Yang L

References (206)

Title : Screening of Active Substances Regulating Alzheimer's Disease in Ginger and Visualization of the Effectiveness on 6-Gingerol Pathway Targets - Pan_2024_Foods_13_
Author(s) : Pan Y , Li Z , Zhao X , Du Y , Zhang L , Lu Y , Yang L , Cao Y , Qiu J , Qian Y
Ref : Foods , 13 : , 2024
Abstract : Ginger has been reported to potentially treat Alzheimer's disease (AD), but the specific compounds responsible for this biological function and their mechanisms are still unknown. In this study, a combination of network pharmacology, molecular docking, and dynamic simulation technology was used to screen active substances that regulate AD and explore their mechanisms. The TCMSP, GeneCards, OMIM, and DisGeNET databases were utilized to obtain 95 cross-targets related to ginger's active ingredients and AD as key targets. A functional enrichment analysis revealed that the pathways in which ginger's active substances may be involved in regulating AD include response to exogenous stimuli, response to oxidative stress, response to toxic substances, and lipid metabolism, among others. Furthermore, a drug-active ingredient-key target interaction network diagram was constructed, highlighting that 6-Gingerol is associated with 16 key targets. Additionally, a protein-protein interaction (PPI) network was mapped for the key targets, and HUB genes (ALB, ACTB, GAPDH, CASP3, and CAT) were identified. Based on the results of network pharmacology and cell experiments, 6-Gingerol was selected as the active ingredient for further investigation. Molecular docking was performed between 6-Gingerol and its 16 key targets, and the top three proteins with the strongest binding affinities (ACHE, MMP2, and PTGS2) were chosen for molecular dynamics analysis together with the CASP3 protein as the HUB gene. The findings indicate that 6-Gingerol exhibits strong binding ability to these disease targets, suggesting its potential role in regulating AD at the molecular level, as well as in abnormal cholinesterase metabolism and cell apoptosis, among other related regulatory pathways. These results provide a solid theoretical foundation for future in vitro experiments using actual cells and animal experiments to further investigate the application of 6-Gingerol.
ESTHER : Pan_2024_Foods_13_
PubMedSearch : Pan_2024_Foods_13_
PubMedID: 38397589

Title : Rational design of a near-infrared fluorescent probe for monitoring butyrylcholinesterase activity and its application in development of inhibitors - Li_2024_Front.Bioeng.Biotechnol_12_1387146
Author(s) : Li H , Li XD , Yan CH , Ni ZH , Lu MH , Zou LW , Yang L
Ref : Front Bioeng Biotechnol , 12 :1387146 , 2024
Abstract : Butyrylcholinesterase (BChE) is widely expressed in multiple tissues and has a vital role in several key human disorders, such as Alzheimer's disease and tumorigenesis. However, the role of BChE in human disorders has not been investigated. Thus, to quantitatively detect and visualize dynamical variations in BChE activity is essential for exploring the biological roles of BChE in the progression of a number of human disorders. Herein, based on the substrate characteristics of BChE, we customized and synthesized three near-infrared (NIR) fluorescent probe substrates with cyanine-skeleton, and finally selected a NIR fluorescence probe substrate named CYBA. The CYBA demonstrated a significant increase in fluorescence when interacting with BChE, but mainly avoided AChE. Upon the addition of BChE, CYBA could be specifically hydrolyzed to TBO, resulting in a significant NIR fluorescence signal enhancement at 710 nm. Systematic evaluation revealed that CYBA exhibited exceptional chemical stability in complex biosamples and possessed remarkable selectivity and sensitivity towards BChE. Moreover, CYBA was successfully applied for real-time imaging of endogenous BChE activity in two types of nerve-related living cells. Additionally, CYBA demonstrated exceptional stability in the detection of complex biological samples in plasma recovery studies (97.51%-104.01%). Furthermore, CYBA was used to construct a high-throughput screening (HTS) method for BChE inhibitors using human plasma as the enzyme source. We evaluated inhibitory effects of a series of natural products and four flavonoids were identified as potent inhibitors of BChE. Collectively, CYBA can serve as a practical tool to track the changes of BChE activity in complicated biological environments due to its excellent capabilities.
ESTHER : Li_2024_Front.Bioeng.Biotechnol_12_1387146
PubMedSearch : Li_2024_Front.Bioeng.Biotechnol_12_1387146
PubMedID: 38638318

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

Title : Virtual screening, activity evaluation, and stability of pancreatic lipase inhibitors in the gastrointestinal degradation of nattokinase - Yang_2024_Heliyon_10_e24868
Author(s) : Yang L , Cao S , Xie M , Shi T
Ref : Heliyon , 10 :e24868 , 2024
Abstract : Nattokinase is an alkaline serine protease secreted by natto during fermentation. Despite its good thrombolytic effect, it is intolerant to gastrointestinal conditions and is easily digested and degraded into polypeptides, oligopeptides, and amino acids. However, whether these peptides inhibit fat-digesting enzymes and other biological activities remains unknown. To explore the bioactivity of peptides produced through nattokinase degradation, nattokinase was subjected to simulated digestion in the gastrointestinal tract, and 41 small peptides were obtained through the enzymolysis of gastric enzymes, pancreases, and chymotrypsin. Four pancreatic lipase (PL) inhibitory peptides (SW, ASF, GAY, and PGGTY) were selected based on their activity scores, water solubility, and toxicity predictions. The molecular docking results revealed that hydrogen bonds and electrostatic interactions were the main forces for inhibiting PL activity. The results of enzyme activity verification revealed that all four peptides inhibited PL activity. Among them, GAY exhibited the strongest inhibitory effect, with an inhibitory rate of 10.93 % at a concentration of 1 mg/mL. Molecular dynamics simulations confirmed that the GAY-1ETH complex demonstrated good stability. Natto foods containing nattokinase own the activity of inhibiting fat-digesting enzymes and show antiobesity potentials.
ESTHER : Yang_2024_Heliyon_10_e24868
PubMedSearch : Yang_2024_Heliyon_10_e24868
PubMedID: 38312550

Title : Gastrodinol derivatives and prenylated flavones from the flower branch of Gastrodia elata - Qin_2024_Nat.Prod.Bioprospect_14_22
Author(s) : Qin SH , Li ZL , Yang L , Hu JM
Ref : Nat Prod Bioprospect , 14 :22 , 2024
Abstract : Based on the research progress and traditional usage with whole herbal of the TCM "Tianma", chemical studies herein on the flower branch of Gastrodia elata were carried out in-depth and got 13 compounds including the gastrodinols (1-4), the flavonoid morins (5-8, 11-12), together with the specialist mulberrofurans (9, 13) and gastrodiamide (10) for the first time from the species. The antibacterial and cholinesterase inhibitory activities were then evaluated and the results showed that compounds 5, 11, 12, 13 have good activity against anti-methicillin-resistant Staphylococcus aureus, and compounds 9, 13 had good acetylcholinesterase inhibitory activity. All these results provide new chemical composition for better understanding the traditional application of "Tianma" and for exploring new pharmacological ingredients.
ESTHER : Qin_2024_Nat.Prod.Bioprospect_14_22
PubMedSearch : Qin_2024_Nat.Prod.Bioprospect_14_22
PubMedID: 38507117

Title : Resolution of N-acetyl-DL-methionine methyl ester by the lipase from Brucella thiophenivorans - Li_2024_Chirality_36_e23643
Author(s) : Li X , Li Q , Yang L , Huang L , Peng C , Zheng J
Ref : Chirality , 36 :e23643 , 2024
Abstract : In this study, lipase-catalyzed resolution of N-acetyl-DL-methionine methyl ester (N-Ac-DL-MetOMe) was evaluated. A lipase from Brucella thiophenivorans was prone to exhibit high activity and excellent enantioselectivity toward N-Ac-DL-MetOMe to produce the key chiral intermediate N-acetyl-L-methionine methyl ester (N-Ac-L-MetOMe). The results showed that the enzymatic reaction was carried out in 100 g/L racemic substrate for 2 h, the conversion reached 51.3%, the enantiomeric excess value N-Ac-L-MetOMe exceeded 99%, and the enantiomeric ratio value >200. Therefore, the lipase from B. thiophenivorans has potential prospects for the resolution of N-Ac-DL-MetOMe to produce the important intermediate N-Ac-L-MetOMe.
ESTHER : Li_2024_Chirality_36_e23643
PubMedSearch : Li_2024_Chirality_36_e23643
PubMedID: 38384156

Title : ANGPTL3 is a novel HDL component that regulates HDL function - Yang_2024_J.Transl.Med_22_263
Author(s) : Yang L , Wang Y , Xu Y , Li K , Yin R , Zhang L , Wang D , Wei L , Lang J , Cheng Y , Wang L , Ke J , Zhao D
Ref : J Transl Med , 22 :263 , 2024
Abstract : BACKGROUND: Angiopoietin-like protein 3 (ANGPTL3) is secreted by hepatocytes and inhibits lipoprotein lipase and endothelial lipase activity. Previous studies reported the correlation between plasma ANGPTL3 levels and high-density lipoprotein (HDL). Recently ANGPTL3 was found to preferentially bind to HDL in healthy human circulation. Here, we examined whether ANGPTL3, as a component of HDL, modulates HDL function and affects HDL other components in human and mice with non-diabetes or type 2 diabetes mellitus. METHODS: HDL was isolated from the plasma of female non-diabetic subjects and type-2 diabetic mellitus (T2DM) patients. Immunoprecipitation, western blot, and ELISA assays were used to examine ANGPTL3 levels in HDL. Db/m and db/db mice, AAV virus mediated ANGPTL3 overexpression and knockdown models and ANGPTL3 knockout mice were used. The cholesterol efflux capacity induced by HDL was analyzed in macrophages preloaded with fluorescent cholesterol. The anti-inflammation capacity of HDL was assessed using flow cytometry to measure VCAM-1 and ICAM-1 expression levels in TNF-alpha-stimulated endothelial cells pretreated with HDL. RESULTS: ANGPTL3 was found to bind to HDL and be a component of HDL in both non-diabetic subjects and T2DM patients. Flag-ANGPTL3 was found in the HDL of transgenic mice overexpressing Flag-ANGPTL3. ANGPLT3 of HDL was positively associated with cholesterol efflux in female non-diabetic controls (r = 0.4102, p = 0.0117) but not in female T2DM patients (r = - 0.1725, p = 0.3224). Lower ANGPTL3 levels of HDL were found in diabetic (db/db) mice compared to control (db/m) mice and were associated with reduced cholesterol efflux and inhibition of VCAM-1 and ICAM-1 expression in endothelial cells (p < 0.05 for all). Following AAV-mediated ANGPTL3 cDNA transfer in db/db mice, ANGPTL3 levels were found to be increased in HDL, and corresponded to increased cholesterol efflux and decreased ICAM-1 expression. In contrast, knockdown of ANGPTL3 levels in HDL by AAV-mediated shRNA transfer led to a reduction in HDL function (p < 0.05 for both). Plasma total cholesterol, total triglycerides, HDL-c, protein components of HDL and the cholesterol efflux function of HDL were lower in ANGPTL3-/- mice than ANGPTL3+/+ mice, suggesting that ANGPTL3 in HDL may regulate HDL function by disrupting the balance of protein components in HDL. CONCLUSION: ANGPTL3 was identified as a component of HDL in humans and mice. ANGPTL3 of HDL regulated cholesterol efflux and the anti-inflammatory functions of HDL in T2DM mice. Both the protein components of HDL and cholesterol efflux capacity of HDL were decreased in ANGPTL3-/- mice. Our findings suggest that ANGPTL3 in HDL may regulate HDL function by disrupting the balance of protein components in HDL. Our study contributes to a more comprehensive understanding of the role of ANGPTL3 in lipid metabolism.
ESTHER : Yang_2024_J.Transl.Med_22_263
PubMedSearch : Yang_2024_J.Transl.Med_22_263
PubMedID: 38462608

Title : Establishment of transgenic fluorescent mice for labeling synapses and screening synaptogenic adhesion molecules - Yang_2024_Elife_13_
Author(s) : Yang L , Zhang J , Liu S , Zhang Y , Wang L , Wang X , Wang S , Li K , Wei M , Zhang C
Ref : Elife , 13 : , 2024
Abstract : Synapse is the fundamental structure for neurons to transmit information between cells. The proper synapse formation is crucial for developing neural circuits and cognitive functions of the brain. The aberrant synapse formation has been proved to cause many neurological disorders, including autism spectrum disorders and intellectual disability. Synaptic cell adhesion molecules (CAMs) are thought to play a major role in achieving mechanistic cell-cell recognition and initiating synapse formation via trans-synaptic interactions. Due to the diversity of synapses in different brain areas, circuits and neurons, although many synaptic CAMs, such as Neurexins (NRXNs), Neuroligins (NLGNs), Synaptic cell adhesion molecules (SynCAMs), Leucine-rich-repeat transmembrane neuronal proteins (LRRTMs) and SLIT and NTRK-like protein (SLITRKs) have been identified as synaptogenic molecules, how these molecules determine specific synapse formation and whether other molecules driving synapse formation remain undiscovered are unclear. Here, to providing a tool for synapse labeling and synaptic CAMs screening by artificial synapse formation (ASF) assay, we generated synaptotagmin-1-tdTomato (Syt1-tdTomato) transgenic mice by inserting the tdTomato-fused synaptotagmin-1 coding sequence into the genome of C57BL/6J mice. In the brain of Syt1-tdTomato transgenic mice, the tdTomato-fused synaptotagmin-1 (SYT1-tdTomato) signals were widely observed in different areas and overlapped with synapsin-1, a widely-used synaptic marker. In olfactory bulb, the SYT1-tdTomato signals are highly enriched in glomerulus. In the cultured hippocampal neurons, the SYT1-tdTomato signals showed colocalization with several synaptic markers. Compared to the wild-type (WT) mouse neurons, cultured hippocampal neurons from Syt1-tdTomato transgenic mice presented normal synaptic neurotransmission. In ASF assays, neurons from Syt1-tdTomato transgenic mice could form synaptic connections with HEK293T cells expressing NLGN2, LRRTM2, and SLITRK2 without immunostaining. Therefore, our work suggested that the Syt1-tdTomato transgenic mice with the ability to label synapses by tdTomato, and it will be a convenient tool for screening synaptogenic molecules.
ESTHER : Yang_2024_Elife_13_
PubMedSearch : Yang_2024_Elife_13_
PubMedID: 38450720

Title : Development of Sustainable Insecticide Candidates for Protecting Pollinators: Insight into the Bioactivities, Selective Mechanism of Action and QSAR of Natural Coumarin Derivatives against Aphids - Zhou_2023_J.Agric.Food.Chem_71_18359
Author(s) : Zhou H , Jian Y , Shao Q , Guo F , Zhang M , Wan F , Yang L , Liu Y , Li Y , Yang P , Li Z , Li S , Ding W
Ref : Journal of Agricultural and Food Chemistry , 71 :18359 , 2023
Abstract : Plants employ abundant toxic secondary metabolites to withstand insect attack, while pollinators can tolerate some natural defensive compounds. Coumarins, as promising green alternatives to chemical insecticides, possess wide application prospects in the crop protection field. Herein, the bioactivities of 30 natural coumarin derivatives against Aphis gossypii were assessed and revealed that 6-methylcoumarin exhibited potent aphicidal activity against aphids but displayed no toxicity to honeybees. Additionally, using biochemical, bioinformatic, and molecular assays, we confirmed that the action mode of 6-methylcoumarin against aphids was by inhibiting acetylcholinesterase (AChE). Meanwhile, functional assays revealed that the difference in action site, which located in Lys585 in aphid AChE (equivalent to Val548 in honeybee AChE), was the principal reason for 6-methylcoumarin being toxic to aphids but safe to pollinators. This action site was further validated by mutagenesis data, which uncovered how 6-methylcoumarin was unique selective to the aphid over honeybee or mammalian AChE. Furthermore, a 2D-QSAR model was established, revealing that the central structural feature was H3m, which offers guidance for the future design of more potent coumarin compounds. This work provides a sustainable strategy to take advantage of coumarin analogues for pest management while protecting nontarget pollinators.
ESTHER : Zhou_2023_J.Agric.Food.Chem_71_18359
PubMedSearch : Zhou_2023_J.Agric.Food.Chem_71_18359
PubMedID: 37965968

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

Title : ABHD6 drives endocytosis of AMPA receptors to regulate synaptic plasticity and learning flexibility - Wei_2023_Prog.Neurobiol__102559
Author(s) : Wei M , Yang L , Su F , Liu Y , Zhao X , Luo L , Sun X , Liu S , Dong Z , Zhang Y , Shi YS , Liang J , Zhang C
Ref : Prog Neurobiol , :102559 , 2023
Abstract : Trafficking of alpha-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors (AMPARs), mediated by AMPAR interacting proteins, enabled neurons to maintain tuning capabilities at rest or active state. alpha/beta-Hydrolase domain-containing 6 (ABHD6), an endocannabinoid hydrolase, was an AMPAR auxiliary subunit found to negatively regulate the surface delivery of AMPARs. While ABHD6 was found to prevent AMPAR tetramerization in endoplasmic reticulum, ABHD6 was also reported to localize at postsynaptic site. Yet, the role of ABHD6 interacting with AMPAR at postsynaptic site, and the physiological significance of ABHD6 regulating AMPAR trafficking remains elusive. Here, we generated the ABHD6 knockout (ABHD6(KO)) mice and found that deletion of ABHD6 selectively enhanced AMPAR-mediated basal synaptic responses and the surface expression of postsynaptic AMPARs. Furthermore, we found that loss of ABHD6 impaired hippocampal long-term depression (LTD) and synaptic downscaling in hippocampal synapses. AMPAR internalization assays revealed that ABHD6 was essential for neuronal activity-dependent endocytosis of surface AMPARs, which is independent of ABHD6's hydrolase activity. The defects of AMPAR endocytosis and LTD are expressed as deficits in learning flexibility in ABHD6(KO) mice. Collectively, we demonstrated that ABHD6 is an endocytic accessory protein promoting AMPAR endocytosis, thereby contributes to the formation of LTD, synaptic downscaling and reversal learning.
ESTHER : Wei_2023_Prog.Neurobiol__102559
PubMedSearch : Wei_2023_Prog.Neurobiol__102559
PubMedID: 38159878
Gene_locus related to this paper: human-ABHD6 , mouse-ABHD6

Title : Design, synthesis, and biological evaluation of novel tryptanthrin derivatives as selective acetylcholinesterase inhibitors for the treatment of Alzheimer's disease - Xia_2023_Bioorg.Chem_143_106980
Author(s) : Xia J , Dong S , Yang L , Wang F , Xing S , Du J , Li Z
Ref : Bioorg Chem , 143 :106980 , 2023
Abstract : Two novel series of tryptanthrin (TRYP) derivatives were designed and synthesized as multifunctional agents for the treatment of Alzheimer's disease (AD). Inhibition assay against cholinesterase (ChE) indicated that these derivatives can act as acetylcholinesterase (AChE) inhibitors with selectivity over butyrylcholinesterase (BuChE). Among them, n1 exhibited the most excellent ChE inhibitory potency (AChE, IC(50) = 12.17 +/- 1.50 nM; BuChE, IC(50) = 6.29 +/- 0.48 micro; selectivity index = 517). Molecular docking studies indicated that compound n1 can interact with amino acid residues in the catalytic active site and peripheral anionic site of AChE and the molecular dynamics (MD) simulation studies demonstrated that the AChE-n1 complex had good stability. N1 also exhibited anti-amyloid-beta (Abeta) aggregation (63.48 % +/- 1.02 %, 100 micro) and anti-neuroinflammation activity (NO, IL-1beta, TNF-alpha; IC(50) = 2.13 +/- 0.54 micro, 2.21 +/- 0.37 micro, 2.47 +/- 0.07 micro, respectively), and n1 had neuroprotective and metal-chelating properties. Further studies indicated n1 had proper blood-brain barrier permeability in the Parallel artificial membrane permeation assay. In vivo studies found that n1 effectively improved learning and memory impairment in scopolamine-induced AD mouse models. Nissl staining ofmice hippocampaltissue sections revealed that n1 restored neuronal cells in the hippocampus CA3 and CA1 regions. These findings suggested that n1 can be a promising compound for further development of multifunctional agents for AD treatment.
ESTHER : Xia_2023_Bioorg.Chem_143_106980
PubMedSearch : Xia_2023_Bioorg.Chem_143_106980
PubMedID: 38006789

Title : Rs15285, a functional polymorphism located in lipoprotein lipase, predicts the risk and prognosis of gastric cancer - Shen_2023_Appl.Microbiol.Biotechnol__
Author(s) : Shen K , Zhou X , Hu L , Xiao J , Cheng Q , Wang Y , Liu K , Fan H , Xu Z , Yang L
Ref : Applied Microbiology & Biotechnology , : , 2023
Abstract : Lipoprotein lipase (LPL), a crucial gene in lipid metabolism, has a significant role in the progression of malignant tumors. The purpose of this research was to investigate the impact of rs15285 found in the LPL gene's 3'UTR region on the risk, biological behavior, and gastric cancer (GC) prognosis as well as to examine its potential function. Genotyping of rs15285 in 888 GC cases and 874 controls was conducted by SNaPshot technology. We used bioinformatics analysis and in vitro experiments to study the role of rs15285. First, this study revealed for the first time that polymorphism rs15285 increases the risk of GC (OR = 1.48, 95%CI = 1.16-1.89, P = 0.002). Although no relationship was found between rs12585 and the pathological features of GC, the prognosis of individuals with the rs12585 TT genotype was poorer than that of patients with the CC or CC+CT genotype (HR = 2.39 for TT vs. CC, P = 0.025; HR = 2.38 for TT vs. CC+CT, P = 0.025). In addition, bioinformatics analysis showed rs12585 may affect the binding of miRNAs to LPL, resulting in an increase of LPL expression to promote cancer progression. Ultimately, in vitro tests revealed that the rs15285 T allele increased LPL expression on the mRNA as well as the protein levels, promoting GC cell proliferation, invasion, and metastasis. The LPL rs12528 TT genotype increased the risk of GC and predicted a poor prognosis. Mechanistically, the rs15285 T allele could improve the expression of LPL, and thus promotes the malignant phenotype of GC. Therefore, our study may provide new biological predictors and a theoretical basis for the prognosis and customized therapy of stomach cancer patients. KEY POINTS: Rs15285 polymorphism is a risk factor for GC. Rs12585 TT genotype predicts a bad outcome in GC individuals. Rs15285 T allele enhances GC cells malignant biological behavior.
ESTHER : Shen_2023_Appl.Microbiol.Biotechnol__
PubMedSearch : Shen_2023_Appl.Microbiol.Biotechnol__
PubMedID: 37036527
Gene_locus related to this paper: human-LPL

Title : Investigating the Regulatory Mechanism of the Sesquiterpenol Nerolidol from a Plant on Juvenile Hormone-Related Genes in the Insect Spodoptera exigua - Dai_2023_Int.J.Mol.Sci_24_
Author(s) : Dai H , Liu B , Yang L , Yao Y , Liu M , Xiao W , Li S , Ji R , Sun Y
Ref : Int J Mol Sci , 24 : , 2023
Abstract : Various plant species contain terpene secondary metabolites, which disrupt insect growth and development by affecting the activity of juvenile hormone-degrading enzymes, and the juvenile hormone (JH) titers maintained in insects. Nerolidol, a natural sesquiterpenol belonging to the terpenoid group, exhibits structural similarities to insect JHs. However, the impact of nerolidol on insect growth and development, as well as its underlying molecular mechanism, remains unclear. Here, the effects of nerolidol on Spodoptera exigua were investigated under treatment at various sub-lethal doses (4.0 mg/mL, 1.0 mg/mL, 0.25 mg/mL). We found that a higher dose (4.0 mg/mL) of nerolidol significantly impaired the normal growth, development, and population reproduction of S. exigua, although a relatively lower dose (0.25 mg/mL) of nerolidol had no significant effect on this growth and development. Combined transcriptome sequencing and gene family analysis further revealed that four juvenile hormone esterase (JHE)-family genes that are involved in juvenile hormone degradation were significantly altered in S. exigua larvae after nerolidol treatment (4.0 mg/mL). Interestingly, the juvenile hormone esterase-like (JHEL) gene Sexi006721, a critical element responsive to nerolidol stress, was closely linked with the significant augmentation of JHE activity and JH titer in S. exigua (R(2) = 0.94, p < 0.01). Taken together, we speculate that nerolidol can function as an analog of JH by modulating the expression of the enzyme genes responsible for degrading JH, resulting in JH disorders and ultimately disrupting the development of insect larvae. This study ultimately provides a theoretical basis for the sustainable control of S. exigua in the field whilst proposing a new perspective for the development of novel biological pesticides.
ESTHER : Dai_2023_Int.J.Mol.Sci_24_
PubMedSearch : Dai_2023_Int.J.Mol.Sci_24_
PubMedID: 37686136

Title : The advantages of penehyclidine hydrochloride over atropine in acute organophosphorus pesticide poisoning: A meta-analysis - Zeng_2023_J.Intensive.Med_3_171
Author(s) : Zeng S , Ma L , Yang L , Hu X , Wang C , Guo X , Li Y , Gou Y , Zhang Y , Li S , Zhang S , Wu X , Li M , Lei J , Li B , Bi C , Luo Q
Ref : J Intensive Med , 3 :171 , 2023
Abstract : BACKGROUND: Penehyclidine hydrochloride (PHC) has been used for many years as an anticholinergic drug for the treatment of acute organophosphorus pesticide poisoning (AOPP). The purpose of this meta-analysis was to explore whether PHC has advantages over atropine in the use of anticholinergic drugs in AOPP. METHODS: We searched Scopus, Embase, Cochrane, PubMed, ProQuest, Ovid, Web of Science, China Science and Technology Journal Database (VIP), Duxiu, Chinese Biomedical literature (CBM), WanFang, and Chinese National Knowledge Infrastructure (CNKI), from inception to March 2022. After all qualified randomized controlled trials (RCTs) were included, we conducted quality evaluation, data extraction, and statistical analysis. Statistics using risk ratios (RR), weighted mean difference (WMD), and standard mean difference (SMD). RESULTS: Our meta-analysis included 20,797 subjects from 240 studies across 242 different hospitals in China. Compared with the atropine group, the PHC group showed decreased mortality rate (RR=0.20, 95% confidence intervals [CI]: 0.16-0.25, P <0.001), hospitalization time (WMD=-3.89, 95% CI: -4.37 to -3.41, P <0.001), overall incidence rate of complications (RR=0.35, 95% CI: 0.28-0.43, P <0.001), overall incidence of adverse reactions (RR=0.19, 95% CI: 0.17-0.22, P <0.001), total symptom disappearance time (SMD=-2.13, 95% CI: -2.35 to -1.90, P <0.001), time for cholinesterase activity to return to normal value 50-60% (SMD=-1.87, 95% CI: -2.03 to -1.70, P <0.001), coma time (WMD=-5.57, 95% CI: -7.20 to -3.95, P <0.001), and mechanical ventilation time (WMD=-2.16, 95% CI: -2.79 to -1.53, P <0.001). CONCLUSION: PHC has several advantages over atropine as an anticholinergic drug in AOPP.
ESTHER : Zeng_2023_J.Intensive.Med_3_171
PubMedSearch : Zeng_2023_J.Intensive.Med_3_171
PubMedID: 37188113

Title : Novel MAGL Inhibitors Alleviate LPS-Induced Acute Kidney Injury by Inhibiting NLRP3 Inflammatory Vesicles, Modulating Intestinal Flora, Repairing the Intestinal Barrier, and Interfering with Serum Metabolism - Xiang_2023_Molecules_28_7245
Author(s) : Xiang H , Wang Y , Yang L , Liu M , Sun C , Gu Y , Yao J
Ref : Molecules , 28 : , 2023
Abstract : Acute kidney injury (AKI) is a complication of a wide range of serious illnesses for which there is still no better therapeutic agent. We demonstrated that M-18C has a favorable inhibitory effect on monoacylglycerol lipase (MAGL), and several studies have demonstrated that nerve inflammation could be effectively alleviated by inhibiting MAGL, suggesting that M-18C has good anti-inflammatory activity. In this study, we investigated the effect of M-18C on LPS-induced acute kidney injury (AKI), both in vivo and in vitro, by using liquid chromatography-mass spectrometry (LC-MS), 16S rRNA gene sequencing, Western blot, and immunohistochemistry. The results showed that both in vivo and in vitro M-18C reduced the release of TNF-alpha and IL-1beta by inhibiting the expression of NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) and apoptosis-associated speck-like protein containing a CARD (ASC) protein; in addition, M-18C was able to intervene in LPS-induced AKI by ameliorating renal pathological injury, repairing the intestinal barrier, and regulating gut bacterial flora and serum metabolism. In conclusion, this study suggests that M-18C has the potential to be a new drug for the treatment of AKI.
ESTHER : Xiang_2023_Molecules_28_7245
PubMedSearch : Xiang_2023_Molecules_28_7245
PubMedID: 37959665
Gene_locus related to this paper: human-MGLL

Title : Molecular insights into the catalytic mechanism of plasticizer degradation by a monoalkyl phthalate hydrolase - Chen_2023_Commun.Chem_6_45
Author(s) : Chen Y , Wang Y , Xu Y , Sun J , Yang L , Feng C , Wang J , Zhou Y , Zhang ZM
Ref : Commun Chem , 6 :45 , 2023
Abstract : Phthalate acid esters (PAEs), a group of xenobiotic compounds used extensively as plasticizers, have attracted increasing concern for adverse effects to human health and the environment. Microbial degradation relying on PAE hydrolases is a promising treatment. However, only a limited number of PAE hydrolases were characterized to date. Here we report the structures of MehpH, a monoalkyl phthalate (MBP) hydrolase that catalyzes the reaction of MBP to phthalic acid and the corresponding alcohol, in apo and ligand-bound form. The structures reveal a positively-charged catalytic center, complementary to the negatively-charged carboxyl group on MBP, and a penetrating tunnel that serves as exit of alcohol. The study provides a first glimpse into the enzyme-substrate binding model for PAE hydrolases, leading strong support to the development of better enzymes in the future.
ESTHER : Chen_2023_Commun.Chem_6_45
PubMedSearch : Chen_2023_Commun.Chem_6_45
PubMedID: 36859434
Gene_locus related to this paper: 9acto-q2mhh5

Title : Sequence-Responsive Multifunctional Supramolecular Nanomicelles Act on the Regression of TNBC and Its Lung Metastasis via Synergic Pyroptosis-Mediated Immune Activation - Wang_2023_Small__e2305101
Author(s) : Wang X , Li Y , Hasrat K , Yang L , Qi Z
Ref : Small , :e2305101 , 2023
Abstract : Design of effective nanodrugs to modulate the immunosuppression of tumor microenvironment is a desirable approach to boost the clinical tumor-therapeutic effect. Supramolecular nanomicelles PolyMN-TO-8, which are constructed by self-assembling supramolecular host MTX-MPEG2000, guest NPX-2S, and TO-8 through hydrophobic forces, have excellent stability and responsiveness to carboxylesterase and glutathione in turn. In vivo studies validate that PolyMN-TO-8 enable to trigger pyroptosis-mediated immunogenic cell death under laser, avoiding the occurrence of immune dysregulation simultaneously. This therapeutic mode strengthens dendritic cells' maturation and accelerates the infiltration of CD8(+) T cells into tumors through moderate activation of pro-inflammatory factors with elimination of immune-escape, ultimately making the tumor inhibition rate as high as 87.44% via synergistic functions of photodynamic therapy, photothermal therapy, chemotherapy, etc. The loss of immune-escape quickens the infiltration of CD8(+) T cells into lungs, and further eschews the generation of tumor nodules in it. Chemotherapy, the release of interferon-gamma, and immune memory effect also strengthen the defense against metastasis. The generation of O(2) catalyzed by PolyMN-TO-8 under laser is indispensable for tumor metastasis inhibition undoubtedly.
ESTHER : Wang_2023_Small__e2305101
PubMedSearch : Wang_2023_Small__e2305101
PubMedID: 37635105

