Liu T

References (76)

Title : Acaricidal activities of paeonol from Moutan Cortex, dried bark of Paeonia suffruticosa, against the grain pest mite Aleuroglyphus ovatus (Acari: Acaridae) - Zou_2023_Exp.Appl.Acarol__
Author(s) : Zou M , Xue Q , Teng Q , Zhang Q , Liu T , Li Y , Zhao J
Ref : Exp Appl Acarol , : , 2023
Abstract : Aleuroglyphus ovatus (Acari: Acaridae) is a major pest mite of stored grains that is distributed worldwide. Paeonol, a phenolic component of the essential oil extracted from the Chinese herb Paeonia moutan, possesses a range of biological activities, including antiviral, antifungal and acaricidal activity. This study investigated the bioactivity of paeonol against A. ovatus and its effect on the activity of detoxification enzymes. The bioactivity of paeonol against A. ovatus was determined by contact, fumigation and repellency bioassays, and the mechanism was preliminarily explored via morphological observation of the color changes of mite epidermis and determination of the changing trend of some important enzymes associated with acaricidal efficacy in the mites. The results showed that the median lethal concentration (LC(50)) in the contact and fumigation bioassays was 9.832 microg/cm(2) and 14.827 microg/cm(3), respectively, and the acaricidal activity of paeonol was higher under direct contact than under fumigation. Dynamic symptomatology studies registered typical neurotoxicity symptoms including excitation, convulsion and paralysis in A. ovatus treated with paeonol. The enzyme activity of catalase (CAT), nitric oxide synthase (NOS) and glutathione-S-transferase (GST) was higher, whereas the activity of superoxide dismutase (SOD) and acetylcholinesterase (AChE) was lower, compared to the control group. CAT, NOS and GST were activated, whereas SOD and AChE activities were inhibited after paeonol intervention. Our findings suggest paeonol has potent acaricidal activity against A. ovatus and thus may be used as an agent to control the stored-product mite A. ovatus.
ESTHER : Zou_2023_Exp.Appl.Acarol__
PubMedSearch : Zou_2023_Exp.Appl.Acarol__
PubMedID: 37979065

Title : Developing a Two-Photon AND Logic Probe and Its Application in Alzheimer's Disease Differentiation - Guo_2023_Anal.Chem__
Author(s) : Guo J , Sun J , Liu D , Liu J , Gui L , Luo M , Kong D , Wusiman S , Yang C , Liu T , Yuan Z , Li R
Ref : Analytical Chemistry , : , 2023
Abstract : In Alzheimer's disease, hypochlorous acid involved in the clearance of invading bacteria or pathogens and butyrylcholinesterase engaged in the hydrolysis of the neurotransmitter acetylcholine are relatively significantly altered. However, there are few dual detection probes for hypochlorous acid and butyrylcholinesterase. In addition, single-response probes suffer from serious off-target effects and near-infrared probes do not easily penetrate the blood-brain barrier due to their excessive molecular weight. In this work, we constructed a two-photon fluorescent probe that recognizes hypochlorous acid and butyrylcholinesterase based on a dual-lock strategy. The thiocarbonyl group is oxidized in the presence of hypochlorous acid, and the hydrolysis occurs at the 7-position ester bond in the existence of butyrylcholinesterase, releasing a strongly fluorescent fluorophore, 4-methylumbelliferone. Excellent imaging was performed in PC12 cells using this probe, and deep two-photon imaging was observed in the brains of AD mice after tail vein injection with this probe. It indicates that the probe can provide a promising tool for the more precise diagnosis of Alzheimer's disease.
ESTHER : Guo_2023_Anal.Chem__
PubMedSearch : Guo_2023_Anal.Chem__
PubMedID: 37947381

Title : Design, synthesis and biological evaluation of new multi-target scutellarein hybrids for treatment of Alzheimer's disease - Luo_2023_Bioorg.Chem_138_106596
Author(s) : Luo K , Chen J , Li H , Wu D , Du Y , Zhao S , Liu T , Li L , Dai Z , Li Y , Zhao Y , Tang L , Fu X
Ref : Bioorg Chem , 138 :106596 , 2023
Abstract : Scutellarein hybrids were designed, synthesized and evaluated as multifunctional therapeutic agents for the treatment of Alzheimer's disease (AD). Compounds 11a-i, containing a 2-hydroxymethyl-3,5,6-trimethylpyrazine fragment at the 7-position of scutellarein, were found to have balanced and effective multi-target potencies against AD. Among them, compound 11e exhibited the most potent inhibition of electric eel and human acetylcholinesterase enzymes with IC(50) values of 6.72 +/- 0.09 and 8.91 +/- 0.08 microM, respectively. In addition, compound 11e displayed not only excellent inhibition of self- and Cu(2+)-induced Abeta(1-42) aggregation (91.85% and 85.62%, respectively) but also induced disassembly of self- and Cu(2+)-induced Abeta fibrils (84.54% and 83.49% disaggregation, respectively). Moreover, 11e significantly reduced tau protein hyperphosphorylation induced by Abeta(25-35), and also exhibited good inhibition of platelet aggregation. A neuroprotective assay demonstrated that pre-treatment of PC12 cells with 11e significantly decreased lactate dehydrogenase levels, increased cell viability, enhanced expression of relevant apoptotic proteins (Bcl-2, Bax and caspase-3) and inhibited RSL3-induced PC12 cell ferroptosis. Furthermore, hCMEC/D3 and hPepT1-MDCK cell line permeability assays indicated that 11e would have optimal blood-brain barrier and intestinal absorption characteristics. In addition, in vivo studies revealed that compound 11e significantly attenuated learning and memory impairment in an AD mice model. Toxicity experiments with the compound did not reveal any safety concerns. Notably, 11e significantly reduced beta-amyloid precursor protein (APP) and beta-site APP cleaving enzyme-1 (BACE-1) protein expression in brain tissue of scopolamine-treated mice. Taken together, these outstanding properties qualified compound 11e as a promising multi-target candidate for AD therapy, worthy of further studies.
ESTHER : Luo_2023_Bioorg.Chem_138_106596
PubMedSearch : Luo_2023_Bioorg.Chem_138_106596
PubMedID: 37186997

Title : Identification of ACHE as the hub gene targeting solasonine associated with non-small cell lung cancer (NSCLC) using integrated bioinformatics analysis - Liu_2023_PeerJ_11_e16195
Author(s) : Liu T , Zhang B , Gao Y , Zhang X , Tong J , Li Z
Ref : PeerJ , 11 :e16195 , 2023
Abstract : BACKGROUND: Solasonine, as a major biological component of Solanum nigrum L., has demonstrated anticancer effects against several malignancies. However, little is understood regarding its biological target and mechanism in non-small cell lung cancer (NSCLC). METHODS: We conducted an analysis on transcriptomic data to identify differentially expressed genes (DEGs), and employed an artificial intelligence (AI) strategy to predict the target protein for solasonine. Subsequently, genetic dependency analysis and molecular docking were performed, with Acetylcholinesterase (ACHE) selected as a pivotal marker for solasonine. We then employed a range of bioinformatic approaches to explore the relationship between ACHE and solasonine. Furthermore, we investigated the impact of solasonine on A549 cells, a human lung cancer cell line. Cell inhibition of A549 cells following solasonine treatment was analyzed using the CCK8 assay. Additionally, we assessed the protein expression of ACHE, as well as markers associated with apoptosis and inflammation, using western blotting. To investigate their functions, we employed a plasmid-based ACHE overexpression system. Finally, we performed dynamics simulations to simulate the interaction mode between solasonine and ACHE. RESULTS: The results of the genetic dependency analysis revealed that ACHE could be identified as the pivotal target with the highest docking affinity. The cell experiments yielded significant findings, as evidenced by the negative regulatory effect of solasonine treatment on tumor cells, as demonstrated by the CCK8 assay. Western blotting analysis revealed that solasonine treatment resulted in the downregulation of the Bcl-2/Bax ratio and upregulation of cleaved caspase-3 protein expression levels. Moreover, we observed that ACHE overexpression promoted the expression of the Bcl-2/Bax ratio and decreased cleaved caspase-3 expression in the OE-ACHE group. Notably, solasonine treatment rescued the Bcl-2/Bax ratio and cleaved caspase-3 expression in OE-ACHE cells compared to OE-ACHE cells without solasonine treatment, suggesting that solasonine induces apoptosis. Besides, solasonine exhibited its anti-inflammatory effects by inhibiting P38 MAPK. This was supported by the decline in protein levels of IL-1beta and TNF-alpha, as well as the phosphorylated forms of JNK and P38 MAPK. The results from the molecular docking and dynamics simulations further confirmed the potent binding affinity and effective inhibitory action between solasonine and ACHE. CONCLUSIONS: The findings of the current investigation show that solasonine exerts its pro-apoptosis and anti-inflammatory effects by suppressing the expression of ACHE.
ESTHER : Liu_2023_PeerJ_11_e16195
PubMedSearch : Liu_2023_PeerJ_11_e16195
PubMedID: 37842037

Title : Detoxification of Fumonisins by Three Novel Transaminases with Diverse Enzymatic Characteristics Coupled with Carboxylesterase - Wang_2023_Foods_12_
Author(s) : Wang Y , Sun J , Zhang M , Pan K , Liu T , Zhang T , Luo X , Zhao J , Li Z
Ref : Foods , 12 : , 2023
Abstract : Fumonisin (FB) is one of the most common mycotoxins contaminating feed and food, causing severe public health threat to human and animals worldwide. Until now, only several transaminases were found to reduce FB toxicity, thus, more fumonisin detoxification transaminases with excellent catalytic properties required urgent exploration for complex application conditions. Herein, through gene mining and enzymatic characterization, three novel fumonisin detoxification transaminases-FumTSTA, FumUPTA, FumPHTA-were identified, sharing only 61-74% sequence identity with reported fumonisin detoxification transaminases. Moreover, the recombinant proteins shared diverse pH reaction ranges, good pH stability and thermostability, and the recombinant protein yields were also improved by condition optimum. Furthermore, the final products were analyzed by liquid chromatography-mass spectrometry. This study provides ideal candidates for fumonisin detoxification and meets diverse required demands in food and feed industries.
ESTHER : Wang_2023_Foods_12_
PubMedSearch : Wang_2023_Foods_12_
PubMedID: 36673508

Title : Preparation of functional oils rich in diverse medium and long-chain triacylglycerols based on a broadly applicable solvent-free enzymatic strategy - Lai_2023_Food.Res.Int_164_112338
Author(s) : Lai Y , Li D , Liu T , Wan C , Zhang Y , Zheng M
Ref : Food Res Int , 164 :112338 , 2023
Abstract : To address the problems of long reaction times and limited range of adaptation in enzymatic synthesis medium- and long-chain triacylglycerols (MLCTs), a broadly applicable solvent-free enzymatic interesterification strategy was proposed. Candida sp. lipase (CSL) was immobilized on hydrophobic hollow mesoporous silica spheres (HHSS) to construct a biocatalyst designated as CSL@HHSS with a 15.3 % immobilization yield and a loading amount of 94.0 mg/g. The expressed activity and the specific activity were 20.14 U/g and 173.62 U/g, which were 4.6 and 5.6 times higher than that of free CSL, respectively. This biocatalyst demonstrated higher activity, wider applicability, and excellent reusability. Linseed oil, sunflower oil, perilla seed oil, algal oil, and malania oleifera oil were applied as substrates to produce MLCTs with medium-chain triacylglycerols (MCT) catalyzed by CSL@HHSS through interesterification in yields ranging from 69.6 % to 78.0 % within 20 min. Specific fatty acids, including linolenic acid, oleic acid, DHA, and nervonic acid (the first reported), were introduced into MLCT's skeleton, respectively. The structures were finely analyzed and identified by GC and UPLC-MS. The catalytic efficiency value of CSL@HHSS in catalyzing interesterification between linseed oil and MCT (70 degC, 20 min, lipase 6 wt%) is 0.86 g/gmin, which is the highest ever reported. This paper presents an effective and sustainable strategy for functional MLCTs production.
ESTHER : Lai_2023_Food.Res.Int_164_112338
PubMedSearch : Lai_2023_Food.Res.Int_164_112338
PubMedID: 36737931

Title : The stereoselective toxicity of dinotefuran to Daphnia magna: A systematic assessment from reproduction, behavior, oxidative stress and digestive function - Zhang_2023_Chemosphere_327_138489
Author(s) : Zhang H , Ren X , Liu T , Zhao Y , Gan Y , Zheng L
Ref : Chemosphere , 327 :138489 , 2023
Abstract : Dinotefuran is a promising neonicotinoid insecticide with chiral structure. In the present study, the stereoselective toxicity of dinotefuran to Daphnia magna (D. magna) was studied. The present result showed that S-dinotefuran inhibited the reproduction of D. magna at 5.0 mg/L. However, both R-dinotefuran and S-dinotefuran had no genotoxicity to D. magna. Additionally, neither R-dinotefuran nor S-dinotefuran had negative influences on the motor behavior of D. magna. However, S-dinotefuran inhibited the feeding behavior of D. magna at 5.0 mg/L. Both R-dinotefuran and S-dinotefuran induced oxidative stress effect in D. magna after exposure. R-dinotefuran significantly activated the activities of superoxide dismutase (SOD) and glutathione S-transferase (GST), while S-dinotefuran showed the opposite effect. S-dinotefuran had more obvious activation effect on the acetylcholinesterase (AchE) activity and trypsin activity compared to R-dinotefuran. The transcriptome sequencing results showed that S-dinotefuran induced more DEGs in D. magna, and affected the normal function of ribosome. The DEGs were mainly related to the synthesis and metabolism of biomacromolecules, indicating the binding mode between dinotefuran enantiomer and biomacromolecules were different. Additionally, the present result indicated that the digestive enzyme activity and digestive gene expression levels in D. magna were greatly enhanced to cope with the inhibition of S-dinotefuran on the feeding.
ESTHER : Zhang_2023_Chemosphere_327_138489
PubMedSearch : Zhang_2023_Chemosphere_327_138489
PubMedID: 36996914

Title : Clinical characteristics and high risk factors of patients with Omicron variant strain infection in Hebei, China - Wang_2023_Front.Cell.Infect.Microbiol_13_1294904
Author(s) : Wang L , Liu T , Yue H , Zhang J , Sheng Q , Wu L , Wang X , Zhang M , Wang J , Yu W
Ref : Front Cell Infect Microbiol , 13 :1294904 , 2023
Abstract : OBJECTIVE: The Omicron variant has a weaker pathogenicity compared to the Delta variant but is highly transmissible and elderly critically ill patients account for the majority. This study has significant implications for guiding clinical personalized treatment and effectively utilizing healthcare resources. METHODS: The study focuses on 157 patients infected with the novel coronavirus Omicron variant, from December, 2022, to February, 2023. The objective is to analyze the baseline data, test results, imaging findings and identify risk factors associated with severe illness. RESULTS: Among the 157 included patients, there were 55 cases in the non-severe group (all were moderate cases) and 102 cases in the severe group (including severe and critical cases). Infection with the Omicron variant exhibits significant differences between non-severe and severe cases (baseline data, blood routine, coagulation, inflammatory markers, cardiac, liver, kidney functions, Chest CT, VTE score, etc.). A multifactorial logistic regression analysis showed that neutrophil percentage >75%, eosinophil percentage <0.4%, D-dimer >0.55 mg/L, PCT >0.25 ng/mL, LDH >250 U/L, albumin <40 g/L, A/G ratio <1.2, cholinesterase<5100 U/L, uric acid >357 mole/L and blood calcium<2.11 mmol/L were the most likely independent risk factors for severe novel coronavirus infection. CONCLUSION: Advanced age, low oxygenation index, elevated neutrophil percentage, decreased eosinophil percentage, elevated PCT, elevated LDH, decreased albumin, decreased A/G ratio, elevated uric acid, decreased blood calcium, and elevated D-dimer are independent prognostic risk factors for non-severe patients progressing to severe illness. These factors should be closely monitored and actively treated to prevent or minimize the occurrence of severe illness.
ESTHER : Wang_2023_Front.Cell.Infect.Microbiol_13_1294904
PubMedSearch : Wang_2023_Front.Cell.Infect.Microbiol_13_1294904
PubMedID: 38145047

