Yu Q

References (47)

Title : FsCGBP, a Cutinase G-Box Binding Protein, Regulates the Growth, Development, and Virulence of Fusarium sacchari, the Pathogen of Sugarcane Pokkah Boeng Disease - Liang_2024_J.Fungi.(Basel)_10_
Author(s) : Liang H , Li F , Huang Y , Yu Q , Huang Z , Zeng Q , Chen B , Meng J
Ref : J Fungi (Basel) , 10 : , 2024
Abstract : Fusarium sacchari is a causal agent of sugarcane Pokkah boeng, an important fungal disease that causes a considerable reduction in yield and sugar content in susceptible varieties of sugarcane worldwide. Despite its importance, the fungal factors that regulate the virulence of this pathogen remain largely unknown. In our previous study, mapping of an insertional mutant defect in virulence resulted in the identification of a cutinase G-box binding protein gene, designated FsCGBP, that encodes a C2H2-type transcription factor (TF). FsCGBP was shown to localize in the nuclei, and the transcript level of FsCGBP was significantly upregulated during the infection process or in response to abiotic stresses. Deletion or silencing of FsCGBP resulted in a reduction in mycelial growth, conidial production, and virulence and a delay in conidial germination in the F. sacchari. Cutinase genes FsCUT2, FsCUT3, and FsCUT4 and the mitogen-activated protein kinase (MAPK) genes FsHOG1, FsMGV1, and FsGPMK1, which were significantly downregulated in deltaFsCGBP. Except for FsHOG1, all of these genes were found to be transcriptionally activated by FsCGBP using the yeast one-hybrid system in vitro. The deletion of individual cutinase genes did not result in any of the phenotypes exhibited in the deltaFsCGBP mutant, except for cutinase activity. However, disruption of the MAPK pathway upon deletion of FsMGV1 or FsGPMK1 resulted in phenotypes similar to those of the deltaFsCGBP mutant. The above results suggest that FsCGBP functions by regulating the MAPK pathway and cutinase genes, providing new insights into the mechanism of virulence regulation in F. sacchari.
ESTHER : Liang_2024_J.Fungi.(Basel)_10_
PubMedSearch : Liang_2024_J.Fungi.(Basel)_10_
PubMedID: 38667917

Title : A novel near-infrared fluorescent probe for high-sensitivity detection of butyrylcholinesterase in various pathological states - Jiang_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_308_123801
Author(s) : Jiang Y , Cui H , Yu Q
Ref : Spectrochim Acta A Mol Biomol Spectrosc , 308 :123801 , 2023
Abstract : Butyrylcholinesterase (BChE) is a crucial hydrolytic enzyme predominantly synthesized in the liver, playing a significant role in conditions like liver disorders, diabetes, Alzheimer's disease, and fat metabolism regulation. This study aims to address the current limitations in visualizing BChE activity in diseases at various states by introducing an ultra-sensitive near-infrared fluorescent probe, FDCM-BChE. The probe was engineered to have several properties, such as a large Stokes shift, rapid response time, high stability, excellent selectivity, and low detection limits. We validated the efficacy of FDCM-BChE in quantifying BChE activity in human serum and leveraged its low cytotoxicity for cellular imaging. The study revealed the downregulation of BChE activity in liver cancer and hepatic injury and the upregulation in diabetes. Thus, FDCM-BChE shows promise as a tool for specific applications, providing insights into diseases associated with BChE activity.
ESTHER : Jiang_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_308_123801
PubMedSearch : Jiang_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_308_123801
PubMedID: 38142494

Title : The NLR immune receptor ADR1 and lipase-like proteins EDS1 and PAD4 mediate stomatal immunity in Nicotiana benthamiana and Arabidopsis - Wang_2023_Plant.Cell__
Author(s) : Wang H , Song S , Gao S , Yu Q , Zhang H , Cui X , Fan J , Xin X , Liu Y , Staskawicz B , Qi T
Ref : Plant Cell , : , 2023
Abstract : In the presence of pathogenic bacteria, plants close their stomata to prevent pathogen entry. Intracellular nucleotide-binding leucine-rich repeat (NLR) immune receptors recognize pathogenic effectors and activate effector-triggered immune responses. However, the regulatory and molecular mechanisms of stomatal immunity involving NLR immune receptors are unknown. Here, we show that the Nicotiana benthamiana RPW8-NLR central immune receptor ACTIVATED DISEASE RESISTANCE 1 (NbADR1), together with the key immune proteins ENHANCED DISEASE SUSCEPTIBILITY 1 (NbEDS1) and PHYTOALEXIN DEFICIENT 4 (NbPAD4), plays an essential role in bacterial pathogen- and flg22-induced stomatal immunity by regulating the expression of salicylic acid (SA) and abscisic acid (ABA) biosynthesis or response-related genes. NbADR1 recruits NbEDS1 and NbPAD4 in stomata to form a stomatal immune response complex. The transcription factor NbWRKY40e, in association with NbEDS1 and NbPAD4, modulates the expression of SA and ABA biosynthesis or response-related genes to influence stomatal immunity. NbADR1, NbEDS1, and NbPAD4 are required for the pathogen infection-enhanced binding of NbWRKY40e to the ISOCHORISMATE SYNTHASE 1 promoter. Moreover, the ADR1-EDS1-PAD4 module regulates stomatal immunity in Arabidopsis (Arabidopsis thaliana). Collectively, our findings show the pivotal role of the core intracellular immune receptor module ADR1-EDS1-PAD4 in stomatal immunity, which enables plants to limit pathogen entry.
ESTHER : Wang_2023_Plant.Cell__
PubMedSearch : Wang_2023_Plant.Cell__
PubMedID: 37851863

Title : Synergistic effects of ferulic acid esterase-producing lactic acid bacteria, cellulase and xylanase on the fermentation characteristics, fibre and nitrogen components and microbial community structure of Broussonetia papyrifera during ensiling - Yu_2023_J.Sci.Food.Agric__
Author(s) : Yu Q , Xu J , Li M , Xi Y , Sun H , Xie Y , Cheng Q , Li P , Chen C , Yang F , Zheng Y
Ref : J Sci Food Agric , : , 2023
Abstract : BACKGROUND: The high fibre content of whole plants of Broussonetia papyrifera limits its efficient utilization. Ferulic acid esterase (FAE), in combination with xylanase, can effectively cleave the lignin-carbohydrate complex, promoting the function of cellulase. However, little is known about the impact of these additives on silage. To effectively utilize natural woody plant resources, FAE-producing Lactobacillus plantarum RO395, xylanase (XY) and cellulase (CE) were used to investigate the dynamic fermentation characteristics, fibre and nitrogen components and microbial community structure during B. papyrifera ensiling. RESULTS: B. papyrifera was either not treated (CK) or treated with FAE-producing lactic acid bacteria (LP), CE, XY, LP+CE, LP+XY or LP+CE+XY for 3, 7, 15, 30 or 60 days, respectively. In comparison with those in the CK treatment, the L. plantarum and enzyme treatments (LP+CE, LP+XY and LP+XY+CE), especially the LP+XY+CE treatment, significantly increased the lactic acid concentration and decreased the pH and the contents of acid detergent insoluble protein and NH(3) -N (P < 0.05). Enzyme addition improved the degradation efficiency of lignocellulose, and a synergistic effect was observed after enzyme treatment in combination with LP; in addition, the lowest acid detergent fibre, neutral detergent fibre, hemicellulose, and cellulose contents were detected after the LP+CE+XY treatment (P < 0.05). Moreover, CE, XY and LP additions significantly improved the microbial community structure, increased the relative abundance of Lactiplantibacillus and Firmicutes, and effectively inhibited undesirable bacterial (Enterobacter) growth during ensiling. CONCLUSION: FAE-producing L. plantarum and the two tested enzymes exhibited synergistic effects on improving the quality of silage, which indicates that this combination can serve as an efficient method for improved B. papyrifera silage utilization. This article is protected by copyright. All rights reserved.
ESTHER : Yu_2023_J.Sci.Food.Agric__
PubMedSearch : Yu_2023_J.Sci.Food.Agric__
PubMedID: 38146051

Title : Efficacy and safety of cetagliptin as monotherapy in patients with type 2 diabetes: A randomized, double-blind, placebo-controlled phase 3 trial - Ji_2023_Diabetes.Obes.Metab_25_3671
Author(s) : Ji L , Lu J , Gao L , Ying C , Sun J , Han J , Zhao W , Gao Y , Wang K , Zheng X , Xie D , Ding J , Zhao J , Yu Q , Wang T
Ref : Diabetes Obes Metab , 25 :3671 , 2023
Abstract : AIM: To assess the efficacy and safety of the dipeptidyl peptidase-4 inhibitor, cetagliptin, as monotherapy in Chinese patients with type 2 diabetes (T2D) and inadequate glycaemic control. MATERIALS AND METHODS: In total, 504 eligible patients with T2D were enrolled and randomized to cetagliptin 50 mg once daily, cetagliptin 100 mg once daily or placebo at a ratio of 2:2:1 for 24 weeks of double-blind treatment, then all patients received cetagliptin 100 mg once daily for 28 weeks of open-label treatment. The primary efficacy endpoint was the change in HbA1c level from baseline at week 24. RESULTS: After 24 weeks, HbA1c from baseline was significantly reduced with cetagliptin 50 mg (-1.08%) and cetagliptin 100 mg (-1.07%) compared with placebo (-0.35%). The placebo-subtracted HbA1c reduction was -0.72% with cetagliptin 50 mg and 100 mg. Patients with a baseline HbA1c of 8.5% or higher had a greater HbA1c reduction with cetagliptin than those patients with a baseline HbA1c of less than 8.5%. Both doses studied led to a significantly higher proportion of patients (42.3% with 100 mg and 45.0% with 50 mg) achieving an HbA1c of less than 7.0% compared with placebo (12.9%). Cetagliptin also significantly lowered fasting plasma glucose and 2-hour postmeal plasma glucose relative to placebo. The incidence of adverse experiences was similar between cetagliptin and placebo. No drug-related hypoglycaemia was reported. CONCLUSIONS: Cetagliptin monotherapy was effective and well tolerated in Chinese patients with T2D who had inadequate glycaemic control on exercise and diet.
ESTHER : Ji_2023_Diabetes.Obes.Metab_25_3671
PubMedSearch : Ji_2023_Diabetes.Obes.Metab_25_3671
PubMedID: 37661308

Title : A randomized, double-blind, placebo controlled, phase 3 trial to evaluate the efficacy and safety of cetagliptin added to ongoing metformin therapy in patients with uncontrolled type 2 diabetes with metformin monotherapy - Ji_2023_Diabetes.Obes.Metab_25_3788
Author(s) : Ji L , Lu J , Gao L , Yan X , Li J , Cheng Z , Zhang L , Tian J , Li P , Bai J , Xie D , Zhao J , Ding J , Yu Q , Wang T
Ref : Diabetes Obes Metab , 25 :3788 , 2023
Abstract : AIM: This trial was designed to assess the efficacy and safety of cetagliptin added to metformin in Chinese patients with type 2 diabetes who had inadequate glycaemic control with metformin monotherapy. METHODS: In total, 446 patients with type 2 diabetes on metformin monotherapy were randomized to receive the addition of once-daily cetagliptin 100mg, cetagliptin 50mg and placebo in a 2:2:1 ratio for 24-week double-blind treatment. At week 24, patients initially randomized to cetagliptin 50mg and placebo were switched to cetagliptin 100mg for 28weeks open-label treatment. The primary endpoint was the change in haemoglobin A1c (HbA1c) from baseline, and the efficacy analyses were based on an all-patients-treated population using an analysis of co-variance. RESULTS: After 24weeks, both add-on therapies led to greater glycaemic control. Reductions in HbA1c from baseline were -1.17+/-0.794%, -1.23+/-0.896% in cetagliptin 100mg and 50mg plus metformin group, respectively. No difference was observed between the cetagliptin 100mg and 50mg plus metformin group. Patients with higher baseline HbA1c levels (<=8.5%) experienced greater reductions in HbA1c. A significantly greater proportion of patients achieved an HbA1c <7.0% with cetagliptin 100mg (49.4%) and cetagliptin 50mg (51.1%) plus metformin than metformin monotherapy (14.4%). Both combination therapies also improved the homeostasis model assessment beta-function index and decreased systolic blood pressure. There was no increased risk of adverse effects with combination therapy, and both combination therapies were generally well tolerated. CONCLUSIONS: The addition of cetagliptin once daily to metformin was more efficacious and well tolerated than metformin monotherapy in Chinese patients with type 2 diabetes who had inadequate glycaemic control with metformin monotherapy.
ESTHER : Ji_2023_Diabetes.Obes.Metab_25_3788
PubMedSearch : Ji_2023_Diabetes.Obes.Metab_25_3788
PubMedID: 37724698

Title : The metabolism and excretion of the dipeptidyl peptidase 4 inhibitor [(14)C] cetagliptin in healthy volunteers - Lu_2022_Xenobiotica_52_38
Author(s) : Lu J , Bian Y , Zhang H , Tang D , Tian X , Zhou X , Xu Z , Xiong Y , Gu Z , Yu Z , Wang T , Ding J , Yu Q
Ref : Xenobiotica , 52 :38 , 2022
Abstract : The metabolism and excretion of cetagliptin were investigated in healthy male subjects after a single oral dose of 100mg/50microCi [(14)C] cetagliptin.The mean concentration-time profile of cetagliptin was similar to that of total radioactivity in plasma after oral administration of [(14)C] cetagliptin in healthy male subjects. Cetagliptin was rapidly absorbed after oral administration. Unchanged cetagliptin was the most abundant radioactive component in all matrices investigated. Approximately 53.13% of plasma AUC of total radioactivity was accounted for by cetagliptin. Each metabolite plasma AUC was not higher than 2.93% of plasma AUC of total radioactivity. By 336h after administration, 91.68% of the administered radioactivity was excreted, and the cumulative excretion in the urine and faeces was 72.88% and 18.81%, respectively. The primary route of excretion of radioactivity was via the kidneys.Four metabolites were detected at trace levels, and it involved hydroxylated (M436-1 and M436-3), N- sulphate (M500), and N-carbamoyl glucuronic acid conjugates (M640B) of cetagliptin. These metabolites were detected also in plasma, urine, and faeces at low levels, except that metabolite M640B was not detected in faeces. All metabolites were observed with <10% of parent compound systemic exposure after oral administration.
ESTHER : Lu_2022_Xenobiotica_52_38
PubMedSearch : Lu_2022_Xenobiotica_52_38
PubMedID: 34743655

Title : Disposition study of the novel dipeptidyl peptidase 4 inhibitor cetagliptin in rats - Lu_2022_Xenobiotica_52_468
Author(s) : Lu J , Hao Y , Zhang F , Pan H , Ding J , Yu Q , Wang T
Ref : Xenobiotica , 52 :468 , 2022
Abstract : Dipeptidyl peptidase-4 (DPP-4) inhibitor is a class of oral antihyperglycemic agents and therapeutic approach for type 2 diabetes. Cetagliptin is a novel oral and selective DPP-4 inhibitor and developed as a promising candidate for treatment of type 2 diabetes mellitus.This study aimed to evaluate the metabolism and excretion of cetagliptin in Sprague-Dawley (SD) rats, and to detect and identify metabolites of cetagliptin.The SD rats were administered with a single oral dose of 6mg/kg with approximately 100microCi of [(14)C] cetagliptin. The mean total recovery of radioactivity was 90.20% within 168h in SD rats excreta. Cetagliptin was the major radioactive component in SD rats plasma, urine and eliminated primarily by faecal excretion. The recovery of cetagliptin in urine and feces was 25.15% and 13.85% of the dose, respectively. Cetagliptin was well absorbed after oral administration in SD rats based on the total recovery of radioactivity in BDC SD rats bile and urine.Six major metabolites were observed and identified in SD rats, comprising 0.20 to 4.53% of total plasma AUC. These major metabolites were the hydroxylated, N-sulphate and N-carbamoyl glucuronic acid conjugates of the cetagliptin, two metabolites formed by glucuronide of a hydroxylated metabolite.
ESTHER : Lu_2022_Xenobiotica_52_468
PubMedSearch : Lu_2022_Xenobiotica_52_468
PubMedID: 35708192