Title : Routine administration of neostigmine after recovery of spontaneous breathing versus neuromuscular monitor-guided administration of neostigmine in pediatric patients: a parallel, randomized, controlled study - Yang_2023_Trials_24_19
Author(s) : Yang L , Hu N , Chang H , Yang D , Zuo Y
Ref : Trials , 24 :19 , 2023
Abstract : BACKGROUND: Neostigmine used to reverse the muscle relaxants should be guided by neuromuscular monitoring, as the degree of spontaneous pre-reversal recovery is the key to success to reverse the neuromuscular block. But neuromuscular monitoring is not always available for some patients during anesthesia and, in consequence, we need to use other clinical judgment to guide the use of neostigmine to reverse the neuromuscular block. In this trial, we aimed to evaluate the incidence of residual neuromuscular blockade (rNMB) in pediatric patients with routine use of neostigmine after recovery of spontaneous breathing compared with the patients with the use of neostigmine guided by neuromuscular monitoring. METHODS: A parallel, randomized, controlled noninferiority study was conducted. We enrolled aged 3 months to 12 years old patients who underwent inguinal hernia repair under general anesthesia. The enrolled patients were randomly divided into experimental and control groups. After surgery, children in the experimental group were given 0.02 mg/kg neostigmine after recovery of spontaneous breathing. Children in the control group were given 0.02 mg/kg neostigmine when the train-of-four (TOF) ratio was between 0.4 and 0.9. However, no neostigmine was administered if the TOF ratio was higher than 0.9. The primary outcome was the incidence of rNMB after extubation (TOF ratio < 0.9). Secondary outcomes included the incidence of neostigmine-induced muscle paralysis, end of surgery - extubation interval, end of surgery - exit OR interval, the length of stay in the PACU, the incidence of hypoxia in the PACU, the number of children who required assisted ventilation during the PACU stay, and neostigmine-related adverse events. RESULTS: A total of 120 children were included in this study, with 60 in the experimental group and 60 in the control group. There was no significant difference in the incidence of rNMB after extubation between the groups (45/60 vs 44/60, RR 1.02 [95% CI, 0.83 to 1.26], p = 0.84). There was no neostigmine-induced muscle paralysis in either group. Adverse events were similar occurred in both groups. However, time from end of the surgery to leaving the operating room was earlier in the experimental group than in the control group (13.6 +/- 5.2 vs 15.7 +/- 5.6 min, MD -2.10 min [95% CI, -3.70 to -0.50], p = 0.04). The risk ratio of the incidence of TOF ratio < 0.3 for the experimental group was 31.12 (95%CI, 1.89 to 512.61) compared with the control group (12/60 vs 0/60, p = 0.00) in exploratory analysis. CONCLUSIONS: Recovery of spontaneous breathing could be used as a substitute of neuromuscular monitoring to guide neostigmine use in pediatric patients following minor surgeries. However, care should be taken for the residual neuromuscular block. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-IOR-17012890.sRegistered on 5sOctobers2017.
ESTHER : Yang_2023_Trials_24_19
PubMedSearch : Yang_2023_Trials_24_19
PubMedID: 36611181

Title : Elamipretide alleviates pyroptosis in traumatically injured spinal cord by inhibiting cPLA2-induced lysosomal membrane permeabilization - Zhang_2023_J.Neuroinflammation_20_6
Author(s) : Zhang H , Chen Y , Li F , Wu C , Cai W , Ye H , Su H , He M , Yang L , Wang X , Zhou K , Ni W
Ref : J Neuroinflammation , 20 :6 , 2023
Abstract : Spinal cord injury (SCI) is a devastating injury that may result in permanent motor impairment. The active ingredients of medications are unable to reach the affected area due to the blood-brain barrier. Elamipretide (SS-31) is a new and innovative aromatic cationic peptide. Because of its alternating aromatic and cationic groups, it freely crosses the blood-brain barrier. It is also believed to decrease inflammation and protect against a variety of neurological illnesses. This study explored the therapeutic value of SS-31 in functional recovery after SCI and its possible underlying mechanism. A spinal cord contusion injury model as well as the Basso Mouse Scale, footprint assessment, and inclined plane test were employed to assess how well individuals could function following SCI. The area of glial scarring, the number of dendrites, and the number of synapses after SCI were confirmed by HE, Masson, MAP2, and Syn staining. Western blotting, immunofluorescence, and enzyme-linked immunosorbent assays were employed to examine the expression levels of pyroptosis-, autophagy-, lysosomal membrane permeabilization (LMP)- and MAPK signalling-related proteins. The outcomes showed that SS-31 inhibited pyroptosis, enhanced autophagy and attenuated LMP in SCI. Mechanistically, we applied AAV vectors to upregulate Pla2g4A in vivo and found that SS-31 enhanced autophagy and attenuated pyroptosis and LMP by inhibiting phosphorylation of cPLA2. Ultimately, we applied asiatic acid (a p38-MAPK agonist) to test whether SS-31 regulated cPLA2 partially through the MAPK-P38 signalling pathway. Our group is the first to suggest that SS-31 promotes functional recovery partially by inhibiting cPLA2-mediated autophagy impairment and preventing LMP and pyroptosis after SCI, which may have potential clinical application value.
ESTHER : Zhang_2023_J.Neuroinflammation_20_6
PubMedSearch : Zhang_2023_J.Neuroinflammation_20_6
PubMedID: 36609266

Title : Characterization of Feruloyl Esterase from Klebsiella oxytoca Z28 and Its Application in the Release of Ferulic Acid from De-Starching Wheat Bran - Zhang_2023_Microorganisms_11_989
Author(s) : Zhang Y , Feng Z , Xiang H , Zhang X , Yang L
Ref : Microorganisms , 11 :989 , 2023
Abstract : Feruloyl esterase (EC3.1.1.73; FAE) can degrade biomass to release ferulic acid (FA), which has a high application in bioprocessing, food, pharmaceutical, paper, feed, and other industrial fields. A strain of Klebsiella oxytoca Z28 with ferulic esterase activity was screened from Daqu. In addition, the FAE gene was expressed in Escherichia coli BL21 (DE3). The enzyme consists of 340 amino acids with a molecular mass of 37.7 kDa. The FAE enzyme activity was 463 U/L when the substrate was ethyl 4-hydroxy-3-methoxycinnamate and the optimum temperature and pH were 50 degreesC and 8.0, respectively. The enzyme had good stability at temperatures of 25-40 degreesC and a pH of 8.0. Ba(2+), Cu(2+), Mn(2+), and Ca(2+) had a strong inhibitory effect on the enzyme activity, and Na(+) had a promotive effect on the enzyme activity. The de-starching wheat bran was degraded by KoFAE, and the FA release was up to 227.15 microg/g. This indicated that the heterologous expression of KoFAE from Klebsiella oxytoca Z28 in E. coli had a certain potential of biodegradation, which can be applied to the degradation of agricultural waste to obtain high value-added FA products.
ESTHER : Zhang_2023_Microorganisms_11_989
PubMedSearch : Zhang_2023_Microorganisms_11_989
PubMedID: 37110412
Gene_locus related to this paper: kleox-KoFae

Title : N-Amidation of Nitrogen-Containing Heterocyclic Compounds: Can We Apply Enzymatic Tools? - Yang_2023_Bioengineering.(Basel)_10_
Author(s) : Yang A , Miao X , Yang L , Xu C , Liu W , Xian M , Zou H
Ref : Bioengineering (Basel) , 10 : , 2023
Abstract : Amide bond is often seen in value-added nitrogen-containing heterocyclic compounds, which can present promising chemical, biological, and pharmaceutical significance. However, current synthesis methods in the preparation of amide-containing N-heterocyclic compounds have low specificity (large amount of by-products) and efficiency. In this study, we focused on reviewing the feasible enzymes (nitrogen acetyltransferase, carboxylic acid reductase, lipase, and cutinase) for the amidation of N-heterocyclic compounds; summarizing their advantages and weakness in the specific applications; and further predicting candidate enzymes through in silico structure-functional analysis. For future prospects, current enzymes demand further engineering and improving for practical industrial applications and more enzymatic tools need to be explored and developed for a broader range of N-heterocyclic substrates.
ESTHER : Yang_2023_Bioengineering.(Basel)_10_
PubMedSearch : Yang_2023_Bioengineering.(Basel)_10_
PubMedID: 36829716

Title : Core-shell ZnO@CoO nitrogen doped nano-composites as highly sensitive electrochemical sensor for organophosphate pesticides detection - Li_2023_Anal.Biochem__115422
Author(s) : Li Z , Lu X , Liu G , Yang L , Gao F
Ref : Analytical Biochemistry , :115422 , 2023
Abstract : Core-shell ZIF-8@ZIF-67 was synthesized by growing a cobalt-based ZIF-67 on a ZIF-8 seed particle. Herein, through selective etching of the ZIF-8@ZIF-67 core and subsequent direct carbonization, core-shell hollow ZnO@CoO nitrogen-doped nanoporous carbon (HZnO@CoO-NPC) nanocomposites were prepared. HZnO@CoO-NPCs possessed a high nitrogen content, large surface area, high degree of graphitization and excellent electrical conductivity, all of which were attributed to successfully integrating the unique advantages of ZIF-8 and ZIF-67. HZnO@CoO-NPCs were used to assemble acetylcholinesterase (AChE) biosensors for organophosphorus pesticides (OPs) detection. The low detection limit of 2.74 x 10(-13) M for chlorpyrifos and 7.6 x 10(-15) M for parathion-methyl demonstrated the superior sensing performance. The results showed that the electrochemical biosensor constructed by HZnO@CoO-NPC provided a sensitive and efficient electrochemical strategy for OPs detection.
ESTHER : Li_2023_Anal.Biochem__115422
PubMedSearch : Li_2023_Anal.Biochem__115422
PubMedID: 38070664

Title : A covalent crosslinking strategy to construct a robust peptide-based artificial esterase - Tian_2023_Soft.Matter__
Author(s) : Tian Y , Yang L , Peng X , Qi W , Wang M
Ref : Soft Matter , : , 2023
Abstract : Peptide-based artificial enzymes derived from the supramolecular assembly of short peptides have attracted growing attention in recent years. However, the stability of these artificial enzymes is still a problem since their noncovalent supramolecular structure is quite sensitive and frail under environmental conditions. In this study, we reported a covalent crosslinking strategy for the fabrication of a robust peptide-based artificial esterase. Inspired by the di-tyrosine bonds in many natural structural proteins, multi-tyrosines were designed into a peptide sequence with histidine as the catalytic residue for the ester hydrolysis reaction. Upon the photo-induced oxidation reaction, the short peptide YYHYY rapidly transferred into nanoparticle-shaped aggregates (CL-YYHYY) and displayed improved esterase-like catalytic activity than some previously reported noncovalent-based artificial esterases. Impressively, CL-YYHYY showed outstanding reusability and superior stability under high temperature, strong acid and alkaline and organic solvent conditions. This study provides a promising approach to improving the catalytic activity and stability of peptide-based artificial enzymes.
ESTHER : Tian_2023_Soft.Matter__
PubMedSearch : Tian_2023_Soft.Matter__
PubMedID: 37129250

Title : Discovery of novel deoxyvasicinone derivatives with benzenesulfonamide substituents as multifunctional agents against Alzheimer's disease - Dong_2023_Eur.J.Med.Chem_264_116013
Author(s) : Dong S , Xia J , Wang F , Yang L , Xing S , Du J , Zhang T , Li Z
Ref : Eur Journal of Medicinal Chemistry , 264 :116013 , 2023
Abstract : A series of deoxyvasicinone derivatives with benzenesulfonamide substituents were designed and synthesized to find a multifunctional anti-Alzheimer's disease (AD) drug. The results of the biological activity evaluation indicated that most compounds demonstrated selective inhibition of acetylcholinesterase (AChE). Among them, g17 exhibited the most potent inhibitory effect on AChE (IC(50) = 0.24 +/- 0.04 microM). Additionally, g17 exhibited promising properties as a metal chelator and inhibitor of amyloid beta peptides self-aggregation (68.34 % +/- 1.16 %). Research on oxidative stress has shown that g17 displays neuroprotective effects and effectively suppresses the intracellular accumulation of reactive oxygen species. Besides, g17 demonstrated remarkable anti-neuroinflammatory effects by significantly reducing the production of pro-inflammatory cytokines (such as NO, IL-1beta, and TNF-alpha) and inhibiting the expression of inflammatory mediators iNOS and COX-2. In vivo studies showed that g17 significantly improved AD model mice's cognitive and memory abilities. Histological examination of mouse hippocampal tissue sections using hematoxylin and eosin staining revealed that g17 effectively mitigates neuronal damage. Considering the multifunctional properties of g17, it is regarded as a promising lead compound for treating AD.
ESTHER : Dong_2023_Eur.J.Med.Chem_264_116013
PubMedSearch : Dong_2023_Eur.J.Med.Chem_264_116013
PubMedID: 38052155

Title : Design of carboxymethylcellulose-conjugated polymeric prodrug micelles for enhanced in vivo performance of docetaxel - Liu_2023_Int.J.Biol.Macromol__127690
Author(s) : Liu Z , Liu Y , Liu H , Lv R , Liu B , Zhao L , Yin T , Zhang Y , He H , Gou J , Tang X , Yang L , Gao S
Ref : Int J Biol Macromol , :127690 , 2023
Abstract : Docetaxel (DTX) has become one of the most important cytotoxic drugs to treat cancer; nevertheless, its poor hydrophilicity and non-specific distribution of DTX lead to detrimental side effects. In this article, we devised carboxymethylcellulose (CMC)-conjugated polymeric prodrug micelles (mPEG-CMC-DTX PMs) for DTX delivery. The ester-bonded polymeric prodrug, mPEG-CMC-DTX, was synthesized and exhibited the capacity for self-assembling into polymeric micelles. The CMC is profusely substituted and acetylated to promote the coupling rate of DTX. Covalent binding of DTX and CMC through an ester bond can be hydrolyzed to dissociate the bond under the action of esterase in the tumor. The mPEG-CMC-DTX PMs displayed promoted drug loading (>50 %, wt), commendable stability, and sustained release behavior in vitro. The gradual release of the prodrug amplified the selectivity of cytotoxicity between normal cells and tumor cells, mitigating the systemic toxicity of mPEG-CMC-DTX PMs and enabling dose intensification. Notably, mPEG-CMC-DTX PMs demonstrated a superior antitumor efficacy and low systemic toxicity due to the elevated tolerance dosage (even at 40 mg/kg DTX). In summation, mPEG-CMC-DTX PMs harmonized the antitumor efficacy and toxicity of DTX. In essence, innovative perspectives for the rational design of CMC-conjugated polymeric prodrug micelles for the delivery of potently toxic drugs were proffered.
ESTHER : Liu_2023_Int.J.Biol.Macromol__127690
PubMedSearch : Liu_2023_Int.J.Biol.Macromol__127690
PubMedID: 37898254

Title : Fibroblast activation protein alpha: Comprehensive detection methods for drug target and tumor marker - Song_2022_Chem.Biol.Interact__109830
Author(s) : Song P , Pan Q , Sun Z , Zou L , Yang L
Ref : Chemico-Biological Interactions , :109830 , 2022
Abstract : Fibroblast activation protein alpha (FAP-alpha, EC3.4.2. B28), a type II transmembrane proteolytic enzyme for the serine protease peptidase family. It is underexpressed in normal tissues but increased significantly in disease states, especially in neoplasm, which is a potencial biomarker to turmor diagnosis. The inhibition of FAP-alpha activity will retard tumor formation, which is expected to be a promising tumor therapeutic target. At present, although the FAP-alpha expression detection methods has diversification, a superlative detection means is necessary for the clinical diagnosis. This review covers the discovery and the latest advances in FAP-alpha, as well as the future research prospects. The tissue distribution, structural characteristics, small-molecule ligands and structure-activity relationship of major inhibitors of FAP-alpha were summarized in this review. Furthermore, a variety of detection methods including traditional detection methods and emerging probes detection were classified and compared, and the design strategy and kinetic parameters of these FAP-alpha probe substrates were summarized. In addition, these comprehensive information provides a series of practical and reliable assays for the optimal design principles of FAP-alpha probes, promoting the application of FAP-alpha as a disease marker in diagnosis, and a drug target in drug design.
ESTHER : Song_2022_Chem.Biol.Interact__109830
PubMedSearch : Song_2022_Chem.Biol.Interact__109830
PubMedID: 35104486

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 : Acquisition of T6SS Effector TseL Contributes to the Emerging of Novel Epidemic Strains of Pseudomonas aeruginosa - Ren_2022_Microbiol.Spectr__e0330822
Author(s) : Ren A , Jia M , Liu J , Zhou T , Wu L , Dong T , Cai Z , Qu J , Liu Y , Yang L , Zhang Y
Ref : Microbiol Spectr , :e0330822 , 2022
Abstract : Pseudomonas aeruginosa is an opportunistic pathogen with multiple strategies to interact with other microbes and host cells, gaining fitness in complicated infection sites. The contact-dependent type VI secretion system (T6SS) is one critical secretion apparatus involved in both interbacterial competition and pathogenesis. To date, only limited numbers of T6SS-effectors have been clearly characterized in P. aeruginosa laboratory strains, and the importance of T6SS diversity in the evolution of clinical P. aeruginosa remains unclear. Recently, we characterized a P. aeruginosa clinical strain LYSZa7 from a COVID-19 patient, which adopted complex genetic adaptations toward chronic infections. Bioinformatic analysis has revealed a putative type VI secretion system (T6SS) dependent lipase effector in LYSZa7, which is a homologue of TseL in Vibrio cholerae and is widely distributed in pathogens. We experimentally validated that this TseL homologue belongs to the Tle2, a subfamily of T6SS-lipase effectors; thereby, we name this effector TseL (TseL(PA) in this work). Further, we showed the lipase-dependent bacterial toxicity of TseL(PA), which primarily targets bacterial periplasm. The toxicity of TseL(PA) can be neutralized by two immunity proteins, TsiP1 and TsiP2, which are encoded upstream of tseL. In addition, we proved this TseL(PA) contributes to bacterial pathogenesis by promoting bacterial internalization into host cells. Our study suggests that clinical bacterial strains employ a diversified group of T6SS effectors for interbacterial competition and might contribute to emerging of new epidemic clonal lineages. IMPORTANCE Pseudomonas aeruginosa is one predominant pathogen that causes hospital-acquired infections and is one of the commonest coinfecting bacteria in immunocompromised patients and chronic wounds. This bacterium harbors a diverse accessory genome with a high frequency of gene recombination, rendering its population highly heterogeneous. Numerous Pa lineages coexist in the biofilm, where successful epidemic clonal lineage or strain-specific type commonly acquires genes to increase its fitness over the other organisms. Current studies of Pa genomic diversity commonly focused on antibiotic resistant genes and novel phages, overlooking the contribution of type VI secretion system (T6SS). We characterized a Pa clinical strain LYSZa7 from a COVID-19 patient, which adopted complex genetic adaptations toward chronic infections. We report, in this study, a novel T6SS-lipase effector that is broadly distributed in Pa clinical isolates and other predominant pathogens. The study suggests that hospital transmission may raise the emergence of new epidemic clonal lineages with specified T6SS effectors.
ESTHER : Ren_2022_Microbiol.Spectr__e0330822
PubMedSearch : Ren_2022_Microbiol.Spectr__e0330822
PubMedID: 36546869
Gene_locus related to this paper: pseae-T6SSTseL

Title : Molecular mechanisms by which targeted muscle reinnervation improves the microenvironment of spinal cord motor neurons and target muscles - Lu_2022_Neurosci.Lett_789_136879
Author(s) : Lu W , Jiang Z , Tang C , Wang P , Yang L
Ref : Neuroscience Letters , 789 :136879 , 2022
Abstract : Targeted muscle reinnervation is a clinically valuable nerve transfers technology used to reconstruct the information sources reconstruct the motor nerve information sources lost because of nerve injury. This study aimed to investigate the effects and underlying molecular mechanisms of hind limb TMR on motor neurons and target muscles in rats after tibial nerve transection (TNT). Immunohistochemistry was performed to detect acetylcholinesterase expression in the target muscles and myelin basic protein, neuregulin-1 (NRG1), and ErbB2 expression in the tibial nerve of rats. Masson's trichrome staining was performed to observe fibrillar collagen expression in the target muscles. Western blot analysis was used to detect the protein expression of NRG1 and its receptor, ErbB2, in the target muscles. TMR significantly enhanced NRG1, ErbB2, and myelin basic protein expression in nerve fibers compared with those in the TNT group and exerted a protective effect on the maintenance of a large number of nerve fibers and myelin sheath thickness. The above results indicated that TMR can regulate NRG1 and ErbB2 expression in residual nerve fibers and protect the integrity of the myelin sheath, thus improving the functional status of the target muscles, which is beneficial for restoring hind limb motor function after TNT.
ESTHER : Lu_2022_Neurosci.Lett_789_136879
PubMedSearch : Lu_2022_Neurosci.Lett_789_136879
PubMedID: 36152746

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

Title : Adipose tissue-specific ablation of Ces1d causes metabolic dysregulation in mice - Li_2022_Life.Sci.Alliance_5_
Author(s) : Li G , Li X , Yang L , Wang S , Dai Y , Fekry B , Veillon L , Tan L , Berdeaux R , Eckel-Mahan K , Lorenzi PL , Zhao Z , Lehner R , Sun K
Ref : Life Sciences Alliance , 5 : , 2022
Abstract : Carboxylesterase 1d (Ces1d) is a crucial enzyme with a wide range of activities in multiple tissues. It has been reported to localize predominantly in ER. Here, we found that Ces1d levels are significantly increased in obese patients with type 2 diabetes. Intriguingly, a high level of Ces1d translocates onto lipid droplets where it digests the lipids to produce a unique set of fatty acids. We further revealed that adipose tissue-specific Ces1d knock-out (FKO) mice gained more body weight with increased fat mass during a high fat-diet challenge. The FKO mice exhibited impaired glucose and lipid metabolism and developed exacerbated liver steatosis. Mechanistically, deficiency of Ces1d induced abnormally large lipid droplet deposition in the adipocytes, causing ectopic accumulation of triglycerides in other peripheral tissues. Furthermore, loss of Ces1d diminished the circulating free fatty acids serving as signaling molecules to trigger the epigenetic regulations of energy metabolism via lipid-sensing transcriptional factors, such as HNF4alpha. The metabolic disorders induced an unhealthy microenvironment in the metabolically active tissues, ultimately leading to systemic insulin resistance.
ESTHER : Li_2022_Life.Sci.Alliance_5_
PubMedSearch : Li_2022_Life.Sci.Alliance_5_
PubMedID: 35459739
Gene_locus related to this paper: mouse-Ces1d

Title : Case Report: Next-Generation Sequencing Identified a Novel Pair of Compound-Heterozygous Mutations of LPL Gene Causing Lipoprotein Lipase Deficiency - Li_2022_Front.Genet_13_831133
Author(s) : Li Y , Hu M , Han L , Feng L , Yang L , Chen X , Du T , Yao H
Ref : Front Genet , 13 :831133 , 2022
Abstract : Lipoprotein lipase deficiency (LPLD) is a rare disease characterized by the accumulation of chylomicronemia with early-onset. Common symptoms are abdominal pain, hepatosplenomegaly, eruptive xanthomas and lipemia retinalis. Serious complications include acute pancreatitis. Gene LPL is one of causative factors of LPLD. Here, we report our experience on an asymptomatic 3.5-month-old Chinese girl with only milky blood. Whole-exome sequencing was performed and identified a pair of compound-heterozygous mutations in LPL gene, c.862G>A (p.A288T) and c.461A>G (p.H154R). Both variants are predicted "deleterious" and classified as "likely pathogenic". This study expanded the LPL mutation spectrum of disease LPLD, thereby offering exhaustive and valuable experience on early diagnosis and proper medication of LPLD.
ESTHER : Li_2022_Front.Genet_13_831133
PubMedSearch : Li_2022_Front.Genet_13_831133
PubMedID: 35309119
Gene_locus related to this paper: human-LPL

Title : Gelsemine relieves the neuropathic pain by down-regulating DPP4 level in rats - Yang_2022_Neurosci.Lett_792_136961
Author(s) : Yang L , Zhou G , Chen J , Zhang S
Ref : Neuroscience Letters , 792 :136961 , 2022
Abstract : BACKGROUND: Based on the previous findings on the relieving role of gelsemine in neuropathic pain, this research aims to further investigate the relevant regulatory mechanism. METHODS: Targets of gelsemine were predicted using SwissTargetPrediction. The peripheral neuropathic pain rat model was established by ligating spinal nerves, and then gelsemine (10 g for one day) or dipeptidyl peptidase 4 (DPP4) oligonucleotides (5 g/day, for 7 days) was injected into intrathecal bolus of rats. The mechanical threshold (0, 1, 2, 4 h after the last injection) was examined to evaluate the mechanical allodynia of rats. After the mechanical threshold measurement, the rats were anesthetized with isoflurane and then sacrificed by cervical dislocation. IBA1- and DPP4-positive cells in the spinal dorsal horn of rats were determined using immunohistochemistry and immunofluorescence assays. The expressions of DPP4, IL-1 and TNF-alpha in the spinal dorsal horn of rats were measured by Western blot and quantitative real-time PCR. RESULTS: DPP4 was one of the targets of gelsemine. Gelsemine could elevate the down-regulated mechanical threshold, and lessen the up-regulated IBA1- and DPP4-positive cells and expressions of DPP4, IL-1 and TNF-alpha in the spinal dorsal horn of rats with neuropathic pain. DPP4 overexpression reversed the role of gelsemine in neuropathic pain. CONCLUSION: Gelsemine relieves neuropathic pain by down-regulating DPP4 level in rats, providing a novel drug candidate and biomarker for neuropathic pain treatment.
ESTHER : Yang_2022_Neurosci.Lett_792_136961
PubMedSearch : Yang_2022_Neurosci.Lett_792_136961
PubMedID: 36370955

Title : Study on pathological and clinical characteristics of chronic HBV infected patients with HBsAg positive, HBV DNA negative, HBeAg negative - Zeng_2022_Front.Immunol_13_1113070
Author(s) : Zeng Z , Liu R , Cao W , Yang L , Lin Y , Bi X , Jiang T , Deng W , Wang S , Lu H , Sun F , Shen G , Chang M , Lu Y , Wu S , Hao H , Xu M , Chen X , Hu L , Zhang L , Wan G , Xie Y , Li M
Ref : Front Immunol , 13 :1113070 , 2022
Abstract : AIMS: Study of clinical characteristics of hepatitis B virus deoxyribonucleic acid (HBV DNA)-negative, hepatitis B surface antigen (HBsAg)-positive, hepatitis B e antigen (HBeAg)-negative patients based on liver histopathology. METHODS: We retrospectively enrolled patients with chronic HBV infection diagnosis at Beijing Ditan Hospital from May 2008 to November 2020. To study the differences between patients with significant hepatic histopathology and those without significant hepatic histopathology. And to study the independent factors of significant hepatic histopathology. RESULTS: 85 HBV DNA-negative and HBeAg-negative patients were 37.90 +/- 10.30 years old, 23.50% of patients with grade of inflammation (G) >1, 35.30% of patients with liver fibrosis stage (S) >1, 44.70% patients were diagnosed with significant hepatic histopathology. Compared to the no significant hepatic histopathology group, another group had older age (41.70 +/- 10.70 vs 34.80 +/- 8.87 years, t=-3.28, P=0.002), higher total bilirubin (TBIL) [14.9(10.3, 22.4) vs 11(8.9, 14.4) micromol/L, z=-2.26, P=0.024], lower cholinesterase (CHE) (t=-2.86, P=0.005, 7388.00 +/- 2156.00 vs 8988.00 +/- 2823.00 U/L) and lower platelet (PLT) (t=2.75, P=0.007, 157.00 +/- 61.40 vs 194.00 +/- 61.00 10^9/L). Abnormal ALT patients are more likely to have significant hepatic histopathology (z=5.44, P=0.020, 66.70% vs 337.50%). G had significant correlation with CHE (P=0.008, r=-0.23), alanine aminotransferase (ALT) (P=0.041, r=0.18), aspartate aminotransferase (AST) (P=0.001, r=0.29). S had significant correlation with TBIL (P = 0.008, r = 0.23), age (P < 0.001, r = 0.32), international normalized ratio (INR) (P = 0.04, r = 0.23), CHE (P < 0.001, r = -0.30), PLT (P < 0.001, r = -0.40) and prothrombin time activity (PTA) (P = 0.046, r = -0.22). Multivariate logistic analysis indicated only age (95%CI=1.014~1.130, OR=1.069, P=0.013) was an impact factor for significant hepatic histopathology. The cutoff point of age was 34.30 years. CONCLUSIONS: A large proportion of chronic HBV infection patients with HBeAg-negative and HBV DNA-negative still have chronic hepatitis. Age is an independent factor for significant hepatic histopathology.
ESTHER : Zeng_2022_Front.Immunol_13_1113070
PubMedSearch : Zeng_2022_Front.Immunol_13_1113070
PubMedID: 36685494

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 : Design, synthesis and insecticidal activity and mechanism research of Chasmanthinine derivatives - Song_2022_Sci.Rep_12_15290
Author(s) : Song Z , Li X , Xu K , Sun G , Yang L , Huang L , Liu J , Yin P , Huang S , Gao F , Zhou X , Chen L
Ref : Sci Rep , 12 :15290 , 2022
Abstract : Unrestricted reproduction and spread of pest had caused great damage to the quality and yield of crops in recent years. Besides the use of traditional chemical pesticides, natural products also make a huge contribution against pests. Chasmanthinine, a diterpenoid alkaloid isolated from Aconitum franchetii var. villosulum, shown extremely antifeedant activity against Spodoptera exigua. Therefore, a series of novel Chasmanthinine derivatives were synthesized and their biological activity was studied in this work. Compound 33 showed the strongest antifeedant activity (EC(50) = 0.10 mg/cm(2)) among all the test compounds. The mechanism research of 33 revealed that its antifeedant effect was related to the inhibition of carboxylesterase (CES), and proved the thiophene acyl group could form a strong binding effect with CES by molecular docking. Moreover, compound 10 exhibited the strongest cytotoxicity (IC(50) = 12.87 microM) against Sf9 cell line and moderate contact toxicity. The mechanism research indicated that compound 10 could induce Sf9 cells apoptosis. In summary, the results lay a foundation for the application of diterpene alkaloids in plant protection.
ESTHER : Song_2022_Sci.Rep_12_15290
PubMedSearch : Song_2022_Sci.Rep_12_15290
PubMedID: 36088472

Title : Acetylcholinesterase-Cu(3)(PO(4))(2) hybrid nanoflowers for electrochemical detection of dichlorvos using square-wave voltammetry - Yang_2022_Anal.Methods__
Author(s) : Yang L , Zhang X , Li M , Qu L , Liu Z
Ref : Anal Methods , : , 2022
Abstract : Immobilization of enzymes is one of the key steps in the development of high-performance enzymatic electrochemical biosensors, and various nanostructured materials have been designed and developed to achieve this goal. Herein, hybrid nanoflowers (HNFs) were synthesized using acetylcholinesterase (AChE) as an organic component and copper phosphate (Cu(3)(PO(4))(2)) as an inorganic component. These AChE-Cu(3)(PO(4))(2) HNFs exhibit a three-dimensional hierarchical flower-like structure, which not only has a large specific surface area but also promotes the affinity between AChE and its substrate with better catalytic activity. Not only that, the surface modification of the glassy carbon electrode (GCE) by the joint use of gold nanoparticles (AuNPs) and graphene oxide (GO) extended the electroactive area. Using square-wave voltammetry (SWV), the as-prepared biosensor (i.e., AChE-Cu(3)(PO(4))(2) HNF/AuNP/GO/GCE) demonstrated superior sensing performance in the detection of dichlorvos. The detection limit is as low as 0.07 pM, and the linear detection range can range from 0.5 pM to 10 microM. In addition, the biosensor was feasible in real agricultural samples with satisfactory recoveries (98.65% to 103.43%). The reported biosensor provides an alternative tool for the direct measurements of AChE activity and its inhibition. Besides organophosphorus pesticides represented by dichlorvos, this biosensor has the potential to detect other AChE inhibitors, such as carbamate pesticides, drugs for Alzheimer's disease, etc., thus having broader applications in food safety and drug screening.
ESTHER : Yang_2022_Anal.Methods__
PubMedSearch : Yang_2022_Anal.Methods__
PubMedID: 36169013