Title : Modelling enzyme inhibition toxicity of ionic liquid from molecular structure via convolutional neural network model - Zhang_2023_SAR.QSAR.Environ.Res__1
Author(s) : Zhang R , Chen Y , Fan D , Liu T , Ma Z , Dai Y , Wang Y , Zhu Z
Ref : SAR QSAR Environ Research , :1 , 2023
Abstract : Deep learning (DL) methods further promote the development of quantitative structure-activity/property relationship (QSAR/QSPR) models by dealing with complex relationships between data. An acetylcholinesterase inhibitory toxicity model of ionic liquids (ILs) was established using a convolution neural network (CNN) combined with support vector machine (SVM), random forest (RF) and multilayer perceptron (MLP). A CNN model was proposed for feature self-learning and extraction of ILs. By comparing with the model results through feature engineering (FE), the model regression results based on the CNN model for feature extraction have been substantially improved. The results showed that all six models (FE-SVM, FE-RF, FE-MLP, CNN-SVM, CNN-RF, and CNN-MLP) had good prediction accuracy, but the results based on the CNN model were better. The hyperparameters of six models were optimized by grid search and the 10-fold cross validation. Compared with the existing models in the literature, the model performance has been further improved. The model could be used as an intelligent tool to guide the design or screening of low-toxicity ILs.
ESTHER : Zhang_2023_SAR.QSAR.Environ.Res__1
PubMedSearch : Zhang_2023_SAR.QSAR.Environ.Res__1
PubMedID: 37722394

Title : Detecting the combined toxicity of 18 binary and 24 ternary pesticide combinations to carboxylesterase based on fluorescence probe technology - Zhu_2022_J.Environ.Sci.Health.B__1
Author(s) : Zhu X , Chen L , Liu T , He S , Zhao X , Tian Y , Fang Y , Cui J
Ref : J Environ Sci Health B , :1 , 2022
Abstract : A rapid test method for the determination of pesticide toxicity was established by using carboxylesterase (CES) and fluorescence probe ACE-NH based on the principle of enzyme inhibition, and this method was applied to detect the combined toxicity of 18 binary and 24 ternary pesticide combinations commonly used for fruits and vegetables to CES. The results show that chlorpyrifos + carbendazim, carbofuran + carbendazim, imidacloprid + carbendazim, imidacloprid + dimethomorph, dimethoate + dimethomorph, prochloraz + carbendazim and imidacloprid + acetamiprid + carbendazim had synergistic effects under three concentration gradients, it indicated that most binary combinations containing carbendazim or imidacloprid had synergistic effects. Based on structure-activity relationship between pesticides and CES, pesticides with phosphate ester bonds had great toxicity to CES, or though they have no toxicity to CES alone, they showed a strong synergistic effect when mixed with other pesticides. Pesticides with amide or ester bond had medium toxicity and little synergistic effect. Pesticides with urea, carbamate or nitrite nitrogen group had little or no toxicity, while there was a strong synergistic effect after mixing with other pesticides. The test method and results in this study can provide scientific basis for risk assessment of cumulative exposure to mixed pesticide residues.
ESTHER : Zhu_2022_J.Environ.Sci.Health.B__1
PubMedSearch : Zhu_2022_J.Environ.Sci.Health.B__1
PubMedID: 35287560

Title : FASN promotes lymph node metastasis in cervical cancer via cholesterol reprogramming and lymphangiogenesis - Du_2022_Cell.Death.Dis_13_488
Author(s) : Du Q , Liu P , Zhang C , Liu T , Wang W , Shang C , Wu J , Liao Y , Chen Y , Huang J , Tan H , Zhao Y , Xia M , Liu J , Yao S
Ref : Cell Death Dis , 13 :488 , 2022
Abstract : Cervical cancer (CC) patients with lymph node metastasis (LNM) have a poor prognosis. Clarification of the detailed mechanisms underlying LNM may provide potential clinical therapeutic targets for CC patients with LNM. However, the molecular mechanism of LNM in CC is unclear. In the present study, we demonstrated that fatty acid synthase (FASN), one of the key enzymes in lipid metabolism, had upregulated expression in the CC samples and was correlated with LNM. Moreover, multivariate Cox proportional hazards analysis identified FASN as an independent prognostic factor of CC patients. Furthermore, gain-of-function and loss-of-function approaches showed that FASN promoted CC cell migration, invasion, and lymphangiogenesis. Mechanistically, on the one hand, FASN could regulate cholesterol reprogramming and then activate the lipid raft-related c-Src/AKT/FAK signaling pathway, leading to enhanced cell migration and invasion. On the other hand, FASN induced lymphangiogenesis by secreting PDGF-AA/IGFBP3. More importantly, knockdown of FASN with FASN shRNA or the inhibitors C75 and Cerulenin dramatically diminished LNM in vivo, suggesting that FASN plays an essential role in LNM of CC and the clinical application potential of FASN inhibitors. Taken together, our findings uncover a novel molecular mechanism in LNM of CC and identify FASN as a novel prognostic factor and potential therapeutic target for LNM in CC.
ESTHER : Du_2022_Cell.Death.Dis_13_488
PubMedSearch : Du_2022_Cell.Death.Dis_13_488
PubMedID: 35597782

Title : Improvement of methanol tolerance and catalytic activity of Rhizomucor miehei lipase for one-step synthesis of biodiesel by semi-rational design - Tian_2022_Bioresour.Technol__126769
Author(s) : Tian M , Yang L , Lv P , Wang Z , Fu J , Miao C , Li Z , Li L , Liu T , Du W , Luo W
Ref : Bioresour Technol , :126769 , 2022
Abstract : Exploiting highly active and methanol-resistant lipase is of great significance for biodiesel production. A semi-rational directed evolution method combined with N-glycosylation is reported, and all mutants exhibiting higher catalytic activity and methanol tolerance than the wild type (WT). Mutant N267 retained 64% activity after incubation in 50% methanol for 8 h, which was 48% greater than that of WT. The catalytic activity of mutants N267 and N167 was 30- and 71- fold higher than that of WT. Molecular dynamics simulations of N267 showed that the formation of new strong hydrogen bonds between glycan and the protein stabilized the structure of lipase and improved its methanol tolerance. N267 achieved biodiesel yields of 99.33% (colza oil) and 81.70% (waste soybean oil) for 24 h, which was much higher than WT (51.6% for rapeseed oil and 44.73% for wasted soybean oil). The engineered ProRML mutant has high potential for commercial biodiesel production.
ESTHER : Tian_2022_Bioresour.Technol__126769
PubMedSearch : Tian_2022_Bioresour.Technol__126769
PubMedID: 35092821

Title : Design, synthesis and evaluation of novel scutellarin and scutellarein-N,N-bis-substituted carbamate-l-amino acid derivatives as potential multifunctional therapeutics for Alzheimer's disease - Wu_2022_Bioorg.Chem_122_105760
Author(s) : Wu D , Chen J , Luo K , Li H , Liu T , Li L , Dai Z , Li Y , Zhao Y , Fu X
Ref : Bioorg Chem , 122 :105760 , 2022
Abstract : In this study, we designed, synthesized and evaluated a series of scutellarin and scutellarein-N,N-bis-substituted carbamate-l-amino acid derivatives as multifunctional therapeutic agents for the treatment of Alzheimer's disease (AD). Compounds containing scutellarein as the parent nucleus (6a-l) had good inhibitory activity against acetyl cholinesterase (AChE), with compound 6 h exhibiting the most potent inhibition of electric eel AChE and human AChE enzymes with IC(50) values of 6.01 +/- 1.66 and 7.91 +/- 0.49 microM, respectively. In addition, compound 6 h displayed not only excellent inhibition of self- and Cu(2+)-induced Abeta(1-42) aggregation (89.17% and 86.19% inhibition) but also induced disassembly of self- and Cu(2+)-induced Abeta fibrils (84.25% and 78.73% disaggregation). Moreover, a neuroprotective assay demonstrated that pre-treatment of PC12 cells with 6 h significantly decreased lactate dehydrogenase levels, increased cell viability, enhanced expression of relevant apoptotic proteins (Bcl-2, Bax, and caspase-3) and inhibited RSL3 induced PC12 cell ferroptosis. Furthermore, hCMEC/D3 and hPepT1-MDCK cell line permeability assays indicated that 6 h would have optimal blood-brain barrier and intestinal absorption characteristics. The in vivo experimental data suggested that 6 h ameliorated learning and memory impairment in mice by decreasing AChE activity, increasing ACh levels and alleviating pathological damage of hippocampal tissue cells. These multifunctional properties highlight compound 6 h as a promising candidate for development as a multifunctional drug against AD.
ESTHER : Wu_2022_Bioorg.Chem_122_105760
PubMedSearch : Wu_2022_Bioorg.Chem_122_105760
PubMedID: 35349945

Title : Epoxyeicosatrienoic Acids Inhibit the Activation of Murine Fibroblasts by Blocking the TGF-beta1-Smad2\/3 Signaling in a PPARgamma-Dependent Manner - Tao_2022_Oxid.Med.Cell.Longev_2022_7265486
Author(s) : Tao JH , Liu T , Zhang CY , Zu C , Yang HH , Liu YB , Yang JT , Zhou Y , Guan CX
Ref : Oxid Med Cell Longev , 2022 :7265486 , 2022
Abstract : BACKGROUND: Epoxyeicosatrienoic acids (EETs), the metabolite of arachidonic acid by cytochrome P450 (CYP), reportedly serve as a vital endogenous protective factor in several chronic diseases. EETs are metabolized by soluble epoxide hydrolase (sEH). We have observed that prophylactic blocking sEH alleviates bleomycin- (BLM-) induced pulmonary fibrosis (PF) in mice. However, the underlying mechanism and therapeutic effects of EETs on PF remain elusive. OBJECTIVE: In this study, we investigated the effect of CYP2J2/EETs on the activation of murine fibroblasts and their mechanisms. RESULTS: we found that administration of the sEH inhibitor (TPPU) 7 days after the BLM injection also reversed the morphology changes and collagen deposition in the lungs of BLM-treated mice, attenuating PF. Fibroblast activation is regarded as a critical role of PF. Therefore, we investigated the effects of EETs on the proliferation and differentiation of murine fibroblasts. Results showed that the overexpression of CYP2J2 reduced the cell proliferation and the expressions of alpha-SMA and PCNA induced by transforming growth factor- (TGF-) beta1 in murine fibroblasts. Then, we found that EETs inhibited the proliferation and differentiation of TGF-beta1-treated-NIH3T3 cells and primary murine fibroblasts. Mechanistically, we found that 14,15-EET disrupted the phosphorylation of Smad2/3 murine fibroblasts by activating PPARgamma, which was completely abolished by a PPARgamma inhibitor GW9662. CONCLUSION: our study shows that EETs inhibit the activation of murine fibroblasts by blocking the TGF-beta1-Smad2/3 signaling in a PPARgamma-dependent manner. Regulating CYP2J2-EET-sEH metabolic pathway may be a potential therapeutic option in PF.
ESTHER : Tao_2022_Oxid.Med.Cell.Longev_2022_7265486
PubMedSearch : Tao_2022_Oxid.Med.Cell.Longev_2022_7265486
PubMedID: 36275905

Title : Synthesis, insecticidal activity, and mode of action of novel imidazopyridine mesoionic derivatives containing an amido group - Liu_2022_Pest.Manag.Sci__
Author(s) : Liu Z , Song R , Zhang D , Wu R , Liu T , Wu Z , Zhang J , Hu D
Ref : Pest Manag Sci , : , 2022
Abstract : BACKGROUND: In our previous work, we applied a new synthetic strategy to design and synthesize a series of imidazopyridine mesoionic derivatives with an ester group. The newly synthesized compounds had excellent insecticidal activity against aphids; however, insecticidal activity against planthoppers was less than satisfactory. In the present study, we designed and synthesized a series of novel imidazopyridine mesoionic compounds, containing an amido group, and these compounds were found to have improved insecticidal activity against planthoppers. RESULTS: The bioassay results demonstrated that most of the target compounds had moderate-to-good insecticidal activity against Sogatella furcifera, and some exhibited good-to-excellent insecticidal activity against Aphis craccivora. Among them, compound C6 had the highest insecticidal activity against S. furcifera and A. craccivora, with LC(50) values of 10.5 and 2.09 microg mL(-1) , respectively. Proteomic results suggested that the differentially expressed proteins mainly were enriched in the nervous system-related pathways after compound C6 treatment. Enzymatic assay results showed that compound C6 and triflumezopyrim had a certain inhibitory effect on acetylcholinesterase. Molecular docking and real-time quantitative PCR results indicated that compound C6 not only may act on the nicotinic acetylcholine receptor, but also may interact with the alpha4 and beta1 subunits of this receptor. CONCLUSION: The results reported here contribute to the development of new mesoionic insecticides and further our understanding of the mode-of-action of imidazopyridine mesoionic derivatives. 2022 Society of Chemical Industry.
ESTHER : Liu_2022_Pest.Manag.Sci__
PubMedSearch : Liu_2022_Pest.Manag.Sci__
PubMedID: 36054072

Title : N-glycosylation as an effective strategy to enhance characteristics of Rhizomucor miehei lipase for biodiesel production - Tian_2022_Enzyme.Microb.Technol_160_110072
Author(s) : Tian M , Wang Z , Fu J , Lv P , Liang C , Li Z , Yang L , Liu T , Li M , Luo W
Ref : Enzyme Microb Technol , 160 :110072 , 2022
Abstract : The construction of methanol-resistant lipases with high catalytic activity is world-shattering for biodiesel production. A semi-rational method has been constructed to enhance the properties of Rhizomucor miehei lipase with propeptide (ProRML) by introducing N-glycosylation sites in the Loop structure. The enzyme activities of the mutants N288 (1448.89 +/- 68.64 U/mg) and N142 (1073.68 +/- 33.87 U/mg) increased to 56.09 and 41.56 times relative to that of wild type ProRML (WT, 25.83 +/- 0.73 U/mg), respectively. After incubation in 50 % methanol for 2.5 h, the residual activities of N314 and N174-1 were 95 % and 85%, which were higher than the WT (27 %). Additionally, the biodiesel yield of all mutants was increased after a one-time addition of methanol for 24 h. Among them, N288 increased the quantity of biodiesel from colza oil from 9.49 % to 88 %, and N314 increased the amount of biodiesel from waste soybean oil from 8.44% to 70%. This study provides an effective method to enhance the properties of lipase and improve its application potential in biodiesel production.
ESTHER : Tian_2022_Enzyme.Microb.Technol_160_110072
PubMedSearch : Tian_2022_Enzyme.Microb.Technol_160_110072
PubMedID: 35689964

Title : Neurotoxins Acting at Synaptic Sites: A Brief Review on Mechanisms and Clinical Applications - Zhou_2022_Toxins.(Basel)_15_
Author(s) : Zhou K , Luo W , Liu T , Ni Y , Qin Z
Ref : Toxins (Basel) , 15 : , 2022
Abstract : Neurotoxins generally inhibit or promote the release of neurotransmitters or bind to receptors that are located in the pre- or post-synaptic membranes, thereby affecting physiological functions of synapses and affecting biological processes. With more and more research on the toxins of various origins, many neurotoxins are now widely used in clinical treatment and have demonstrated good therapeutic outcomes. This review summarizes the structural properties and potential pharmacological effects of neurotoxins acting on different components of the synapse, as well as their important clinical applications, thus could be a useful reference for researchers and clinicians in the study of neurotoxins.
ESTHER : Zhou_2022_Toxins.(Basel)_15_
PubMedSearch : Zhou_2022_Toxins.(Basel)_15_
PubMedID: 36668838

Title : Structurally diverse alkaloids with nine frameworks from Zephyranthes candida and their acetylcholinesterase inhibitory and anti-inflammatory activities - Zhan_2022_Phytochemistry__113564
Author(s) : Zhan G , Gao B , Zhou J , Liu T , Zheng G , Jin Z , Yao G
Ref : Phytochemistry , :113564 , 2022
Abstract : Twenty-six structurally diverse Amaryllidaceae alkaloids, including ten undescribed compounds named zephyranines A-I and 6-O-ethylnerinine, two undescribed natural products zephyranthine-6-one and 3-O-deacetyl-sternbergine, were isolated from whole plants of Zephyranthes candida. Their structures were determined by HRESIMS, 1D and 2D NMR, CD data analysis, NMR and ECD calculations, and single-crystal X-ray diffraction analysis. All structures were classified into nine framework types: 10 b,11-seco-crinine, graciline, crinine, homolycorine, trisphaeridine, lycorine, galasine, tazettine, and belladine. Zephyranine A represents the first naturally occurring 10 b,11-seco-crinine type alkaloid, and zephyranine B is the sixth graciline type alkaloid. 6-O-ethylnerinine is an artifact from the extraction and isolation. All isolates were evaluated for their acetylcholinesterase (AChE) inhibitory and anti-inflammatory activities. Zephyranines A, G, and H exhibited moderate AChE inhibitory activities, with IC(50) values of 8.2, 39.0, and 10.8 microM, respectively. Zephyranine B, haemanthamine, haemanthidine, 11-hydroxyvittatine, and 8-demethoxy-10-O-methylhostasine exhibited potent anti-inflammatory activity on the LPS-induced NO production in RAW264.7 mouse macrophages with IC(50) values of 21.3, 4.6, 12.2, 5.6, and 17.4 microM, respectively. Structure-activity-relationship analysis and docking studies indicated that interactions with the key Trp286 and Tyr337 residues are required for potent AChE inhibitors.
ESTHER : Zhan_2022_Phytochemistry__113564
PubMedSearch : Zhan_2022_Phytochemistry__113564
PubMedID: 36535411

