutrients_14_
PubMedSearch : Lin_2022_Nutrients_14_
PubMedID: 35684146

Title : Identification of novel immune-related targets mediating disease progression in acute pancreatitis - Liu_2022_Front.Cell.Infect.Microbiol_12_1052466
Author(s) : Liu Q , Li L , Xu D , Zhu J , Huang Z , Yang J , Cheng S , Gu Y , Zheng L , Zhang X , Shen H
Ref : Front Cell Infect Microbiol , 12 :1052466 , 2022
Abstract : INTRODUCTION: Acute pancreatitis (AP) is an inflammatory disease with very poor outcomes. However, the order of induction and coordinated interactions of systemic inflammatory response syndrome (SIRS) and compensatory anti-inflammatory response syndrome (CARS) and the potential mechanisms in AP are still unclear. METHODS: An integrative analysis was performed based on transcripts of blood from patients with different severity levels of AP (GSE194331), as well as impaired lung (GSE151572), liver (GSE151927) and pancreas (GSE65146) samples from an AP experimental model to identify inflammatory signals and immune response-associated susceptibility genes. An AP animal model was established in wild-type (WT) mice and Tlr2-deficient mice by repeated intraperitoneal injection of cerulein. Serum lipase and amylase, pancreas impairment and neutrophil infiltration were evaluated to assess the effects of Tlr2 in vivo. RESULTS: The numbers of anti-inflammatory response-related cells, such as M2 macrophages (P = 3.2 x 10(-3)), were increased with worsening AP progression, while the numbers of pro-inflammatory response-related cells, such as neutrophils (P = 3.0 x 10(-8)), also increased. Then, 10 immune-related AP susceptibility genes (SOSC3, ITGAM, CAMP, FPR1, IL1R1, TLR2, S100A8/9, HK3 and MMP9) were identified. Finally, compared with WT mice, Tlr2-deficient mice exhibited not only significantly reduced serum lipase and amylase levels after cerulein induction but also alleviated pancreatic inflammation and neutrophil accumulation. DISCUSSION: In summary, we discovered SIRS and CARS were stimulated in parallel, not activated consecutively. In addition, among the novel susceptibility genes, TLR2might be a novel therapeutic target that mediates dysregulation of inflammatory responses during AP progression.
ESTHER : Liu_2022_Front.Cell.Infect.Microbiol_12_1052466
PubMedSearch : Liu_2022_Front.Cell.Infect.Microbiol_12_1052466
PubMedID: 36590588

Title : Effects of the hemolytic index on the test results of a dry chemistry analyzer and a verification of the hemolytic interference threshold - Yang_2022_Ann.Palliat.Med_11_1381
Author(s) : Yang Q , Huang S , Han R , Lin B , Liu Q , Duan X , Ma Z , Zhang H , Shou H , Zhang S
Ref : Ann Palliat Med , 11 :1381 , 2022
Abstract : BACKGROUND: This study verified and assessed 26 biochemical indicators tested by a dry chemistry analyzer using the hemolytic index test function to determine the degree of interference and the trends among the hemolysis samples on the test results. This study also sought to ensure that reasonable test reports could be issued taking into account practical clinical needs. METHODS: The samples were manually divided into the control group and the test group. The hemolytic index and biochemical indicators of the samples were tested using the Ortho Vitros 5600 to compare the deviation of the test results between the 2 groups. The judgment standard was set as 1/3 of the total error allowable as required by the quality assessment criterion of the National Center for Clinical Laboratories. The interference degree of hemolysis on the dry chemistry-based biochemical indicators was assessed, and the hemolytic thresholds of 26 biochemical indicators provided by the manufacturer were verified in terms of their validity and rationality. RESULTS: The hemolytic thresholds of 26 dry chemistry-based biochemical indicators were verified to analyze the degree of interference. The results revealed that hemolysis interfered with 17 indicators. Hemolysis positively interfered with the test results of phosphorus, creatine kinase, gamma glutamyl transpeptidase (gamma-GGT), magnesium, iron, total protein, potassium, total bilirubin, lactate dehydrogenase, albumin, and aspartate aminotransferase, but negatively interfered with cholinesterase, direct high-density lipoprotein cholesterol, glucose, elevated carbon dioxide alkaline phosphatase, and alanine aminotransferase. A negative deviation of gamma-GGT by hemoglobin was described in the manufacturer's statement, but our test data showed a positive deviation by hemolysis. The hemolytic threshold verification results of the other biochemical indicators were consistent with the manufacturer's statement. CONCLUSIONS: The hemolytic index test function was used to determine which samples were interfered with by hemolysis to make an analytical judgment according to the hemolytic interference thresholds of the different test items, verify the validity of the hemolytic thresholds of the test items, perform reasonable tests on the hemolytic samples, and issue valid reports to reduce the rejection rate of the hemolytic samples, shorten the turnaround time (TAT) of laboratories.
ESTHER : Yang_2022_Ann.Palliat.Med_11_1381
PubMedSearch : Yang_2022_Ann.Palliat.Med_11_1381
PubMedID: 35523746

Title : Antibacterial Efficacy and Mechanisms of Curcumin-Based Photodynamic Treatment against Staphylococcus aureus and Its Application in Juices - Yuan_2022_Molecules_27_
Author(s) : Yuan Y , Liu Q , Huang Y , Qi M , Yan H , Li W , Zhuang H
Ref : Molecules , 27 : , 2022
Abstract : Antimicrobial Photodynamic Treatment (aPDT) is a non-thermal sterilization technology, which can inactivate common foodborne pathogens. In the present study, photodynamic inactivation on Staphylococcus aureus (S. aureus) with different concentrations of curcumin and light dose was evaluated and the mechanisms were also investigated. The results showed that curcumin-based aPDT could inactivate S. aureus cells by 6.9 log CFU/mL in phosphate buffered saline (PBS). Moreover, the modified Gompertz model presented a good fit at the inactivation data of S. aureus. Photodynamic treatment caused cell membrane damage as revealed by analyzing scanning electron microscopy (SEM) images. Leakage of intracellular constituents further indicated that cell membrane permeability was changed. Flow cytometry with double staining demonstrated that cell membrane integrity and the activity of nonspecific esterase were destroyed. Compared with the control group, intracellular reactive oxygen species (ROS) levels caused by photodynamic treatment significantly increased. Furthermore, curcumin-based aPDT reduced S. aureus by 5 log CFU/mL in juices. The color of the juices was also tested using a Chromatic meter, and it was found that b* values were the most markedly influenced by photodynamic treatment. Overall, curcumin-based aPDT had strong antibacterial activity against S. aureus. This approach has the potential to remove foodborne pathogens from liquid food.
ESTHER : Yuan_2022_Molecules_27_
PubMedSearch : Yuan_2022_Molecules_27_
PubMedID: 36296729

Title : Integrating network pharmacology analysis and pharmacodynamic evaluation for exploring the active components and molecular mechanism of moutan seed coat extract to improve cognitive impairment - Wang_2022_Front.Pharmacol_13_952876
Author(s) : Wang Y , Wu X , Yang K , Liu Q , Jiang B , Yang R , Xiao P , He C
Ref : Front Pharmacol , 13 :952876 , 2022
Abstract : Paeonia suffruticosa (Moutan) is a traditional medicinal plant in China. Its seed coat is rich in resveratrol oligomer, especially suffruticosol B (SB). Previous studies had shown that the seed coat extracts of Paeonia suffruticosa (PSCE) had good cholinesterase inhibitory activity and neuroprotective effect, but the effective dose range was unknown, and the pharmacodynamic components and molecular mechanism of PSCE had not been discussed. The current study aimed to screen the pharmacodynamic components in PSCE and investigate the improvement effect of PSCE and the selected SB on scopolamine-induced cognitive dysfunction in mice and its mechanism. The results of high-throughput sequencing and bioinformatics analysis showed that suffruticosol B (SB) and trans-gnetin H (GH) might be the main active components of PSCE; PSCE might improve cognitive dysfunction through p53, HIF-1, MAPK, and PI3K-Akt signaling pathways, while SB and GH might improve cognitive dysfunction through HIF-1 signaling pathway. SB and GH had good molecular docking activity with the target of HIF-1 signaling pathway. The pharmacodynamic activities of PSCE and SB were further verified by behavioral experiments. PSCE and SB could improve the recognition ability of familiar and new objects and shorten the escape latency in the Morris Water Maze test (PSCE 120 mgkg-1, p < 0.05; SB 60 mgkg-1, p < 0.01); PSCE and SB could increase Ach and GSH levels, enhance the activities of ChAT, SOD and CAT, decrease the levels of IL-1beta, IL-6, and TNF-alpha, and decrease the activity of AChE. In conclusion, the results indicated that PSCE might exert pharmacodynamic activity through multiple components, targets, and pathways, and SB and GH might be the main active components of PSCE. PSCE and SB might improve cognitive dysfunction by regulating cholinergic, antioxidant, and anti-inflammatory effects. These results indicated that PSCE and SB might be potential anti-AD drug candidates, providing a scientific basis for the development and utilization of Moutan bark.
ESTHER : Wang_2022_Front.Pharmacol_13_952876
PubMedSearch : Wang_2022_Front.Pharmacol_13_952876
PubMedID: 36034803

Title : Carboxylesterase 2 induces mitochondrial dysfunction via disrupting lipid homeostasis in oral squamous cell carcinoma - Chen_2022_Mol.Metab__101600
Author(s) : Chen X , Liu Q , Chen Y , Wang L , Yang R , Zhang W , Pan X , Zhang S , Chen C , Wu T , Xia J , Cheng B , Ren X
Ref : Mol Metab , :101600 , 2022
Abstract : OBJECTIVE: Oral squamous cell carcinoma (OSCC) is characterized by high recurrence and metastasis and places a heavy burden on societies worldwide. Cancer cells thrive in a changing microenvironment by reprogramming lipidomic metabolic processes to provide nutrients and energy, activate oncogenic signaling pathways, and manage redox homeostasis to avoid lipotoxicity. The mechanism by which OSCC cells maintain lipid homeostasis during malignant progression is unclear. METHODS: The altered expression of fatty acid (FA) metabolism genes in OSCC, compared with that in normal tissues, and in OSCC patients with or without recurrence or metastasis were determined using public data from the TCGA and GEO databases. Immunohistochemistry was performed to examine the carboxylesterase 2 (CES2) protein level in our own cohort. CCK-8 and Transwell assays and an in vivo xenograft model were used to evaluate the biological functions of CES2. Mass spectrometry and RNA sequencing were performed to determine the lipidome and transcriptome alterations induced by CES2. Mitochondrial mass, mtDNA content, mitochondrial membrane potential, ROS levels, and oxygen consumption and apoptosis rates were evaluated to determine the effects of CES2 on mitochondrial function in OSCC. RESULTS: CES2 was downregulated in OSCC patients, especially those with recurrence or metastasis. CES2(high) OSCC patients showed better overall survival than CES2(low) OSCC patients. Restoring CES2 expression reduced OSCC cell viability and suppressed their migration and invasion in vitro, and it inhibited OSCC tumor growth in vivo. CES2 reprogrammed lipid metabolism in OSCC cells by hydrolyzing neutral lipid diacylglycerols (DGs) to release free fatty acids and reduce the membrane structure lipid phospholipids (PLs) synthesis. Free FAs were converted to acyl-carnitines (CARs) and transferred to mitochondria for oxidation, which induced reactive oxygen species (ROS) accumulation, mitochondrial damage, and apoptosis activation. Furthermore, the reduction in signaling lipids, e.g., DGs, PLs and substrates, suppressed PI3K/AKT/MYC signaling pathways. Restoring MYC rescued the diminished cell viability, suppressed migratory and invasive abilities, damaged mitochondria and reduced apoptosis rate induced by CES2. CONCLUSIONS: We demonstrated that CES2 downregulation plays an important role in OSCC by maintaining lipid homeostasis and reducing lipotoxicity during tumor progression and may provide a potential therapeutic target for OSCC.
ESTHER : Chen_2022_Mol.Metab__101600
PubMedSearch : Chen_2022_Mol.Metab__101600
PubMedID: 36113774

Title : Stilbenoids isolated from the roots of Rheum lhasaense under the guidance of the acetylcholinesterase inhibition activity - Liu_2021_J.Nat.Med__
Author(s) : Liu Q , Shen J , Li P , Li Y , He C , Xiao P
Ref : J Nat Med , : , 2021
Abstract : Four unknown stilbenoids, including one dimer, namely 4'-methoxy-scirpusin A (5) and three monomeric stilbene glycosides, namely piceatannol-3'-O-[2''-(3,5-dihydroxy-4-methoxybenzoyl)]-beta-D-glucopyranoside (13), piceatannol-3'-O-(2''-galloyl)-beta-D-glucopyranoside (14) and piceatannol-3'-O-(6''-p-coumaroyl)-beta-D-glucopyranoside (16) together with 15 described compounds, were isolated from the ethyl acetate fraction of the ethanol extract of roots of Rheum lhasaense based on the guidance of the inhibitory effect on acetylcholinesterase. The structures of the unknown compounds were established by combined spectroscopic analysis and comparing their spectral data with compounds with similar structures. Some selected components were also investigated for their inhibitory abilities on acetylcholinesterase (AChE), indicating that compound 13 may be responsible for higher inhibitory activity of the ethyl acetate fraction on AChE.
ESTHER : Liu_2021_J.Nat.Med__
PubMedSearch : Liu_2021_J.Nat.Med__
PubMedID: 33411157

Title : The Efficacy and Safety of Alzheimer's Disease Therapies: An Updated Umbrella Review - Fan_2021_J.Alzheimers.Dis__
Author(s) : Fan F , Liu H , Shi X , Ai Y , Liu Q , Cheng Y
Ref : J Alzheimers Dis , : , 2021
Abstract : BACKGROUND: Evidence summaries for efficacy and safety of frequently employed treatments of Alzheimer's disease (AD) are sparse. OBJECTIVE: We aimed to perform an updated umbrella review to identify an efficacious and safe treatment for AD patients. METHODS: We conducted a search for meta-analyses and systematic reviews on the Embase, PubMed, The Cochrane Library, and Web of Science to address this knowledge gap. We examined the cognitive functions, behavioral symptoms, global clinical assessment, and Activities of Daily Living as efficacy endpoints, and the incidence of adverse events as safety profiles. RESULTS: Sixteen eligible papers including 149 studies were included in the umbrella review. The results showed that AChE inhibitors (donepezil, galantamine, rivastigmine, Huperzine A), Ginkgo biloba, and cerebrolysin appear to be beneficial for cognitive, global performances, and activities of daily living in patients with AD. Furthermore, anti-Abeta agents are unlikely to have an important effect on slowing cognitive or functional impairment in mild to moderate AD. CONCLUSION: Our study demonstrated that AChE inhibitors, Ginkgo biloba, and cerebrolysin are the optimum cognitive and activities of daily living medication for patients with AD.
ESTHER : Fan_2021_J.Alzheimers.Dis__
PubMedSearch : Fan_2021_J.Alzheimers.Dis__
PubMedID: 34924395

Title : Discovery of memantyl urea derivatives as potent soluble epoxide hydrolase inhibitors against lipopolysaccharide-induced sepsis - Du_2021_Eur.J.Med.Chem_223_113678
Author(s) : Du F , Sun W , Morisseau C , Hammock BD , Bao X , Liu Q , Wang C , Zhang T , Yang H , Zhou J , Xiao W , Liu Z , Chen G
Ref : Eur Journal of Medicinal Chemistry , 223 :113678 , 2021
Abstract : Sepsis, a systemic inflammatory response, caused by pathogenic factors including microorganisms, has high mortality and limited therapeutic approaches. Herein, a new soluble epoxide hydrolase (sEH) inhibitor series comprising a phenyl ring connected to a memantyl moiety via a urea or amide linkage has been designed. A preferential urea pharmacophore that improved the binding properties of the compounds was identified for those series via biochemical assay in vitro and in vivo studies. Molecular docking displayed that 3,5-dimethyl on the adamantyl group in B401 could make van der Waals interactions with residues at a hydrophobic pocket of sEH active site, which might indirectly explain the subnanomolar level activities of memantyl urea derivatives in vitro better than AR-9281. Among them, compound B401 significantly improved the inhibition potency with human and murine sEH IC(50) values as 0.4 nM and 0.5 nM, respectively. Although the median survival time of C57BL/6 mice in LPS-induced sepsis model was slightly increased, the survival rate did not reach significant efficacy. Based on safety profile, metabolic stability, pharmacokinetic and in vivo efficacy, B401 demonstrated the proof of potential for this class of memantyl urea-based sEH inhibitors as therapeutic agents in sepsis.
ESTHER : Du_2021_Eur.J.Med.Chem_223_113678
PubMedSearch : Du_2021_Eur.J.Med.Chem_223_113678
PubMedID: 34218083

Title : Blood-Brain Barrier Permeable and NO-Releasing Multifunctional Nanoparticles for Alzheimer's Disease Treatment: Targeting NO\/cGMP\/CREB Signaling Pathways - Liu_2021_J.Med.Chem_64_13853
Author(s) : Liu Z , Liu Q , Zhang B , Fang L , Gou S
Ref : Journal of Medicinal Chemistry , 64 :13853 , 2021
Abstract : The development of novel therapeutic strategies for combating Alzheimer's disease (AD) is challenging but imperative. Multifunctional nanoparticles are promising tools for regulating complex pathological dysfunctions for AD treatment. Herein, we constructed multifunctional nanoparticles consisting of regadenoson (Reg), nitric oxide (NO) donor, and YC-1 in a single molecular entity that can spontaneously self-assemble into nanoparticles and load donepezil to yield Reg-nanoparticles (Reg-NPs). The Reg moiety enabled the Reg-NPs to effectively regulate tight junction-associated proteins in the blood-brain barrier, thus facilitating the permeation of donepezil through the barrier and its accumulation in the brain. Moreover, the released NO and YC-1 activated the NO/cGMP/CREB signaling pathway by stimulating soluble guanylyl cyclase and inhibiting phosphodiesterase activity, which finally reduced cytotoxicity induced by aggregated Abeta in the neurons and was beneficial for synaptic plasticity and memory formation.
ESTHER : Liu_2021_J.Med.Chem_64_13853
PubMedSearch : Liu_2021_J.Med.Chem_64_13853
PubMedID: 34517696

Title : Smart nanozyme of silver hexacyanoferrate with versatile bio-regulated activities for probing different targets - Zhang_2021_Talanta_228_122268
Author(s) : Zhang L , Zhang Q , Liu Q , Wu X , Dong Y , Wang GL
Ref : Talanta , 228 :122268 , 2021
Abstract : Smart nanozymes that can be facile and rapidly produced, while with efficiently bio-regulated activity, are attractive for biosensing applications. Herein, a smart nanozyme, silver hexacyanoferrate (Ag(4)[Fe(CN)(6)]), was constructed in situ via the rapid, direct reaction between silver(I) and K(4)[Fe(CN)(6)]. And the activity of the nanozyme can be rationally modulated by different enzymatic reactions including the glucose oxidase (GOx, taken as a model oxidoreductase), alkaline phosphatase (ALP), and acetylcholinesterase (AChE). On the basis of which, a multiple function platform for the highly sensitive detection of glucose, ALP and AChE were developed through colorimetry. Corresponding detection limits for the above three targets were found to be as low as 0.32 microM, 3.3 U/L and 0.083 U/L (S/N = 3), respectively. The present study provides a novel nanozyme that can be produced in situ, which rules out the harsh, cumbersome, and time-consuming synthesis/purification procedures. In addition, it establishes a multiple function platform for the amplified detection of versatile targets by the aid of the developed nanozyme, whose detection has the advantages of low cost, ease-of-use, high sensitivity, and good selectivity.
ESTHER : Zhang_2021_Talanta_228_122268
PubMedSearch : Zhang_2021_Talanta_228_122268
PubMedID: 33773716

Title : A highly sensitive acetylcholinesterase electrochemical biosensor based on Au-Tb alloy nanospheres for determining organophosphate pesticides - Yang_2021_Nanotechnology__
Author(s) : Yang Y , Zhao Y , Liu Q , You T , Gao Y , Chen H , Yin P
Ref : Nanotechnology , : , 2021
Abstract : Accurately detect the residues of organophosphate pesticides(OPs) in food and environment is critical to our daily lives. In this study, we developed a novel acetylcholinesterase (AChE) biosensor based on Au-Tb alloy nanospheres (NSs) for rapid and sensitive detection of OPs for the first time. Au-Tb alloy nanospheres that with good conductivity and biocompatibility were produced with a mild hydrothermal. Under optimal conditions, the AChE biosensor was obtained by a simple assembly process, with a big linear range (10-13 M - 10-7 M) and the limit of detection was 2.51 x 10-14 M for the determination of methyl parathion. Moreover, the determination of methyl parathion with the prepared biosensor presented a high sensitivity, outstanding repeatability and superior stability compared with other reported biosensors. Through the determination of tap water and Yanming lake samples, it was proved that the modified biosensor with satisfactory recoveries (96.76 %-108.6 %), and are realizable in the determination of OPs in real samples.
ESTHER : Yang_2021_Nanotechnology__
PubMedSearch : Yang_2021_Nanotechnology__
PubMedID: 34256363

Title : FumDSB Can Reduce the Toxic Effects of Fumonisin B(1) by Regulating Several Brain-Gut Peptides in Both the Hypothalamus and Jejunum of Growing Pigs - Liu_2021_Toxins.(Basel)_13_874
Author(s) : Liu Q , Li F , Huang L , Chen W , Li Z , Wang C
Ref : Toxins (Basel) , 13 :874 , 2021
Abstract : Fumonisin B(1) (FB(1)) is the most common food-borne mycotoxin produced by the Fusarium species, posing a potential threat to human and animal health. Pigs are more sensitive to FB(1) ingested from feed compared to other farmed livestock. Enzymatic degradation is an ideal detoxification method that has attracted much attention. This study aimed to explore the functional characteristics of the carboxylesterase FumDSB in growing pigs from the perspective of brain-gut regulation. A total of 24 growing pigs were divided into three groups. The control group was fed a basal diet, the FB(1) group was supplemented with FB(1) at 5 mg/kg feed, and the FumDSB group received added FumDSB based on the diet of the FB(1) group. After 35 days of animal trials, samples from the hypothalamus and jejunum were analyzed through HE staining, qRT-PCR and immunohistochemistry. The results demonstrated that the ingestion of FB(1) can reduce the feed intake and weight gain of growing pigs, indicating that several appetite-related brain-gut peptides (including NPY, PYY, ghrelin and obestatin, etc.) play important roles in the anorexia response induced by FB(1). After adding FumDSB as detoxifying enzymes, however, the anorexia effects of FB(1) were alleviated, and the expression and distribution of the corresponding brain-gut peptides exhibited a certain degree of regulation. In conclusion, the addition of FumDSB can reduce the anorexia effects of FB(1) by regulating several brain-gut peptides in both the hypothalamus and the jejunum of growing pigs.
ESTHER : Liu_2021_Toxins.(Basel)_13_874
PubMedSearch : Liu_2021_Toxins.(Basel)_13_874
PubMedID: 34941712
Gene_locus related to this paper: 9sphn-a0a101vlk1

Title : Soluble Epoxide Hydrolase Inhibitors Regulate Ischemic Arrhythmia by Targeting MicroRNA-1 - Chen_2021_Front.Physiol_12_717119
Author(s) : Chen Y , Liu Q , Yang T , Shen L , Xu D
Ref : Front Physiol , 12 :717119 , 2021
Abstract : Background: Soluble epoxide hydrolase inhibitors (sEHis) inhibit the degradation of epoxyeicosatrienoic acids (EETs) in cells, and EETs have antiarrhythmic effects. Our previous experiments confirmed that t-AUCB, a preparation of sEHis, inhibited ischemic arrhythmia by negatively regulating microRNA-1 (miR-1), but its specific mechanism remained unclear. Aim: This study aimed to examine the role of serum response factor (SRF) and the PI3K/Akt/GSK3beta pathway in t-AUCB-mediated regulation of miR-1 and the interaction between them. Methods/Results: We used SRF small interfering RNA (siSRF), SRF small hairpin (shSRF) RNA sequence adenovirus, PI3K/Akt/GSK3beta pathway inhibitors, t-AUCB, and 14,15-EEZE (a preparation of EETs antagonists) to treat mouse cardiomyocytes overexpressing miR-1 and mice with myocardial infarction (MI). We found that silencing SRF attenuated the effects on miR-1 and its target genes KCNJ2 and GJA1 in the presence of t-AUCB, and inhibition of the PI3K/Akt/GSK3beta pathway antagonized the effects of t-AUCB on miR-1, KCNJ2, and GJA1, which were associated with PI3Kalpha, Akt, and Gsk3beta but not PI3Kbeta or PI3Kgamma. Moreover, the PI3K/Akt/GSK3beta pathway was involved in the regulation of SRF by t-AUCB, and silencing SRF inhibited the t-AUCB-induced increases in Akt and Gsk3beta phosphorylation. Conclusions: Both the SRF and the PI3K/Akt/GSK3beta pathway are involved in the t-AUCB-mediated regulation of miR-1, and these factors interact with each other.
ESTHER : Chen_2021_Front.Physiol_12_717119
PubMedSearch : Chen_2021_Front.Physiol_12_717119
PubMedID: 34646152