Title : Discovery of triterpenoids as potent dual inhibitors of pancreatic lipase and human carboxylesterase 1 - Zhang_2022_J.Enzyme.Inhib.Med.Chem_37_629
Author(s) : Zhang J , Pan QS , Qian XK , Zhou XL , Wang YJ , He RJ , Wang LT , Li YR , Huo H , Sun CG , Sun L , Zou LW , Yang L
Ref : J Enzyme Inhib Med Chem , 37 :629 , 2022
Abstract : Pancreatic lipase (PL) is a well-known key target for the prevention and treatment of obesity. Human carboxylesterase 1A (hCES1A) has become an important target for the treatment of hyperlipidaemia. Thus, the discovery of potent dual-target inhibitors based on PL and hCES1A hold great potential for the development of remedies for treating related metabolic diseases. In this study, a series of natural triterpenoids were collected and the inhibitory effects of these triterpenoids on PL and hCES1A were determined using fluorescence-based biochemical assays. It was found that oleanolic acid (OA) and ursolic acid (UA) have the excellent inhibitory effects against PL and hCES1A, and highly selectivity over hCES2A. Subsequently, a number of compounds based on the OA and UA skeletons were synthesised and evaluated. Structure-activity relationship (SAR) analysis of these compounds revealed that the acetyl group at the C-3 site of UA (compound 41) was very essential for both PL and hCES1A inhibition, with IC(50) of 0.75 microM and 0.014 microM, respectively. In addition, compound 39 with 2-enol and 3-ketal moiety of OA also has strong inhibitory effects against both PL and hCES1A, with IC(50) of 2.13 microM and 0.055 microM, respectively. Furthermore, compound 39 and 41 exhibited good selectivity over other human serine hydrolases including hCES2A, butyrylcholinesterase (BChE) and dipeptidyl peptidase IV (DPP-IV). Inhibitory kinetics and molecular docking studies demonstrated that both compounds 39 and 41 were effective mixed inhibitors of PL, while competitive inhibitors of hCES1A. Further investigations demonstrated that both compounds 39 and 41 could inhibit adipocyte adipogenesis induced by mouse preadipocytes. Collectively, we found two triterpenoid derivatives with strong inhibitory ability on both PL and hCES1A, which can be served as promising lead compounds for the development of more potent dual-target inhibitors targeting on PL and hCES1A.
ESTHER : Zhang_2022_J.Enzyme.Inhib.Med.Chem_37_629
PubMedSearch : Zhang_2022_J.Enzyme.Inhib.Med.Chem_37_629
PubMedID: 35100926

Title : Strigolactone signaling complex formation in yeast: A paradigm for studying hormone-induced receptor interaction with multiple downstream proteins - Yu_2022_Methods.Enzymol_674_519
Author(s) : Yu H , Yang L , Long H , Su X , Wang Y , Xing Q , Yao R , Zhang M , Chen L
Ref : Methods Enzymol , 674 :519 , 2022
Abstract : Strigolactones (SLs) are bioactive carotenoid derivatives which function as signaling molecules to regulate plant architecture, nutrient absorption and communication with other organisms. The alpha/beta-fold hydrolase, D14, hydrolyzes SLs, and the hydrolysis product activates D14 to bind to downstream signaling partners, including an E3 ubiquitin ligase MAX2 and SMXL6/7/8 proteins. What was not known was whether binding with one downstream partner would alter the affinity of D14 for other binding partners. Here, we developed an efficient yeast four-hybrid (Y4H) detection system and demonstrate that SL induces the interaction of D14 with both SMXL7 and MAX2 in a dose-dependent manner. Moreover, using our newly established yeast four-hybrid system, we found that the SL-induced D14 interaction with SMXL7 was strengthened by MAX2 while SMXL7 weakened the SL-induced D14 interaction with MAX2. Our findings provide novel insights into the regulatory effects of these signaling components and shed light on the molecular mechanism controlling the core SL signaling pathway. Furthermore, the heterologous yeast platform used for investigating SL complex formation has great potential to explore dynamic interactions in other signaling pathways or elucidate the unknown complex formation for biosynthesis of the parent carotenoids of SLs.
ESTHER : Yu_2022_Methods.Enzymol_674_519
PubMedSearch : Yu_2022_Methods.Enzymol_674_519
PubMedID: 36008019

Title : Triterpenoids as bivalent and dual inhibitors of acetylcholinesterase\/butyrylcholinesterase from the fruiting bodies of Inonotus obliquus - Wei_2022_Phytochemistry__113182
Author(s) : Wei YM , Yang L , Wang H , Cai CH , Chen ZB , Chen HQ , Mei WL , Dai HF
Ref : Phytochemistry , :113182 , 2022
Abstract : Inonotus obliquus, an edible and medicinal mushroom parasitic on birches, has been used in human diet and for traditional therapies in the high latitude regions of Europe and Asia for a long time. Our phytochemical study of this fungus led to the identification of fourteen triterpenoids including four undescribed ones, and two pairs of undescribed phenolic enantiomers. The undescribed compounds were elucidated by extensive spectroscopic analysis including 1D and 2D NMR and HRESIMS, quantum chemical NMR and ECD calculations, as well as single-crystal X-ray diffraction analysis. Bioassays revealed that eight compounds showed dual inhibition against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) with IC(50) values ranging from 2.40 +/- 0.05 to 28.72 +/- 0.46 microM, while 3beta-hydroxy-lanosra-8,24-dien-21-al and trametenolic acid only presented BuChE inhibitory activities with IC(50) values of 22.21 +/- 1.01 and 7.68 +/- 0.13 microM, respectively. In the kinetic studies, the most active three compounds acted as non-competitive inhibitors for both cholinesterases. Furthermore, molecular docking simulations revealed that three compounds demonstrated dual-sites bounding to AChE/BuChE. These triterpenoids emerged as bivalent and dual inhibitors of AChE/BuChE and could be effective drug candidates to prevent and treat Alzheimer's disease in the future.
ESTHER : Wei_2022_Phytochemistry__113182
PubMedSearch : Wei_2022_Phytochemistry__113182
PubMedID: 35427650

Title : Baseline lymphocyte and cholinesterase levels may be the predictors of chronic herbal drug-induced liver injury - Zeng_2022_Front.Pharmacol_13_962480
Author(s) : Zeng Z , Yi W , Dong JP , Chen QQ , Sun FF , Lu HH , Lin YJ , Bi XY , Yang L , Lu Y , Zhang L , Li MH , Xie Y
Ref : Front Pharmacol , 13 :962480 , 2022
Abstract : Objective: To investigate the factors influencing the chronicity of drug-induced liver injury (DILI) caused by Chinese herbal medicine. Methods: Patients with DILI diagnosed by using the RUCAM score were enrolled retrospectively. The subjects were patients with DILI induced by taking Chinese herbal medicine and were followed up for 48 weeks. These patients were divided into a cure group and a chronic group. The biochemical indicators were monitored at baseline and every 3 months. Logistic regression was used to analyze the risk factors of DILI chronicity. The ROC (receiver operator characteristic) curve was used to analyze the diagnostic efficiency of each factor. Results: A total of 420 patients with DILI were enrolled; 122 of them were caused by Chinese herbal medicine, 70.5% (86/122) of them were female, chronic group 31.2% (39/122), and cure group 68.0% (83/122); cholinesterase (ChE) in the chronic group was lower than that in the cure group (5467.10 +/- 2010.40 U/L vs. 6248.52 +/- 1901.78 U/L, p = 0.04, t = 2.078). There was no significant difference in the age between cured patients and chronic patients (p = 0.156, Z = -1.417). There was no significant difference between the prognosis of different genders (p = 0.521, Z = -0.639). The logistic regression analysis showed that baseline lymphocyte (OR = 0.429, 95%CI = 0.205-0.898, p = 0.025) and cholinesterase (OR = 0.088, 95%CI = 0.008-0.994, p = 0.049) were independent risk factors of drug-induced chronicity. Conclusion: Baseline lymphocyte and cholinesterase may be the predictive factors for the chronicity of Chinese herbal medicine-induced liver injury.
ESTHER : Zeng_2022_Front.Pharmacol_13_962480
PubMedSearch : Zeng_2022_Front.Pharmacol_13_962480
PubMedID: 35991883

Title : Neurotoxicity of tetrabromobisphenol A and SiO2 nanoparticle co-exposure in zebrafish and barrier function of the embryonic chorion - Zhu_2022_Sci.Total.Environ_845_157364
Author(s) : Zhu B , Lei L , Fu K , Zhao S , Hua J , Yang L , Han J , Li R , Zhou B
Ref : Sci Total Environ , 845 :157364 , 2022
Abstract : Silicon dioxide nanoparticles (n-SiO(2)) absorb tetrabromobisphenol A (TBBPA) and modify its bioavailability and toxicity in the aquatic phase; embryonic chorion is an efficient barrier against nanoparticles (e.g., SiO(2)) and influences their toxicity. However, few studies have investigated developmental neurotoxicity in fish after co-exposure to TBBPA and n-SiO(2), especially considering the barrier function of the chorion. In the present study, zebrafish embryos were exposed to TBBPA (50, 100, and 200 microg/L) alone or in combination with n-SiO(2) (25 mg/L) until 24 or 120 h post fertilization (hpf), in the presence and absence of the chorion. The results confirmed that TBBPA exposure alone significantly downregulated the expression of neurodevelopment marker genes (mbp, alpha-tubulin, shha, and gfap), altered acetylcholinesterase activity and acetylcholine content, and affected locomotor behavior at different developmental stages. Moreover, the results indicated that n-SiO(2) promoted TBBPA-induced neurotoxic effects in zebrafish larvae at 120 hpf, including further repression of the transcription of CNS-related genes, disruption of the cholinergic system, and decrease in the average swimming speed under dark/light stimulation. However, scanning electron microscopy/energy dispersive spectroscopy analysis revealed that at 24 hpf, the embryonic chorion efficiently blocked n-SiO(2) and consequently decreased the bioaccumulation of TBBPA and TBBPA-induced neurotoxicity in dechorionated zebrafish embryos. Taken together, the results demonstrate that n-SiO(2) affected the bioavailability and neurodevelopmental toxicity of TBBPA, and their combined toxicity to zebrafish embryos was mitigated by embryonic chorion, which will facilitate risk assessment on n-SiO(2) and TBBPA and improve understanding the function of the fish embryonic chorion.
ESTHER : Zhu_2022_Sci.Total.Environ_845_157364
PubMedSearch : Zhu_2022_Sci.Total.Environ_845_157364
PubMedID: 35843329

Title : Plasma exchange therapy for familial chylomicronemia syndrome in infant: A case report - Han_2022_Medicine.(Baltimore)_101_e29689
Author(s) : Han L , Qiang G , Yang L , Kou R , Li Q , Xin M , Liu R , Zhang Z
Ref : Medicine (Baltimore) , 101 :e29689 , 2022
Abstract : INTRODUCTION: Familial chylomicronemia syndrome (FCS) is a rare genetic disease. FCS usually manifests by the age of 10 years, and 25% of cases of FCS occur during infancy. Here we present a case of FCS in a male infant and summarize our experiences on the diagnosis and therapy of this case. PATIENT CONCERNS: A male infant aged 1 month and 8 days had recurrent hematochezia and hyperchylomicronemia. DIAGNOSIS: FCS based on symptoms and genetic test. INTERVENTIONS: Plasma exchange therapy. OUTCOMES: His development was normal with a good spirit and satisfactory weight gain, and no hematochezia occurred again. CONCLUSION: Genetic test is important for accurate diagnosis of FCS, and we identified a new mutation of lipoprotein lipase gene c.88C>A which conformed to autosomal recessive inheritance. Plasma exchange therapy can be applied to infants with FCS with low risk and good outcomes.
ESTHER : Han_2022_Medicine.(Baltimore)_101_e29689
PubMedSearch : Han_2022_Medicine.(Baltimore)_101_e29689
PubMedID: 35960041
Gene_locus related to this paper: human-LPL

Title : A stable biosensor based on chitosan-modified graphene for detecting organophosphorus pesticides - Zhang_2021_Biotechnol.Appl.Biochem__
Author(s) : Zhang J , Hu H , Wang P , Zhang C , Wuma J , Yang L
Ref : Biotechnol Appl Biochem , : , 2021
Abstract : An acetylcholinesterase (AChE) biosensor was successfully fabricated with a stable structure and high detection accuracy. Graphene (Gra) nano-fragments modified with chitosan and acetylcholinesterase were successively drip-coated on the surface of a glassy carbon electrode via a layer-by-layer assembly method. The concentration range of the sensor to detect dichlorvos was 0.1 nM to 100000 nM, and the limit of detection was 54 pM. Chitosan (CS) was used to modify graphene for the first time, which enhanced the mechanical flexibility of these graphene nanostructures, significantly improving the stability and detection accuracy of this sensor. This article is protected by copyright. All rights reserved.
ESTHER : Zhang_2021_Biotechnol.Appl.Biochem__
PubMedSearch : Zhang_2021_Biotechnol.Appl.Biochem__
PubMedID: 33660328

Title : Association analysis between FASN genotype and milk traits in Mediterranean buffalo and its expression among different buffalo tissues - Ye_2021_Trop.Anim.Health.Prod_53_366
Author(s) : Ye T , Deng T , Hosseini SM , Raza SHA , Du C , Chen C , Zhang X , Hu X , Yang L
Ref : Trop Anim Health Prod , 53 :366 , 2021
Abstract : Fatty acid synthase (FASN) is a multifunctional protein that catalyzes the synthesis of long-chain saturated fatty acid. In this study, we identified the single nucleotide polymorphisms (SNPs), and their association with milk traits in Mediterranean buffalo, and the expression of FASN gene in different tissues was measured. Nine SNPs (g.-1640G > A, g.-1099C > T, g.1095C > A, g.3221G > A, g.4762G > A, g.5299G > A, g.7164G > A, g.7272 T > C, and g.8927 T > C) were identified by DNA pooled sequencing and then genotyped. Seven identified SNPs except g.3221G > A and g.8927 T > C were found significantly associated with both fat and protein percentage, and also the g.7164G > A and g.8927 T > C had significant association with peak milk yield and protein percentage, respectively. One haplotype block was successfully constructed by linkage disequilibrium (LD) analysis and it showed a significant association with both fat percentage and protein percentage. Expression of FASN gene was found in almost all the buffalo tissues including mammary gland, heart, liver, spleen, lung, kidney, uterus, and ovary, and to be highest in lung and mammary gland. Our findings suggest that polymorphisms in the buffalo FASN gene are associated with milk production traits and can be used as a candidate gene for milk traits and marker-assisted selection in buffalo breeding program.
ESTHER : Ye_2021_Trop.Anim.Health.Prod_53_366
PubMedSearch : Ye_2021_Trop.Anim.Health.Prod_53_366
PubMedID: 34156604

Title : New 2-(2-Phenylethyl)chromone derivatives from agarwood originating from Aquilaria sinensis - Li_2021_J.Asian.Nat.Prod.Res__1
Author(s) : Li JT , Kuang TD , Chen HQ , Yang L , Wang H , Cai CH , Liu SB , Mei WL , Dai HF
Ref : J Asian Nat Prod Res , :1 , 2021
Abstract : Two new dimeric 2-(2-phenylethyl)chromones, aquilasinenones L and M (1 and 2), and one new monomer analogue, 5S, 6 R, 7S, 8 R-tetrahydroxy-[2-(3-methoxy-4-hydroxyphenyl)ethyl]- 5,6,7,8-tetrahydrochromone (3), together with two known compounds, were isolated from the artificial agarwood originating from Aquilaria sinensis. Compound 1 was the first structure found with C8-O-C4"' linkage among 2-(2-phenylethyl)chromone dimers. Their structures were unambiguously elucidated based on 1 D and 2 D NMR spectroscopy, as well as by comparison with the literature. The absolute configuration was determined by ECD calculation. None of the compounds exhibited acetylcholinesterase inhibitory activity.
ESTHER : Li_2021_J.Asian.Nat.Prod.Res__1
PubMedSearch : Li_2021_J.Asian.Nat.Prod.Res__1
PubMedID: 34958625

Title : ANGPTL8 in metabolic homeostasis: more friend than foe? - Guo_2021_Open.Biol_11_210106
Author(s) : Guo C , Wang C , Deng X , He J , Yang L , Yuan G
Ref : Open Biol , 11 :210106 , 2021
Abstract : ANGPTL8 is an important cytokine, which is significantly increased in type 2 diabetes mellitus (T2DM), obesity and metabolic syndrome. Many studies have shown that ANGPTL8 can be used as a bio-marker of these metabolic disorders related diseases, and the baseline ANGPTL8 level has also been found to be positively correlated with retinopathy and all-cause mortality in patients with T2DM. This may be related to the inhibition of lipoprotein lipase activity and the reduction of circulating triglyceride (TG) clearance by ANGPTL8. Consistently, inhibition of ANGPTL8 seems to prevent or improve atherosclerosis. However, it is puzzling that ANGPTL8 seems to have a directing function for TG uptake in peripheral tissues; that is, ANGPTL8 specifically enhances the reserve and buffering function of white adipose tissue, which may alleviate the ectopic lipid accumulation to a certain extent. Furthermore, ANGPTL8 can improve insulin sensitivity and inhibit hepatic glucose production. These contradictory results lead to different opinions on the role of ANGPTL8 in metabolic disorders. In this paper, the correlation between ANGPTL8 and metabolic diseases, the regulation of ANGPTL8 and the physiological role of ANGPTL8 in the process of glucose and lipid metabolism were summarized, and the physiological/pathological significance of ANGPTL8 in the process of metabolic disorder was discussed.
ESTHER : Guo_2021_Open.Biol_11_210106
PubMedSearch : Guo_2021_Open.Biol_11_210106
PubMedID: 34582711

Title : Neurotoxicity induced by combined exposure of microcystin-LR and nitrite in male zebrafish (Danio rerio): Effects of oxidant-antioxidant system and neurotransmitter system - Yang_2021_Comp.Biochem.Physiol.C.Toxicol.Pharmacol_253_109248
Author(s) : Yang L , Guo H , Kuang Y , Yang H , Zhang X , Tang R , Li D , Li L
Ref : Comparative Biochemistry & Physiology C Toxicol Pharmacol , 253 :109248 , 2021
Abstract : With the intensification of water eutrophication around the world, cyanobacterial blooms have been becoming a common environmental pollution problem. The levels of microcystin-LR (MC-LR) and nitrite rise sharply during the cyanobacterial bloom period, which may have potential joint toxicity on aquatic organisms. In this study, adult male zebrafish were immersed into different joint solutions of MC-LR (0, 3, 30 microg/L) and nitrite (0, 2, 20 mg/L) for 30 days to explore the neurotoxic effects and underlying mechanisms. The results showed that single factor MC-LR or nitrite caused a concentration-dependent damage in brain ultrastructure and the effects of their joint exposure were much more intense. Downregulated expression of mbp and bdnf associated with myelination of nerve fibers further confirmed that MC-LR and nitrite could damage the structure and function of neuron. The decreases in dopamine content, acetylcholinesterase activity and related gene mRNA levels indicated that MC-LR and nitrite adversely affected the normal function of the dopaminergic and cholinergic systems in zebrafish brain. In addition, the significant increase in malondialdehyde content suggested the occurrence of oxidative stress caused by MC-LR, nitrite and their joint-exposure, which paralleled a significant decrease in antioxidant enzymemanganese superoxide dismutase activity and its transcription level. In conclusion, MC-LR + Nitrite joint-exposure has synergistic neurotoxic effects on the structure and neurotransmitter systems of fish brain, and antioxidant capacity disruption caused by these two factors might be one of the underlying synergistic mechanisms. Therefore, there is a risk of being induced neurotoxicity in fish during sustained cyanobacterial bloom events.
ESTHER : Yang_2021_Comp.Biochem.Physiol.C.Toxicol.Pharmacol_253_109248
PubMedSearch : Yang_2021_Comp.Biochem.Physiol.C.Toxicol.Pharmacol_253_109248
PubMedID: 34826614

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 : Protein engineering of stable IsPETase for PET plastic degradation by Premuse - Meng_2021_Int.J.Biol.Macromol_180_667
Author(s) : Meng X , Yang L , Liu H , Li Q , Xu G , Zhang Y , Guan F , Zhang W , Wu N , Tian J
Ref : Int J Biol Macromol , 180 :667 , 2021
Abstract : Poly(ethylene terephthalate) (PET) is used widely by human beings, but is very difficult to degrade. Up to now, the PET degradation effect of PETase from Ideonella sakaiensis 201-F6 (IsPETase) variants with low stability and activity was not ideal. In this study, a mutation design tool, Premuse, was developed to integrate the sequence alignment and quantitative selection of the preferred mutations based on natural sequence evolution. Ten single point mutants were selected from 1486 homologous sequences using Premuse, and then two mutations (W159H and F229Y) with improved stability were screened from them. The derived double point mutant, W159H/F229Y, exhibited a strikingly enhanced enzymatic performance. Its T(m) and catalytic efficiency values (k(cat)/K(m)) respectively increased by 10.4 degreesC and 2.0-fold using p-NPP as the substrate compared with wild type. The degradation activity for amorphous PET was increased by almost 40-fold in comparison with wild type at 40 degreesC in 24 h. Additionally, the variant could catalyze biodegradation of PET bottle preform at a mean rate of 23.4 mg(PET)/h/mg(enzyme). This study allowed us to design the mutation more efficiently, and provides a tool for achieving biodegradation of PET pollution under mild natural environments.
ESTHER : Meng_2021_Int.J.Biol.Macromol_180_667
PubMedSearch : Meng_2021_Int.J.Biol.Macromol_180_667
PubMedID: 33753197
Gene_locus related to this paper: idesa-peth

Title : Tracing the genetic footprints of vertebrate landing in non-teleost ray-finned fishes - Bi_2021_Cell_184_1377
Author(s) : Bi X , Wang K , Yang L , Pan H , Jiang H , Wei Q , Fang M , Yu H , Zhu C , Cai Y , He Y , Gan X , Zeng H , Yu D , Zhu Y , Qiu Q , Yang H , Zhang YE , Wang W , Zhu M , He S , Zhang G
Ref : Cell , 184 :1377 , 2021
Abstract : Rich fossil evidence suggests that many traits and functions related to terrestrial evolution were present long before the ancestor of lobe- and ray-finned fishes. Here, we present genome sequences of the bichir, paddlefish, bowfin, and alligator gar, covering all major early divergent lineages of ray-finned fishes. Our analyses show that these species exhibit many mosaic genomic features of lobe- and ray-finned fishes. In particular, many regulatory elements for limb development are present in these fishes, supporting the hypothesis that the relevant ancestral regulation networks emerged before the origin of tetrapods. Transcriptome analyses confirm the homology between the lung and swim bladder and reveal the presence of functional lung-related genes in early ray-finned fishes. Furthermore, we functionally validate the essential role of a jawed vertebrate highly conserved element for cardiovascular development. Our results imply the ancestors of jawed vertebrates already had the potential gene networks for cardio-respiratory systems supporting air breathing.
ESTHER : Bi_2021_Cell_184_1377
PubMedSearch : Bi_2021_Cell_184_1377
PubMedID: 33545088
Gene_locus related to this paper: atrsp-a0a8j7tiu5

Title : Muscle-Specific Tyrosine Kinase Antibody Positive Myasthenia Gravis With Peripheral Nerve Hyperexcitability: Case Report and Literature Review - Yang_2021_Clin.Neuropharmacol__
Author(s) : Yang L
Ref : Clinical Neuropharmacology , : , 2021
Abstract : OBJECTIVES: Administration of acetylcholinesterase inhibitors can bring about peripheral nerve hyperexcitability symptom in muscle-specific tyrosine kinase antibody positive myasthenia gravis, but the changes in electromyography before and after drug withdrawal have not been described in detail. METHODS: Electromyography was performed on a case of muscle-specific tyrosine kinase antibody positive myasthenia gravis with peripheral nerve hyperexcitability correlated with the administration of pyridostigmine bromide before and after drug withdrawal, respectively. RESULTS: Afterdischarges close after M waves appeared on the tibial nerve, common peroneal nerve, median nerve, and ulnar nerve, and these presented unique characteristics in repetitive nerve stimulation. Ten days after pyridostigmine bromide withdrawal, the second electromyography examination was carried out and showed that the afterdischarges on all nerves disappeared dramatically and the amplitude of tibial nerve F waves was elevated than before. CONCLUSIONS: Afterdischarges can be an important indicator of muscle-specific tyrosine kinase antibody positive myasthenia gravis with peripheral nerve hyperexcitability correlated with acetylcholinesterase inhibitors.
ESTHER : Yang_2021_Clin.Neuropharmacol__
PubMedSearch : Yang_2021_Clin.Neuropharmacol__
PubMedID: 33470659

Title : Ric8 acts as a regulator of G-protein signaling required for nematode-trapping lifecycle of Arthrobotrys oligospora - Bai_2021_Environ.Microbiol__
Author(s) : Bai N , Zhang G , Wang W , Feng H , Yang X , Zheng Y , Yang L , Xie M , Zhang KQ , Yang J
Ref : Environ Microbiol , : , 2021
Abstract : Resistance to inhibitors of cholinesterase 8 (Ric8) is a conserved guanine nucleotide exchange factor that is involved in the regulation of G-protein signaling in filamentous fungi. Here, we characterized an orthologous Ric8 (AoRic8) in Arthrobotrys oligospora by multi-omics analyses. The Aoric8 deletion (deltaAoric8) mutants lost an ability to produce traps essential for nematode predation, accompanied by a marked reduction in cAMP level. Yeast two-hybrid assay revealed that AoRic8 interacted with G-protein subunit Galpha1. Moreover, the mutants were compromised in mycelia growth, conidiation, stress resistance, endocytosis, cellular components, and intrahyphal hyphae. Revealed by transcriptomic analysis differentially upregulated genes in the absence of Aoric8 were involved in cell cycle, DNA replication, and recombination during trap formation while downregulated genes were primarily involved in organelles, carbohydrate metabolism, and amino acid metabolism. Metabolomic analysis showed that many compounds were markedly downregulated in deltaAoric8 mutants versus the wild-type strain. Our results demonstrated a crucial role for AoRic8 in the fungal growth, environmental adaption, and nematode predation through control of cell cycle, organelle, and secondary metabolism by G-protein signaling. This article is protected by copyright. All rights reserved.
ESTHER : Bai_2021_Environ.Microbiol__
PubMedSearch : Bai_2021_Environ.Microbiol__
PubMedID: 34431203

Title : Bioactivities and modes of action of VUAA1 - Yang_2021_Pest.Manag.Sci_77_3685
Author(s) : Yang L , Demares F , Norris EJ , Jiang S , Bernier UR , Bloomquist JR
Ref : Pest Manag Sci , 77 :3685 , 2021
Abstract : BACKGROUND: The compound 2-((4-ethyl-5-(pyridin-3-yl)-4H-1,2,4-triazol-3-yl)thio)-N-(4-ethylphenyl) acetamide (VUAA1) is reported to be an odorant receptor co-receptor (Orco) agonist in insects with potential use as an insect repellent. For this study, the biological activity of VUAA1 was investigated in several bioassays with Aedes aegypti, including adult contact, spatial repellency, and larval repellency assays, as well as topical, injection, and feeding toxicity assays. Neurophysiological action was further explored by analysis of fruit fly central nervous system firing, cockroach axon recordings, patch clamp analysis of Kv2 potassium channel, and acetylcholinesterase inhibition studies. Finally, the metabolic impact on the toxicity of VUAA1 was explored by applying it in combination with established metabolic synergists. RESULTS: In repellency and bite protection screens, VUAA1 showed little activity against adult mosquitoes, apparently due to its low volatility, since its effectiveness was increased by heating or mixing with transfluthrin acid and citronella oil. It did produce measurable repellency of mosquito larvae that was more potent than N,N-diethyl-m-toluamide (DEET). Overall, VUAA1 showed low acute toxicity to both insects and mice, and it was weakly synergized by triphenyl phosphate. There was no observed cross-resistance in a pyrethroid-resistant strain of Anopheles gambiae. VUAA1 showed a two-phase effect on the central nervous system, with neuroexcitation at 1 micromol L(-1) and an inhibitory effect at 100micromol L(-1) that may relate to block of Kv2 potassium channels. CONCLUSIONS: VUAA1 presented low toxicity, similar to other insect repellents. Its limited solubility, low volatility, and resulting poor adult repellency without additional adjuvants may restrict the utility of VUAA1 in typical public health applications.
ESTHER : Yang_2021_Pest.Manag.Sci_77_3685
PubMedSearch : Yang_2021_Pest.Manag.Sci_77_3685
PubMedID: 32741076

Title : Construction of Peroxidase-like Metal-Organic Frameworks in TiO(2) Nanochannels: Robust Free-Standing Membranes for Diverse Target Sensing - Xu_2021_Anal.Chem__
Author(s) : Xu H , Guo J , Yang L , Gao Z , Song YY
Ref : Analytical Chemistry , : , 2021
Abstract : The high cost and easy denaturation of natural enzymes under environmental conditions hinder their practical usefulness in sensing devices. In this study, peroxidase (POD)-like metal-organic frameworks (MOFs) were in situ grown in the nanochannels of an anodized TiO(2) membrane (TiO(2)NM) as an electrochemical platform for multitarget sensing. By directly using a nanochannel wall as the precursor of metal nodes, Ti-MOFs were in situ derived on the nanochannel wall. Benefitting from the presence of bipyridine groups on the ligands, the MOFs in the nanochannels provide plenty of sites for Fe(3+) anchoring, thus endowing the resulting membrane (named as Fe(3+):MOFs/TiO(2)NM) with remarkable POD-like activity. Such Fe(3+)-induced POD-like activity is very sensitive to thiol-containing molecules owing to the strong coordination effect of thiols on Fe(3+). Most importantly, the POD-like activity of nanochannels can be in situ characterized by the current-potential (I-V) properties via catalyzing the oxidation of 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) substrate to the corresponding positively charged product ABTS(+). As a proof-of-concept application, the free-standing POD-like membranes were applied as a label-free assay in sensing cysteine, as well as monitoring acetylcholinesterase (AChE) activity through the generated thiol-containing product. Furthermore, based on the toxicity effect of organophosphorus (OP) compounds on AChE, the robust membranes were successfully utilized to evaluate the toxicity of diverse OP compounds. The POD-like nanochannels open up an innovative way to expand the application of nanochannel-based electrochemical sensing platforms in drug inspection, food safety, and environmental pollution.
ESTHER : Xu_2021_Anal.Chem__
PubMedSearch : Xu_2021_Anal.Chem__
PubMedID: 34170111