Title : Sweet potato extract alleviates high-fat-diet-induced obesity in C57BL\/6J mice, but not by inhibiting pancreatic lipases - Liu_2022_Front.Nutr_9_1016020
Author(s) : Liu T , Wu F , Chen K , Pan B , Yin X , You Y , Song Z , Li D , Huang D
Ref : Front Nutr , 9 :1016020 , 2022
Abstract : SCOPE AND AIM: Sweet potato is widely consumed as a healthy and nutritive vegetable containing bioactive constituents for health promotion. This study investigated the beneficial impact of white-fleshed sweet potato extract (SPE) on high fat diet (HFD)-induced obese mice. METHODS AND RESULTS: First, SPE, in which resin glycoside was found as the dominant constituent, was suggested as a potential anti-obesity agent, because 20-70% pancreatic lipase (PL) inhibition was measured with SPE by in vitro turbidity assay and pNPP assay. Hence, next, the effect of SPE on obese mice was detected by oral administration of HFD supplemented with 6% SPE on C57BL/6J mice for 9 weeks. Surprisingly, being the opposite of what was typically observed from a lipase inhibitor such as orlistat, the fecal fat content in SPE-fed obese mice was decreased (p < 0.01). Meanwhile, 6% SPE supplement indeed significantly ameliorated HFD-induced obesity in mice, including body weight gain, fat accumulation, adipocyte enlargement, insulin resistance, and hepatic steatosis (p < 0.05). The improved liver steatosis was found associated with a down-regulating action of SPE on nuclear factor kappa B activation in HFD-fed mice. The anti-obesity influence of SPE was also confirmed on the HepG2 cell model for non-alcoholic fatty liver disease (NAFLD). CONCLUSION: These results indicate that SPE, as a dietary supplement, has the great potential for weight control and treating hepatic steatosis, possibly through a different action mechanism from that of orlistat.
ESTHER : Liu_2022_Front.Nutr_9_1016020
PubMedSearch : Liu_2022_Front.Nutr_9_1016020
PubMedID: 36505243

Title : Insecticidal Activity of a Component, (-)-4-Terpineol, Isolated from the Essential Oil of Artemisia lavandulaefolia DC. against Plutella xylostella (L.) - Huang_2022_Insects_13_
Author(s) : Huang X , Du L , Liu T , Ma R , Liu X , Yuan H , Liu S
Ref : Insects , 13 : , 2022
Abstract : Plutella xylostella (L.) is one of the most serious pests of cruciferous vegetables. Our previous work demonstrated that the essential oil of Artemisia lavandulaefolia DC. exhibits promising insecticidal activities against P. xylostella. This study further characterizes the key components that are responsible for the insecticidal effect. In total, 47 compounds (96.52% of the total compounds) were identified from the total oil using GC-MS, and the major compounds were eucalyptol (21.57%), D(+)-camphor (17.33%), (-)-4-terpineol (9.96%) and caryophyllene oxide (10.96%). Among them, (-)-4-terpineol showed significantly larvicidal and fumigant activities against P. xylostella. The LD(50) of (-)-4-terpineol was 43.15 mg/mL at 12 h and 31.22 mg/mL at 24 h for 3rd instar larvae, and the LC(50) for adults was 8.34 mg/mL at 12 h and 7.35 mg/mL at 24 h. In addition, the adults treated with (-)-4-terpineol showed varying degrees of inhibitory activity toward glutathione S-transferase, catalase, acetylcholinesterase and Na(+)/K(+)-ATPase at different post-treatment intervals and concentrations. The results indicate that (-)-4-terpineol has promising insecticidal activities against P. xylostella, and it has good inhibitory effects on the four enzymes of P. xylostella adults.
ESTHER : Huang_2022_Insects_13_
PubMedSearch : Huang_2022_Insects_13_
PubMedID: 36555036

Title : Phthalate Esters Metabolic Strain Gordonia sp. GZ-YC7, a Potential Soil Degrader for High Concentration Di-(2-ethylhexyl) Phthalate - Hu_2022_Microorganisms_10_
Author(s) : Hu T , Yang C , Hou Z , Liu T , Mei X , Zheng L , Zhong W
Ref : Microorganisms , 10 : , 2022
Abstract : As commonly used chemical plasticizers in plastic products, phthalate esters have become a serious ubiquitous environmental pollutant, such as in soil of plastic film mulch culture. Microbial degradation or transformation was regarded as a suitable strategy to solve the phthalate esters pollution. Thus, a new phthalate esters degrading strain Gordonia sp. GZ-YC7 was isolated in this study, which exhibited the highest di-(2-ethylhexyl) phthalate degradation efficiency under 1000 mg/L and the strongest tolerance to 4000 mg/L. The comparative genomic analysis results showed that there exist diverse esterases for various phthalate esters such as di-(2-ethylhexyl) phthalate and dibutyl phthalate in Gordonia sp. GZ-YC7. This genome characteristic possibly contributes to its broad substrate spectrum, high degrading efficiency, and high tolerance to phthalate esters. Gordonia sp. GZ-YC7 has potential for the bioremediation of phthalate esters in polluted soil environments.
ESTHER : Hu_2022_Microorganisms_10_
PubMedSearch : Hu_2022_Microorganisms_10_
PubMedID: 35336217

Title : Dwarf and High Tillering1 represses rice tillering through mediating the splicing of D14 pre-mRNA - Liu_2022_Plant.Cell_34_3301
Author(s) : Liu T , Zhang X , Zhang H , Cheng Z , Liu J , Zhou C , Luo S , Luo W , Li S , Xing X , Chang Y , Shi C , Ren Y , Zhu S , Lei C , Guo X , Wang J , Zhao Z , Wang H , Zhai H , Lin Q , Wan J
Ref : Plant Cell , 34 :3301 , 2022
Abstract : Strigolactones (SLs) constitute a class of plant hormones that regulate many aspects of plant development, including repressing tillering in rice (Oryza sativa). However, how SL pathways are regulated is still poorly understood. Here, we describe a rice mutant dwarf and high tillering1 (dht1), which exhibits pleiotropic phenotypes (such as dwarfism and increased tiller numbers) similar to those of mutants defective in SL signaling. We show that DHT1 encodes a monocotyledon-specific hnRNP-like protein that acts as a previously unrecognized intron splicing factor for many precursor mRNAs (pre-mRNAs), including for the SL receptor gene D14. We find that the dht1 (DHT1I232F) mutant protein is impaired in its stability and RNA binding activity, causing defective splicing of D14 pre-mRNA and reduced D14 expression, and consequently leading to the SL signaling-defective phenotypes. Overall, our findings deepen our understanding of the functional diversification of hnRNP-like proteins and establish a connection between posttranscriptional splicing and SL signaling in the regulation of plant development.
ESTHER : Liu_2022_Plant.Cell_34_3301
PubMedSearch : Liu_2022_Plant.Cell_34_3301
PubMedID: 35670739

Title : Functional Characterization and Crystal Structure of the Bifunctional Thioesterase Catalyzing Epimerization and Cyclization in Skyllamycin Biosynthesis - Yu_2021_ACS.Catalysis_11_11733
Author(s) : Yu J , Juan S , Chi C , Liu T , Geng T , Cai Z , Dong W , Shi C , Ma X , Zhang Z , Xing B , Jin H , Zhang L , Dong S , Yang D , Ma M
Ref : ACS Catal , 11 :11733 , 2021
Abstract : The d-amino acid residues are hallmark building blocks of nonribosomal peptides. Here, we report the bifunctional thioesterase domain (TE domain) Skyxy-TE that catalyzes both epimerization and cyclization in skyllamycin biosynthesis. Skyxy-TE specifically catalyzes the epimerization of the C-terminal l-amino acid residue of the linear substrate, then catalyzes regioselective intramolecular cyclization. The crystal structure of Skyxy-TE was solved at 2.25 and site-directed mutagenesis was performed, revealing key residues involved in the epimerization and cyclization. This study expands the understanding of the versatile TE domains and facilitates chemoenzymatic synthesis or combinatorial biosynthesis in the future.
ESTHER : Yu_2021_ACS.Catalysis_11_11733
PubMedSearch : Yu_2021_ACS.Catalysis_11_11733
Gene_locus related to this paper: strsq-a0a1j0r317

Title : Isolation and Insecticidal Activity of Essential Oil from Artemisia lavandulaefolia DC. against Plutella xylostella - Huang_2021_Toxins.(Basel)_13_
Author(s) : Huang X , Huang Y , Yang C , Liu T , Liu X , Yuan H
Ref : Toxins (Basel) , 13 : , 2021
Abstract : Many plants show significant biological activity against pests due to their unique chemical constituents. It is important to identify effective constituents for their development and utilization as botanical pesticides. Our previous study showed that Artemisia lavandulaefolia essential oil had biological activity against Plutella xylostella. Here, we isolated and identified the constituents of essential oil from A. lavandulaefolia by silica gel column chromatography. The main constituents identified were eucalyptol and caryophyllene oxide, and they were confirmed by gas chromatography-mass spectrometry (GC-MS). Eucalyptol and caryophyllene oxide showed strong contact toxicity against P. xylostella larvae after 24 h of application (Median lethal dose, LD(50) = 76.97 microL/mL and 20.71 mg/mL. Furthermore, the two active constituents against P. xylostella adults showed significant fumigant activity (Mmedian lethal concentration, LC(50) = 3.25 microL/L and 1.06 mg/L, respectively. Finally, we measured the detoxification enzymes and acetylcholinesterase of the larvae treated with active constituents. The eucalyptol-treated larvae displayed enhanced carboxylesterase (CarE) and glutathione-S-transferase (GST) activities in an in vivo experiment, but it was lower for acetylcholinesterase (AchE) activity. The activities of the CarE and GST significantly decreased when exposed to caryophyllene oxide. In general, the two active constituents, eucalyptol and caryophyllene oxide, showed high insecticidal activity, which demonstrates their potential to be used as natural insecticides.
ESTHER : Huang_2021_Toxins.(Basel)_13_
PubMedSearch : Huang_2021_Toxins.(Basel)_13_
PubMedID: 34941680

Title : The facile formation of hierarchical mesoporous silica nanocarriers for tumor-selective multimodal theranostics - Guo_2021_Biomater.Sci__
Author(s) : Guo X , Zhu M , Yuan P , Liu T , Tian R , Bai Y , Zhang Y , Chen X
Ref : Biomater Sci , : , 2021
Abstract : The combination of therapeutic and diagnostic functions in a single platform has aroused great interest due to the more optimal synergistic effects that can be obtained as compared to any single theranostic approach alone. However, current nanotheranostics are normally formed via complicated construction steps involving the pre-synthesis of each component and further conjugation via chemical bonds, which may cause low integration efficiency and limit production and applications. Herein, a tumor-targeting and tumor-responsive all-in-one nanoplatform based on mesoporous silica nanocarriers (MSNs) was fabricated via a facile approach utilizing efficient and nondestructive physical interactions for long-wavelength fluorescence imaging-guided synergistic chemo-catalytic-photothermal tumor therapy. The MSNs were endowed with these multimodal theranostics via a simple hydrothermal method after coordinating with Fe2+ and glutathione (GSH) to introduce ferroferric oxide and carbon dots in situ. The former acts as a photothermal agent and catalytic agent to generate local heat under 808 nm irradiation and also when toxic hydroxyl radicals (OH) are in contact with abundant hydrogen peroxide in cancer cells, while the latter participates in fluorescence imaging. After loading with paclitaxel (PTX), polyester and folic-acid-conjugated cyclodextrin were employed to serve as an esterase-sensitive gatekeeper controlling PTX release from the MSN pores and as a tumor-targeting agent for accurate therapy, respectively. As expected, the nanoplatform was efficiently taken up by tumor cells over healthy cells, and then, synergetic chemo-catalytic-photothermal therapy was performed, resulting in 5-fold greater apoptosis of tumor cells as compared to healthy cells under 808 nm irradiation. Moreover, in vivo data from tumor-bearing mouse models showed that tumors were significantly inhibited, and the survival rates of these mice increased to greater than 80% after 5 weeks of treatment with our nanoplatform. These therapeutic processes could be directly tracked via fluorescence imaging enabled by carbon dots and, therefore, our nanoplatform provides a promising theranostics approach for tumor treatment.
ESTHER : Guo_2021_Biomater.Sci__
PubMedSearch : Guo_2021_Biomater.Sci__
PubMedID: 34223579

Title : Improved methanol tolerance of Rhizomucor miehei lipase based on Nglycosylation within the alpha-helix region and its application in biodiesel production - Tian_2021_Biotechnol.Biofuels_14_237
Author(s) : Tian M , Yang L , Wang Z , Lv P , Fu J , Miao C , Li M , Liu T , Luo W
Ref : Biotechnol Biofuels , 14 :237 , 2021
Abstract : BACKGROUND: Liquid lipases are widely used to convert oil into biodiesel. Methanol-resistant lipases with high catalytic activity are the first choice for practical production. Rhizomucor miehei lipase (RML) is a single-chain alpha/beta-type protein that is widely used in biodiesel preparation. Improving the catalytic activity and methanol tolerance of RML is necessary to realise the industrial production of biodiesel. RESULTS: In this study, a semi-rational design method was used to optimise the catalytic activity and methanol tolerance of ProRML. After N-glycosylation modification of the alpha-helix of the mature peptide in ProRML, the resulting mutants N218, N93, N115, N260, and N183 increased enzyme activity by 66.81, 13.54, 10.33, 3.69, and 2.39 times than that of WT, respectively. The residual activities of N218 and N260 were 88.78% and 86.08% after incubation in 50% methanol for 2.5 h, respectively. In addition, the biodiesel yield of all mutants was improved when methanol was added once and reacted for 24 h with colza oil as the raw material. N260 and N218 increased the biodiesel yield from 9.49% to 88.75% and 90.46%, respectively. CONCLUSIONS: These results indicate that optimising N-glycosylation modification in the alpha-helix structure is an effective strategy for improving the performance of ProRML. This study provides an effective approach to improve the design of the enzyme and the properties of lipase mutants, thereby rendering them suitable for industrial biomass conversion.
ESTHER : Tian_2021_Biotechnol.Biofuels_14_237
PubMedSearch : Tian_2021_Biotechnol.Biofuels_14_237
PubMedID: 34911574

Title : Peroxidase-mimicking Activity of PCN-222(Fe) for Colorimetric Sensing of Acetylcholinesterase Activity and Inhibition - Xia_2021_Anal.Sci_37_1023
Author(s) : Xia M , Liu T , Zhang Y
Ref : Anal Sci , 37 :1023 , 2021
Abstract : A colorimetric method for detection of acetylcholinesterase (AChE) activity and inhibition was developed using metal organic frameworks (i.e., PCN-222(Fe)) with peroxidase-like activity. The blue tetramethylbenzidine oxidized by PCN-222(Fe) fades due to the reduction by acetylthiocholine chloride produced from AChE catalysis. The detection method shows a linear range of 0.05 - 10 mU mL(-1) and a detection limit of 0.03 mU mL(-1) AChE. Average recoveries in serum samples varied from 93 to 115% and relative standard deviation (RSD) was lower than 4.9%.
ESTHER : Xia_2021_Anal.Sci_37_1023
PubMedSearch : Xia_2021_Anal.Sci_37_1023
PubMedID: 33071263