Title : A double-blind, randomized, placebo and positive-controlled study in healthy volunteers to evaluate pharmacokinetic and pharmacodynamic properties of multiple oral doses of cetagliptin - Lu_2022_Br.J.Clin.Pharmacol_88_2946
Author(s) : Lu J , Wang L , Zhou S , Zhou C , Xie L , Chen J , Tang D , Tian X , Xie D , Ding J , Wang T , Yu Q , Shao F
Ref : British Journal of Clinical Pharmacology , 88 :2946 , 2022
Abstract : AIMS: This study investigated the pharmacokinetics and pharmacodynamics properties, safety and tolerability of cetagliptin. METHODS: Forty-eight healthy subjects were enrolled in this study. Three cohorts were investigated in sequential order: 50, 100 and 200mg cetagliptin. Positive control (sitagliptin 100mg) was designed as open label. Blood samples were collected and analysed for pharmacokinetic and pharmacodynamic properties. Safety and tolerability were assessed throughout the study. RESULTS: Following multiple oral doses, cetagliptin was rapidly absorbed and reached peak plasma concentrations after approximately 1.0-1.5 hours. Plasma cetagliptin concentrations increased at a rate greater than dose. Accumulation of cetagliptin was modest, and steady state was generally achieved at day 5. Doses <=50mg of cetagliptin administered once daily will result in sustained dipeptidyl peptidase-4 (DPP-4) inhibition (<=80%). The plasma concentration giving 50% of maximum drug effect of DPP-4 inhibition for cetagliptin (5.29ng/mL) was lower than that of sitagliptin (7.03ng/mL). Active glucagon-like-1 peptide (GLP-1) concentrations were significantly increased in the cetagliptin groups by 2.3- to 3.1-fold at day 1 and 3.1- to 3.6-fold at steady state compared with that of placebo, and active GLP-1 concentrations were increased with increasing dose. Compared with sitagliptin, doses <=100mg once daily of cetagliptin produced postprandial increases in active GLP-1 level and induced to long-lasting glucose-lowering efficacy. Cetagliptin was well tolerated across all doses studied. CONCLUSION: Cetagliptin demonstrates the great potential for treatment with type 2 diabetes patients based on the inhibition of DPP-4, the increase in GLP-1 and insulin, the decrease in glucose, and might be more effective in DPP-4 inhibition than sitagliptin.
ESTHER : Lu_2022_Br.J.Clin.Pharmacol_88_2946
PubMedSearch : Lu_2022_Br.J.Clin.Pharmacol_88_2946
PubMedID: 34965609

Title : Acute thiamethoxam exposure induces hepatotoxicity and neurotoxicity in juvenile Chinese mitten crab (Eriocheir sinensis) - Yang_2022_Ecotoxicol.Environ.Saf_249_114399
Author(s) : Yang Y , Yu Q , Zhang C , Wang X , He L , Huang Y , Li E , Qin J , Chen L
Ref : Ecotoxicology & Environmental Safety , 249 :114399 , 2022
Abstract : The similar nervous system structure between crustaceans and insects and the high-water solubility of thiamethoxam can lead to the more severe toxicity of thiamethoxam to crustaceans. However, the effects of thiamethoxam on crustaceans are unclear. Therefore, a 96-h acute toxicity test was performed to explore the hepatotoxicity and neurotoxicity effects of thiamethoxam on Chinese mitten crab (Eriocheir sinensis) at concentrations 0 microg/L, 150 microg/L and 300 microg/L. The antioxidant and detoxification systems (including phases I and II) were significantly activated after exposure of juvenile crabs to thiamethoxam for 24sh in 300 microg/L group, whereas the toxic activation effect in 150 microg/L group was delayed. Moreover, a similar pattern was observed for the transcription levels of immune-related genes. Further analysis of inflammatory signaling pathway-related genes showed that thiamethoxam exposure with 300 microg/L for 24sh may induce a pro-inflammatory response through the NF-kappaB pathway. In contrast, the gene expression levels in 150 microg/L group were significantly upregulated compared with 0 microg/L group after 96sh. In addition, although the acute exposure of 150 microg/L thiamethoxam did not seem to induce significant neurotoxicity, the acetylcholinesterase activity was significantly decreased in 300 microg/L group after thiamethoxam exposure for 96sh. Correspondingly, thiamethoxam exposure with 300 microg/L for 24sh resulted in significantly downregulated transcriptional levels of synaptic transmission-related genes (e.g. dopamine-, gamma-aminobutyric acid- and serotonin-related receptors). Therefore, thiamethoxam may be harmful and cause potential toxic threats such as neurotoxicity and metabolic damage to crustaceans.
ESTHER : Yang_2022_Ecotoxicol.Environ.Saf_249_114399
PubMedSearch : Yang_2022_Ecotoxicol.Environ.Saf_249_114399
PubMedID: 36508784

Title : [(18)F]MAGL-4-11 positron emission tomography molecular imaging of monoacylglycerol lipase changes in preclinical liver fibrosis models - Shao_2022_Acta.Pharm.Sin.B_12_308
Author(s) : Shao T , Chen Z , Rong J , Belov V , Chen J , Jeyarajan A , Deng X , Fu H , Yu Q , Rwema SH , Lin W , Papisov M , Josephson L , Chung RT , Liang SH
Ref : Acta Pharm Sin B , 12 :308 , 2022
Abstract : Monoacylglycerol lipase (MAGL) is a pivotal enzyme in the endocannabinoid system, which metabolizes 2-arachidonoylglycerol (2-AG) into the proinflammatory eicosanoid precursor arachidonic acid (AA). MAGL and other endogenous cannabinoid (EC) degrading enzymes are involved in the fibrogenic signaling pathways that induce hepatic stellate cell (HSC) activation and ECM accumulation during chronic liver disease. Our group recently developed an (18)F-labeled MAGL inhibitor ([(18)F]MAGL-4-11) for PET imaging and demonstrated highly specific binding in vitro and in vivo. In this study, we determined [(18)F]MAGL-4-11 PET enabled imaging MAGL levels in the bile duct ligation (BDL) and carbon tetrachloride (CCl(4)) models of liver cirrhosis; we also assessed the hepatic gene expression of the enzymes involved with EC system including MAGL, NAPE-PLD, FAAH and DAGL that as a function of disease severity in these models; [(18)F]MAGL-4-11 autoradiography was performed to assess tracer binding in frozen liver sections both in animal and human. [(18)F]MAGL-4-11 demonstrated reduced PET signals in early stages of fibrosis and further significantly decreased with disease progression compared with control mice. We confirmed MAGL and FAAH expression decreases with fibrosis severity, while its levels in normal liver tissue are high; in contrast, the EC synthetic enzymes NAPE-PLD and DAGL are enhanced in these different fibrosis models. In vitro autoradiography further supported that [(18)F]MAGL-4-11 bound specifically to MAGL in both animal and human fibrotic liver tissues. Our PET ligand [(18)F]MAGL-4-11 shows excellent sensitivity and specificity for MAGL visualization in vivo and accurately reflects the histological stages of liver fibrosis in preclinical models and human liver tissues.
ESTHER : Shao_2022_Acta.Pharm.Sin.B_12_308
PubMedSearch : Shao_2022_Acta.Pharm.Sin.B_12_308
PubMedID: 35127387

Title : Spleen volume-based non-invasive tool for predicting hepatic decompensation in people with compensated cirrhosis (CHESS1701) - Yu_2022_JHEP.Rep_4_100575
Author(s) : Yu Q , Xu C , Li Q , Ding Z , Lv Y , Liu C , Huang Y , Zhou J , Huang S , Xia C , Meng X , Lu C , Li Y , Tang T , Wang Y , Song Y , Qi X , Ye J , Ju S
Ref : JHEP Rep , 4 :100575 , 2022
Abstract : BACKGROUND & AIMS: Non-invasive stratification of the liver decompensation risk remains unmet in people with compensated cirrhosis. This study aimed to develop a non-invasive tool (NIT) to predict hepatic decompensation. METHODS: This retrospective study recruited 689 people with compensated cirrhosis (median age, 54 years; 441 men) from 5 centres from January 2016 to June 2020. Baseline abdominal computed tomography (CT), clinical features, and liver stiffness were collected, and then the first decompensation was registered during the follow-up. The spleen-based model was designed for predicting decompensation based on a deep learning segmentation network to generate the spleen volume and least absolute shrinkage and selection operator (LASSO)-Cox. The spleen-based model was trained on the training cohort of 282 individuals (Institutions I-III) and was validated in 2 external validation cohorts (97 and 310 individuals from Institutions IV and V, respectively) and compared with the conventional serum-based models and the Baveno VII criteria. RESULTS: The decompensation rate at 3 years was 23%, with a 37.6-month median (IQR 21.1-52.1 months) follow-up. The proposed model showed good performance in predicting decompensation (C-index <=0.84) and outperformed the serum-based models (C-index comparison test p <0.05) in both the training and validation cohorts. The hazard ratio (HR) for decompensation in individuals with high risk was 7.3 (95% CI 4.2-12.8) in the training and 5.8 (95% CI 3.9-8.6) in the validation (log-rank test, p <0.05) cohorts. The low-risk group had a negligible 3-year decompensation risk (>=1%), and the model had a competitive performance compared with the Baveno VII criteria. CONCLUSIONS: This spleen-based model provides a non-invasive and user-friendly method to help predict decompensation in people with compensated cirrhosis in diverse healthcare settings where liver stiffness is not available. LAY SUMMARY: People with compensated cirrhosis with larger spleen volume would have a higher risk of decompensation. We developed a spleen-based model and validated it in external validation cohorts. The proposed model might help predict hepatic decompensation in people with compensated cirrhosis when invasive tools are unavailable.
ESTHER : Yu_2022_JHEP.Rep_4_100575
PubMedSearch : Yu_2022_JHEP.Rep_4_100575
PubMedID: 36204707

Title : Efficacy and safety of sugammadex for neuromuscular blockade reversal in pediatric patients: an updated meta-analysis of randomized controlled trials with trial sequential analysis - Lang_2022_BMC.Pediatr_22_295
Author(s) : Lang B , Han L , Zeng L , Zhang Q , Chen S , Huang L , Jia Z , Yu Q , Zhang L
Ref : BMC Pediatr , 22 :295 , 2022
Abstract : BACKGROUND: A recent survey revealed that extensive off-label use of sugammadex in pediatric anesthesia deserved particular attention. The present study with trial sequential analysis (TSA) aimed to evaluate the effects of sugammadex for antagonizing neuromuscular blockade (NMB) in pediatric patients, and to investigate whether the findings achieved the required information size to draw conclusions. METHODS: PubMed, Embase, Cochrane Library and China National Knowledge Infrastructure (CNKI) were searched from inception to April 2021. All randomized controlled trials used sugammadex as reversal agent in pediatric patients were enrolled. Time from NMB reversal to recovery of the train-of-four ratio (TOFr) to 0.9 and extubation time were considered as co-primary outcomes, and incidences of adverse events were considered as secondary outcomes. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used to rate the quality of evidences. RESULTS: Data from 18 studies involving 1,065 pediatric patients were acquired. The results revealed that use of sugammadex was associated with shorter duration from administration of reversal agents to TOFr > 0.9 (MD = -14.42, with 95% CI [-17.08, -11.75]) and shorter interval from reversal from NMB to extubation (MD = -13.98, with 95% CI [-16.70, -11.26]) compared to control groups. TSA also indicated that the current sample sizes were sufficient with unnecessary further trials. Analysis of secondary outcomes indicated that administration of sugammadex was associated with less incidence of postoperative nausea and vomiting (PONV), bradycardia, and dry mouth compared to control groups. CONCLUSION: Considering of satisfactory and rapid neuromuscular blockade reversal with low incidences of adverse events, sugammadex might be considered as the preferred option for children in clinical anesthesia practice compared to acetylcholinesterase inhibitors. However, overall low-quality evidences in present study rated by GRADE system indicated that superiority of sugammadex employed in pediatric patients needs to be confirmed by more studies with high quality and large sample size in future.
ESTHER : Lang_2022_BMC.Pediatr_22_295
PubMedSearch : Lang_2022_BMC.Pediatr_22_295
PubMedID: 35590273

Title : Development and validation of an ultrasensitive LC-MS\/MS method for the quantification of cetagliptin in human plasma and its application in a microdose clinical trial - Bai_2021_Biomed.Chromatogr_35_e4994
Author(s) : Bai H , Lu J , Cheng X , Liu L , Zhang W , Wei Y , Wang Y , Liu J , Ding J , Yu Q , Zhang Y , Chen G , Fan Y , Wang X
Ref : Biomedical Chromatography , 35 :e4994 , 2021
Abstract : This study established and validated an LC-MS/MS method for the ultrasensitive determination of cetagliptin in human plasma. Sample pretreatment was achieved by liquid-liquid extraction with ethyl acetate, and chromatographic separation was performed on an XB-C(18) analytical column (50x2.1mm, 5microm) with gradient elution (0.1% formic acid in acetonitrile and 0.1% formic acid) at a flow rate of 1.0mL/min. For mass spectrometric detection, multiple reaction monitoring was used, and the ion transitions monitored were m/z 421.2-86.0 for cetagliptin and m/z 424.2-88.0 for cetagliptin-d3. Method validation was performed according to the U.S. Food and Drug Administration Bioanalytical Method Validation Guidance, for which the calibration curve was linear in the range of 50.0-2000pg/mL. All of the other results, such as selectivity, lower limit of quantitation, precision, accuracy, matrix effect, recovery, and stability, met the acceptance criteria. The validated method was successfully applied in a microdose clinical trial to systematically investigate the pharmacokinetic profile of cetagliptin in healthy subjects. Both rapid absorption and prolonged duration demonstrate the potential value of cetagliptin for diabetes treatment.
ESTHER : Bai_2021_Biomed.Chromatogr_35_e4994
PubMedSearch : Bai_2021_Biomed.Chromatogr_35_e4994
PubMedID: 32986878

Title : In vitro study of the drug-drug interaction potential of cetagliptin and clinical study of pharmacokinetic interaction of cetagliptin and metformin in healthy volunteers - Lu_2021_Xenobiotica_51_1122
Author(s) : Lu J , Tian X , Tang D , Zhou X , Xu Z , Ding J , Wang T , Yu Q
Ref : Xenobiotica , 51 :1122 , 2021
Abstract : Cetagliptin is an oral, potent, and newly developed selective inhibitor of dipeptidyl peptidase-4 (DPP-4). We evaluated the in vitro drug-drug interaction (DDI) potential of cetagliptin, as well as the pharmacokinetics of cetagliptin and metformin and the interaction between cetagliptin and metformin.Cetagliptin did not inhibit CYP1A2, CYP2C8, CYP2B6, CYP2C9, CYP2C19, and CYP3A4, only has a moderate inhibitory effect on CYP2D6, and did not induce CYP1A2, CYP2B6, and CYP3A4. Plasma protein binding of cetagliptin didn't have species differences or concentration dependence. Cetagliptin was a substrate for P-glycoprotein (P-gp).The 34 healthy subjects enrolled were randomly divided into two sequences (A and B) with 17 subjects in each sequence. Coadministration with metformin had no effect on cetagliptin AUC(0-120) (GMR, 99.25%; 90% CI, 95.96%-102.65%). There was a slightly increase in cetagliptin C(max) (GMR, 117.33%; 90% CI, 102.54%-134.25%). Coadministration with cetagliptin did not affect the metformin's AUC(0-24) (GMR, 108.54%; 90% CI, 101.41%-116.17%) or C(max) (GMR, 97.67%; 90% CI, 90.96%-104.89%).Based on in vitro study results, cetagliptin is unlikely to cause CYP-mediated, clinically relevant DDI. Although the possibility of transporter-mediated, clinically relevant DDI cannot be ruled out, there is little or no risk of side effects. Coadministration of cetagliptin and metformin had no clinically meaningful effect on the pharmacokinetics of each drug. There was no drug-drug interaction between cetagliptin and metformin. Both monotherapies and combination therapy were well tolerated. No serious AEs and hypoglycaemia was reported.
ESTHER : Lu_2021_Xenobiotica_51_1122
PubMedSearch : Lu_2021_Xenobiotica_51_1122
PubMedID: 34329567