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 : BCL6B hypermethylation predicts metastasis and poor prognosis in early-stage hepatocellular carcinoma after thermal ablation - Li_2021_J.Cancer.Res.Ther_17_644
Author(s) : Li X , Guo M , Yang L , Cheng Z , Yu X , Han Z , Liu F , Sun Q , Han X , Yu J , Liang P
Ref : J Cancer Research Ther , 17 :644 , 2021
Abstract : AIMS: The aim of this study was to evaluate the role of BCL6B methylation in the progression of early-stage hepatocellular carcinoma (HCC) after thermal ablation. SETTINGS AND DESIGN: This is a retrospective study and written informed consent was obtained from all patients or their legal guardians. SUBJECTS AND METHODS: Between October 2008 and December 2013, 73 patients with early-stage HCC within the Milan criteria, who received thermal ablation, were recruited. STATISTICAL ANALYSIS USED: Based on methylation-specific polymerase chain reaction, the relationship between BCL6B methylation and patient characteristics and prognosis was analyzed using univariate, multivariate, and Kaplan-Meier analysis. RESULTS: The median follow-up period was 56 (8-110) months. For the BCL6B unmethylated group, the 1-, 3- and 5-year metastasis and overall survival (OS) rates after thermal ablation were 10.0%, 10.0%, and 40.0% and 100%, 100% and 90.0%, respectively. The 1-, 3-, and 5-year metastasis and OS rates of the methylated group were 23.8%, 66.7% and 88.9% and 66.2%, 71.4% and 41.3%, respectively. Levels of absolute count lymphocyte, serum cholinesterase and albumin in the BCL6B unmethylated group were higher than those in the methylated group (P = 0.020, 0.000, and 0.009, respectively). Kaplan-Meier analysis revealed that BCL6B methylation was related to metastasis and poor prognosis (P = 0.001 and 0.018, respectively). Univariate analysis revealed that BCL6B methylation was a risk factor for metastasis and poor prognosis (odds ratio [OR]: 5.663; 95% confidence interval [CI], 1.745-18.375, P = 0.004 and OR: 3.734; 95% CI, 1.151-12.110, P = 0.028, respectively). Multivariate analysis revealed that BCL6B methylation was an independent risk factor for metastasis (OR: 3.736; 95% CI, 1.000-13.963,P = 0.05) and not for prognosis (OR: 2.780; 95% CI, 0.835-9.250,P = 0.096). CONCLUSIONS: BCL6B methylation could be a valuable prognostic factor for metastasis and poor prognosis in early-stage HCC after thermal ablation, which is an independent risk factor for metastasis. Our findings provide insights for combining ablation and epigenetic therapy for patients with HCC.
ESTHER : Li_2021_J.Cancer.Res.Ther_17_644
PubMedSearch : Li_2021_J.Cancer.Res.Ther_17_644
PubMedID: 34269294

Title : Development of enzymatic electrochemical biosensors for organophosphorus pesticide detection - Hu_2020_J.Environ.Sci.Health.B__1
Author(s) : Hu H , Yang L
Ref : J Environ Sci Health B , :1 , 2020
Abstract : The enzymatic electrochemical biosensor has the advantages of simple operation, speed, and integration in the detection of organophosphorus pesticide (OPs) residues. It has the potential to become the best alternative to the traditional OP detection technology. This article introduces the OP identification principle of different enzymes, the OP detection mechanism of several common sensors, and the enzyme assembly method. In addition, the article discusses application of nanomaterials in sensor preparation and sensor performance parameters in the past decade. The related content of early sensors is outside the scope of this article.
ESTHER : Hu_2020_J.Environ.Sci.Health.B__1
PubMedSearch : Hu_2020_J.Environ.Sci.Health.B__1
PubMedID: 33284686

Title : Serum Cholinesterases, a Novel Marker of Clinical Activity in Inflammatory Bowel Disease: A Retrospective Case-Control Study - Shao_2020_Mediators.Inflamm_2020_4694090
Author(s) : Shao X , Yang L , Hu K , Shen R , Ye Q , Yuan X , Zhao Q , Shen J
Ref : Mediators Inflamm , 2020 :4694090 , 2020
Abstract : BACKGROUND: The aim of our study was to investigate whether serum cholinesterase (ChE) levels were associated with inflammatory bowel disease (IBD). MATERIALS AND METHODS: We conducted a retrospective case-control study to clarify the relationship between serum ChE levels and IBD that included 142 patients with ulcerative colitis (UC), 60 patients with Crohn's disease (CD), and 264 healthy controls (HCs). We used ROC curves to evaluate the diagnostic value of serum ChE levels for IBD. RESULTS: Substantially lower serum ChE levels were detected in patients with UC than in HCs (6376 U/L versus 8418 U/L, P < 0.001) and in patients with CD than in HCs (5181 U/L versus 8418 U/L, P < 0.001). Additionally, patients with CD displayed significantly lower serum ChE levels than patients with UC (5181 U/L versus 6376 U/L, P < 0.01). We also found that there was a negative association between serum ChE levels and the Crohn's Disease Activity Index (CDAI) score of patients with CD (P = 0.011) and the Simple Clinical Colitis Activity Index (SCCAI) score of patients with UC (P = 0.018). The area under the curve (AUC) for serum ChE for the diagnosis of IBD was 0.826, and the AUCs of serum ChE for the diagnosis of CD and UC were 0.890 and 0.800, respectively. CONCLUSIONS: Serum ChE levels have important clinical significance in the diagnosis and assessment of clinical activity in patients with IBD, and the cholinergic anti-inflammatory pathway may provide new ideas for targeted treatment of IBD.
ESTHER : Shao_2020_Mediators.Inflamm_2020_4694090
PubMedSearch : Shao_2020_Mediators.Inflamm_2020_4694090
PubMedID: 32733165

Title : Traditional uses, phytochemistry, pharmacology and toxicological aspects of the genus Hosta (Liliaceae): A comprehensive review - Yang_2020_J.Ethnopharmacol__113323
Author(s) : Yang L , He J
Ref : J Ethnopharmacol , :113323 , 2020
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: The genus Hosta (Liliaceae family) represents an interesting source of natural bio-constituents, and the 50 species of this genus are widespread in the world. Five species have been used as traditional East Asian medicines for treating inflammation and pain-related diseases. However, the available data for this genus have not been comprehensively reviewed regarding their extracts and secondary metabolites. AIM OF THE STUDY: The present review aims to provide a deeper insight, better awareness and detailed knowledge of traditional uses, phytochemistry, pharmacology along with toxicological aspects of the genus Hosta in the past decades (February 1964 to August 2020). In addition, the relevance among traditional uses, pharmacology and phytochemistry in folk medicines were extensively discussed. MATERIALS AND METHODS: The relevant information of Hosta species was obtained from several databases. Moreover, the medical books, PhD and MSc dissertations in Chinese were also used to perform this work. RESULTS: Comprehensive analysis of the afore-mentioned databases, medical books and dissertations confirmed that ethnomedical uses of Hosta genus plants had been recorded in China, Japan, Korea and other countries. To date, only eight species have been studied for chemical constituents, and a total of 200 secondary metabolites (not include essential oil constituents), including steroids, flavonoids, alkaloids, furan derivatives, phenylpropanoids, phenethyl derivatives, terpenoids, aliphatics, and others. The crude extracts and isolated chemical constituents exhibited anti-inflammatory and analgesic, antioxidant, anti-tumor, anti-viral, acetylcholinesterase inhibitory, antimicrobial, anti-chronic prostatitis, and other effects. Moreover, only the n-butanol fraction of H. ventricosa (Salisb.) Stearn roots showed moderate acute toxicity in mice. In addition, the relevance among traditional uses, pharmacology and phytochemistry in folk medicines were extensively discussed. CONCLUSIONS: Hosta spp. are plants rich in steroids and flavonoids with valuable medicinal properties; though, there are several gaps in understanding the traditional uses in the current available data. More high scientific quality preclinical studies with new methodology are necessary to assess the safety, efficacy and mechanism of these plants.
ESTHER : Yang_2020_J.Ethnopharmacol__113323
PubMedSearch : Yang_2020_J.Ethnopharmacol__113323
PubMedID: 32871235

Title : Acetylcholinesterase electrochemical biosensors with graphene-transition metal carbides nanocomposites modified for detection of organophosphate pesticides - Wang_2020_PLoS.One_15_e0231981
Author(s) : Wang B , Li Y , Hu H , Shu W , Yang L , Zhang J
Ref : PLoS ONE , 15 :e0231981 , 2020
Abstract : An acetylcholinesterase biosensor modified with graphene and transition metal carbides was prepared to detect organophosphorus pesticides. Cyclic voltammetry, differential pulse voltammetry, and electrochemical impedance spectroscopy were used to characterize the electrochemical catalysis of the biosensor: acetylcholinesterase/chitosan-transition metal carbides/graphene/glassy carbon electrode. With the joint modification of graphene and transition metal carbides, the biosensor has a good performance in detecting dichlorvos with a linear relationship from 11.31 muM to 22.6 nM and the limit of detection was 14.45 nM. Under the premise of parameter optimization, the biosensor showed a good catalytic performance for acetylcholine. Compared to the biosensors without modification, it expressed a better catalytic performance due to the excellent electrical properties, biocompatibility and high specific surface area of graphene, transition metal carbides. Finally, the biosensor exhibits good stability, which can be stored at room temperature for one month without significant performance degradation, and has practical potential for sample testing.
ESTHER : Wang_2020_PLoS.One_15_e0231981
PubMedSearch : Wang_2020_PLoS.One_15_e0231981
PubMedID: 32348360

Title : The MERS-CoV receptor DPP4 as a candidate binding target of the SARS-CoV-2 spike - Li_2020_iScience__101160
Author(s) : Li Y , Zhang Z , Yang L , Lian X , Xie Y , Li S , Xin S , Cao P , Lu J
Ref : iScience , :101160 , 2020
Abstract : The ongoing outbreak of the novel coronavirus pneumonia COVID-19 has caused great number of cases and deaths, but our understanding about the pathogen SARS-CoV-2 remains largely unclear. The attachment of the virus with the cell-surface receptor and a co-factor is the first step for the infection. Here, bioinformatics approaches combining human-virus protein interaction prediction and protein docking based on crystal structures have revealed the high affinity between human dipeptidyl peptidase 4 (DPP4) and the spike (S) receptor-binding domain of SARS-CoV-2. Intriguingly, the crucial binding residues of DPP4 are identical to those as bound to the MERS-CoV-S. Moreover, E484 insertion and adjacent substitutions should be most essential for this DPP4-binding ability acquirement of SARS-CoV-2-S compared with SARS-CoV-S. This potential utilization of DPP4 as a binding target for SARS-CoV-2 may offer novel insight into the viral pathogenesis, and help the surveillance and therapeutics strategy for meeting the challenge of COVID-19.
ESTHER : Li_2020_iScience__101160
PubMedSearch : Li_2020_iScience__101160
PubMedID: 32405622

Title : Colonization of Beauveria bassiana 08F04 in root-zone soil and its biocontrol of cereal cyst nematode (Heterodera filipjevi) - Zhang_2020_PLoS.One_15_e0232770
Author(s) : Zhang J , Fu B , Lin Q , Riley IT , Ding S , Chen L , Cui J , Yang L , Li H
Ref : PLoS ONE , 15 :e0232770 , 2020
Abstract : Cereal cyst nematodes cause serious yield losses of wheat in Hunaghuai winter wheat growing region in China. Beauveria bassiana 08F04 isolated from the surface of cysts is a promising biological control agent for cereal cyst nematodes. As the colonization capacity is a crucial criteria to assess biocontrol effectiveness for a microbial agent candidate, we aimed to label B. bassiana 08F04 for efficient monitoring of colonization in the soil. The binary pCAM-gfp plasmid containing sgfp and hph was integrated into B. bassiana 08F04 using the Agrobacterium tumefaciens-mediated transformation. The transformation caused a significant change in mycelial and conidial yields, and in extracellular chitinase activity in some transformants. The cultural filtrates of some transformants also decreased acetylcholinesterase activity and the survival of Heterodera filipjevi second-stage juveniles relative to the wild-type strain. One transformant (G10) had a growth rate and biocontrol efficacy similar to the wild-type strain, so it was used for a pilot study of B. bassiana colonization conducted over 13 weeks. Real-time PCR results and CFU counts revealed that the population of G10 increased quickly over the first 3 weeks, then decreased slowly over the following 4 weeks before stabilizing. In addition, the application of wild-type B. bassiana 08F04 and transformant G10 significantly reduced the number of H. filipjevi females in roots by 64.4% and 60.2%, respectively. The results of this study have practical applications for ecological, biological and functional studies of B. bassiana 08F04 and for bionematicide registration.
ESTHER : Zhang_2020_PLoS.One_15_e0232770
PubMedSearch : Zhang_2020_PLoS.One_15_e0232770
PubMedID: 32369513

Title : Bioluminescent Sensor Reveals that Carboxylesterase 1A is a Novel Endoplasmic Reticulum-Derived Serologic Indicator for Hepatocyte Injury - Wang_2020_ACS.Sens_5_1987
Author(s) : Wang DD , Zou LW , Jin Q , Guan XQ , Yu Y , Zhu YD , Huang J , Gao P , Wang P , Ge GB , Yang L
Ref : ACS Sens , 5 :1987 , 2020
Abstract : Discovery of novel liver injury indicators and development of practical assays to detect target indicator(s) would strongly facilitate the diagnosis of liver disorders. Herein, an alternative biomarker discovery strategy was applied to find suitable endoplasmic reticulum-resident protein(s) as serologic indicator(s) for hepatocyte injury via analysis of the human proteome database among plasma and various organs. Both database searching and preliminary experiments suggested that human carboxylesterase 1A (CES1A), one of the most abundant and hepatic-restricted proteins, could serve as a good serologic indicator for hepatocyte injury. Then, a highly selective and practical bioluminescent sensor was developed for real-time sensing of CES1A in various biological systems including plasma. With the help of this bioluminescent sensor, the release of hepatic CES1A into the extracellular medium or the circulation system could be directly monitored. Further investigations demonstrated that serum activity levels of CES1A were elevated dramatically in mice with liver injury or patients with liver diseases. Collectively, this study provided solid evidence to support that CES1A was a novel serological indicator for hepatocyte injury. Furthermore, the strategy used in this study paved a new way for the rational discovery of practical indicators to monitor the dynamic progression of injury in a given tissue or organ.
ESTHER : Wang_2020_ACS.Sens_5_1987
PubMedSearch : Wang_2020_ACS.Sens_5_1987
PubMedID: 32529833

Title : Bioconcentration and developmental neurotoxicity of novel brominated flame retardants, hexabromobenzene and pentabromobenzene in zebrafish - Chen_2020_Environ.Pollut_268_115895
Author(s) : Chen X , Guo W , Lei L , Guo Y , Yang L , Han J , Zhou B
Ref : Environ Pollut , 268 :115895 , 2020
Abstract : The flame retardants hexabromobenzene (HBB) and pentabromobenzene (PBB) have been extensively used and become ubiquitous pollutants in the aquatic environment and biota, but their potential toxic effects on wildlife remained unknown. In this study, by using zebrafish (Danio rerio) as a model, the bioconcentration and developmental neurotoxicity were investigated. Zebrafish embryos were exposed to HBB and PBB (0, 30, 100 and 300 g/L) from 2 until 144 h post-fertilization (hpf). Chemical analysis showed bioconcentrations of both chemicals, while HBB is readily metabolized to PBB in zebrafish larvae. Embryonic exposure to both chemicals did not cause developmental toxicity, but induced locomotor behavioral anomalies in larvae. Molecular docking results indicated that both chemicals could bind to zebrafish acetylcholinesterase (AChE). Furthermore, HBB and PBB significantly inhibited AChE activities, accompanied by increased contents of acetylcholine and decreased choline in larvae. Downregulation of the genes associated with central nervous system (CNS) development (e.g., mbp, alpha1-tubulin, gfap, shha) as well as the corresponding proteins (e.g., Mbp, alpha1-Tubulin) was observed, but gap-43 was upregulated at both gene and protein levels. Together, our results indicate that both HBB and PBB exhibit developmental neurotoxicity by affecting various parameters related to CNS development and indications for future toxicological research and risk assessment of the novel brominated flame retardants.
ESTHER : Chen_2020_Environ.Pollut_268_115895
PubMedSearch : Chen_2020_Environ.Pollut_268_115895
PubMedID: 33120153

Title : Rapid bioluminescence assay for monitoring rat CES1 activity and its alteration by traditional Chinese medicines - Zhang_2020_J.Pharm.Anal_10_253
Author(s) : Zhang J , Wang D , Zou L , Xiao M , Zhang Y , Li Z , Yang L , Ge G , Zuo Z
Ref : J Pharm Anal , 10 :253 , 2020
Abstract : In traditional Chinese medicine herbs (TCM), including Radix Salviae Miltiorrhizae (Danshen), Radix Puerariae Lobatae (Gegen), Radix Angelicae Sinensis (Danggui), and Rhizoma Chuanxiong (Chuanxiong) are widely used for the prevention and treatment of cardiovascular diseases and also often co-administered with Western drugs as a part of integrative medicine practice. Carboxylesterase 1 (CES1) plays a pivotal role in the metabolisms of pro-drugs. Since (S)-2-(2-(6-dimethylamino)-benzothiazole)-4,5-dihydro-thiazole-4-carboxylate (NLMe) has recently been identified by us as a selective CES1 bioluminescent sensor, we developed a rapid method using this substrate for the direct measurement of CES1 activity in rats. This bioluminescence assay was applied to determine CES1 activity in rat tissues after a two-week oral administration of each of the four herbs noted above. The results demonstrated the presence of CES1 enzyme in rat blood and all tested tissues with much higher enzyme activity in the blood, liver, kidney and heart than that in the small intestine, spleen, lung, pancreas, brain and stomach. In addition, the four herbs showed tissue-specific effects on rat CES1 expression. Based on the CES1 biodistribution and its changes after treatment in rats, the possibility that Danshen, Gegen and Danggui might alter CES1 activities in human blood and kidney should be considered. In summary, a selective and sensitive bioluminescence assay was developed to rapidly evaluate CES1 activity and the effects of orally administered TCMs in rats.
ESTHER : Zhang_2020_J.Pharm.Anal_10_253
PubMedSearch : Zhang_2020_J.Pharm.Anal_10_253
PubMedID: 32612872

Title : Aberrant mPFC GABAergic Synaptic Transmission and Fear Behavior in Neuroligin-2 R215H Knock-in Mice - Chen_2020_Brain.Res__146671
Author(s) : Chen J , Dong B , Feng X , Jiang D , Chen G , Long C , Yang L
Ref : Brain Research , :146671 , 2020
Abstract : Aberrant medial prefrontal cortex (mPFC) activity is associated with neuropsychiatric disorders such as schizophrenia, but the precise role of mPFC GABAergic neurotransmission in the pathogenesis of schizophrenia remains not well understood. Neuroligin-2 (Nlgn 2) is a postsynaptic cell-adhesion protein playing an important role in inhibitory synapse formation and function. Mutations of Nlgn 2 have been reported to be associated with schizophrenia. Using a Nlgn 2 Arg(215)-->His(215) mutation knock-in (NL2 R215H KI) mouse model of schizophrenia, we show here that inhibitory synaptic transmission, such as miniature and evoked inhibitory postsynaptic currents (mIPSCs, eIPSCs), is significantly reduced in the mPFC of NL2 R215H KI mice. The levels of inhibition-related proteins, including parvalbumin (PV), the gamma2 subunit of the GABAA receptor, and a vesicular GABA transporter vGAT, are also reduced significantly in NL2 R215H KI mPFC. The reduction of GABAergic inhibition disrupts the excitation/inhibition (E/I) ratio in mPFC, and results in the subsequent abnormal gamma oscillation in the mPFC of R215H KI mice. Behavioral evaluation suggests that GABAergic deficits contribute, at least in part, to alterations in fear response, which requires balanced E/I ratio of mPFC neurons. These results suggest a pivotal role of Nlgn 2 in maintaining E/I balance in the mPFC and in the maintenance of normal behaviors governed by the mPFC.
ESTHER : Chen_2020_Brain.Res__146671
PubMedSearch : Chen_2020_Brain.Res__146671
PubMedID: 31953212

Title : In vitro biolayer interferometry analysis of acetylcholinesterase as a potential target of aryl-organophosphorus flame-retardants - Shi_2020_J.Hazard.Mater_409_124999
Author(s) : Shi Q , Guo W , Shen Q , Han J , Lei L , Chen L , Yang L , Feng C , Zhou B
Ref : J Hazard Mater , 409 :124999 , 2020
Abstract : Organophosphorus flame retardants (OPFRs) have been implicated as neurotoxicants, but their potential neurotoxicity and mechanisms remain poorly understood. Herein, we investigated the neurotoxicity of selected OPFRs using zebrafish as a model organism. Environmentally relevant concentrations (3-1500 nM) of three classes of OPFRs (aryl-OPFRs, chlorinated-OPFRs, and alkyl-OPFRs) were tested in zebrafish larvae (2-144 h post-fertilisation) alongside the neurotoxic chemical chlorpyrifos (CPF) that inhibits acetylcholinesterase (AChE). Exposure to aryl-OPFRs and CPF inhibited AChE activities, while chlorinated- and alkyl-OPFRs did not inhibit these enzymes. Biolayer interferometry (BLI) was used to probe interactions between OPFRs and AChE. The association and dissociation response curves showed that, like CPF, all three selected aryl-OPFRs, triphenyl phosphate (TPHP), tricresyl phosphate (TCP) and cresyl diphenyl phosphate (CDP), bound directly to AChE. The affinity constant (K(D)) for TPHP, TCP, CDP and CPF was 2.18 x 10(-4), 5.47 x 10(-5), 1.05 x 10(-4) and 1.70 x 10(-5) M, respectively. In addition, molecular docking revealed that TPHP, TCP, CDP and CPF bound to AChE with glide scores of - 7.8, - 8.3, - 8.1 and - 7.3, respectively. Furthermore, the calculated binding affinity between OPFRs and AChE correlated well with the K(D) values measured by BLI. The present study revealed that aryl-OPFRs can act as potent AChE inhibitors, and may therefore present a significant ecological risk to aquatic organisms.
ESTHER : Shi_2020_J.Hazard.Mater_409_124999
PubMedSearch : Shi_2020_J.Hazard.Mater_409_124999
PubMedID: 33454525

Title : An enzyme inhibition-based lab-in-a-syringe device for point-of-need determination of pesticides - Yang_2020_Analyst__
Author(s) : Yang L , Wang J , Qu L , Liu Z , Jiang L
Ref : Analyst , : , 2020
Abstract : An enzyme inhibition-based lab-in-a-syringe (EI-LIS) device was developed by integrating a 1-naphthol-linked bi-enzymatic reaction (sensor core) into the LIS (sensor device) for point-of-need monitoring of pesticide residues. The integration relies on the rational design of two reaction pads. The conjugate pad is a polyester fiber membrane loaded with plant-esterase, an alternative to acetylcholinesterase. Besides pesticide capture, plant-esterase also mediates the hydrolysis of 1-naphthyl acetate, generating 1-naphthol. The detection pad is an agarose gel entrapping oxidized 3,3',5,5'-tetramethylbenzidine (oxTMB) from Fe(iii) meso-tetra(N-methyl-4-pyridyl) porphyrin (FeTMPyP4)-catalyzed TMB oxidation. Both pads were embedded into their cartridges and then connected to a syringe. Under syringe pumping, 1-naphthol vertically flowed from the conjugate to the detection cartridge, linking the two pads. If plant-esterase was intact, 1-naphthol would reduce oxTMB, causing a color change of the detection pad from blue to colorless. If the plant-esterase activity was inhibited by pesticides, less 1-naphthol was produced, and the blue color of the detection pad would be partially or wholly retained. The deeper the blue color, the greater the pesticide concentration. This chromogenic pattern is responsible for a highly sensitive readout (detection limits of dichlorvos: 0.1 nM with the naked eye and 0.07 nM with a spectrometer).
ESTHER : Yang_2020_Analyst__
PubMedSearch : Yang_2020_Analyst__
PubMedID: 32319482

Title : Neurological effects of subchronic exposure to dioctyl phthalate (DOP), lead, and arsenic, individual and mixtures, in immature mice - Feng_2020_Environ.Sci.Pollut.Res.Int_27_9247
Author(s) : Feng W , Wu X , Mao G , Zhao T , Wang W , Chen Y , Zhang M , Yang L
Ref : Environ Sci Pollut Res Int , 27 :9247 , 2020
Abstract : Dioctyl phthalate (DOP) (200, 500, and 1000 mg kg(-1) bw, i.g.), Pb (Ac)(2) (50 mg L(-1), p.o.), and NaAsO(2) (10 mg L(-1), p.o.) were administered individually and as mixtures to weanling male mice for 8 weeks. It was observed that Pb, As, and DOP exposure could significantly inhibit the growth and development of mice. Compared with the Pb, As, and Pb + As groups, the activities of iNOS and TNOS were significantly increased, the levels of AChE and SOD were significantly decreased, and the level of MDA was significantly increased in the Pb + DOP-H, As + DOP-H, and Pb + As + DOP-H groups. The factorial analysis shows that the iNOS, TNOS, and AChE present synergistic effects on Pb, As, and DOP. A significant increase of escape latency and a significant decrease of original platform quadrant stops were observed between Pb + As + DOP-H and Pb + As groups. The factorial analysis shows that there was a synergistic effect on Pb, As, and DOP. Compared with that of the control group, the expression levels of caspase-3 and Bax expression in Pb + As, DOP-H, Pb + DOP-H, As + DOP-H, and Pb + As + DOP-H groups were significantly increased in the hippocampus. The expression levels of Bcl-2 expression decreased significantly and the Bax/Bcl-2 ratio increased significantly. Pathological alterations on the hippocampus were found in exposed groups. This result shows that combined exposure of Pb, As, and DOP could induce neurotoxicity, of which possible mechanism is hippocampal neuronal apoptosis. Graphical abstract This study shows that there were three components with eigenvalues greater than 1, which together explained 89.40% of total variance. The first component (PC1) showed high loadings on B-SOD, L-SOD, B-MDA, L-MDA, K-MDA, iNOS, tNOS, and AChE and accounted for 46.55% of the total variance after Varimax rotation. PC2 accounted for 23.81% of the total variance with high loadings on B-As, L-As, K-As, and K-SOD, whereas PC3 showed high loadings on B-Pb, L-Pb, and K-Pb and accounted for 19.04% of the total variance.
ESTHER : Feng_2020_Environ.Sci.Pollut.Res.Int_27_9247
PubMedSearch : Feng_2020_Environ.Sci.Pollut.Res.Int_27_9247
PubMedID: 31916164

Title : Inhibition of pancreatic lipase by the constituents in St. John's Wort: In vitro and in silico investigations - Hou_2020_Int.J.Biol.Macromol_145_620
Author(s) : Hou XD , Guan XQ , Cao YF , Weng ZM , Hu Q , Liu HB , Jia SN , Zang SZ , Zhou Q , Yang L , Ge GB , Hou J
Ref : Int J Biol Macromol , 145 :620 , 2020
Abstract : Herbal medicines are frequently used for the prevention and treatment of obesity and obesity-related disorders. Our preliminary screening showed that St. John's Wort (SJW) displayed potent inhibition on pancreatic lipase (PL), a key hydrolase responsible for lipid digestion and absorption in mammals. Herein, the inhibition potentials and inhibitory mechanism of SJW extract and its major constituents on PL were fully investigated by a set of in vitro and in silico studies. The results clearly demonstrated that the naphthodianthrones, biflavones and most of flavonoids in SJW displayed strong to moderate inhibition on PL. Among all tested natural compounds, two naphthodianthrones (hypericin and pseudohypericin) and one biflavone (I3,II8-biapigenin) isolated from SJW exhibited potent PL inhibition activity, with the IC(50) values of <1 microM. Inhibition kinetics analyses showed that hypericin, pseudohypericin and I3,II8-biapigenin inhibited PL via a mixed manner, while molecular dynamics simulations revealed that three newly identified PL inhibitors could bind on PL at both the catalytic cavity and the interface between colipase and the C-terminal domain of PL. Collectively, our findings suggested that part of major constituents in SJW displayed potent PL inhibition activities, which could be used as lead compounds for the development of novel PL inhibitors.
ESTHER : Hou_2020_Int.J.Biol.Macromol_145_620
PubMedSearch : Hou_2020_Int.J.Biol.Macromol_145_620
PubMedID: 31883893

Title : New sesquiterpenoids bearing 11-methyl ester group of agarwood - Li_2020_Fitoterapia__104557
Author(s) : Li W , Yang YL , Yang L , Wang H , Dong WH , Cai CH , Yuan JZ , Jiang B , Mei WL , Dai HF
Ref : Fitoterapia , :104557 , 2020
Abstract : Five new sesquiterpenoids (1-5), together with a known compound 6 was isolated from ethyl ether extract of agarwood. Their structures were elucidated on the basis of spectroscopic techniques (UV, IR, MS, 1D and 2D NMR), as well as by comparison with literature data. Compound 5 exhibited inhibitory activity against acetylcholinesterase with inhibition ratio of 48.33+/-0.17% at the concentration of 50mug/mL.
ESTHER : Li_2020_Fitoterapia__104557
PubMedSearch : Li_2020_Fitoterapia__104557
PubMedID: 32198109

Title : Construction and application of a high-content analysis for identifying human carboxylesterase 2 inhibitors in living cell system - Xue_2020_Anal.Bioanal.Chem__
Author(s) : Xue L , Qian X , Jin Q , Zhu Y , Wang X , Wang D , Ge G , Yang L
Ref : Anal Bioanal Chem , : , 2020
Abstract : Human carboxylesterase 2 (hCE2), one of the most principal drug-metabolizing enzymes, catalyzes the hydrolysis of a variety of endogenous esters, anticancer agents, and environmental toxicants. The significant roles of hCE2 in both endobiotic and xenobiotic metabolism sparked great interest in the discovery and development of efficacious and selective inhibitors. However, the safe and effective inhibitors of hCE2 are scarce, due to the lack of efficient screening and evaluation systems for complex biological systems. To offer a solution to this problem, a high-content analysis (HCA)-based cell imaging and multiparametric assay method was constructed for evaluating the inhibitory effect and safety of hCE2 inhibitors in living cell system. In this study, we first established a cell imaging-based method for identifying hCE2 inhibitors at the living cell level with hCE2 fluorescent probe NCEN. Meanwhile, two nuclear probes, Hoechst 33342 and PI, were integrated to evaluate the potential cytotoxicity of compounds simultaneously. Then, the accuracy of the HCA-based method was verified by the LC-FD-based method with a positive inhibitor BNPP, and the results showed that the HCA-based method exhibited excellent precision, robustness, and reliability. Finally, the newly established HCA-based multiparametric assay panel was successfully applied to re-evaluate a series of reported hCE2 inhibitors in living cells. In summary, the HCA-based multiparametric method could serve as an efficient tool for the accuracy measurement inhibitory effect and cytotoxicity of compounds against hCE2 in living cell system. Graphical abstract.
ESTHER : Xue_2020_Anal.Bioanal.Chem__
PubMedSearch : Xue_2020_Anal.Bioanal.Chem__
PubMedID: 32123952

Title : Liver Function of Male Rats Exposed to Manganese at Different Time Points - Zhu_2020_Biol.Trace.Elem.Res__
Author(s) : Zhu X , Yang L , He Y , Sun Y , Shi W , Ou C
Ref : Biol Trace Elem Res , : , 2020
Abstract : As an essential trace element in the human body, manganese (Mn) is involved in many important biochemical reactions. However, excessive exposure to manganese can cause multiple systematic damages to the body. This study aims to investigate the effects of manganese exposure on serum hepatic enzymes in male rats at different time points. After adaptive feeding for 7 days, male Sprague-Dawley (SD) rats were injected intraperitoneally with 30 mg/kg MnCl2.4H2O once a day for 21 days at zeitgeber time point 2 (ZT2), ZT8, ZT14, and ZT20, respectively. We found that short-term repeated exposure to manganese caused slower body weight gain and increased relative liver and spleen weight index in male rats at different time points. Moreover, serum total bile acid (TBA) increased while aspartate aminotransferase (AST) decreased at ZT2, ZT8, and ZT20. Cholinesterase (ChE) decreased at ZT2 and ZT20, lactic dehydrogenase (LDH) decreased at ZT2, ZT14, and ZT20, and acid phosphatase (ACP) decreased at ZT2 and ZT14. Alkaline phosphatase (ALP) decreased at ZT2, ZT14, and ZT20, but increased at ZT8. Alanine amino transferase (ALT) decreased at ZT2 and ZT20, but increased at ZT8. There was a negative correlation between relative liver weight index with AST, ACP, ALP, and LDH, while a positive correlation with TBA. However, relative spleen weight index had a positive correlation with relative liver weight index and TBA, while a negative correlation with ALT, AST, ACP, ALP, LDH, and ChE. Our study shows that the injury of liver function is caused by short-term repeated manganese exposure at different time points. The time effect should be considered in manganese toxicity evaluation.
ESTHER : Zhu_2020_Biol.Trace.Elem.Res__
PubMedSearch : Zhu_2020_Biol.Trace.Elem.Res__
PubMedID: 32100273