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

Title : Protein tyrosine phosphatase 1B (PTP1B) inhibitorsfrom the deep-sea fungus Penicillium chrysogenum SCSIO 07007 - Han_2020_Bioorg.Chem_96_103646
Author(s) : Han W , Cai J , Zhong W , Xu G , Wang F , Tian X , Zhou X , Liu Q , Liu Y , Wang J
Ref : Bioorg Chem , 96 :103646 , 2020
Abstract : Three new compounds, including two new 3,4,6-trisubstituted alpha-pyrone derivatives, chrysopyrones A and B (1 and 2), and one new indolyl diketopiperazine derivative, penilline C (3), along with twelve known compounds (4-15), were isolated and identified from the fungus Penicillium chrysogenum SCSIO 07007, separated from deep-sea hydrothermal vent environment sample collected from the Western Atlantic. Their structures and absolute configurations were determined by extensive spectroscopic analysis and electronic circular dichroism (ECD) calculations. All of the isolated compounds (1-15) were evaluated for their cytotoxic, antibacterial activities and enzyme inhibitory activities against acetylcholinesterase (AChE), alpha-glycosidase, and protein tyrosine phosphatase 1B (PTP1B). Among them, new compounds chrysopyrones A and B (1 and 2) displayed obvious inhibitory activities against PTP1B with IC50 values of 9.32 and 27.8 mug/mL, respectively. Furthermore, molecular docking was performed to investigate the inside perspective of the action in PTP1B enzyme.
ESTHER : Han_2020_Bioorg.Chem_96_103646
PubMedSearch : Han_2020_Bioorg.Chem_96_103646
PubMedID: 32036160

Title : Resveratrol oligomers from Paeonia suffruticosa protect mice against cognitive dysfunction by regulating cholinergic, antioxidant and anti-inflammatory pathways - Liu_2020_J.Ethnopharmacol__112983
Author(s) : Liu S , Li Y , Yi F , Liu Q , Chen N , He X , He C , Xiao P
Ref : J Ethnopharmacol , :112983 , 2020
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Paeonia suffruticosa Andr. has been widely used in traditional Chinese medicine as an anti-tumour, anti-oxidant, anti-inflammatory and neuroprotective agent. Resveratrol oligomers are the main components of the seed coat extracts of Paeonia suffruticosa (PSCE) and have DPPH free radical scavenging and beta-secretase inhibitory activity. However, studies of its effect on ameliorating cognitive deficits are limited, and analyses of the underlying mechanisms are insufficient. AIM OF STUDY: This study aimed to investigate the cholinesterase inhibitory activities of resveratrol oligomers from P. suffruticosa in vitro and their effects on diminishing the oxygen-glucose deprivation/reoxygenation (OGD/R) -induced cytotoxicity in PC12cells and scopolamine-induced cognitive deficits in mice. Moreover, the underlying mechanisms were further explored. MATERIALS AND METHODS: In vitro, the inhibitory effects of PSCE and its 10 stilbenes on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) were evaluated using the Ellmann assay, and its protective effects on normal and OGD/R-injured PC12cells were evaluated using the MTT assay. For the in vivo assay, C57BL/6 mice were orally administered PSCE at doses of 150 and 600mg/kg for 28 days, and injected with scopolamine (1.5mg/kg) to induce cognitive deficits. The memory behaviours were evaluated using the novel object recognition, Morris water maze and inhibitory avoidance test. Levels of various biochemical markers were also examined, including AChE, choline acetyltransferase (ChAT), acetylcholine (ACh), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) in the mouse brain and interleukin-1beta (IL-1beta), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), interleukin-4 (IL-4) in serum. RESULTS: PSCE and its 10 stilbenes display good inhibition of AChE and BuChE activities and significantly increase the viability of normal and OGD/R-injured PC12cells. PSCE improves the cognitive performance of scopolamine-treated mice in behavioural tests. Meanwhile, PSCE increases AChE, ChAT, SOD, and CAT activities and ACh, GSH, IL-4 levels, and decreases IL-1beta, IL-6, TNF-alpha levels in the model animals. CONCLUSIONS: Resveratrol oligomers from P. suffruticosa show neuroprotective effect in vitro and in vivo by regulating cholinergic, antioxidant and anti-inflammatory pathways, may have promising application in the treatment of Alzheimer's disease.
ESTHER : Liu_2020_J.Ethnopharmacol__112983
PubMedSearch : Liu_2020_J.Ethnopharmacol__112983
PubMedID: 32442589

Title : Inhibition of soluble epoxide hydrolase attenuates airway remodeling in a chronic asthma model - Jiang_2020_Eur.J.Pharmacol_868_172874
Author(s) : Jiang JX , Guan Y , Shen HJ , Jia YL , Shen J , Zhang LH , Liu Q , Zhu YL , Xie QM
Ref : European Journal of Pharmacology , 868 :172874 , 2020
Abstract : Airway remodeling in asthma is difficult to treat because of its complex pathophysiology that involves proinflammatory cytokines, as well as the arachidonic acid cytochrome P-450 (CYP) pathway; however, it has received little attention. In this study, we assessed the efficacy of a soluble epoxide hydrolase (sEH) on airway remodeling in a mouse model of chronic asthma. The expression of sEH and CYP2J2 and the level of 14,15-epoxyeicosatrienoic acid (14,15-EET), airway remodeling and hyperresponsiveness (AHR) were analyzed to determine the level of sEH inhibition. AUDA, a sEH inhibitor, was given daily for 9 weeks orally, which significantly increased the level of 14,15-EET by inhibiting the expression of sEH and increasing the expression of CYP2J2 in lung tissues. The inhibition of sEH reduced the expression of remodeling-related molecular markers, such as interleukin (IL)-13, IL-17, matrix metalloproteinase 9, N-cadherin, alpha-smooth muscle actin (alpha-SMA), S100A4, Twist, epithelial goblet cell metaplasia, and collagen deposition in bronchoalveolar lavage fluid (BAL fluid) and lung tissues. Moreover, remodeling-related eosinophil accumulation in the BAL fluid and infiltration into the lung tissue were improved by AUDA. Finally, AUDA alleviated AHR, which is a functional indicator of airway remodeling. The effect of AUDA on airway remodeling was related to the downregulation of extracellular-regulated protein kinases (Erk1/2), c-Jun N-terminal kinases (JNK) and signal transducer and activator of transcription 3 (STAT3). To our knowledge, this is the first report to demonstrate that inhibition of sEH exerts significant protective effects on airway remodeling in asthma.
ESTHER : Jiang_2020_Eur.J.Pharmacol_868_172874
PubMedSearch : Jiang_2020_Eur.J.Pharmacol_868_172874
PubMedID: 31866410

Title : Relief of Cadmium-Induced Intestinal Motility Disorder in Mice by Lactobacillus plantarum CCFM8610 - Liu_2020_Front.Immunol_11_619574
Author(s) : Liu Y , Wu J , Xiao Y , Liu Q , Yu L , Tian F , Zhao J , Zhang H , Chen W , Zhai Q
Ref : Front Immunol , 11 :619574 , 2020
Abstract : Cadmium (Cd) is a toxic metal inducing a range of adverse effects on organs including liver and kidneys. However, the underlying molecular mechanisms of Cd-induced intestinal toxicity through dietary intake is poorly studied. This study evaluated the toxic effects of Cd on intestinal physiology and confirmed the effectiveness of the protective mechanism of the probiotic Lactobacillus plantarum CCFM8610 against chronic Cd toxicity. After treatment with Cd, the HT-29 cell line was subjected to iTRAQ analysis, which revealed that changes in the proteomic profiles after Cd exposure were related to pathways involved in the stress response and carbohydrate metabolism. The results of an animal trial also indicated that 10 weeks of Cd exposure decreased the fecal water content and contractile response of colonic muscle strips in mice, and delayed the excretion time of the first black feces. L. plantarum CCFM8610 treatment provided protective effects against these Cd-induced intestinal motility dysfunctions by recovering the levels of neurotransmitters, including substance P, acetyl cholinesterase, vasoactive intestinal peptide, 5-hydroxytryptamine, calcitonin gene-related peptide, and nitric oxide, and suppressing the cellular stress response in mice (e.g., the inhibition of mitogen-activated protein kinase pathways). The administration of this probiotic was also observed to reduce Cd levels in the tissues and blood of the mice. Our results suggest a newly identified protective mechanism of probiotics against Cd toxicity that involves the recovery of intestinal motility and increase in fecal cadmium excretion.
ESTHER : Liu_2020_Front.Immunol_11_619574
PubMedSearch : Liu_2020_Front.Immunol_11_619574
PubMedID: 33362802

Title : Real-world effectiveness, its predictors and onset of action of cholinesterase inhibitors and memantine in dementia: retrospective health record study - Vaci_2020_Br.J.Psychiatry__1
Author(s) : Vaci N , Koychev I , Kim CH , Kormilitzin A , Liu Q , Lucas C , Dehghan A , Nenadic G , Nevado-Holgado A
Ref : British Journal of Psychiatry , :1 , 2020
Abstract : BACKGROUND: The efficacy of acetylcholinesterase inhibitors and memantine in the symptomatic treatment of Alzheimer's disease is well-established. Randomised trials have shown them to be associated with a reduction in the rate of cognitive decline. AIMS: To investigate the real-world effectiveness of acetylcholinesterase inhibitors and memantine for dementia-causing diseases in the largest UK observational secondary care service data-set to date. METHOD: We extracted mentions of relevant medications and cognitive testing (Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores) from de-identified patient records from two National Health Service (NHS) trusts. The 10-year changes in cognitive performance were modelled using a combination of generalised additive and linear mixed-effects modelling. RESULTS: The initial decline in MMSE and MoCA scores occurs approximately 2 years before medication is initiated. Medication prescription stabilises cognitive performance for the ensuing 2-5 months. The effect is boosted in more cognitively impaired cases at the point of medication prescription and attenuated in those taking antipsychotics. Importantly, patients who are switched between agents at least once do not experience any beneficial cognitive effect from pharmacological treatment. CONCLUSIONS: This study presents one of the largest real-world examination of the efficacy of acetylcholinesterase inhibitors and memantine for symptomatic treatment of dementia. We found evidence that 68% of individuals respond to treatment with a period of cognitive stabilisation before continuing their decline at the pre-treatment rate.
ESTHER : Vaci_2020_Br.J.Psychiatry__1
PubMedSearch : Vaci_2020_Br.J.Psychiatry__1
PubMedID: 32713359

Title : Inhibition of acetylcholinesterase attenuated retinal inflammation via suppressing NF-kappaB activation - Li_2020_Exp.Eye.Res__108003
Author(s) : Li J , Chen Y , Zhang X , Ye S , Yi J , Chen Q , Liu Q
Ref : Experimental Eye Research , :108003 , 2020
Abstract : Elevated inflammatory cytokines contribute to the pathogenesis of various retinal diseases such as diabetic retinopathy, retinal vasculitis and retinitis. However, the underlying mechanism of retinal inflammation remains largely unknown. Recent studies demonstrated that acetylcholinesterase (ACHE) is an inflammatory indicator in central neural system. This study was aimed to dissect the role of ACHE in retinal inflammation, and its mechanism of action. Retinal inflammation was induced by intravitreal injection of tumor necrosis factor-alpha (TNF-alpha) in heterozygous ACHE knockout mice (ACHE(+/-)) and wild type mice (ACHE(+/+)). Donepezil, a well-known ACHE inhibitor, was administrated by daily gavage. Expression of ACHE and intercellular adherent molecule-1 (ICAM-1), infiltration of CD11b(+) inflammatory cells, retinal leukostasis and vascular leakage was determined in both ACHE (+/-) and ACHE(+/+) mice. ARPE-19cells, a human retinal pigment epithelial cell line, were cultured for in vitro assay. Knockdown of ACHE was achieved by lipofectamine-mediated siRNA transfection and pharmaceutical suppression of ACHE was manipulated by donepezil. Cellular expression and distribution of ACHE, ICAM-1, and phosphorylation of NF-kappaB, IkappaB and IKKalpha/beta were detected by western-blot analysis or immunocytochemistry. Retinal expression of ACHE was dramatically upregulated, in parallel with increased ICAM-1 expression, enhanced leukostasis and augmented CD11b(+) inflammatory cells infiltration as well as vascular hyperpermeability in ACHE(+/+) mice injected with TNF-alpha. However, TNF-alpha-injected ACHE (+/-) mice showed lower level of ICAM-1, less leukostasis and fewer infiltrated CD11b(+) cells. Moreover, TNF-alpha-induced retinal vascular leakage was significantly reduced in ACHE (+/-) mice. Similarly, TNF-alpha-induced retinal inflammatory response were also attenuated by donepezil intervention. In addition, TNF-alpha treatment resulted in significant induction of ACHE, upregulation of ICAM-1 and nuclear translocation of NF-kappaB in cultured-ARPE-19cells. Genetic and pharmaceutical suppression of ACHE markedly attenuated TNF-alpha-induced ICAM-1 expression. Meanwhile, inhibition of ACHE reduced TNF-alpha-induced phosphorylation of NF-kappaB, IkappaB and IKKalpha/beta in ARPE-19cells. The present study reveals a pivotal role of ACHE in retinal inflammation. Inhibition of ACHE attenuates retinal inflammation and retinal leakage likely through suppressing NF-kappaB signaling activation.
ESTHER : Li_2020_Exp.Eye.Res__108003
PubMedSearch : Li_2020_Exp.Eye.Res__108003
PubMedID: 32184102

Title : HFIP-Functionalized Co3 O4 Micro-Nano-Octahedra\/rGO as a Double-Layer Sensing Material for Chemical Warfare Agents - Alali_2019_Chemistry_25_11892
Author(s) : Alali KT , Liu J , Chen R , Liu Q , Zhang H , Li J , Hou J , Li R , Wang J
Ref : Chemistry , 25 :11892 , 2019
Abstract : Semiconductor metal oxides (SMO)-based gas-sensing materials suffer from insufficient detection of a specific target gas. Reliable selectivity, high sensitivity, and rapid response-recovery times under various working conditions are the main requirements for optimal gas sensors. Chemical warfare agents (CWA) such as sarin are fatal inhibitors of acetylcholinesterase in the nerve system. So, sensing materials with high sensitivity and selectivity toward CWA are urgently needed. Herein, micro-nano octahedral Co3 O4 functionalized with hexafluoroisopropanol (HFIP) were deposited on a layer of reduced graphene oxide (rGO) as a double-layer sensing materials. The Co3 O4 micro-nano octahedra were synthesized by direct growth from electrospun fiber templates calcined in ambient air. The double-layer rGO/Co3 O4 -HFIP sensing materials presented high selectivity toward DMMP (sarin agent simulant, dimethyl methyl phosphonate) versus rGO/Co3 O4 and Co3 O4 sensors after the exposure to various gases owing to hydrogen bonding between the DMMP molecules and Co3 O4 -HFIP. The rGO/Co3 O4 -HFIP sensors showed high stability with a response signal around 11.8 toward 0.5 ppm DMMP at 125 degrees C, and more than 75 % of the initial response was maintained under a saturated humid environment (85 % relative humidity). These results prove that these double-layer inorganic-organic composite sensing materials are excellent candidates to serve as optimal gas-sensing materials.
ESTHER : Alali_2019_Chemistry_25_11892
PubMedSearch : Alali_2019_Chemistry_25_11892
PubMedID: 31309626

Title : Screening of acetylcholinesterase inhibitors and characterizing of phytochemical constituents from Dichocarpum auriculatum (Franch.) W.T. Wang & P. K. Hsiao through UPLC-MS combined with an acetylcholinesterase inhibition assay in vitro - Li_2019_J.Ethnopharmacol_245_112185
Author(s) : Li P , Liu S , Liu Q , Shen J , Yang R , Jiang B , He C , Xiao P
Ref : J Ethnopharmacol , 245 :112185 , 2019
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: The genus Dichocarpum is endemic to East Asia, and many of them are traditionally used folk medicine in China. Dichocarpum auriculatum (Franch.) W. T. Wang et P. K. Hsiao has the effect of clearing away heat, removing toxicity, and relieving swelling in southwestern China. Intriguingly, its root and whole herb also used as remedy for the neurological disease epilepsy. However, there are not any scientific reports on the phytochemistry and pharmacological activities of D. auriculatum. AIM OF STUDY: Traditional and folk medicinal knowledge would be useful for finding new pharmaceutical resources. There are many evidences over the years reported that an interaction probably exists between epilepsy and Alzheimer's disease (AD). The aim of the study was to investigate the potential AChE inhibitors and the phytochemical profiles of the specie D. auriculatum. MATERIALS AND METHODS: The AChE inhibitory activity of plant extracts of D. auriculatum and other 6 species from different regions of the genus Dichocarpum were evaluated in vitro assays and the UPLC-Q-TOF-MS technique was used to analyze the chemical constituents. Moreover, UPLC-ESI-MS/MS was used to determine the distribution of 12 standard compounds in samples. RESULTS: As a preferred source of potential acetylcholinesterase inhibitors of the genus Dichocarpum, D. auriculatum has been further investigated. The screening results show that the ability of root extracts from D. auriculatum (IC50=0.15mg.mL(-)(1)) to inhibit AChE was better than other samples, it is consistent with traditional medicinal records. The phytochemical constituents of D. auriculatum was surveyed firstly by UPLC-Q-TOF-MS analysis, and 36 compounds, including 14 alkaloids, 16 flavonoids, 6 others, were identified tentatively. Further experiments showed that five compounds (columbamine, palmatine, dauricine, jatrorrhizine and berberine) from D. auriculatum were confirmed the potential inhibition of AChE activity in vitro (IC50: 0.24-6.37muM) and UPLC-ESI-MS/MS results showed that the content of most active compounds in roots was much higher than in aerial parts. Palmatine (IC50=0.34muM) and columbamine (IC50=0.24muM) showed prominent AChE inhibitory activity among the tested compounds. CONCLUSIONS: This is the first report about the evaluation of AChE inhibitory activity and phytochemical profiles of D. auriculatum, led to the identification of 36 compounds including alkaloids and flavonoids, and five alkaloids exhibited a significant AChE inhibitory activity and had the potential as AChE inhibitors. This study provided scientific experimental basis for the traditional efficacy of neurological disease of the plant.
ESTHER : Li_2019_J.Ethnopharmacol_245_112185
PubMedSearch : Li_2019_J.Ethnopharmacol_245_112185
PubMedID: 31446073

Title : Large-scale separation of acetylcholinesterase inhibitors from Zanthoxylum nitidum by pH-zone-refining counter-current chromatography target-guided by ultrafiltration high-performance liquid chromatography with ultraviolet and mass spectrometry screening - Liu_2019_J.Sep.Sci_42_1194
Author(s) : Liu M , Liu Q , Chen M , Huang X , Chen X
Ref : J Sep Sci , 42 :1194 , 2019
Abstract : A new strategy by converging ultrafiltration high-performance liquid chromatography with ultraviolet and mass spectrometry and pH-zone-refining counter-current chromatography was developed for the rapid screening and separation of potential acetylcholinesterase inhibitors from the crude alkaloidals extract of Zanthoxylum nitidum. An optimized two-phase solvent system composed of chloroform/methanol/water (4:3:3, v/v) was used in this study. And, in the optimal solvent system, 45 mM hydrochloric acid was added to the aqueous stationary phase as the retainer, while 5 mM triethylamine was added to the organic mobile phase as the eluter. As a result, with the purity of over 95%, five alkaloids including jatrorrhizine (1, 340 mg), columbamine (2, 112 mg), skimmianine (3, 154 mg), palmatine (4, 226 mg), and epiberberine (5, 132 mg) were successfully purified in one step from 3.0 g crude alkaloidals extract. And their structures were identified by ultraviolet, mass spectrometry, (1) H and (13) C NMR spectroscopy. Notably, compounds 2, 4 and 5 were firstly reported in Z. nitidum. In addition, acetylcholinesterase inhibitory activities of compounds 1-5 were evaluated, and compounds 3, 4 and 5 exhibited stronger acetylcholinesterase inhibitory activity (IC50 values at 8.52 +/- 0.64, 14.82 +/- 1.21 and 3.12 +/- 0.32 mug/mL, respectively) than berberine (IC50 value at 32.86 +/- 2.14 mug/mL, positive control). The results indicated that the proposed method is an efficient technique to rapidly screen acetylcholinesterase inhibitors from complex samples, and could be served as a large-scale preparative technique for separating ionizable active compounds.
ESTHER : Liu_2019_J.Sep.Sci_42_1194
PubMedSearch : Liu_2019_J.Sep.Sci_42_1194
PubMedID: 30638299

Title : A Conserved Tyrosine Residue in Slitrk3 Carboxyl-Terminus Is Critical for GABAergic Synapse Development - Li_2019_Front.Mol.Neurosci_12_213
Author(s) : Li J , Han W , Wu K , Li YD , Liu Q , Lu W
Ref : Front Mol Neurosci , 12 :213 , 2019
Abstract : Single-passing transmembrane protein, Slitrk3 (Slit and Trk-like family member 3, ST3), is a synaptic cell adhesion molecule highly expressed at inhibitory synapses. Recent studies have shown that ST3, through its extracellular domain, selectively regulates inhibitory synapse development via the trans-synaptic interaction with presynaptic cell adhesion molecule, receptor protein tyrosine phosphatase delta (PTPdelta) and the cis-interaction with postsynaptic cell adhesion molecule, Neuroligin 2 (NL2). However, little is known about the physiological function of ST3 intracellular, carboxyl (C)-terminal region. Here we report that in heterologous cells, ST3 C-terminus is not required for ST3 homo-dimerization and trafficking to the cell surface. In contrast, in hippocampal neurons, ST3 C-terminus, more specifically, the conserved tyrosine Y969 (in mice), is critical for GABAergic synapse development. Indeed, overexpression of ST3 Y969A mutant markedly reduced the gephyrin puncta density and GABAergic transmission in hippocampal neurons. In addition, single-cell genetic deletion of ST3 strongly impaired GABAergic transmission. Importantly, wild-type (WT) ST3, but not the ST3 Y969A mutant, could fully rescue GABAergic transmission deficits in neurons lacking endogenous ST3, confirming a critical role of Y969 in the regulation of inhibitory synapses. Taken together, our data identify a single critical residue in ST3 C-terminus that is important for GABAergic synapse development and function.
ESTHER : Li_2019_Front.Mol.Neurosci_12_213
PubMedSearch : Li_2019_Front.Mol.Neurosci_12_213
PubMedID: 31551708

Title : NOTUM inhibition increases endocortical bone formation and bone strength - Brommage_2019_Bone.Res_7_2
Author(s) : Brommage R , Liu J , Vogel P , Mseeh F , Thompson AY , Potter DG , Shadoan MK , Hansen GM , Jeter-Jones S , Cui J , Bright D , Bardenhagen JP , Doree DD , Moverare-Skrtic S , Nilsson KH , Henning P , Lerner UH , Ohlsson C , Sands AT , Tarver JE , Powell DR , Zambrowicz B , Liu Q
Ref : Bone Res , 7 :2 , 2019
Abstract : The disability, mortality and costs caused by non-vertebral osteoporotic fractures are enormous. Existing osteoporosis therapies are highly effective at reducing vertebral but not non-vertebral fractures. Cortical bone is a major determinant of non-vertebral bone strength. To identify novel osteoporosis drug targets, we phenotyped cortical bone of 3 366 viable mouse strains with global knockouts of druggable genes. Cortical bone thickness was substantially elevated in Notum (-/-) mice. NOTUM is a secreted WNT lipase and we observed high NOTUM expression in cortical bone and osteoblasts but not osteoclasts. Three orally active small molecules and a neutralizing antibody inhibiting NOTUM lipase activity were developed. They increased cortical bone thickness and strength at multiple skeletal sites in both gonadal intact and ovariectomized rodents by stimulating endocortical bone formation. Thus, inhibition of NOTUM activity is a potential novel anabolic therapy for strengthening cortical bone and preventing non-vertebral fractures.
ESTHER : Brommage_2019_Bone.Res_7_2
PubMedSearch : Brommage_2019_Bone.Res_7_2
PubMedID: 30622831
Gene_locus related to this paper: human-NOTUM