Title : Biological detoxification of fumonisin by a novel carboxylesterase from Sphingomonadales bacterium and its biochemical characterization - Li_2021_Int.J.Biol.Macromol_169_18
Author(s) : Li Z , Wang Y , Liu Z , Jin S , Pan K , Liu H , Liu T , Li X , Zhang C , Luo X , Song Y , Zhao J , Zhang T
Ref : Int J Biol Macromol , 169 :18 , 2021
Abstract : Fumonisins have posed hazardous threat to human and animal health worldwide. Enzymatic degradation is a desirable detoxification approach but is severely hindered by serious shortage of detoxification enzymes. After mining enzymes by bioinformatics analysis, a novel carboxylesterase FumDSB from Sphingomonadales bacterium was expressed in Escherichia coli, and confirmed to catalyze fumonisin B1 to produce hydrolyzed fumonisin B1 by liquid chromatography mass spectrometry for the first time. FumDSB showed high sequence novelty, sharing only ~34% sequence identity with three reported fumonisin detoxification carboxylesterases. Besides, FumDSB displayed its high degrading activity at 30-40 degreesC within a broad pH range from 6.0 to 9.0, which is perfectly suitable to be used in animal physiological condition. It also exhibited excellent pH stability and moderate thermostability. This study provides a FB1 detoxification carboxylesterase which could be further used as a potential food and feed additive.
ESTHER : Li_2021_Int.J.Biol.Macromol_169_18
PubMedSearch : Li_2021_Int.J.Biol.Macromol_169_18
PubMedID: 33309671
Gene_locus related to this paper: 9sphn-a0a101vlk1

Title : Discovery of 7-O-1, 2, 3-triazole hesperetin derivatives as multi-target-directed ligands against Alzheimer's disease - Wang_2021_Chem.Biol.Interact__109489
Author(s) : Wang M , Fang L , Liu T , Chen X , Zheng Y , Zhang Y , Chen S , Li Z
Ref : Chemico-Biological Interactions , :109489 , 2021
Abstract : The development of multi-target-directed ligands (MTDLs) may improve complex central nervous system diseases such as Alzheimer's disease (AD). Here, a series of 7-O-1, 2, 3-triazole hesperetin derivatives was evaluated for their inhibition of cholinesterase, anti-neuroinflammatory, and neuroprotective activity. Among the hesperetin derivatives, compound a8 (7-O-((1-(3-chlorobenzyl)-1H-1,2,3-triazol-4-yl)methyl)hesperetin) possessed excellent anti-butyrylcholinesterase activity (IC(50) = 3.08 +/- 0.29 microM) and exhibited good anti-neuroinflammatory activity (IC(50) = 2.91 +/- 0.47 microM) against NO production through remarkably blocking the NF-kappaB signaling pathway and inhibiting the phosphorylation of P65. In addition, a8 showed a remarkable neuroprotective effect and lacked neurotoxicity up to 50 microM concentration. Furthermore, possessing significant self-mediated Abeta(1-42) aggregation inhibitory activity, chelated biometals and reduced ROS production were found in compound a8. In the bi-directional transport assay, a8 exhibited a blood-brain barrier penetrating ability. In this study, the Morris water maze task showed that compound a8 significantly improved the learning and memory impairment of the scopolamine-induced AD mice model. Results highlighted the potential of compound a8 to be a potential MTDL for the development of anti-AD agents.
ESTHER : Wang_2021_Chem.Biol.Interact__109489
PubMedSearch : Wang_2021_Chem.Biol.Interact__109489
PubMedID: 33905740

Title : Enhanced activity of Rhizomucor miehei lipase by directed saturation mutation of the propeptide - Tian_2021_Enzyme.Microb.Technol_150_109870
Author(s) : Tian M , Huang S , Wang Z , Fu J , Lv P , Miao C , Liu T , Yang L , Luo W
Ref : Enzyme Microb Technol , 150 :109870 , 2021
Abstract : The propeptide is a short sequence that facilitates protein folding. In this study, four highly active Rhizomucor miehei lipase (RML) mutants were obtained through saturation mutagenesis at three propeptide positions: Ser8, Pro35, and Pro47. The enzyme activities of mutants P35 N, P47 G, P47 N, and S8E/P35S/P47A observed at 40 degreesC, and pH 8.0 were 10.19, 7.53, 6.15, and 8.24 times of that wild-type RML, respectively. The S8E/P35S/P47A mutant showed good thermostability. After incubation at 40 degreesC for 1 h, 98.98 % of its initial activity remained, whereas wild-type RML retained only 78.76 %. This result indicated that the enhancement of hydrophilicity of 35- and 47- amino-acid residues could promote the interaction between the propeptide and the mature peptide and the enzyme activity and expression level. Highly conserved sites had a more significant impact on enzyme performance than did other sites, similar to the Pro35 and Pro47 mutants showed in this study. This study provides a new idea for protein modification: enzyme performance can be improved through propeptide regulation.
ESTHER : Tian_2021_Enzyme.Microb.Technol_150_109870
PubMedSearch : Tian_2021_Enzyme.Microb.Technol_150_109870
PubMedID: 34489029

Title : Enantioselective bioaccumulation and detoxification mechanisms of earthworms (Eisenia fetida) exposed to mandipropamid - Fang_2021_Sci.Total.Environ_796_149051
Author(s) : Fang K , Han L , Liu Y , Fang J , Wang X , Liu T
Ref : Sci Total Environ , 796 :149051 , 2021
Abstract : As a novel chiral amide fungicide, the enantioselective behaviors of mandipropamid in the soil environment are unclear. Furthermore, there is a need to understand the stress response mechanisms of soil organisms exposed to mandipropamid isomers. Therefore, the selective bioaccumulation of mandipropamid isomers and detoxification mechanisms of earthworms (Eisenia fetida) were investigated in this study. Our results suggested that the enantioselective bioaccumulation of mandipropamid in earthworms occurred with the preferential enrichment of S-(+)-isomer. The activities of detoxification enzymes, such as cytochrome P450 (CYP450), glutathione-S-transferases (GST), and carboxylesterase (CarE), changed significantly upon exposure to S-(+)- and R-(-)-mandipropamid (particularly for CYP450 and GST). A transcriptome analysis revealed that more differentially expressed genes (DEGs) were observed under S-(+)-isomer exposure (15,798) than those under R-(-)-isomer exposure (12,222), as compared to the control group. These DEGs were mainly enriched in bile secretion and thyroid hormone signaling pathways, which were related to the detoxification process in earthworms. Moreover, the 20 DEGs, which exhibited the most profound changes (such as CYP2 and CYP3A4) in these pathways, were screened, clustered, and observed to be mainly involved in regulating the detoxification function of earthworm cells. These results indicated that detoxification systems played an essential role in the stress response to mandipropamid exposure. Additionally, earthworms were more sensitive to the stress induced by S-(+)-mandipropamid than that induced by R-(-)-mandipropamid. This is the first study to elucidate the mandipropamid detoxification mechanism of earthworms at the enantiomer level, which can be beneficial for remediating chiral pollutants.
ESTHER : Fang_2021_Sci.Total.Environ_796_149051
PubMedSearch : Fang_2021_Sci.Total.Environ_796_149051
PubMedID: 34280637

Title : Design, synthesis, and biological evaluation of novel (4-(1,2,4-oxadiazol-5-yl)phenyl)-2-aminoacetamide derivatives as multifunctional agents for the treatment of Alzheimer's disease - Liu_2021_Eur.J.Med.Chem_227_113973
Author(s) : Liu T , Chen S , Du J , Xing S , Li R , Li Z
Ref : Eur Journal of Medicinal Chemistry , 227 :113973 , 2021
Abstract : On the basis of our previous work, a novel series of (4-(1,2,4-oxadiazol-5-yl)phenyl)-2-aminoacetamide derivatives were synthesized and evaluated as multifunctional ligands for the treatment of Alzheimer's disease (AD). Biological evaluations indicated that the derivatives can be used as anti-AD drugs that have multifunctional properties, inhibit the activity of butyrylcholinesterase (BuChE), inhibit neuroinflammation, have neuroprotective properties, and inhibit the self-aggregation of Abeta. Compound f9 showed good potency in BuChE inhibition (IC(50): 1.28 +/- 0.18 microM), anti-neuroinflammatory potency (NO, IL-1beta, TNF-alpha; IC(50): 0.67 +/- 0.14, 1.61 +/- 0.21, 4.15 +/- 0.44 microM, respectively), and inhibited of Abeta self-aggregation (51.91 +/- 3.90%). Preliminary anti-inflammatory mechanism studies indicated that the representative compound f9 blocked the activation of the NF-kappaB signaling pathway. Moreover, f9 exhibited 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radical scavenging effect, and an inhibitory effect on the production of intracellular reactive oxygen species (ROS). In the bi-directional transport assay, f9 displayed proper blood-brain barrier (BBB) permeability. In addition, the title compound improved memory and cognitive functions in a mouse model induced by scopolamine. Hence, the compound f9 can be considered as a promising lead compound for further investigation in the treatment of AD.
ESTHER : Liu_2021_Eur.J.Med.Chem_227_113973
PubMedSearch : Liu_2021_Eur.J.Med.Chem_227_113973
PubMedID: 34752955

Title : Genomics-driven discovery of the biosynthetic gene cluster of maduramicin and its overproduction in Actinomadura sp. J1-007 - Liu_2020_J.Ind.Microbiol.Biotechnol_47_275
Author(s) : Liu R , Fang F , An Z , Huang R , Wang Y , Sun X , Fu S , Fu A , Deng Z , Liu T
Ref : J Ind Microbiol Biotechnol , 47 :275 , 2020
Abstract : Maduramicin is the most efficient and possesses the largest market share of all anti-coccidiosis polyether antibiotics (ionophore); however, its biosynthetic gene cluster (BGC) has yet to been identified, and the associated strains have not been genetically engineered. Herein, we performed whole-genome sequencing of a maduramicin-producing industrial strain of Actinomadura sp. J1-007 and identified its BGC. Additionally, we analyzed the identified BGCs in silico to predict the biosynthetic pathway of maduramicin. We then developed a conjugation method for the non-spore-forming Actinomadura sp. J1-007, consisting of a site-specific integration method for gene overexpression. The maduramicin titer increased by 30% to 7.16 g/L in shake-flask fermentation following overexpression of type II thioesterase MadTE that is the highest titer at present. Our findings provide insights into the biosynthetic mechanism of polyethers and provide a platform for the metabolic engineering of maduramicin-producing microorganisms for overproduction and development of maduramicin analogs in the future.
ESTHER : Liu_2020_J.Ind.Microbiol.Biotechnol_47_275
PubMedSearch : Liu_2020_J.Ind.Microbiol.Biotechnol_47_275
PubMedID: 31853778
Gene_locus related to this paper: 9actn-a0a6i4pr03

Title : Enantioselective toxicity and oxidative stress effects of acetochlor on earthworms (Eisenia fetida) by mediating the signaling pathway - Liu_2020_Sci.Total.Environ__142630
Author(s) : Liu Y , Fang K , Zhang X , Liu T , Wang X
Ref : Sci Total Environ , :142630 , 2020
Abstract : Acetochlor (ACT) as a widely used chiral chloroacetamide herbicide is appropriate to evaluate the potential toxicity in soil ecosystems at enantiomeric level. The acute and subchronic toxicities of R-acetochlor (R-ACT) and S-acetochlor (S-ACT) on earthworms (Eisenia fetida) were investigated in the present study. Residual analyses showed that S-ACT degraded faster than R-ACT in artificial soil with half-lives of 16.5 and 21.7 d, respectively. Additionally, significant enantioselective acute toxicity in earthworms from between S-ACT and R-ACT (p < 0.05) was observed, and the acute toxicity of R-ACT were 1.9 and 1.5 times higher than those of S-ACT in the filter paper test and artificial soil test. The hydroxyl radical (OH(-)) content, superoxide dismutase (SOD) and antioxidant enzyme catalase (CAT) activities, and cytochrome P450 content in earthworms significantly increased under the influence of ACT enantiomers; however, the acetylcholinesterase (AchE) activity was significantly inhibited after exposure to the two enantiomers. Moreover, lipid peroxidation and DNA damage were induced by ACT enantiomers. The results of transcriptome sequencing indicated that R-ACT induced a stronger oxidative stress effect than S-ACT in earthworms by mediating signaling pathways, which may be the primary reason for the enantioselective toxicity between S-ACT and R-ACT. Overall, the results demonstrated that R-ACT has a higher risk than S-ACT in the soil environment, which is important for understanding the enantioselective behavior of chloroacetamide pesticides.
ESTHER : Liu_2020_Sci.Total.Environ__142630
PubMedSearch : Liu_2020_Sci.Total.Environ__142630
PubMedID: 33069465

Title : Biodegradation of bis(2-hydroxyethyl) terephthalate by a newly isolated Enterobacter sp. HY1 and characterization of its esterase properties - Qiu_2020_J.Basic.Microbiol_60_699
Author(s) : Qiu L , Yin X , Liu T , Zhang H , Chen G , Wu S
Ref : J Basic Microbiol , 60 :699 , 2020
Abstract : Bis(2-hydroxyethyl) terephthalate (BHET) is an important compound produced from poly(ethylene terephthalate) (PET) cleavage. It was selected as the representative substance for the study of PET degradation. A bacterial strain HY1 that could degrade BHET was isolated and identified as Enterobacter sp. The optimal temperature and pH for BHET biodegradation were determined to be 30 degreesC and 8.0, respectively. The half-life of degradation was 70.20h at an initial BHET concentration of 1,000mg/L. The results of metabolites' analysis by liquid chromatograph-mass spectrometer revealed that BHET was first converted to mono-(2-hydroxyethyl) terephthalate (MHET) and then to terephthalic acid. Furthermore, an esterase-encoding gene, estB, was cloned from strain HY1, and the expressed enzyme EstB was characterized. The esterase has a molecular mass of approximately 25.13kDa, with an isoelectric point of 4.68. Its optimal pH and temperature were pH 8.0 and 40 degreesC, respectively. The analysis of the enzymatic products showed that EstB could hydrolyze one ester bond of BHET to MHET. To the best of authors' knowledge, this is the first report on the biodegradation characteristics of BHET by a member of the Enterobacter genus.
ESTHER : Qiu_2020_J.Basic.Microbiol_60_699
PubMedSearch : Qiu_2020_J.Basic.Microbiol_60_699
PubMedID: 32510669

Title : Inhibition of soluble epoxide hydrolase attenuates renal tubular mitochondrial dysfunction and ER stress by restoring autophagic flux in diabetic nephropathy - Jiang_2020_Cell.Death.Dis_11_385
Author(s) : Jiang XS , Xiang XY , Chen XM , He JL , Liu T , Gan H , Du XG
Ref : Cell Death Dis , 11 :385 , 2020
Abstract : Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD), and renal tubular cell dysfunction contributes to the pathogenesis of DN. Soluble epoxide hydrolase (sEH) is an enzyme that can hydrolyze epoxyeicosatrienoic acids (EETs) and other epoxy fatty acids (EpFAs) into the less biologically active metabolites. Inhibition of sEH has multiple beneficial effects on renal function, however, the exact role of sEH in hyperglycemia-induced dysfunction of tubular cells is still not fully elucidated. In the present study, we showed that human proximal tubular epithelial (HK-2) cells revealed an upregulation of sEH expression accompanied by the impairment of autophagic flux, mitochondrial dysfunction, ubiquitinated protein accumulation and enhanced endoplasmic reticulum (ER) stress after high glucose (HG) treatment. Furthermore, dysfunctional mitochondria accumulated in the cytoplasm, which resulted in excessive reactive oxygen species (ROS) generation, Bax translocation, cytochrome c release, and apoptosis. However, t-AUCB, an inhibitor of sEH, partially reversed these negative outcomes. Moreover, we also observed increased sEH expression, impaired autophagy flux, mitochondrial dysfunction and enhanced ER stress in the renal proximal tubular cells of db/db diabetic mice. Notably, inhibition of sEH by treatment with t-AUCB attenuated renal injury and partially restored autophagic flux, improved mitochondrial function, and reduced ROS generation and ER stress in the kidneys of db/db mice. Taken together, these results suggest that inhibition of sEH by t-AUCB plays a protective role in hyperglycemia-induced proximal tubular injury and that the potential mechanism of t-AUCB-mediated protective autophagy is involved in modulating mitochondrial function and ER stress. Thus, we provide new evidence linking sEH to the autophagic response during proximal tubular injury in the pathogenesis of DN and suggest that inhibition of sEH can be considered a potential therapeutic strategy for the amelioration of DN.
ESTHER : Jiang_2020_Cell.Death.Dis_11_385
PubMedSearch : Jiang_2020_Cell.Death.Dis_11_385
PubMedID: 32439839