Title : Discovery of natural pentacyclic triterpenoids as potent and selective inhibitors against human carboxylesterase 1 - Song_2019_Fitoterapia_137_104199
Author(s) : Song PF , Zhu YD , Ma HY , Wang YN , Wang DD , Zou LW , Ge GB , Yang L
Ref : Fitoterapia , 137 :104199 , 2019
Abstract : Human carboxylesterase 1 (CES1), primarily expressed in the liver and adipocytes, is responsible for the hydrolysis of endogenous esters (such as cholesteryl esters and triacylglycerols) and the metabolism of xenobiotic esters (such as clopidogrel and oseltamivir), thus participates in physiological and pathological processes. In this study, a series of natural pentacyclic triterpenoids were collected and their inhibitory effects against CES1 and CES2 were assayed using D-luciferin methyl ester (DME) and N-(2-butyl-1,3-dioxo-2,3-dihydro-1H-benzo[de] isoquinolin- 6-yl)- 2-chloroacetamide (NCEN) as specific optical substrate for CES1, and CES2, respectively. To this end, betulinic acid (BA) was found with strong inhibitory effect on CES1 (IC50, 15nM) and relative high selectivity over CES2 (>2400-fold). Primary structure-activity relationships (SAR) analysis and docking simulations revealed that the carboxyl group at the C-28 site of BA is very essential for CES1 inhibition. The inhibition kinetic analyses demonstrated that BA was a potent competitive inhibitor against CES1-mediated DME hydrolysis. Further investigation on the inhibitory effect of BA in living cells (HepG2) based assays demonstrated that BA displayed potent inhibitory effects on intracellular CES1 activities, with the low IC50 value of 1.30muM. These results demonstrated that BA is potent and highly selective CES1 inhibitor, which might be used as the promising tool for exploring the biological functions of CES1 in complex biological systems.
ESTHER : Song_2019_Fitoterapia_137_104199
PubMedSearch : Song_2019_Fitoterapia_137_104199
PubMedID: 31175950

Title : Converting solution viscosity to distance-readout on paper substrates based on enzyme-mediated alginate hydrogelation: Quantitative determination of organophosphorus pesticides - Xu_2019_Anal.Chim.Acta_1071_1
Author(s) : Xu J , Hu X , Khan H , Tian M , Yang L
Ref : Anal Chim Acta , 1071 :1 , 2019
Abstract : Quantitatively paper-based senor is performed with simple distance-readout on mixed cellulose ester (MCE) filter paper based on acetylcholinesterase (AChE)-mediated alginate hydrogel. The method is accomplished with the aid of the inhibition effect of target samples on the AChE enzyme-catalyzed hydrolysis of acetylcholine, which changes the pH value of the solution to release Ca(2+) and trigger alginate hydrogelation. The viscosity of the solution is thus regulated with the presence of target samples in the reaction mixture, leading to a significant change in the diffusion diameter of the solution spotted on the filter paper. The concentration in the sample is quantitatively determined by ruler-measureable diffusion diameter of the spot on the paper. With successfully application for quantitatively sensing of organophosphorus pesticides (OPs), we show that the method exhibits excellent reproducibility with RSD (n=5) as low as 0.09% and good selectivity for detection of OPs. The dynamic range of the method is up to 66.7ng/mL with the limit-of-detection (LOD) of 3.3ng/mL. The present study provides a new approach for developing paper-based sensors with quantitative distance-readout, by utilizing enzymatic inhibition to modulate liquid viscosity, which would be of value for target detection in complex samples.
ESTHER : Xu_2019_Anal.Chim.Acta_1071_1
PubMedSearch : Xu_2019_Anal.Chim.Acta_1071_1
PubMedID: 31128750

Title : Capillary electrophoresis-immobilized enzyme microreactors for acetylcholinesterase assay with surface modification by highly-homogeneous microporous layer - Liu_2019_J.Chromatogr.A__460454
Author(s) : Liu X , Azhar I , Khan H , Qu Q , Tian M , Yang L
Ref : Journal of Chromatography A , :460454 , 2019
Abstract : We propose a new capillary electrophoresis (CE)-based open-tubular immobilized enzyme microreactor (OT-IMER) and its application in acetylcholinesterase (AChE) assays. The IMER is fabricated at the capillary inlet (reactor length of approximately 1cm) with the inner surface modified by a micropore-structured layer (thickness of approximately 220nm, pore size of approximately 15-20nm). The use of IMER accomplishes the enzymatic reaction and separation/detection of the products in the same capillary within 3 min. The feasibility of the proposed method is evaluated via online analysis of the activity and inhibition of AChE enzymes. Such method exhibits good reproducibility with relative standard deviation (RSD) of less than 4% for 20 runs, and the enzyme remains over 82% of the initial activity after usage of 7 days. The IMERs are successfully applied to detect the organophosphorus pesticide, paraoxon, in three types of vegetable juice samples with a limit of detection of as low as 61ng mL(-1). Results show that the spiked samples are in the range of 89.6-105.9% with RSD less than 2.7%, thereby indicating its satisfactory level of accurate and reliable analysis of real samples by using the proposed method. Our study indicates that, with combination of advantages of both porous-layer capillary and CE OT-IMER, the proposed method is capable to enhance enzymatic reactions and to achieve rapid analysis with simple instrumentation and operation, thus would pave the way for extensive application of CE-based IMERs in a variety of bioanalysis.
ESTHER : Liu_2019_J.Chromatogr.A__460454
PubMedSearch : Liu_2019_J.Chromatogr.A__460454
PubMedID: 31443966

Title : The adverse effect of TCIPP and TCEP on neurodevelopment of zebrafish embryos\/larvae - Li_2019_Chemosphere_220_811
Author(s) : Li R , Wang H , Mi C , Feng C , Zhang L , Yang L , Zhou B
Ref : Chemosphere , 220 :811 , 2019
Abstract : Tris (1-chloro-2-propyl) phosphate (TCIPP) and tris (2-chloroethyl)phosphate (TCEP) are two widely used chlorinated organophosphate flame retardants (ClOPFRs), and have been frequently detected in various environmental media. Concern is now growing whether TCIPP and TCEP can cause neurotoxicity since they have similar chemical structure with organophosphorus pesticide. Therefore, in this study, zebrafish embryos (2-120h post-fertilization [hpf]) were exposed to TCIPP or TCEP (0, 100, 500 or 2500mug/L) or a model neurotoxicant, chlorpyrifos (CPF, 100mug/L) to investigate the adverse effects and possible mechanisms of TCIPP and TCEP on neurodevelopment. Our results showed that CPF exposure resulted in developmental toxicity including decreased hatching, survival rates and increased malformation rates (e.g., spinal curvature) as well as behavior changes such as decreased locomotive activity in dark stimulation. In contrast, TCIPP and TCEP showed no significant effects on developmental parameters, but caused similar effects on locomotive activity at high concentration, indicating that although not as potent as CPF, TCIPP and TCEP may still cause adverse effects on neurodevelopment. Furthermore, our results suggest that TCIPP and TCEP showed no effects on acetylcholine content or AChE activity, which were considered as the main targets of CPF. However, TCIPP and TCEP exposure can significantly down-regulate the expression of selected genes and proteins related to neurodevelopment (e.g., mbp, syn2a, and alpha1-tubulin) similar as CPF did. Besides that, TCIPP and TCEP can also affect the transcription of shha and gap43, which were not affected by CPF, pointing out a complex mechanism underlying TCIPP and TCEP's neurodevelopmental toxicity. Overall, our results demonstrated that TCEP and TCIPP may have adverse effect on the neurodevelopment of zebrafish embryos/larvae, but the underlying mechanism is not via the inhibition of acetyl cholinesterase activity.
ESTHER : Li_2019_Chemosphere_220_811
PubMedSearch : Li_2019_Chemosphere_220_811
PubMedID: 30612050

Title : Design, synthesis and molecular modeling of isothiochromanone derivatives as acetylcholinesterase inhibitors - Shuai_2019_Future.Med.Chem_11_2687
Author(s) : Shuai W , Li W , Yin Y , Yang L , Xu F , Xu S , Yao H , Zhu Z , Xu J
Ref : Future Med Chem , 11 :2687 , 2019
Abstract : Aim: A series of novel isothio- and isoselenochromanone derivatives bearing N-benzyl pyridinium moiety were designed, synthesized and evaluated as acetylcholinesterase (AChE) inhibitors. Results: Most of the target compounds exhibited potent anti-AChE activities with IC50 values in nanomolar ranges. Among them, compound 15a exhibited the most potent anti-AChE activity (IC50 = 2.7 nM), moderate antioxidant activity and low neurotoxicity. Moreover, the kinetic and docking studies revealed that compound 15a was a mixed-type inhibitor, which bounds to peripheral anionic site and catalytic active site of AChE. Conclusion: Those results suggested that compound 15a might be a potential candidate for AD treatment.
ESTHER : Shuai_2019_Future.Med.Chem_11_2687
PubMedSearch : Shuai_2019_Future.Med.Chem_11_2687
PubMedID: 31596141

Title : Diagnosis of Hirschsprung's Disease by Immunostaining Rectal Suction Biopsies for Calretinin, S100 Protein and Protein Gene Product 9.5 - Chi_2019_J.Vis.Exp__
Author(s) : Chi S , Fang M , Li K , Yang L , Tang ST
Ref : J Vis Exp , : , 2019
Abstract : Hirschsprung's disease (HD) is a congenital intestinal disease that is clinically manifested as an inability to pass meconium in infants or as long-term constipation in children. Rectal suction biopsy (RSB) to determine the absence of ganglion cells and neural hypertrophy is the most accurate test for the diagnosis of HD at present. Traditional hematoxylin-eosin staining lacks sensitivity and specificity. Acetylcholinesterase staining cannot be widely used due to its complex process. Our novel protocol of immunostaining for calretinin, S100 protein, and protein gene product 9.5 (PGP9.5), which we conducted on RSBs, exhibits high sensitivity and specificity rates of 96.49% (95% confidence interval, 0.88-0.99) and 100% (95% confidence interval, 0.97-1.00), respectively. The HD-affected segments often present as the absence of the expression of calretinin, S100 protein, and PGP9.5, which are markers of neural hypertrophy in the submucosal tissue. This protocol describes the detailed operating process of this new diagnostic method.
ESTHER : Chi_2019_J.Vis.Exp__
PubMedSearch : Chi_2019_J.Vis.Exp__
PubMedID: 31081806

Title : Monoacylglycerol Lipase Inactivation by Using URB602 Mitigates Myocardial Damage in a Rat Model of Cardiac Arrest - Hai_2019_Crit.Care.Med_47_e144
Author(s) : Hai K , Chen G , Gou X , Jang H , Gong D , Cheng Y , Gong C , Li X , Liu Y , Li H , Zhang G , Yang L , Ke B , Liu J
Ref : Critical Care Medicine , 47 :e144 , 2019
Abstract : OBJECTIVES: Monoacylglycerol lipase participates in organ protection by regulating the hydrolysis of the endocannabinoid 2-arachidonoylglycerol. This study investigated whether blocking monoacylglycerol lipase protects against postresuscitation myocardial injury and improves survival in a rat model of cardiac arrest and cardiopulmonary resuscitation. DESIGN: Prospective randomized laboratory study. SETTING: University research laboratory. SUBJECTS: Male Sprague-Dawley rat (n = 96). INTERVENTIONS: Rats underwent 8-minute asphyxia-based cardiac arrest and resuscitation. Surviving rats were randomly divided into cardiopulmonary resuscitation + URB602 group, cardiopulmonary resuscitation group, and sham group. One minute after successful resuscitation, rats in the cardiopulmonary resuscitation + URB602 group received a single dose of URB602 (5 mg/kg), a small-molecule monoacylglycerol lipase inhibitor, whereas rats in the cardiopulmonary resuscitation group received an equivalent volume of vehicle solution. The sham rats underwent all of the procedures performed on rats in the cardiopulmonary resuscitation and cardiopulmonary resuscitation + URB602 groups minus cardiac arrest and asphyxia. MEASUREMENTS AND MAIN RESULTS: Survival was recorded 168 hours after the return of spontaneous circulation (n = 22 in each group). Compared with vehicle treatment (31.8%), URB602 treatment markedly improved survival (63.6%) 168 hours after cardiopulmonary resuscitation. Next, we used additional surviving rats to evaluate myocardial and mitochondrial injury 6 hours after return of spontaneous circulation, and we found that URB602 significantly reduced myocardial injury and prevented myocardial mitochondrial damage. In addition, URB602 attenuated the dysregulation of endocannabinoid and eicosanoid metabolism 6 hours after return of spontaneous circulation and prevented the acceleration of mitochondrial permeability transition 15 minutes after return of spontaneous circulation. CONCLUSIONS: Monoacylglycerol lipase blockade may reduce myocardial and mitochondrial injury and significantly improve the resuscitation effect after cardiac arrest and cardiopulmonary resuscitation.
ESTHER : Hai_2019_Crit.Care.Med_47_e144
PubMedSearch : Hai_2019_Crit.Care.Med_47_e144
PubMedID: 30431495

Title : A Unique Role of Carboxylesterase 3 (Ces3) in beta-Adrenergic Signaling-Stimulated Thermogenesis - Yang_2019_Diabetes_68_1178
Author(s) : Yang L , Li X , Tang H , Gao Z , Zhang K , Sun K
Ref : Diabetes , 68 :1178 , 2019
Abstract : Carboxylesterase 3 (Ces3) is a hydrolase with a wide range of activities in liver and adipose tissue. In this study, we identified Ces3 as a major lipid droplet surface-targeting protein in adipose tissue upon cold exposure by liquid chromatography-tandem mass spectrometry. To investigate the function of Ces3 in the beta-adrenergic signaling-activated adipocytes, we applied WWL229, a specific Ces3 inhibitor, or genetic inhibition by siRNA to Ces3 on isoproterenol (ISO)-treated 3T3-L1 and brown adipocyte cells. We found that blockage of Ces3 by WWL229 or siRNA dramatically attenuated the ISO-induced lipolytic effect in the cells. Furthermore, Ces3 inhibition led to impaired mitochondrial function measured by Seahorse. Interestingly, Ces3 inhibition attenuated an ISO-induced thermogenic program in adipocytes by downregulating Ucp1 and Pgc1alpha genes via peroxisome proliferator-activated receptor gamma. We further confirmed the effects of Ces3 inhibition in vivo by showing that the thermogenesis in adipose tissues was significantly attenuated in WWL229-treated or adipose tissue-specific Ces3 heterozygous knockout (Adn-Cre-Ces3(flx/wt)) mice. As a result, the mice exhibited dramatically impaired ability to defend their body temperature in coldness. In conclusion, our study highlights a lipolytic signaling induced by Ces3 as a unique process to regulate thermogenesis in adipose tissue.
ESTHER : Yang_2019_Diabetes_68_1178
PubMedSearch : Yang_2019_Diabetes_68_1178
PubMedID: 30862682
Gene_locus related to this paper: human-CES3 , mouse-Ces1d

Title : Fishing for contaminants: identification of three mechanism specific transcriptome signatures using Danio rerio embryos - Hausen_2018_Environ.Sci.Pollut.Res.Int_25_4023
Author(s) : Hausen J , Otte JC , Legradi J , Yang L , Strahle U , Fenske M , Hecker M , Tang S , Hammers-Wirtz M , Hollert H , Keiter SH , Ottermanns R
Ref : Environ Sci Pollut Res Int , 25 :4023 , 2018
Abstract : In ecotoxicology, transcriptomics is an effective way to detect gene expression changes in response to environmental pollutants. Such changes can be used to identify contaminants or contaminant classes and can be applied as early warning signals for pollution. To do so, it is important to distinguish contaminant-specific transcriptomic changes from genetic alterations due to general stress. Here we present a first step in the identification of contaminant class-specific transcriptome signatures. Embryos of zebrafish (Danio rerio) were exposed to three substances (methylmercury, chlorpyrifos and Aroclor 1254, each from 24 to 48 hpf exposed) representing sediment typical contaminant classes. We analyzed the altered transcriptome to detect discriminative genes significantly regulated in reaction to the three applied contaminants. By comparison of the results of the three contaminants, we identified transcriptome signatures and biologically important pathways (using Cytoscape/ClueGO software) that react significantly to the contaminant classes. This approach increases the chance of finding genes that play an important role in contaminant class-specific pathways rather than more general processes.
ESTHER : Hausen_2018_Environ.Sci.Pollut.Res.Int_25_4023
PubMedSearch : Hausen_2018_Environ.Sci.Pollut.Res.Int_25_4023
PubMedID: 28391457

Title : Omega-6 fatty acids down-regulate matrix metalloproteinase expression in a coronary heart disease-induced rat model - Lu_2018_Int.J.Exp.Pathol_99_210
Author(s) : Lu N , Du Y , Li H , Luo Y , Ouyang B , Chen Y , Yang Y , Yang L
Ref : International Journal of Experimental Pathology , 99 :210 , 2018
Abstract : The present study investigated the therapeutic potential of omega-6 fatty acids, according to their effects on antioxidant markers and matrix metalloproteinases (MMPs), in coronary heart disease-induced rats. Rats were grouped into group I (sham control), group II (control), group III (0.5 g/kg bwt of omega-6 fatty acids) and group IV (1 g/kg bwt of omega-6 fatty acids). Reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), reduced glutathione (GSH), catalase, glutathione peroxidase (Gpx) and acetylcholinesterase (AChE) enzyme activities were determined. ROS and MDA were substantially reduced, whereas SOD, catalase, Gpx and AChE were significantly increased, following supplementation with omega-6 fatty acids. MMP-2 mRNA expression was drastically increased by 95% in group II. Treatment significantly reduced MMP-2 mRNA expression by 12.3% and 26.7% in groups III and IV respectively. MMP-9 mRNA expression drastically increased, by 121%, in group II. Treatment significantly reduced MMP-9 mRNA expression by 22.6% and 29.4% in groups III and IV respectively. MMP-2 protein expression was drastically increased, by 81%, in group II. Treatment significantly reduced MMP-2 protein expression by 9.4% and 26% in groups III and IV respectively. MMP-9 protein expression was drastically increased, by 100%, in group II. Treatment significantly reduced MMP-9 protein expression by 18.9% and 26.9% in groups III and IV respectively. In summary, the consumption of omega-6 fatty acids significantly decreased MDA and ROS, while SOD, catalase, GHS, Gpx and AChE were increased. Furthermore, omega-6 fatty acids significantly downregulated MMP-2 and MMP-9 expression in our coronary heart disease-induced rat model.
ESTHER : Lu_2018_Int.J.Exp.Pathol_99_210
PubMedSearch : Lu_2018_Int.J.Exp.Pathol_99_210
PubMedID: 30443948

Title : Theoretical Studies on Catalysis Mechanisms of Serum Paraoxonase 1 and Phosphotriesterase Diisopropyl Fluorophosphatase Suggest the Alteration of Substrate Preference from Paraoxonase to DFP - Zhang_2018_Molecules_23_
Author(s) : Zhang H , Yang L , Ma YY , Zhu C , Lin S , Liao RZ
Ref : Molecules , 23 : , 2018
Abstract : The calcium-dependent β-propeller proteins mammalian serum paraoxonase 1 (PON1) and phosphotriesterase diisopropyl fluorophosphatase (DFPase) catalyze the hydrolysis of organophosphorus compounds and enhance hydrolysis of various nerve agents. In the present work, the phosphotriesterase activity development between PON1 and DFPase was investigated by using the hybrid density functional theory method B3LYP. Based on the active-site difference between PON1 and DFPase, both the wild type and the mutant (a water molecule replacing Asn270 in PON1) models were designed. The results indicated that the substitution of a water molecule for Asn270 in PON1 had little effect on the enzyme activity in kinetics, while being more efficient in thermodynamics, which is essential for DFP hydrolysis. Structure comparisons of evolutionarily related enzymes show that the mutation of Asn270 leads to the catalytic Ca(2+) ion indirectly connecting the buried structural Ca(2+) ion via hydrogen bonds in DFPase. It can reduce the plasticity of enzymatic structure, and possibly change the substrate preference from paraoxon to DFP, which implies an evolutionary transition from mono- to dinuclear catalytic centers. Our studies shed light on the investigation of enzyme catalysis mechanism from an evolutionary perspective.
ESTHER : Zhang_2018_Molecules_23_
PubMedSearch : Zhang_2018_Molecules_23_
PubMedID: 29986514

Title : Carboxylesterase Inhibitors: An Update - Zou_2018_Curr.Med.Chem_25_1627
Author(s) : Zou LW , Jin Q , Wang DD , Qian QK , Hao DC , Ge GB , Yang L
Ref : Curr Med Chem , 25 :1627 , 2018
Abstract : Mammalian carboxylesterases are key serine hydrolases that catalyze the hydrolysis of a wide variety of ester compounds in the corresponding carboxylic acids and alcohols. In human, two major carboxylesterases, CES1 and CES2, have been identified and well-studied over the past decade. CES1 inhibitors have potential applications in the treatment of hypertriglyceridaemia, obesity and type 2 diabetes, owing to that this enzyme plays prominent role in the metabolism of cholesteryl esters. CES2 plays crucial roles in the metabolic activation of many prodrugs including anticancer agents capecitabine and CPT-11. Co-administration with CES2 inhibitors may ameliorate CPT-11 associated lifethreatening diarrhea or improve the half-lives of CES2-substrate drugs. The important roles of carboxylesterases in both endogenous and xenobiotic metabolism arouse great interest in the discovery and development of potent and selective inhibitors against these enzymes. This review is focused on the application potentials and recent advances in the discovery and development of carboxylesterases inhibitors. The inhibitory capacities and inhibition mechanism of a variety of carboxylesterases inhibitors including synthetic, semi-synthetic and natural compounds are comprehensively summarized. Furthermore, the key structural features and structure-activity relationships (SARs) of different classes of CES1 and CES2 inhibitors are discussed. All information and knowledge summarized in this review will be very helpful for the medicinal chemists to design and develop more potent and highly selective carboxylesterases inhibitors for potential biomedical applications.
ESTHER : Zou_2018_Curr.Med.Chem_25_1627
PubMedSearch : Zou_2018_Curr.Med.Chem_25_1627
PubMedID: 29210644

Title : Novel Method of Preparation and Activity Research on Arctigenin from Fructus Arctii - Cai_2018_Pharmacogn.Mag_14_87
Author(s) : Cai E , Han J , Yang L , Zhang W , Zhao Y , Chen Q , Guo M , He X
Ref : Pharmacogn Mag , 14 :87 , 2018
Abstract : Background: Arctigenin has many pharmacological activities with clinical significance and is derived from Arctium lappa L. However, the present extraction method is inefficient and does not have meaningful industrial production. Objective: A new method to directly prepare arctigenin was established by combining enzyme-assisted extraction and central composite design. Arctigenin's further pharmacological activity was also surveyed in vitro. Materials and Methods: beta-D-Glucosidase, a food-grade enzyme, was added directly to the fruits of A. lappa L. to hydrolyze the arctiin to arctigenin, and the obtained samples were subsequently subjected to ethanol (30%, v/v) extraction. The pharmacological activity of the extraction and arctigenin was determined by inhibiting acetylcholinesterase (AChE) and scavenging nitrite. Results: The factors investigated include the enzyme concentration (0.5%-2.5%), ultrasound time (10 min(-3) 0 min), and extraction temperature (30 degrees C-50 degrees C). From the analysis of the results by Design-Expert (V8.0.6), the optimal extraction conditions were obtained: enzyme concentration (1.4%), ultrasound time (25 min), and extraction temperature (45 degrees C). The highest yield of arctigenin, obtained under the optimal conditions was 6.39%, representing an increase of 28.15% compared to the reference extraction without enzyme processing. The IC50 values of the extraction and arctigenin, respectively, for inhibiting AChE were 0.572 mg/ml and 0.462 mg/ml, and those for nitrite-scavenging were 34.571 mg/ml and 17.49 mg/ml. Conclusions: The results demonstrate that using an enzyme directly in the production is an effective means for extracting arctigenin from Fructus arctii. The extraction has the activities of inhibiting AChE and scavenging nitrite, probably because there has arctigenin in it. It is implied that the extraction and arctigenin could contribute to human health in clinical applications. SUMMARY: The new method of adding enzyme directly to the preparation of arctigenin was carried out instead of preparing arctigenin by two-step methodThree factors affecting the efficiency of preparation were analyzed and discussed include the enzyme concentration, ultrasound time, and extraction temperature by central composite designThis new method of preparing arctigenin improved the yield significantly than other methodsArctigenin has remarkable pharmacological activities of inhibiting acetylcholinesterase and scavenging nitrite. Abbreviations used: AChE: Acetylcholinesterase, CCD: Central composite design, TCM: Traditional Chinese medicines, AD.
ESTHER : Cai_2018_Pharmacogn.Mag_14_87
PubMedSearch : Cai_2018_Pharmacogn.Mag_14_87
PubMedID: 29576707

Title : Oxidation pretreatment by calcium hypochlorite to improve the sensitivity of enzyme inhibition-based detection of organophosphorus pesticides - Yang_2018_J.Sci.Food.Agric_98_2624
Author(s) : Yang X , Dai J , Yang L , Ma M , Zhao SJ , Chen XG , Xiao H
Ref : J Sci Food Agric , 98 :2624 , 2018
Abstract : BACKGROUND: Enzyme inhibition-based detection is the most widely used method for rapid detection of organophosphorus pesticides (OPs) in food and agricultural products. However, the accuracy of the method is negatively affected by low inhibitory activities of OPs with PS moiety on acetylcholinesterase. RESULTS: We demonstrated that oxidation pretreatments with bromine, hydrogen peroxide, or calcium hypochlorite significantly enhanced the enzyme inhibitory activities of these OPs. Especially, calcium hypochlorite (0.05%) pretreatment converted the PS moiety in OPs to PO and produced the most potent and steady inhibitory effect on the enzyme. This, in turn, resulted in a dramatic increase in the sensitivity of enzyme inhibition-based detection of these OPs by as much as 2 to 7 orders of magnitude. Importantly, this enhanced detection of OPs was validated in various vegetable samples. CONCLUSION: Our findings provide a solid basis to use calcium hypochlorite pretreatment for the improved detection of OPs by the enzyme inhibition-based method. (c) 2017 Society of Chemical Industry.
ESTHER : Yang_2018_J.Sci.Food.Agric_98_2624
PubMedSearch : Yang_2018_J.Sci.Food.Agric_98_2624
PubMedID: 29072792

Title : Design, synthesis and cholinesterase inhibitory activity of alpha-mangostin derivatives - Chi_2018_Nat.Prod.Res__1
Author(s) : Chi XQ , Hou B , Yang L , Zi CT , Lv YF , Li JY , Ren FC , Yuan MY , Hu JM , Zhou J
Ref : Nat Prod Res , :1 , 2018
Abstract : alpha-mangostin, a polyphenol xanthone derivative, was mainly isolated from pericarps of the mangosteen fruit (Garcinia mangostana L.). In present investigation, a series of derivatives were designed, synthesised and evaluated in vitro for their inhibitory activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Among the synthesised xanthones, compounds 1, 9, 13 and 16 showed AChE selective inhibitory activity, 15 was a BuChE selective inhibitor while 2, 3, 5, 6, 7, 12 and 14 were dual inhibitors. The most potent inhibitor of AChE was 16 while 5 was the most potent inhibitor of BuChE with IC50 values of 5.26 muM and 7.55 muM respectively.
ESTHER : Chi_2018_Nat.Prod.Res__1
PubMedSearch : Chi_2018_Nat.Prod.Res__1
PubMedID: 30456989

Title : Developmental neurotoxicity of triphenyl phosphate in zebrafish larvae - Shi_2018_Aquat.Toxicol_203_80
Author(s) : Shi Q , Wang M , Shi F , Yang L , Guo Y , Feng C , Liu J , Zhou B
Ref : Aquat Toxicol , 203 :80 , 2018
Abstract : Triphenyl phosphate (TPhP), a typical organophosphate ester, is frequently detected in the environment and biota samples. It has been implicated as a neurotoxin as its structure is similar to neurotoxic organophosphate pesticides. The purpose of the present study was to investigate its potential developmental neurotoxicity in fish by using zebrafish larvae as a model. Zebrafish (Danio rerio) embryos were exposed to 0.8, 4, 20 and 100 mug/L of TPhP from 2 until 144 h post-fertilization. TPhP was found to have high bioconcentrations in zebrafish larvae after exposure. Further, it significantly reduced locomotor activity as well as the heart rate at the 100 mug/L concentration. TPhP exposure significantly altered the content of the neurotransmitters gamma-aminobutyric and histamine. Downregulation of the genes related to central nervous system development (e.g., alpha1-tubulin, mbp, syn2a, shha, and elavl3) as well as the corresponding proteins (e.g., alpha1-tubulin, mbp, and syn2a) was observed, but the gap-43 protein was found to upregulated. Finally, marked inhibition of total acetylcholinesterase activity, which is considered as a biomarker of neurotoxicant exposure, was also observed in the larvae. Our results indicate that exposure to environmentally relevant concentrations of TPhP can affect different parameters related to center nervous system development, and thus contribute to developmental neurotoxicity in early developing zebrafish larvae.
ESTHER : Shi_2018_Aquat.Toxicol_203_80
PubMedSearch : Shi_2018_Aquat.Toxicol_203_80
PubMedID: 30096480

Title : Enantioselective synthesis of novel pyrano[3,2-c]chromene derivatives as AChE inhibitors via an organocatalytic domino reaction - Zheng_2018_Org.Biomol.Chem_16_472
Author(s) : Zheng J , He M , Xie B , Yang L , Hu Z , Zhou HB , Dong C
Ref : Org Biomol Chem , 16 :472 , 2018
Abstract : A series of optically active pyrano[3,2-c]chromenes have been synthesized through an asymmetric domino reaction of 4-hydroxy-2H-chromen-2-ones with malononitriles. The targeted molecules were obtained in excellent yields and enantioselectivities (up to 94% yield, 99% ee). The AChE inhibitory activity studies revealed that compounds 4n (IC50 = 21.3 muM) and 4p (IC50 = 19.2 muM) displayed potent acetylcholinesterase inhibition. In most cases, the S-enantiomers were superior to the corresponding R-enantiomers. Moreover, molecular modelling provides a practical method for understanding the enantioselective discrimination of AChE with these kinds of compounds.
ESTHER : Zheng_2018_Org.Biomol.Chem_16_472
PubMedSearch : Zheng_2018_Org.Biomol.Chem_16_472
PubMedID: 29265146