Title : First-in-Human, Single-Ascending Dose and Food Effect Studies to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Cetagliptin, a Dipeptidyl Peptidase-4 Inhibitor for the Treatment of Type 2 Diabetes Mellitus - Wang_2021_Clin.Drug.Investig_41_999
Author(s) : Wang L , Lu J , Zhou S , Zhao Y , Xie L , Zhou C , Chen J , Ding S , Xie D , Ding J , Yu Q , Shen H , Hao G , Shao F
Ref : Clin Drug Investig , 41 :999 , 2021
Abstract : BACKGROUND AND OBJECTIVES: Cetagliptin is a highly selective dipeptidyl peptidase-4 inhibitor under development to treat type 2 diabetes mellitus. This first-in-human study was conducted to characterise the pharmacokinetics, pharmacodynamics and tolerability of single-ascending oral doses of cetagliptin in healthy subjects. In addition, the effect of food on pharmacokinetics was evaluated. METHODS: Study 1 enrolled 66 healthy subjects in a double-blind, randomised, placebo-controlled, single-dose escalation study; sitagliptin was employed as a positive open-label control. Forty-four subjects were assigned to seven cohorts (cetagliptin 12.5, 25, 50, 100, 200, 300 or 400 mg); 12 subjects were assigned to the placebo group. The remaining ten subjects received sitagliptin 100 mg as the positive control. Blood, urine and faeces were collected for the pharmacokinetic analysis and determination of plasma dipeptidyl peptidase-4 inhibition, active glucagon-like peptide-1, glucose and insulin levels. In Study 2, 14 healthy subjects were assigned to a randomised, open-label, two-period crossover study, and received a single oral dose of cetagliptin 100 mg in the fasted state or after a high-fat meal, with a 14-day washout period between treatments. Blood samples were collected to evaluate the effects of food on the pharmacokinetics of cetagliptin. RESULTS: Following administration of a single oral dose, cetagliptin was rapidly absorbed, presenting a median time to maximum concentration of 1.0-3.25 h. The terminal half-life ranged between 25.8 and 41.3 h, which was considerably longer than that of sitagliptin. The area under the plasma concentration-time curve was approximately dose proportional between 25 mg and 400 mg, and the increase in maximum concentration was greater than dose proportional. The unchanged drug was mainly excreted in the urine (27.2-46.2% of dose) and minimally via the faeces (1.4% of dose). Dipeptidyl peptidase-4 inhibition, an increase in active glucagon-like peptide-1 and a slight decrease in blood glucose were observed, whereas insulin was not significantly altered when compared with placebo. The weighted average dipeptidyl peptidase-4 inhibition by cetagliptin 100 mg was higher than that mediated by sitagliptin 100 mg. Cetagliptin was well tolerated up to a single oral dose of 400 mg. No food effects were noted. CONCLUSIONS: Cetagliptin inhibited plasma dipeptidyl peptidase-4 activity, increased levels of active glucagon-like peptide-1 and was well tolerated at single doses up to 400 mg, eliciting no dose-limiting toxicity in healthy volunteers. Food did not affect the pharmacokinetics of cetagliptin. CLINICAL TRIAL REGISTRATION: The studies were registered at http://www.chinadrugtrials.org.cn (Nos. CTR20180167 and CTR20181331).
ESTHER : Wang_2021_Clin.Drug.Investig_41_999
PubMedSearch : Wang_2021_Clin.Drug.Investig_41_999
PubMedID: 34655432

Title : Development of a highly-specific (18)F-labeled irreversible positron emission tomography tracer for monoacylglycerol lipase mapping - Chen_2021_Acta.Pharm.Sin.B_11_1686
Author(s) : Chen Z , Mori W , Rong J , Schafroth MA , Shao T , Van RS , Ogasawara D , Yamasaki T , Hiraishi A , Hatori A , Chen J , Zhang Y , Hu K , Fujinaga M , Sun J , Yu Q , Collier TL , Shao Y , Cravatt BF , Josephson L , Zhang MR , Liang SH
Ref : Acta Pharm Sin B , 11 :1686 , 2021
Abstract : As a serine hydrolase, monoacylglycerol lipase (MAGL) is principally responsible for the metabolism of 2-arachidonoylglycerol (2-AG) in the central nervous system (CNS), leading to the formation of arachidonic acid (AA). Dysfunction of MAGL has been associated with multiple CNS disorders and symptoms, including neuroinflammation, cognitive impairment, epileptogenesis, nociception and neurodegenerative diseases. Inhibition of MAGL provides a promising therapeutic direction for the treatment of these conditions, and a MAGL positron emission tomography (PET) probe would greatly facilitate preclinical and clinical development of MAGL inhibitors. Herein, we design and synthesize a small library of fluoropyridyl-containing MAGL inhibitor candidates. Pharmacological evaluation of these candidates by activity-based protein profiling identified 14 as a lead compound, which was then radiolabeled with fluorine-18 via a facile S(N)Ar reaction to form 2-[(18)F]fluoropyridine scaffold. Good blood-brain barrier permeability and high in vivo specific binding was demonstrated for radioligand [(18)F]14 (also named as [(18)F]MAGL-1902). This work may serve as a roadmap for clinical translation and further design of potent (18)F-labeled MAGL PET tracers.
ESTHER : Chen_2021_Acta.Pharm.Sin.B_11_1686
PubMedSearch : Chen_2021_Acta.Pharm.Sin.B_11_1686
PubMedID: 34221877
Gene_locus related to this paper: human-MGLL

Title : Double-enzymes-mediated fluorescent assay for sensitive determination of organophosphorus pesticides based on the quenching of upconversion nanoparticles by Fe(3) - Lin_2020_Food.Chem_345_128809
Author(s) : Lin X , Yu Q , Yang W , He C , Zhou Y , Duan N , Wu S
Ref : Food Chem , 345 :128809 , 2020
Abstract : Herein, a new double-enzymes-modulated fluorescent assay based on the quenching of upconversion nanoparticles (UCNPs) by Fe(3+) was constructed for sensitive determination of OPs. OPs can inhibit the activity of acetylcholinesterase to reduce the production of choline and further lead to the lack of H(2)O(2) in the presence of choline oxidase. Therefore, Fe(2+) cannot be converted into Fe(3+), resulting in "turn-on" fluorescence of UCNPs. Under optimal conditions, an excellent linear correlation between the inhibition efficiency and the logarithm of the chlorpyrifos concentration was achieved with a detection limit (LOD) of 6.7 ng/mL in the range of 20-2000 ng/mL. The recovery for chlorpyrifos in apples and cucumbers was 89.5-97.1%. The results were consistent with those obtained by GC-MS. Overall, the integration of UCNPs into the double-enzymes-mediated Fe(3+)/Fe(2+) conversion endows this method with desirable rapidity, sensitivity, selectivity, stability, operational simplicity, and strong anti-interference capability, holding great potential in the application of food safety.
ESTHER : Lin_2020_Food.Chem_345_128809
PubMedSearch : Lin_2020_Food.Chem_345_128809
PubMedID: 33338834

Title : Acupuncture of the Beishu acupoint participates in regulatory effects of ginsenoside Rg1 on T cell subsets of rats with chronic fatigue syndrome - He_2020_Ann.Palliat.Med_9_3436
Author(s) : He J , Yu Q , Wu C , Sun Z , Wu X , Liu R , Zhang H
Ref : Ann Palliat Med , 9 :3436 , 2020
Abstract : BACKGROUND: There are close relationships between the spleen and limb muscles and thoughts. The study aims to test the effects of ginsenoside Rg1 in combination with acupuncture of the Beishu acupoint on T cell subsets of rats with chronic fatigue syndrome (CFS). METHODS: The model was set up by combining forced cold-water swimming with chronic restraint. The rats were randomly divided into blank control, model, ginsenoside, acupuncture, and ginsenoside plus acupuncture groups (n=10). For the acupuncture group, the Beishu acupoint was acupunctured on the 2nd day after modeling. For the ginsenoside group, the ginsenoside Rg1 solution was injected into the tail vein on the 2nd day after modeling. For the combination group, both processes were conducted. These groups were compared regarding exhausted swimming time, number of struggles, resting time, serum levels of IgA, IgG, IgM, IFN-alpha, IFN-beta, and IFN-gamma, lymphocyte transformation rate, T cell subsets, and skeletal muscle activities of malondialdehyde (MDA), total antioxidative capacity (T-AOC) and acetylcholinesterase (Ache). RESULTS: The exhausted swimming time, number of struggles, and resting time of combination group surpassed those in the ginsenoside and acupuncture groups significantly (P<0.05). The serum levels of IgA, IgG, IgM, IFN-beta, IFN-gamma, T-AOC, and Ache, together with CD3+ and CD8+ T cell percentages of combination groups, were significantly higher than those of ginsenoside and acupuncture groups. However, the IFN-alpha level, MDA activity, and CD4+ T cell percentage were significantly lower (P<0.05). Compared with the model group, the CD4+/CD8+ T cell ratios of acupuncture, ginsenoside, and combination groups decreased significantly (P<0.05). Compared with the combination group, the ratio of the ginsenoside group increased significantly (P<0.05). CONCLUSIONS: Both acupuncture of the Beishu acupoint and intravenous injection of ginsenoside Rg1 have anti-fatigue effects, and their combination works synergistically. This study supplies an experimental basis for joint therapy using acupuncture and drugs to combat fatigue synergistically.
ESTHER : He_2020_Ann.Palliat.Med_9_3436
PubMedSearch : He_2020_Ann.Palliat.Med_9_3436
PubMedID: 33065794

Title : Design, synthesis and biological evaluation of xanthone derivatives for possible treatment of Alzheimer's disease based on multi-target strategy - Yang_2020_Chem.Biodivers_17_e2000442
Author(s) : Yang A , Yu Q , Ju H , Song L , Kou X , Shen R
Ref : Chem Biodivers , 17 :e2000442 , 2020
Abstract : Four xanthone derivatives were synthesized and evaluated as acetylcholinesterase inhibitors (AChEIs) with metal chelating ability and antioxidant ability against Alzheimer's disease (AD). Most of them exhibited potential acetylcholinesterase (AChE), butylcholinesterase (BuChE) inhibitory, antioxidant and metal chelating properties. Among them, 3-(2-( pyrrolidinyl)ethoxy)-1- hydroxy-9H-xanthen-9-one ( 2 ) had the highest ability to inhibit AChE and displayed high selectivity towards AChE (IC 50 =2.403+/-0.002 muM for AChE and IC 50 =31.221+/-0.002 muM for BuChE). And it was also a good antioxidant (IC 50 =2.662+/-0.003 muM). Enzyme kinetic studies showed that compound 2 was a mixed-type inhibitor, which could interact simultaneously with the catalytic anionic site (CAS) and the peripheral anionic site (PAS) of AChE. Interestingly, the copper complex ( 2 -Cu 2+ ) showed more significant inhibitory activity for AChE (IC 50 =0.934+/-0.002 muM) and antioxidant activity (IC 50 =1.064+/-0.003 muM). Molecular dockings were carried out for the four xanthone derivatives in order to further investigate the binding modes. Finally, the blood-brain barrier (BBB) penetration prediction indicated that all compounds might penetrate BBB. These results suggested that compound 2 was promising AChEI with metal chelating ability and antioxidant ability for the further investigation.
ESTHER : Yang_2020_Chem.Biodivers_17_e2000442
PubMedSearch : Yang_2020_Chem.Biodivers_17_e2000442
PubMedID: 32692899

Title : Design, synthesis and anti-Alzheimer's disease activity study of xanthone derivatives based on multi-target strategy - Kou_2019_Bioorg.Med.Chem.Lett__126927
Author(s) : Kou X , Song L , Wang Y , Yu Q , Ju H , Yang A , Shen R
Ref : Bioorganic & Medicinal Chemistry Lett , :126927 , 2019
Abstract : A series of xanthone derivatives were designed, synthesized and evaluated as multifunctional ligands against Alzheimer's disease (AD). In vitro studies showed all xanthone derivatives had good metal chelating property and exhibited selective inhibitory activity against Acetylcholinesterase (AChE). In particular, compound 2a showed the highest inhibitory activity against AChE, and the IC50 value was (0.328 +/- 0.001) muM, which was comparable to tacrine. Kinetic analysis and molecular docking studies indicated that these derivatives targeted both the catalytically active site (CAS) and the peripheral anion site (PAS) of AChE. Moreover, all derivatives showed higher anti-oxidative activity than vitamin C. Furthermore, copper complex had higher anti-AChE activity and antioxidant activity. Thus, these xanthone derivatives are potential multi-targeted-directed ligands for further development for the treatment of AD.
ESTHER : Kou_2019_Bioorg.Med.Chem.Lett__126927
PubMedSearch : Kou_2019_Bioorg.Med.Chem.Lett__126927
PubMedID: 31901382

Title : Carotid baroreceptor stimulation suppresses ventricular fibrillation in canines with chronic heart failure - Wang_2019_Basic.Res.Cardiol_114_41
Author(s) : Wang J , Dai M , Cao Q , Yu Q , Luo Q , Shu L , Zhang Y , Bao M
Ref : Basic Res Cardiol , 114 :41 , 2019
Abstract : Carotid baroreceptor stimulation (CBS) has been shown to improve cardiac dysfunction and pathological structure remodelling. This study aimed to investigate the effects of CBS on the ventricular electrophysiological properties in canines with chronic heart failure (CHF). Thirty-eight beagles were randomized into control (CON), CHF, low-level CBS (LL-CBS), and moderate-level CBS (ML-CBS) groups. The CHF model was established with 6 weeks of rapid right ventricular pacing (RVP), and concomitant LL-CBS and ML-CBS were applied in the LL-CBS and ML-CBS groups, respectively. After 6 weeks of RVP, ventricular electrophysiological parameters and left stellate ganglion (LSG) neural activity and function were measured. Autonomic neural remodelling in the LSG and left ventricle (LV) and ionic remodelling in the LV were detected. Compared with the CHF group, both LL-CBS and ML-CBS decreased spatial dispersion of action potential duration (APD), suppressed APD alternans, reduced ventricular fibrillation (VF) inducibility, and inhibited enhanced LSG neural discharge and function. Only ML-CBS significantly inhibited ventricular repolarization prolongation and increased the VF threshold. Moreover, ML-CBS inhibited the increase in growth-associated protein-43 and tyrosine hydroxylase-positive nerve fibre densities in LV, increased acetylcholinesterase protein expression in LSG, and decreased nerve growth factor protein expression in LSG and LV. Chronic RVP resulted in a remarkable reduction in protein expression encoding both potassium and L-type calcium currents; these changes were partly amended by ML-CBS and LL-CBS. In conclusion, CBS suppresses VF in CHF canines, potentially by modulating autonomic nerve and ion channels. In addition, the effects of ML-CBS on ventricular electrophysiological properties, autonomic remodelling, and ionic remodelling were superior to those of LL-CBS.
ESTHER : Wang_2019_Basic.Res.Cardiol_114_41
PubMedSearch : Wang_2019_Basic.Res.Cardiol_114_41
PubMedID: 31502080

Title : Design, Synthesis, and Evaluation of (18)F-Labeled Monoacylglycerol Lipase Inhibitors as Novel Positron Emission Tomography Probes - Chen_2019_J.Med.Chem_62_8866
Author(s) : Chen Z , Mori W , Fu H , Schafroth MA , Hatori A , Shao T , Zhang G , Van RS , Zhang Y , Hu K , Fujinaga M , Wang L , Belov V , Ogasawara D , Giffenig P , Deng X , Rong J , Yu Q , Zhang X , Papisov MI , Shao Y , Collier TL , Ma JA , Cravatt BF , Josephson L , Zhang MR , Liang SH
Ref : Journal of Medicinal Chemistry , 62 :8866 , 2019
Abstract : Dysfunction of monoacylglycerol lipase (MAGL) is associated with several psychopathological disorders, including drug addiction and neurodegenerative diseases. Herein we design, synthesize, and evaluate several irreversible fluorine-containing MAGL inhibitors for positron emission tomography (PET) ligand development. Compound 6 (identified from a therapeutic agent) was advanced for (18)F-labeling via a novel spirocyclic iodonium ylide (SCIDY) strategy, which demonstrated high brain permeability and excellent specific binding. This work supports further development of novel (18)F-labeled MAGL PET probes.
ESTHER : Chen_2019_J.Med.Chem_62_8866
PubMedSearch : Chen_2019_J.Med.Chem_62_8866
PubMedID: 31518130