Title : New Sesquiterpenoids from the Fermented Broth of Termitomyces albuminosus and their Anti-Acetylcholinesterase Activity - Li_2019_Molecules_24_2980
Author(s) : Li W , Liu Q , Li S , Zheng Y
Ref : Molecules , 24 :2980 , 2019
Abstract : Termitomyces albuminosus is the symbiotic edible mushroom of termites and cannot be artificially cultivated at present. In the project of exploring its pharmaceutical metabolites by microbial fermentation, four new selinane type sesquiterpenoids-teucdiol C (1), D (2), E (3), and F (4), together with two known sesquiterpenoids teucdiol B (5) and epi-guaidiol A (6)-were obtained from its fermented broth of T. albuminosus. Their structures were elucidated by the analysis of NMR data, HR Q-TOF MS spectral data, CD, IR, UV, and single crystal X-ray diffraction. Epi-guaidiol A showed obvious anti-acetylcholinesterase activity in a dose-dependent manner. The experimental results displayed that T. albuminosus possess the pharmaceutical potential for Alzheimer's disease, and it was an effective way to dig new pharmaceutical agent of T. albuminosus with the microbial fermentation technique.
ESTHER : Li_2019_Molecules_24_2980
PubMedSearch : Li_2019_Molecules_24_2980
PubMedID: 31426402

Title : Dental malocclusion stimulates neuromuscular circuits associated with temporomandibular disorders - Liu_2018_Eur.J.Oral.Sci_126_466
Author(s) : Liu X , Zhang C , Liu Q , Zhou K , Yin N , Zhang H , Shi M , Wang M
Ref : Eur J Oral Sci , 126 :466 , 2018
Abstract : Unilateral anterior crossbite (UAC) has been demonstrated to cause masseter hyperactivity via the periodontal trigeminal mesencephalic nucleus (Vme)-trigeminal motor nucleus circuit. Here, we studied activation of motor neurons of the facial nucleus (VII), hypoglossal nucleus (XII), nucleus ambiguus (Amb), and spinal nucleus of the accessory nerve (SNA) in rats with UAC via their similar connections with Vme. An anterograde tracer, biotinylated dextran amine (BDA), was injected into the Vme to identify the central axon terminals around the motor neurons of VII, XII, Amb, and SNA. The expression of vesicular glutamate transporter 1 (VGLUT1) in neurons of VII, XII, Amb, and SNA, and the expression of acetylcholinesterase (AChE) were measured in the stapedius, lingualis, palatopharyngeal, and sternocleidomastoid muscles. In BDA-treated rats, many BDA-labeled cell bodies in the Vme and terminals in VII, XII, Amb, and SNA were identified. Compared with control rats, rats with UAC showed higher expression of VGLUT1 in these nuclei, and statistically significantly higher expression of AChE in the stapedius, lingualis, and sternocleidomastoid muscles, but not in the palatopharyngeal muscle. These findings suggest that UAC activates orofacial, head, and cervical multimotor behaviors via connections between the Vme and the corresponding motor nuclei.
ESTHER : Liu_2018_Eur.J.Oral.Sci_126_466
PubMedSearch : Liu_2018_Eur.J.Oral.Sci_126_466
PubMedID: 30341927

Title : Plasma exosome levels in non-small-cell lung cancer: Correlation with clinicopathological features and prognostic implications - Liu_2018_Cancer.Biomark_22_267
Author(s) : Liu Q , Xiang Y , Yuan S , Xie W , Li C , Hu Z , Wu N , Wu L , Yu Z , Bai L , Li Y
Ref : Cancer Biomark , 22 :267 , 2018
Abstract : BACKGROUND: Biomarker studies revealed important clinical significance of exosome for cancer patients. However, there is currently no consensus on exosome quantification methods. METHODS: Bicinchoninic acid (BCA) method, acetylcholinesterase (AChE) method and nanoparticle tracking analysis (NTA) were utilized to quantify 20 plasma exosome samples, and interrelations between these three methods were explored. Associations of plasma exosome levels with characteristics and prognosis of 208 non-small-cell lung cancer (NSCLC) patients were investigated. RESULTS: Results of the three methods for exosome quantification were significantly correlated with each other. Correlation coefficient between AChE and NTA (r= 0.79, P< 0.001) was greater than that between BCA and NTA (r= 0.64, P= 0.003). Plasma exosome levels of 208 NSCLC patients were then quantified with AChE method. Exosome level was significantly associated with tumour stage (P< 0.001) and the history of chronic obstructive pulmonary disease (P= 0.023). Cox proportional hazard analysis demonstrated that higher exosome level was independently associated with poorer overall survival (P= 0.033; hazard ratio = 1.72, 95% confidence interval: 1.05-2.83). CONCLUSIONS: Plasma exosome level correlates with tumor stage and the history of chronic obstructive pulmonary disease, and may serve as a prognostic factor for NSCLC.
ESTHER : Liu_2018_Cancer.Biomark_22_267
PubMedSearch : Liu_2018_Cancer.Biomark_22_267
PubMedID: 29660899

Title : Development of a Luminescent Dinuclear Ir(III) Complex for Ultrasensitive Determination of Pesticides - Lu_2018_Anal.Chem_90_11716
Author(s) : Lu L , Su H , Liu Q , Li F
Ref : Analytical Chemistry , 90 :11716 , 2018
Abstract : To improve the G-quadruplex specificity of Ir(III) complexes, a novel dinuclear Ir(III) complex (Din Ir(III)-1) was designed and synthesized through connecting two mononuclear Ir(III) complexes via a diphenyl bridge. Din Ir(III)-1 presents 3.4-4.1-fold enhancements for G-quadruplex relative to ssDNA and 4.3-5.3-fold enhancements relative to dsDNA in luminescence intensity, respectively, demonstrating an excellent G-quadruplex selectivity. Ascribed to its superior specificity to G-quadruplex, Din Ir(III)-1 was employed to construct a highly sensitive luminescent pesticides' detection platform. The detection is based on acetylcholinesterase (AChE)-catalyzed hydrolysis product-induced DNA conformational transformation and subsequent terminal deoxynucleotidyl transferase (TdT) directed G-quadruplex formation. The assay exhibited a linear response between the emission intensity of Din Ir(III)-1 and the pesticide concentration in the range of 0.5-25 mug/L ( R(2) = 0.994), and the limit of detection for the pesticide was as low as 0.37 mug/L when using aldicarb as the model pesticide. Moreover, this strategy demonstrates good applicability for the pesticide detection in real samples. It is also versatile for the detection of other organophosphate or carbamate pesticides, which have the inhibition ability toward AChE. Therefore, the proposed approach is scalable for practical application in food safety and environmental monitoring fields and will provide promising solutions for the assay of pesticide residues.
ESTHER : Lu_2018_Anal.Chem_90_11716
PubMedSearch : Lu_2018_Anal.Chem_90_11716
PubMedID: 30192517

Title : Ultrasonic pretreatment promotes diacylglycerol production from lard by lipase-catalysed glycerolysis and its physicochemical properties - Zhao_2018_Ultrason.Sonochem_48_11
Author(s) : Zhao X , Sun Q , Qin Z , Liu Q , Kong B
Ref : Ultrason Sonochem , 48 :11 , 2018
Abstract : The objective of this study was to evaluate the effect of ultrasonic pretreatment on diacylglycerol (DAG) synthesis by lipase-catalysed glycerolysis of lard and to analyse the physicochemical properties of lard-based DAG. The optimal ultrasonic pretreatment conditions were: Rhizomucor miehei (Lipozyme(R) RMIM)-to-lard ratio 4:100 (W/W), 45 degrees C for 5min, and power 250W. The lard-based DAG samples for 4h of glycerolysis reactions with ultrasonic pretreatment (named DAG-U) and 11h of glycerolysis reactions without ultrasonic pretreatment (named DAG-N) had similar DAG contents and were used for further analysis. The major FA compositions and iodine value of lard, DAG-U and DAG-N were similar. Fourier transform infrared spectroscopy analysis proved that enzymatic glycerolysis with and without ultrasonic pretreatment did not change the structure of the lard. Differential scanning calorimetry analysis showed that the crystallization onset of DAG-U and DAG-N shifted to higher temperatures than that of lard, which indicated that DAG oils accelerated nucleation and crystal growth. X-ray diffraction analysis revealed that both DAG-U and DAG-N contained beta' crystal and a substantially lower amount of beta crystal. Overall, ultrasonic pretreatment promotes diacylglycerol production from lard through lipase-catalysed glycerolysis, and DAG-U and DAG-N have similar physicochemical properties.
ESTHER : Zhao_2018_Ultrason.Sonochem_48_11
PubMedSearch : Zhao_2018_Ultrason.Sonochem_48_11
PubMedID: 30080532

Title : Identification of interneurons required for the aversive response of Caenorhabditis elegans to graphene oxide - Xiao_2018_J.Nanobiotechnology_16_45
Author(s) : Xiao G , Chen H , Krasteva N , Liu Q , Wang D
Ref : J Nanobiotechnology , 16 :45 , 2018
Abstract : BACKGROUND: So far, how the animals evade the environmental nanomaterials is still largely unclear. In this study, we employed in vivo assay system of Caenorhabditis elegans to investigate the aversive behavior of nematodes to graphene oxide (GO) and the underlying neuronal basis. RESULTS: In this assay model, we detected the significant aversive behavior of nematodes to GO at concentrations more than 50 mg/L. Loss-of-function mutation of nlg-1 encoding a neuroligin with the function in connecting pre- and post-synaptic neurons suppressed the aversive behavior of nematodes to GO. Moreover, based on the neuron-specific activity assay, we found that the NLG-1 activity in AIY or AIB interneurons was required for the regulation of aversive behavior to GO. The neuron-specific activities of NLG-1 in AIY or AIB interneurons were also required for the regulation of GO toxicity. CONCLUSIONS: Using nlg-1 mutant as a genetic tool, we identified the AIY and AIB interneurons required for the regulation of aversive behavior to GO. Our results provide an important neuronal basis for the aversive response of animals to environmental nanomaterials.
ESTHER : Xiao_2018_J.Nanobiotechnology_16_45
PubMedSearch : Xiao_2018_J.Nanobiotechnology_16_45
PubMedID: 29703212

Title : Novel 8-hydroxyquinoline derivatives targeting beta-amyloid aggregation, metal chelation and oxidative stress against Alzheimer's disease - Yang_2018_Bioorg.Med.Chem_26_3191
Author(s) : Yang X , Cai P , Liu Q , Wu J , Yin Y , Wang X , Kong L
Ref : Bioorganic & Medicinal Chemistry , 26 :3191 , 2018
Abstract : A series of multitargeted 8-hydroxyquinoline derivatives were designed and synthesized for the treatment of Alzheimer's disease (AD). In vitro studies indicated that most of the prepared compounds exhibited significant inhibitory effects against self-induced Abeta(1-42) aggregation and potential antioxidant properties especially compound 5b (IC(50) = 5.64 microM for self-induced Abeta aggregation; the oxygen radical absorbance capacity using fluorescein (ORAC-FL) value is 2.63 Trolox equivalents). Notably, 5b can chelate biometals and inhibit Cu(2+)/Zn(2+)-induced Abeta(1-42) aggregation. The cell assays showed that 5b had excellent protective effects against oxidative toxin H(2)O(2) and presented low neurotoxicity in PC12 cells. Furthermore, 5b could penetrate the blood-brain barrier (BBB) in vitro and did not show any acute toxicity in mice at doses up to 2000 mg/kg in vivo. Our findings provide a rationale for the potential application of compound 5b as a lead compound in AD therapy.
ESTHER : Yang_2018_Bioorg.Med.Chem_26_3191
PubMedSearch : Yang_2018_Bioorg.Med.Chem_26_3191
PubMedID: 29729985

Title : Responses of Antioxidant Defense and Immune Gene Expression in Early Life Stages of Large Yellow Croaker (Pseudosciaena crocea) Under Methyl Mercury Exposure - Wu_2018_Front.Physiol_9_1436
Author(s) : Wu F , Huang W , Liu Q , Xu X , Zeng J , Cao L , Hu J , Gao Y , Jia S
Ref : Front Physiol , 9 :1436 , 2018
Abstract : Early life stages of marine organisms are the most sensitive stages to environment stressors including pollutants. In order to understand the toxicological effects induced by MeHg exposure on juveniles of large yellow croaker (Pseudosciaena crocea), a toxicity test was performed wherein fish were exposed to sub-lethal concentrations of MeHg under laboratory conditions (18 +/- 1 degrees C; 26 +/- 1 in salinity). After 30 days of 0-4.0 mug L(-1) MeHg exposure, SOD activity was significantly decreased in the 0.25, 1.0, and 4.0 mug L(-1) treatments; while CAT activity was significantly increased in the 4.0 mug L(-1) treatments; GSH level, GPx activity were significantly elevated in the 4.0 mug L(-1) treatments, respectively. Meanwhile, malondialdehyde content was also significantly increased in the 1.0 and 4.0 mug L(-1) treatments with respect to the control. Acetylcholinesterase activity was significantly decreased by 18.3, 25.2, and 21.7% in the 0.25, 1.0, and 4.0 mug L(-1) treatments, respectively. The expression of TCTP, GST3, Hsp70, Hsp27 mRNA were all up-regulated in juveniles with a dose-dependent manner exposed to MeHg. These results suggest that large yellow croaker juveniles have the potential to regulate the levels of antioxidant enzymes and initiate immune response in order to protect fish to some extent from oxidative stress induced by MeHg.
ESTHER : Wu_2018_Front.Physiol_9_1436
PubMedSearch : Wu_2018_Front.Physiol_9_1436
PubMedID: 30364149

Title : A Human DPP4-Knockin Mouse's Susceptibility to Infection by Authentic and Pseudotyped MERS-CoV - Fan_2018_Viruses_10_
Author(s) : Fan C , Wu X , Liu Q , Li Q , Liu S , Lu J , Yang Y , Cao Y , Huang W , Liang C , Ying T , Jiang S , Wang Y
Ref : Viruses , 10 : , 2018
Abstract : Infection by the Middle East respiratory syndrome coronavirus (MERS-CoV) causes respiratory illness and has a high mortality rate (~35%). The requirement for the virus to be manipulated in a biosafety level three (BSL-3) facility has impeded development of urgently-needed antiviral agents. Here, we established anovel mouse model by inserting human dipeptidyl peptidase 4 (hDPP4) into the Rosa26 locus using CRISPR/Cas9, resulting in global expression of the transgene in a genetically stable mouse line. The mice were highly susceptible to infection by MERS-CoV clinical strain hCoV-EMC, which induced severe diffuse pulmonary disease in the animals, and could also be infected by an optimized pseudotyped MERS-CoV. Administration of the neutralizing monoclonal antibodies, H111-1 and m336, as well as a fusion inhibitor peptide, HR2P-M2, protected mice from challenge with authentic and pseudotyped MERS-CoV. These results confirmed that the hDPP4-knockin mouse is a novel model for studies of MERS-CoV pathogenesis and anti-MERS-CoV antiviral agents in BSL-3 and BSL-2facilities, respectively.
ESTHER : Fan_2018_Viruses_10_
PubMedSearch : Fan_2018_Viruses_10_
PubMedID: 30142928

Title : [Effects of tenofovir and telbivudine on HBV RNA in pregnant women with different genotypes of HBeAg-positive hepatitis B in Guizhou Province] - Zhang_2018_Zhonghua.Yi.Xue.Za.Zhi_98_3503
Author(s) : Zhang BF , Cheng ML , Lu S , Wu J , Wu YY , Liu Q , Zhao XK , Li YY , Hu YX , Liu W
Ref : Zhonghua Yi Xue Za Zhi , 98 :3503 , 2018
Abstract : Objective: To investigate whether HBV genotype influences HBV DNA and RNA responses to tenofovir(TDF) and telbivudine(LDT) in pregnant women with HBeAg-positive in Guizhou. Methods: This was a retrospective analysis of 75 pregnant women hepatitis B with HBsAg and HBeAg double-positive(19-38 years old, median age 26 years old), who were enrolled in the Department of Infectious Diseases and Obstetrics Clinic of the Affiliated Hospital of Guizhou Medical University from May 2016 to July 2017.Blood samples were collected at 12-24, 28-32 and 36-40 weeks of pregnancy for analyses of genotype, including hepatitis B surface antigen(HBsAg), hepatitis B e antigen (HBeAg), HBV DNA, HBV RNA and liver function, alanine transaminase(ALT), aspartate transaminase(AST), total bilirubin(TBiL), total bile acids(TBA), cholinesterase(CHE), alkaline phosphatase (ALP). Continuous variable was adopted by means of mean+/-standard deviation, and categorical variables were used for statistical analysis. Results: The HBV genotype was B in 64.0%(48/75)and C in 36.0%(27/75). The TDF and LDT groups showed no differences in demographic and clinical characteristics, including liver function tests, HBsAg, HBeAg, log(10)HBV DNA and log(10)HBV RNA.TDF groups, pre-treatment: HBV DNA (4.8+/-2.0), HBV RNA (6.4+/-1.1); at 4 weeks of treatment: HBV DNA (4.0+/-0.8), HBV RNA (6.0+/-0.9); at the end of treatment: HBV DNA (3.1+/-0.7), HBV RNA (5.5+/-0.8). LDT groups, pre-treatment HBV DNA (5.1+/-2.0), HBV RNA(6.5+/-0.9); at 4 weeks of treatment: HBV DNA (4.4+/-1.2), HBV RNA(6.5+/-0.8); at the end of treatment: HBV DNA(3.5+/-1.2), HBV RNA (6.1+/-0.7). Compared with pre-treatment (12-24 weeks), the TDF and LDT group showed significant reductions in log(10)(HBV DNA) and log(10)(HBV RNA) at 36-40 weeks ( P<0.05). Under the influence of excluding other variables, the genotype had a certain influence on the HBV RNA load.That was, HBV RNA in patients with the C genome decreased by 0.54 units(log(10)) at the end of the treatment compared to patients with the B genome, and the P value was less than 0.05. Conclusion: B and C genotypes are predominant in pregnant women with hepatitis B in Guizhou Province. B-type viruses are more easily controlled when different genotypes are treated with nucleotide analogues.
ESTHER : Zhang_2018_Zhonghua.Yi.Xue.Za.Zhi_98_3503
PubMedSearch : Zhang_2018_Zhonghua.Yi.Xue.Za.Zhi_98_3503
PubMedID: 30481899

Title : Repeated Autologous Bone Marrow Transfusion through Portal Vein for Treating Decompensated Liver Cirrhosis after Splenectomy - Zhang_2018_Gastroenterol.Res.Pract_2018_4136082
Author(s) : Zhang W , Teng M , Liu B , Liu Q , Liu X , Si Y , Li L
Ref : Gastroenterol Res Pract , 2018 :4136082 , 2018
Abstract : Objective: This study is aimed at examining the impact of repeated intraportal autologous bone marrow transfusion (ABMT) in patients with decompensated liver cirrhosis after splenectomy. Methods: A total of 25 patients with decompensated liver cirrhosis undergoing splenectomy were divided into ABMT and control groups. The portal vein was cannulated intraoperatively using Celsite Implantofix through the right gastroomental vein. Both groups were given a routine medical treatment. Then, 18 mL of autologous bone marrow was transfused through the port in the patients of the ABMT group 1 week, 1 month, and 3 months after laminectomy, while nothing was given to the control group. All patients were monitored for adverse events. Liver function tests, including serum albumin (ALB), alanine aminotransferase (ALT), total bilirubin (TB), prothrombin activity (PTA), cholinesterase (CHE), alpha-fetoprotein (AFP), and liver stiffness measurement (LSM), were conducted before surgery and 1, 3, and 6 months after surgery. Results: Significant improvements in ALB, ALT, and CHE levels and decreased LSM were observed in the ABMT group compared with those in the control group (P < 0.05). TB and PTA improved in both groups but with no significant differences between the groups. No significant changes were observed in AFP in the control group, but it decreased in the ABMT group. No major adverse effects were noted during the follow-up period in the patients of either group. Conclusions: Repeated intraportal ABMT was clinically safe, and liver function of patients significantly improved. Therefore, this therapy has the potential to treat patients with decompensated liver cirrhosis after splenectomy. This trial was registered with the identification number of ChiCTR-ONC-17012592.
ESTHER : Zhang_2018_Gastroenterol.Res.Pract_2018_4136082
PubMedSearch : Zhang_2018_Gastroenterol.Res.Pract_2018_4136082
PubMedID: 30510572

Title : The dual DPP4 inhibitor and GPR119 agonist HBK001 regulates glycemic control and beta cell function ex and in vivo - Huan_2017_Sci.Rep_7_4351
Author(s) : Huan Y , Jiang Q , Li G , Bai G , Zhou T , Liu S , Li C , Liu Q , Sun S , Yang M , Guo N , Wang X , Wang S , Liu Y , Wang G , Huang H , Shen Z
Ref : Sci Rep , 7 :4351 , 2017
Abstract : Glucagon like peptide-1 (GLP-1) plays a vital role in glucose homeostasis and sustaining beta-cell function. Currently there are two major methods to enhance endogenous GLP-1 activity; inhibiting dipeptidyl peptidase-4 (DPP4) or activating G protein-coupled receptor 119 (GPR119). Here we describe and validate a novel dual-target compound, HBK001, which can both inhibit DPP4 and activate GPR119 ex and in vivo. We show that HBK001 can promote glucose-stimulated insulin secretion in mouse and human primary islets. A single administration of HBK001 in ICR mice can increase plasma incretins levels much more efficiently than linagliptin, a classic DPP4 inhibitor. Long-term treatment of HBK001 in KKAy mice can ameliorate hyperglycemia as well as improve glucose tolerance, while linagliptin fails to achieve such glucose-lowing effects despite inhibiting 95% of serum DPP4 activity. Moreover, HBK001 can increase first-phase insulin secretion in KKAy mice, suggesting a direct effect on islet beta-cells via GPR119 activation. Furthermore, HBK001 can improve islet morphology, increase beta-cell proliferation and up-regulate genes involved in improved beta-cell function. Thus, we have identified, designed and synthesized a novel dual-target compound, HBK001, which represents a promising therapeutic candidate for type 2 diabetes, especially for patients who are insensitive to current DPP4 inhibitors.
ESTHER : Huan_2017_Sci.Rep_7_4351
PubMedSearch : Huan_2017_Sci.Rep_7_4351
PubMedID: 28659588

Title : Non-neuronal cholinergic activity is potentiated in myasthenia gravis - Han_2017_BMC.Neurol_17_28
Author(s) : Han B , Zhang C , Liu S , Xia Y , Sun H , Gong Z , Simard AR , Liu Q , Hao J
Ref : BMC Neurol , 17 :28 , 2017
Abstract : BACKGROUND: Non-neuronal acetylcholine (ACh) restricts autoimmune responses and attenuates inflammation by cholinergic anti-inflammation pathway. To date, the implication of ACh in myasthenia gravis (MG) remained unexplored. This study aimed to investigate the possible relationship between ACh levels, anti-muscle-specific tyrosine kinase (MuSK) antibody titers, main clinical features and outcomes of MG patients. METHODS: We successfully measured ACh levels in human peripheral blood mononuclear cells (PBMCs) from 125 MG patients and 50 matched healthy controls by using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). We assessed the quantitative MG (QMG) scores for each patient and titered anti-MuSK antibody. RESULTS: We found that PBMC-derived ACh level was significantly higher in MG patients, especially in patients of class III, IV-V, compared with that in controls (0.142 +/- 0.108 vs. 0.075 +/- 0.014 ng/million cells, p = 0.0003) according to the Myasthenia Gravis Foundation of America clinical classification. Importantly, we also found that ACh levels were positively correlated with QMG scores (r = 0.83, p < 0.0001) and anti-MuSK Ab levels (r = 0.85, p < 0.0001). CONCLUSIONS: Our demonstration of elevated ACh levels in PBMCs of MG patients foreshadows potential new avenues for MG research and treatment.
ESTHER : Han_2017_BMC.Neurol_17_28
PubMedSearch : Han_2017_BMC.Neurol_17_28
PubMedID: 28178923