Title : A computational method for the design of nested proteins by loop-directed domain insertion - Blacklock_2018_Proteins_86_354
Author(s) : Blacklock KM , Yang L , Mulligan VK , Khare SD
Ref : Proteins , 86 :354 , 2018
Abstract : The computational design of novel nested proteins-in which the primary structure of one protein domain (insert) is flanked by the primary structure segments of another (parent)-would enable the generation of multifunctional proteins. Here we present a new algorithm, called Loop-Directed Domain Insertion (LooDo), implemented within the Rosetta software suite, for the purpose of designing nested protein domain combinations connected by flexible linker regions. Conformational space for the insert domain is sampled using large libraries of linker fragments for linker-to-parent domain superimposition followed by insert-to-linker superimposition. The relative positioning of the two domains (treated as rigid bodies) is sampled efficiently by a grid-based, mutual placement compatibility search. The conformations of the loop residues, and the identities of loop as well as interface residues, are simultaneously optimized using a generalized kinematic loop closure algorithm and Rosetta EnzymeDesign, respectively, to minimize interface energy. The algorithm was found to consistently sample near-native conformations and interface sequences for a benchmark set of structurally similar but functionally divergent domain-inserted enzymes from the alpha/beta hydrolase superfamily, and discriminates well between native and nonnative conformations and sequences, although loop conformations tended to deviate from the native conformations. Furthermore, in cross-domain placement tests, native insert-parent domain combinations were ranked as the best-scoring structures compared to nonnative domain combinations. This algorithm should be broadly applicable to the design of multi-domain protein complexes with any combination of inserted or tandem domain connections.
ESTHER : Blacklock_2018_Proteins_86_354
PubMedSearch : Blacklock_2018_Proteins_86_354
PubMedID: 29250820

Title : Breed Differences in Pig Liver Esterase (PLE) between Tongcheng (Chinese Local Breed) and Large White Pigs - Xiao_2018_Sci.Rep_8_16364
Author(s) : Xiao Q , Zhou Q , Yang L , Tian Z , Wang X , Xiao Y , Shi D
Ref : Sci Rep , 8 :16364 , 2018
Abstract : Human carboxylesterases has been proven to be age and race-related and a sound basis of clinical medication. PLE involve in signal transduction and highly catalyze hydrolysis. Therefore, the expression level of PLE most probably exist age and breed difference and lead to significant differences of pharmacology and physiology. Four age groups of Tongcheng (TC) and Large White (LW) pigs were selected to explore PLE breed and age differences, and it was found that PLE mRNA was most abundant in liver in both breeds. In liver, PLE levels and hydrolytic activities increased with age, and PLE levels (except for 3 month) and the hydrolytic activities were higher in LW than in TC across all age groups. Abundance of PLE isoenzymes was obvious different between breeds and among age groups. The most abundant PLE isoenzyme in LW and TC pigs was PLE-A1 (all age groups) and PLE-B9 (three early age groups) or PLE-G3 (adult groups), respectively. 103 new PLE isoenzymes were found, and 55 high-frequency PLE isoenzymes were accordingly classified into seven categories (A-G). The results of this research provide a necessary basis not only for clinical medication of pigs but also for pig breeding purposes.
ESTHER : Xiao_2018_Sci.Rep_8_16364
PubMedSearch : Xiao_2018_Sci.Rep_8_16364
PubMedID: 30397234
Gene_locus related to this paper: pig-a9gyw6 , pig-EST1 , pig-PLE1 , pig-a0a1s6l948 , pig-a0a1s6l959 , pig-a0a1s6l967

Title : The Prognostic Value of Lipoprotein-Associated Phospholipase A(2) in the Long-Term Care of Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention - Yang_2018_Clin.Appl.Thromb.Hemost_24_822
Author(s) : Yang L , Wang H , Zhang Y , Han T , Wang W
Ref : Clin Appl Thromb Hemost , 24 :822 , 2018
Abstract : Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is an independent risk factor for cardiovascular disease. Accordingly, studies from many countries around the world have shown an association between Lp-PLA(2) and cardiovascular events in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI), but this association has not been documented among the Chinese. The aim of this study was to assess the use of Lp-PLA(2) as a useful marker for predicting the long-term prognosis of Chinese patients with ACS undergoing PCI. A total of 651 consecutive patients undergoing PCI between September 2013 and January 2015 were divided into 2 groups: the high Lp-PLA(2) group (n = 262, Lp-PLA(2) > 138 nmol/L) and the low Lp-PLA(2) group (n = 389, Lp-PLA(2) >= 138 nmol/L). The end point was all-cause mortality and rehospitalization. The median follow-up was 24 months. Multivariate analysis showed that high Lp-PLA(2) was an independent predictor of all-cause mortality and rehospitalization (hazard ratio: 1.429, 95% confidence interval [CI]: 1.411-1.448; P < .05). The Lp-PLA(2) had good accuracy for predicting all-cause mortality and rehospitalization among patients with ACS undergoing PCI (area under the receiver-operating characteristic curve: 0.858, 95% CI: 0.819-0.898; P < .05), and a good correlation with the Global Registry of Acute Coronary Event score ( r = 0.525, P < .05). This study provided evidence that Lp-PLA(2) could predict all-cause mortality and rehospitalization risk among patients with ACS undergoing PCI.
ESTHER : Yang_2018_Clin.Appl.Thromb.Hemost_24_822
PubMedSearch : Yang_2018_Clin.Appl.Thromb.Hemost_24_822
PubMedID: 29121808
Gene_locus related to this paper: human-PLA2G7

Title : Lychee seed extract protects against neuronal injury and improves cognitive function in rats with type II diabetes mellitus with cognitive impairment - Tang_2018_Int.J.Mol.Med_41_251
Author(s) : Tang Y , Yu C , Wu J , Chen H , Zeng Y , Wang X , Yang L , Mei Q , Cao S , Qin D
Ref : Int J Mol Med , 41 :251 , 2018
Abstract : Lychee seed is a traditional Chinese medicine and has many beneficial effects such as modulation of blood sugar and lipids, antioxidation, antivirus and antitumor. Studies have indicated that type II diabetes mellitus (T2DM) and Alzheimer's disease (AD) share common biological mechanisms including insulin resistance, impaired glucose metabolism, betaamyloid (Abeta) formation, oxidative stress and presence of advanced glycation end products (AGEs). The present study investigated the effects of lychee seed extract (LSE) on neuroprotection, cognitive function improvement and possible underlying mechanisms in a rat model of T2DM with cognitive impairment. We analyzed the chemical profile of LSE using a UHPLCSPD chromatogram and evaluated its effect on the improvement of spatial learning and memory of rats by a Morris water maze. The levels of glucose, insulin, Abeta, AGEs, Tau protein and acetylcholinesterase in the blood and/or hippocampus of rats were determined by bloodglucose meter, radioimmunoassay, chemical chromatometry, enzymelinked immunosorbent assay (ELISA) and immunohistochemical analysis, respectively. Results demonstrated that LSE consists of eight major and around 20 minor ingredients, and it remarkably prevents neuronal injury and improves cognitive functions in T2DM rats. The levels of glucose, insulin, Abeta, AGEs and Tau protein were significantly increased in the blood and/or hippocampus of T2DM rats, while LSE remarkably decreased their levels compared to vehicle treatment (P<0.01). The possible mechanisms may be associated with IR improvement and decreased formations of Abeta, AGEs and Tau protein in the hippocampus of T2DM rats. LSE may be developed as the agent for the treatment of T2DM and/or AD clinically.
ESTHER : Tang_2018_Int.J.Mol.Med_41_251
PubMedSearch : Tang_2018_Int.J.Mol.Med_41_251
PubMedID: 29138799

Title : Single-Step In Situ Acetylcholinesterase-Mediated Alginate Hydrogelation for Enzyme Encapsulation in CE - Yang_2018_Anal.Chem_90_4071
Author(s) : Yang J , Hu X , Xu J , Liu X , Yang L
Ref : Analytical Chemistry , 90 :4071 , 2018
Abstract : A novel capillary electrophoresis-integrated immobilized enzyme reactor (CE-integrated IMER) is developed using single-step in situ acetylcholinesterase (AChE)-mediated alginate hydrogelation and enzyme encapsulation. Alginate hydrogelation with "egg-box" structure is triggered inside a capillary with releasing of Ca(2+) by changing the pH of the sol solution, which is accomplished in situ by AChE-catalyzed hydrolysis reaction of acetylthiocholine to produce acetic acid. AChE and any other enzyme initially contained in the sol solution [e.g., xanthine oxidase (XO)] are efficiently encapsulated as the hydrogel network grows, forming CE-integrated IMERs without any additional manipulation process. The proposed method facilitates the analysis of different kinds of enzymes using the same IMER depending on the substrate injected for CE analysis. Approximately 68% of the original enzyme in the sol mixture can be encapsulated, indicating high loading capacity for the CE-integrated IMERs. The IMERs exhibit excellent intraday and interday stability and batch-to-batch reproducibility, and these characteristics imply the reliability of the proposed IMERs for accurate online enzyme assays. Enzymatic activities and inhibition of immobilized AChE and XO are analyzed, and the results are compared with those using free enzymes. The feasibility of the proposed method for potential application in real sample analysis is demonstrated by the successful application of the IMERs in detecting organophosphorus pesticides in apple juice samples using AChE-catalyzed reactions. The proposed method is a simple, efficient, and universal approach for online CE assays with immobilized enzymes, which can be widely applied in bioanalysis.
ESTHER : Yang_2018_Anal.Chem_90_4071
PubMedSearch : Yang_2018_Anal.Chem_90_4071
PubMedID: 29469571

Title : Enhancement of brain-targeting delivery of danshensu in rat through conjugation with pyrazine moiety to form danshensu-pyrazine ester - Hui_2018_Drug.Deliv.Transl.Res_8_787
Author(s) : Hui A , Yin H , Zhang Z , Zhou A , Chen J , Yang L , Wu Z , Zhang W
Ref : Drug Deliv Transl Res , 8 :787 , 2018
Abstract : Tetramethylpyrazine was introduced to the structure of danshensu (DSS) as P-glycoprotein (P-gp)-inhibiting carrier, designing some novel brain-targeting DSS-pyrazine derivatives via prodrug delivery strategy. Following the virtual screening, three DSS-pyrazine esters (DT1, DT2, DT3) were selected because of their better prediction parameters related to brain-targeting. Among them, DT3 was thought to be a promising candidate due to its appropriate bioreversible property in vitro release assay. Further investigation with regard to DT3's brain-targeting effects in vivo was also reported in this study. High-performance liquid chromatography-diode array detection (HPLC-DAD) method was established for the quantitative determination of DT3 and DSS in rat plasma, brain homogenate after intravenous injection. In vivo metabolism of DT3 indicated that it was first converted into DT1, DT2, then the generation of DSS, which could be the result of carboxylesterase activity in rat blood and brain tissue. Moreover, the brain pharmacokinetics of DT3 was significantly altered with 2.16 times increase in half-life compared with that of DSS, and its drug targeting index (DTI) was up to 16.95. Above these data demonstrated that DT3 had better tendency of brain-targeting delivery, which would be positive for the treatment of brain-related disorders.
ESTHER : Hui_2018_Drug.Deliv.Transl.Res_8_787
PubMedSearch : Hui_2018_Drug.Deliv.Transl.Res_8_787
PubMedID: 29524164

Title : Human carboxylesterases: a comprehensive review - Wang_2018_Acta.Pharm.Sin.B_8_699
Author(s) : Wang D , Zou L , Jin Q , Hou J , Ge G , Yang L
Ref : Acta Pharm Sin B , 8 :699 , 2018
Abstract : Mammalian carboxylesterases (CEs) are key enzymes from the serine hydrolase superfamily. In the human body, two predominant carboxylesterases (CES1 and CES2) have been identified and extensively studied over the past decade. These two enzymes play crucial roles in the metabolism of a wide variety of endogenous esters, ester-containing drugs and environmental toxicants. The key roles of CES in both human health and xenobiotic metabolism arouse great interest in the discovery of potent CES modulators to regulate endobiotic metabolism or to improve the efficacy of ester drugs. This review covers the structural and catalytic features of CES, tissue distributions, biological functions, genetic polymorphisms, substrate specificities and inhibitor properties of CES1 and CES2, as well as the significance and recent progress on the discovery of CES modulators. The information presented here will help pharmacologists explore the relevance of CES to human diseases or to assign the contribution of certain CES in xenobiotic metabolism. It will also facilitate medicinal chemistry efforts to design prodrugs activated by a given CES isoform, or to develop potent and selective modulators of CES for potential biomedical applications.
ESTHER : Wang_2018_Acta.Pharm.Sin.B_8_699
PubMedSearch : Wang_2018_Acta.Pharm.Sin.B_8_699
PubMedID: 30245959

Title : Activity-dependent Synaptic Recruitment of Neuroligin 1 in Spinal Dorsal Horn Contributed to Inflammatory Pain - Zhao_2018_Neurosci_388_1
Author(s) : Zhao JY , Duan XL , Yang L , Liu JP , He YT , Guo Z , Hu XD , Suo ZW
Ref : Neuroscience , 388 :1 , 2018
Abstract : Neuroligin 1 (NLGN1), a cell adhesion molecule present at excitatory glutamatergic synapses, has been shown to be critical for synaptic specialization and N-methyl-d-aspartate (NMDA)-subtype glutamate receptor-dependent synaptic plasticity. Whether and how NLGN1 is engaged in nociceptive behavioral sensitization remains largely unknown. In this study, we found an activity-dependent regulation of NLGN1 synaptic expression in pain-related spinal cord dorsal horns of mice. The enhancement of neuronal activity by pharmacological activation of NMDA receptor (NMDAR) or removal of GABAergic inhibition in intact mice significantly increased NLGN1 concentration at synaptosomal membrane fraction. Intraplantar injection of complete Freund's adjuvant (CFA) also increased the NLGN1 expression at synapses. NMDAR might act through Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and Src-family protein tyrosine kinase member Fyn to induce the synaptic redistribution of NLGN1. We also found that one of the important roles of NLGN1 was to facilitate the clustering of NMDAR at synapses. The NLGN1-targeting siRNA suppressed the synaptic expression of GluN2B-containing NMDAR in CFA-injected mice and meanwhile, attenuated the inflammatory mechanical allodynia and thermal hypersensitivity. These data suggested that tissue injury-induced synaptic redistribution of NLGN1 was involved in the development of pain hypersensitivity through facilitating the synaptic incorporation of NMDARs.
ESTHER : Zhao_2018_Neurosci_388_1
PubMedSearch : Zhao_2018_Neurosci_388_1
PubMedID: 30049666

Title : Two Bombyx mori acetylcholinesterase genes influence motor control and development in different ways - Ye_2017_Sci.Rep_7_4985
Author(s) : Ye X , Yang L , Stanley D , Li F , Fang Q
Ref : Sci Rep , 7 :4985 , 2017
Abstract : Among its other biological roles, acetylcholinesterase (AChE, EC, encoded by two ace in most insects, catalyses the breakdown of acetylcholine, thereby terminating synaptic transmission. ace1 encodes the synaptic enzyme and ace2 has other essential actions in many insect species, such as Chilo suppressalis and Plutella xylostella. The silkworm, Bombyx mori, has been domesticated for more than two thousand years and its aces have no history of pesticide exposure. Here, we investigated the functional differences between two ace genes, BmAce1 and BmAce2, in the silkworm. qPCR analysis indicated that BmAce1 is highly expressed in muscle and BmAce2 is more ubiquitously expressed among tissues and enriched in the head. Both genes were separately suppressed using chemically synthesized siRNAs. The mRNA abundance of the two ace genes was significantly reduced to about 13% - 75% of the control levels after siRNA injection. The AChE activities were decreased to 32% to 85% of control levels. Silencing BmAce2 resulted in about 26% mortality, faster and higher than the 20% in the siBmAce1-treated group. Silencing BmAce1 impacted motor control and development to a greater extent than silencing BmAce2, although both treatment groups suffered motor disability, slowed development and reduced cocoons. Both genes have essential, differing biological significance.
ESTHER : Ye_2017_Sci.Rep_7_4985
PubMedSearch : Ye_2017_Sci.Rep_7_4985
PubMedID: 28694460
Gene_locus related to this paper: bommo-ACHE1 , bommo-ACHE2

Title : Comparative metabolism of DDAO benzoate in liver microsomes from various species - Ma_2017_Toxicol.In.Vitro_44_280
Author(s) : Ma HY , Yang JD , Hou J , Zou LW , Jin Q , Hao DC , Ning J , Ge GB , Yang L
Ref : Toxicol In Vitro , 44 :280 , 2017
Abstract : DDAB (6,8-dichloro-9,9-dimethyl-7-oxo-7,9-dihydroacridin-2-yl benzoate) is a newly developed near-infrared fluorescent probe for human carboxylesterase 2 (hCE2), exhibiting high specificity and good reactivity for real-time monitoring the enzymatic activities of hCE2 in complex biological systems. In order to explore the applicability of DDAB in commonly used animal species, the interspecies difference in DDAB hydrolysis was carefully investigated by using liver microsomes from human and five experimental animals including mouse, rat, dog, minipig and monkey. Metabolite profiling demonstrated that DDAB hydrolysis could be catalyzed by all tested liver microsomes from different animals but displayed significant difference in the reaction rate. Chemical inhibition assays demonstrated that carboxylesterases (CEs) were the major enzymes involved in DDAB hydrolysis in all tested liver microsomes, indicating that DDAB was a selective substrate of CEs in a variety of mammals. However, the differential effects of loperamide (LPA, a specific inhibitor against hCE2) on DDAB hydrolysis among various species were observed. The apparent kinetic parameters and the maximum intrinsic clearances (CLmax) for DDAB hydrolysis in liver microsomes from different animals were determined, and the order of CLmax values for the formation of DDAO was CyLM>MLM approximately PLM>RLM>HLM approximately DLM. These findings were helpful for the rational use of DDAB as an imaging tool for CE2 in different mammals, as well as for translational researches on the function of mammalian CEs and CE2-associated drug-drug interactions.
ESTHER : Ma_2017_Toxicol.In.Vitro_44_280
PubMedSearch : Ma_2017_Toxicol.In.Vitro_44_280
PubMedID: 28647665

Title : [Design and development of fluorescent probe substrates for carboxylesterase 1 using BODIPY as the basic fluorophore] - Ding_2017_Yao.Xue.Xue.Bao_52_58
Author(s) : Ding LL , Tian ZH , Hou J , Weng ZM , Cui JN , Yang L , Ge GB
Ref : Yao Xue Xue Bao , 52 :58 , 2017
Abstract : Carboxylesterase 1 (CE1) is an important serine hydrolase in mammals, which involved in the hydrolysis of a variety of compounds (endogenous substrates like cholesterol and xenobiotic compounds like ester-contain drugs and pesticides). This study aimed to design and develop the fluorescent probe substrates for human carboxylesterase 1 (hCE1), on the basis of the structural features of hCE1 preferred substrates. Four carboxylic esters deriving from BODIPY-8-carboxylic acid were designed and synthesized. After then, reaction phenotyping assays and chemical inhibition assays were used to evaluate the selectivity of these four ester derivatives towards hCE1. Our results clearly demonstrated that the substrate specificity of these ester substrates towards hCE1 would be improved with the decrease of the alcohol group on BODIPY-8-carboxylesters, while BODIPY-8-carboxylesters with small alcohol groups including methyl (BCM) and ethyl (BCE) esters could serve as the ideal probe substrates for hCE1. Given that BCM exhibit rapid hydrolytic rate in hCE1, we further investigate the enzymatic kinetics of this fluorescent probe substrate in both human liver microsomes (HLM) and recombinant hCE1, as well as to explore its potential application in high-throughput screening of hCE1 inhibitors by using HLM as enzyme source. The results showed that the kinetic behaviors and the affinity of BCM in HLM is much closed to those in recombinant hCE1, implying that hCE1 played the key roles in BCM hydrolysis in HLM. Furthermore, the inhibition study demonstrated that BCM could be used for rapid screening and characterization of hCE1 inhibitors, by using HLM to replace recombinant hCE1 as enzyme source.
ESTHER : Ding_2017_Yao.Xue.Xue.Bao_52_58
PubMedSearch : Ding_2017_Yao.Xue.Xue.Bao_52_58
PubMedID: 29911769

Title : Association of plasma dipeptidyl peptidase-4 activity with non-alcoholic fatty liver disease in nondiabetic Chinese population - Zheng_2017_Metabolism_73_125
Author(s) : Zheng T , Chen B , Yang L , Hu X , Zhang X , Liu H , Qin L
Ref : Metabolism , 73 :125 , 2017
Abstract : OBJECTIVE: The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is attributed to a "multi-hits hypothesis" involving insulin resistance, oxidative stress and inflammation. Dipeptidyl peptidase-4 (DPP4) was identified as a novel adipokine capable of enhancing the"multi-hits". Hence, we investigated the association between plasma DPP4 activity and NAFLD in nondiabetic Chinese population. DESIGN AND METHODS: We performed a cross-sectional study using data from 1105 subjects (36-79years) in Guilin between 2015 and 2016. Plasma DPP4 activity, homeostatic model assessment of insulin resistance (HOMA-IR), oxidative stress parameters, and inflammatory markers were measured in all participants. NAFLD and its severity were diagnosed by ultrasound after the exclusion of alcohol abuse and other liver diseases. RESULTS: Participants in the highest quartile of DPP4 activity had higher HOMA-IR, nitrotyrosine, 8-iso-PGF2a, interleukin-6, CRP, alanine aminotransferase, aspartate aminotransferase and gamma-glutamyltransferase compared with those in the lowest quartile (all P<0.05). Plasma DPP4 activity gradually increased across the groups according to the ultrasonographic severity of steatosis (P<0.001 for the trend). In the highest DPP4 quartile, NAFLD risk was higher (odds ratio 1.88; 95% CI 1.04-3.37) than in the lowest quartile after adjustment for confounders. The risk for NAFLD increased more with higher levels of DPP4 activity, HOMA-IR, nitrotyrosine, 8-iso-PGF2a, interleukin-6 and CRP. CONCLUSIONS: Plasma DPP4 activity is significantly associated with NAFLD. The underlying mechanisms may be partly attributed to the interactions between insulin resistance, oxidative stress, inflammation, and DPP4.
ESTHER : Zheng_2017_Metabolism_73_125
PubMedSearch : Zheng_2017_Metabolism_73_125
PubMedID: 28637594

Title : Structure-Activity Relationships of Pentacyclic Triterpenoids as Potent and Selective Inhibitors against Human Carboxylesterase 1 - Zou_2017_Front.Pharmacol_8_435
Author(s) : Zou LW , Dou TY , Wang P , Lei W , Weng ZM , Hou J , Wang DD , Fan YM , Zhang WD , Ge GB , Yang L
Ref : Front Pharmacol , 8 :435 , 2017
Abstract : Human carboxylesterase 1 (hCE1), one of the most important serine hydrolases distributed in liver and adipocytes, plays key roles in endobiotic homeostasis and xenobiotic metabolism. This study aimed to find potent and selective inhibitors against hCE1 from phytochemicals and their derivatives. To this end, a series of natural triterpenoids were collected and their inhibitory effects against human carboxylesterases (hCEs) were assayed using D-Luciferin methyl ester (DME) and 6,8-dichloro-9,9-dimethyl-7-oxo-7,9-dihydroacridin-2-yl benzoate (DDAB) as specific optical substrate for hCE1, and hCE2, respectively. Following screening of a series of natural triterpenoids, oleanolic acid (OA), and ursolic acid (UA) were found with strong inhibitory effects on hCE1 and relative high selectivity over hCE2. In order to get the highly selective and potent inhibitors of hCE1, a series of OA and UA derivatives were synthesized from OA and UA by chemical modifications including oxidation, reduction, esterification, and amidation. The inhibitory effects of these derivatives on hCEs were assayed and the structure-activity relationships of tested triterpenoids as hCE1 inhibitors were carefully investigated. The results demonstrated that the carbonyl group at the C-28 site is essential for hCE1 inhibition, the modifications of OA or UA at this site including esters, amides and alcohols are unbeneficial for hCE1 inhibition. In contrast, the structural modifications on OA and UA at other sites, such as converting the C-3 hydroxy group to 3-O-beta-carboxypropionyl (compounds 20 and 22), led to a dramatically increase of the inhibitory effects against hCE1 and very high selectivity over hCE2. 3D-QSAR analysis of all tested triterpenoids including OA and UA derivatives provide new insights into the fine relationships linking between the inhibitory effects on hCE1 and the steric-electrostatic properties of triterpenoids. Furthermore, both inhibition kinetic analyses and docking simulations demonstrated that compound 22 was a potent competitive inhibitor against hCE1-mediated DME hydrolysis. All these findings are very helpful for medicinal chemists to design and develop highly selective and more potent hCE1 inhibitors for biomedical applications.
ESTHER : Zou_2017_Front.Pharmacol_8_435
PubMedSearch : Zou_2017_Front.Pharmacol_8_435
PubMedID: 28713276

Title : Mechanisms of Vascular Dysfunction in COPD and Effects of a Novel Soluble Epoxide Hydrolase Inhibitor in Smokers - Yang_2017_Chest_151_555
Author(s) : Yang L , Cheriyan J , Gutterman DD , Mayer RJ , Ament Z , Griffin JL , Lazaar AL , Newby DE , Tal-Singer R , Wilkinson IB
Ref : Chest , 151 :555 , 2017
Abstract : BACKGROUND: Smoking and COPD are risk factors for cardiovascular disease, and the pathogenesis may involve endothelial dysfunction. We tested the hypothesis that endothelium-derived epoxyeicosatrienoic acid (EET)-mediated endothelial function is impaired in patients with COPD and that a novel soluble epoxide hydrolase inhibitor, GSK2256294, attenuates EET-mediated endothelial dysfunction in human resistance vessels both in vitro and in vivo. METHODS: Endogenous and stimulated endothelial release of EETs was assessed in 12 patients with COPD, 11 overweight smokers, and two matched control groups, using forearm plethysmography with intraarterial infusions of fluconazole, bradykinin, and the combination. The effects of GSK2256294 on EET-mediated vasodilation in human resistance arteries were assessed in vitro and in vivo in a phase I clinical trial in healthy overweight smokers. RESULTS: Compared with control groups, there was reduced vasodilation with bradykinin (P = .005), a blunted effect of fluconazole on bradykinin-induced vasodilation (P = .03), and a trend toward reduced basal EET/dihydroxyepoxyeicosatrienoic acid ratio in patients with COPD (P = .08). A similar pattern was observed in overweight smokers. In vitro, 10 muM GSK2256294 increased 11,12-EET-mediated vasodilation compared with vehicle (90% +/- 4.2% vs 72.6% +/- 6.2% maximal dilatation) and shifted the bradykinin half-maximal effective concentration (EC50) (-8.33 +/- 0.172 logM vs -8.10 +/- 0.118 logM; P = .001 for EC50). In vivo, 18 mg GSK2256294 improved the maximum bradykinin response from 338% +/- 46% before a dose to 566% +/- 110% after a single dose (P = .02) and to 503% +/- 123% after a chronic dose (P = .003). CONCLUSIONS: GSK2256294 attenuates smoking-related EET-mediated endothelial dysfunction, suggesting potential therapeutic benefits in patients with COPD. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01762774; URL: www.clinicaltrials.gov.
ESTHER : Yang_2017_Chest_151_555
PubMedSearch : Yang_2017_Chest_151_555
PubMedID: 27884766

Title : A highly specific ratiometric two-photon fluorescent probe to detect dipeptidyl peptidase IV in plasma and living systems - Zou_2017_Biosens.Bioelectron_90_283
Author(s) : Zou LW , Wang P , Qian XK , Feng L , Yu Y , Wang DD , Jin Q , Hou J , Liu ZH , Ge GB , Yang L
Ref : Biosensors & Bioelectronics , 90 :283 , 2017
Abstract : In this study, a highly specific ratiometric two-photon fluorescent probe GP-BAN was developed and well-characterized to monitor dipeptidyl peptidase IV in plasma and living systems. GP-BAN was designed on the basis of the catalytic properties and substrate preference of DPP-IV, and it could be readily hydrolyzed upon addition of DPP-IV under physiological conditions. Both reaction phenotyping and inhibition assays demonstrated that GP-BAN displayed good reactivity and high selectivity towards DPP-IV over other human serine hydrolases including FAP, DPP-VIII, and DPP-IX. The probe was successfully used to monitor the real activities of DPP-IV in complex biological systems including diluted plasma, while it could be used for high throughput screening of DPP-IV inhibitors by using human plasma or tissue preparations as enzyme sources. As a two-photon fluorescent probe, GP-BAN was also successfully used for two-photon imaging of endogenous DPP-IV in living cells and tissues, and showed high ratiometric imaging resolution and deep-tissue penetration ability. Taken together, a ratiometric two-photon fluorescent probe GP-BAN was developed and well-characterized for highly selective and sensitive detection of DPP-IV in complex biological systems, which could serve as a promising imaging tool to explore the biological functions and physiological roles of this key enzyme in living systems.
ESTHER : Zou_2017_Biosens.Bioelectron_90_283
PubMedSearch : Zou_2017_Biosens.Bioelectron_90_283
PubMedID: 27923191

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 : Screening of a natural compound library identifies emodin, a natural compound from Rheum palmatum Linn that inhibits DPP4 - Wang_2017_PeerJ_5_e3283
Author(s) : Wang Z , Yang L , Fan H , Wu P , Zhang F , Zhang C , Liu W , Li M
Ref : PeerJ , 5 :e3283 , 2017
Abstract : Historically, Chinese herbal medicines have been widely used in the treatment of hyperglycemia, but the mechanisms underlying their effectiveness remain largely unknown. Here, we screened a compound library primarily comprised of natural compounds extracted from herbs and marine organisms. The results showed that emodin, a natural compound from Rheum palmatum Linn, inhibited DPP4 activity with an in vitro IC50 of 5.76 microM without inhibiting either DPP8 or DPP9. A docking model revealed that emodin binds to DPP4 protein through Glu205 and Glu206, although with low affinity. Moreover, emodin treatment (3, 10 and 30 mg/kg, P.O.) in mice decreased plasma DPP4 activity in a dose-dependent manner. Our study suggests that emodin inhibits DPP4 activity and may represent a novel therapeutic for the treatment of type 2 diabetes.
ESTHER : Wang_2017_PeerJ_5_e3283
PubMedSearch : Wang_2017_PeerJ_5_e3283
PubMedID: 28507818

Title : Assessment of the inhibitory effects of pyrethroids against human carboxylesterases - Lei_2017_Toxicol.Appl.Pharmacol_321_48
Author(s) : Lei W , Wang DD , Dou TY , Hou J , Feng L , Yin H , Luo Q , Sun J , Ge GB , Yang L
Ref : Toxicol Appl Pharmacol , 321 :48 , 2017
Abstract : Pyrethroids are broad-spectrum insecticides that widely used in many countries, while humans may be exposed to these toxins by drinking or eating pesticide-contaminated foods. This study aimed to investigate the inhibitory effects of six commonly used pyrethroids against two major human carboxylesterases (CES) including CES1 and CES2. Three optical probe substrates for CES1 (DME, BMBT and DMCB) and a fluorescent probe substrate for CES2 (DDAB) were used to characterize the inhibitory effects of these pyrethroids. The results demonstrated that most of the tested pyrethroids showed moderate to weak inhibitory effects against both CES1 and CES2, but deltamethrin displayed strong inhibition towards CES1. The IC50 values of deltamethrin against CES1-mediated BMBT, DME, and DMCB hydrolysis were determined as 1.58muM, 2.39muM, and 3.3muM, respectively. Moreover, deltamethrin was cell membrane permeable and capable of inhibition endogenous CES1 in living cells. Further investigation revealed that deltamethrin inhibited CES1-mediated BMBT hydrolysis via competitive manner but noncompetitively inhibited DME or DMCB hydrolysis. The inhibition behaviors of deltamethrin against CES1 were also studied by molecular docking simulation. The results demonstrated that CES1 had at least two different ligand-binding sites, one was the DME site and another was the BMBT site which was identical to the binding site of deltamethrin. In summary, deltamethrin was a strong reversible inhibitor against CES1 and it could tightly bind on CES1 at the same ligand-binding site as BMBT. These findings are helpful for the deep understanding of the interactions between xenobiotics and CES1.
ESTHER : Lei_2017_Toxicol.Appl.Pharmacol_321_48
PubMedSearch : Lei_2017_Toxicol.Appl.Pharmacol_321_48
PubMedID: 28242322