Title : Clinical characteristics and treatment of mixed-pesticide poisoning in a patient: reflections on a particular case - Tao_2020_J.Int.Med.Res_48_300060520977392
Author(s) : Tao Y , Liu T , Han J , Jian X , Kan B
Ref : J Internal Medicine Res , 48 :300060520977392 , 2020
Abstract : Patients who commit suicide often deliberately hide their medical history. Given that taking pesticides is one of the most common methods of suicide, other forms of poisoning may be neglected in clinical practice. We report here a case of mixed-pesticide poisoning. The patient was poisoned by oral administration of a coumarin rodenticide in combination with an intramuscular injection of organophosphorus (OP) pesticide. The patient was treated with vitamin K1, cholinesterase reactivators, atropine, ventilator-assisted ventilation, and bedside debridement. Her condition gradually stabilized and she eventually recovered and was discharged. Assessment of the causes of delayed diagnosis and treatment suggests that we need to improve early detection and treatment of acute poisoning. It is especially important to ask about the patient's medical history, conduct a careful physical examination, and track the clinical symptoms and differential diagnosis of common poisoning. In addition to the three common routes of poisoning-oral, inhalation, and cutaneous mucosal contact-intramuscular injection of OP can also lead to severe poisoning, which manifests as respiratory failure.
ESTHER : Tao_2020_J.Int.Med.Res_48_300060520977392
PubMedSearch : Tao_2020_J.Int.Med.Res_48_300060520977392
PubMedID: 33356707

Title : Biological evaluation of 7-O-amide hesperetin derivatives as multitarget-directed ligands for the treatment of Alzheimer's disease - Wu_2020_Chem.Biol.Interact_334_109350
Author(s) : Wu M , Zhu X , Zhang Y , Wang M , Liu T , Han J , Li J , Li Z
Ref : Chemico-Biological Interactions , 334 :109350 , 2020
Abstract : A series of 7-O-amide hesperetin derivatives were subjected to multi-target biological evaluation of anti-Alzheimer's disease. Most of the compounds showed good in vitro inhibitory activity against cholinesterase, of which compound 7c (7-O-(4-(morpholinoethyl)-acetamide) hesperetin) was the most effective anti-eqBuChE derivative (IC(50) = 0.28 +/- 0.05 M) and exerted neuroprotective effects. Further biological evaluation found that compounds 4d, 4e and 7c showed strong antioxidant, anti-Abeta self-aggregation and anti-neuroinflammatory activities. Compound 7c could inhibit the expression of iNOS and COX-2 proteins and prevent LPS-induced inflammatory response in BV2 cells. In addition, compound 7c could chelate biometal ions such as Cu(2+) and Zn(2+). In the vivo study, the MWM test confirmed that compound 7c could improve the cognitive impairment caused by scopolamine. In summary, the above studies have shown that the optimized compound 7c has great development potential as MTDL for the treatment of AD.
ESTHER : Wu_2020_Chem.Biol.Interact_334_109350
PubMedSearch : Wu_2020_Chem.Biol.Interact_334_109350
PubMedID: 33307048

Title : Synthesis and biological evaluation of 3-(4-aminophenyl)-coumarin derivatives as potential anti-Alzheimer's disease agents - Hu_2019_J.Enzyme.Inhib.Med.Chem_34_1083
Author(s) : Hu YH , Yang J , Zhang Y , Liu KC , Liu T , Sun J , Wang XJ
Ref : J Enzyme Inhib Med Chem , 34 :1083 , 2019
Abstract : The work is focused on the design of drugs that prevent and treat Alzheimer's disease (AD) and its complications. A series of 3-(4-aminophenyl)-coumarin derivatives designed, synthesised, fully characterised and evaluated in vitro/vivo. The biological assay experiments showed that some compounds displayed a clearly selective inhibition for acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Among all compounds, compound 4m exhibited the highest AChE inhibition with an IC50 value of 0.091 +/- 0.011 microM and compound 4k exhibited the highest BuChE inhibition with an IC50 value of 0.559 +/- 0.017 microM. A zebrafish behaviour analyser (Zebrobox) was used to determine the behavioural effects of the active compound on the movement distance of the aluminium chloride-induced zebrafish. Compound 4m offered a potential drug design concept for the development of therapeutic or preventive agents for AD and its complications.
ESTHER : Hu_2019_J.Enzyme.Inhib.Med.Chem_34_1083
PubMedSearch : Hu_2019_J.Enzyme.Inhib.Med.Chem_34_1083
PubMedID: 31117844

Title : Accumulation, biodegradation and toxicological effects of N-ethyl perfluorooctane sulfonamidoethanol on the earthworms Eisenia fetida exposed to quartz sands - Zhao_2019_Ecotoxicol.Environ.Saf_181_138
Author(s) : Zhao S , Liu T , Wang B , Fu J , Liang T , Zhong Z , Zhan J , Liu L
Ref : Ecotoxicology & Environmental Safety , 181 :138 , 2019
Abstract : While N-ethyl perfluorooctane sulfonamidoethanol (EtFOSE) is a precursor of perfluorooctane sulfonate (PFOS), its bioaccumulation, transformation and toxicological effects in earthworms (Eisenia fetida) exposed to quartz sands are poorly understood. The present study showed that except for parent EtFOSE, N-ethylperfluorooctane sulfonamide acetate (EtFOSAA), N-ethyl perfluorooctane sulfonamide (EtFOSA), perfluorooctane sulfonamide acetate (FOSAA), perfluorooctane sulfonamide (FOSA) and PFOS were detected in earthworms, with EtFOSAA as the primary biotransformation product. The biota-to-sand accumulation factor (BSAF) and uptake rate coefficient (ku) of EtFOSE were 5.7 and 0.542/d, respectively. The elimination rate constants (ke) decreased in the order EtFOSA (0.167/d) approximately FOSAA (0.147/d)>FOSA (0.119/d) approximately EtFOSAA (0.117/d)>EtFOSE (0.095/d)>PFOS (0.069/d). No significant effects were observed in malondialdehyde (MDA) contents and acetylcholinesterase (AChE) activities between EtFOSE treatments and controls. EtFOSE could cause significant accumulation of reactive oxygen species (ROS) in earthworms. Peroxidase (POD), superoxide dismutase (SOD) and catalase (CAT) were significantly activated by 41.4-74.3%, 37.2-44.4% and 32.4-52.3% from day 4-10, respectively, while 8-Hydroxy-2-deoxyguanosine (8-OHdG) levels were elevated by 47.7-70.3% from day 8-10, demonstrating that EtFOSE induced oxidative stress and oxidative DNA damage in earthworms. Significant increase of glutathione-S-transferase (GST) with 41.6-62.8% activation (8-10d) gave indirect evidence on the conjugation of EtFOSE or its corresponding metabolites during phase II of detoxication. This study provides important information on the fate and potential risks of EtFOSE to terrestrial invertebrates.
ESTHER : Zhao_2019_Ecotoxicol.Environ.Saf_181_138
PubMedSearch : Zhao_2019_Ecotoxicol.Environ.Saf_181_138
PubMedID: 31176248

Title : Copper exposure enhances Spodoptera litura larval tolerance to beta-cypermethrin - Lu_2019_Pestic.Biochem.Physiol_160_127
Author(s) : Lu K , Li W , Cheng Y , Ni H , Chen X , Li Y , Tang B , Sun X , Liu T , Qin N , Chen D , Zeng R , Song Y
Ref : Pestic Biochem Physiol , 160 :127 , 2019
Abstract : Environmental xenobiotics can influence the tolerance of insects to chemical insecticides. Heavy metals are widespread distributed, can be easily bio-accumulated in plants and subsequently within phytophagous insects via the food chains. However, less attention has been paid to the effect of heavy metal exposure on their insecticide tolerance. In this study, pre-exposure of copper (Cu, 25-100mgkg(-1)) significantly enhanced the subsequent tolerance of Spodoptera litura to beta-cypermethrin, a widely used pyrethroid insecticide in crop field. Cytochrome P450 monooxygenases (CYPs) activities were cross-induced in larvae exposed to Cu and beta-cypermethrin, while the activities of glutathione S-transferase (GST) and carboxylesterase (CarE) were not affected. Application of piperonyl butoxide (PBO), a P450 synergist, effectively impaired the tolerance to beta-cypermethrin in Cu-exposed S. litura larvae with a synergistic ratio of 1.72, indicating that P450s contribute to larval tolerance to beta-cypermethrin induced by Cu exposure. Among the four CYP6AB family genes examined, only larval midgut-specific CYP6AB12 was found to be cross-induced by Cu and beta-cypermethrin. RNA interference (RNAi)-mediated silencing of CYP6AB12 effectively decreased the mRNA levels of the target gene, and significantly reduced the larval tolerance to beta-cypermethrin following exposure to Cu. These results showed that pre-exposure of heavy metal Cu enhanced larval tolerance to beta-cypermethrin in S. litura, possibly through the cross-induction of P450s. Our findings provide new insights on the relationship between heavy metals and chemical insecticides that may benefit both the risk evaluation of heavy metal contamination and development of pest management strategies.
ESTHER : Lu_2019_Pestic.Biochem.Physiol_160_127
PubMedSearch : Lu_2019_Pestic.Biochem.Physiol_160_127
PubMedID: 31519247

Title : Structural Insights into the Dual-Substrate Recognition and Catalytic Mechanisms of a Bifunctional Acetyl Ester-Xyloside Hydrolase from Caldicellulosiruptor lactoaceticus - Cao_2019_ACS.Catal_9_1739
Author(s) : Cao H , Sun L , Huang Y , Liu X , Yang D , Liu T , Jia X , Wen B , Gu T , Wang F , Xin F
Ref : ACS Catal , 9 :1739 , 2019
Abstract : Enzymes are usually characterized by their evolutionarily conserved catalytic domains; however, this work presents the incidental gain-of-function of an enzyme in a loop region by natural evolution of its amino acids. A bifunctional acetyl ester-xyloside hydrolase (CLH10) was heterologously expressed, purified, and characterized. The primary sequence of CLH10 contains the fragments of the conserved sequence of esterase and glycosidase, which distribute in a mixed type. The crystal structure revealed that the primary sequence folded into two independent structural regions to undertake both acetyl esterase and beta-1,4-xylanase hydrolase functions. CLH10 is capable of cleaving both the beta-1,4-xylosidic bond-linked main chain and the ester bond-linked acetylated side chain of xylan, which renders it valuable because it can degrade acetylated xylan within one enzyme. Significantly, the beta-1,4-xylanase activity of CLH10 appears to have been fortuitously obtained because of the variable Asp10 and Glu139 located in its loop region, which suggested that the exposed loop region might act as a potential hot-spot for the design and generation of promising enzyme function in both directed evolution and rational protein design.
ESTHER : Cao_2019_ACS.Catal_9_1739
PubMedSearch : Cao_2019_ACS.Catal_9_1739
Gene_locus related to this paper: 9firm-g2pvg6

Title : Synthesis and biological evaluation of 3-arylcoumarins as potential anti-Alzheimer's disease agents - Yang_2019_J.Enzyme.Inhib.Med.Chem_34_651
Author(s) : Yang J , Zhang P , Hu Y , Liu T , Sun J , Wang X
Ref : J Enzyme Inhib Med Chem , 34 :651 , 2019
Abstract : Alzheimer's disease, a neurodegenerative illness, has the extremely complex pathogenesis. Accumulating evidence indicates there is a close relationship between several enzymes and Alzheimer's disease. Various substituted 3-arylcoumarin derivatives were synthesised, and their in vitro activity, including cholinesterase inhibitory activity, monoamine oxidase inhibitory activity, and antioxidant activity were investigated. Most of the compounds exhibited high activity; therefore 3-arylcoumarin compounds have the potential as drug candidates for the treatment of Alzheimer's disease.
ESTHER : Yang_2019_J.Enzyme.Inhib.Med.Chem_34_651
PubMedSearch : Yang_2019_J.Enzyme.Inhib.Med.Chem_34_651
PubMedID: 30746966

Title : Protoilludane-type sesquiterpenoids from Armillaria sp. by co-culture with the endophytic fungus Epicoccumsp. associated with Gastrodia elata - Li_2019_Bioorg.Chem_95_103503
Author(s) : Li HT , Tang LH , Liu T , Yang RN , Yang YB , Zhou H , Ding ZT
Ref : Bioorg Chem , 95 :103503 , 2019
Abstract : An investigation of a co-culture of the Armillaria sp. and endophytic fungus Epicoccum sp. YUD17002 associated with Gastrodia elata led to the isolation of eight new compounds, including five protoilludane-type sesquiterpenes (1-5) and three aryl esters (6-8), together with six known analogues (9-14). The assignments of their structures were conducted via extensive analyses of the spectroscopic data and comparison of experimental and calculatedelectronic circular dichroism(ECD)data. Notably, these new compounds were not present in the pure culture controls and were only detected in the co-cultures. Compound 4 is the first example of an ent-protoilludane sesquiterpenoid scaffold bearing a five-membered lactone. Compound 6 exhibited moderate in vitro cytotoxic activities against five human cancer cell lines (HL-60, A549, MCF-7, SMMC-7721, and SW480) with IC50 values ranging from 15.80 to 23.03 muM. Moreover, 6 showed weak acetylcholinesterase inhibitory activity (IC50 value of 23.85 muM).
ESTHER : Li_2019_Bioorg.Chem_95_103503
PubMedSearch : Li_2019_Bioorg.Chem_95_103503
PubMedID: 31855825

Title : Activatable Near-Infrared Fluorescent Probe for Dipeptidyl Peptidase IV and Its Bioimaging Applications in Living Cells and Animals - Liu_2018_Anal.Chem_90_3965
Author(s) : Liu T , Ning J , Wang B , Dong B , Li S , Tian X , Yu Z , Peng Y , Wang C , Zhao X , Huo X , Sun C , Cui J , Feng L , Ma X
Ref : Analytical Chemistry , 90 :3965 , 2018
Abstract : Visualization of endogenous disease-associated enzymes is of great clinical significance, as it could allow earlier clinical diagnosis and timely intervention. Herein, we first synthesized and characterized an enzyme-activatable near-infrared fluorescent probe, GP-DM, for determining the activity of dipeptidyl peptidase IV (DPP IV), which is associated with various pathological processes, especially in diabetes and malignant tumors. GP-DM emitted significant turn-on NIR fluorescent signals simultaneously in response to DPP IV, making it favorable for accurately and dynamically monitoring DPP IV activity in vitro and in vivo. GP-DM exhibited excellent specificity and sensitivity in DPP IV imaging, as indicated by its higher catalytic activity than other human serine hydrolases and by its strong anti-interference ability to a complex biological matrix, which was fully characterized in a series of phenotyping reactions and inhibition assays. Encouraged by the advantages mentioned above, we successfully used GP-DM to evaluate endogenous DPP IV activity in various biological samples (plasma and tissue preparations) and living tumor cells and performed real-time in vivo bioimaging of DPP IV in zebrafish and tumor-bearing nude mice. All of the results reflected and highlighted the potential application value of GP-DM in the early detection of pathologies, individual tailoring of drug therapy, and image-guided tumor resection. Furthermore, our results revealed that DPP IV, a key target enzyme, is closely associated with the migration and proliferation of cancer cells and regulating the biological activity of DPP IV may be a useful approach for cancer therapy.
ESTHER : Liu_2018_Anal.Chem_90_3965
PubMedSearch : Liu_2018_Anal.Chem_90_3965
PubMedID: 29493228

Title : Synthesis and activity towards Alzheimer's disease in vitro: Tacrine, phenolic acid and ligustrazine hybrids - Li_2018_Eur.J.Med.Chem_148_238
Author(s) : Li G , Hong G , Li X , Zhang Y , Xu Z , Mao L , Feng X , Liu T
Ref : Eur Journal of Medicinal Chemistry , 148 :238 , 2018
Abstract : A series of novel tacrine-phenolic acid dihybrids and tacrine-phenolic acid-ligustrazine trihybrids were synthesized, characterized and screened as novel potential anti-Alzheimer drug candidates. These compounds showed potent inhibition activity towards cholinesterases (ChEs), among of them, 9i was the most potent one towards acetylcholinesterase (eeAChE, IC50=3.9nM; hAChE, IC50=65.2nM). 9i could also effectively block beta-amyloid (Abeta) self-aggregation with an inhibition ratio of 47% at 20muM. In addition, its strong anti-oxidation activity could protect PC12cells from CoCl2-damage in the experimental condition while no neurotoxicity. Furthermore, its hepatotoxicity was lower than tacrine in vitro and in vivo. Kinetic and molecular modeling studies revealed that 9i worked in a mixed-type way, could interact simultaneously with catalytic active site (CAS) and peripheral anionic site (PAS) of AChE. Therefore, 9i was a promising multifunctional candidate for the treatment of AD.
ESTHER : Li_2018_Eur.J.Med.Chem_148_238
PubMedSearch : Li_2018_Eur.J.Med.Chem_148_238
PubMedID: 29466774