Title : Structure-Guided Discovery of Novel, Potent, and Orally Bioavailable Inhibitors of Lipoprotein-Associated Phospholipase A2 - Liu_2017_J.Med.Chem_60_10231
Author(s) : Liu Q , Huang F , Yuan X , Wang K , Zou Y , Shen J , Xu Y
Ref : Journal of Medicinal Chemistry , 60 :10231 , 2017
Abstract : Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a promising therapeutic target for atherosclerosis, Alzheimer's disease, and diabetic macular edema. Here we report the identification of novel sulfonamide scaffold Lp-PLA2 inhibitors derived from a relatively weak fragment. Similarity searching on this fragment followed by molecular docking leads to the discovery of a micromolar inhibitor with a 300-fold potency improvement. Subsequently, by the application of a structure-guided design strategy, a successful hit-to-lead optimization was achieved and a number of Lp-PLA2 inhibitors with single-digit nanomolar potency were obtained. After preliminary evaluation of the properties of drug-likeness in vitro and in vivo, compound 37 stands out from this congeneric series of inhibitors for good inhibitory activity and favorable oral bioavailability in male Sprague-Dawley rats, providing a quality candidate for further development. The present study thus clearly demonstrates the power and advantage of integrally employing fragment screening, crystal structures determination, virtual screening, and medicinal chemistry in an efficient lead discovery project, providing a good example for structure-based drug design.
ESTHER : Liu_2017_J.Med.Chem_60_10231
PubMedSearch : Liu_2017_J.Med.Chem_60_10231
PubMedID: 29193967
Gene_locus related to this paper: human-PLA2G7

Title : Bioconcentration of the antidepressant fluoxetine and its effects on the physiological and biochemical status in Daphnia magna - Ding_2017_Ecotoxicol.Environ.Saf_142_102
Author(s) : Ding J , Zou H , Liu Q , Zhang S , Mamitiana Razanajatovo R
Ref : Ecotoxicology & Environmental Safety , 142 :102 , 2017
Abstract : The aim of this study was to evaluate the bioconcentration potential of fluoxetine and its biological effects in Daphnia magna. After 48h of waterborne exposure, the bioconcentration of fluoxetine in D. magna was determined to be 460.61 and 174.41Lkg-1 for nominal exposure concentrations of 0.5 and 5microgL-1, respectively. Moreover, various biological endpoints, including physiological responses (filtration and ingestion rates), enzymatic biomarkers related to neurotoxicity [acetylcholinesterase (AChE)] and antioxidant defense [superoxide dismutase (SOD)], and an oxidative stress damage marker [malondialdehyde (MDA)], were assessed. Fluoxetine exposure increased the filtration rate of daphnia, while the ingestion rate was not obviously modified. AChE activity was significantly inhibited, highlighting the neurotoxicity of fluoxetine on D. magna. However, with some alterations in the SOD activity and MDA content, no obvious oxidative damage was observed in D. magna exposed to fluoxetine at the tested concentrations. These results indicate that fluoxetine can be accumulated and consequently induce physiological and biochemical perturbations in D. magna.
ESTHER : Ding_2017_Ecotoxicol.Environ.Saf_142_102
PubMedSearch : Ding_2017_Ecotoxicol.Environ.Saf_142_102
PubMedID: 28395202

Title : MicroRNA-132 attenuates neurobehavioral and neuropathological changes associated with intracerebral hemorrhage in mice - Zhang_2017_Neurochem.Int_107_182
Author(s) : Zhang Y , Han B , He Y , Li D , Ma X , Liu Q , Hao J
Ref : Neurochem Int , 107 :182 , 2017
Abstract : Recent studies suggest that microRNA-132 (miR-132) potentiates the cholinergic blockade of inflammatory reactions by targeting acetylcholinesterase (AChE) and affords robust protection against ischemia-induced neuronal death. However, the role of miR-132 in intracerebral hemorrhage (ICH) remains unexplored. This study aimed to determine whether miR-132 participates in the process and launches an anti-inflammatory response in a mouse model of ICH. To establish a relationship between miR-132 and ICH-induced neuronal inflammation and death, we used unilateral stereotaxic injections to deliver lentiviruses encoding miR-132, anti-miR-132 or an empty lentiviral vector directly into the right caudate nuclei of 192 living male C57BL/6 mice. Fourteen days later, ICH was induced by injection of autologous blood into these three groups. Neurodeficits, brain edema, blood-brain barrier (BBB) integrity, inflammatory reactions, together with cell death were assessed after ICH. Compared with the control group, the mice overexpressing miR-132 in the brain responded with attenuated neurological deficits and brain edema. The counts of activated microglia and the expression of proinflammatory cytokines were also decreased in these mice. Additionally, BBB integrity improved, and the extent of neuronal death decreased in ICH mice injected with lentivirus encoding miR-132. On the contrary, a decrease of miR-132 expression aggravated the severity of inflammation and increased cell apoptosis. Overall, these findings support a protective role of miR-132 in a mouse model of ICH, providing new opportunities for therapeutic intervention.
ESTHER : Zhang_2017_Neurochem.Int_107_182
PubMedSearch : Zhang_2017_Neurochem.Int_107_182
PubMedID: 27940326

Title : Soluble epoxide hydrolase inhibitors might prevent ischemic arrhythmias via microRNA-1 repression in primary neonatal mouse ventricular myocytes - Liu_2017_Mol.Biosyst_13_556
Author(s) : Liu Q , Zhao X , Peng R , Wang M , Zhao W , Gui YJ , Liao CX , Xu DY
Ref : Mol Biosyst , 13 :556 , 2017
Abstract : Ischemic arrhythmias are the main causes of sudden cardiac death. It has been reported that soluble epoxide hydrolase inhibitors (sEHis) could prevent arrhythmias; however, the underlying molecular mechanisms remain unclear. In recent years, the proarrhythmic role of microRNA-1 (miR-1) has been investigated. This study aimed to elucidate whether sEHis prevented ischemic arrhythmias by suppressing miR-1. The primary neonatal mouse ventricular myocyte model of miR-1 overexpression was established by incubating with agonist microONTM mmu-miR-1a-3p agomir (DAEDstainTM Dye) (agomiR-1). The sEHi, trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB), was administered following miR-1 overexpression. Quantitative real-time PCR (qPCR) and western blotting were used to test alterations in the expression of miR-1 and its target mRNAs GJA1 and KCNJ2 and their respective encoded proteins connexin 43 (Cx43) and the K+ channel subunit (Kir2.1). The whole-cell patch-clamp technique was used to record the alterations of the inward rectifying K+ current (IK1). Compared with the control group, miR-1 levels were significantly increased in the agomiR-1 group (p < 0.05), which suggested the successful construction of the miR-1 overexpression model. Compared with the control group, the levels of GJA1 and KCNJ2 mRNAs and Cx43 and Kir2.1 proteins in the agomiR-1 group were significantly decreased, and IK1 was significantly impaired (all p < 0.05). The miR-1 levels were dose-dependently decreased by t-AUCB, whereas t-AUCB dose-dependently increased the levels of GJA1 and KCNJ2 mRNAs and Cx43 and Kir2.1 proteins. Furthermore, t-AUCB restored the impaired IK1 (all p < 0.05). In conclusion, the sEHi t-AUCB has the ability to down-regulate proarrhythmic miR-1 and up-regulate its target genes and proteins, eventually restoring IK1.
ESTHER : Liu_2017_Mol.Biosyst_13_556
PubMedSearch : Liu_2017_Mol.Biosyst_13_556
PubMedID: 28112313

Title : Effect of the R92H and A379V genotypes of platelet-activating factor acetylhydrolase on its enzyme activity, oxidative stress and metabolic profile in Chinese women with polycystic ovary syndrome - Zhang_2017_Lipids.Health.Dis_16_57
Author(s) : Zhang R , Song Q , Liu H , Bai H , Zhang Y , Liu Q , Guan L , Fan P
Ref : Lipids Health Dis , 16 :57 , 2017
Abstract : BACKGROUND: The G994T polymorphism in platelet-activating factor acetylhydrolase (PAF-AH) gene is associated with the risk of polycystic ovary syndrome (PCOS). The aim of this study was to investigate the relationship between R92H and A379V variants of the PAF-AH gene and the risk of PCOS and to evaluate the effects of the genotypes on PAF-AH activities and clinical, metabolic and oxidative stress indexes in Chinese women.
METHODS: A total of 862 patients with PCOS based on the Rotterdam consensus criteria and 750 control women from a population of Chinese Han nationality in the Chengdu area were studied from 2006-2015. PAF-AH genotypes were determined by PCR and restriction fragment length polymorphism analysis. Plasma PAF-AH, high-density lipoprotein (HDL)-associated PAF-AH (H-PAF-AH) and apolipoprotein (apo) B-containing lipoprotein-associated PAF-AH (apoB-PAF-AH) activities were measured using the trichloroacetic acid precipitation procedure with PAF C-16 as a substrate. Circulating markers of oxidative stress, including serum total oxidant status, total antioxidant capacity, oxidative stress index and malondialdehyde levels, and clinical and metabolic parameters were also analyzed.
RESULTS: No significant differences were observed in the frequencies of R92H and A379V genotypes and alleles of the PAF-AH gene between PCOS and control groups (P > 0.05). Compared with patients with the 92RR genotype, patients with H allele of R92H (RH + HH genotype) had significantly higher plasma PAF-AH and apoB-PAF-AH activities (P < 0.05) and tended to exhibit increased H-PAF-AH activity (P = 0.063) after adjusted for age and BMI. However, when serum LDL-C, HDL-C, TG and HOMA index were added as covariates, the comparisons no longer remained statistical significance (P > 0.05). There were no significant differences in clinical, hormonal, metabolic and circulating oxidative stress parameters and the frequencies of PAF-AH G449T genotype according to PAF-AH R92H or A379V genotyping in patients with PCOS and control women.
CONCLUSIONS: There were no significant associations between R92H and A379V variants of PAF-AH gene and risk of PCOS in Chinese women. The increased plasma PAF-AH and apoB-PAF-AH activities in patients with H allele of R92H are related to the R92 --> H variation, changes in plasma lipoprotein levels, insulin resistance, aging, and gaining weight and thus may be involved in the pathogenesis of PCOS and the increased risks of future cardiovascular diseases.
ESTHER : Zhang_2017_Lipids.Health.Dis_16_57
PubMedSearch : Zhang_2017_Lipids.Health.Dis_16_57
PubMedID: 28320416

Title : Effects of abhydrolase domain containing 5 gene (ABHD5) expression and variations on chicken fat metabolism - Ouyang_2016_Poult.Sci_95_99
Author(s) : Ouyang H , Liu Q , Xu J , Zeng F , Pang X , Jebessa E , Liang S , Nie Q , Zhang X
Ref : Poult Sci , 95 :99 , 2016
Abstract : Abhydrolase domain containing 5 gene (ABHD5), also known as comparative gene identification 58 (CGI-58), is a member of the alpha/beta-hydrolase family as a protein cofactor of ATGL stimulating its triacylglycerol hydrolase activity. In this study, we aim to characterize the expression and variations of ABHD5 and to study their functions in chicken fat metabolism. We compared the ABHD5 expression level in various tissues and under different nutrition conditions, identified the variations of ABHD5, and associated them with production traits in an F2 resource population of chickens. Overexpression analysis with two different genotypes and siRNA interfering analysis of ABHD5 were performed in chicken preadipocytes. Chicken ABDH5 was expressed widely and most predominantly in adipose tissue. Five SNPs of the ABHD5 gene were identified and genotyped in the F2 resource population. The c.490C > T SNP was associated with subcutaneous fat thickness (P < 0.01), carcass weight (P < 0.05), body weight (P < 0.05), shank diameter (P < 0.05), and shank length (P < 0.05). The c.423T > C SNP was also associated with chicken body weight (P < 0.05) and shank diameter (P < 0.05). In chicken preadipocytes, overexpression of wild type ABDH5 did not affect the mRNA level of ATGL (adipose triglyceride lipase) but markedly decreased (P < 0.05) the TG (triglyceride) content of the cell, whereas overexpression of mutation type ABHD5 did not affect either ATGL expression or TG content of the cell. The expression of ATGL and TG content of the cell were decreased (P < 0.05) after ABHD5 knockdown in preadipocytes. The mRNA level of ABHD5 was regulated by both feeding and fasting, and by consumption of a high fat diet. It was increased greatly by fasting (P < 0.05) and was returned to control levels after re-feeding in the adipose tissues, and down-regulated in abdominal fat (P < 0.05) and the liver (P < 0.01) of chickens with a high fat diet. These results suggest that expression and variations of ABHD5 may affect fat metabolism through regulating the activity of ATGL in chickens.
ESTHER : Ouyang_2016_Poult.Sci_95_99
PubMedSearch : Ouyang_2016_Poult.Sci_95_99
PubMedID: 26574024

Title : Activity changes of antioxidant and detoxifying enzymes in Tenebrio molitor (Coleoptera: Tenebrionidae) larvae infected by the entomopathogenic nematode Heterorhabditis beicherriana (Rhabditida: Heterorhabditidae) - Li_2016_Parasitol.Res_115_4485
Author(s) : Li X , Liu Q , Lewis EE , Tarasco E
Ref : Parasitol Res , 115 :4485 , 2016
Abstract : Entomopathogenic nematodes (EPNs) of the genera Steinernema and Heterorhabditis are lethal parasites of many insect species. To investigate defensive mechanisms towards EPNs in relation to antioxidative and detoxifying enzymes, we chose Tenebrio molitor (Coleoptera: Tenebrionidae) as experimental insect. We studied the activity changes of superoxide dismutases (SODs), peroxidases (PODs), and catalases (CATs), as well as tyrosinase (TYR), acetylcholinesterase (AChE), carboxylesterase (CarE), and glutathione S-transferase (GSTs) for 40 h in T. molitor larvae infected with Heterorhabditis beicherriana infective juveniles (IJs) at 5 rates (0, 20, 40, 80, and 160 IJs/larva). We found that when T. molitor larvae infected with H. beicherriana at higher rates (80 and 160 IJs/larva), SOD activity quickly increased to more than 70 % higher than that control levels. The activities of POD and CAT increased after 24 h. TYR activity increased slowly at lower rates of infection for 16 h, followed by a slight decrease, and then increasing from 32 to 40 h. The other detoxifying enzymes (GST, CarE, and AChE) were enhanced at lower infection rates, but were inhibited at higher rates. Our results suggested that host antioxidative response and detoxification reactions played a central role in the defensive reaction to EPNs, and that this stress which was reflected by the higher level enzymes activity contributed to the death of hosts. Further study should explore the exact function of these enzymes using different species of EPNs and investigate the links between enzyme activity and host susceptibility to EPNs.
ESTHER : Li_2016_Parasitol.Res_115_4485
PubMedSearch : Li_2016_Parasitol.Res_115_4485
PubMedID: 27637224

Title : Structural and Thermodynamic Characterization of Protein-Ligand Interactions Formed between Lipoprotein-Associated Phospholipase A2 and Inhibitors - Liu_2016_J.Med.Chem_59_5115
Author(s) : Liu Q , Chen X , Chen W , Yuan X , Su H , Shen J , Xu Y
Ref : Journal of Medicinal Chemistry , 59 :5115 , 2016
Abstract : Lipoprotein-associated phospholipase A2 (Lp-PLA2) represents a promising therapeutic target for atherosclerosis and Alzheimer's disease. Here we reported the first crystal structures of Lp-PLA2 bound with reversible inhibitors and the thermodynamic characterization of complexes. High rigidity of Lp-PLA2 structure and similar binding modes of inhibitors with completely different scaffolds are revealed. It not only provides the molecular basis for inhibitory activity but also sheds light on the essential features of Lp-PLA2 recognition with reversible inhibitors.
ESTHER : Liu_2016_J.Med.Chem_59_5115
PubMedSearch : Liu_2016_J.Med.Chem_59_5115
PubMedID: 27078579
Gene_locus related to this paper: human-PLA2G7

Title : Aurone Mannich base derivatives as promising multifunctional agents with acetylcholinesterase inhibition, anti-beta-amyloid aggragation and neuroprotective properties for the treatment of Alzheimer's disease - Li_2016_Eur.J.Med.Chem_126_762
Author(s) : Li Y , Qiang X , Luo L , Yang X , Xiao G , Liu Q , Ai J , Tan Z , Deng Y
Ref : Eur Journal of Medicinal Chemistry , 126 :762 , 2016
Abstract : A series of aurone Mannich base derivatives were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease. In vitro assays demonstrated that most of the derivatives were selective AChE inhibitors with good multifunctional properties. Among them, compound 7d exhibited outstanding inhibitory activity for RatAChE, EeAChE and HuAChE (IC50 = 0.00878 +/- 0.0002 muM, 0.0212 +/- 0.006 muM and 0.0371 +/- 0.004 muM, respectively). Moreover, 7d displayed high antioxidant activity and could confer significant neuroprotective effect against H2O2-induced PC-12 cell injury. In addition, 7d also showed biometal chelating abilities, good self- and Cu2+-induced Abeta1-42 aggregation inhibitory potency and high BBB permeability. These multifunctional properties highlight 7d as promising candidate for further studies directed to the development of novel drugs against AD.
ESTHER : Li_2016_Eur.J.Med.Chem_126_762
PubMedSearch : Li_2016_Eur.J.Med.Chem_126_762
PubMedID: 27951485

Title : Fumonisins: oxidative stress-mediated toxicity and metabolism in vivo and in vitro - Wang_2016_Arch.Toxicol_90_81
Author(s) : Wang X , Wu Q , Wan D , Liu Q , Chen D , Liu Z , Martinez-Larranaga MR , Martinez MA , Anadon A , Yuan Z
Ref : Archives of Toxicology , 90 :81 , 2016
Abstract : Fumonisins (FBs) are widespread Fusarium toxins commonly found as corn contaminants. FBs could cause a variety of diseases in animals and humans, such as hepatotoxic, nephrotoxic, hepatocarcinogenic and cytotoxic effects in mammals. To date, almost no review has addressed the toxicity of FBs in relation to oxidative stress and their metabolism. The focus of this article is primarily intended to summarize the progress in research associated with oxidative stress as a plausible mechanism for FB-induced toxicity as well as the metabolism. The present review showed that studies have been carried out over the last three decades to elucidate the production of reactive oxygen species (ROS) and oxidative stress as a result of FBs treatment and have correlated them with various types of FBs toxicity, indicating that oxidative stress plays critical roles in the toxicity of FBs. The major metabolic pathways of FBs are hydrolysis, acylation and transamination. Ceramide synthase, carboxylesterase FumD and aminotransferase FumI could degrade FB1 and FB2. The cecal microbiota of pigs and alkaline processing such as nixtamalization can also transform FB1 into metabolites. Most of the metabolites of FB1 were less toxic than FB1, except its partial (pHFB1) metabolites. Further understanding of the role of oxidative stress in FB-induced toxicity will throw new light on the use of antioxidants, scavengers of ROS, as well as on the blind spots of metabolism and the metabolizing enzymes of FBs. The present review might contribute to reveal the toxicity of FBs and help to protect against their oxidative damage.
ESTHER : Wang_2016_Arch.Toxicol_90_81
PubMedSearch : Wang_2016_Arch.Toxicol_90_81
PubMedID: 26419546

Title : The potential neurotoxicity of emerging tetrabromobisphenol A derivatives based on rat pheochromocytoma cells - Liu_2016_Chemosphere_154_194
Author(s) : Liu Q , Ren X , Long Y , Hu L , Qu G , Zhou Q , Jiang G
Ref : Chemosphere , 154 :194 , 2016
Abstract : Tetrabromobisphenol A (TBBPA) can cause diverse adverse effects including neurotoxicity. Emerging TBBPA derivatives, with high structure similarity to the parent compound, are now being concerned. In this study, the potential neurotoxicities of four TBBPA derivatives and their parent compound were studied by cell viability inhibition in rat pheochromocytoma cells (PC12) and the corresponding molecular mechanisms were investigated. The cellular toxicity was correlated with the chemical hydrophobicity. Tetrabromobisphenol A bis(2-hydroxyethyl ether) (TBBPA-BHEE) exhibited the highest cellular toxicity to PC12 due to its lowest hydrophobicity among these 5 tested compounds. Further experiments showed that TBBPA-BHEE disturbed dopamine (DA) secretion and altered acetylcholinesterase (AChE) enzymatic activity in PC12 cells. The molecular mechanism study indicated that TBBPA-BHEE induced cellular toxicity to PC12 cells through ROS-mediated caspase activation to a large extent, which was partially attenuated by the anti-oxidation of Vitamin E. Moreover, in contrast to TBBPA, the occurrence of TBBPA-BHEE toxicity to PC12 was not attributed to activation of mitogen-activated protein kinases (MAPKs) or thyroid hormone (TH) signaling pathway. These findings suggest TBBPA derivatives, especially TBBPA-BHEE, as potential neurotoxins need urgent attention.
ESTHER : Liu_2016_Chemosphere_154_194
PubMedSearch : Liu_2016_Chemosphere_154_194
PubMedID: 27055180

Title : [Effect of Bacillus thuringiensis var. israelensis (Bti) on detoxification en- zyme activity of larvae of Culex pipiens pallens and Aedes aegypti] - Han_2015_Zhongguo.Xue.Xi.Chong.Bing.Fang.Zhi.Za.Zhi_27_385
Author(s) : Han GJ , Li CM , Sun J , Liu Q , Zhao S , Qi JH , Xu J
Ref : Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi , 27 :385 , 2015
Abstract : OBJECTIVE: To investigate the effect of Bacillus thuringiensis var. israelensis (Bti) on the activities of three detoxification enzymes of Culex pipiens pallens and Aedes aegypti larvae.
METHODS: The activities of glutathione transferase, acetyl cholinesterase and carboxyl esterase, were detected after two kinds of mosquito larvae were treated by Bti at different time and concentrations.
RESULTS: The activities of three detoxification enzymes of the two kinds of mosquito larvae were influenced by Bti treatment. The activity of glutathione transferase was increased after the Bti treatment, but declined significantly and inhibited at a low level sustainably. The activity of carboxyl esterase was increased after the Bti treatment, but recovered to normal level quickly. Acetyl cholinesterase was affected slightly by the Bti treatment, shortly inhibited in the first time and then recovered. The active effects of the three detoxification enzymes were positively related to the concentration of Bti. CONCLUSION: The enzyme activities of glutathione transferase, acetyl cholinesterase and carboxyl esterase could be affected by Bti significantly.
ESTHER : Han_2015_Zhongguo.Xue.Xi.Chong.Bing.Fang.Zhi.Za.Zhi_27_385
PubMedSearch : Han_2015_Zhongguo.Xue.Xi.Chong.Bing.Fang.Zhi.Za.Zhi_27_385
PubMedID: 26767261

Title : In vitro and in vivo metabolism and inhibitory activities of vasicine, a potent acetylcholinesterase and butyrylcholinesterase inhibitor - Liu_2015_PLoS.One_10_e0122366
Author(s) : Liu W , Shi X , Yang Y , Cheng X , Liu Q , Han H , Yang B , He C , Wang Y , Jiang B , Wang Z , Wang C
Ref : PLoS ONE , 10 :e0122366 , 2015
Abstract : Vasicine (VAS), a potential natural cholinesterase inhibitor, exhibited promising anticholinesterase activity in preclinical models and has been in development for treatment of Alzheimer's disease. This study systematically investigated the in vitro and in vivo metabolism of VAS in rat using ultra performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight mass spectrometry. A total of 72 metabolites were found based on a detailed analysis of their 1H- NMR and 13C NMR data. Six key metabolites were isolated from rat urine and elucidated as vasicinone, vasicinol, vasicinolone, 1,2,3,9-tetrahydropyrrolo [2,1-b] quinazolin-3-yl hydrogen sulfate, 9-oxo-1,2,3,9-tetrahydropyrrolo [2,1-b] quinazolin-3-yl hydrogen sulfate, and 1,2,3,9-tetrahydropyrrolo [2,1-b] quinazolin-3-beta-D-glucuronide. The metabolic pathway of VAS in vivo and in vitro mainly involved monohydroxylation, dihydroxylation, trihydroxylation, oxidation, desaturation, sulfation, and glucuronidation. The main metabolic soft spots in the chemical structure of VAS were the 3-hydroxyl group and the C-9 site. All 72 metabolites were found in the urine sample, and 15, 25, 45, 18, and 11 metabolites were identified from rat feces, plasma, bile, rat liver microsomes, and rat primary hepatocyte incubations, respectively. Results indicated that renal clearance was the major excretion pathway of VAS. The acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities of VAS and its main metabolites were also evaluated. The results indicated that although most metabolites maintained potential inhibitory activity against AChE and BChE, but weaker than that of VAS. VAS undergoes metabolic inactivation process in vivo in respect to cholinesterase inhibitory activity.
ESTHER : Liu_2015_PLoS.One_10_e0122366
PubMedSearch : Liu_2015_PLoS.One_10_e0122366
PubMedID: 25849329