Title : Design, Synthesis, and Evaluation of Reversible and Irreversible Monoacylglycerol Lipase Positron Emission Tomography (PET) Tracers Using a Tail Switching Strategy on a Piperazinyl Azetidine Skeleton - Chen_2019_J.Med.Chem_62_3336
Author(s) : Chen Z , Mori W , Deng X , Cheng R , Ogasawara D , Zhang G , Schafroth MA , Dahl K , Fu H , Hatori A , Shao T , Zhang Y , Yamasaki T , Zhang X , Rong J , Yu Q , Hu K , Fujinaga M , Xie L , Kumata K , Gou Y , Chen J , Gu S , Bao L , Wang L , Collier TL , Vasdev N , Shao Y , Ma JA , Cravatt BF , Fowler C , Josephson L , Zhang MR , Liang SH
Ref : Journal of Medicinal Chemistry , 62 :3336 , 2019
Abstract : Monoacylglycerol lipase (MAGL) is a serine hydrolase that degrades 2-arachidonoylglycerol (2-AG) in the endocannabinoid system (eCB). Selective inhibition of MAGL has emerged as a potential therapeutic approach for the treatment of diverse pathological conditions, including chronic pain, inflammation, cancer, and neurodegeneration. Herein, we disclose a novel array of reversible and irreversible MAGL inhibitors by means of "tail switching" on a piperazinyl azetidine scaffold. We developed a lead irreversible-binding MAGL inhibitor 8 and reversible-binding compounds 17 and 37, which are amenable for radiolabeling with (11)C or (18)F. [(11)C]8 ([(11)C]MAGL-2-11) exhibited high brain uptake and excellent binding specificity in the brain toward MAGL. Reversible radioligands [(11)C]17 ([(11)C]PAD) and [(18)F]37 ([(18)F]MAGL-4-11) also demonstrated excellent in vivo binding specificity toward MAGL in peripheral organs. This work may pave the way for the development of MAGL-targeted positron emission tomography tracers with tunability in reversible and irreversible binding mechanisms.
ESTHER : Chen_2019_J.Med.Chem_62_3336
PubMedSearch : Chen_2019_J.Med.Chem_62_3336
PubMedID: 30829483
Gene_locus related to this paper: human-MGLL

Title : Molecular Characterization and Bioactivity of Coumarin Derivatives from the Fruits of Cucumis bisexualis - Ma_2018_J.Agric.Food.Chem_66_5540
Author(s) : Ma QG , Wei RR , Yang M , Huang XY , Wang F , Sang ZP , Liu WM , Yu Q
Ref : Journal of Agricultural and Food Chemistry , 66 :5540 , 2018
Abstract : Cucumis bisexualis (Cucurbitaceae) is known as "mapao egg" or "muskmelon egg", which has been widely used as a wild melon in Chinese folk. Nine new coumarin derivatives (1-9), named 7-hydroxy-3-(4',6'-dihydroxy-5'-isopropyl-3'',3''-dimethyl-2 H-chromen)-6-prenyl-2 H-chro-men-2-one (1), 7-hydroxy-3-(5'-prenyl-3'',3''-dimethyl-2 H-chromen)-6-prenyl-2 H-chromen-2-one (2), 3-(6'-hydroxy-5'-prenyl-3'',3''-dimethyl-2 H-chromen)-6-prenyl-2 H-chromen-2-one (3), 3-(5'-ethyl-3'',3''-dimethyl-2 H-chromen)-6-prenyl-2 H-chromen-2-one (4), 3-(4',6'-dihydroxy-5'-dimeth-ylallyl-3'',3''-dimethyl-2 H-chromen)-6-prenyl-2 H-chromen-2-one (5), 3-[4',6'-dihydroxy-5'-(2-pro-penyl)-3'',3''-dimethyl-2 H-chromen]-14,15-dimethyl-pyrano-chromen-2-one (6), 3-(6'-dihydroxy-5'-isopropanol-3'',3''-dimethyl-2 H-chromen)-14,15-dimethyl-pyrano-chromen-2-one (7), 3-(5'-iso-pentenol-3'',3''-dimethyl-2 H-chromen)-14,15-dimethyl-pyrano-chromen-2-one (8), 3-(4',6'-dihydr-oxy-5'-prenyl-3'',3''-dimethyl-2 H-chromen)-14,15-dimethyl-pyrano-chromen-2-one (9), together with 12 known compounds (10-21), were isolated and identified by spectroscopic analysis and references from the active site (EtOAc soluble fraction) of the fruits of C. bisexualis for the first time. Compounds (1-21) were evaluated for antiacetylcholinesterase (AChE) and hepatoprotective activities for the first time. Compounds 1, 3, 5, 6, 7, and 9 showed anti-AChE activities with IC50 values ranging from 11.23 to 89.69 muM, and compounds 2, 4, 12, 15, 17, 18, and 19 (10 muM) exhibited moderate hepatoprotective activities. These findings shed much light on a better understanding of the anti-AChE and hepatoprotective effects of these coumarin derivatives and provided new insights into developing better anti-AChE and hepatoprotective drugs in the future.
ESTHER : Ma_2018_J.Agric.Food.Chem_66_5540
PubMedSearch : Ma_2018_J.Agric.Food.Chem_66_5540
PubMedID: 29775541

Title : Neuroligin-3 protects retinal cells from H2O2-induced cell death via activation of Nrf2 signaling - Li_2018_Biochem.Biophys.Res.Commun_502_166
Author(s) : Li XM , Huang D , Yu Q , Yang J , Yao J
Ref : Biochemical & Biophysical Research Communications , 502 :166 , 2018
Abstract : Intensified oxidative stress can cause severe damage to human retinal pigment epithelium (RPE) cells and retinal ganglion cells (RGCs). The potential effect of neuroligin-3 (NLGN3) against the process is studied here. Our results show that NLGN3 efficiently inhibited hydrogen peroxide (H2O2)-induced death and apoptosis in human RPE cells and RGCs. H2O2-induced reactive oxygen species (ROS) production, lipid peroxidation and DNA damage in retinal cells were alleviated by NLGN3. NLGN3 activated nuclear-factor-E2-related factor 2 (Nrf2) signaling, enabling Nrf2 protein stabilization, nuclear translocation and expression of key anti-oxidant enzymes (HO1, NOQ1 and GCLC) in RPE cells and RGCs. Further results demonstrate that NLGN3 activated Akt-mTORC1 signaling in retinal cells. Conversely, Akt-mTORC1 inhibitors (RAD001 and LY294002) reduced NLGN3-induced HO1, NOQ1 and GCLC mRNA expression. Significantly, Nrf2 silencing by targeted shRNAs reversed NLGN3-induced retinal cytoprotection against H2O2. We conclude that NLGN3 activates Nrf2 signaling to protect human retinal cells from H2O2. NLGN3 could be further tested as a valuable retinal protection agent.
ESTHER : Li_2018_Biochem.Biophys.Res.Commun_502_166
PubMedSearch : Li_2018_Biochem.Biophys.Res.Commun_502_166
PubMedID: 29792861

Title : Luciferases with Tunable Emission Wavelengths - Hiblot_2017_Angew.Chem.Int.Ed.Engl_56_14556
Author(s) : Hiblot J , Yu Q , Sabbadini MDB , Reymond L , Xue L , Schena A , Sallin O , Hill N , Griss R , Johnsson K
Ref : Angew Chem Int Ed Engl , 56 :14556 , 2017
Abstract : We introduce luciferases whose emission maxima can be tuned to different wavelengths by chemical labeling. The luciferases are chimeras of NanoLuc with either SNAP-tag or HaloTag7. Labeling of the self-labeling tag with a fluorophore shifts the emission maximum of NanoLuc to that of the fluorophore. Luciferases with tunable colors have applications as reporter genes, for the construction of biosensors and in bioimaging.
ESTHER : Hiblot_2017_Angew.Chem.Int.Ed.Engl_56_14556
PubMedSearch : Hiblot_2017_Angew.Chem.Int.Ed.Engl_56_14556
PubMedID: 28941028

Title : Scallop genome provides insights into evolution of bilaterian karyotype and development - Wang_2017_Nat.Ecol.Evol_1_120
Author(s) : Wang S , Zhang J , Jiao W , Li J , Xun X , Sun Y , Guo X , Huan P , Dong B , Zhang L , Hu X , Sun X , Wang J , Zhao C , Wang Y , Wang D , Huang X , Wang R , Lv J , Li Y , Zhang Z , Liu B , Lu W , Hui Y , Liang J , Zhou Z , Hou R , Li X , Liu Y , Li H , Ning X , Lin Y , Zhao L , Xing Q , Dou J , Mao J , Guo H , Dou H , Li T , Mu C , Jiang W , Fu Q , Fu X , Miao Y , Liu J , Yu Q , Li R , Liao H , Kong Y , Jiang Z , Chourrout D , Bao Z
Ref : Nat Ecol Evol , 1 :120 , 2017
Abstract : Reconstructing the genomes of bilaterian ancestors is central to our understanding of animal evolution, where knowledge from ancient and/or slow-evolving bilaterian lineages is critical. Here we report a high-quality, chromosome-anchored reference genome for the scallop Patinopecten yessoensis, a bivalve mollusc that has a slow-evolving genome with many ancestral features. Chromosome-based macrosynteny analysis reveals a striking correspondence between the 19 scallop chromosomes and the 17 presumed ancestral bilaterian linkage groups at a level of conservation previously unseen, suggesting that the scallop may have a karyotype close to that of the bilaterian ancestor. Scallop Hox gene expression follows a new mode of subcluster temporal co-linearity that is possibly ancestral and may provide great potential in supporting diverse bilaterian body plans. Transcriptome analysis of scallop mantle eyes finds unexpected diversity in phototransduction cascades and a potentially ancient Pax2/5/8-dependent pathway for noncephalic eyes. The outstanding preservation of ancestral karyotype and developmental control makes the scallop genome a valuable resource for understanding early bilaterian evolution and biology.
ESTHER : Wang_2017_Nat.Ecol.Evol_1_120
PubMedSearch : Wang_2017_Nat.Ecol.Evol_1_120
PubMedID: 28812685
Gene_locus related to this paper: mizye-a0a210qls6 , mizye-a0a210qis3 , mizye-a0a210qg00 , mizye-a0a210ped6 , mizye-a0a210q4h5 , mizye-a0a210q4h9 , mizye-a0a210q4j1 , mizye-a0a210qf86 , mizye-a0a210q332 , mizye-a0a210pqn0 , mizye-a0a210q7t5 , mizye-a0a210pij5 , mizye-a0a210qyk8 , mizye-a0a210pwl7 , mizye-a0a210q8u5 , mizye-a0a210r5n9 , mizye-a0a210qbv2 , mizye-a0a210pu25 , mizye-a0a210pek1 , mizye-a0a210pul3 , mizye-a0a210pum3 , mizye-a0a210ptr6 , mizye-a0a210ptq5 , mizye-a0a210ptc4.1 , mizye-a0a210ptc4.2 , mizye-a0a210ptv1 , mizye-a0a210ptv7 , mizye-a0a210qgl6 , mizye-a0a210qg90 , mizye-a0a210ptq0 , mizye-a0a210qg72 , mizye-a0a210ptb1 , mizye-a0a210pjd3 , mizye-a0a210qg92 , mizye-a0a210q8v2 , mizye-a0a210qg93 , mizye-a0a210q160.1 , mizye-a0a210q160.2 , mizye-a0a210qes4 , mizye-a0a210pk25 , mizye-a0a210q1b8 , mizye-a0a210q110 , mizye-a0a210r503 , mizye-P021348901.1 , mizye-P021348901.2

Title : End-to-side neurorrhaphy repairs peripheral nerve injury: sensory nerve induces motor nerve regeneration - Yu_2017_Neural.Regen.Res_12_1703
Author(s) : Yu Q , Zhang SH , Wang T , Peng F , Han D , Gu YD
Ref : Neural Regen Res , 12 :1703 , 2017
Abstract : End-to-side neurorrhaphy is an option in the treatment of the long segment defects of a nerve. It involves suturing the distal stump of the disconnected nerve (recipient nerve) to the side of the intimate adjacent nerve (donor nerve). However, the motor-sensory specificity after end-to-side neurorrhaphy remains unclear. This study sought to evaluate whether cutaneous sensory nerve regeneration induces motor nerves after end-to-side neurorrhaphy. Thirty rats were randomized into three groups: (1) end-to-side neurorrhaphy using the ulnar nerve (mixed sensory and motor) as the donor nerve and the cutaneous antebrachii medialis nerve as the recipient nerve; (2) the sham group: ulnar nerve and cutaneous antebrachii medialis nerve were just exposed; and (3) the transected nerve group: cutaneous antebrachii medialis nerve was transected and the stumps were turned over and tied. At 5 months, acetylcholinesterase staining results showed that 34% +/- 16% of the myelinated axons were stained in the end-to-side group, and none of the myelinated axons were stained in either the sham or transected nerve groups. Retrograde fluorescent tracing of spinal motor neurons and dorsal root ganglion showed the proportion of motor neurons from the cutaneous antebrachii medialis nerve of the end-to-side group was 21% +/- 5%. In contrast, no motor neurons from the cutaneous antebrachii medialis nerve of the sham group and transected nerve group were found in the spinal cord segment. These results confirmed that motor neuron regeneration occurred after cutaneous nerve end-to-side neurorrhaphy.
ESTHER : Yu_2017_Neural.Regen.Res_12_1703
PubMedSearch : Yu_2017_Neural.Regen.Res_12_1703
PubMedID: 29171436

Title : Selective blockade of the hydrolysis of the endocannabinoid 2-arachidonoylglycerol impairs learning and memory performance while producing antinociceptive activity in rodents - Griebel_2015_Sci.Rep_5_7642
Author(s) : Griebel G , Pichat P , Beeske S , Leroy T , Redon N , Jacquet A , Francon D , Bert L , Even L , Lopez-Grancha M , Tolstykh T , Sun F , Yu Q , Brittain S , Arlt H , He T , Zhang B , Wiederschain D , Bertrand T , Houtmann J , Rak A , Vallee F , Michot N , Auge F , Menet V , Bergis OE , George P , Avenet P , Mikol V , Didier M , Escoubet J
Ref : Sci Rep , 5 :7642 , 2015
Abstract : Monoacylglycerol lipase (MAGL) represents a primary degradation enzyme of the endogenous cannabinoid (eCB), 2-arachidonoyglycerol (2-AG). This study reports a potent covalent MAGL inhibitor, SAR127303. The compound behaves as a selective and competitive inhibitor of mouse and human MAGL, which potently elevates hippocampal levels of 2-AG in mice. In vivo, SAR127303 produces antinociceptive effects in assays of inflammatory and visceral pain. In addition, the drug alters learning performance in several assays related to episodic, working and spatial memory. Moreover, long term potentiation (LTP) of CA1 synaptic transmission and acetylcholine release in the hippocampus, two hallmarks of memory function, are both decreased by SAR127303. Although inactive in acute seizure tests, repeated administration of SAR127303 delays the acquisition and decreases kindled seizures in mice, indicating that the drug slows down epileptogenesis, a finding deserving further investigation to evaluate the potential of MAGL inhibitors as antiepileptics. However, the observation that 2-AG hydrolysis blockade alters learning and memory performance, suggests that such drugs may have limited value as therapeutic agents.
ESTHER : Griebel_2015_Sci.Rep_5_7642
PubMedSearch : Griebel_2015_Sci.Rep_5_7642
PubMedID: 25560837
Gene_locus related to this paper: mouse-ABHD6