Title : Alogliptin prevents diastolic dysfunction and preserves left ventricular mitochondrial function in diabetic rabbits - Zhang_2018_Cardiovasc.Diabetol_17_160
Author(s) : Zhang X , Zhang Z , Yang Y , Suo Y , Liu R , Qiu J , Zhao Y , Jiang N , Liu C , Tse G , Li G , Liu T
Ref : Cardiovasc Diabetol , 17 :160 , 2018
Abstract : BACKGROUND: There are increasing evidence that left ventricle diastolic dysfunction is the initial functional alteration in the diabetic myocardium. In this study, we hypothesized that alogliptin prevents diastolic dysfunction and preserves left ventricular mitochondrial function and structure in diabetic rabbits. METHODS: A total of 30 rabbits were randomized into control group (CON, n = 10), alloxan-induced diabetic group (DM, n = 10) and alogliptin-treated (12.5 mg/kd/day for 12 weeks) diabetic group (DM-A, n = 10). Echocardiographic and hemodynamic studies were performed in vivo. Mitochondrial morphology, respiratory function, membrane potential and reactive oxygen species (ROS) generation rate of left ventricular tissue were assessed. The serum concentrations of glucagon-like peptide-1, insulin, inflammatory and oxidative stress markers were measured. Protein expression of TGF-beta1, NF-kappaB p65 and mitochondrial biogenesis related proteins were determined by Western blotting. RESULTS: DM rabbits exhibited left ventricular hypertrophy, left atrial dilation, increased E/e' ratio and normal left ventricular ejection fraction. Elevated left ventricular end diastolic pressure combined with decreased maximal decreasing rate of left intraventricular pressure (- dp/dtmax) were observed. Alogliptin alleviated ventricular hypertrophy, interstitial fibrosis and diastolic dysfunction in diabetic rabbits. These changes were associated with decreased mitochondrial ROS production rate, prevented mitochondrial membrane depolarization and improved mitochondrial swelling. It also improved mitochondrial biogenesis by PGC-1alpha/NRF1/Tfam signaling pathway. CONCLUSIONS: The DPP-4 inhibitor alogliptin prevents cardiac diastolic dysfunction by inhibiting ventricular remodeling, explicable by improved mitochondrial function and increased mitochondrial biogenesis.
ESTHER : Zhang_2018_Cardiovasc.Diabetol_17_160
PubMedSearch : Zhang_2018_Cardiovasc.Diabetol_17_160
PubMedID: 30591063

Title : The Herb-Drug Interaction of Clopidogrel and Xuesaitong Dispersible Tablet by Modulation of the Pharmacodynamics and Liver Carboxylesterase 1A Metabolism - Ma_2018_Evid.Based.Complement.Alternat.Med_2018_5651989
Author(s) : Ma S , Dai G , Bi X , Gong M , Miao C , Chen H , Gao L , Zhao W , Liu T , Zhang N
Ref : Evid Based Complement Alternat Med , 2018 :5651989 , 2018
Abstract : Objective: Clopidogrel and Xuesaitong dispersible tablet (XST) have been clinically proven to be effective for treating cardiocerebrovascular disease. The present study was to investigate the herb-drug interaction of Clopidogrel and XST by modulation of the pharmacodynamics and liver Carboxylesterase 1A(CES1A) metabolism. Methods: 30 male SD rats were randomly divided into a control group (equal volumes of saline, 6 rats for mRNA analysis), a clopidogrel group (clopidogrel with dose 30 mg/kg), and a combination group (clopidogrel and XST, with dose 30 and 50 mg/kg respectively, each group continuous administration once daily for 30 days). The clopidogrel and combination group comprised 12 rats, with 6 designated for mRNA analysis and 6 for the pharmacokinetic study. The 2-bromo-3'-methoxyacetophenone- (MPB-) derivatized clopidogrel active thiol metabolite (CAMD) was measured by UHPLC-MS/MS for pharmacokinetics (n=6). The expression of CES1A mRNA was examined with real-time RT-PCR (n=6). Molecular simulation was used to investigate the inhibition effect of XST on the CES1A protein. The CAMD pharmacodynamics and CES1A metabolism were investigated to evaluated the herb-drug interaction. Results: Clopidogrel and XST coadministration appreciably increased the Cmax, AUC, and MRT of CAMD. However, the expression of CES1A mRNA was decreased accordingly. It also indicated that the bioactive components in XST had good interaction with the CES1A metabolism target by molecular simulation. The animal study indicated that clopidogrel and XST coadministration produced significant herb-drug interactions at active CAMD pharmacokinetic and CES1A metabolic enzyme aspect. Conclusion: 30-days dose of coadministration altered hepatic CES1A protein and resulted in reduced plasma levels of active CAMD. both the decreased CES1A mRNA expression and the inhibition on the protein were due to the combination of XST, which accordingly upregulated the pharmacokinetics of plasma active CAMD.
ESTHER : Ma_2018_Evid.Based.Complement.Alternat.Med_2018_5651989
PubMedSearch : Ma_2018_Evid.Based.Complement.Alternat.Med_2018_5651989
PubMedID: 30498515

Title : Effect of elevated CO2 concentration and temperature on antioxidant capabilities of multiple generations of Bemisia tabaci MEAM1 (Hemiptera: Aleyrodidae) - Li_2017_J.Insect.Physiol_103_91
Author(s) : Li N , Li Y , Zhang S , Fan Y , Liu T
Ref : J Insect Physiol , 103 :91 , 2017
Abstract : A rise in atmospheric carbon dioxide concentration ([CO2]) and a warming climate are two of the most conspicuous characteristics of global climate change in this century. However, studies addressing the combined impact of rising [CO2] and temperature on herbivore insect physiology are still limited. In this study we investigated the combined effects of elevated [CO2] and temperature on major antioxidative enzymes, including superoxide dismutase (SOD), catalase (CAT), peroxidases (POD) and detoxification enzymes of glutathione-S-transferases (GST) and acetylcholinesterase (AChE) in three consecutive generations of Bemisia tabaci Middle East-Asia Minor 1 (MEAM1, commonly known as B biotype) adults. The results indicated that the antioxidant capabilities of B. tabaci differed significantly during different treatments across different generations. Elevated [CO2] markedly increased POD, GST and AChE activities in the first generation, and SOD, CAT and GST activities in the second generation, but reduced POD activity in the third generation at ambient temperature. Under elevated temperature, elevated [CO2] significantly increased GST and AChE activities in the first generation and CAT activity in the third generation, reduced SOD activity in the third generation and reduced AChE activity in the second generation. [CO2], temperature and insect generation interacted to affect the antioxidant capabilities of B. tabaci. These results suggest both that changes in antioxidant capabilities vary in response to either [CO2] or temperature, or a combination of both, leading to oxidative stress and also that antioxidant enzymes play important roles in reducing oxidative damage in B. tabaci. Changes in the exposure of antioxidant compounds over the course of three generations suggest that acclimation and/or adaptation to elevated [CO2] and temperature may have occurred. This study represents the first comprehensive report on the antioxidant defense mechanism in successive multiple generations of an insect species under combined elevated [CO2] and temperature levels. These results offer further insights into the effects of elevated [CO2] and temperature on different generations of insect herbivores and provide more detailed information for population predictions.
ESTHER : Li_2017_J.Insect.Physiol_103_91
PubMedSearch : Li_2017_J.Insect.Physiol_103_91
PubMedID: 29056516

Title : Association between Lp-PLA2 and coronary heart disease in Chinese patients - Yang_2017_J.Int.Med.Res_45_159
Author(s) : Yang L , Liu Y , Wang S , Liu T , Cong H
Ref : J Internal Medicine Res , 45 :159 , 2017
Abstract : Objective To evaluate the association between plasma lipoprotein-associated phospholipase A2 (Lp-PLA2; known to release inflammatory mediators that promote atherosclerosis) and coronary heart disease (CHD) in Chinese patients. Methods This observational, cross-sectional study included a patient cohort who were assessed by coronary angiography and divided into patients with coronary heart disease and patients with normal coronary angiography (controls). Data for several biochemical indicators were collected. Plasma Lp-PLA2 concentrations were measured by enzyme-linked immunosorbent assay. Univariate and multivariate logistic regression were used to analyse the association between Lp-PLA2 concentration and CHD. Results A total of 531 patients were included, comprising 391 with CHD and 140 with normal coronary angiography (controls). Plasma Lp-PLA2 concentration was significantly higher in patients with CHD versus controls (median, 251 microg/l versus 219 microg/l, respectively), and particularly among patients with acute myocardial infarction and stable angina pectoris (249 microg/l and 266 microg/l, respectively). Multivariate analysis showed that Lp-PLA2 <= 292 microg/l (upper quartile of the whole cohort) was independently associated with CHD (odds ratio 2.814, 95% confidence interval 1.519, 5.214). Conclusion Plasma Lp-PLA2 concentration was independently associated with CHD in Chinese patients.
ESTHER : Yang_2017_J.Int.Med.Res_45_159
PubMedSearch : Yang_2017_J.Int.Med.Res_45_159
PubMedID: 28222638
Gene_locus related to this paper: human-PLA2G7

Title : Soluble Epoxide Hydrolase Inhibitor Suppresses the Expression of Triggering Receptor Expressed on Myeloid Cells-1 by Inhibiting NF-kB Activation in Murine Macrophage - Dong_2017_Inflammation_40_13
Author(s) : Dong L , Zhou Y , Zhu ZQ , Liu T , Duan JX , Zhang J , Li P , Hammcok BD , Guan CX
Ref : Inflammation , 40 :13 , 2017
Abstract : Triggering receptors expressed on myeloid cell-1 (TREM-1) is a superimmunoglobulin receptor expressed on myeloid cells. TREM-1 amplifies the inflammatory response. Epoxyeicosatrienoic acids (EETs), the metabolites of arachidonic acid derived from the cytochrome P450 enzyme, have anti-inflammatory properties. However, the effects of EETs on TREM-1 expression under inflammatory stimulation remain unclear. Therefore, inhibition of soluble epoxide hydrolase (sEH) with a highly selective inhibitor [1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea, TPPU] was used to stabilize EETs. LPS was intratracheally injected into mice to induce pulmonary inflammation, after TPPU treatment for 3 h. Histological examination showed TPPU treatment-alleviated LPS-induced pulmonary inflammation. TPPU decreased TREM-1 expression, but not DAP12 or MyD88 expression. Murine peritoneal macrophages were challenged with LPS in vitro. We found that TPPU reduced LPS-induced TREM-1 expression in a dose-dependent manner, but not DAP12 or MyD88 expression. TPPU also decreased downstream signal from TREM-1, reducing pro-inflammatory cytokine TNF-alpha and IL-1beta mRNA expression. Furthermore, TPPU treatment inhibited IkB degradation in vivo and in vitro. Our results indicate that the inhibition of sEH suppresses LPS-induced TREM-1 expression and inflammation via inhibiting NF-kB activation in murine macrophage.
ESTHER : Dong_2017_Inflammation_40_13
PubMedSearch : Dong_2017_Inflammation_40_13
PubMedID: 27696333

Title : Soluble Epoxide Hydrolase Inhibitor Attenuates Lipopolysaccharide-Induced Acute Lung Injury and Improves Survival in Mice - Zhou_2017_Shock_47_638
Author(s) : Zhou Y , Liu T , Duan JX , Li P , Sun GY , Liu YP , Zhang J , Dong L , Lee KSS , Hammock BD , Jiang JX , Guan CX
Ref : Shock , 47 :638 , 2017
Abstract : Acute lung injury (ALI) is characterized by rapid alveolar injury, vascular leakage, lung inflammation, neutrophil accumulation, and induced cytokines production leading to lung edema. The mortality rate of patients suffering from ALI remains high. Epoxyeicosatrienoic acids (EETs) are cytochrome P450-dependent derivatives of polyunsaturated fatty acid with antihypertensive, profibrinolytic, and anti-inflammatory functions. EETs are rapidly hydrated by soluble epoxide hydrolase (sEH) to their less potent diols. The aim of this study was to investigate the role of sEH inhibitor trifluoromethoxyphenyl propionylpiperidin urea (TPPU) and EETs in lipopolysaccharide (LPS)-induced ALI of mice. Our studies revealed that inhibition of sEH with TPPU attenuated the morphological changes in mice, decreased the neutrophil infiltration to the lung, pro-inflammatory cytokine levels (IL-1beta and TNF-alpha) in serum and bronchoalveolar lavage fluid (BALF), and alveolar capillary leakage (lung wet/dry ratio and total protein concentration in BALF). TPPU improved the survival rate of LPS-induced ALI. In addition, in vitro experiments revealed that both TPPU and EETs (11,12-EET and 14,15-EET) suppressed the expression of IL-1beta and TNF-alpha, and LDH release in RAW264.7 cells. These results indicate that EETs play a role in dampening LPS-induced acute lung inflammation, and suggest that sEH could be a valuable candidate for the treatment of ALI.
ESTHER : Zhou_2017_Shock_47_638
PubMedSearch : Zhou_2017_Shock_47_638
PubMedID: 27753791

Title : Soluble epoxide hydrolase inhibitor 1-trifluoromethoxyphenyl-3- (1-propionylpiperidin-4-yl) urea attenuates bleomycin-induced pulmonary fibrosis in mice - Zhou_2016_Cell.Tissue.Res_363_399
Author(s) : Zhou Y , Sun GY , Liu T , Duan JX , Zhou HF , Lee KS , Hammock BD , Fang X , Jiang JX , Guan CX
Ref : Cell Tissue Research , 363 :399 , 2016
Abstract : Epoxyeicosatrienoic acids (EETs), the metabolites of arachidonic acid derived from the cytochrome P450 (CYP450) epoxygenases, are mainly metabolized by soluble epoxide hydrolase (sEH) to their corresponding diols. EETs but not their diols, have anti-inflammatory properties and inhibition of sEH might provide protective effects against inflammatory fibrosis. We test the effects of a selected sEH inhibitor, 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), on bleomycin-induced pulmonary fibrosis (PF) in mice. A mouse model of PF was established by intratracheal injection of bleomycin and TPPU was administered for 21 days after bleomycin injection. We found TPPU treatment improved the body weight loss and survival rate of bleomycin-stimulated mice. Histological examination showed that TPPU treatment alleviated bleomycin-induced inflammation and maintained the alveolar structure of the pulmonary tissues. TPPU also decreased the bleomycin-induced deposition of collagen and the expression of procollagen I mRNA in lung tissues of mice. TPPU decreased the transforming growth factor-beta1 (TGF-beta1), interleukin-1beta (IL-1beta) and IL-6 levels in the serum of bleomycin-stimulated mice. Furthermore, TPPU inhibited the proliferation and collagen synthesis of mouse fibroblasts and partially reversed TGF-beta1-induced alpha-smooth muscle actin expression. Our results indicate that the inhibition of sEH attenuates bleomycin-induced inflammation and collagen deposition and therefore prevents bleomycin-induced PF in a mouse model.
ESTHER : Zhou_2016_Cell.Tissue.Res_363_399
PubMedSearch : Zhou_2016_Cell.Tissue.Res_363_399
PubMedID: 26310139

Title : Galanthamine, Plicamine, and Secoplicamine Alkaloids from Zephyranthes candida and Their Anti-acetylcholinesterase and Anti-inflammatory Activities - Zhan_2016_J.Nat.Prod_79_760
Author(s) : Zhan G , Zhou J , Liu R , Liu T , Guo G , Wang J , Xiang M , Xue Y , Luo Z , Zhang Y , Yao G
Ref : Journal of Natural Products , 79 :760 , 2016
Abstract : Sixteen new alkaloids belonging to the galanthamine (1-6), plicamine (7-14), and secoplicamine (15 and 16) classes, together with eight known analogues (17-24), were isolated from Zephyranthes candida. The structures of 1-16 were determined by extensive spectroscopic analyses, and the absolute configurations of 1, 2, 7, 8, and 17 were confirmed by single-crystal X-ray diffraction analysis. The orientation of 3-OCH3 in N-methyl-5,6-dihydroplicane (22) was revised. Alkaloids 3, 12-14, and 18-21 exhibited anti-acetylcholinesterase activities with IC50 values ranging from 0.48 to 168.7 muM. Compounds 10-12, 14, and 16 showed in vitro anti-inflammatory activities with IC50 values ranging from 7.50 to 23.55 muM.
ESTHER : Zhan_2016_J.Nat.Prod_79_760
PubMedSearch : Zhan_2016_J.Nat.Prod_79_760
PubMedID: 26913788