Title : Design, synthesis and evaluation of scutellarein-O-alkylamines as multifunctional agents for the treatment of Alzheimer's disease - Sang_2015_Eur.J.Med.Chem_94_348
Author(s) : Sang Z , Qiang X , Li Y , Yuan W , Liu Q , Shi Y , Ang W , Luo Y , Tan Z , Deng Y
Ref : Eur Journal of Medicinal Chemistry , 94 :348 , 2015
Abstract : A series of scutellarein-O-alkylamine derivatives were designed, synthesized and tested as multifunctional agents for the treatment of Alzheimer's disease (AD). The results showed that most of these compounds exhibited good multifunctional activities. Among them, compound 16d demonstrated significant metal chelating properties, moderate acetylcholinesterase (AChE) inhibitory and anti-oxidative activity, and excellent inhibitory effects on self-induced Abeta1-42 aggregation, Cu2+-induced Abeta1-42 aggregation, human AChE-induced Abeta1-40 aggregation and disassembled Cu2+-induced aggregation of the well-structured Abeta1-42 fibrils. Both kinetic analysis of AChE inhibition and molecular modeling study suggested that 16d binds simultaneously to the catalytic active site and peripheral anionic site of AChE. Moreover, compound 16d showed a good protective effect against H2O2-induced PC12 cell injury, with low toxicity in SH-SY5Y cells. Furthermore, the step-down passive avoidance test showed this compound significantly reversed scopolamine-induced memory deficit in mice. Thus, 16d was shown to be an interesting multifunctional lead compound worthy of further study.
ESTHER : Sang_2015_Eur.J.Med.Chem_94_348
PubMedSearch : Sang_2015_Eur.J.Med.Chem_94_348
PubMedID: 25778991

Title : Design, synthesis and evaluation of chromone-2-carboxamido-alkylbenzylamines as multifunctional agents for the treatment of Alzheimer's disease - Liu_2015_Bioorg.Med.Chem_23_911
Author(s) : Liu Q , Qiang X , Li Y , Sang Z , Tan Z , Deng Y
Ref : Bioorganic & Medicinal Chemistry , 23 :911 , 2015
Abstract : A series of chromone-2-carboxamido-alkylbenzylamines were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease (AD). The results showed that most of these compounds exhibited good multifunctional activities. Among them, compound 49 displayed excellent inhibitory potency toward acetylcholinesterase (AChE), moderate anti-oxidative activity, selective biometal chelating, and possessed good inhibitory effects on self-induced and Cu(2+)-induced Abeta aggregation. Both kinetic analysis of AChE inhibition and molecular modeling study indicated that 49 was a mixed-type inhibitor, binding simultaneously to the catalytic active site and peripheral anionic site of AChE. These results suggested that 49 might be a potential multifunctional agent for AD treatment.
ESTHER : Liu_2015_Bioorg.Med.Chem_23_911
PubMedSearch : Liu_2015_Bioorg.Med.Chem_23_911
PubMedID: 25678013

Title : Trade-off between thermal tolerance and insecticide resistance in Plutella xylostella - Zhang_2015_Ecol.Evol_5_515
Author(s) : Zhang LJ , Wu ZL , Wang KF , Liu Q , Zhuang HM , Wu G
Ref : Ecol Evol , 5 :515 , 2015
Abstract : Fitness costs associated with resistance to insecticides have been well documented, usually at normal temperature conditions, in many insect species. In this study, using chlorpyrifos-resistant homozygote (RR) and chlorpyrifos-susceptible homozygote (SS) of resistance ace1 allele of Plutella xylostella (DBM), we confirmed firstly that high temperature experience in pupal stage influenced phenotype of wing venation in insecticide-resistant and insecticide-susceptible Plutella xylostella, and SS DBM showed significantly higher thermal tolerance and lower damages of wing veins under heat stress than RR DBM. As compared to SS DBM, RR DBM displayed significantly lower AChE sensitivity to chlorpyrifos, higher basal GSTs activity and P450 production at 25 degrees C, but higher inhibitions on the enzyme activities and P450 production as well as reduced resistance to chlorpyrifos under heat stress. Furthermore, RR DBM displayed significantly higher basal expressions of hsp69s, hsp72s, hsp20,hsp90,Apaf-1, and caspase-7 at 25 degrees C, but lower induced expressions of hsps and higher induced expressions of Apaf-1,caspase-9, and caspase-7 under heat stress. These results suggest that fitness costs of chlorpyrifos resistance in DBM may partly attribute to excess consumption of energy caused by over production of detoxification enzymes and hsps when the proteins are less demanded at conducive environments but reduced expressions when they are highly demanded by the insects to combat environmental stresses, or to excess expressions of apoptotic genes under heat stress, which results in higher apoptosis. The evolutionary and ecological implications of these findings at global warming are discussed.
ESTHER : Zhang_2015_Ecol.Evol_5_515
PubMedSearch : Zhang_2015_Ecol.Evol_5_515
PubMedID: 25691976
Gene_locus related to this paper: pluxy-ACHE1

Title : Poster: Diverse nicotinic mechanisms in a model of multiple sclerosis -
Author(s) : Lukas RJ , Liu Q , Lucero L , Simard AR , Whiteaker P , Morley BJ , Shi FD
Ref : Biochemical Pharmacology , 97 :633 , 2015

Title : Flavisolibacter ginsenosidimutans sp. nov., with ginsenoside-converting activity isolated from soil used for cultivating ginseng - Zhao_2015_Int.J.Syst.Evol.Microbiol_65_4868
Author(s) : Zhao Y , Liu Q , Kang MS , Jin F , Yu H , Im WT
Ref : Int J Syst Evol Microbiol , 65 :4868 , 2015
Abstract : A Gram-reaction-negative, aerobic, non-motile and rod-shaped bacterial strain designated Gsoil 636T was isolated from soil of a ginseng cultivation field in Pocheon Province, South Korea and its taxonomic position was investigated using a polyphasic approach. Gsoil 636T grew at 18-30 degreesC and at pH 6.0-8.0 on R2A medium. Gsoil 636T possessed beta-glucosidase activity, which was responsible for its ability to transform ginsenoside Rb1 (ones of the dominant active components of ginseng) to F2. On the basis of 16S rRNA gene sequence similarity, Gsoil 636T was shown to belong to the family Chitinophagaceae and to be related to Flavisolibacter ginsengiterrae Gsoil 492T (96.7 % sequence similarity), Flavisolibacter ginsengisoli Gsoil 643T (96.6 %) and Flavisolibacter rigui 02SUJ3T (96.6 %). The G+C content of the genomic DNA was 48.9 %. The predominant respiratory quinone was MK-7 and the major fatty acids were iso-C15 : 0, summed feature 3 (comprising C16 : 1omega6c and/or C16 : 1omega7c) and iso-C17 : 0 3-OH. DNA and chemotaxonomic data supported the affiliation of Gsoil 636T to the genus Flavisolibacter. Gsoil 636T could be differentiated genotypically and phenotypically from the species of the genus Flavisolibacter with validly published names. The isolate therefore represents a novel species, for which the name Flavisolibacter ginsenosidimutans sp. nov. is proposed, with the type strain Gsoil 636T (KCTC 22818T = JCM 18197T = KACC 14277T).
ESTHER : Zhao_2015_Int.J.Syst.Evol.Microbiol_65_4868
PubMedSearch : Zhao_2015_Int.J.Syst.Evol.Microbiol_65_4868
PubMedID: 26442990
Gene_locus related to this paper: 9bact-a0a5b8uge7

Title : Multifunctional scutellarin-rivastigmine hybrids with cholinergic, antioxidant, biometal chelating and neuroprotective properties for the treatment of Alzheimer's disease - Sang_2015_Bioorg.Med.Chem_23_668
Author(s) : Sang Z , Li Y , Qiang X , Xiao G , Liu Q , Tan Z , Deng Y
Ref : Bioorganic & Medicinal Chemistry , 23 :668 , 2015
Abstract : To discover multifunctional agents for the treatment of Alzheimer's disease (AD), a series of scutellarein carbamate derivatives were designed and synthesized based on the multitarget-directed ligand strategy. Their acetylcholinesterase and butyrylcholinesterase inhibitory activities, antioxidant activities, metal-chelating properties and neuroprotective effects against hydrogen peroxide induced PC12 cell injury were evaluated in vitro. The results showed that most of the synthetic compounds exhibited good multifunctional activities. In particular, compound 15c exhibited dual inhibitory potency on acetylcholinesterase and butyrylcholinesterase with IC50 values of 0.57 and 22.6muM, respectively, and good antioxidative activity, with a value 1.3-fold of Trolox. In addition, 15c acted as a selective biometal chelator and possessed neuroprotective effects. Furthermore, 15c could cross the blood-brain barrier (BBB) in vitro and had significant neuroprotective effects in scopolamine-induced cognitive impairment in mice. Taken together, these results suggest that compound 15c might be a potential multifunctional agent for the treatment of AD.
ESTHER : Sang_2015_Bioorg.Med.Chem_23_668
PubMedSearch : Sang_2015_Bioorg.Med.Chem_23_668
PubMedID: 25614117

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

Title : Determination of nerve agent metabolites in human urine by isotope-dilution gas chromatography-tandem mass spectrometry after solid phase supported derivatization - Lin_2014_Anal.Bioanal.Chem_406_5213
Author(s) : Lin Y , Chen J , Yan L , Guo L , Wu B , Li C , Feng J , Liu Q , Xie J
Ref : Anal Bioanal Chem , 406 :5213 , 2014
Abstract : A simple and sensitive method has been developed and validated for determining ethyl methylphosphonic acid (EMPA), isopropyl methylphosphonic acid (IMPA), isobutyl methylphosphonic acid (iBuMPA), and pinacolyl methylphosphonic acid (PMPA) in human urine using gas chromatography-tandem mass spectrometry (GC-MS/MS) coupled with solid phase derivatization (SPD). These four alkyl methylphosphonic acids (AMPAs) are specific hydrolysis products and biomarkers of exposure to classic organophosphorus (OP) nerve agents VX, sarin, RVX, and soman. The AMPAs in urine samples were directly derivatized with pentafluorobenzyl bromide on a solid support and then extracted by liquid-liquid extraction. The analytes were quantified with isotope-dilution by negative chemical ionization (NCI) GC-MS/MS in a selected reaction monitoring (SRM) mode. This method is highly sensitive, with the limits of detection of 0.02 ng/mL for each compound in a 0.2 mL sample of human urine, and an excellent linearity from 0.1 to 50 ng/mL. It is proven to be very suitable for the qualitative and quantitative analyses of degradation markers of OP nerve agents in biomedical samples.
ESTHER : Lin_2014_Anal.Bioanal.Chem_406_5213
PubMedSearch : Lin_2014_Anal.Bioanal.Chem_406_5213
PubMedID: 24633564

Title : A visible light photoelectrochemical biosensor coupling enzyme-inhibition for organophosphates monitoring based on a dual-functional Cd(0.5)Zn(0.5)S-reduced graphene oxide nanocomposite - Liu_2014_Analyst_139_1121
Author(s) : Liu Q , Cai J , Huan J , Dong X , Wang C , Qiu B , Wang K
Ref : Analyst , 139 :1121 , 2014
Abstract : A novel visible light photoelectrochemical (PEC) platform coupled with enzyme-inhibition for rapid and sensitive determination of organophosphates (OPs) was constructed based on a dual-functional Cd0.5Zn0.5S-reduced graphene oxide (Cd0.5Zn0.5S-rGO) nanocomposite. Due to the inherent biocompatibility of the Cd0.5Zn0.5S-rGO nanocomposite, acetylcholinesterase (AChE) immobilized on the Cd0.5Zn0.5S-rGO modified electrode can hydrolyze acetylthiocholine chloride into thiocholine, which could increase the photocurrent of the enzyme electrode, and the further inhibition of OPs on the enzyme electrode could decrease the photocurrent response. Based on the notable change in the PEC response of the AChE-Cd0.5Zn0.5S-rGO modified electrode and using Dursban as a model, a simple and effective way for PEC monitoring of OPs is proposed, which showed a wide linear range of 0.001-1 mug mL(-1) with a low detection limit of 0.3 ng mL(-1) (S/N = 3). Moreover, the biosensor was successfully challenged with water samples, demonstrating a new method for rapid and sensitive screening/evaluating exposure to organophosphorus pesticides and other hazardous substances.
ESTHER : Liu_2014_Analyst_139_1121
PubMedSearch : Liu_2014_Analyst_139_1121
PubMedID: 24416761

Title : A Novel alpha\/beta-Hydrolase Gene IbMas Enhances Salt Tolerance in Transgenic Sweetpotato - Liu_2014_PLoS.One_9_e115128
Author(s) : Liu D , Wang L , Zhai H , Song X , He S , Liu Q
Ref : PLoS ONE , 9 :e115128 , 2014
Abstract : Salt stress is one of the major environmental stresses in agriculture worldwide and affects crop productivity and quality. The development of crops with elevated levels of salt tolerance is therefore highly desirable. In the present study, a novel maspardin gene, named IbMas, was isolated from salt-tolerant sweetpotato (Ipomoea batatas (L.) Lam.) line ND98. IbMas contains maspardin domain and belongs to alpha/beta-hydrolase superfamily. Expression of IbMas was up-regulated in sweetpotato under salt stress and ABA treatment. The IbMas-overexpressing sweetpotato (cv. Shangshu 19) plants exhibited significantly higher salt tolerance compared with the wild-type. Proline content was significantly increased, whereas malonaldehyde content was significantly decreased in the transgenic plants. The activities of superoxide dismutase (SOD) and photosynthesis were significantly enhanced in the transgenic plants. H2O2 was also found to be significantly less accumulated in the transgenic plants than in the wild-type. Overexpression of IbMas up-regulated the salt stress responsive genes, including pyrroline-5-carboxylate synthase, pyrroline-5-carboxylate reductase, SOD, psbA and phosphoribulokinase genes, under salt stress. These findings suggest that overexpression of IbMas enhances salt tolerance of the transgenic sweetpotato plants by regulating osmotic balance, protecting membrane integrity and photosynthesis and increasing reactive oxygen species scavenging capacity.
ESTHER : Liu_2014_PLoS.One_9_e115128
PubMedSearch : Liu_2014_PLoS.One_9_e115128
PubMedID: 25501819
Gene_locus related to this paper: ipoba-a0a076l3m2

Title : Design, synthesis and evaluation of genistein-O-alkylbenzylamines as potential multifunctional agents for the treatment of Alzheimer's disease - Qiang_2014_Eur.J.Med.Chem_76_314
Author(s) : Qiang X , Sang Z , Yuan W , Li Y , Liu Q , Bai P , Shi Y , Ang W , Tan Z , Deng Y
Ref : Eur Journal of Medicinal Chemistry , 76C :314 , 2014
Abstract : A series of genistein derivatives with carbon spacer-linked alkylbenzylamines were designed, synthesized and tested as multifunctional agents for the treatment of Alzheimer's disease (AD). The results showed that most of these compounds exhibited good acetylcholinesterase (AChE) inhibitory activity, with moderate-to-good anti-oxidative activity. Specifically, compounds 10b, 19d and 25d exhibited significant inhibition of beta-amyloid (Abeta) aggregation and exhibited metal chelating properties. In particular, 25d inhibited: self-induced Abeta1-42 aggregation, Cu2+-induced Abeta1-42 aggregation, and human AChE-induced Abeta1-40 aggregation by 35%, 77.8%, and 36.2%, respectively. Moreover, both kinetic analysis of AChE inhibition and the molecular modeling study suggested that 25d binds simultaneously to catalytic active site and peripheral anionic site of AChE. More importantly, compound 25d disassembled the well-structured Abeta fibrils generated by Cu2+-induced Abeta aggregation by 72.1%. Furthermore, the step-down passive avoidance test showed this compound significantly reversed scopolamine-induced memory deficit in mice. These results suggest that 25d may be a promising multifunctional agent for AD treatment.
ESTHER : Qiang_2014_Eur.J.Med.Chem_76_314
PubMedSearch : Qiang_2014_Eur.J.Med.Chem_76_314
PubMedID: 24589487

Title : Arthrobacter enclensis sp. nov., isolated from sediment sample - Dastager_2014_Arch.Microbiol_196_775
Author(s) : Dastager SG , Liu Q , Tang SK , Krishnamurthi S , Lee JC , Li WJ
Ref : Arch Microbiol , 196 :775 , 2014
Abstract : A novel bacterial strain designated as NIO-1008(T) was isolated from marine sediments sample in Chorao Island India. Cells of the strains were gram positive and non-motile, displayed a rod-coccus life cycle and formed cream to light grey colonies on nutrient agar. Strain NIO-1008(T) had the chemotaxonomic markers that were consistent for classification in the genus Arthrobacter, i.e. MK-9(H2) (50.3 %), as the major menaquinone, and the minor amount of MK-7 (H2-27.5 %), MK-8 (H4-11.6 %) and MK-8 (H2-10.4 %). anteiso-C15:0, iso-C15:0, iso-C16:0 and C15:0 were the predominant fatty acids. Galactose, glucose and rhamnose are the cell-wall sugars, and DNA G+C content was 61.3 mol%. Phylogenetic analysis, based on 16S rRNA gene sequencing, showed that the strains were most similar to Arthrobacter equi IMMIB L-1606(T), Arthrobacter chlorophenolicus DSM 12829(T), Arthrobacter defluvii KCTC 19209(T) and Arthrobacter niigatensis CCTCC AB 206012(T) with 98.5, 98.4, 98.0 and 97.8 %, respectively, and formed a separate lineage. Combined phenotypic data and DNA-DNA hybridization data supported the conclusion that strains NIO-1008(T) represent a novel species within the genus Arthrobacter, for which the name Arthrobacter enclensis sp. nov., is proposed. The type strain is NIO-1008(T) = (NCIM 5488(T) = DSM 25279(T)).
ESTHER : Dastager_2014_Arch.Microbiol_196_775
PubMedSearch : Dastager_2014_Arch.Microbiol_196_775
PubMedID: 25052022
Gene_locus related to this paper: 9micc-a0a0v8imb2 , 9micc-a0a0v8inc9

Title : Human alpha4beta2 nicotinic acetylcholine receptor as a novel target of oligomeric alpha-synuclein - Liu_2013_PLoS.One_8_e55886
Author(s) : Liu Q , Emadi S , Shen JX , Sierks MR , Wu J
Ref : PLoS ONE , 8 :e55886 , 2013
Abstract : Cigarette smoking is associated with a decreased incidence of Parkinson disease (PD) through unknown mechanisms. Interestingly, a decrease in the numbers of alpha4beta2 nicotinic acetylcholine receptors (alpha4beta2-nAChRs) in PD patients suggests an alpha4beta2-nAChR-mediated cholinergic deficit in PD. Although oligomeric forms of alpha-synuclein have been recognized to be toxic and involved in the pathogenesis of PD, their direct effects on nAChR-mediated cholinergic signaling remains undefined. Here, we report for the first time that oligomeric alpha-synuclein selectively inhibits human alpha4beta2-nAChR-mediated currents in a dose-dependent, non-competitive and use-independent manner. We show that pre-loading cells with guanyl-5'-yl thiophosphate fails to prevent this inhibition, suggesting that the alpha-synuclein-induced inhibition of alpha4beta2-nAChR function is not mediated by nAChR internalization. By using a pharmacological approach and cultures expressing transfected human nAChRs, we have shown a clear effect of oligomeric alpha-synuclein on alpha4beta2-nAChRs, but not on alpha4beta4- or alpha7-nAChRs, suggesting nAChR subunit selectivity of oligomeric alpha-synuclein-induced inhibition. In addition, by combining the size exclusion chromatography and atomic force microscopy (AFM) analyses, we find that only large (>4 nm) oligomeric alpha-synuclein aggregates (but not monomeric, small oligomeric or fibrillar alpha-synuclein aggregates) exhibit the inhibitory effect on human alpha4beta2-nAChRs. Collectively, we have provided direct evidence that alpha4beta2-nAChR is a sensitive target to mediate oligomeric alpha-synuclein-induced modulation of cholinergic signaling, and our data imply that therapeutic strategies targeted toward alpha4beta2-nAChRs may have potential for developing new treatments for PD.
ESTHER : Liu_2013_PLoS.One_8_e55886
PubMedSearch : Liu_2013_PLoS.One_8_e55886
PubMedID: 23437071

Title : An Inhibitory Antibody against Dipeptidyl Peptidase IV Improves Glucose Tolerance in Vivo - Tang_2013_J.Biol.Chem_288_1307
Author(s) : Tang J , Majeti J , Sudom A , Xiong Y , Lu M , Liu Q , Higbee J , Zhang Y , Wang Y , Wang W , Cao P , Xia Z , Johnstone S , Min X , Yang X , Shao H , Yu T , Sharkov N , Walker N , Tu H , Shen W , Wang Z
Ref : Journal of Biological Chemistry , 288 :1307 , 2013
Abstract : Dipeptidyl peptidase IV (DPP-IV) degrades the incretin hormone glucagon-like peptide 1 (GLP-1). Small molecule DPP-IV inhibitors have been used as treatments for type 2 diabetes to improve glucose tolerance. However, each of the marketed small molecule drugs has its own limitation in terms of efficacy and side effects. To search for an alternative strategy of inhibiting DPP-IV activity, we generated a panel of tight binding inhibitory mouse monoclonal antibodies (mAbs) against rat DPP-IV. When tested in vitro, these mAbs partially inhibited the GLP-1 cleavage activity of purified enzyme and rat plasma. To understand the partial inhibition, we solved the co-crystal structure of one of the mAb Fabs (Ab1) in complex with rat DPP-IV. Although Ab1 does not bind at the active site, it partially blocks the side opening, which prevents the large substrates such as GLP-1 from accessing the active site, but not small molecules such as sitagliptin. When Ab1 was tested in vivo, it reduced plasma glucose and increased plasma GLP-1 concentration during an oral glucose tolerance test in rats. Together, we demonstrated the feasibility of using mAbs to inhibit DPP-IV activity and to improve glucose tolerance in a diabetic rat model.
ESTHER : Tang_2013_J.Biol.Chem_288_1307
PubMedSearch : Tang_2013_J.Biol.Chem_288_1307
PubMedID: 23184939
Gene_locus related to this paper: ratno-dpp4

Title : Free energy landscape for the binding process of Huperzine A to acetylcholinesterase - Bai_2013_Proc.Natl.Acad.Sci.U.S.A_110_4273
Author(s) : Bai F , Xu Y , Chen J , Liu Q , Gu J , Wang X , Ma J , Li H , Onuchic JN , Jiang H
Ref : Proc Natl Acad Sci U S A , 110 :4273 , 2013
Abstract : Drug-target residence time (t = 1/k(off), where k(off) is the dissociation rate constant) has become an important index in discovering better- or best-in-class drugs. However, little effort has been dedicated to developing computational methods that can accurately predict this kinetic parameter or related parameters, k(off) and activation free energy of dissociation (DeltaG(off) not equal). In this paper, energy landscape theory that has been developed to understand protein folding and function is extended to develop a generally applicable computational framework that is able to construct a complete ligand-target binding free energy landscape. This enables both the binding affinity and the binding kinetics to be accurately estimated. We applied this method to simulate the binding event of the anti-Alzheimer's disease drug (-)-Huperzine A to its target acetylcholinesterase (AChE). The computational results are in excellent agreement with our concurrent experimental measurements. All of the predicted values of binding free energy and activation free energies of association and dissociation deviate from the experimental data only by less than 1 kcal/mol. The method also provides atomic resolution information for the (-)-Huperzine A binding pathway, which may be useful in designing more potent AChE inhibitors. We expect this methodology to be widely applicable to drug discovery and development.
ESTHER : Bai_2013_Proc.Natl.Acad.Sci.U.S.A_110_4273
PubMedSearch : Bai_2013_Proc.Natl.Acad.Sci.U.S.A_110_4273
PubMedID: 23440190