Title : Whole-genome sequence of a flatfish provides insights into ZW sex chromosome evolution and adaptation to a benthic lifestyle - Chen_2014_Nat.Genet_46_253
Author(s) : Chen S , Zhang G , Shao C , Huang Q , Liu G , Zhang P , Song W , An N , Chalopin D , Volff JN , Hong Y , Li Q , Sha Z , Zhou H , Xie M , Yu Q , Liu Y , Xiang H , Wang N , Wu K , Yang C , Zhou Q , Liao X , Yang L , Hu Q , Zhang J , Meng L , Jin L , Tian Y , Lian J , Yang J , Miao G , Liu S , Liang Z , Yan F , Li Y , Sun B , Zhang H , Zhu Y , Du M , Zhao Y , Schartl M , Tang Q , Wang J
Ref : Nat Genet , 46 :253 , 2014
Abstract : Genetic sex determination by W and Z chromosomes has developed independently in different groups of organisms. To better understand the evolution of sex chromosomes and the plasticity of sex-determination mechanisms, we sequenced the whole genomes of a male (ZZ) and a female (ZW) half-smooth tongue sole (Cynoglossus semilaevis). In addition to insights into adaptation to a benthic lifestyle, we find that the sex chromosomes of these fish are derived from the same ancestral vertebrate protochromosome as the avian W and Z chromosomes. Notably, the same gene on the Z chromosome, dmrt1, which is the male-determining gene in birds, showed convergent evolution of features that are compatible with a similar function in tongue sole. Comparison of the relatively young tongue sole sex chromosomes with those of mammals and birds identified events that occurred during the early phase of sex-chromosome evolution. Pertinent to the current debate about heterogametic sex-chromosome decay, we find that massive gene loss occurred in the wake of sex-chromosome 'birth'.
ESTHER : Chen_2014_Nat.Genet_46_253
PubMedSearch : Chen_2014_Nat.Genet_46_253
PubMedID: 24487278
Gene_locus related to this paper: cynse-a0a3p8wch2 , cynse-a0a3p8vd14 , cynse-a0a3p8w747 , cynse-a0a3p8wq40 , cynse-a0a3p8wul3 , cynse-a0a3p8vqr4 , cynse-a0a3p8vmz4

Title : Enhanced therapeutic efficacy of combined use of sorafenib and transcatheter arterial chemoembolization for treatment of advanced hepatocellular carcinoma - Zhou_2014_Jpn.J.Clin.Oncol_44_711
Author(s) : Zhou L , Li J , Ai DL , Fu JL , Peng XM , Zhang LZ , Wang JY , Zhao Y , Yang B , Yu Q , Liu CZ , Wang HM
Ref : Japanese Journal of Clinical Oncology , 44 :711 , 2014
Abstract : OBJECTIVE: Clinical trials suggest that combining transcatheter arterial chemoembolization with sorafenib in patients with advanced hepatocellular carcinoma shows a superior safety and tolerability profile. Our study aimed to retrospectively analyze the utility and prognostic factors of this combined therapy in these patients.
METHODS: Patients with advanced hepatocellular carcinoma, treated by transcatheter arterial chemoembolization and sorafenib subsequently, between February 2010 and September 2012 in our hospital, were retrospectively analyzed. After sorafenib treatment for 12 weeks, abdominal enhanced computed tomography or magnetic resonance imaging was used to evaluate short-term outcomes and clinical benefit rate. Overall survival and adverse events were recorded during follow-up. Univariate and multivariate analyses were used to identify relationships between baseline characteristics and overall survival.
RESULTS: Fifty-one advanced hepatocellular carcinoma patients were included. Common adverse events for sorafenib were hand-foot skin reaction, alopecia, diarrhea, anorexia and fatigue. The clinical benefit rate was 64% and the median survival time was 7.5 months. Median survival of patients with and without portal vein tumor thrombi was 6.0 months and 10.3 months (P < 0.001), respectively. Median survival of patients with cholinesterase >/=5000 U/l and < 5000 U/l was 10.6 months and 6.1 months (P < 0.001), respectively. Multivariate analysis identified the presence of portal vein tumor thrombi and low cholinesterase level as independent negative predictors of survival.
CONCLUSIONS: Combining sorafenib and transcatheter arterial chemoembolization was safe and effective for advanced hepatocellular carcinoma patients with extrahepatic spread but without portal vein tumor thrombi. Portal vein tumor thrombi and cholinesterase level are independent predictors of prognosis following this combined therapy.
ESTHER : Zhou_2014_Jpn.J.Clin.Oncol_44_711
PubMedSearch : Zhou_2014_Jpn.J.Clin.Oncol_44_711
PubMedID: 24855686

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

Title : Genome of the long-living sacred lotus (Nelumbo nucifera Gaertn.) - Ming_2013_Genome.Biol_14_R41
Author(s) : Ming R , VanBuren R , Liu Y , Yang M , Han Y , Li LT , Zhang Q , Kim MJ , Schatz MC , Campbell M , Li J , Bowers JE , Tang H , Lyons E , Ferguson AA , Narzisi G , Nelson DR , Blaby-Haas CE , Gschwend AR , Jiao Y , Der JP , Zeng F , Han J , Min XJ , Hudson KA , Singh R , Grennan AK , Karpowicz SJ , Watling JR , Ito K , Robinson SA , Hudson ME , Yu Q , Mockler TC , Carroll A , Zheng Y , Sunkar R , Jia R , Chen N , Arro J , Wai CM , Wafula E , Spence A , Xu L , Zhang J , Peery R , Haus MJ , Xiong W , Walsh JA , Wu J , Wang ML , Zhu YJ , Paull RE , Britt AB , Du C , Downie SR , Schuler MA , Michael TP , Long SP , Ort DR , Schopf JW , Gang DR , Jiang N , Yandell M , dePamphilis CW , Merchant SS , Paterson AH , Buchanan BB , Li S , Shen-Miller J
Ref : Genome Biol , 14 :R41 , 2013
Abstract : BACKGROUND: Sacred lotus is a basal eudicot with agricultural, medicinal, cultural and religious importance. It was domesticated in Asia about 7,000 years ago, and cultivated for its rhizomes and seeds as a food crop. It is particularly noted for its 1,300-year seed longevity and exceptional water repellency, known as the lotus effect. The latter property is due to the nanoscopic closely packed protuberances of its self-cleaning leaf surface, which have been adapted for the manufacture of a self-cleaning industrial paint, Lotusan. RESULTS: The genome of the China Antique variety of the sacred lotus was sequenced with Illumina and 454 technologies, at respective depths of 101x and 5.2x. The final assembly has a contig N50 of 38.8 kbp and a scaffold N50 of 3.4 Mbp, and covers 86.5% of the estimated 929 Mbp total genome size. The genome notably lacks the paleo-triplication observed in other eudicots, but reveals a lineage-specific duplication. The genome has evidence of slow evolution, with a 30% slower nucleotide mutation rate than observed in grape. Comparisons of the available sequenced genomes suggest a minimum gene set for vascular plants of 4,223 genes. Strikingly, the sacred lotus has 16 COG2132 multi-copper oxidase family proteins with root-specific expression; these are involved in root meristem phosphate starvation, reflecting adaptation to limited nutrient availability in an aquatic environment. CONCLUSIONS: The slow nucleotide substitution rate makes the sacred lotus a better resource than the current standard, grape, for reconstructing the pan-eudicot genome, and should therefore accelerate comparative analysis between eudicots and monocots.
ESTHER : Ming_2013_Genome.Biol_14_R41
PubMedSearch : Ming_2013_Genome.Biol_14_R41
PubMedID: 23663246
Gene_locus related to this paper: nelnu-a0a1u8aj84 , nelnu-a0a1u8bpe4 , nelnu-a0a1u7z9m9 , nelnu-a0a1u7ywy5 , nelnu-a0a1u8aik2 , nelnu-a0a1u7zmb5 , nelnu-a0a1u8a7m7 , nelnu-a0a1u8b0n9 , nelnu-a0a1u8b461 , nelnu-a0a1u7zzj3 , nelnu-a0a1u8ave7 , nelnu-a0a1u7yn26

Title : Functional motor nerve regeneration without motor-sensory specificity following end-to-side neurorrhaphy: an experimental study - Yu_2011_J.Hand.Surg.Am_36_2010
Author(s) : Yu Q , Lin ZK , Ding J , Wang T , Chi YL , Gao WY
Ref : J Hand Surg Am , 36 :2010 , 2011
Abstract : PURPOSE: To evaluate the quality of regenerating myelinated axons and motor-sensory specificity in an end-to-side nerve repair model. METHODS: We divided 20 rats into 3 groups: (1) end-to-side neurorrhaphy using the ulnar nerve as donor nerve and the musculocutaneous nerve as recipient nerve; (2) normal control; and (3) transected nerve with the stumps buried. At 5 months, we monitored the grooming test, the electrophysiological response, and the histologic changes in nerve and muscle. RESULTS: Grooming recovered successfully, and electrophysiological investigations revealed that the target muscles had been reinnervated in the end-to-side group. The mean wet weight of the reinnervated biceps brachii muscle was 72% of the normal muscle, and the mean muscle fiber cross-sectional area of the reinnervated muscle was similar to the normal muscle. The implanted musculocutaneous nerve contained varying but satisfactory numbers of axons (end-to-side group: 596 +/- 348 vs normal group: 1,340 +/- 241). Acetylcholinesterase staining revealed a similar percentage of myelinated fibers in the musculocutaneous nerve (39%) and the biceps brachii branch of the musculocutaneous nerve (38%) in the end-to-side group. This was similar to the number of myelinated fibers in the donor ulnar nerve (37%). CONCLUSIONS: The present study confirms that limited but functional reinnervation can occur on the basis of collateral sprouting of intact axons from the ulnar nerve. The motor-sensory specificity is not important.
ESTHER : Yu_2011_J.Hand.Surg.Am_36_2010
PubMedSearch : Yu_2011_J.Hand.Surg.Am_36_2010
PubMedID: 22123048

Title : Lipoprotein lipase gene polymorphisms and risks of childhood obesity in Chinese preschool children - Wang_2011_Eur.J.Pediatr_170_1309
Author(s) : Wang LN , Yu Q , Xiong Y , Liu LF , Zhang Z , Zhang XN , Cheng H , Wang B
Ref : Eur J Pediatr , 170 :1309 , 2011
Abstract : Childhood obesity is increasingly prevalent in the community and is related to many adult diseases. Lipoprotein lipase (LPL) plays a central role in dyslipidemia, and polymorphisms of the LPL gene may result in the disturbance in the lipid's metabolism. The aim of this study is to test the hypothesis that genetic variants of LPL and serum lipid levels are associated with the risk of childhood obesity. We genotyped +495T > G and PvuII T > C in an LPL gene and measured the serum lipid levels in a case-control study of 124 obese children and 346 frequency-matched normal controls in preschool Chinese children. The variant genotypes of LPL + 495GG and PvuII CC were associated with a significantly increased risk of childhood obesity [adjusted odds ratio (OR) = 2.39, 95% CI = 1.09-5.23 for +495 GG; adjusted OR = 2.00, 95% CI = 1.04-3.83 for PvuII CC], compared with their wild-type genotypes, respectively. In addition, compared with the lower serum level cut off by the control median, the higher level of serum triglyceride (TG) (>0.59 mmol/L) was associated with a 1.32-fold increased risk of childhood obesity, and the higher level of high density lipoprotein cholesterol (HDLC) (>1.14 mmol/L) was associated with a 36% decrease in risk of childhood obesity. Furthermore, the median levels of TG were higher in obese children carrying LPL +495TT/TG and PvuII TT/CT genotypes than those in controls, the HDLC levels were lower in obese children carrying LPL +495TG and PvuII CT/CC genotypes than those in controls. In conclusion, the LPL gene +495T > G and PvuII T > C polymorphisms may modulate the magnitude of dyslipidemia in Chinese early-onset obesity.
ESTHER : Wang_2011_Eur.J.Pediatr_170_1309
PubMedSearch : Wang_2011_Eur.J.Pediatr_170_1309
PubMedID: 21431783

Title : Tacrine treatment at high dose suppresses the recognition memory in juvenile and adult mice with attention to hepatotoxicity - Pan_2011_Basic.Clin.Pharmacol.Toxicol_108_421
Author(s) : Pan SY , Guo BF , Zhang Y , Yu Q , Yu ZL , Dong H , Ye Y , Han YF , Ko KM
Ref : Basic Clin Pharmacol Toxicol , 108 :421 , 2011
Abstract : It is well established that cholinergic over-stimulation can interfere with memory processes. The aim of this study was to evaluate the effect of tacrine, an acetylcholinesterase inhibitor, on recognition memory as well as the associated hepatotoxicity in juvenile (20-day-old) and adult (100-day-old) ICR male mice. Recognition memory was assessed by open-field test and step-through task without footshocks for three sessions between 08:00 and 13:00, with a 24-hr retention interval. Tacrine (10 or 40 mumol/kg) or vehicle was administered (s.c.) 20 min. prior to the first session. During the acquisition session, tacrine suppressed the open-field behaviours, including locomotor activity, rearing, grooming and defecation (by 77-100%) in mice of both ages. During the recall (observable in both ages) and re-recall (observable in juvenile mice) session, the locomotor activity and rearing number were significantly increased, indicative of impairment in recognition memory, in mice treated with tacrine 40 mumol/kg. During the training trial, tacrine decreased the step-through number in mice of both ages. In contrast, during the retention and re-retention trials, the step-through number was increased (by 92% and 93%, respectively), indicative of impairment in step-through memory, in juvenile but not adult mice treated with tacrine 40 mumol/kg. Tacrine 40 mumol/kg elevated the serum alanine aminotransferase (ALT) activity (by 135%) in juvenile mice, but reduced the ALT activity (by 42%) in adult mice. The results indicated that 20-day-old mice seemed to be more sensitive than 100-day-old mice to tacrine-induced impairment in recognition memory and the associated liver damage.
ESTHER : Pan_2011_Basic.Clin.Pharmacol.Toxicol_108_421
PubMedSearch : Pan_2011_Basic.Clin.Pharmacol.Toxicol_108_421
PubMedID: 21232021

Title : Indole alkaloids from Ervatamia hainanensis with potent acetylcholinesterase inhibition activities - Zhan_2010_Bioorg.Med.Chem.Lett_20_6185
Author(s) : Zhan ZJ , Yu Q , Wang ZL , Shan WG
Ref : Bioorganic & Medicinal Chemistry Lett , 20 :6185 , 2010
Abstract : Through bioassay-guided fractionation and chromatography technique, eight indole alkaloids were furnished from the stems of Ervatamia hainanensis. All isolates were evaluated for acetylcholinesterase (AChE) inhibition activities, in which compounds 1 and 3 exhibited the same level of activities as galantamine, a marketed cholinesterase inhibitor for the treatment of Alzheimer's disease. Discussion about the relationships between structure and activity of these alkaloids was also presented.
ESTHER : Zhan_2010_Bioorg.Med.Chem.Lett_20_6185
PubMedSearch : Zhan_2010_Bioorg.Med.Chem.Lett_20_6185
PubMedID: 20850311