Title : Lactate Promotes Synthetic Phenotype in Vascular Smooth Muscle Cells - Yang_2017_Circ.Res_121_1251
Author(s) : Yang L , Gao L , Nickel T , Yang J , Zhou J , Gilbertsen A , Geng Z , Johnson C , Young B , Henke C , Gourley GR , Zhang J
Ref : Circulation Research , 121 :1251 , 2017
Abstract : RATIONALE: The phenotypes of vascular smooth muscle cells (vSMCs) comprise a continuum bounded by predominantly contractile and synthetic cells. Some evidence suggests that contractile vSMCs can assume a more synthetic phenotype in response to ischemic injury, but the mechanisms that activate this phenotypic switch are poorly understood. OBJECTIVE: To determine whether lactate, which increases in response to regional ischemia, may promote the synthetic phenotype in vSMCs. METHODS AND RESULTS: Experiments were performed with vSMCs that had been differentiated from human induced pluripotent stem cells and then cultured in glucose-free, lactate-enriched (L(+)) medium or in standard (L(-)) medium. Compared with the L(-) medium, the L(+) medium was associated with significant increases in synthetic vSMC marker expression, proliferation, and migration and with significant declines in contractile and apoptotic activity. Furthermore, these changes were accompanied by increases in the expression of monocarboxylic acid transporters and were generally attenuated both by the blockade of monocarboxylic acid transporter activity and by transfection with iRNA for NDRG (N-myc downstream regulated gene). Proteomics, biomarker, and pathway analyses suggested that the L(+) medium tended to upregulate the expression of synthetic vSMC markers, the production of extracellular proteins that participate in tissue construction or repair, and the activity of pathways that regulate cell proliferation and migration. Observations in hypoxia-cultured vSMCs were similar to those in L(+)-cultured vSMCs, and assessments in a swine myocardial infarction model suggested that measurements of lactate levels, lactate-dehydrogenase levels, vSMC proliferation, and monocarboxylic acid transporter and NDRG expression were greater in the ischemic zone than in nonischemic tissues. CONCLUSIONS: These results demonstrate for the first time that vSMCs assume a more synthetic phenotype in a microenvironment that is rich in lactate. Thus, mechanisms that link glucose metabolism to vSMC phenotypic switching could play a role in the pathogenesis and treatment of cardiovascular disease.
ESTHER : Yang_2017_Circ.Res_121_1251
PubMedSearch : Yang_2017_Circ.Res_121_1251
PubMedID: 29021296

Title : Identification and characterization of naturally occurring inhibitors against human carboxylesterase 2 in White Mulberry Root-bark - Liu_2016_Fitoterapia_115_57
Author(s) : Liu YJ , Li SY , Hou J , Liu YF , Wang DD , Jiang YS , Ge GB , Liang XM , Yang L
Ref : Fitoterapia , 115 :57 , 2016
Abstract : White Mulberry Root-bark (WMR) is an edible Chinese herbal used for the treatment of inflammation, nephritis and asthma. This study aimed to investigate the inhibitory effects of ethanol extract from WMR against human carboxylesterase 2 (hCE2), as well as to identity and character natural hCE2 inhibitors in this herbal. Our results demonstrated that the ethanol extract of WMR displayed potent inhibitory effects against hCE2, while three major bioactive constitutes in WMR were identified on the basis of LC fingerprinting combined with activity-based screening of LC fractions. Three bioactive compounds including SD, KG and SC were efficiently identified by comparison of LC retention times, UV and MS spectral data, with the help of authentic standards. The inhibition potentials and inhibition types of these natural compounds against hCE2 were further investigated in human liver microsomes. The results demonstrated that these bioactive compounds are potent non-competitive inhibitors against hCE2, with the Ki values ranging from 0.76muM to 1.09muM. All these findings suggested that three abundant natural compounds in WMR displayed potent inhibitory effects against hCE2, which could be used as lead compounds to develop more potent hCE2 inhibitors for the alleviation of hCE2-mediated severe delayed-onset diarrhea.
ESTHER : Liu_2016_Fitoterapia_115_57
PubMedSearch : Liu_2016_Fitoterapia_115_57
PubMedID: 27702666

Title : Calretinin, S100 and protein gene product 9.5 immunostaining of rectal suction biopsies in the diagnosis of Hirschsprung' disease - Jiang_2016_Am.J.Transl.Res_8_3159
Author(s) : Jiang M , Li K , Li S , Yang L , Yang D , Zhang X , Fang M , Cao G , Wang Y , Chen W , Tang S
Ref : Am J Transl Res , 8 :3159 , 2016
Abstract : Evaluation of rectal suction biopsies for the ganglion cells and neural hypertrophy is the basic modality for the diagnosis of Hirschsprung's disease (HD). However, the traditional hematoxylin and eosin staining coupled with acetylcholinesterase histochemistry remain challenging, especially in newborns. Thus we conducted a prospective study to evaluate the usefulness of calretinin combined with S100 and protein gene product 9.5 (PGP9.5) immunostaining of rectal suction biopsies for the diagnosis of HD. A total of 195 patients were enrolled in our study. Of the 195 patients 69% had ganglion cells on the initial diagnostic protocol. Sixty cases were devoid of ganglion cells, and of these, 90% and 91% showed submucosal neural hypertrophy on S-100 staining and PGP9.5 staining, respectively. Eighty-one patients underwent a colonic resection, and of these, 59 had confirmed aganglionic segment, the other 22 patients were diagnosed as intestinal neuronal dysplasia type B (n=13) and isolated hypoganglionosis (n=9). Of the rest 114 patients, 51 cases underwent a full-thickness biopsy, and HD was excluded; sixty-three patients were thoroughly followed-up with no evidence of HD. We encountered two false-negatives and they were proved to be short segment HD after the surgery. The sensitivity and specificity rates of our diagnostic protocol was 96.49% (95% CI, 0.88-0.99) and 100% (95% CI, 0.97-1.00), respectively, excluding 5 patients with inconclusive results. Our findings demonstrated that calretinin coupled with S100 and PGP9.5 immunostaining on suction rectal biopsies is sensitive and specific for diagnosing HD.
ESTHER : Jiang_2016_Am.J.Transl.Res_8_3159
PubMedSearch : Jiang_2016_Am.J.Transl.Res_8_3159
PubMedID: 27508037

Title : The in Vitro and in Vivo Degradation of Cross-Linked Poly(trimethylene carbonate)-Based Networks - Yang_2016_Polymers.(Basel)_8_
Author(s) : Yang L , Li J , Li M , Gu Z
Ref : Polymers (Basel) , 8 : , 2016
Abstract : The degradation of the poly(trimethylene carbonate) (PTMC) and poly(trimethylene carbonate-co-sigma-caprolactone) (P(TMC-co-CL)) networks cross-linked by 0.01 and 0.02 mol % 2,2'-bis(trimethylene carbonate-5-yl)-butylether (BTB) was carried out in the conditions of hydrolysis and enzymes in vitro and subcutaneous implantation in vivo. The results showed that the cross-linked PTMC networks exhibited much faster degradation in enzymatic conditions in vitro and in vivo versus in a hydrolysis case due to the catalyst effect of enzymes; the weight loss and physical properties of the degraded networks were dependent on the BTB amount. The morphology observation in lipase and in vivo illustrated that enzymes played an important role in the surface erosion of cross-linked PTMC. The hydrolytic degradation rate of the cross-linked P(TMC-co-CL) networks increased with increasing sigma-caprolactone (CL) content in composition due to the preferential cleavage of ester bonds. Cross-linking is an effective strategy to lower the degradation rate and enhance the form-stability of PTMC-based materials.
ESTHER : Yang_2016_Polymers.(Basel)_8_
PubMedSearch : Yang_2016_Polymers.(Basel)_8_
PubMedID: 30979246

Title : Pharmacokinetics, pharmacodynamics and adverse event profile of GSK2256294, a novel soluble epoxide hydrolase inhibitor - Lazaar_2016_Br.J.Clin.Pharmacol_81_971
Author(s) : Lazaar AL , Yang L , Boardley RL , Goyal NS , Robertson J , Baldwin SJ , Newby DE , Wilkinson IB , Tal-Singer R , Mayer RJ , Cheriyan J
Ref : British Journal of Clinical Pharmacology , 81 :971 , 2016
Abstract : AIMS: Endothelial-derived epoxyeicosatrienoic acids may regulate vascular tone and are metabolized by soluble epoxide hydrolase enzymes (sEH). GSK2256294 is a potent and selective sEH inhibitor that was tested in two phase I studies.
METHODS: Single escalating doses of GSK2256294 2-20 mg or placebo were administered in a randomized crossover design to healthy male subjects or obese smokers. Once daily doses of 6 or 18 mg or placebo were administered for 14 days to obese smokers. Data were collected on safety, pharmacokinetics, sEH enzyme inhibition and blood biomarkers. Single doses of GSK2256294 10 mg were also administered to healthy younger males or healthy elderly males and females with and without food. Data on safety, pharmacokinetics and biliary metabolites were collected.
RESULTS: GSK2256294 was well-tolerated with no serious adverse events (AEs) attributable to the drug. The most frequent AEs were headache and contact dermatitis. Plasma concentrations of GSK2256294 increased with single doses, with a half-life averaging 25-43 h. There was no significant effect of age, food or gender on pharmacokinetic parameters. Inhibition of sEH enzyme activity was dose-dependent, from an average of 41.9% on 2 mg (95% confidence interval [CI] -51.8, 77.7) to 99.8% on 20 mg (95% CI 99.3, 100.0) and sustained for up to 24 h. There were no significant changes in serum VEGF or plasma fibrinogen.
CONCLUSIONS: GSK2256294 was well-tolerated and demonstrated sustained inhibition of sEH enzyme activity. These data support further investigation in patients with endothelial dysfunction or abnormal tissue repair, such as diabetes, wound healing or COPD.
ESTHER : Lazaar_2016_Br.J.Clin.Pharmacol_81_971
PubMedSearch : Lazaar_2016_Br.J.Clin.Pharmacol_81_971
PubMedID: 26620151

Title : Endothelial lipase genetic polymorphisms and the lipid-lowering response in patients with coronary artery disease on rosuvastatin - Cai_2016_Lipids.Health.Dis_15_148
Author(s) : Cai G , Zhang B , Shi G , Weng W , Yang L , Xue S
Ref : Lipids Health Dis , 15 :148 , 2016
Abstract : BACKGROUND: Endothelial lipase (EL) plays an important role in the regulation of lipid metabolism by reducing the high density lipoprotein cholesterol (HDL-C) levels and inducing the macrophages to take up native low density lipoprotein cholesterol (LDL-C). Our purpose was to investigate the impact of EL genetic polymorphisms on the lipid-lowering effects of rosuvastatin in Chinese coronary artery disease (CAD) patients.
METHODS: One hundred twenty-one unrelated CAD patients, who underwent the treatment with rosuvastatin (10mg/day) for four to eight weeks, were enrolled in this study. Before and after treatment, serum lipids levels were measured. Genotypes of EL 2037T/C and 2237 G/A polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.
RESULTS: Patients with EL 2037C allele (CC + CT) had significantly lower LDL-C levels than those with TT genotype (CC + CT: 2.60 +/- 0.74 mmol/l; TT: 2.90 +/- 0.87 mmol/l; P = 0.047), before rosuvastatin treatment. No significant differences between baseline lipid levels and the EL 2237G/A genotypes were observed. After treatment with rosuvastatin, total cholesterol (TC), high triglyceride (TG) and LDL-C levels decreased from baseline, on average, by 23.09 % (4.59 +/- 0.96 mmol/l to 3.47 +/- 0.83 mmol/l), 6.36 % (2.01 +/- 1.18 mmol/l to 1.68 +/- 1.16 mmol/l), 32.48 % (2.77 +/- 0.83 mmol/l to 1.79 +/- 0.62 mmol/l), respectively (all P < 0.05) in all patients. While changes in HDL-C levels did not reach statistical significance. No significant effects of EL 2037T/C or 2237G/A polymorphism were observed on lipid-lowering effects of rosuvastatin.
CONCLUSIONS: EL 2037T/C and 2237 G/A polymorphisms might not affect the lipid-owing effects of rosuvastatin in Chinese CAD patients.
ESTHER : Cai_2016_Lipids.Health.Dis_15_148
PubMedSearch : Cai_2016_Lipids.Health.Dis_15_148
PubMedID: 27600285

Title : A bioluminescent sensor for highly selective and sensitive detection of human carboxylesterase 1 in complex biological samples - Wang_2016_Chem.Commun.(Camb)_52_3183
Author(s) : Wang DD , Jin Q , Zou LW , Hou J , Lv X , Lei W , Cheng HL , Ge GB , Yang L
Ref : Chem Commun (Camb) , 52 :3183 , 2016
Abstract : A highly selective and sensitive bioluminescent sensor (DME) for human carboxylesterase 1 (hCE1) has been developed and well characterized. DME could be used for real-time monitoring of hCE1 activities in complex biological samples and for bio-imaging of endogenous hCE1 in living cells.
ESTHER : Wang_2016_Chem.Commun.(Camb)_52_3183
PubMedSearch : Wang_2016_Chem.Commun.(Camb)_52_3183
PubMedID: 26809686

Title : Design, synthesis, and structure-activity relationship study of glycyrrhetinic acid derivatives as potent and selective inhibitors against human carboxylesterase 2 - Zou_2016_Eur.J.Med.Chem_112_280
Author(s) : Zou LW , Li YG , Wang P , Zhou K , Hou J , Jin Q , Hao DC , Ge GB , Yang L
Ref : Eur Journal of Medicinal Chemistry , 112 :280 , 2016
Abstract : Human carboxylesterase 2 (hCE2), one of the major carboxylesterases in the human intestine and various tumour tissues, plays important roles in the oral bioavailability and treatment outcomes of ester- or amide-containing drugs or prodrugs, such as anticancer agents CPT-11 (irinotecan) and LY2334737 (gemcitabine). In this study, 18beta-glycyrrhetinic acid (GA), the most abundant pentacyclic triterpenoid from natural source, was selected as a reference compound for the development of potent and specific inhibitors against hCE2. Simple semi-synthetic modulation on GA was performed to obtain a series of GA derivatives. Structure-activity relationship analysis brought novel insights into the structure modification of GA. Converting the 11-oxo-12-ene of GA to 12-diene moiety, and C-3 hydroxyl and C-30 carboxyl group to 3-O-beta-carboxypropionyl and ethyl ester respectively, led to a significant enhancement of the inhibitory effect on hCE2 and the selectivity over hCE1. These exciting findings inspired us to design and synthesize the more potent compound 15 (IC50 0.02 muM) as a novel and highly selective inhibitor against hCE2, which was 3463-fold more potent than the parent compound GA and demonstrated excellent selectivity (>1000-fold over hCE1). The molecular docking study of compound 15 and the active site of hCE1 and hCE2 demonstrated that the potent and selective inhibition of compound 15 toward hCE2 could partially be attributed to its relatively stronger interactions with hCE2 than with hCE1.
ESTHER : Zou_2016_Eur.J.Med.Chem_112_280
PubMedSearch : Zou_2016_Eur.J.Med.Chem_112_280
PubMedID: 26900660

Title : A phenome-wide association study of a lipoprotein-associated phospholipase A2 loss-of-function variant in 90 000 Chinese adults - Millwood_2016_Int.J.Epidemiol_45_1588
Author(s) : Millwood IY , Bennett DA , Walters RG , Clarke R , Waterworth D , Johnson T , Chen Y , Yang L , Guo Y , Bian Z , Hacker A , Yeo A , Parish S , Hill MR , Chissoe S , Peto R , Cardon L , Collins R , Li L , Chen Z
Ref : Int J Epidemiol , 45 :1588 , 2016
Abstract : BACKGROUND: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) has been implicated in development of atherosclerosis; however, recent randomized trials of Lp-PLA(2) inhibition reported no beneficial effects on vascular diseases. In East Asians, a loss-of-function variant in the PLA2G7 gene can be used to assess the effects of genetically determined lower Lp-PLA(2) METHODS: PLA2G7 V279F (rs76863441) was genotyped in 91 428 individuals randomly selected from the China Kadoorie Biobank of 0.5 M participants recruited in 2004-08 from 10 regions of China, with 7 years' follow-up. Linear regression was used to assess effects of V279F on baseline traits. Logistic regression was conducted for a range of vascular and non-vascular diseases, including 41 ICD-10 coded disease categories. RESULTS: PLA2G7 V279F frequency was 5% overall (range 3-7% by region), and 9691 (11%) participants had at least one loss-of-function variant. V279F was not associated with baseline blood pressure, adiposity, blood glucose or lung function. V279F was not associated with major vascular events [7141 events; odds ratio (OR) = 0.98 per F variant, 95% confidence interval (CI) 0.90-1.06] or other vascular outcomes, including major coronary events (922 events; 0.96, 0.79-1.18) and stroke (5967 events; 1.00, 0.92-1.09). Individuals with V279F had lower risks of diabetes (7031 events; 0.91, 0.84-0.98) and asthma (182 events; 0.53, 0.28-0.98), but there was no association after adjustment for multiple testing. CONCLUSIONS: Lifelong lower Lp-PLA(2) activity was not associated with major risks of vascular or non-vascular diseases in Chinese adults. Using functional genetic variants in large-scale prospective studies with linkage to a range of health outcomes is a valuable approach to inform drug development and repositioning.
ESTHER : Millwood_2016_Int.J.Epidemiol_45_1588
PubMedSearch : Millwood_2016_Int.J.Epidemiol_45_1588
PubMedID: 27301456
Gene_locus related to this paper: human-PLA2G7

Title : A highly selective near-infrared fluorescent probe for carboxylesterase 2 and its bioimaging applications in living cells and animals - Jin_2016_Biosens.Bioelectron_83_193
Author(s) : Jin Q , Feng L , Wang DD , Wu JJ , Hou J , Dai ZR , Sun SG , Wang JY , Ge GB , Cui JN , Yang L
Ref : Biosensors & Bioelectronics , 83 :193 , 2016
Abstract : A near-infrared fluorescent probe (DDAB) for highly selective and sensitive detection of carboxylesterase 2 (CE2) has been designed, synthesized, and systematically studied both in vitro and in vivo. Upon addition of CE2, the ester bond of DDAB could be rapidly cleaved and then release a near-infrared (NIR) fluorophore DDAO, which brings a remarkable yellow-to-blue color change and strong NIR fluorescence emission in physiological solutions. The newly developed probe exhibits excellent properties including good specificity, ultrahigh sensitivity and high imaging resolution. Moreover, DDAB has been applied to measure the real activities of CE2 in complex biological samples, as well as to screen CE2 inhibitors by using tissue preparations as the enzymes sources. The probe has also been successfully used to detect endogenous CE2 in living cells and in vivo for the first time, and the results demonstrate that such detection is highly reliable. All these prominent features of DDAB make it holds great promise for further investigation on CE2-associated biological process and for exploring the physiological functions of CE2 in living systems.
ESTHER : Jin_2016_Biosens.Bioelectron_83_193
PubMedSearch : Jin_2016_Biosens.Bioelectron_83_193
PubMedID: 27129028

Title : Enzymatic degradation of poly(butylene succinate) by cutinase cloned from Fusarium solani - Hu_2016_Polym.Degrad.Stab_134_211
Author(s) : Hu X , Gao Z , Wang Z , Su T , Yang L , Li P
Ref : Polymer Degradation and Stability , 134 :211 , 2016
Abstract : A gene encoding cutinase from Fusarium solani was cloned and overexpressed in Pichia pastoris. The recombinant cutinase with a molecular weight of 24 kDa was then purified to homogeneity. The enzyme presents degradation capacity for poly(butylene succinate) (PBS) and exhibits the optimum pH and temperature of 8.0 and 50 C, respectively. Enzyme activity is enhanced by K+ and Na+ and inhibited by Zn2+,Fe2+ ,Mn2+, and Co2+. The inhibitions of different chemicals on recombinant enzyme activity were examined. EDTA and b-mercaptoethanol exert significant inhibitory effect. The degradation of PBS films in the presence of the recombinant enzyme was further studied. Results showed that enzymatic degradation is a rapid process, and the PBS fi lms were degraded completely after approximately 6 h. The characteristics of PBS films after degradation were analyzed. With the extension of degradation time, the surfaces of PBS films became rougher and holes appeared with a gradually increasing trend. Differential scanning calorimetry and scanning electron microscopy analyses revealed that both amorphous and crystalline regions of PBS were degraded by the recombinant enzyme. Wide-angle X-ray diffractometer also indicated the crystallinity of PBS has a gradual downward trend with the extension of degradation time. Gel permeation chromatography showed the molecular weight of PBS has no obvious change before and after degradation.
ESTHER : Hu_2016_Polym.Degrad.Stab_134_211
PubMedSearch : Hu_2016_Polym.Degrad.Stab_134_211
Gene_locus related to this paper: fusso-cutas

Title : An automated Genomes-to-Natural Products platform (GNP) for the discovery of modular natural products - Johnston_2015_Nat.Commun_6_8421
Author(s) : Johnston CW , Skinnider MA , Wyatt MA , Li X , Ranieri MR , Yang L , Zechel DL , Ma B , Magarvey NA
Ref : Nat Commun , 6 :8421 , 2015
Abstract : Bacterial natural products are a diverse and valuable group of small molecules, and genome sequencing indicates that the vast majority remain undiscovered. The prediction of natural product structures from biosynthetic assembly lines can facilitate their discovery, but highly automated, accurate, and integrated systems are required to mine the broad spectrum of sequenced bacterial genomes. Here we present a genome-guided natural products discovery tool to automatically predict, combinatorialize and identify polyketides and nonribosomal peptides from biosynthetic assembly lines using LC-MS/MS data of crude extracts in a high-throughput manner. We detail the directed identification and isolation of six genetically predicted polyketides and nonribosomal peptides using our Genome-to-Natural Products platform. This highly automated, user-friendly programme provides a means of realizing the potential of genetically encoded natural products.
ESTHER : Johnston_2015_Nat.Commun_6_8421
PubMedSearch : Johnston_2015_Nat.Commun_6_8421
PubMedID: 26412281
Gene_locus related to this paper: 9actn-a0a514jvg4

Title : Inhibition of miR-134 Protects Against Hydrogen Peroxide-Induced Apoptosis in Retinal Ganglion Cells - Shao_2015_J.Mol.Neurosci_56_461
Author(s) : Shao Y , Yu Y , Zhou Q , Li C , Yang L , Pei CG
Ref : Journal of Molecular Neuroscience , 56 :461 , 2015
Abstract : MicroRNAs (miRNAs) have been suggested to play an important role in neurological diseases. Particularly, miR-134 is reportedly involved in regulating neuron survival. However, the association between miR-134 and retinal ganglion cell (RGC) survival under adverse stimulus has not been extensively investigated. In this study, we aimed to explore the role and underlying mechanism of miR-134 in regulating RGC apoptosis in response to hydrogen peroxide (H2O2) treatment. Results showed that the expression of miR-134 dose- and time-dependently increased in RGC after H2O2 treatment. H2O2-induced RGC apoptosis was significantly attenuated by the inhibition of miR-134 expression by antagomiR-134 and was enhanced by miR-134 overexpression. Luciferase reporter assay revealed a direct interaction between miR-134 and the 3'-untranslated region of cyclic AMP-response element-binding protein (CREB), a critical transcription factor for neuronal protection. In H2O2-treated RGCs, the inhibition of miR-134 significantly elevated the expression of CREB and its downstream genes, including brain-derived neurotrophic factor (BDNF) and Bcl-2. Furthermore, the inhibition of miR-134 also increased the expression of miR-132, a rapid response gene downstream of CREB. In addition, the target gene of miR-132, acetylcholinesterase was expectedly decreased by miR-134 inhibition. However, the overexpression of miR-134 exerted an opposite effect. The knockdown of CREB apparently abolished the protective effect of miR-134 inhibition against H2O2-induced RGC apoptosis. The increased expression of BDNF and Bcl-2 induced by miR-134 inhibition was also abrogated by CREB knockdown. Overall, our results suggested that the downregulation of miR-134 can effectively protect against H2O2-induced RGC apoptosis by negatively modulating CREB expression.
ESTHER : Shao_2015_J.Mol.Neurosci_56_461
PubMedSearch : Shao_2015_J.Mol.Neurosci_56_461
PubMedID: 25744098

Title : Highly sensitive and selective detection of human carboxylesterase 1 activity by liquid chromatography with fluorescence detection - Wang_2015_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_1008_212
Author(s) : Wang DD , Jin Q , Hou J , Feng L , Li N , Li SY , Zhou Q , Zou LW , Ge GB , Wang JG , Yang L
Ref : Journal of Chromatography B Analyt Technol Biomed Life Sciences , 1008 :212 , 2015
Abstract : Human carboxylesterases 1 (hCE1), one of the most important human drug metabolizing enzymes, catalyzes the hydrolysis of a large number of structurally diverse of endogenous and exogenous substrates. However, a practical, reliable and sensitive method for the precise measurement of hCE1 activities in complex biological samples has been rarely reported. In this study, a liquid chromatography-fluorescence detection (LC-FD) based method was developed for highly selective and sensitive measurement of hCE1 activities in human tissue and cell preparations. This method was based on the fluorimetric detection of HMBT, the hydrolyzed product of BMBT which was a newly developed specific probe substrate for hCE1. The developed LC-FD method was fully validated in terms of specificity, sensitivity, linearity, precision, recovery and stability. With the help of LC separation, most polar endogenous compounds in biological samples could be eluted in the column dead time, which is very beneficial for accurate determination of hCE1 activities in complex biological samples. The lower limit of quantification for HMBT (product of hCE1) of this LC-FD based method was as low as 20nM, which was quite lower than other reported methods. The method also exhibited good precision, both intra- and inter- assay variances were both lower than 2.5%. Furthermore, the newly developed method was successfully applied to measure hCE1 activity in human liver preparations from individual donors (n=12), as well as in homogenates from eleven different human cell lines. All these findings combined with this practical method are very helpful for the deep understanding of the expression and function of hCE1 in human biological samples.
ESTHER : Wang_2015_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_1008_212
PubMedSearch : Wang_2015_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_1008_212
PubMedID: 26673230

Title : Conversion of inhibition biosensing to substrate-like biosensing for quinalphos selective detection - Yang_2015_Anal.Chem_87_5270
Author(s) : Yang L , Han J , Liu W , Li J , Jiang L
Ref : Analytical Chemistry , 87 :5270 , 2015
Abstract : Since all of the organophosphorus pesticides (OPP) inhibit the cholinesterases with a common mechanism, it is still challenging to detect OPP selectively with inhibition-based biosensors. This study focuses on the conversion of a typical inhibition biosensing to a selective substrate-like biosensing. The interaction of quinalphos with plant-esterase involves not only a decrease in enzyme activity but also a heterolytic bond cleavage of quinalphos. The leaving group eliminated from quinalphos is an ideal biomarker due to its specificity in most OPP. Thus, using 2-hydroxyquinoxaline (HQO), the leaving group of quinalphos, as the biomarker and meso-tetra (4-sulfonatophenyl) porphine (TPPS4) as an optical probe, quinalphos can be selectively detected. The molecular recognition between TPPS4 and HQO leads to a considerable sensitivity of the detection. The spectral responses of TPPS4 show a linear dependence on quinalphos concentration in the presence of plant-esterase within the 0.01-1 mg kg(-1) range. The detection limit is 0.01 mg kg(-1), well below the maximum residue limits (MRLs) defined by European Union (0.05 mg kg(-1)) and China (0.2 mg kg(-1)).
ESTHER : Yang_2015_Anal.Chem_87_5270
PubMedSearch : Yang_2015_Anal.Chem_87_5270
PubMedID: 25921798

Title : Increase of Oleic Acid Content in Phosphatidylcholine through Lipase-catalyzed Interesterification: Optimization by Response Surface Methodology - Yang_2015_J.Oleo.Sci_64_673
Author(s) : Yang G , Yang L
Ref : J Oleo Sci , 64 :673 , 2015
Abstract : In order to obtain phosphatidylcholine (PC) with higher amount of oleic acid, the interesterification between soybean PC and Camellia oleifera oil (COO) rich in oleic acid catalyzed by lipase was studied in hexane. For this aim three commercially available immobilized lipases (Novozym 435, Lipozyme TLIM and Lipozyme RMIM) were assayed and Novozym 435 was finally selected for further optimization. The effects of the factors, such as PC concentration, substrate ratio, water amount, lipase dosage and temperature, on the oleic acid content in PC and PC recovery during the interesterification were investigated. The conditions of the interesterification were optimized using response surface methodology. The optimum conditions were as follows: lipase dosage 13 % (based on the mass of PC and COO), reaction temperature 55 degC, water amount 5% (based on the mass of PC), reaction time 8 h, PC concentration 0.3g/mL (PC/hexane), PC-to-COO ratio 1:3 (acyl groups in PC/acyl groups in COO, mol/mol). Under these conditions, oleic acid content and PC recovery were 40.8 +/- 0.5% and 69.0 +/- 2.8%, respectively. Analysis of variance (ANOVA) showed that the regression models were adequate for predicting the interesterifiction. The orders of reaction variables affecting on oleic acid content and PC recovery were water amount > reaction time > lipase dosage > reaction temperature, and water amount > reaction temperature > lipase dosage > reaction time, respectively.
ESTHER : Yang_2015_J.Oleo.Sci_64_673
PubMedSearch : Yang_2015_J.Oleo.Sci_64_673
PubMedID: 25891113

Title : A Two-Photon Ratiometric Fluorescent Probe for Imaging Carboxylesterase 2 in Living Cells and Tissues - Jin_2015_ACS.Appl.Mater.Interfaces_7_28474
Author(s) : Jin Q , Feng L , Wang DD , Dai ZR , Wang P , Zou LW , Liu ZH , Wang JY , Yu Y , Ge GB , Cui JN , Yang L
Ref : ACS Appl Mater Interfaces , 7 :28474 , 2015
Abstract : In this study, a two-photon ratiometric fluorescent probe NCEN has been designed and developed for highly selective and sensitive sensing of human carboxylesterase 2 (hCE2) based on the catalytic properties and substrate preference of hCE2. Upon addition of hCE2, the probe could be readily hydrolyzed to release 4-amino-1,8-naphthalimide (NAH), which brings remarkable red-shift in fluorescence (90 nm) spectrum. The newly developed probe exhibits good specificity, ultrahigh sensitivity, and has been successfully applied to determine the real activities of hCE2 in complex biological samples such as cell and tissue preparations. NCEN has also been used for two-photon imaging of intracellular hCE2 in living cells as well as in deep-tissues for the first time, and the results showed that the probe exhibited high ratiometric imaging resolution and deep-tissue imaging depth. All these findings suggested that this probe holds great promise for applications in bioimaging of endogenous hCE2 in living cells and in exploring the biological functions of hCE2 in complex biological systems.
ESTHER : Jin_2015_ACS.Appl.Mater.Interfaces_7_28474
PubMedSearch : Jin_2015_ACS.Appl.Mater.Interfaces_7_28474
PubMedID: 26641926

Title : Discovery and expression of a Pseudomonas sp. esterase as a novel biocatalyst for the efficient biosynthesis of a chiral intermediate of pregabalin -
Author(s) : Xu F , Chen S , Xu G , Wu J , Yang L
Ref : Biotechnol Bioprocess Eng , 20 :473 , 2015