Title : The duck genome and transcriptome provide insight into an avian influenza virus reservoir species - Huang_2013_Nat.Genet_45_776
Author(s) : Huang Y , Li Y , Burt DW , Chen H , Zhang Y , Qian W , Kim H , Gan S , Zhao Y , Li J , Yi K , Feng H , Zhu P , Li B , Liu Q , Fairley S , Magor KE , Du Z , Hu X , Goodman L , Tafer H , Vignal A , Lee T , Kim KW , Sheng Z , An Y , Searle S , Herrero J , Groenen MA , Crooijmans RP , Faraut T , Cai Q , Webster RG , Aldridge JR , Warren WC , Bartschat S , Kehr S , Marz M , Stadler PF , Smith J , Kraus RH , Ren L , Fei J , Morisson M , Kaiser P , Griffin DK , Rao M , Pitel F , Wang J , Li N
Ref : Nat Genet , 45 :776 , 2013
Abstract : The duck (Anas platyrhynchos) is one of the principal natural hosts of influenza A viruses. We present the duck genome sequence and perform deep transcriptome analyses to investigate immune-related genes. Our data indicate that the duck possesses a contractive immune gene repertoire, as in chicken and zebra finch, and this repertoire has been shaped through lineage-specific duplications. We identify genes that are responsive to influenza A viruses using the lung transcriptomes of control ducks and ones that were infected with either a highly pathogenic (A/duck/Hubei/49/05) or a weakly pathogenic (A/goose/Hubei/65/05) H5N1 virus. Further, we show how the duck's defense mechanisms against influenza infection have been optimized through the diversification of its beta-defensin and butyrophilin-like repertoires. These analyses, in combination with the genomic and transcriptomic data, provide a resource for characterizing the interaction between host and influenza viruses.
ESTHER : Huang_2013_Nat.Genet_45_776
PubMedSearch : Huang_2013_Nat.Genet_45_776
PubMedID: 23749191
Gene_locus related to this paper: anapl-BCHE , anapl-r0lw36 , anapl-r0m5n4 , anapl-thioe , anapl-u3iqr9 , anapl-r0l4n7 , anapl-u3j4v8 , anapl-u3icy5 , anapl-u3ivv9 , anapl-u3j4g1 , anapl-u3j4i2 , anapl-u3j4v5 , anapl-r0kv25 , anapl-u3ild2 , anapl-u3imh5 , anapl-b6dzk9 , anapl-u3imp7 , anapl-u3i5h5 , anapl-u3id17 , anapl-r0m1y3 , anapl-r0lhc4 , anapl-r0ktn0 , anapl-r0l8l1 , anapl-r0lin6 , anapl-r0jhf3

Title : A new pancreatic lipase inhibitor from Broussonetia kanzinoki - Ahn_2012_Bioorg.Med.Chem.Lett_22_2760
Author(s) : Ahn JH , Liu Q , Lee C , Ahn MJ , Yoo HS , Hwang BY , Lee MK
Ref : Bioorganic & Medicinal Chemistry Lett , 22 :2760 , 2012
Abstract : A new phenolic compound, broussonone A (1) were isolated from the stem barks of Broussonetia kanzinoki (Moraceae), together with two diphenylpropanes, broussonin A (2), broussonin B (3), two flavans, 7,4'-dihydroxyflavan (4), 3',7-dihydroxy-4'-methoxyflavan (5), and two flavones, 3,7-dihydroxy-4'-methoxyflavone (6), 3,7,3'-trihydroxy-4'-methoxyflavone (7). Compound 1 showed noncompetitive inhibitory activity on pancreatic lipase with an IC(50) of 28.4 muM. In addition, compounds 1-5 significantly inhibited adipocyte differentiation in 3T3-L1 cells as measured fat accumulation using Oil Red O assay.
ESTHER : Ahn_2012_Bioorg.Med.Chem.Lett_22_2760
PubMedSearch : Ahn_2012_Bioorg.Med.Chem.Lett_22_2760
PubMedID: 22450131

Title : Functional alpha7beta2 nicotinic acetylcholine receptors expressed in hippocampal interneurons exhibit high sensitivity to pathological level of amyloid beta peptides - Liu_2012_BMC.Neurosci_13_155
Author(s) : Liu Q , Huang Y , Shen J , Steffensen S , Wu J
Ref : BMC Neurosci , 13 :155 , 2012
Abstract : BACKGROUND: beta-amyloid (Abeta) accumulation is described as a hallmark of Alzheimer's disease (AD). Abeta perturbs a number of synaptic components including nicotinic acetylcholine receptors containing alpha7 subunits (alpha7-nAChRs), which are abundantly expressed in the hippocampus and found on GABAergic interneurons. We have previously demonstrated the existence of a novel, heteromeric alpha7beta2-nAChR in basal forebrain cholinergic neurons that exhibits high sensitivity to acute Abeta exposure. To extend our previous work, we evaluated the expression and pharmacology of alpha7beta2-nAChRs in hippocampal interneurons and their sensitivity to Abeta.
RESULTS: GABAergic interneurons in the CA1 subregion of the hippocampus expressed functional alpha7beta2-nAChRs, which were characterized by relatively slow whole-cell current kinetics, pharmacological sensitivity to dihydro-beta-erythroidine (DHbetaE), a nAChR beta2* subunit selective blocker, and alpha7 and beta2 subunit interaction using immunoprecipitation assay. In addition, alpha7beta2-nAChRs were sensitive to 1 nM oligomeric Abeta. Similar effects were observed in identified hippocampal interneurons prepared from GFP-GAD mice. CONCLUSION: These findings suggest that Abeta modulation of cholinergic signaling in hippocampal GABAergic interneurons via alpha7beta2-nAChRs could be an early and critical event in Abeta-induced functional abnormalities of hippocampal function, which may be relevant to learning and memory deficits in AD.
ESTHER : Liu_2012_BMC.Neurosci_13_155
PubMedSearch : Liu_2012_BMC.Neurosci_13_155
PubMedID: 23272676

Title : Edwardsiella comparative phylogenomics reveal the new intra\/inter-species taxonomic relationships, virulence evolution and niche adaptation mechanisms - Yang_2012_PLoS.One_7_e36987
Author(s) : Yang M , Lv Y , Xiao J , Wu H , Zheng H , Liu Q , Zhang Y , Wang Q
Ref : PLoS ONE , 7 :e36987 , 2012
Abstract : Edwardsiella bacteria are leading fish pathogens causing huge losses to aquaculture industries worldwide. E. tarda is a broad-host range pathogen that infects more than 20 species of fish and other animals including humans while E. ictaluri is host-adapted to channel catfish causing enteric septicemia of catfish (ESC). Thus, these two species consist of a useful comparative system for studying the intricacies of pathogen evolution. Here we present for the first time the phylogenomic comparisons of 8 genomes of E. tarda and E. ictaluri isolates. Genome-based phylogenetic analysis revealed that E. tarda could be separate into two kinds of genotypes (genotype I, EdwGI and genotype II, EdwGII) based on the sequence similarity. E. tarda strains of EdwGI were clustered together with the E. ictaluri lineage and showed low sequence conservation to E. tarda strains of EdwGII. Multilocus sequence analysis (MLSA) of 48 distinct Edwardsiella strains also supports the new taxonomic relationship of the lineages. We identified the type III and VI secretion systems (T3SS and T6SS) as well as iron scavenging related genes that fulfilled the criteria of a key evolutionary factor likely facilitating the virulence evolution and adaptation to a broad range of hosts in EdwGI E. tarda. The surface structure-related genes may underlie the adaptive evolution of E. ictaluri in the host specification processes. Virulence and competition assays of the null mutants of the representative genes experimentally confirmed their contributive roles in the evolution/niche adaptive processes. We also reconstructed the hypothetical evolutionary pathway to highlight the virulence evolution and niche adaptation mechanisms of Edwardsiella. This study may facilitate the development of diagnostics, vaccines, and therapeutics for this under-studied pathogen.
ESTHER : Yang_2012_PLoS.One_7_e36987
PubMedSearch : Yang_2012_PLoS.One_7_e36987
PubMedID: 22590641
Gene_locus related to this paper: 9gamm-a0a076lfv2

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

Title : alpha7beta2 nicotinic acetylcholine receptors assemble, function, and are activated primarily via their alpha7-alpha7 interfaces - Murray_2012_Mol.Pharmacol_81_175
Author(s) : Murray TA , Bertrand D , Papke RL , George AA , Pantoja R , Srinivasan R , Liu Q , Wu J , Whiteaker P , Lester HA , Lukas RJ
Ref : Molecular Pharmacology , 81 :175 , 2012
Abstract : We investigated assembly and function of nicotinic acetylcholine receptors (nAChRs) composed of alpha7 and beta2 subunits. We measured optical and electrophysiological properties of wild-type and mutant subunits expressed in cell lines and Xenopus laevis oocytes. Laser scanning confocal microscopy indicated that fluorescently tagged alpha7 and beta2 subunits colocalize. Forster resonance energy transfer between fluorescently tagged subunits strongly suggested that alpha7 and beta2 subunits coassemble. Total internal reflection fluorescence microscopy revealed that assemblies localized to filopodia-like processes of SH-EP1 cells. Gain-of-function alpha7 and beta2 subunits confirmed that these subunits coassemble within functional receptors. Moreover, alpha7beta2 nAChRs composed of wild-type subunits or fluorescently tagged subunits had pharmacological properties similar to those of alpha7 nAChRs, although amplitudes of alpha7beta2 nAChR-mediated, agonist-evoked currents were generally ~2-fold lower than those for alpha7 nAChRs. It is noteworthy that alpha7beta2 nAChRs displayed sensitivity to low concentrations of the antagonist dihydro-beta-erythroidine that was not observed for alpha7 nAChRs at comparable concentrations. In addition, cysteine mutants revealed that the alpha7-beta2 subunit interface does not bind ligand in a functionally productive manner, partly explaining lower alpha7beta2 nAChR current amplitudes and challenges in identifying the function of native alpha7beta2 nAChRs. On the basis of our findings, we have constructed a model predicting receptor function that is based on stoichiometry and position of beta2 subunits within the alpha7beta2 nAChRs.
ESTHER : Murray_2012_Mol.Pharmacol_81_175
PubMedSearch : Murray_2012_Mol.Pharmacol_81_175
PubMedID: 22039094

Title : Identification and characterization of a novel non-coding RNA involved in sperm maturation - Ni_2011_PLoS.One_6_e26053
Author(s) : Ni MJ , Hu ZH , Liu Q , Liu MF , Lu MH , Zhang JS , Zhang L , Zhang YL
Ref : PLoS ONE , 6 :e26053 , 2011
Abstract : A long and ever-expanding roster of small ( approximately 20-30 nucleotides) RNAs has emerged during the last decade, and most can be subsumed under the three main headings of microRNAs (miRNAs), Piwi-interacting RNAs (piRNAs), and short interfering RNAs (siRNAs). Among the three categories, miRNAs is the most quickly expanded group. The most recent number of identified miRNAs is 16,772 (Sanger miRbase, April 2011). However, there are insufficient publications on their primary forms, and no tissue-specific small RNAs precursors have been reported in the epididymis. Here, we report the identification in rats of an epididymis-specific, chimeric, noncoding RNA that is spliced from two different chromosomes (chromosomes 5 and 19), which we named HongrES2. HongrES2 is a 1.6 kb mRNA-like precursor that gives rise to a new microRNA-like small RNA (mil-HongrES2) in rat epididymis. The generation of mil-HongrES2 is stimulated during epididymitis. An epididymis-specific carboxylesterase named CES7 had 100% cDNA sequence homology at the 3'end with HongrES2 and its protein product could be downregulated by HongrES2 via mil-HongrES2. This was confirmed in vivo by initiating mil-HongrES2 over-expression in rats and observing an effect on sperm capacitation.
ESTHER : Ni_2011_PLoS.One_6_e26053
PubMedSearch : Ni_2011_PLoS.One_6_e26053
PubMedID: 22022505

Title : Strigolactones are transported through the xylem and play a key role in shoot architectural response to phosphate deficiency in nonarbuscular mycorrhizal host Arabidopsis - Kohlen_2011_Plant.Physiol_155_974
Author(s) : Kohlen W , Charnikhova T , Liu Q , Bours R , Domagalska MA , Beguerie S , Verstappen F , Leyser O , Bouwmeester H , Ruyter-Spira C
Ref : Plant Physiol , 155 :974 , 2011
Abstract : The biosynthesis of the recently identified novel class of plant hormones, strigolactones, is up-regulated upon phosphate deficiency in many plant species. It is generally accepted that the evolutionary origin of strigolactone up-regulation is their function as a rhizosphere signal that stimulates hyphal branching of arbuscular mycorrhizal fungi. In this work, we demonstrate that this induction is conserved in Arabidopsis (Arabidopsis thaliana), although Arabidopsis is not a host for arbuscular mycorrhizal fungi. We demonstrate that the increase in strigolactone production contributes to the changes in shoot architecture observed in response to phosphate deficiency. Using high-performance liquid chromatography, column chromatography, and multiple reaction monitoring-liquid chromatography-tandem mass spectrometry analysis, we identified two strigolactones (orobanchol and orobanchyl acetate) in Arabidopsis and have evidence of the presence of a third (5-deoxystrigol). We show that at least one of them (orobanchol) is strongly reduced in the putative strigolactone biosynthetic mutants more axillary growth1 (max1) and max4 but not in the signal transduction mutant max2. Orobanchol was also detected in xylem sap and up-regulated under phosphate deficiency, which is consistent with the idea that root-derived strigolactones are transported to the shoot, where they regulate branching. Moreover, two additional putative strigolactone-like compounds were detected in xylem sap, one of which was not detected in root exudates. Together, these results show that xylem-transported strigolactones contribute to the regulation of shoot architectural response to phosphate-limiting conditions.
ESTHER : Kohlen_2011_Plant.Physiol_155_974
PubMedSearch : Kohlen_2011_Plant.Physiol_155_974
PubMedID: 21119045

Title : TiO2-decorated graphene nanohybrids for fabricating an amperometric acetylcholinesterase biosensor - Wang_2011_Analyst_136_3349
Author(s) : Wang K , Li HN , Wu J , Ju C , Yan JJ , Liu Q , Qiu B
Ref : Analyst , 136 :3349 , 2011
Abstract : This work describes a highly sensitive and rapid amperometric biosensor for organophosphate compounds (OPs) based on immobilization of acetylcholinesterase (AChE) on a novel TiO(2)-decorated graphene (TiO(2)-G) nanohybrid, which was constructed by in situ growth of TiO(2) nanoparticles (NPs) on the graphene sheet. The well-dispersed TiO(2) NPs eliminated the restacking of TiO(2)-G nanohybrids. Due to the integrating of TiO(2)-G nanohybrids, the as-prepared biosensor showed high affinity to acetylthiocholine (ATCl) with a Michaelis-Menten constant (K(m)) value of 0.22 mM, and rapid inhibition time (3 min). Further, based on the inhibition of OPs on the enzymatic activity of the immobilized AChE, and using carbaryl as a model compound, the inhibition of carbaryl was proportional to its concentration ranging from 0.001 to 0.015 and 0.015 to 2 mug mL(-1) with a detection limit of 0.3 ng mL(-1) (S/N = 3). The developed biosensor exhibited a good performance for organophosphate pesticide detection, including good reproducibility and acceptable stability, which provided a new and promising tool for the analysis of enzyme inhibitors.
ESTHER : Wang_2011_Analyst_136_3349
PubMedSearch : Wang_2011_Analyst_136_3349
PubMedID: 21738917

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

Title : Complete genome analysis of Sulfobacillus acidophilus strain TPY, isolated from a hydrothermal vent in the Pacific Ocean - Li_2011_J.Bacteriol_193_5555
Author(s) : Li B , Chen Y , Liu Q , Hu S , Chen X
Ref : Journal of Bacteriology , 193 :5555 , 2011
Abstract : Sulfobacillus acidophilus strain TPY is a moderately thermoacidophilic bacterium originally isolated from a hydrothermal vent in the Pacific Ocean. Ferrous iron and sulfur oxidation in acidic environments in strain TPY have been confirmed. Here we report the genome sequence and annotation of the strain TPY, which is the first complete genome of Sulfobacillus acidophilus.
ESTHER : Li_2011_J.Bacteriol_193_5555
PubMedSearch : Li_2011_J.Bacteriol_193_5555
PubMedID: 21914875
Gene_locus related to this paper: sulat-f8ic83

Title : A highly sensitive and rapid organophosphate biosensor based on enhancement of CdS-decorated graphene nanocomposite - Wang_2011_Anal.Chim.Acta_695_84
Author(s) : Wang K , Liu Q , Dai L , Yan J , Ju C , Qiu B , Wu X
Ref : Anal Chim Acta , 695 :84 , 2011
Abstract : This work reports a rapid and sensitive organophosphates (OPs) amperometric biosensor based on acetylcholinesterase (AChE) immobilized on CdS-decorated graphene (CdS-G) nanocomposite. The as-prepared biosensor shows high affinity to acetylthiocholine (ATCl) with a Michaelis-Menten constant (K(m)) value of 0.24 mM. A rapid inhibition time (2 min) is obtained due to the integration of the CdS-G nanocomposite. Based on the inhibition of OPs on the enzymatic activity of the immobilized AChE, and used carbaryl as the model compound, the resulting biosensor exhibits excellent performance for OPs detection including good reproducibility, acceptable stability, and a reliable linear relationship between the inhibition and log[carbaryl] from 2 ng mL(-)(1) up to 2 mug mL(-)(1) with a detection limit of 0.7 ng mL(-)(1),which provides a new promising tool for analysis of enzyme inhibitors.
ESTHER : Wang_2011_Anal.Chim.Acta_695_84
PubMedSearch : Wang_2011_Anal.Chim.Acta_695_84
PubMedID: 21601034

Title : Coadministration of huperzine A and ligustrazine phosphate effectively reverses scopolamine-induced amnesia in rats - Shi_2010_Pharmacol.Biochem.Behav_96_449
Author(s) : Shi J , Liu Q , Wang Y , Luo G
Ref : Pharmacol Biochem Behav , 96 :449 , 2010
Abstract : In the present study, whether coadministration of huperzine A (HA) and ligustrazine phosphate (LP) could effectively improve the memory deficits in association with ameliorating cholinergic impairment and oxidative stress in the scopolamine-induced amnesia rats was assessed. The effects of treatment with Coa [HA (0.14 mg/kg, i.g.) and LP (110 mg/kg, i.g.)] on amnesia were investigated in Morris water maze. Furthermore, the effects on the activities of acetylcholinesterase (AChE) and antioxidant enzymes within the cerebral cortex and hippocampus were evaluated, and the lipid peroxidation product malondialdehyde (MDA) was also analyzed. As a result, coadministration of HA and LP for 10 consecutive days could markedly reverse the scopolamine-induced learning and memory impairment determined by the Morris water maze test. Moreover, AChE activity was significantly inhibited, and superoxide dismutases (SOD) and glutathione peroxidase (GSH-Px) activities were significantly increased with a remarkable reduction in the level of MDA. In conclusion, coadministration of HA and LP effectively prevented cholinergic impairment and oxidative damage, thereby resulting in improvement of spatial learning memory in rats induced by scopolamine. The results suggested that coadministration of HA and LP might offer a novel poly-therapeutic drug regimen for preventing Alzheimer's disease (AD).
ESTHER : Shi_2010_Pharmacol.Biochem.Behav_96_449
PubMedSearch : Shi_2010_Pharmacol.Biochem.Behav_96_449
PubMedID: 20624417

Title : Non-peptidic glucose-like peptide-1 receptor agonists: aftermath of a serendipitous discovery - Wang_2010_Acta.Pharmacol.Sin_31_1026
Author(s) : Wang MW , Liu Q , Zhou CH
Ref : Acta Pharmacol Sin , 31 :1026 , 2010
Abstract : Glucagon-like peptide-1 (GLP-1) receptor is an ideal target in the development of incretin-based therapies for diabetes and obesity. Two approaches have been adopted: GLP-1 receptor agonists that mimic the effects of native GLP-1 and dipeptidyl peptidase-4 inhibitors that increase endogenous GLP-1 levels. During the past two decades, search for orally active, non-peptidic GLP-1 receptor agonists has been the focal point of research and development activities in many multinational pharmaceutical companies. Such efforts have not resulted in any success thus far. Serendipitous discovery of substituted cyclobutanes represented by Boc5 as a new class of GLP-1 receptor agonists led us to believe that a small molecule approach to class B G-protein coupled receptor agonism is no longer a fantasy but a reality. However, major obstacles still pose great challenges, and the reasons of which are discussed in this perspectives.
ESTHER : Wang_2010_Acta.Pharmacol.Sin_31_1026
PubMedSearch : Wang_2010_Acta.Pharmacol.Sin_31_1026
PubMedID: 20676118

Title : The anticonvulsive drug lamotrigine blocks neuronal {alpha}4{beta}2 nicotinic acetylcholine receptors - Zheng_2010_J.Pharmacol.Exp.Ther_335_401
Author(s) : Zheng C , Yang K , Liu Q , Wang MY , Shen J , Valles AS , Lukas RJ , Barrantes FJ , Wu J
Ref : Journal of Pharmacology & Experimental Therapeutics , 335 :401 , 2010
Abstract : Lamotrigine (LTG), an anticonvulsive drug, is often used for the treatment of a variety of epilepsies. In addition to block of sodium channels, LTG may act on other targets to exert its antiepileptic effect. In the present study, we evaluated the effects of LTG on neuronal nicotinic acetylcholine receptors (nAChRs) using the patch-clamp technique on human alpha4beta2-nAChRs heterologously expressed in the SH-EP1 cell line and on native alpha4beta2-nAChRs in dopaminergic (DA) neurons in rat ventral tegmental area (VTA). In SH-EP1 cells, LTG diminished the peak and steady-state components of the inward alpha4beta2-nAChR-mediated currents. This effect exhibited concentration-, voltage- and use-dependent behavior. Nicotine dose-response curves showed that in the presence of LTG, the nicotine-induced maximal current was reduced, suggesting a noncompetitive inhibition. These findings suggest that LTG inhibits human neuronal alpha4beta2-nAChR function through an open-channel blocking mechanism. LTG-induced inhibition in alpha4beta2-nAChRs was more profound when preceded by a 2-min pretreatment, after which the nicotine-induced current was reduced even without coapplication of LTG, suggesting that LTG is also able to inhibit alpha4beta2-nAChRs without channel activation. In freshly dissociated VTA DA neurons, LTG inhibited alpha4beta2-nAChR-mediated currents but did not affect glutamate- or GABA-induced currents, indicating that LTG selectively inhibits nAChR function. Collectively, our data suggest that the neuronal alpha4beta2-nAChR is likely an important target for mediating the anticonvulsive effect of LTG and the blockade of alpha4beta2-nAChR possibly underlying the mechanism through which LTG effectively controls some types of epilepsy, such as autosomal dominant nocturnal frontal lobe epilepsy or juvenile myoclonic epilepsy.
ESTHER : Zheng_2010_J.Pharmacol.Exp.Ther_335_401
PubMedSearch : Zheng_2010_J.Pharmacol.Exp.Ther_335_401
PubMedID: 20688974

Title : A novel GLP-1 analog, BPI3006, with potent DPP IV resistance and good glucoregulatory effect - Li_2010_Biochem.Biophys.Res.Commun_400_563
Author(s) : Li C , Huan Y , Shen N , Ji L , Sun S , Liu S , Liu Q , Gao L , Tan F , Wang Y , Shen Z
Ref : Biochemical & Biophysical Research Communications , 400 :563 , 2010
Abstract : Glucagon-like peptide-1 (GLP-1) is an incretin hormone that decreases postprandial glycemic excursions by enhancing insulin secretion but with short half-life due to rapid inactivation by enzymatic N-terminal truncation. Therefore, efforts are being made to improve the stability of GLP-1 via modifying its structure or inhibiting dipeptidyl-peptidase IV (DPP IV), which is responsible for its degradation. Here we report a novel GLP-1 analog BPI3006 with -NHCO- of Ala(8) replaced by -CH(CF(3))NH- and features of its metabolic stability, GLP-1 receptor trans-activation and in vivo biological activity. BPI3006 is highly resistant to DPP IV-mediated degradation with 91.1% of parental peptide left after 24h exposure to the enzyme. BPI3006 also effectively activates its target gene promoter through GLP-1 receptor activation by measuring the transiently transfected reporter gene green fluorescence protein (GFP) expression in NIT-1 cells. Furthermore, BPI3006 could well restrain the glycemia variation in fasted normal ICR mice after a single administration followed by an oral glucose loading. In spontaneous type 2 diabetic KKA(y) mice, BPI3006 injected twice daily could significantly improve the oral glucose tolerance and hyperinsulinemia, as well as ameliorate the food and water consumption. In conclusion, BPI3006 has enhanced resistance to DPP IV leading to improved stability, and shows excellent in vivo biological activity. Thus it may be a new candidate for T2DM treatment and its novel modification may provide valuable guidance for the future development of long-acting GLP-1 analogs.
ESTHER : Li_2010_Biochem.Biophys.Res.Commun_400_563
PubMedSearch : Li_2010_Biochem.Biophys.Res.Commun_400_563
PubMedID: 20804731