Title : The genome of a lepidopteran model insect, the silkworm Bombyx mori - Xia_2008_Insect.Biochem.Mol.Biol_38_1036
Author(s) : Xia Q , Wang J , Zhou Z , Li R , Fan W , Cheng D , Cheng T , Qin J , Duana J , Xu H , Li Q , Li N , Wang M , Dai F , Liu C , Lin Y , Zhao P , Zhang H , Liu S , Zha X , Li C , Zhao A , Pan M , Pan G , Shen Y , Gao Z , Wang Z , Wang G , Wu Z , Hou Y , Chai C , Yu Q , He N , Zhang Z , Li S , Yang H , Lu C , Xiang Z , Mita K , Kasahara M , Nakatani Y , Yamamoto K , Abe H , Ahsan B , Daimoni T , Doi K , Fujii T , Fujiwara H , Fujiyama A , Futahashi R , Hashimotol S , Ishibashi J , Iwami M , Kadono-Okuda K , Kanamori H , Kataoka H , Katsuma S , Kawaoka S , Kawasaki H , Kohara Y , Kozaki T , Kuroshu RM , Kuwazaki S , Matsushima K , Minami H , Nagayasu Y , Nakagawa T , Narukawa J , Nohata J , Ohishi K , Ono Y , Osanai-Futahashi M , Ozaki K , Qu W , Roller L , Sasaki S , Sasaki T , Seino A , Shimomura M , Shin-I T , Shinoda T , Shiotsuki T , Suetsugu Y , Sugano S , Suwa M , Suzuki Y , Takiya S , Tamura T , Tanaka H , Tanaka Y , Touhara K , Yamada T , Yamakawa M , Yamanaka N , Yoshikawa H , Zhong YS , Shimada T , Morishita S
Ref : Insect Biochemistry & Molecular Biology , 38 :1036 , 2008
Abstract : Bombyx mori, the domesticated silkworm, is a major insect model for research, and the first lepidopteran for which draft genome sequences became available in 2004. Two independent data sets from whole-genome shotgun sequencing were merged and assembled together with newly obtained fosmid- and BAC-end sequences. The remarkably improved new assembly is presented here. The 8.5-fold sequence coverage of an estimated 432 Mb genome was assembled into scaffolds with an N50 size of approximately 3.7 Mb; the largest scaffold was 14.5 million base pairs. With help of a high-density SNP linkage map, we anchored 87% of the scaffold sequences to all 28 chromosomes. A particular feature was the high repetitive sequence content estimated to be 43.6% and that consisted mainly of transposable elements. We predicted 14,623 gene models based on a GLEAN-based algorithm, a more accurate prediction than the previous gene models for this species. Over three thousand silkworm genes have no homologs in other insect or vertebrate genomes. Some insights into gene evolution and into characteristic biological processes are presented here and in other papers in this issue. The massive silk production correlates with the existence of specific tRNA clusters, and of several sericin genes assembled in a cluster. The silkworm's adaptation to feeding on mulberry leaves, which contain toxic alkaloids, is likely linked to the presence of new-type sucrase genes, apparently acquired from bacteria. The silkworm genome also revealed the cascade of genes involved in the juvenile hormone biosynthesis pathway, and a large number of cuticular protein genes.
ESTHER : Xia_2008_Insect.Biochem.Mol.Biol_38_1036
PubMedSearch : Xia_2008_Insect.Biochem.Mol.Biol_38_1036
PubMedID: 19121390
Gene_locus related to this paper: bommo-a0mnw6 , bommo-a1yw85 , bommo-a9ls22 , bommo-ACHE1 , bommo-ACHE2 , bommo-b0fgv8 , bommo-b1q137 , bommo-b1q139 , bommo-b1q140 , bommo-b1q141 , bommo-b2zdz0 , bommo-b3gef6 , bommo-b3gef7 , bommo-b3gs55 , bommo-b3gs56 , bommo-d2ktu3 , bommo-d2ktu5 , bommo-d9ile0 , bommo-e1cga5 , bommo-e1cga6 , bommo-g8fpz6 , bommo-h9iu43 , bommo-h9iu46 , bommo-h9iu47.1 , bommo-h9iu47.2 , bommo-h9iue5 , bommo-h9ivg2 , bommo-h9iwj7 , bommo-h9iwj8 , bommo-h9ix58 , bommo-h9ixi1.1 , bommo-h9ixi1.2 , bommo-h9iy47 , bommo-h9izw1 , bommo-h9j0s4 , bommo-h9j1y0 , bommo-h9j3r0 , bommo-h9j3w6 , bommo-h9j3w7 , bommo-h9j5t0 , bommo-h9j8g3 , bommo-h9j9k9 , bommo-h9j066 , bommo-h9j067 , bommo-h9j593 , bommo-h9j594 , bommo-h9j990 , bommo-h9jde8 , bommo-h9jde9 , bommo-h9jdf0 , bommo-h9jds4 , bommo-h9jle7 , bommo-h9jn83 , bommo-h9jn85 , bommo-h9jrg2 , bommo-h9jyh9 , bommo-JHE , bommo-m1rmh6 , bommo-q1hq05 , bommo-q4tte1 , bommo-h9j592 , bommo-h9j604 , bommo-h9jpm8 , bommo-h9iss4 , bommo-h9j2c7