Title : Genome-wide identification, classification and expression analysis in fungal-plant interactions of cutinase gene family and functional analysis of a putative ClCUT7 in Curvularia lunata - Liu_2016_Mol.Genet.Genomics_291_1105
Author(s) : Liu T , Hou J , Wang Y , Jin Y , Borth W , Zhao F , Liu Z , Hu J , Zuo Y
Ref : Mol Genet Genomics , 291 :1105 , 2016
Abstract : Cutinase is described as playing various roles in fungal-plant pathogen interactions, such as eliciting host-derived signals, fungal spore attachment and carbon acquisition during saprophytic growth. However, the characteristics of the cutinase genes, their expression in compatible interactions and their roles in pathogenesis have not been reported in Curvularia lunata, an important leaf spot pathogen of maize in China. Therefore, a cutinase gene family analysis could have profound significance. In this study, we identified 13 cutinase genes (ClCUT1 to ClCUT13) in the C. lunata genome. Multiple sequence alignment showed that most fungal cutinase proteins had one highly conserved GYSQG motif and a similar DxVCxG[ST]-[LIVMF](3)-x(3)H motif. Gene structure analyses of the cutinases revealed a complex intron-exon pattern with differences in the position and number of introns and exons. Based on phylogenetic relationship analysis, C. lunata cutinases and 78 known cutinase proteins from other fungi were classified into four groups with subgroups, but the C. lunata cutinases clustered in only three of the four groups. Motif analyses showed that each group of cutinases from C. lunata had a common motif. Real-time PCR indicated that transcript levels of the cutinase genes in a compatible interaction between pathogen and host had varied expression patterns. Interestingly, the transcript levels of ClCUT7 gradually increased during early pathogenesis with the most significant up-regulation at 3 h post-inoculation. When ClCUT7 was deleted, pathogenicity of the mutant decreased on unwounded maize (Zea mays) leaves. On wounded maize leaves, however, the mutant caused symptoms similar to the wild-type strain. Moreover, the ClCUT7 mutant had an approximately 10 % reduction in growth rate when cutin was the sole carbon source. In conclusion, we identified and characterized the cutinase family genes of C. lunata, analyzed their expression patterns in a compatible host-pathogen interaction, and explored the role of ClCUT7 in pathogenicity. This work will increase our understanding of cutinase genes in other fungal-plant pathogens.
ESTHER : Liu_2016_Mol.Genet.Genomics_291_1105
PubMedSearch : Liu_2016_Mol.Genet.Genomics_291_1105
PubMedID: 26767524

Title : Lipoprotein lipase deficiency leads to alpha-synuclein aggregation and ubiquitin C-terminal hydrolase L1 reduction - Yang_2015_Neurosci_290_1
Author(s) : Yang H , Zhou T , Wang H , Liu T , Ueda K , Zhan R , Zhao L , Tong Y , Tian X , Zhang T , Jin Y , Han X , Li Z , Zhao Y , Guo X , Xiao W , Fan D , Liu G , Chui D
Ref : Neuroscience , 290 :1 , 2015
Abstract : We have previously reported that presynaptic dysfunction and cognitive decline have been found in lipoprotein lipase (LPL) deficient mice, but the mechanism remains to be elucidated. Accumulating evidence supported that alpha-synuclein (alpha-syn) and ubiquitin C-terminal hydrolase L1 (UCHL1) are required for normal synaptic and cognitive function. In this study, we found that alpha-syn aggregated and the expression of UCHL1 decreased in the brain of LPL deficient mice. Reduction of UCHL1 was resulted from nuclear retention of DNA cytosine-5-methyltransferase 1 in LPL knockout mice. Reverse changes were found in cultured cells overexpressing LPL. Furthermore, deficiency of LPL increased ubiquitination of alpha-syn. These results indicated that aggregation of alpha-syn and reduction of UCHL1 expression in LPL-deficient mice may affect synaptic function.
ESTHER : Yang_2015_Neurosci_290_1
PubMedSearch : Yang_2015_Neurosci_290_1
PubMedID: 25595992

Title : Bioaccumulation of isocarbophos enantiomers from laboratory-contaminated aquatic environment by tubificid worms - Liu_2015_Chemosphere_124_77
Author(s) : Liu T , Diao J , Di S , Zhou Z
Ref : Chemosphere , 124 :77 , 2015
Abstract : The benthic fauna is of great importance to assess the environmental fate of contaminations in aquatic ecosystem. In this study, tubificids were exposed to both laboratory-contaminated aqueous phases and spiked sediment to study the bioaccumulation of isocarbophos (ICP). Two types of spiked sediments were used in the spiked sediment experiment. During the exposure period, an enantioselective bioaccumulation was found in spiked water treatment, with concentrations of the (-)-ICP higher than that of the (+)-ICP, but no enantioselectivity was detected in the spiked sediment treatments. However, different bioaccumulation patterns were observed in the two spiked sediment treatments. Results showed that for spiked forest field sediment (FF sediment) incubation, bioaccumulation was governed by the concentrations in soil. Whereas ICP was bioaccumulated dominantly from overlying water in spiked Chagan Lake sediment (CG sediment) test. The dissipation rates were proved different in the two sediments and ICP dissipated much faster in CG sediment than that in FF sediment. Significant difference in ICP's half-life was also observed between worm-present and worm-free treatments in FF sediment. The detections of concentrations in overlying water indicated that much more ICP diffused to aquatic phase with the present of tubificids.
ESTHER : Liu_2015_Chemosphere_124_77
PubMedSearch : Liu_2015_Chemosphere_124_77
PubMedID: 25475969

Title : A novel oriented immobilized lipase on magnetic nanoparticles in reverse micelles system and its application in the enrichment of polyunsaturated fatty acids - Liu_2013_Bioresour.Technol_132C_99
Author(s) : Liu T , Zhao Y , Wang X , Li X , Yan Y
Ref : Bioresour Technol , 132C :99 , 2013
Abstract : A novel oriented immobilized lipase was derived from Yarrowia lipolytica lipase LIP2 covalently immobilized on functionalized Fe(3)O(4) magnetic nanoparticles (MNPs) in reverse micelles system (RMS). The activity recovery reached 382% compared with 29% in aqueous phase, and further ran up to 1425% under optimum conditions. (3-Aminopropyl) triethoxysilane (APTES) coated Fe(3)O(4) nanoparticles were characterized by Fourier transform infrared (FT-IR) and X-ray diffraction (XRD). A significant alteration in the secondary structure of the lipase in RMS with a 15.5% increase of alpha-helix content and a 12.5% decrease of beta-sheet content was detected by circular dichroism (CD). The immobilized lipase was employed to enrich polyunsaturated fatty acids in fish oil, a 90% increase of DHA content was obtained after 12h, and after 20 cycles of successive usage, it still remained over 80% of relative hydrolysis degree, which shows a good recyclability.
ESTHER : Liu_2013_Bioresour.Technol_132C_99
PubMedSearch : Liu_2013_Bioresour.Technol_132C_99
PubMedID: 23395761

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

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

Title : Genome Sequences of 28 Bordetella pertussis U.S. Outbreak Strains Dating from 2010 to 2012 - Harvill_2013_Genome.Announc_1_e01075
Author(s) : Harvill ET , Goodfield LL , Ivanov Y , Meyer JA , Newth C , Cassiday P , Tondella ML , Liao P , Zimmerman J , Meert K , Wessel D , Berger J , Dean JM , Holubkov R , Burr J , Liu T , Brinkac L , Kim M , Losada L
Ref : Genome Announc , 1 : , 2013
Abstract : Despite the availability of highly effective vaccines, Bordetella pertussis incidence has been rapidly rising in highly vaccinated populations. Recent outbreaks have received media attention, feeding concerns about the emergence of dangerous new strains with increased virulence or that escape vaccine-induced immunity. To accelerate the study of this reemerging pathogen, we sequenced the genomes of 28 B. pertussis strains isolated during outbreaks from 2010 through 2012, making both strains and sequence data available to the scientific community.
ESTHER : Harvill_2013_Genome.Announc_1_e01075
PubMedSearch : Harvill_2013_Genome.Announc_1_e01075
PubMedID: 24356839

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 : Constitutive expression of Yarrowia lipolytica lipase LIP2 in Pichia pastoris using GAP as promoter - Wang_2012_Appl.Biochem.Biotechnol_166_1355
Author(s) : Wang X , Sun Y , Ke F , Zhao H , Liu T , Xu L , Liu Y , Yan Y
Ref : Appl Biochem Biotechnol , 166 :1355 , 2012
Abstract : A gene encoding Yarrowia lipolytica lipase LIP2 (YlLIP2) was cloned into a constitutive expression vector pGAPZalphaA and electrotransformed into the Pichia pastoris X-33 strain. The high-yield clones obtained by high copy and enzyme activity screening were chosen as the host strains for shaking flask and fermentor culture. The results showed that glucose was the optimum carbon source for YlLIP2 production, and the maximum hydrolytic activity of recombinant YlLIP2 reached 1,315 U/ml under the flask culture at 28 degrees C, pH 7.0, for 48 h. The fed-batch fermentation was carried out in 3- and 10-l bioreactors by continuously feeding glucose into the growing medium for achieving high cell density and YlLIP2 yields. The maximum hydrolytic activity of YlLIP2 and cell density obtained in the 3-l bioreactor were 10,300 U/ml and 116 g dry cell weight (DCW)/l, respectively. The peak hydrolytic activity of YlLIP2 and cell density were further improved in the 10-l fermentor where the values respectively attained were 13,500 U/ml and 120 g DCW/l. The total protein concentration in the supernatant reached 3.3 g/l and the cell viability remained approximately 99% after 80 h of culture. Furthermore, the recombinant YlLIP2 produced in P. pastoris pGAP and pAOX1 systems have similar content of sugar (about 12%) and biochemical characteristics. The above results suggest that the GAP promoter-derived expression system of P. pastoris is effective for the expression of YlLIP2 by high cell density culture and is probably an alternative to the conventional AOX1 promoter expression system in large-scale production of industrial lipases.
ESTHER : Wang_2012_Appl.Biochem.Biotechnol_166_1355
PubMedSearch : Wang_2012_Appl.Biochem.Biotechnol_166_1355
PubMedID: 22246727

Title : Recent advances in non-peptidomimetic dipeptidyl peptidase 4 inhibitors: medicinal chemistry and preclinical aspects - Liu_2012_Curr.Med.Chem_19_3982
Author(s) : Liu Y , Hu Y , Liu T
Ref : Curr Med Chem , 19 :3982 , 2012
Abstract : Dipeptidyl peptidase 4 DPP-4 a substrate-specific serine protease has been validated as a promising drug target for the treatment of type 2 diabetes DPP-4 inhibitors significantly lowered blood glucose levels in patients with type 2 diabetes without common body weight gain hypoglycemia and gastrointestinal disturbance side effects Therefore DPP-4 inhibitors attracted more and more attention In particular non-peptidomimetic DPP-4 inhibitors have been a focus of research and development and made great progress in recent years which resulted in the discovery of a wide variety of potent non-peptidomimetic DPP-4 inhibitors Some of them such as sitagliptin alogliptin and linagliptin have already been used as marketed drugs while others have been into clinical trials Based on the core structural features of non-peptidomimetic DPP-4 inhibitors seven types were classified in the article For each type we focused on the description of strategies for design and optimization together with a discussion on concluded structure-activity relationships SAR In addition the contribution of specific substituents to the inhibition of DPP-4 was summarized Selectivity towards the inhibition of DPP-4 over dipeptidyl peptidase 8 DPP-8 and dipeptidyl peptidase 9 DPP-9 was also presented.
ESTHER : Liu_2012_Curr.Med.Chem_19_3982
PubMedSearch : Liu_2012_Curr.Med.Chem_19_3982
PubMedID: 22709010

Title : Repeated polyploidization of Gossypium genomes and the evolution of spinnable cotton fibres - Paterson_2012_Nature_492_423
Author(s) : Paterson AH , Wendel JF , Gundlach H , Guo H , Jenkins J , Jin D , Llewellyn D , Showmaker KC , Shu S , Udall J , Yoo MJ , Byers R , Chen W , Doron-Faigenboim A , Duke MV , Gong L , Grimwood J , Grover C , Grupp K , Hu G , Lee TH , Li J , Lin L , Liu T , Marler BS , Page JT , Roberts AW , Romanel E , Sanders WS , Szadkowski E , Tan X , Tang H , Xu C , Wang J , Wang Z , Zhang D , Zhang L , Ashrafi H , Bedon F , Bowers JE , Brubaker CL , Chee PW , Das S , Gingle AR , Haigler CH , Harker D , Hoffmann LV , Hovav R , Jones DC , Lemke C , Mansoor S , ur Rahman M , Rainville LN , Rambani A , Reddy UK , Rong JK , Saranga Y , Scheffler BE , Scheffler JA , Stelly DM , Triplett BA , Van Deynze A , Vaslin MF , Waghmare VN , Walford SA , Wright RJ , Zaki EA , Zhang T , Dennis ES , Mayer KF , Peterson DG , Rokhsar DS , Wang X , Schmutz J
Ref : Nature , 492 :423 , 2012
Abstract : Polyploidy often confers emergent properties, such as the higher fibre productivity and quality of tetraploid cottons than diploid cottons bred for the same environments. Here we show that an abrupt five- to sixfold ploidy increase approximately 60 million years (Myr) ago, and allopolyploidy reuniting divergent Gossypium genomes approximately 1-2 Myr ago, conferred about 30-36-fold duplication of ancestral angiosperm (flowering plant) genes in elite cottons (Gossypium hirsutum and Gossypium barbadense), genetic complexity equalled only by Brassica among sequenced angiosperms. Nascent fibre evolution, before allopolyploidy, is elucidated by comparison of spinnable-fibred Gossypium herbaceum A and non-spinnable Gossypium longicalyx F genomes to one another and the outgroup D genome of non-spinnable Gossypium raimondii. The sequence of a G. hirsutum A(t)D(t) (in which 't' indicates tetraploid) cultivar reveals many non-reciprocal DNA exchanges between subgenomes that may have contributed to phenotypic innovation and/or other emergent properties such as ecological adaptation by polyploids. Most DNA-level novelty in G. hirsutum recombines alleles from the D-genome progenitor native to its New World habitat and the Old World A-genome progenitor in which spinnable fibre evolved. Coordinated expression changes in proximal groups of functionally distinct genes, including a nuclear mitochondrial DNA block, may account for clusters of cotton-fibre quantitative trait loci affecting diverse traits. Opportunities abound for dissecting emergent properties of other polyploids, particularly angiosperms, by comparison to diploid progenitors and outgroups.
ESTHER : Paterson_2012_Nature_492_423
PubMedSearch : Paterson_2012_Nature_492_423
PubMedID: 23257886
Gene_locus related to this paper: gosra-a0a0d2qg22 , gosra-a0a0d2w3z1 , gosra-a0a0d2uuz7 , gosra-a0a0d2rxs2 , gosra-a0a0d2sdk0 , gosra-a0a0d2tng2 , gosra-a0a0d2twz7 , gosra-a0a0d2vdc5 , gosra-a0a0d2vj24 , gosra-a0a0d2sr31 , goshi-a0a1u8knd1 , goshi-a0a1u8nhw9 , goshi-a0a1u8kis4 , gosra-a0a0d2pul0 , gosra-a0a0d2p3f2 , gosra-a0a0d2ril5 , gosra-a0a0d2s7d5 , gosra-a0a0d2t9b3 , gosra-a0a0d2tw88 , gosra-a0a0d2umz5 , gosra-a0a0d2pzd7 , gosra-a0a0d2scu7 , gosra-a0a0d2vcx6