Title : The sequence and de novo assembly of the giant panda genome - Li_2010_Nature_463_311
Author(s) : Li R , Fan W , Tian G , Zhu H , He L , Cai J , Huang Q , Cai Q , Li B , Bai Y , Zhang Z , Zhang Y , Wang W , Li J , Wei F , Li H , Jian M , Nielsen R , Li D , Gu W , Yang Z , Xuan Z , Ryder OA , Leung FC , Zhou Y , Cao J , Sun X , Fu Y , Fang X , Guo X , Wang B , Hou R , Shen F , Mu B , Ni P , Lin R , Qian W , Wang G , Yu C , Nie W , Wang J , Wu Z , Liang H , Min J , Wu Q , Cheng S , Ruan J , Wang M , Shi Z , Wen M , Liu B , Ren X , Zheng H , Dong D , Cook K , Shan G , Zhang H , Kosiol C , Xie X , Lu Z , Li Y , Steiner CC , Lam TT , Lin S , Zhang Q , Li G , Tian J , Gong T , Liu H , Zhang D , Fang L , Ye C , Zhang J , Hu W , Xu A , Ren Y , Zhang G , Bruford MW , Li Q , Ma L , Guo Y , An N , Hu Y , Zheng Y , Shi Y , Li Z , Liu Q , Chen Y , Zhao J , Qu N , Zhao S , Tian F , Wang X , Wang H , Xu L , Liu X , Vinar T , Wang Y , Lam TW , Yiu SM , Liu S , Huang Y , Yang G , Jiang Z , Qin N , Li L , Bolund L , Kristiansen K , Wong GK , Olson M , Zhang X , Li S , Yang H
Ref : Nature , 463 :311 , 2010
Abstract : Using next-generation sequencing technology alone, we have successfully generated and assembled a draft sequence of the giant panda genome. The assembled contigs (2.25 gigabases (Gb)) cover approximately 94% of the whole genome, and the remaining gaps (0.05 Gb) seem to contain carnivore-specific repeats and tandem repeats. Comparisons with the dog and human showed that the panda genome has a lower divergence rate. The assessment of panda genes potentially underlying some of its unique traits indicated that its bamboo diet might be more dependent on its gut microbiome than its own genetic composition. We also identified more than 2.7 million heterozygous single nucleotide polymorphisms in the diploid genome. Our data and analyses provide a foundation for promoting mammalian genetic research, and demonstrate the feasibility for using next-generation sequencing technologies for accurate, cost-effective and rapid de novo assembly of large eukaryotic genomes.
ESTHER : Li_2010_Nature_463_311
PubMedSearch : Li_2010_Nature_463_311
PubMedID: 20010809
Gene_locus related to this paper: ailme-ABH15 , ailme-ACHE , ailme-BCHE , ailme-d2gtv3 , ailme-d2gty9 , ailme-d2gu87 , ailme-d2gu97 , ailme-d2gve7 , ailme-d2gwu1 , ailme-d2gx08 , ailme-d2gyt0 , ailme-d2gz36 , ailme-d2gz37 , ailme-d2gz38 , ailme-d2gz39 , ailme-d2gz40 , ailme-d2h5r9 , ailme-d2h7b7 , ailme-d2h9c9 , ailme-d2h794 , ailme-d2hau7 , ailme-d2hau8 , ailme-d2hcd9 , ailme-d2hdi6 , ailme-d2heu6 , ailme-d2hga4 , ailme-d2hqw5 , ailme-d2hs98 , ailme-d2hsx4 , ailme-d2hti6 , ailme-d2htv3 , ailme-d2htz6 , ailme-d2huc7 , ailme-d2hwj8 , ailme-d2hwy7 , ailme-d2hxm1 , ailme-d2hyc8 , ailme-d2hyv2 , ailme-d2hz11 , ailme-d2hza3 , ailme-d2hzr4 , ailme-d2i1l4 , ailme-d2i2g8 , ailme-g1l7m3 , ailme-g1lu36 , ailme-g1m769 , ailme-g1mc29 , ailme-g1mdj8 , ailme-g1mdr5 , ailme-g1mfp4 , ailme-g1mfx5 , ailme-g1lj41 , ailme-g1lm28 , ailme-g1l3u1 , ailme-g1l7l1 , ailme-g1m5i3 , ailme-g1l2f6 , ailme-g1lji5 , ailme-g1lqk3 , ailme-g1l8s9 , ailme-d2h717 , ailme-d2h718 , ailme-d2h719 , ailme-d2h720 , ailme-g1m5v0 , ailme-g1m5y7 , ailme-g1lkt7 , ailme-g1l2a1 , ailme-g1lsc8 , ailme-g1lrp4 , ailme-d2gv02 , ailme-g1mik5 , ailme-g1ljr1 , ailme-g1lxw7 , ailme-d2h8b5 , ailme-d2h2r2 , ailme-d2h9w7 , ailme-g1meh3 , ailme-g1m719

Title : Baculo-expression and enzymatic characterization of CES7 esterase - Zhang_2009_Acta.Biochim.Biophys.Sin.(Shanghai)_41_731
Author(s) : Zhang L , Liu Q , Zhou Y , Zhang Y
Ref : Acta Biochim Biophys Sin (Shanghai) , 41 :731 , 2009
Abstract : The male reproductive tracts in different species are characterized by similar patterns of male-dependent overexpression of carboxylesterases. This phenomenon indicates male sex-associated functions of these enzymes for spermatogenesis, sperm maturation, and sperm use. Recently, a novel epididymis-specific gene named Ces7 was cloned and characterized, which belongs to the carboxylesterase family. To study the functions of CES7 in sperm maturation and storage, CES7 recombinant protein was expressed in baculovirus system. The recombinant protein had carboxylesterase activity hydrolyzing cholesterol ester and choline ester. CES7 as carboxylesterase might be involved in ester hydrolysis, sperm maturation, and storage in male reproductive tract.
ESTHER : Zhang_2009_Acta.Biochim.Biophys.Sin.(Shanghai)_41_731
PubMedSearch : Zhang_2009_Acta.Biochim.Biophys.Sin.(Shanghai)_41_731
PubMedID: 19727521

Title : Impact of cigarette smoking in type 2 diabetes development - Xie_2009_Acta.Pharmacol.Sin_30_784
Author(s) : Xie XT , Liu Q , Wu J , Wakui M
Ref : Acta Pharmacol Sin , 30 :784 , 2009
Abstract : Many patients with type 2 diabetes mellitus (DM2) are at risk for micro and macro vascular complications, which could be observed in heavy smokers. Cigarette smoking increases the risk for type 2 diabetes incidence. Nicotine, acknowledged as the major pharmacologically active chemical in tobacco, is responsible for the association between cigarette smoking and development of diabetes. This minireview summarized recent studies on nicotine effects on insulin action and insulin secretion, indicating the impact of nicotine on type 2 diabetes development.
ESTHER : Xie_2009_Acta.Pharmacol.Sin_30_784
PubMedSearch : Xie_2009_Acta.Pharmacol.Sin_30_784
PubMedID: 19434055

Title : A novel nicotinic acetylcholine receptor subtype in basal forebrain cholinergic neurons with high sensitivity to amyloid peptides - Liu_2009_J.Neurosci_29_918
Author(s) : Liu Q , Huang Y , Xue F , Simard AR , DeChon J , Li G , Zhang J , Lucero L , Wang M , Sierks M , Hu G , Chang Y , Lukas RJ , Wu J
Ref : Journal of Neuroscience , 29 :918 , 2009
Abstract : Nicotinic acetylcholine receptors (nAChRs) containing alpha7 subunits are thought to assemble as homomers. alpha7-nAChR function has been implicated in learning and memory, and alterations of alpha7-nAChR have been found in patients with Alzheimer's disease (AD). Here we report findings consistent with a novel, naturally occurring nAChR subtype in rodent, basal forebrain cholinergic neurons. In these cells, alpha7 subunits are coexpressed, colocalize, and coassemble with beta2 subunit(s). Compared with homomeric alpha7-nAChRs from ventral tegmental area neurons, functional, presumably heteromeric alpha7beta2-nAChRs on cholinergic neurons freshly dissociated from medial septum/diagonal band (MS/DB) exhibit relatively slow kinetics of whole-cell current responses to nicotinic agonists and are more sensitive to the beta2 subunit-containing nAChR-selective antagonist, dihydro-beta-erythroidine (DHbetaE). Interestingly, presumed, heteromeric alpha7beta2-nAChRs are highly sensitive to functional inhibition by pathologically relevant concentrations of oligomeric, but not monomeric or fibrillar, forms of amyloid beta(1-42) (Abeta(1-42)). Slow whole-cell current kinetics, sensitivity to DHbetaE, and specific antagonism by oligomeric Abeta(1-42) also are characteristics of heteromeric alpha7beta2-nAChRs, but not of homomeric alpha7-nAChRs, heterologously expressed in Xenopus oocytes. Moreover, choline-induced currents have faster kinetics and less sensitivity to Abeta when elicited from MS/DB neurons derived from nAChR beta2 subunit knock-out mice rather than from wild-type mice. The presence of novel, functional, heteromeric alpha7beta2-nAChRs on basal forebrain cholinergic neurons and their high sensitivity to blockade by low concentrations of oligomeric Abeta(1-42) suggests possible mechanisms for deficits in cholinergic signaling that could occur early in the etiopathogenesis of AD and might be targeted by disease therapies.
ESTHER : Liu_2009_J.Neurosci_29_918
PubMedSearch : Liu_2009_J.Neurosci_29_918
PubMedID: 19176801

Title : Distinctive nicotinic acetylcholine receptor functional phenotypes of rat ventral tegmental area dopaminergic neurons - Yang_2009_J.Physiol_587_345
Author(s) : Yang K , Hu J , Lucero L , Liu Q , Zheng C , Zhen X , Jin G , Lukas RJ , Wu J
Ref : Journal of Physiology , 587 :345 , 2009
Abstract : Dopaminergic (DAergic) neuronal activity in the ventral tegmental area (VTA) is thought to contribute generally to pleasure, reward, and drug reinforcement and has been implicated in nicotine dependence. nAChRs expressed in the VTA exhibit diverse subunit compositions, but the functional and pharmacological properties are largely unknown. Here, using patch-clamp recordings in single DAergic neurons freshly dissociated from rat VTA, we clarified three functional subtypes of nAChRs (termed ID, IID and IIID receptors) based on whole-cell current kinetics and pharmacology. Kinetic analysis demonstrated that comparing to ID, IID receptor-mediated current had faster activation and decay constant and IIID receptor-mediated current had larger current density. Pharmacologically, ID receptor-mediated current was sensitive to the alpha4beta2-nAChR agonist RJR-2403 and antagonist dihydro-beta-erythroidine (DHbetaE); IID receptor-mediated current was sensitive to the selective alpha7-nAChR agonist choline and antagonist methyllycaconitine (MLA); while IIID receptor-mediated current was sensitive to the beta4-containing nAChR agonist cytisine and antagonist mecamylamine (MEC). The agonist concentration-response relationships demonstrated that IID receptor-mediated current exhibited the highest EC(50) value compared to ID and IIID receptors, suggesting a relatively low agonist affinity of type IID receptors. These results suggest that the type ID, IID and IIID nAChR-mediated currents are predominately mediated by activation of alpha4beta2-nAChR, alpha7-nAChR and a novel nAChR subtype(s), respectively. Collectively, these findings indicate that the VTA DAergic neurons express diversity and multiplicity of functional nAChR subtypes. Interestingly, each DAergic neuron predominantly expresses only one particularly functional nAChR subtype, which may have distinct but important roles in regulation of VTA DA neuronal function, DA transmission and nicotine dependence.
ESTHER : Yang_2009_J.Physiol_587_345
PubMedSearch : Yang_2009_J.Physiol_587_345
PubMedID: 19047205

Title : Kinetics of desensitization and recovery from desensitization for human alpha4beta2-nicotinic acetylcholine receptors stably expressed in SH-EP1 cells - Yu_2009_Acta.Pharmacol.Sin_30_805
Author(s) : Yu KD , Liu Q , Wu J , Lukas RJ
Ref : Acta Pharmacol Sin , 30 :805 , 2009
Abstract : AIM: Studies were conducted to define the kinetics of the onset of and recovery from desensitization for human alpha4beta2-nicotinic acetylcholine receptors (nAChR) heterologously expressed in the SH-EP1 human epithelial cell line.
METHODS: Whole-cell patch clamp recordings were performed to evaluate alpha4beta2-nAChR currents.
RESULTS: Application of 0.1 micromol/L nicotine or 1 mmol/L acetylcholine (ACh) for 1 s or longer induced two phases, with time constants of approximately 70 and approximately 700 ms, for the onset of alpha4beta2-nAChR desensitization. For a given duration of agonist exposure, recovery from desensitization induced by nicotine was slower than recovery from ACh-induced desensitization. Comparisons with published reports indicate that time constants for the recovery of alpha4beta2-nAChRs from desensitization are smaller than those for the recovery of human muscle-type nAChRs(1) from desensitization produced by the same concentrations and durations of exposure to an agonist. Moreover, the extent of human alpha4beta2-nAChR desensitization and rate of recovery are the same, regardless of whether they are measured using whole-cell recording or based on published findings(2) using isotopic ion flux assays; this equality demonstrates the equivalent legitimacy of these techniques in the evaluation of nAChR desensitization. Perhaps most significantly, recovery from desensitization also was best fit to a biphasic process. Regardless of whether it was fit to single or double exponentials, however, half-times for recovery from desensitization grew progressively longer with an increased duration of agonist exposure during the desensitizing pulse. CONCLUSION: These findings indicate the existence of alpha4beta2-nAChRs in many distinctive states of desensitization, as well as the induction of progressively deeper states of desensitization with the increased duration of agonist exposure.
ESTHER : Yu_2009_Acta.Pharmacol.Sin_30_805
PubMedSearch : Yu_2009_Acta.Pharmacol.Sin_30_805
PubMedID: 19498421

Title : The angiopoietin-like proteins ANGPTL3 and ANGPTL4 inhibit lipoprotein lipase activity through distinct mechanisms - Shan_2009_J.Biol.Chem_284_1419
Author(s) : Shan L , Yu XC , Liu Z , Hu Y , Sturgis LT , Miranda ML , Liu Q
Ref : Journal of Biological Chemistry , 284 :1419 , 2009
Abstract : Two members of the angiopoietin-like family of proteins, ANGPTL3 and ANGPTL4, have been shown to play important roles in modulating lipoprotein metabolism in the body. Both proteins were found to suppress lipoprotein lipase (LPL) activity in vitro as well as in vivo. However, their mechanisms of inhibition remained poorly understood. Using enzyme kinetic analysis with purified recombinant proteins, we have found key mechanistic differences between ANGPTL3 and ANGPTL4. ANGPTL3 reduced LPL catalytic activity but did not significantly alter its self-inactivation rate. In contrast, ANGPTL4 suppressed LPL by accelerating the irreversible inactivation of LPL. Furthermore, heparin was able to overcome the inhibitory effect of ANGPTL3 on LPL but not that of ANGPTL4. Site-directed mutagenesis demonstrated the critical function of Glu(40) in ANGPTL4. In contrast, when cysteine residues involved in disulfide bond formation were mutated to serines, ANGPTL4 retained its activity. Taken together, our data provide a more detailed view of the structure and mechanisms of these proteins. The finding that ANGPTL3 and ANGPTL4 inhibit LPL activity through distinct mechanisms indicates that the two proteins play unique roles in modulation of lipid metabolism in vivo.
ESTHER : Shan_2009_J.Biol.Chem_284_1419
PubMedSearch : Shan_2009_J.Biol.Chem_284_1419
PubMedID: 19028676
Gene_locus related to this paper: human-LPL

Title : Multiple doses of sitagliptin, a selective DPP-4 inhibitor, do not meaningfully alter pharmacokinetics and pharmacodynamics of warfarin - Wright_2009_J.Clin.Pharmacol_49_1157
Author(s) : Wright DH , Herman GA , Maes A , Liu Q , Johnson-Levonas AO , Wagner JA
Ref : Journal of Clinical Pharmacology , 49 :1157 , 2009
Abstract : Sitagliptin is an orally active, highly selective dipeptidyl peptidase IV (DPP-4) inhibitor for treatment of type 2 diabetes mellitus. This randomized, open-label, 2-part, 2-period crossover study assessed pharmacokinetics/pharmacodynamics of warfarin in the presence/absence of multiple-dose sitagliptin. Twelve participants received treatments A and B separated by >7-day washout: treatment A involved coadministration of sitagliptin 200 mg/d for 11 days (days 1-11) and warfarin 30 mg on day 5, and treatment B involved warfarin 30 mg alone on day 1. R(+) warfarin, S(-) warfarin, and international normalized ratio (INR) were assayed predose and up to 168 hours postdose. The geometric mean ratios (GMRs; warfarin + sitagliptin/warfarin alone) (90% confidence intervals [CIs]) were 0.99 (0.95, 1.03) and 0.95 (0.90, 1.02) for the AUC(0-infinity) of R(+) and S(-) warfarin, respectively. GMRs (warfarin + sitagliptin/warfarin alone) (90% CIs) were 0.89 (0.86, 0.93) and 0.89 (0.86, 0.92) for the C(max) of R(+) and S(-) warfarin, respectively. INR AUC(0-168 h) and INR(max) GMRs were 1.01 (0.96, 1.06) and 1.08 (1.00, 1.17), respectively. Coadministration of sitagliptin and warfarin was generally well tolerated. Pharmacokinetics (AUC for R(+) and S(-) warfarin) and pharmacodynamics (INR of R(+) or S(-) warfarin) were not meaningfully altered following coadministration of multiple-dose sitagliptin and single-dose warfarin, indicating that no dosage adjustment for warfarin is necessary when coadministered with sitagliptin.
ESTHER : Wright_2009_J.Clin.Pharmacol_49_1157
PubMedSearch : Wright_2009_J.Clin.Pharmacol_49_1157
PubMedID: 19783710

Title : U18666A, a cholesterol-inhibition agent, modulates human neuronal nicotinic acetylcholine receptors heterologously expressed in SH-EP1 cell line - Zheng_2009_J.Neurochem_108_1526
Author(s) : Zheng C , Wang MY , Liu Q , Wakui M , Whiteaker P , Lukas RJ , Wu J
Ref : Journal of Neurochemistry , 108 :1526 , 2009
Abstract : In this study, we evaluate the effects of (3beta)-3-[2-(diethylamino)ethoxy]androst-5-en-17-one dihydrochloride (U18666A), a cholesterol synthesis/transporter inhibitor, on selected human neuronal nicotinic acetylcholine receptors (nAChRs) heterologously expressed in the SH-EP1 cell line using whole-cell patch-clamp recordings. The results indicate that with 2-min pretreatment, U18666A inhibited different nAChR subtypes with a rank-order of potency (IC(50) of whole-cell peak current): alpha4beta2 (8.0 +/- 3.0 nM) > alpha3beta2 (1.7 +/- 0.4 microM) > alpha4beta4 (26 +/- 7.2 microM) > alpha7 (> 100 microM), suggesting this compound is more selective to alpha4beta2-nAChRs. Thus, the pharmacological profiles and mechanisms of U18666A acting on alpha4beta2-nAChRs were investigated in detail. U18666A suppresses both peak and steady state components of whole-cell currents mediated by human alpha4beta2-nAChRs in response to nicotine. In nicotine-induced concentration-response curves, U18666A reduces nicotine-induced current at maximally effective agonist concentrations without influencing nicotine's EC(50) value, suggesting a non-competitive inhibition. U18666A-induced inhibition of nAChR function is concentration-, voltage-, and use-dependent, suggesting an open channel block. Taken into consideration of approximately 10 000-fold enhancement of the potency of U18666A after 2-min pre-treatment, this compound also likely inhibits alpha4beta2-nAChRs through a close channel block. In addition, the U18666A-induced inhibition in alpha4beta2-nAChRs is not mediated by either increased receptor endocytosis or altered cell cholesterol. These data indicate that U18666A is a potent antagonist of alpha4beta2-nAChRs and may be useful as a tool in the functional characterization and pharmacological profiling of nAChRs, as well as a potential candidate for smoking cessation.
ESTHER : Zheng_2009_J.Neurochem_108_1526
PubMedSearch : Zheng_2009_J.Neurochem_108_1526
PubMedID: 19183258

Title : [Protective effect of glial cell line-derived neurotrophic factor infused into the tube setted into cavitas subarachnoidealis on spinal front corner motor neurons] - Pan_2009_Zhongguo.Gu.Shang_22_122
Author(s) : Pan SP , Liu Q , Wu D
Ref : Zhongguo Gu Shang , 22 :122 , 2009
Abstract : OBJECTIVE: To investigate the effect of exogenous glial cell line-derived neurotrophic factor (GDNF) infused into the cavitas subarachnoidealis on cornu anterius medullae spinalis motor neurons after sciatic nerve axotomy. METHODS: Forty-eight healthy SD rats were divided into 2 groups randomly: GDNF group and NS group. The left sciatic nerve in rats were cut off. And then 0.9% saline (6 microl) and GDNF solution (6 microl) were injected into cavitas subarachnoidealis at L4-L6 in NS group and GDNF group,respectively. The rats were sacrificed on postoperative 1, 2, 4 and 8 weeks respectively. Their specimen of L4-L6 spinal cord were taken at different time and sectioned. The HE staining, Nissl staining and cholinesterase (ChE) staining in motor neurons were used for counting of motor neurons. RESULTS: In GDNF group the number of motor neurons in cornu anterius medullae spinalis and the ChE activity were higher than that of NS group. CONCLUSION: The exogenous GDNF infused into the cavitas subarachnoidealis are supposed to protect the degenerated spinal motor neuron from death after sciatic nerve injury.
ESTHER : Pan_2009_Zhongguo.Gu.Shang_22_122
PubMedSearch : Pan_2009_Zhongguo.Gu.Shang_22_122
PubMedID: 19281023

Title : Genome sequence of the versatile fish pathogen Edwardsiella tarda provides insights into its adaptation to broad host ranges and intracellular niches - Wang_2009_PLoS.One_4_e7646
Author(s) : Wang Q , Yang M , Xiao J , Wu H , Wang X , Lv Y , Xu L , Zheng H , Wang S , Zhao G , Liu Q , Zhang Y
Ref : PLoS ONE , 4 :e7646 , 2009
Abstract : BACKGROUND: Edwardsiella tarda is the etiologic agent of edwardsiellosis, a devastating fish disease prevailing in worldwide aquaculture industries. Here we describe the complete genome of E. tarda, EIB202, a highly virulent and multi-drug resistant isolate in China. METHODOLOGY/PRINCIPAL FINDINGS: E. tarda EIB202 possesses a single chromosome of 3,760,463 base pairs containing 3,486 predicted protein coding sequences, 8 ribosomal rRNA operons, and 95 tRNA genes, and a 43,703 bp conjugative plasmid harboring multi-drug resistant determinants and encoding type IV A secretion system components. We identified a full spectrum of genetic properties related to its genome plasticity such as repeated sequences, insertion sequences, phage-like proteins, integrases, recombinases and genomic islands. In addition, analysis also indicated that a substantial proportion of the E. tarda genome might be devoted to the growth and survival under diverse conditions including intracellular niches, with a large number of aerobic or anaerobic respiration-associated proteins, signal transduction proteins as well as proteins involved in various stress adaptations. A pool of genes for secretion systems, pili formation, nonfimbrial adhesions, invasions and hemagglutinins, chondroitinases, hemolysins, iron scavenging systems as well as the incomplete flagellar biogenesis might feature its surface structures and pathogenesis in a fish body. CONCLUSION/SIGNIFICANCE: Genomic analysis of the bacterium offered insights into the phylogeny, metabolism, drug-resistance, stress adaptation, and virulence characteristics of this versatile pathogen, which constitutes an important first step in understanding the pathogenesis of E. tarda to facilitate construction of a practical effective vaccine used for combating fish edwardsiellosis.
ESTHER : Wang_2009_PLoS.One_4_e7646
PubMedSearch : Wang_2009_PLoS.One_4_e7646
PubMedID: 19865481
Gene_locus related to this paper: edwte-d0zav8 , edwte-d0zg19 , edwtf-e0t1p5 , edwte-d0za01 , edwte-d0z9v1