Title : Evolution of genes and genomes on the Drosophila phylogeny - Clark_2007_Nature_450_203
Author(s) : Clark AG , Eisen MB , Smith DR , Bergman CM , Oliver B , Markow TA , Kaufman TC , Kellis M , Gelbart W , Iyer VN , Pollard DA , Sackton TB , Larracuente AM , Singh ND , Abad JP , Abt DN , Adryan B , Aguade M , Akashi H , Anderson WW , Aquadro CF , Ardell DH , Arguello R , Artieri CG , Barbash DA , Barker D , Barsanti P , Batterham P , Batzoglou S , Begun D , Bhutkar A , Blanco E , Bosak SA , Bradley RK , Brand AD , Brent MR , Brooks AN , Brown RH , Butlin RK , Caggese C , Calvi BR , Bernardo de Carvalho A , Caspi A , Castrezana S , Celniker SE , Chang JL , Chapple C , Chatterji S , Chinwalla A , Civetta A , Clifton SW , Comeron JM , Costello JC , Coyne JA , Daub J , David RG , Delcher AL , Delehaunty K , Do CB , Ebling H , Edwards K , Eickbush T , Evans JD , Filipski A , Findeiss S , Freyhult E , Fulton L , Fulton R , Garcia AC , Gardiner A , Garfield DA , Garvin BE , Gibson G , Gilbert D , Gnerre S , Godfrey J , Good R , Gotea V , Gravely B , Greenberg AJ , Griffiths-Jones S , Gross S , Guigo R , Gustafson EA , Haerty W , Hahn MW , Halligan DL , Halpern AL , Halter GM , Han MV , Heger A , Hillier L , Hinrichs AS , Holmes I , Hoskins RA , Hubisz MJ , Hultmark D , Huntley MA , Jaffe DB , Jagadeeshan S , Jeck WR , Johnson J , Jones CD , Jordan WC , Karpen GH , Kataoka E , Keightley PD , Kheradpour P , Kirkness EF , Koerich LB , Kristiansen K , Kudrna D , Kulathinal RJ , Kumar S , Kwok R , Lander E , Langley CH , Lapoint R , Lazzaro BP , Lee SJ , Levesque L , Li R , Lin CF , Lin MF , Lindblad-Toh K , Llopart A , Long M , Low L , Lozovsky E , Lu J , Luo M , Machado CA , Makalowski W , Marzo M , Matsuda M , Matzkin L , McAllister B , McBride CS , McKernan B , McKernan K , Mendez-Lago M , Minx P , Mollenhauer MU , Montooth K , Mount SM , Mu X , Myers E , Negre B , Newfeld S , Nielsen R , Noor MA , O'Grady P , Pachter L , Papaceit M , Parisi MJ , Parisi M , Parts L , Pedersen JS , Pesole G , Phillippy AM , Ponting CP , Pop M , Porcelli D , Powell JR , Prohaska S , Pruitt K , Puig M , Quesneville H , Ram KR , Rand D , Rasmussen MD , Reed LK , Reenan R , Reily A , Remington KA , Rieger TT , Ritchie MG , Robin C , Rogers YH , Rohde C , Rozas J , Rubenfield MJ , Ruiz A , Russo S , Salzberg SL , Sanchez-Gracia A , Saranga DJ , Sato H , Schaeffer SW , Schatz MC , Schlenke T , Schwartz R , Segarra C , Singh RS , Sirot L , Sirota M , Sisneros NB , Smith CD , Smith TF , Spieth J , Stage DE , Stark A , Stephan W , Strausberg RL , Strempel S , Sturgill D , Sutton G , Sutton GG , Tao W , Teichmann S , Tobari YN , Tomimura Y , Tsolas JM , Valente VL , Venter E , Venter JC , Vicario S , Vieira FG , Vilella AJ , Villasante A , Walenz B , Wang J , Wasserman M , Watts T , Wilson D , Wilson RK , Wing RA , Wolfner MF , Wong A , Wong GK , Wu CI , Wu G , Yamamoto D , Yang HP , Yang SP , Yorke JA , Yoshida K , Zdobnov E , Zhang P , Zhang Y , Zimin AV , Baldwin J , Abdouelleil A , Abdulkadir J , Abebe A , Abera B , Abreu J , Acer SC , Aftuck L , Alexander A , An P , Anderson E , Anderson S , Arachi H , Azer M , Bachantsang P , Barry A , Bayul T , Berlin A , Bessette D , Bloom T , Blye J , Boguslavskiy L , Bonnet C , Boukhgalter B , Bourzgui I , Brown A , Cahill P , Channer S , Cheshatsang Y , Chuda L , Citroen M , Collymore A , Cooke P , Costello M , D'Aco K , Daza R , De Haan G , DeGray S , DeMaso C , Dhargay N , Dooley K , Dooley E , Doricent M , Dorje P , Dorjee K , Dupes A , Elong R , Falk J , Farina A , Faro S , Ferguson D , Fisher S , Foley CD , Franke A , Friedrich D , Gadbois L , Gearin G , Gearin CR , Giannoukos G , Goode T , Graham J , Grandbois E , Grewal S , Gyaltsen K , Hafez N , Hagos B , Hall J , Henson C , Hollinger A , Honan T , Huard MD , Hughes L , Hurhula B , Husby ME , Kamat A , Kanga B , Kashin S , Khazanovich D , Kisner P , Lance K , Lara M , Lee W , Lennon N , Letendre F , LeVine R , Lipovsky A , Liu X , Liu J , Liu S , Lokyitsang T , Lokyitsang Y , Lubonja R , Lui A , Macdonald P , Magnisalis V , Maru K , Matthews C , McCusker W , McDonough S , Mehta T , Meldrim J , Meneus L , Mihai O , Mihalev A , Mihova T , Mittelman R , Mlenga V , Montmayeur A , Mulrain L , Navidi A , Naylor J , Negash T , Nguyen T , Nguyen N , Nicol R , Norbu C , Norbu N , Novod N , O'Neill B , Osman S , Markiewicz E , Oyono OL , Patti C , Phunkhang P , Pierre F , Priest M , Raghuraman S , Rege F , Reyes R , Rise C , Rogov P , Ross K , Ryan E , Settipalli S , Shea T , Sherpa N , Shi L , Shih D , Sparrow T , Spaulding J , Stalker J , Stange-Thomann N , Stavropoulos S , Stone C , Strader C , Tesfaye S , Thomson T , Thoulutsang Y , Thoulutsang D , Topham K , Topping I , Tsamla T , Vassiliev H , Vo A , Wangchuk T , Wangdi T , Weiand M , Wilkinson J , Wilson A , Yadav S , Young G , Yu Q , Zembek L , Zhong D , Zimmer A , Zwirko Z , Alvarez P , Brockman W , Butler J , Chin C , Grabherr M , Kleber M , Mauceli E , MacCallum I
Ref : Nature , 450 :203 , 2007
Abstract : Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
ESTHER : Clark_2007_Nature_450_203
PubMedSearch : Clark_2007_Nature_450_203
PubMedID: 17994087
Gene_locus related to this paper: droan-ACHE , droan-b3lx10 , droan-b3lx75 , droan-b3lxv7 , droan-b3ly87 , droan-b3lyh4 , droan-b3lyh5 , droan-b3lyh7 , droan-b3lyh9 , droan-b3lyi0 , droan-b3lyi2 , droan-b3lyi3 , droan-b3lyi4 , droan-b3lyj8 , droan-b3lyj9 , droan-b3lyx4 , droan-b3lyx5 , droan-b3lyx6 , droan-b3lyx7 , droan-b3lyx9 , droan-b3lz72 , droan-b3m1x3 , droan-b3m2d4 , droan-b3m3d9 , droan-b3m4e3 , droan-b3m5w1 , droan-b3m6i7 , droan-b3m7v2 , droan-b3m9a5 , droan-b3m9f4 , droan-b3m9p3 , droan-b3m254 , droan-b3m259 , droan-b3m260 , droan-b3m262 , droan-b3m524 , droan-b3m635 , droan-b3m845 , droan-b3m846 , droan-b3md01 , droan-b3mdh7 , droan-b3mdm6 , droan-b3mdw8 , droan-b3mee1 , droan-b3mf47 , droan-b3mf48 , droan-b3mg94 , droan-b3mgk2 , droan-b3mgn6 , droan-b3mii3 , droan-b3mjk2 , droan-b3mjk3 , droan-b3mjk4 , droan-b3mjk5 , droan-b3mjl2 , droan-b3mjl4 , droan-b3mjl7 , droan-b3mjl9 , droan-b3mjm8 , droan-b3mjm9 , droan-b3mjs6 , droan-b3mkr0 , droan-b3ml20 , droan-b3mly4 , droan-b3mly5 , droan-b3mly6 , droan-b3mmm8 , droan-b3mnb5 , droan-b3mny9 , droan-b3mtj5 , droan-b3muw4 , droan-b3muw8 , droan-b3n0e7 , droan-b3n2j7 , droan-b3n247 , droan-c5idb2 , droer-ACHE , droer-b3n5c7 , droer-b3n5d0 , droer-b3n5d8 , droer-b3n5d9 , droer-b3n5t7 , droer-b3n5y4 , droer-b3n7d2 , droer-b3n7d3 , droer-b3n7d4 , droer-b3n7k8 , droer-b3n8e4 , droer-b3n8f7 , droer-b3n8f8 , droer-b3n9e1 , droer-b3n319 , droer-b3n547 , droer-b3n549 , droer-b3n558 , droer-b3n560 , droer-b3n577 , droer-b3n612 , droer-b3nar5 , droer-b3nb91 , droer-b3nct9 , droer-b3nd53 , droer-b3ndh9 , droer-b3ndq8 , droer-b3ne66 , droer-b3ne67 , droer-b3ne97 , droer-b3nfk3 , droer-b3nfq9 , droer-b3nim7 , droer-b3nkn2 , droer-b3nm11 , droer-b3nmh4 , droer-b3nmy2 , droer-b3npx2 , droer-b3npx3 , droer-b3nq76 , droer-b3nqg9 , droer-b3nqm8 , droer-b3nr28 , droer-b3nrd3 , droer-b3nst4 , droer-b3nwa7 , droer-b3nyp5.1 , droer-b3nyp5.2 , droer-b3nyp6 , droer-b3nyp7 , droer-b3nyp8 , droer-b3nyp9 , droer-b3nyq3 , droer-b3nz06 , droer-b3nz14 , droer-b3nzj0 , droer-b3p0c0 , droer-b3p0c1 , droer-b3p0c2 , droer-b3p2x6 , droer-b3p2x7 , droer-b3p2x9 , droer-b3p2y1 , droer-b3p2y2 , droer-b3p6d4 , droer-b3p6d5 , droer-b3p6w3 , droer-b3p7b4 , droer-b3p7h9 , droer-b3p152 , droer-b3p486 , droer-b3p487 , droer-b3p488 , droer-b3p489 , droer-EST6 , droer-q670j5 , drogr-ACHE , drogr-b4iwp3 , drogr-b4iww3 , drogr-b4iwy3 , drogr-b4ixf7 , drogr-b4ixh4 , drogr-b4iyz5 , drogr-b4j2s2 , drogr-b4j2u8 , drogr-b4j3u1 , drogr-b4j3v3 , drogr-b4j4g7 , drogr-b4j4x9 , drogr-b4j6e6 , drogr-b4j9c9 , drogr-b4j9y4 , drogr-b4j156 , drogr-b4j384 , drogr-b4j605 , drogr-b4j685 , drogr-b4ja76 , drogr-b4jay5 , drogr-b4jcf0 , drogr-b4jcf1 , drogr-b4jdg6 , drogr-b4jdg7 , drogr-b4jdh6 , drogr-b4jdz1 , drogr-b4jdz2 , drogr-b4jdz4 , drogr-b4je66 , drogr-b4je79 , drogr-b4je82 , drogr-b4je88 , drogr-b4je89 , drogr-b4je90 , drogr-b4je91 , drogr-b4jf76 , drogr-b4jf79 , drogr-b4jf80 , drogr-b4jf81 , drogr-b4jf82 , drogr-b4jf83 , drogr-b4jf84 , drogr-b4jf85 , drogr-b4jf87 , drogr-b4jf91 , drogr-b4jf92 , drogr-b4jg66 , drogr-b4jgh0 , drogr-b4jgh1 , drogr-b4jgr9 , drogr-b4ji67 , drogr-b4jls2 , drogr-b4jnh9 , drogr-b4jpc6 , drogr-b4jpq3 , drogr-b4jpx9 , drogr-b4jql2 , drogr-b4jrh5 , drogr-b4jsb2 , drogr-b4jth3 , drogr-b4jti1 , drogr-b4jul5 , drogr-b4jur4 , drogr-b4jvh3 , drogr-b4jz00 , drogr-b4jz03 , drogr-b4jz04 , drogr-b4jz05 , drogr-b4jzh2 , drogr-b4k0u2 , drogr-b4k2r1 , drogr-b4k234 , drogr-b4k235 , drome-BEM46 , drome-CG3734 , drome-CG9953 , drome-CG11626 , drome-GH02439 , dromo-ACHE , dromo-b4k6a7 , dromo-b4k6a8 , dromo-b4k6q8 , dromo-b4k6q9 , dromo-b4k6r1 , dromo-b4k6r3 , dromo-b4k6r4 , dromo-b4k6r5 , dromo-b4k6r6 , dromo-b4k6r7 , dromo-b4k6r8 , dromo-b4k6r9 , dromo-b4k6s0 , dromo-b4k6s1 , dromo-b4k6s2 , dromo-b4k9c7 , dromo-b4k9d3 , dromo-b4k571 , dromo-b4k721 , dromo-b4ka74 , dromo-b4ka89 , dromo-b4kaj4 , dromo-b4kc20 , dromo-b4kcl2 , dromo-b4kcl3 , dromo-b4kd55.1 , dromo-b4kd55.2 , dromo-b4kd56 , dromo-b4kd57 , dromo-b4kde1 , dromo-b4kdg2 , dromo-b4kdh4 , dromo-b4kdh5 , dromo-b4kdh6 , dromo-A0A0Q9XDF2 , dromo-b4kdh8.1 , dromo-b4kdh8.2 , dromo-b4kg04 , dromo-b4kg05 , dromo-b4kg06 , dromo-b4kg16 , dromo-b4kg44 , dromo-b4kg90 , dromo-b4kh20 , dromo-b4kh21 , dromo-b4kht7 , dromo-b4kid3 , dromo-b4kik0 , dromo-b4kjx0 , dromo-b4kki1 , dromo-b4kkp6 , dromo-b4kkp8 , dromo-b4kkq8 , dromo-b4kkr0 , dromo-b4kkr3 , dromo-b4kkr4 , dromo-b4kks0 , dromo-b4kks1 , dromo-b4kks2 , dromo-b4kla1 , dromo-b4klv8 , dromo-b4knt4 , dromo-b4kp08 , dromo-b4kp16 , dromo-b4kqa6 , dromo-b4kqa7 , dromo-b4kqa8 , dromo-b4kqh1 , dromo-b4kst4 , dromo-b4ksy6 , dromo-b4kt84 , dromo-b4ktf5 , dromo-b4ktf6 , dromo-b4kvl3 , dromo-b4kvw2 , dromo-b4kwv4 , dromo-b4kwv5 , dromo-b4kxz6 , dromo-b4ky12 , dromo-b4ky36 , dromo-b4ky44 , dromo-b4kzu7 , dromo-b4l0n8 , dromo-b4l4u5 , dromo-b4l6l9 , dromo-b4l084 , drope-ACHE , drope-b4g3s6 , drope-b4g4p7 , drope-b4g6v4 , drope-b4g8m0 , drope-b4g8n6 , drope-b4g8n7 , drope-b4g9p2 , drope-b4g815 , drope-b4g816 , drope-b4gat7 , drope-b4gav5 , drope-b4gb05 , drope-b4gc08 , drope-b4gcr3 , drope-b4gdk2 , drope-b4gdl9 , drope-b4gdv9 , drope-b4gei8 , drope-b4gei9 , drope-b4gej0 , drope-b4ghz9 , drope-b4gj62 , drope-b4gj64 , drope-b4gj74 , drope-b4gkf4 , drope-b4gkv2 , drope-b4gky9 , drope-b4gl76 , drope-b4glf3 , drope-b4gmt3 , drope-b4gmt7 , drope-b4gmt9 , drope-b4gmu2 , drope-b4gmu3 , drope-b4gmu4 , drope-b4gmu5 , drope-b4gmu6 , drope-b4gmu7 , drope-b4gmv1 , drope-b4gn08 , drope-b4gpa7 , drope-b4gq13 , drope-b4grh7 , drope-b4gsf9 , drope-b4gsw4 , drope-b4gsw5 , drope-b4gsx2 , drope-b4gsx7 , drope-b4gsy6 , drope-b4gsy7 , drope-b4guj8 , drope-b4gw36 , drope-b4gzc2 , drope-b4gzc6 , drope-b4gzc7 , drope-b4h4p9 , drope-b4h5l3 , drope-b4h6a0 , drope-b4h6a8 , drope-b4h6a9 , drope-b4h6b0 , drope-b4h7m7 , drope-b4h462 , drope-b4h601 , drope-b4h602 , drope-b4hay1 , drope-b4hb18 , drope-est5a , drope-est5b , drope-est5c , drops-ACHE , drops-b5dhd2 , drops-b5dk96 , drops-b5dpe3 , drops-b5drp9 , drops-b5dwa7 , drops-b5dwa8 , drops-b5dz85 , drops-b5dz86 , drops-est5a , drops-est5b , drops-q29bq2 , drops-q29dd7 , drops-q29ew0 , drops-q291d5 , drops-q291e8 , drops-q293n1 , drops-q293n4 , drops-q293n5 , drops-q293n6 , drops-q294n6 , drops-q294n7 , drops-q294n9 , drops-q294p4 , drose-b4he97 , drose-b4hfu2 , drose-b4hg54 , drose-b4hga0 , drose-b4hgu9 , drose-b4hgv0 , drose-b4hgv3 , drose-b4hgv4 , drose-b4hhm8 , drose-b4hhs6 , drose-b4hie4 , drose-b4him9 , drose-b4hk63 , drose-b4hkj5 , drose-b4hr07 , drose-b4hr81 , drose-b4hre7 , drose-b4hs13 , drose-b4hsj9 , drose-b4hsk0 , drose-b4hsm8 , drose-b4hvr5 , drose-b4hwr7 , drose-b4hwr8 , drose-b4hwr9 , drose-b4hws6 , drose-b4hws7 , drose-b4hwt0 , drose-b4hwt2 , drose-b4hwu1 , drose-b4hwu2 , drose-b4hxs9 , drose-b4hxu4 , drose-b4hxz1 , drose-b4hyp8 , drose-b4hyp9 , drose-b4hyq0 , drose-b4hyz4 , drose-b4hyz5 , drose-b4i1k8 , drose-b4i2f3 , drose-b4i2w5 , drose-b4i4u3 , drose-b4i4u7 , drose-b4i4u9 , drose-b4i4v0 , drose-b4i4v1 , drose-b4i4v4 , drose-b4i4v5 , drose-b4i4v6 , drose-b4i4v7 , drose-b4i4v8 , drose-b4i4w0 , drose-b4i7s6 , drose-b4i133 , drose-b4i857 , drose-b4iam7 , drose-b4iam9 , drose-b4iaq6 , drose-b4icf6 , drose-b4icf7 , drose-b4id80 , drose-b4ifc5 , drose-b4ihv9 , drose-b4iie9 , drose-b4ilj8 , drose-b4in13 , drose-b4inj9 , drosi-ACHE , drosi-aes04a , drosi-b4nsh8 , drosi-b4q3d7 , drosi-b4q4w5 , drosi-b4q4y7 , drosi-b4q6h6 , drosi-b4q7u2 , drosi-b4q7u3 , drosi-b4q9c6 , drosi-b4q9c7 , drosi-b4q9d3 , drosi-b4q9d4 , drosi-b4q9r0 , drosi-b4q9r1 , drosi-b4q9r3 , drosi-b4q9s2 , drosi-b4q9s3 , drosi-b4q429 , drosi-b4q530 , drosi-b4q734 , drosi-b4q782 , drosi-b4q783 , drosi-b4q942 , drosi-b4qet1 , drosi-b4qfv6 , drosi-b4qge5 , drosi-b4qgh5 , drosi-b4qgs5 , drosi-b4qhf3 , drosi-b4qhf4 , drosi-b4qhi5 , drosi-b4qjr2 , drosi-b4qjr3 , drosi-b4qjv6 , drosi-b4qk23 , drosi-b4qk51 , drosi-b4qlt1 , drosi-b4qlz9 , drosi-b4qmn9 , drosi-b4qrq7 , drosi-b4qs01 , drosi-b4qs57 , drosi-b4qs82 , drosi-b4qs83 , drosi-b4qs84 , drosi-b4qs85 , drosi-b4qs86 , drosi-b4qsq1 , drosi-b4quk6 , drosi-b4qvg5 , drosi-b4qvg6 , drosi-b4qzn2 , drosi-b4qzn3 , drosi-b4qzn5 , drosi-b4qzn7 , drosi-b4qzn8 , drosi-b4qzp2 , drosi-b4qzp3 , drosi-b4qzp4 , drosi-b4qzp5 , drosi-b4qzp6 , drosi-b4qzp7 , drosi-b4r1a4 , drosi-b4r025 , drosi-b4r207 , drosi-b4r662 , drosi-este6 , drosi-q670k8 , drovi-ACHE , drovi-b4lev2 , drovi-b4lf33 , drovi-b4lf51 , drovi-b4lg54 , drovi-b4lg72 , drovi-b4lgc6 , drovi-b4lgd5 , drovi-b4lgg0 , drovi-b4lgk5 , drovi-b4lgn2 , drovi-b4lh17 , drovi-b4lh18 , drovi-b4lk43 , drovi-b4ll59 , drovi-b4ll60 , drovi-b4llm5 , drovi-b4lln3 , drovi-b4lmk4 , drovi-b4lmp0 , drovi-b4lnr4 , drovi-b4lp47 , drovi-b4lpd0 , drovi-b4lps0 , drovi-b4lqc6 , drovi-b4lr00 , drovi-b4lrp6 , drovi-b4lrw2 , drovi-b4lse7 , drovi-b4lse9 , drovi-b4lsf0 , drovi-b4lsn0 , drovi-b4lsq5 , drovi-b4lt32 , drovi-b4ltr1 , drovi-b4lui7 , drovi-b4lui9 , drovi-b4luj8 , drovi-b4luk0 , drovi-b4luk3 , drovi-b4luk8 , drovi-b4luk9 , drovi-b4lul0 , drovi-b4lve2 , drovi-b4lxi9 , drovi-b4lxj8 , drovi-b4lyf3 , drovi-b4lyq2 , drovi-b4lyq3 , drovi-b4lz07 , drovi-b4lz13 , drovi-b4lz14 , drovi-b4lz15 , drovi-b4m0j7 , drovi-b4m0s0 , drovi-b4m2b6 , drovi-b4m4h7 , drovi-b4m4h8 , drovi-b4m4i0 , drovi-b4m4i2 , drovi-b4m4i3.A , drovi-b4m4i3.B , drovi-b4m4i4 , drovi-b4m4i5 , drovi-b4m4i6 , drovi-b4m4i7 , drovi-b4m4i8 , drovi-b4m4i9 , drovi-b4m4j2 , drovi-b4m5a0 , drovi-b4m5a1 , drovi-b4m5a2 , drovi-b4m6b9 , drovi-b4m7k9 , drovi-b4m9g9 , drovi-b4m9h0 , drovi-b4m564 , drovi-b4m599 , drovi-b4m918 , drovi-b4mb87 , drovi-b4mc71 , drovi-b4mfa4 , drowi-ACHE , drowi-b4mjb9 , drowi-b4mkt7 , drowi-b4mlc1 , drowi-b4mp68 , drowi-b4mqe9 , drowi-b4mqf0.2 , drowi-b4mqf1 , drowi-b4mqf3 , drowi-b4mqf4 , drowi-b4mqf5 , drowi-b4mqq6 , drowi-b4mrd1 , drowi-b4mrk3 , drowi-b4mtl5 , drowi-b4mug2 , drowi-b4muj8 , drowi-b4mv18 , drowi-b4mw32 , drowi-b4mw85 , drowi-b4mwp2 , drowi-b4mwp6 , drowi-b4mwq5 , drowi-b4mwr0 , drowi-b4mwr8 , drowi-b4mwr9 , drowi-b4mwt1 , drowi-b4mwz7 , drowi-b4mxn5 , drowi-b4my54 , drowi-b4myg1 , drowi-b4myh5 , drowi-b4n0d4 , drowi-b4n1a7 , drowi-b4n1c8 , drowi-b4n3s9 , drowi-b4n3x7 , drowi-b4n4x9 , drowi-b4n4y0 , drowi-b4n6m1 , drowi-b4n6n0 , drowi-b4n6n7 , drowi-b4n6u6 , drowi-b4n7s6 , drowi-b4n7s7 , drowi-b4n7s8 , drowi-b4n899.1 , drowi-b4n8a1 , drowi-b4n8a2 , drowi-b4n8a3 , drowi-b4n8a4 , drowi-b4n8a9 , drowi-b4n023 , drowi-b4n075 , drowi-b4n543 , drowi-b4n888 , drowi-b4n889 , drowi-b4n891 , drowi-b4n893 , drowi-b4n895 , drowi-b4n897 , drowi-b4n898 , drowi-b4n899.2 , drowi-b4nae3 , drowi-b4ner8 , drowi-b4ng76 , drowi-b4nga7 , drowi-b4ngb5 , drowi-b4nhz9 , drowi-b4nj18 , drowi-b4nj19 , drowi-b4nja7 , drowi-b4nja8 , drowi-b4nja9 , drowi-b4njk8 , drowi-b4nkc8 , drowi-b4nky0 , drowi-b4nl36 , drowi-b4nm27 , drowi-b4nn59 , drowi-b4nnc1 , drowi-b4nng1 , drowi-b4nng2 , droya-ACHE , droya-aes04 , droya-b4itg2 , droya-b4itg6 , droya-b4itu9 , droya-b4iuv4 , droya-b4iuv5 , droya-b4nxe6 , droya-b4nxg5 , droya-b4nxg6 , droya-b4nxg8 , droya-b4nxw4 , droya-b4ny57 , droya-b4ny58 , droya-b4ny86 , droya-b4nzz8 , droya-b4p0b5 , droya-b4p0q9 , droya-b4p0r0 , droya-b4p0r7 , droya-b4p0r8 , droya-b4p0r9 , droya-b4p0s0 , droya-b4p0s2 , droya-b4p0t0 , droya-b4p0t1 , droya-b4p3h4 , droya-b4p3x8 , droya-b4p5g8 , droya-b4p6c9 , droya-b4p6l9 , droya-b4p6r1 , droya-b4p6r2 , droya-b4p7u4 , droya-b4p8w7 , droya-b4p023 , droya-b4p241 , droya-b4p774 , droya-b4pat9 , droya-b4pbl1 , droya-b4pd22 , droya-b4pd70 , droya-b4pdm8 , droya-b4pet9 , droya-b4pff9 , droya-b4pga7 , droya-b4pgu0 , droya-b4pig3 , droya-b4pjt8 , droya-b4pka2 , droya-b4plh2 , droya-b4pma3 , droya-b4pmv3 , droya-b4pmv4 , droya-b4pmv5 , droya-b4pn92 , droya-b4pp65 , droya-b4ppc5 , droya-b4ppc6 , droya-b4ppc7 , droya-b4ppc8 , droya-b4pq03 , droya-b4prg6B , droya-b4prg9 , droya-b4prh3 , droya-b4prh4 , droya-b4prh6 , droya-b4prh7 , droya-b4psz8 , droya-b4psz9 , droya-b4pv22 , droya-b4q0g5 , droya-b4q246 , droya-EST6 , droya-q71d76 , drowi-b4n7m9 , drope-b4gkk1 , droer-b3n5s3 , drose-b4i1w5 , drowi-a0a0q9x0t3 , drogr-b4jvm7 , dromo-b4ku70 , drovi-b4mcn9 , drovi-b4lty2 , drogr-b4jdu1 , drovi-a0a0q9wiq8 , dromo-b4kf70 , drosi-b2zi86 , droya-b4p2y4 , drose-b2zic5 , droer-b3n895