Title : Genome sequences of wild and domestic bactrian camels - Jirimutu_2012_Nat.Commun_3_1202
Author(s) : Jirimutu , Wang Z , Ding G , Chen G , Sun Y , Sun Z , Zhang H , Wang L , Hasi S , Zhang Y , Li J , Shi Y , Xu Z , He C , Yu S , Li S , Zhang W , Batmunkh M , Ts B , Narenbatu , Unierhu , Bat-Ireedui S , Gao H , Baysgalan B , Li Q , Jia Z , Turigenbayila , Subudenggerile , Narenmanduhu , Wang J , Pan L , Chen Y , Ganerdene Y , Dabxilt , Erdemt , Altansha , Altansukh , Liu T , Cao M , Aruuntsever , Bayart , Hosblig , He F , Zha-ti A , Zheng G , Qiu F , Zhao L , Zhao W , Liu B , Li C , Tang X , Guo C , Liu W , Ming L , Temuulen , Cui A , Li Y , Gao J , Wurentaodi , Niu S , Sun T , Zhai Z , Zhang M , Chen C , Baldan T , Bayaer T , Meng H
Ref : Nat Commun , 3 :1202 , 2012
Abstract : Bactrian camels serve as an important means of transportation in the cold desert regions of China and Mongolia. Here we present a 2.01 Gb draft genome sequence from both a wild and a domestic bactrian camel. We estimate the camel genome to be 2.38 Gb, containing 20,821 protein-coding genes. Our phylogenomics analysis reveals that camels shared common ancestors with other even-toed ungulates about 55-60 million years ago. Rapidly evolving genes in the camel lineage are significantly enriched in metabolic pathways, and these changes may underlie the insulin resistance typically observed in these animals. We estimate the genome-wide heterozygosity rates in both wild and domestic camels to be 1.0 x 10(-3). However, genomic regions with significantly lower heterozygosity are found in the domestic camel, and olfactory receptors are enriched in these regions. Our comparative genomics analyses may also shed light on the genetic basis of the camel's remarkable salt tolerance and unusual immune system.
ESTHER : Jirimutu_2012_Nat.Commun_3_1202
PubMedSearch : Jirimutu_2012_Nat.Commun_3_1202
PubMedID: 23149746
Gene_locus related to this paper: 9ceta-s9yik4 , 9ceta-s9yb99 , 9ceta-s9x0n3 , 9ceta-s9xqa3 , 9ceta-s9xi02 , camfr-s9wiw9 , camfr-s9x3r3 , camfr-s9xce1 , camfr-s9xcr2 , camfr-s9yuz0 , camfr-s9xlc8 , camfr-s9w5f6 , camfr-s9xmm4

Title : Therapeutic effects of human amniotic epithelial cell transplantation on double-transgenic mice co-expressing APPswe and PS1DeltaE9-deleted genes - Xue_2012_Sci.China.Life.Sci_55_132
Author(s) : Xue S , Chen C , Dong W , Hui G , Liu T , Guo L
Ref : Sci China Life Sciences , 55 :132 , 2012
Abstract : Human amniotic epithelial cells (HAECs), which exhibit characteristics of embryonic and pluripotent stem cells, could be utilized for cell therapy without legal or ethical problems. Double-transgenic (TG) mice (n=20) and wild-type (WT) mice (n=20) were randomly assigned to two groups, respectively. The transplantation group was treated with HAECs and the control group with PBS. A six-radial arm water maze was used to assess spatial memory. Immunofluorescence was utilized to track HAEC survival. Immunohistochemistry was used to determine octamer-binding protein 4 (oct-4) and nanog expression in the HAECs. High-performance liquid chromatography (HPLC) was used to measure acetylcholine levels in the hippocampus. The density of cholinergic neurons in the basal forebrain and nerve fibers in the hippocampus was measured following acetylcholinesterase staining. Results showed that transplanted HAECs survived for at least eight weeks and migrated to the third ventricle without immune rejection. Graft HAECs also expressed the specific stem cell markers oct-4 and nanog. Compared with the control group, HAEC transplantation significantly ameliorated spatial memory deficits in TG mice, as well as increased acetylcholine levels and the number of hippocampal cholinergic neurites. Intracerebroventricular HAEC transplantation improved spatial memory in double-TG mice, and results suggested that increased acetylcholine levels in the hippocampus, released by surviving cholinergic neurites, were responsible for this improvement.
ESTHER : Xue_2012_Sci.China.Life.Sci_55_132
PubMedSearch : Xue_2012_Sci.China.Life.Sci_55_132
PubMedID: 22415684

Title : Implication of lipid metabolism disturbance and Alzheimer's disease: focus on the lipoprotein lipase plays an important role in learning and memory function PMCID: PMC3287633 -
Author(s) : Chui D , Zhou T , Zhou L , Yang H , Liu X , Liu T , Yu J , Liu Y , Wu XF , Zhang H , Fan D
Ref : Mol Neurodegener , 7 Suppl 1 :O9 , 2012

Title : Structure and dynamics of the M3 muscarinic acetylcholine receptor - Kruse_2012_Nature_482_552
Author(s) : Kruse AC , Hu J , Pan AC , Arlow DH , Rosenbaum DM , Rosemond E , Green HF , Liu T , Chae PS , Dror RO , Shaw DE , Weis WI , Wess J , Kobilka BK
Ref : Nature , 482 :552 , 2012
Abstract : Acetylcholine, the first neurotransmitter to be identified, exerts many of its physiological actions via activation of a family of G-protein-coupled receptors (GPCRs) known as muscarinic acetylcholine receptors (mAChRs). Although the five mAChR subtypes (M1-M5) share a high degree of sequence homology, they show pronounced differences in G-protein coupling preference and the physiological responses they mediate. Unfortunately, despite decades of effort, no therapeutic agents endowed with clear mAChR subtype selectivity have been developed to exploit these differences. We describe here the structure of the G(q/11)-coupled M3 mAChR ('M3 receptor', from rat) bound to the bronchodilator drug tiotropium and identify the binding mode for this clinically important drug. This structure, together with that of the G(i/o)-coupled M2 receptor, offers possibilities for the design of mAChR subtype-selective ligands. Importantly, the M3 receptor structure allows a structural comparison between two members of a mammalian GPCR subfamily displaying different G-protein coupling selectivities. Furthermore, molecular dynamics simulations suggest that tiotropium binds transiently to an allosteric site en route to the binding pocket of both receptors. These simulations offer a structural view of an allosteric binding mode for an orthosteric GPCR ligand and provide additional opportunities for the design of ligands with different affinities or binding kinetics for different mAChR subtypes. Our findings not only offer insights into the structure and function of one of the most important GPCR families, but may also facilitate the design of improved therapeutics targeting these critical receptors.
ESTHER : Kruse_2012_Nature_482_552
PubMedSearch : Kruse_2012_Nature_482_552
PubMedID: 22358844

Title : Surrogate based accurate quantification of endogenous acetylcholine in murine brain by hydrophilic interaction liquid chromatography-tandem mass spectrometry - Peng_2011_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_879_3927
Author(s) : Peng L , Jiang T , Rong Z , Liu T , Wang H , Shao B , Ma J , Yang L , Kang L , Shen Y , Li H , Qi H , Chen H
Ref : Journal of Chromatography B Analyt Technol Biomed Life Sciences , 879 :3927 , 2011
Abstract : Cholinergic dysfunction is known as a hallmark feature of Alzheimer's disease (AD). Measurement of endogenous acetylcholine (ACh) in specific brain regions is important in understanding the pathology of AD and in designing and evaluating novel cholinomimetic agents for the treatment of AD. Since ACh is an endogenous neurotransmitter, there is no real blank matrix available to construct standard curves. It has been a challenging task to determine ACh in complex brain matrices. To overcome these difficulties, we employed a surrogate analyte strategy using ACh-d(4) instead of ACh to generate calibration curves and Ch-d(9) as internal standard (IS). The brain samples were deproteinized by acetonitrile with IS. Analytes and IS were separated by a HILIC column with the mobile phase composed of 20 mM ammonium formate in water-acetonitrile (30:70, v/v, adjusted to pH 3.0 with formic acid) and monitored in multiple reaction monitoring (MRM) mode using a positive electrospray source. The concentrations of endogenous ACh were calculated based on the peak area ratio of the analyte to the IS using a regression equation for the corresponding surrogate standard (ACh-d(4)). The lower limit of detection was 0.2 ng/mL and linearity was maintained over the range of 10-1000 ng/mL. Compared to other currently available methods, this approach offers improved accuracy and precision for efficient analysis of ACh. The proposed method was proved successfully by evaluating the action of typical acetylcholinesterase inhibitor huperzine A in senescence accelerated mouse prone 8 (SAMP8).
ESTHER : Peng_2011_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_879_3927
PubMedSearch : Peng_2011_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_879_3927
PubMedID: 22088352

Title : Induction of a 55 kDa acetylcholinesterase protein during apoptosis and its negative regulation by the Akt pathway - Xie_2011_J.Mol.Cell.Biol_3_250
Author(s) : Xie J , Jiang H , Wan YH , Du AY , Guo KJ , Liu T , Ye WY , Niu X , Wu J , Dong XQ , Zhang XJ
Ref : J Molecular & Cellular Biology , 3 :250 , 2011
Abstract : Acetylcholinesterase (AChE) is emerging as an important contributor to apoptosis in various cell types. However, overexpression of AChE does not initiate apoptosis, and cells which express AChE at basal levels grow normally, suggesting that AChE may function differently between normal and apoptotic conditions. In this study, we determined that an AChE-derived protein ( approximately 55 kDa) positively correlated with cellular apoptotic levels. The 55 kDa AChE protein was not a result of a novel splice variant of the AChE primary transcript. Instead, it was determined to be a cleaved fragment of the full-length 68 kDa AChE protein that could not be inhibited by cycloheximide (CHX) but could be suppressed by caspase inhibitors in apoptotic PC-12 cells. Furthermore, activation of the Akt cascade abolished the 55 kDa protein, and both AChE protein forms (68 and 55 kDa) accumulated in the nucleus during apoptosis. In a mouse model for ischemia/reperfusion (I/R)-induced acute renal failure, the 55 kDa AChE protein was detected in the impaired organs but not in the normal ones, and its levels correlated with the genotype of the mice. In summary, a 55 kDa AChE protein resulting from the cleavage of 68 kDa AChE is induced during apoptosis, and it is negatively regulated by the Akt pathway. This study suggests that an alternative form of AChE may play a role in apoptosis.
ESTHER : Xie_2011_J.Mol.Cell.Biol_3_250
PubMedSearch : Xie_2011_J.Mol.Cell.Biol_3_250
PubMedID: 21377978

Title : Stage-dependent tolerance of the German cockroach, Blattella germanica for dichlorvos and propoxur - Qian_2010_J.Insect.Sci_10_201
Author(s) : Qian K , Wei X , Zeng X , Liu T , Gao X
Ref : J Insect Sci , 10 :201 , 2010
Abstract : tage-dependent dichlorvos and propoxur tolerance in a field population of the German cockroach, Blattella germanica Linnaeus (Blatodea: Blattellidae), was investigated in the laboratory using a topical application bioassay. The results showed the 6 week-old nymphs were more tolerant to dichlorvos and propoxur than the other ages tested. LD(5)(0) values of dichlorvos and propoxur for the 6 week-old nymphs were 2.003 microg per insect and 5.296 microg per insect, respectively. Tolerance ratios of 18.55-fold and 4.98-fold for LD(5)(0) were obtained from 6-week-old nymphs compared to 4 week-old nymphs. The specific activity of acetylcholinesterase (AChE) from 1 week-old nymphs was the highest among all tested developmental stages of nymphs and adult males and females. The specific activity of AChE decreased significantly with increasing age. The sensitivity of AChE to dichlorvos was the highest with a k(i) value of 3.12 x 10(4) mol(-)(1)min(-)(1) in the last nymphal stage of B. germanica (about 6 weeks-old). The AChE from 4 week-old nymphs was the most sensitive to propoxur, with the highest k(i) value being 2.63 x 10(5) mol(-)(1) min(-)(1). These results indicated that the different developmental stages and sexes of B. germanica affected the inhibition of AChE by dichlorvos and propoxur.
ESTHER : Qian_2010_J.Insect.Sci_10_201
PubMedSearch : Qian_2010_J.Insect.Sci_10_201
PubMedID: 21268698

Title : Hypertriglyceridemia in Watanabe heritable hyperlipidemic rabbits was associated with increased production and reduced catabolism of very-low-density lipoproteins - Zhang_2009_Pathobiology_76_315
Author(s) : Zhang C , Jin Y , Liu T , Liu F , Ito T
Ref : Pathobiology , 76 :315 , 2009
Abstract : Watanabe heritable hyperlipidemic (WHHL) rabbit is an animal model for human familial hypercholesterolemia. Recently, we segregated a new mutant of WHHL rabbits with plasma levels of triglycerides (TG) >500 mg/dl (designated as TGH-WHHL). To investigate the underlying mechanisms for hypertriglyceridemia, we compared TGH-WHHL with WHHL rabbits with lower plasma TG levels (<250 mg/dl, designated as TGL-WHHL). A Triton WR-1339 injection experiment revealed that TGH-WHHL rabbits had increased secretion and decreased clearance of TG-rich lipoproteins. Furthermore, TGH-WHHL rabbits had lower a post-heparin activity of lipoprotein lipase and a higher cholesterol ester transfer protein activity than TGL-WHHL rabbits. Cultured hepatocytes isolated from TGH-WHHL rabbits showed a higher secretion rate of TG and cholesterol than those of TGL-WHHL rabbits. In addition, TGH-WHHL rabbits exhibited marked insulin resistance. These data suggest that hypertriglyceridemia exhibited by WHHL rabbits is caused by both increased production and impaired catabolism of TG-rich lipoproteins and associated with insulin resistance.
ESTHER : Zhang_2009_Pathobiology_76_315
PubMedSearch : Zhang_2009_Pathobiology_76_315
PubMedID: 19955843

Title : [3D visualization research on microstructure of human ulnar nerve] - Liu_2008_Zhongguo.Xiu.Fu.Chong.Jian.Wai.Ke.Za.Zhi_22_1026
Author(s) : Liu T , Hu P , Zhang J , Zhang M , Li H , Chen Z , Chen T
Ref : Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi , 22 :1026 , 2008
Abstract : OBJECTIVE: To explore the application of 3D nerve visualization system in processing 2D image information of human ulnar nerve acquired by series freezing tissue section, staining and scanning. And to draw the 3D anatomical atlas of human ulnar nerve through 3D Nerve visualization software system. METHODS: One left ulnar nerve (from medial fasciculus of brachial plexus to transverse carpal ligament, about 50 cm) was taken from a fresh donated cadaver. After marked with human hair and embedded in OCT, series freezing tissue sections were made and stained with acetylcholinesterase histochemically. Series 2D image information was obtained through high resolution scanner. Then the microstructure of ulnar nerve was reconstructed with 3D Nerve visualization software system. RESULTS: Different cross sections of ulnar nerve have different numbers, positions and characters of the internal nerve fibers. The microstructure of ulnar nerve could be observed in magnifying visual field at any cross section after reconstructed in 3D Nerve visualization soft ware system, which made it possible to track stereo course of fascicles. CONCLUSION: Reconstructed 3D Nerve visualization software system shows the whole microstructure of ulnar nerve and the 3D stereo-structure of its internal fascicles, thus provides exact topography atlas for medical teaching and facilitates precise repair of ulnar nerve injury to improve therapeutic effect.
ESTHER : Liu_2008_Zhongguo.Xiu.Fu.Chong.Jian.Wai.Ke.Za.Zhi_22_1026
PubMedSearch : Liu_2008_Zhongguo.Xiu.Fu.Chong.Jian.Wai.Ke.Za.Zhi_22_1026
PubMedID: 18822720

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 : Polyhydroxyalkanoate synthases PhaC1 and PhaC2 from Pseudomonas stutzeri 1317 had different substrate specificities - Chen_2004_FEMS.Microbiol.Lett_234_231
Author(s) : Chen JY , Liu T , Zheng Z , Chen JC , Chen GQ
Ref : FEMS Microbiology Letters , 234 :231 , 2004
Abstract : The whole polyhydroxyalkanoate (PHA) synthesis gene locus of Pseudomonas stutzeri strain 1317 containing PHA synthase genes phaC1Ps, phaC2Ps and PHA depolymerase gene phaZPs was cloned using a PCR cloning strategy. The sequence analysis results of the phaC1Ps, phaC2Ps and phaZPs showed high homology to the corresponding pha loci of the known Pseudomonas strains, respectively. PhaC1Ps and PhaC2Ps were functionally expressed in recombinant Escherichia coli strains and their substrate specificity was compared. The results demonstrated that PhaC1Ps and PhaC2Ps from P. stutzeri 1317 had different substrate specificities when expressed in E. coli. In details, PhaC2Ps could incorporate both short-chain-length 3-hydroxybutyrate and medium-chain-length 3-hydroxyalkanoates (mcl 3HA) into PHA, while PhaC1Ps only favored mcl 3HA for polymerization.
ESTHER : Chen_2004_FEMS.Microbiol.Lett_234_231
PubMedSearch : Chen_2004_FEMS.Microbiol.Lett_234_231
PubMedID: 15135527
Gene_locus related to this paper: pseme-PHAC1 , pseme-PHAZ , psest-PHAC2