Title : Facile synthesis of three bidesmosidic oleanolic acid saponins with strong inhibitory activity on pancreatic lipase - Guo_2009_Carbohydr.Res_344_1167
Author(s) : Guo T , Liu Q , Wang P , Zhang L , Zhang W , Li Y
Ref : Carbohydr Res , 344 :1167 , 2009
Abstract : The first synthesis of scabiosaponins E (1), F (2), and G (3), three new oleanolic acid saponins with strong inhibitory activity on pancreatic lipase isolated from the Chinese traditional medicinal herb Scabiosa tschiliensis, was efficiently achieved in an one-pot strategy under the combined use of glycosyl trichloroacetimidates and p-toluene 1-thioglycosides (STol) as donors.
ESTHER : Guo_2009_Carbohydr.Res_344_1167
PubMedSearch : Guo_2009_Carbohydr.Res_344_1167
PubMedID: 19463989

Title : Agonist-induced hump current production in heterologously-expressed human alpha4beta2-nicotinic acetylcholine receptors - Liu_2008_Acta.Pharmacol.Sin_29_305
Author(s) : Liu Q , Yu KW , Chang YC , Lukas RJ , Wu J
Ref : Acta Pharmacol Sin , 29 :305 , 2008
Abstract : AIM: To characterize the functional and pharmacological features of agonist-induced hump currents in human alpha4beta2-nicotinic acetylcholine receptors (nAChR).
METHODS: Whole-cell and outside-out patch recordings were performed using human alpha4beta2-nAChR heterologously expressed in stably-transfected, native nAChR-null subclonal human epithelial 1 (SH-EP1) cells. RT-PCR was used to test the mRNA expression of transfected nAChR. Homology modeling and acetylcholine (ACh) docking were applied to show the possible ACh-binding site in the channel pore.
RESULTS: The rapid exposure of 10 mmol/L ACh induced an inward current with a decline from peak to steady-state. However, after the removal of ACh, an additional inward current, called phumpq current, reoccurred. The ability of agonists to produce these hump currents cannot be easily explained based on drug size, charge, acute potency, or actions as full or partial agonists. Hump currents were associated with a rebound increase in whole-cell conductance, and they had voltage dependence-like peak currents induced by agonist action. Hump currents blocked by the alpha4beta2-nAChR antagonist dihydro-beta-erythroidine were reduced when alpha4beta2-nAChR were desensitized, and were more pronounced in the absence of external Ca2+. Outside-out single-channel recordings demonstrated that compared to 1 micromol/L nicotine, 100 micromol/L nicotine reduced channel current amplitude, shortened the channel mean open time, and prolonged the channel mean closed time, supporting an agonist-induced open-channel block before hump current production. A docking model also simulated the agonist-binding site in the channel pore. CONCLUSION: These results support the hypothesis that hump currents reflect a rapid release of agonists from the alpha4beta2-nAChR channel pore and a rapid recovery from desensitized alpha4beta2-nAChR.
ESTHER : Liu_2008_Acta.Pharmacol.Sin_29_305
PubMedSearch : Liu_2008_Acta.Pharmacol.Sin_29_305
PubMedID: 18298895

Title : Tasigna for chronic and accelerated phase Philadelphia chromosome--positive chronic myelogenous leukemia resistant to or intolerant of imatinib - Hazarika_2008_Clin.Cancer.Res_14_5325
Author(s) : Hazarika M , Jiang X , Liu Q , Lee SL , Ramchandani R , Garnett C , Orr MS , Sridhara R , Booth B , Leighton JK , Timmer W , Harapanhalli R , Dagher R , Justice R , Pazdur R
Ref : Clin Cancer Research , 14 :5325 , 2008
Abstract : PURPOSE: This Food and Drug Administration (FDA) approval report describes the data and analyses leading to the approval by the FDA of nilotinib (Tasigna, AMN-107; Novartis Pharmaceuticals Corporation), an inhibitor of Bcr-Abl tyrosine kinase, for the treatment of chronic-phase (CP) and accelerated-phase (AP) chronic myelogenous leukemia (CML) resistant to or intolerant of imatinib. EXPERIMENTAL DESIGN: The FDA approval of the efficacy and safety of nilotinib was based on the results of an ongoing single-arm, open-label, phase 2 clinical trial. The primary end point for CML-CP was unconfirmed major cytogenetic response. The efficacy end point for CML-AP was confirmed hematologic response.
RESULTS: The major cytogenetic response rate in 232 evaluable CP patients was 40% (95% confidence interval, 33%, 46%). The hematologic response rate in 105 evaluable AP patients was 26% (95% confidence interval, 18%, 35%). The median duration of response has not been reached for both CML-CP and CML-AP responding patients. In CML-CP patients, the common serious drug-related adverse reactions were thrombocytopenia and neutropenia. In CML-AP patients, the common serious drug-related adverse reactions were thrombocytopenia, neutropenia, pneumonia, febrile neutropenia, leukopenia, intracranial hemorrhage, elevated lipase, and pyrexia. Nilotinib prolongs the QT interval and sudden deaths have been reported; these risks and appropriate risk minimization strategies are described in a boxed warning on the labeling.
CONCLUSIONS: On October 29, 2007, the U.S. FDA granted accelerated approval to nilotinib (Tasigna) for use in the treatment of CP and AP Philadelphia chromosome positive CML in adult patients resistant to or intolerant of prior therapy that included imatinib.
ESTHER : Hazarika_2008_Clin.Cancer.Res_14_5325
PubMedSearch : Hazarika_2008_Clin.Cancer.Res_14_5325
PubMedID: 18765523

Title : Sequence and genetic map of Meloidogyne hapla: A compact nematode genome for plant parasitism - Opperman_2008_Proc.Natl.Acad.Sci.U.S.A_105_14802
Author(s) : Opperman CH , Bird DM , Williamson VM , Rokhsar DS , Burke M , Cohn J , Cromer J , Diener S , Gajan J , Graham S , Houfek TD , Liu Q , Mitros T , Schaff J , Schaffer R , Scholl E , Sosinski BR , Thomas VP , Windham E
Ref : Proc Natl Acad Sci U S A , 105 :14802 , 2008
Abstract : We have established Meloidogyne hapla as a tractable model plant-parasitic nematode amenable to forward and reverse genetics, and we present a complete genome sequence. At 54 Mbp, M. hapla represents not only the smallest nematode genome yet completed, but also the smallest metazoan, and defines a platform to elucidate mechanisms of parasitism by what is the largest uncontrolled group of plant pathogens worldwide. The M. hapla genome encodes significantly fewer genes than does the free-living nematode Caenorhabditis elegans (most notably through a reduction of odorant receptors and other gene families), yet it has acquired horizontally from other kingdoms numerous genes suspected to be involved in adaptations to parasitism. In some cases, amplification and tandem duplication have occurred with genes suspected of being acquired horizontally and involved in parasitism of plants. Although M. hapla and C. elegans diverged >500 million years ago, many developmental and biochemical pathways, including those for dauer formation and RNAi, are conserved. Although overall genome organization is not conserved, there are areas of microsynteny that may suggest a primary biological function in nematodes for those genes in these areas. This sequence and map represent a wealth of biological information on both the nature of nematode parasitism of plants and its evolution.
ESTHER : Opperman_2008_Proc.Natl.Acad.Sci.U.S.A_105_14802
PubMedSearch : Opperman_2008_Proc.Natl.Acad.Sci.U.S.A_105_14802
PubMedID: 18809916
Gene_locus related to this paper: melha-a0a1i8byx0 , melha-a0a1i8bkb4

Title : Lipase-catalyzed selective synthesis of monolauroyl maltose using continuous stirred tank reactor - Liu_2008_Biotechnol.Lett_30_497
Author(s) : Liu Q , Jia C , Kim JM , Jiang P , Zhang X , Feng B , Xu S
Ref : Biotechnol Lett , 30 :497 , 2008
Abstract : Monolauroyl maltose was synthesized by an immobilized lipase that catalyzed condensation of maltose and lauric acid in acetone using a batch reactor or a continuous stirred tank reactor. Mono- and di-lauroyl maltoses were identified by FT-IR, (1)H NMR, (13)C NMR and MS. Monolauroyl maltose was selectively synthesized in a continuous stirred tank reactor and no diester was detected. The highest concentration of monolauroyl maltose at 28 mmol/l was obtained in 250 ml acetone when maltose was added at 4 g/d and the molar ratio of lauric acid to maltose was fixed at 4:1 at a flow rate of 0.15 ml/min for both influx and effluent without supplement of fresh molecular sieve.
ESTHER : Liu_2008_Biotechnol.Lett_30_497
PubMedSearch : Liu_2008_Biotechnol.Lett_30_497
PubMedID: 17968509

Title : Roles of nicotinic acetylcholine receptor beta subunits in function of human alpha4-containing nicotinic receptors - Wu_2006_J.Physiol_576_103
Author(s) : Wu J , Liu Q , Yu K , Hu J , Kuo YP , Segerberg M , St John PA , Lukas RJ
Ref : Journal of Physiology , 576 :103 , 2006
Abstract : Naturally expressed nicotinic acetylcholine receptors (nAChR) containing alpha4 subunits (alpha4*-nAChR) in combination with beta2 subunits (alpha4beta2-nAChR) are among the most abundant, high-affinity nicotine binding sites in the mammalian brain. beta4 subunits are also richly expressed and colocalize with alpha4 subunits in several brain regions implicated in behavioural responses to nicotine and nicotine dependence. Thus, alpha4beta4-nAChR also may exist and play important functional roles. In this study, properties were determined of human alpha4beta2- and alpha4beta4-nAChR heterologously expressed de novo in human SH-EP1 epithelial cells. Whole-cell currents mediated via human alpha4beta4-nAChR have approximately 4-fold higher amplitude than those mediated via human alpha4beta2-nAChR and exhibit much slower acute desensitization and functional rundown. Nicotinic agonists induce peak whole-cell current responses typically with higher functional potency at alpha4beta4-nAChR than at alpha4beta2-nAChR. Cytisine and lobeline serve as full agonists at alpha4beta4-nAChR but are only partial agonists at alpha4beta2-nAChR. However, nicotinic antagonists, except hexamethonium, have comparable affinities for functional alpha4beta2- and alpha4beta4-nAChR. Whole-cell current responses show stronger inward rectification for alpha4beta2-nAChR than for alpha4beta4-nAChR at a positive holding potential. Collectively, these findings demonstrate that human nAChR beta2 or beta4 subunits can combine with alpha4 subunits to generate two forms of alpha4*-nAChR with distinctive physiological and pharmacological features. Diversity in alpha4*-nAChR is of potential relevance to nervous system function, disease, and nicotine dependence.
ESTHER : Wu_2006_J.Physiol_576_103
PubMedSearch : Wu_2006_J.Physiol_576_103
PubMedID: 16825297

Title : Iptakalim inhibits nicotine-induced enhancement of extracellular dopamine and glutamate levels in the nucleus accumbens of rats - Liu_2006_Brain.Res_1085_138
Author(s) : Liu Q , Li Z , Ding JH , Liu SY , Wu J , Hu G
Ref : Brain Research , 1085 :138 , 2006
Abstract : Iptakalim (Ipt) is a novel ATP-sensitive potassium channel opener. It has been reported that Ipt inhibited cocaine-induced dopamine and glutamate release, suggesting that Ipt may regulate drug addiction. Recently, we found that Ipt blocked nicotinic acetylcholine receptor (nAChR)-mediated currents in a heterologously expressed SH-EP1 cell line and in native midbrain dopamine neurons. In the present study, we examined whether Ipt prevents nicotine-induced neurotransmitter release in the nucleus accumbens (NAc) using in vivo microdialysis methods in awake, freely moving rats. Ipt was administered through a microdialysis probe, following systemic administration of nicotine (0.5 mg/kg, s.c.). The results show that acute nicotine treatment induced an increase of both dopamine and glutamate levels in the rat NAc, and that Ipt significantly attenuated nicotine's effects in a concentration-dependent manner. Therefore, Ipt may serve as a novel compound to block nicotine-induced dopamine and glutamate release in the brain reward center, in turn decreasing nicotine reinforcement and dependence.
ESTHER : Liu_2006_Brain.Res_1085_138
PubMedSearch : Liu_2006_Brain.Res_1085_138
PubMedID: 16647046

Title : Neuronal nicotinic acetylcholine receptors serve as sensitive targets that mediate beta-amyloid neurotoxicity - Liu_2006_Acta.Pharmacol.Sin_27_1277
Author(s) : Liu Q , Wu J
Ref : Acta Pharmacol Sin , 27 :1277 , 2006
Abstract : Alzheimer's disease (AD) is the most common form of brain dementia characterized by the accumulation of beta-amyloid peptides (Abeta) and loss of forebrain cholinergic neurons. Abeta accumulation and aggregation are thought to contribute to cholinergic neuronal degeneration, in turn causing learning and memory deficits, but the specific targets that mediate Abeta neurotoxicity remain elusive. Recently, accumulating lines of evidence have demonstrated that Abeta directly modulates the function of neuronal nicotinic acetylcholine receptors (nAChRs), which leads to the new hypothesis that neuronal nAChRs may serve as important targets that mediate Abeta neurotoxicity. In this review, we summarize current studies performed in our laboratory and in others to address the question of how Abeta modulates neuronal nAChRs, especially nAChR subunit function.
ESTHER : Liu_2006_Acta.Pharmacol.Sin_27_1277
PubMedSearch : Liu_2006_Acta.Pharmacol.Sin_27_1277
PubMedID: 17007734

Title : Evaluation of effect of hybrid bioartificial liver using end-stage liver disease model - Liu_2004_World.J.Gastroenterol_10_1379
Author(s) : Liu Q , Duan ZP , Huang C , Zhao CH
Ref : World J Gastroenterol , 10 :1379 , 2004
Abstract : AIM: To study the role of hybrid bioartificial liver (HBL) in clearing proinflammatory cytokines and endotoxin in patients with acute and sub-acute liver failure and the effects of HBL on systemic inflammatory syndrome (SIRS) and multiple organ dysfunction syndrome (MODS).
METHODS: Five cases with severe liver failure (3 acute and 2 subacute) were treated with HBL. The clinical signs and symptoms, total bilirubin (TBIL), serum ammonia, endotoxin TNF-alpha, IL-6 and prothrombin activity (PTA),cholinesterase (CHE) were recorded before, during and after treatment. The end-stage liver disease (MELD) was used for the study.
RESULTS: Two patients were bridged for spontaneous recovery and 1 patient was bridged for OLT successfully. Another 2 patients died on d 8 and d 21. The spontaneous recovery rate was 30.0%. PTA and CHE in all patients were significantly increased (P<0.01), while the serum TBIL, endotoxin, TNF-alpha, IL-6 were decreased. MELD score (mean 43.6) predicted 100% deaths within 3 mo before treatment with HBL. After treatment with HBL, four out of 5 patients had decreased MELD scores (mean 36.6). The MELD score predicted 66% mortalities. CONCLUSION: The proinflammatory cytokines (TNFalpha, IL-6 and endotoxin)can be significantly removed by hybrid bioartificial liver and HBL appears to be effective in blocking SIRS and MODS in patients with acute and sub-acute liver failure. MELD is a reliable measure for predicting short-term mortality risk in patients with end-stage liver disease. The prognostic result also corresponds to clinical outcome.
ESTHER : Liu_2004_World.J.Gastroenterol_10_1379
PubMedSearch : Liu_2004_World.J.Gastroenterol_10_1379
PubMedID: 15112365

Title : Cloning, identification and expression of an entE homologue angE from Vibrio anguillarum serotype O1 - Liu_2004_Arch.Microbiol_181_287
Author(s) : Liu Q , Ma Y , Wu H , Shao M , Liu H , Zhang Y
Ref : Arch Microbiol , 181 :287 , 2004
Abstract : Anguibactin, an important virulent factor in Vibrio anguillarum serotype O1, is synthesized by a nonribosomal peptide synthetases (NRPS) system encoded on a 65-kb virulence plasmid pJM1. angE, as one of the NRPS genes, is responsible for selecting and activating 2,3-dihydroxybenzoic acid (2,3-DHBA), an important precursor in anguibactin synthesis, into 2,3-DHBA-AMP by adenylylation in the presence of ATP. In this work, an entE homologue, angE, was identified on pEIB1 (a pJM1-like plasmid) from virulent V. anguillarum serotype O1 strain MVM425. A recombinant clone carrying the complete angE was able to complement an Escherichia coli entE mutant. The angE-encoded protein was overexpressed in E. coli and purified by a three-step procedure. Purified AngE was then used to establish an in vitro enzymatic reaction in which its enzymatic activity of 1-(5'-monophosphate adenyl) 2,3-dihydroxybenzoic acid ligase (2,3-DHBA-AMP ligase) was proved using HPLC to detect AMP formation in the reaction mixture. Moreover, evidence at the level of both transcription and translation confirmed that angE was actively expressed in vivo in V. anguillarum MVM425, and interestingly, unlike many other iron-uptake-system-related genes, its expression is not induced by a low iron concentration in the surrounding environment.
ESTHER : Liu_2004_Arch.Microbiol_181_287
PubMedSearch : Liu_2004_Arch.Microbiol_181_287
PubMedID: 14758470
Gene_locus related to this paper: viban-sast

Title : Epoxide hydrolase-catalyzed resolution of ethyl 3-phenylglycidate using whole cells of Pseudomonas sp - Li_2003_Biotechnol.Lett_25_2113
Author(s) : Li C , Liu Q , Song X , Di D , Ji A , Qu Y
Ref : Biotechnol Lett , 25 :2113 , 2003
Abstract : A Pseudomonas sp. was isolated with enantioselective epoxide hydrolase activity to ethyl 3-phenylglycidate. Cells grown on sucrose and suspended in 10% (v/v) dimethyl formamide as co-solvent produced (2R,3S) ethyl 3-phenylglycidate with 95% ee and 26% yield in 12 h from 0.2% (w/v) of the racemate.
ESTHER : Li_2003_Biotechnol.Lett_25_2113
PubMedSearch : Li_2003_Biotechnol.Lett_25_2113
PubMedID: 14969419

Title : beta -Amyloid peptide blocks the response of alpha 7-containing nicotinic receptors on hippocampal neurons - Liu_2001_Proc.Natl.Acad.Sci.U.S.A_98_4734
Author(s) : Liu Q , Kawai H , Berg DK
Ref : Proc Natl Acad Sci U S A , 98 :4734 , 2001
Abstract : Alzheimer's disease produces a devastating decline in mental function, with profound effects on learning and memory. Early consequences of the disease include the specific loss of cholinergic neurons in brain, diminished cholinergic signaling, and the accumulation of beta-amyloid peptide in neuritic plaques. Of the nicotinic acetylcholine receptors at risk, the most critical may be those containing the alpha7 gene product (alpha7-nAChRs), because they are widespread, have a high relative permeability to calcium, and regulate numerous cellular events in the nervous system. With the use of whole-cell patch-clamp recording we show here that nanomolar concentrations of beta-amyloid peptides specifically and reversibly block alpha7-nAChRs on rat hippocampal neurons in culture. The block is noncompetitive, voltage-independent, and use-independent and is mediated through the N-terminal extracellular domain of the receptor. It does not appear to require either calcium influx or G protein activation. beta-Amyloid blockade is likely to be a common feature of alpha7-nAChRs because it applies to the receptors at both somato-dendritic and presynaptic locations on rat hippocampal neurons and extends to homologous receptors on chick ciliary ganglion neurons as well. Because alpha7-nAChRs in the central nervous system are thought to have numerous functions and recently have been implicated in learning and memory, impaired receptor function in this case may contribute to cognitive deficits associated with Alzheimer's disease.
ESTHER : Liu_2001_Proc.Natl.Acad.Sci.U.S.A_98_4734
PubMedSearch : Liu_2001_Proc.Natl.Acad.Sci.U.S.A_98_4734
PubMedID: 11274373

Title : Lipoprotein lipase D9N, N291S and S447X polymorphisms: their influence on premature coronary heart disease and plasma lipids - van Bockxmeer_2001_Atherosclerosis_157_123
Author(s) : van Bockxmeer FM , Liu Q , Mamotte C , Burke V , Taylor R
Ref : Atherosclerosis , 157 :123 , 2001
Abstract : Lipoprotein lipase (LPL) plays a pivotal role in lipoprotein metabolism. Three recently described exonic polymorphisms of the gene, D9N, N291S and S447X, have been variably found to influence plasma lipids while effects on coronary heart disease (CHD) are less well documented. Two predominantly Caucasian groups were studied: CHD patients <50 years of age, with angiographically documented CHD; and a randomly recruited community control group without a history of heart disease. The 9N allele of the D9N polymorphism was present in 25 of 428 (5.8%) of Caucasian males with CHD and in seven of 291 (2.4%) of corresponding community subjects (odds ratio, 2.5; 95% confidence interval (CI), 1.1-5.9; P=0.03) and was also significantly over-represented in the Caucasian males with myocardial infarction (MI) (21 of 308 or 6.8%; odds ratio, 2.6; 95% CI, 1.1-5.9; P=0.01). The distributions of the other two polymorphisms were similar in the CHD and community groups. In multivariate models adjusted for age, sex, diabetes, body mass index, smoking, lipid levels and race, the D9N polymorphism remained significantly related to both CHD and MI, with an odds ratio >2. There were, generally, trends to more adverse fasting plasma high-density lipoprotein (HDL) cholesterol and triglycerides in carriers of the 291S and 9N alleles, and the opposite trends for triglycerides in 447X carriers. In the community group, male carriers of 291S (n=13) had significantly (20%) lower HDL cholesterol than corresponding non-carriers (n=323), 0.98+/-0.07 mmol/l (mean+/-S.E.) versus 1.22+/-0.02 mmol/l (P<0.005), while HDL cholesterol was not different in male carriers (n=8) and non-carriers (n=296) of 9N (1.23+/-0.13 mmol/l versus 1.22+/-0.02 mmol/l). Multivariate analysis confirmed that the 291S allele carrier status conferred a significantly lower HDL cholesterol (P=0.001) and the 447X allele lower triglyceride (P<0.01) in the community group. In conclusion, LPL 9N carrier status was unequivocally related to premature CHD and to MI in males, strongly supporting recent results in older aged males. The somewhat different effects of the D9N and N291S polymorphisms on plasma lipids, and the absence of a clear effect of the N291S on CHD, raise the possibility that the effect of 9N carrier status might be mediated through effects on LPL function in addition to those influencing fasting plasma lipids.
ESTHER : van Bockxmeer_2001_Atherosclerosis_157_123
PubMedSearch : van Bockxmeer_2001_Atherosclerosis_157_123
PubMedID: 11427211

Title : Actin filaments and the opposing actions of CaM kinase II and calcineurin in regulating alpha7-containing nicotinic receptors on chick ciliary ganglion neurons - Liu_1999_J.Neurosci_19_10280
Author(s) : Liu Q , Berg DK
Ref : Journal of Neuroscience , 19 :10280 , 1999
Abstract : Nicotinic acetylcholine receptors containing alpha7 subunits have a high relative permeability to calcium and influence numerous calcium-dependent cellular events. On chick ciliary ganglion neurons the receptors are concentrated on somatic spines containing actin filaments. Using conventional whole-cell patch-clamp recording from dissociated ciliary ganglion neurons, we show that responses from alpha7-containing receptors undergo substantial rundown when the receptors are repeatedly challenged with nicotine. Stabilization of actin filaments with phalloidin partially prevents the rundown, whereas collapse of actin filaments with latrunculin A exacerbates it. The rundown depends on calcium influx through the receptors because it requires receptor activation and can be prevented by replacing extracellular calcium with barium or by intracellular dialysis with BAPTA. Thapsigargin and ryanodine each inhibit the rundown, demonstrating further a requirement for calcium release from internal stores. Blockade of calmodulin by calmidazolium or blockade of CaM kinase II with either KN93 or autocamtide-2-related inhibitory peptide each prevents the rundown; blockade of the phosphatase calcineurin with either cyclosporin A or deltamethrin increases the rundown. The results indicate a balance of calcium-dependent kinase and phosphatase activities in regulating the function of alpha7-containing receptors. Manifestation of the rundown depends in part on the loss of intracellular components via dialysis because little rundown is seen if perforated patch-clamp recording is used to monitor receptor responses even in latrunculin A-treated cells. A membrane-permeable calcineurin inhibitor, however, still decreases the nicotinic response in a calcium-dependent manner, confirming that calcium-dependent phosphoregulation of alpha7-containing receptors occurs in the intact cell.
ESTHER : Liu_1999_J.Neurosci_19_10280
PubMedSearch : Liu_1999_J.Neurosci_19_10280
PubMedID: 10575025