Title : Identification of NanE as the thioesterase for polyether chain release in nanchangmycin biosynthesis - Liu_2006_Chem.Biol_13_945
Author(s) : Liu T , You D , Valenzano C , Sun Y , Li J , Yu Q , Zhou X , Cane DE , Deng Z
Ref : Chemical Biology , 13 :945 , 2006
Abstract : The polyketide synthase (PKS) for the biosynthesis of the polyether nanchangmycin lacks an apparent thioesterase comparable to the type I thioesterase domains of the modular PKSs responsible for macrolide biosynthesis. Three candidate polyether chain-releasing factors were examined. Both the putative CR domain and the NanE protein appeared to be genetically relevant. Among the three heterologously expressed soluble proteins (recombinant CR domain, the ACP-CR didomain, and NanE) tested, only NanE hydrolyzed the polyether-SNAC. By contrast, recombinant DEBS TE from the erythromycin pathway, and the recombinant MonAX, a type II TE associated with the polyether monensin biosynthesis for which a homolog has not been detected in the nanchangmycin cluster, hydrolyzed a diketide-SNAC but not the polyether-SNAC. We could thus conclude that NanE is a dedicated thioesterase mediating the specific release of the polyether chain during nanchangmycin biosynthesis.
ESTHER : Liu_2006_Chem.Biol_13_945
PubMedSearch : Liu_2006_Chem.Biol_13_945
PubMedID: 16984884
Gene_locus related to this paper: sacer-ery3 , strci-MONAX , strna-NANE

Title : Genome sequence, comparative analysis and haplotype structure of the domestic dog - Lindblad-Toh_2005_Nature_438_803
Author(s) : Lindblad-Toh K , Wade CM , Mikkelsen TS , Karlsson EK , Jaffe DB , Kamal M , Clamp M , Chang JL , Kulbokas EJ, 3rd , Zody MC , Mauceli E , Xie X , Breen M , Wayne RK , Ostrander EA , Ponting CP , Galibert F , Smith DR , deJong PJ , Kirkness E , Alvarez P , Biagi T , Brockman W , Butler J , Chin CW , Cook A , Cuff J , Daly MJ , Decaprio D , Gnerre S , Grabherr M , Kellis M , Kleber M , Bardeleben C , Goodstadt L , Heger A , Hitte C , Kim L , Koepfli KP , Parker HG , Pollinger JP , Searle SM , Sutter NB , Thomas R , Webber C , Baldwin J , Abebe A , Abouelleil A , Aftuck L , Ait-Zahra M , Aldredge T , Allen N , An P , Anderson S , Antoine C , Arachchi H , Aslam A , Ayotte L , Bachantsang P , Barry A , Bayul T , Benamara M , Berlin A , Bessette D , Blitshteyn B , Bloom T , Blye J , Boguslavskiy L , Bonnet C , Boukhgalter B , Brown A , Cahill P , Calixte N , Camarata J , Cheshatsang Y , Chu J , Citroen M , Collymore A , Cooke P , Dawoe T , Daza R , Decktor K , DeGray S , Dhargay N , Dooley K , Dorje P , Dorjee K , Dorris L , Duffey N , Dupes A , Egbiremolen O , Elong R , Falk J , Farina A , Faro S , Ferguson D , Ferreira P , Fisher S , FitzGerald M , Foley K , Foley C , Franke A , Friedrich D , Gage D , Garber M , Gearin G , Giannoukos G , Goode T , Goyette A , Graham J , Grandbois E , Gyaltsen K , Hafez N , Hagopian D , Hagos B , Hall J , Healy C , Hegarty R , Honan T , Horn A , Houde N , Hughes L , Hunnicutt L , Husby M , Jester B , Jones C , Kamat A , Kanga B , Kells C , Khazanovich D , Kieu AC , Kisner P , Kumar M , Lance K , Landers T , Lara M , Lee W , Leger JP , Lennon N , Leuper L , LeVine S , Liu J , Liu X , Lokyitsang Y , Lokyitsang T , Lui A , MacDonald J , Major J , Marabella R , Maru K , Matthews C , McDonough S , Mehta T , Meldrim J , Melnikov A , Meneus L , Mihalev A , Mihova T , Miller K , Mittelman R , Mlenga V , Mulrain L , Munson G , Navidi A , Naylor J , Nguyen T , Nguyen N , Nguyen C , Nicol R , Norbu N , Norbu C , Novod N , Nyima T , Olandt P , O'Neill B , O'Neill K , Osman S , Oyono L , Patti C , Perrin D , Phunkhang P , Pierre F , Priest M , Rachupka A , Raghuraman S , Rameau R , Ray V , Raymond C , Rege F , Rise C , Rogers J , Rogov P , Sahalie J , Settipalli S , Sharpe T , Shea T , Sheehan M , Sherpa N , Shi J , Shih D , Sloan J , Smith C , Sparrow T , Stalker J , Stange-Thomann N , Stavropoulos S , Stone C , Stone S , Sykes S , Tchuinga P , Tenzing P , Tesfaye S , Thoulutsang D , Thoulutsang Y , Topham K , Topping I , Tsamla T , Vassiliev H , Venkataraman V , Vo A , Wangchuk T , Wangdi T , Weiand M , Wilkinson J , Wilson A , Yadav S , Yang S , Yang X , Young G , Yu Q , Zainoun J , Zembek L , Zimmer A , Lander ES
Ref : Nature , 438 :803 , 2005
Abstract : Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.
ESTHER : Lindblad-Toh_2005_Nature_438_803
PubMedSearch : Lindblad-Toh_2005_Nature_438_803
PubMedID: 16341006
Gene_locus related to this paper: canfa-1lipg , canfa-2neur , canfa-3neur , canfa-ACHE , canfa-BCHE , canfa-cauxin , canfa-CESDD1 , canfa-e2qsb1 , canfa-e2qsl3 , canfa-e2qsz2 , canfa-e2qvk3 , canfa-e2qw15 , canfa-e2qxs8 , canfa-e2qzs6 , canfa-e2r5t3 , canfa-e2r6f6 , canfa-e2r7e8 , canfa-e2r8v9 , canfa-e2r8z1 , canfa-e2r9h4 , canfa-e2r455 , canfa-e2rb70 , canfa-e2rcq9 , canfa-e2rd94 , canfa-e2rgi0 , canfa-e2rkq0 , canfa-e2rlz9 , canfa-e2rm00 , canfa-e2rqf1 , canfa-e2rss9 , canfa-f1p6w8 , canfa-f1p8b6 , canfa-f1p9d8 , canfa-f1p683 , canfa-f1pb79 , canfa-f1pgw0 , canfa-f1phd0 , canfa-f1phx2 , canfa-f1pke8 , canfa-f1pp08 , canfa-f1ppp9 , canfa-f1ps07 , canfa-f1ptf1 , canfa-f1pvp4 , canfa-f1pw93 , canfa-f1pwk3 , canfa-pafa , canfa-q1ert3 , canfa-q5jzr0 , canfa-e2rmb9 , canlf-f6v865 , canlf-e2rjg6 , canlf-e2r2h2 , canlf-f1p648 , canlf-f1pw90 , canlf-j9p8v6 , canlf-f1pcc4 , canlf-e2qxh0 , canlf-e2r774 , canlf-f1pf96 , canlf-e2rq56 , canlf-j9nwb1 , canlf-f1ptw2 , canlf-j9p8h1 , canlf-e2ree2 , canlf-f1prs1 , canlf-j9nus1 , canlf-e2rf91 , canlf-f1pg57 , canlf-f1q111

Title : Phenotypic correction of lipid storage and growth arrest in wolman disease fibroblasts by gene transfer of lysosomal acid lipase - Tietge_2001_Hum.Gene.Ther_12_279
Author(s) : Tietge UJ , Sun G , Czarnecki S , Yu Q , Lohse P , Du H , Grabowski GA , Glick JM , Rader DJ
Ref : Hum Gene Therapy , 12 :279 , 2001
Abstract : Wolman disease is a lethal lysosomal storage disease due to deficiency of lysosomal acid lipase (LAL). Wolman disease is characterized by pronounced hepatic involvement while neurological symptoms are uncommon, making Wolman disease an attractive candidate for liver-directed gene therapy. This study was performed to test the effects of gene replacement in fibroblasts lacking LAL, using a recombinant adenovirus encoding the human LAL cDNA (AdhLAL). Human fibroblasts from a Wolman disease patient were infected with AdhLAL and showed a dose-dependent increase in LAL protein and activity up to 5-fold above levels in control fibroblasts. Furthermore, 72 hr after infection with AdhLAL there was a dose-dependent correction of the severe lipid storage phenotype of Wolman disease fibroblasts. Electron microscopy confirmed significant correction of the lysosomal lipid storage in AdhLAL-infected Wolman disease fibroblasts at the ultrastructural level. Intravenous injection of AdhLAL into wild-type mice resulted in a 13.5-fold increase in hepatic LAL activity, and overexpression of LAL was not associated with toxic side effects. These data demonstrate high-level lysosomal expression of recombinant LAL in vitro and in vivo and show the feasibility of gene therapeutic strategies for the treatment of Wolman disease.
ESTHER : Tietge_2001_Hum.Gene.Ther_12_279
PubMedSearch : Tietge_2001_Hum.Gene.Ther_12_279
PubMedID: 11177564
Gene_locus related to this paper: human-LIPA

Title : A new therapeutic target in Alzheimer's disease treatment: attention to butyrylcholinesterase - Greig_2001_Curr.Med.Res.Opin_17_159
Author(s) : Greig NH , Utsuki T , Yu Q , Zhu X , Holloway HW , Perry T , Lee B , Ingram DK , Lahiri DK
Ref : Curr Med Res Opin , 17 :159 , 2001
Abstract : Alzheimer's disease (AD) is a progressive neurodegenerative disorder of the elderly, characterised by widespread loss of central cholinergic function. The only symptomatic treatment proven effective to date is the use of cholinesterase (ChE) inhibitors to augment surviving cholinergic activity. ChE inhibitors act on the enzymes that hydrolyse acetylcholine (ACh) following synaptic release. In the healthy brain, acetylcholinesterase (AChE) predominates (80%) and butyrylcholinesterase (BuChE) is considered to play a minor role in regulating brain ACh levels. In the AD brain, BuChE activity rises while AChE activity remains unchanged or declines. Therefore both enzymes are likely to have involvement in regulating ACh levels and represent legitimate therapeutic targets to ameliorate the cholinergic deficit. The two enzymes differ in location, substrate specificity and kinetics. Recent evidence suggests that BuChE may also have a role in the aetiology and progression of AD beyond regulation of synaptic ACh levels. Experimental evidence from the use of agents with enhanced selectivity for BuChE (cymserine, MF-8622) and ChE inhibitors such as rivastigmine, which have a dual inhibitory action on both AChE and BuChE, indicate potential therapeutic benefits of inhibiting both AChE and BuChE in AD and related dementias. The development of specific BuChE inhibitors and the continued use of ChE inhibitors with the ability to inhibit BuChE in addition to AChE should lead to improved clinical outcomes.
ESTHER : Greig_2001_Curr.Med.Res.Opin_17_159
PubMedSearch : Greig_2001_Curr.Med.Res.Opin_17_159
PubMedID: 11900310

Title : Methyl analogues of the experimental Alzheimer drug phenserine: synthesis and structure\/activity relationships for acetyl- and butyrylcholinesterase inhibitory action - Yu_2001_J.Med.Chem_44_4062
Author(s) : Yu Q , Holloway HW , Flippen-Anderson JL , Hoffman B , Brossi A , Greig NH
Ref : Journal of Medicinal Chemistry , 44 :4062 , 2001
Abstract : With the goal of developing potential Alzheimer's pharmacotherapeutics, we have synthesized a series of novel analogues of the potent anticholinesterases phenserine (2) and physostigmine (1). These derivatives contain methyl (3, 4, 6), dimethyl (5, 7, 8, 10, 11) and trimethyl (14) substituents in each position of the phenyl group of the phenylcarbamoyl moieties, and with N-methyl and 6-methyl substituents (12, 13, 31, 33). We also quantified the inhibitory action of these compounds against human acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). An analysis of the structure/anticholinesterase activity relationship of the described compounds, together with molecular modeling, confirmed the catalytic triad mechanism of the binding of this class of carabamate analogues within AChE and BChE and defined structural requirements for their differential inhibition.
ESTHER : Yu_2001_J.Med.Chem_44_4062
PubMedSearch : Yu_2001_J.Med.Chem_44_4062
PubMedID: 11708910

Title : Synthesis of novel phenserine-based-selective inhibitors of butyrylcholinesterase for Alzheimer's disease - Yu_1999_J.Med.Chem_42_1855
Author(s) : Yu Q , Holloway HW , Utsuki T , Brossi A , Greig NH
Ref : Journal of Medicinal Chemistry , 42 :1855 , 1999
Abstract : Four novel analogues (8-11) of cymserine (2) were synthesized by methods similar to those recently developed for the total syntheses of N8-norphenserine (Yu, Q. S.; et al. J. Med. Chem. 1997, 40, 2895-2901) and N1,N8-bisnorphenserine (Yu, Q. S.; et al. J. Med. Chem. 1998, 41, 2371-2379). As our structure-activity studies predicted, these compounds are highly potent and selective inhibitors of human butyrylcholinesterase (BChE) and will test the novel hypothesis that BChE inhibitors are useful in the treatment of Alzheimer's disease. In a similar manner, the same modifications that provided BChE selectivity were applied to the acetylcholinesterase (AChE)-selective inhibitor, tolserine (5), to provide the novel tolserine analogues 12-15. As predicted, these modifications altered the AChE-selective action of tolserine (5) to favor a lack of cholinesterase enzyme subtype selectivity.
ESTHER : Yu_1999_J.Med.Chem_42_1855
PubMedSearch : Yu_1999_J.Med.Chem_42_1855
PubMedID: 10346939

Title : Syntheses and anticholinesterase activities of (3aS)-N1, N8- bisnorphenserine, (3aS)-N1,N8-bisnorphysostigmine, their antipodal isomers, and other potential metabolites of phenserine - Yu_1998_J.Med.Chem_41_2371
Author(s) : Yu Q , Greig NH , Holloway HW , Brossi A
Ref : Journal of Medicinal Chemistry , 41 :2371 , 1998
Abstract : Hydrolysis of the carbamate side chains in phenserine [(-)1] and physostigmine [(-)2] yields the metabolite (-)-eseroline (3), and the red dye rubreserine (4) on air oxidation of the former compound. Both compounds lacked anticholinesterase activity in concentrations up to 30 mM, which would be unachievable in vivo. A second group of potential metabolites of 1 and 2 are the N1,N8-bisnorcarbamates (-)9 and (-)10, prepared from (3aS)-N8-benzylnoresermethole (-)12 by the carbinolamine route. These entirely novel compounds proved to be highly potent inhibitors of acetylcholinesterase [(-)9] and of acetyl- and butyrylcholinesterase (AChE and BChE) [(-)10], respectively. To elucidate further the structure/anticholinesterase activity relationship of the described compounds, the antipodal isomers (3aR)-N1,N8-bisnorcarbamates (+)9 and (+)10 were likewise synthesized from (3aR)-N8-benzylnoresermethole (+)12 and assessed. The compounds possessed moderate but less potent anticholinesterase activity, with the same selectivity as their 3aS enantiomers. Finally, the anticholinesterase activities of intermediates N1, N8-bisnorbenzylcarbamates (-)18, (-) 19, (+)18, and (+)19, also novel compounds, were additionally measured. The 3aS enantiomers proved to be potent and selective inhibitors of BChE, particularly (-)19, whereas the antipodal isomers lacked activity.
ESTHER : Yu_1998_J.Med.Chem_41_2371
PubMedSearch : Yu_1998_J.Med.Chem_41_2371
PubMedID: 9632370