Title : Bactericidal Dendritic Polycation Cloaked with Stealth Material via Lipase-Sensitive Intersegment Acquires Neutral Surface Charge without Losing Membrane-Disruptive Activity - Xu_2015_ACS.Appl.Mater.Interfaces_7_27602
Author(s) : Xu L , He C , Hui L , Xie Y , Li JM , He WD , Yang L
Ref : ACS Appl Mater Interfaces , 7 :27602 , 2015
Abstract : Net cationicity of membrane-disruptive antimicrobials is necessary for their activity but may elicit immune attack when administered intravenously. By cloaking a dendritic polycation (G2) with poly(caprolactone-b-ethylene glycol) (PCL-b-PEG), we obtain a nanoparticle antimicrobial, G2-g-(PCL-b-PEG), which exhibits neutral surface charge but kills >99.9% of inoculated bacterial cells at >=8 microg/mL. The observed activity may be attributed PCL's responsive degradation by bacterial lipase and the consequent exposure of the membrane-disruptive, bactericidal G2 core. Moreover, G2-g-(PCL-b-PEG) exhibits good colloidal stability in the presence of serum and insignificant hemolytic toxicity even at <=2048 microg/mL. suggesting good blood compatibility required for intravenous administration.
ESTHER : Xu_2015_ACS.Appl.Mater.Interfaces_7_27602
PubMedSearch : Xu_2015_ACS.Appl.Mater.Interfaces_7_27602
PubMedID: 26632646

Title : Fructus Psoraleae contains natural compounds with potent inhibitory effects towards human carboxylesterase 2 - Li_2015_Fitoterapia_101_99
Author(s) : Li YG , Hou J , Li SY , Lv X , Ning J , Wang P , Liu ZM , Ge GB , Ren JY , Yang L
Ref : Fitoterapia , 101 :99 , 2015
Abstract : Fructus Psoraleae (FP) is an edible Chinese herbal which is widely used in Asia for the treatment of various diseases including asthma, diarrhea, and osteoporosis. This study aimed to investigate the inhibitory effects of the crude ethanol extract from FP on human carboxylesterase 2 (hCE2), as well as to identity and characterize the naturally occurring inhibitors of hCE2 in FP. Our results demonstrated that the ethanol extract of FP displayed potent inhibitory effects towards hCE2, while five major bioactive constitutes in FP were efficiently identified by LC-DAD-ESI-MS/MS, with the aid of LC-based activity profiling. The identified bioactive compounds including neobavaisoflavone, isobavachalcone, bavachinin, corylifol A and bakuchiol were found to be naturally occurring potent inhibitors of hCE2, with low Ki values ranging from 0.62muM to 3.89muM. This is the first report of the chemical constitutes in FP as potent inhibitors of hCE2.
ESTHER : Li_2015_Fitoterapia_101_99
PubMedSearch : Li_2015_Fitoterapia_101_99
PubMedID: 25596095

Title : Genome and transcriptome analysis of the fungal pathogen Fusarium oxysporum f. sp. cubense causing banana vascular wilt disease - Guo_2014_PLoS.One_9_e95543
Author(s) : Guo L , Han L , Yang L , Zeng H , Fan D , Zhu Y , Feng Y , Wang G , Peng C , Jiang X , Zhou D , Ni P , Liang C , Liu L , Wang J , Mao C , Fang X , Peng M , Huang J
Ref : PLoS ONE , 9 :e95543 , 2014
Abstract : BACKGROUND: The asexual fungus Fusarium oxysporum f. sp. cubense (Foc) causing vascular wilt disease is one of the most devastating pathogens of banana (Musa spp.). To understand the molecular underpinning of pathogenicity in Foc, the genomes and transcriptomes of two Foc isolates were sequenced. METHODOLOGY/PRINCIPAL FINDINGS: Genome analysis revealed that the genome structures of race 1 and race 4 isolates were highly syntenic with those of F. oxysporum f. sp. lycopersici strain Fol4287. A large number of putative virulence associated genes were identified in both Foc genomes, including genes putatively involved in root attachment, cell degradation, detoxification of toxin, transport, secondary metabolites biosynthesis and signal transductions. Importantly, relative to the Foc race 1 isolate (Foc1), the Foc race 4 isolate (Foc4) has evolved with some expanded gene families of transporters and transcription factors for transport of toxins and nutrients that may facilitate its ability to adapt to host environments and contribute to pathogenicity to banana. Transcriptome analysis disclosed a significant difference in transcriptional responses between Foc1 and Foc4 at 48 h post inoculation to the banana 'Brazil' in comparison with the vegetative growth stage. Of particular note, more virulence-associated genes were up regulated in Foc4 than in Foc1. Several signaling pathways like the mitogen-activated protein kinase Fmk1 mediated invasion growth pathway, the FGA1-mediated G protein signaling pathway and a pathogenicity associated two-component system were activated in Foc4 rather than in Foc1. Together, these differences in gene content and transcription response between Foc1 and Foc4 might account for variation in their virulence during infection of the banana variety 'Brazil'. CONCLUSIONS/SIGNIFICANCE: Foc genome sequences will facilitate us to identify pathogenicity mechanism involved in the banana vascular wilt disease development. These will thus advance us develop effective methods for managing the banana vascular wilt disease, including improvement of disease resistance in banana.
ESTHER : Guo_2014_PLoS.One_9_e95543
PubMedSearch : Guo_2014_PLoS.One_9_e95543
PubMedID: 24743270
Gene_locus related to this paper: fusox-w9hvf0 , fusox-x0d9n6

Title : Characterization and structure basis of Pseudomonas alcaligenes lipase's enantiopreference towards d,l-menthyl propionate - Chen_2014_J.Mol.Catal.B.Enzym_102_81
Author(s) : Chen H , Wu J , Yang L , Xu G
Ref : J Mol Catal B Enzym , 102 :81 , 2014
Abstract : In this work, a lipase from Pseudomonas alcaligenes CGMCC4405 (PaL) was cloned and expressed. It was very attractive that the recombinant PaL exhibited excellent enantioselectivity (E > 200) in the resolution of racemic d,l-menthyl propionate to produce l-menthol. The structure basis of enantiopreference is a fundamental scientific problem which needs to be resolved. In our research, molecular dynamic simulation (MD) research was employed to research the different binding modes of d and l-menthyl propionate. The results showed that when bound with slow-reacting enantiomer (d-menthyl propionate), the steric requirements of the large substituent (isopropyl) of the d-menthyl propionate force a rotation of the imidazole ring of catalytic residue His271 and further pushed the active site His271 away from its proper orientation. Moreover, the average distance between alcohol oxygen (Oalc) and HNe of catalytic His271 increased to 3.7 A, which was too far to form an essential hydrogen bond and further prevented efficient catalysis of slow enantiomer. This correlation of the distance between alcohol oxygen (Oalc) and HNe of catalytic His271 and the enantioselectivity was also confirmed by the result of site-directed mutagenesis.
ESTHER : Chen_2014_J.Mol.Catal.B.Enzym_102_81
PubMedSearch : Chen_2014_J.Mol.Catal.B.Enzym_102_81
Gene_locus related to this paper: stema-s4tny8

Title : A highly selective ratiometric fluorescent probe for in vitro monitoring and cellular imaging of human carboxylesterase 1 - Liu_2014_Biosens.Bioelectron_57C_30
Author(s) : Liu ZM , Feng L , Ge GB , Lv X , Hou J , Cao YF , Cui JN , Yang L
Ref : Biosensors & Bioelectronics , 57C :30 , 2014
Abstract : A new ratiometric fluorescent probe derived from 2-(2-hydroxy-3-methoxyphenyl) benzothiazole (HMBT) has been developed for selective monitoring of human carboxylesterase 1 (hCE1). The probe is designed by introducing benzoyl moiety to HMBT. The prepared latent spectroscopic probe 1 displays satisfying stability under physiological pH conditions with very low background signal. Both the reaction phynotyping and chemical inhibition assays demonstrated that hCE1 mediated the specific cleavage of the carboxylic ester bond of probe 1 in human biological samples. The release of HMBT leads to a remarkable red-shifted emission in fluorescence spectrum (120nm large emission shift). Furthermore, human cell-based assays show that probe 1 is cell membrane permeable, and it can be used for bioassay and cellular imaging of hCE1 activity in HepG2 cells. These findings lead to the development of a simple and sensitive fluorescent method for measurement of hCE1 activity in vitro or in living cells, in the presence of additional enzymes or endogenous compounds.
ESTHER : Liu_2014_Biosens.Bioelectron_57C_30
PubMedSearch : Liu_2014_Biosens.Bioelectron_57C_30
PubMedID: 24534577

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

Title : A ratiometric fluorescent sensor for highly selective detection of human carboxylesterase 2 and its application in living cells, - Liu_2014_Sens.Actuators.B.Chem_205_151
Author(s) : Liu ZM , Feng L , Hou J , Lv X , Ning J , Ge GB , Wang KW , Cui JN , Yang L
Ref : Sensors and Actuators B: Chemical , 205 :151 , 2014
Abstract : A new ratiometric fluorescent probe derived from 4-hydroxy-N-butyl-1,8-naphthalimide (HNN) has been developed for selective detection of human carboxylesterase 2 (hCE2). The probe is designed by introducing benzoyl moiety to HNN, based on the intramolecular charge transfer (ICT) mechanism. The probe displays satisfying stability under physiological pH conditions with very low background fluorescence signal, but it can be rapidly hydrolyzed by hCE2 and release of HNN which leads to a remarkable red shift in emission spectra (148nm). The newly designed probe exhibits excellent selectivity towards hCE2 over other human hydrolases, while the interference from various biologically relevant chemicals can be negligible. Its potential biological applications including inhibitor screening using human tissue preparations as enzyme sources, as well as fluorescence imaging of endogenous hCE2 in human living cells, have also been demonstrated.
ESTHER : Liu_2014_Sens.Actuators.B.Chem_205_151
PubMedSearch : Liu_2014_Sens.Actuators.B.Chem_205_151

Title : Rapid and sensitive detection of the inhibitive activities of acetyl- and butyryl-cholinesterases inhibitors by UPLC-ESI-MS\/MS - Liu_2014_J.Pharm.Biomed.Anal_94_215
Author(s) : Liu W , Yang Y , Cheng X , Gong C , Li S , He D , Yang L , Wang Z , Wang C
Ref : J Pharm Biomed Anal , 94 :215 , 2014
Abstract : Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are legitimate therapeutic targets for Alzheimer's disease. The classical approach for screening potential AChE/BChE inhibitors was developed by Ellman. However, the background color of compounds or plant extracts remained uncertain and frequently interfered with the detection of the secondary reaction, thereby easily yielding false positive or false negative results. Rapid, selective, and sensitive ultra-performance liquid chromatography combined with electrospray ionization tandem mass spectrometry method was developed and used for the detection of AChE and BChE inhibition by directly determining the common product, choline (Ch). Proper separation was achieved for choline and chlormequat (internal standard) within 1.2min via isocratic elution (0.1% fromic acid:methanol=98:2) on an HSS T3 column following a simple precipitation of proteins for sample treatment. The relative standard deviations of the intra- and inter-day precisions were below 7.34 and 9.09%, respectively, whereas the mean accuracy for the quality control samples was 100.31+/-10.93%. The method exhibited the advantages of small total reaction volume (100muL), short analysis time (1.2min), high sensitivity (LOQ of 0.036muM for Ch), and low cost (little consumption enzymes of 0.0035 and 0.008unitmL(-1) for AChE and BChE, and substrates of 5.505 and 7.152muM for ACh and BCh in individual inhibition, respectively), and without matrix effect (90.00-105.03%). The developed method was successfully applied for detecting the AChE and BChE inhibitive activities for model drugs, including galanthamine, tacrine, neostigmine methylsulfate, eserine, as well as beta-carboline and quinazoline alkaloids from Peganum harmala.
ESTHER : Liu_2014_J.Pharm.Biomed.Anal_94_215
PubMedSearch : Liu_2014_J.Pharm.Biomed.Anal_94_215
PubMedID: 24631841

Title : Design and synthesis of systemically active metabotropic glutamate subtype-2 and -3 (mGlu2\/3) receptor positive allosteric modulators (PAMs): pharmacological characterization and assessment in a rat model of cocaine dependence - Dhanya_2014_J.Med.Chem_57_4154
Author(s) : Dhanya RP , Sheffler DJ , Dahl R , Davis M , Lee PS , Yang L , Nickols HH , Cho HP , Smith LH , D'Souza MS , Conn PJ , Der-Avakian A , Markou A , Cosford ND
Ref : Journal of Medicinal Chemistry , 57 :4154 , 2014
Abstract : As part of our ongoing small-molecule metabotropic glutamate (mGlu) receptor positive allosteric modulator (PAM) research, we performed structure-activity relationship (SAR) studies around a series of group II mGlu PAMs. Initial analogues exhibited weak activity as mGlu2 receptor PAMs and no activity at mGlu3. Compound optimization led to the identification of potent mGlu2/3 selective PAMs with no in vitro activity at mGlu1,4-8 or 45 other CNS receptors. In vitro pharmacological characterization of representative compound 44 indicated agonist-PAM activity toward mGlu2 and PAM activity at mGlu3. The most potent mGlu2/3 PAMs were characterized in assays predictive of ADME/T and pharmacokinetic (PK) properties, allowing the discovery of systemically active mGlu2/3 PAMs. On the basis of its overall profile, compound 74 was selected for behavioral studies and was shown to dose-dependently decrease cocaine self-administration in rats after intraperitoneal administration. These mGlu2/3 receptor PAMs have significant potential as small molecule tools for investigating group II mGlu pharmacology.
ESTHER : Dhanya_2014_J.Med.Chem_57_4154
PubMedSearch : Dhanya_2014_J.Med.Chem_57_4154
PubMedID: 24735492

Title : Phaeodactylibacter xiamenensis gen. nov., sp. nov., a member of the family Saprospiraceae isolated from the marine alga Phaeodactylum tricornutum - Chen_2014_Int.J.Syst.Evol.Microbiol_64_3496
Author(s) : Chen Z , Lei X , Lai Q , Li Y , Zhang B , Zhang J , Zhang H , Yang L , Zheng W , Tian Y , Yu Z , Xu H , Zheng T
Ref : Int J Syst Evol Microbiol , 64 :3496 , 2014
Abstract : A novel Gram-staining-negative, aerobic, rod-shaped, non-motile, reddish-orange and chemoheterotrophic bacteria, designated strain KD52(T), was isolated from a culture of the alga Phaeodactylum tricornutum from Xiamen, Fujian Province, China. 16S rRNA gene sequence comparison showed that strain KD52(T) was a member of the family Saprospiraceae, forming a distinct lineage with 'Portibacter lacus' KCTC 23747. The 16S rRNA gene sequence similarity between strain KD52(T) and the type strains of species of the family Saprospiraceae ranged from 86% to 89%. Growth occurred at 20-37 degrees C (optimum, 28 degrees C), in the presence of 1-9% (w/v) NaCl (optimum, 2.5%) and at pH 5-8.5 (optimum, pH 6.0). The dominant fatty acids (>10%) of strain KD52(T) were iso-C15:0 (33.1%), iso-C15:1 G (14.8%) and summed feature 3 (comprising C16:1omega7c and/or C16:1omega6c, 13.8%). The major polar lipids were diphosphatidylglycerol, three unidentified phospholipids, four unknown lipids and one unidentified aminolipid. The DNA G+C content was 51 mol% and the major respiratory quinone was menaquinone-7 (MK-7). On the basis of phenotypic data and phylogenetic inference, strain KD52(T) represents a novel species of a new genus, for which the name Phaeodactylibacter xiamenensis gen. nov., sp. nov., is proposed. The type strain is KD52(T) ( = MCCC 1F01213(T) = KCTC 32575(T)).
ESTHER : Chen_2014_Int.J.Syst.Evol.Microbiol_64_3496
PubMedSearch : Chen_2014_Int.J.Syst.Evol.Microbiol_64_3496
PubMedID: 25052393
Gene_locus related to this paper: 9bact-a0a098s2s4 , 9bact-a0a098s0v5

Title : A novel acetylcholinesterase biosensor based on carboxylic graphene coated with silver nanoparticles for pesticide detection - Liu_2014_Mater.Sci.Eng.C.Mater.Biol.Appl_35_253
Author(s) : Liu Y , Wang G , Li C , Zhou Q , Wang M , Yang L
Ref : Mater Sci Eng C Mater Biol Appl , 35 :253 , 2014
Abstract : A novel acetylcholinesterase (AChE) biosensor based on Ag NPs, carboxylic graphene (CGR) and Nafion (NF) hybrid modified glass carbon electrode (GCE) has been successfully developed. Ag NPs-CGR-NF possessed predominant conductivity, catalysis and biocompatibility and provided a hydrophilic surface for AChE adhesion. Chitosan (CS) was used to immobilize AChE on the surface of Ag NPs-CGR-NF/GCE to keep the AChE activities. The AChE biosensor showed favorable affinity to acetylthiocholine chloride (ATCl) and could catalyze the hydrolysis of ATCl with an apparent Michaelis-Menten constant value of 133muM, which was then oxidized to produce a detectable and fast response. Under optimum conditions, the biosensor detected chlorpyrifos and carbaryl at concentrations ranging from 1.0x10(-13) to 1x10(-8)M and from 1.0x10(-12) to 1x10(-8)M. The detection limits for chlorpyrifos and carbaryl were 5.3x10(-14)M and 5.45x10(-13)M, respectively. The developed biosensor exhibited good sensitivity, stability, reproducibility and low cost, thus providing a promising tool for analysis of enzyme inhibitors. This study could provide a simple and effective immobilization platform for meeting the demand of the effective immobilization enzyme on the electrode surface.
ESTHER : Liu_2014_Mater.Sci.Eng.C.Mater.Biol.Appl_35_253
PubMedSearch : Liu_2014_Mater.Sci.Eng.C.Mater.Biol.Appl_35_253
PubMedID: 24411376

Title : A highly selective long-wavelength fluorescent probe for the detection of human carboxylesterase 2 and its biomedical applications - Feng_2014_Chem.Commun.(Camb)_50_14519
Author(s) : Feng L , Liu ZM , Xu L , Lv X , Ning J , Hou J , Ge GB , Cui JN , Yang L
Ref : Chem Commun (Camb) , 50 :14519 , 2014
Abstract : A highly selective long-wavelength fluorescent probe TCFB has been developed for the detection of hCE2. The probe can be used for real-time monitoring of hCE2 activity in complex biological systems.
ESTHER : Feng_2014_Chem.Commun.(Camb)_50_14519
PubMedSearch : Feng_2014_Chem.Commun.(Camb)_50_14519
PubMedID: 25303144
Gene_locus related to this paper: human-CES2

Title : A highly selective fluorescent ESIPT probe for the detection of Human carboxylesterase 2 and its biological applications - Feng_2014_Biosens.Bioelectron_65C_9
Author(s) : Feng L , Liu ZM , Hou J , Lv X , Ning J , Ge GB , Cui JN , Yang L
Ref : Biosensors & Bioelectronics , 65C :9 , 2014
Abstract : A new ratiometric florescence probe derived from 3-hydroxyflavone (3-HF) has been developed for selective and sensitive detection of human carboxylesterase 2 (CE2). The probe is designed by modulating the excited state intramolecular proton transfer (ESIPT) emission of 3-HF via introducing of 4-ethylbenzoyloxy group. Under physiological conditions, probe 1 displays satisfying stability with very low background signal, but it can be selectively hydrolyzed by CE2 to release free 3-HF which brings remarkable changes in fluorescence spectrum. Both reaction phenotyping and chemical inhibition assays demonstrate that probe 1 is highly selective for CE2 over other human hydrolases including carboxylesterase 1, cholinesterases and paraoxonases. Probe 1 has been applied successfully to measure the real activities of CE2 in human biological samples, as well as to screen CE2 inhibitors by using tissue preparations as the enzymes sources. Additionally, probe 1 is cell membrane permeable and can be used for cellular imaging of endogenous CE2 in living cells. All of these features make it possible to serve as a promising tool for exploring the individual differences in biological function of CE2, as well as for rapid screening of selective and potent inhibitors of CE2 for further clinical use.
ESTHER : Feng_2014_Biosens.Bioelectron_65C_9
PubMedSearch : Feng_2014_Biosens.Bioelectron_65C_9
PubMedID: 25461132

Title : Galantamine, an acetylcholinesterase inhibitor, reduces brain damage induced by hypoxia-ischemia in newborn rats - Furukawa_2014_Int.J.Dev.Neurosci_37C_52
Author(s) : Furukawa S , Yang L , Sameshima H
Ref : Int J Developmental Neuroscience , 37C :52 , 2014
Abstract : AIM: Our aim is to elucidate whether galantamine, known as an acetylcholinesterase inhibitor, reduces brain damage induced by hypoxia-ischemia (HI). STUDY DESIGN: 7-day-old Wistar rats were used. Rats were subjected to left carotid artery ligation followed by 2h of hypoxia (8% oxygen). We injected galantamine intraperitoneally just before hypoxia (5.0mg/kg, n=14; 2.5mg/kg, n=9; 1.0mg/kg, n=11) and after hypoxia (5.0mg/kg, n=7) to determine its neuroprotective effect. An equivalent volume of saline was administered as a control before (n=31) and after hypoxic load (n=7). We also examined the production of IL-1beta in the ligated hemisphere side after injection of galantamine (prior hypoxia; 5.0mg/kg, n=7) or saline (n=8). Brains were analyzed 7 days after HI.
RESULTS: Two of the 5.0mg/kg galantamine pre-treated rats and a post-treated rat died during experiments. The remaining survived and 5.0mg/kg galantamine pre-treated rats showed a marked reduction of brain damage (p<0.01) compared with the control. The other galantamine groups had severe brain damage similar to controls. Microglial accumulation was significantly reduced in rats pre-treated with 5.0mg/kg of galantamine compared to control rats on both the hippocampus (p=0.02) and cortex (p<0.01). In contrast, the other galantamine groups showed a lower suppressive effect on microglial accumulation compared to the control. Galantamine significantly reduced IL-1beta productions when compared to the control (p<0.01). CONCLUSION: Pre-treatment of galantamine reduced brain damage with a suppressive effect on microglial accumulation and IL-1beta production in a newborn rat model of HI.
ESTHER : Furukawa_2014_Int.J.Dev.Neurosci_37C_52
PubMedSearch : Furukawa_2014_Int.J.Dev.Neurosci_37C_52
PubMedID: 24972037

Title : Evidences for B6C3-Tg (APPswe\/PSEN1dE9) Double-Transgenic Mice Between 3 and 10 Months as an Age-Related Alzheimer's Disease Model - Zhong_2014_J.Mol.Neurosci_53_370
Author(s) : Zhong Z , Yang L , Wu X , Huang W , Yan J , Liu S , Sun X , Liu K , Lin H , Kuang S , Tang X
Ref : Journal of Molecular Neuroscience , 53 :370 , 2014
Abstract : Transgenic mouse has shown great advantages in the study of Alzheimer's disease (AD) and drug screening as AD develops rapidly resent years, while more detail information of these transgenic mice and experience of application are needed. To obtain the basic background information of the B6C3-Tg (APPswe/PSEN1dE9) double-transgenic mouse, which was reported with early onset AD, three- to ten-month-old B6C3-Tg AD mice and normal C57BL/6 mice were selected randomly to test the ability of learning memory by Morris water maze, the brain acetylcholinesterase (AChE) activity by AChE kit, and beta amyloid protein level by immunohistochemistry staining. Compared with the control group, the escape latency time of B6C3-Tg AD mice at 9 and 10 months of age is significantly longer (P < 0.05) in Morris maze test, and the activity of brain AChE is higher. beta-Amyloid plaques were observed at 3 months of age and developed rapidly. Statistical analysis showed a positive correlation between the area of these plaques and the ages of B6C3-Tg AD mouse (y = 0.0355e(0.5557x), R = 0.9557). The model's behavior is conformed to simulate behaviors of human Alzheimer's disease at the early stage and may provide detail background information a new choice when transgenic mice are needed in the research of AD.
ESTHER : Zhong_2014_J.Mol.Neurosci_53_370
PubMedSearch : Zhong_2014_J.Mol.Neurosci_53_370
PubMedID: 24362678

Title : Association of serum adipose triglyceride lipase levels with obesity and diabetes - Yang_2014_Genet.Mol.Res_13_6746
Author(s) : Yang L , Chen SJ , Yuan GY , Zhou LB , Wang D , Wang XZ , Chen JJ
Ref : Genet Mol Res , 13 :6746 , 2014
Abstract : The aim of this study was to detect the serum adipose triglyceride lipase (ATGL) levels in obesity and newly diagnosed type 2 diabetes patients, and to explore the association between ATGL with glucose and lipid metabolism. We enrolled 66 patients with type 2 diabetes and 48 patients with normal glucose regulation, who were divided into an overweight or obese subgroup and a normal weight subgroup according to body mass index (BMI) >/= 25 kg/m(2). The enzyme-linked immunosorbent assay was used to detect fasting blood glucose, blood lipids, fasting insulin, and ATGL levels. The serum ATGL level in the overweight or obese group was lower than that in the non-obese group including patients with type 2 diabetes and normal glucose regulation: 239 +/- 61 vs 355 +/- 54 mg/L and 242 +/- 60 vs 383 +/- 58 mg/L, respectively (t = 22.53, t = 8.23, P < 0.05). The Pearson correlation analysis showed that fasting serum ATGL was negatively correlated with body fat content, BMI, waist-to-hip ratio, triglycerides, and the homeostatic model assessment-insulin resistance level (r = -0.271, r = -0.238, r = -0.375, r = -0.313, and r = -0.164, respectively, P < 0.05). The stepwise regression analysis showed that the waist-to-hip ratio and body fat content were independently associated with the serum ATGL level. Our results indicated that the ATGL level may be closely related to obesity.
ESTHER : Yang_2014_Genet.Mol.Res_13_6746
PubMedSearch : Yang_2014_Genet.Mol.Res_13_6746
PubMedID: 25177954

Title : Fe(3)O(4) magnetic nanoparticle peroxidase mimetic-based colorimetric assay for the rapid detection of organophosphorus pesticide and nerve agent - Liang_2013_Anal.Chem_85_308
Author(s) : Liang M , Fan K , Pan Y , Jiang H , Wang F , Yang D , Lu D , Feng J , Zhao J , Yang L , Yan X
Ref : Analytical Chemistry , 85 :308 , 2013
Abstract : Rapid and sensitive detection methods are in urgent demand for the screening of extensively used organophosphorus pesticides and highly toxic nerve agents for their neurotoxicity. In this study, we developed a novel Fe(3)O(4) magnetic nanoparticle (MNP) peroxidase mimetic-based colorimetric method for the rapid detection of organophosphorus pesticides and nerve agents. The detection assay is composed of MNPs, acetylcholinesterase (AChE), and choline oxidase (CHO). The enzymes AChE and CHO catalyze the formation of H(2)O(2) in the presence of acetylcholine, which then activates MNPs to catalyze the oxidation of colorimetric substrates to produce a color reaction. After incubation with the organophosphorus neurotoxins, the enzymatic activity of AChE was inhibited and produced less H(2)O(2), resulting in a decreased catalytic oxidation of colorimetric substrates over MNP peroxidase mimetics, accompanied by a drop in color intensity. Three organophosphorus compounds were tested on the assay: acephate and methyl-paraoxon as representative organophosphorus pesticides and the nerve agent Sarin. The novel assay displayed substantial color change after incubation in organophosphorus neurotoxins in a concentration-dependent manner. As low as 1 nM Sarin, 10 nM methyl-paraoxon, and 5 muM acephate are easily detected by the novel assay. In conclusion, by employing the peroxidase-mimicking activity of MNPs, the developed colorimetric assay has the potential of becoming a screening tool for the rapid and sensitive assessment of the neurotoxicity of an overwhelming number of organophosphate compounds.
ESTHER : Liang_2013_Anal.Chem_85_308
PubMedSearch : Liang_2013_Anal.Chem_85_308
PubMedID: 23153113

Title : Design, synthesis and evaluation of novel tacrine-coumarin hybrids as multifunctional cholinesterase inhibitors against Alzheimer's disease - Xie_2013_Eur.J.Med.Chem_64C_540
Author(s) : Xie SS , Wang XB , Li JY , Yang L , Kong LY
Ref : Eur Journal of Medicinal Chemistry , 64C :540 , 2013
Abstract : A series of tacrine-coumarin hybrids (8a-t) were designed, synthesized and evaluated as multifunctional cholinesterase (ChE) inhibitors against Alzheimer's disease (AD). The screening results showed that most of them exhibited a significant ability to inhibit ChE and self-induced beta-amyloid (Abeta) aggregation, and to act as metal chelators. Especially, 8f displayed the greatest ability to inhibit acetylcholinesterase (AChE, IC50 = 0.092 muM) and Abeta aggregation (67.8%, 20 muM). It was also a good butyrylcholinesterase inhibitor (BCHE, IC50 = 0.234 muM) and metal chelator. Besides, kinetic and molecular modeling studies indicated that 8f was a mixed-type inhibitor, binding simultaneously to active, peripheral and mid-gorge sites of AChE. These results suggested that 8f might be an excellent multifunctional agent for AD treatment.
ESTHER : Xie_2013_Eur.J.Med.Chem_64C_540
PubMedSearch : Xie_2013_Eur.J.Med.Chem_64C_540
PubMedID: 23685572

Title : Development of a biosensor based on immobilization of acetylcholinesterase on NiO nanoparticles-carboxylic graphene-nafion modified electrode for detection of pesticides - Yang_2013_Talanta_113_135
Author(s) : Yang L , Wang G , Liu Y , Wang M
Ref : Talanta , 113 :135 , 2013
Abstract : A sensitive amperometric acetylcholinesterase (AChE) biosensor based on NiO nanoparticles (NiO NPs), carboxylic graphene (CGR) and nafion (NF) modified glassy carbon electrode (GCE) has been developed. NiO NPs-CGR-NF nanocomposites with excellent conductivity, catalysis and biocompatibility offered an extremely hydrophilic surface for AChE adhesion. The AChE biosensor showed favorable affinity to acetylthiocholine chloride (ATCl) and could catalyze the hydrolysis of ATCl with an apparent Michaelis-Menten constant value of 135muM. Under optimum conditions, the biosensor detected methyl parathion and chlorpyrifos in the linear range from 1.0x10(-13) to 1x10(-10)M and from 1.0x10(-10) to 1x10(-8)M with the detection limits 5x10(-14)M. The biosensor detected carbofuran in the linear range from 1.0x10(-12) to 1x10(-10)M and from 1.0x10(-10) to 1x10(-8)M with the detection limit of 5x10(-13)M. The developed biosensor exhibited good sensitivity, stability and reproducibility, thus providing a promising tool for analysis of enzyme inhibitors.
ESTHER : Yang_2013_Talanta_113_135
PubMedSearch : Yang_2013_Talanta_113_135
PubMedID: 23708635

Title : Acetylcholinesterase biosensor based on SnO nanoparticles-carboxylic graphene-nafion modified electrode for detection of pesticides - Yang_2013_Biosens.Bioelectron_49C_25
Author(s) : Yang L , Zhou Q , Wang G , Yang Y
Ref : Biosensors & Bioelectronics , 49C :25 , 2013
Abstract : A sensitive amperometric acetylcholinesterase (AChE) biosensor, based on SnO2 nanoparticles (SnO2 NPs), carboxylic graphene (CGR) and nafion (NF) modified glassy carbon electrode (GCE) for the detection of methyl parathion and carbofuran has been developed. The nanocomposites of SnO2 NPs and CGR was synthesized and characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR), respectively. Chitosan (CS) was used to immobilize AChE on SnO2 NPs-CGR-NF/GCE and to improve electronic transmission between AChE and SnO2 NPs-CGR-NF/GCE. NF was used as the protective membrane for the AChE biosensor. The SnO2 NPs-CGR-NF nanocomposites with excellent conductivity, catalysis and biocompatibility offered an extremely hydrophilic surface for AChE adhesion. The AChE biosensor showed favorable affinity to acetylthiocholine chloride (ATCl) and could catalyze the hydrolysis of ATCl with an apparent Michaelis-Menten constant value of 131muM. The biosensor detected methyl parathion in the linear range from 10-13 to 10-10M and from 10-10 to 10-8M. The biosensor detected carbofuran in the linear range from 10-12 to 10-10M and from 10-10 to 10-8M. The detection limits of methyl parathion and carbofuran were 5x10-14M and 5x10-13M, respectively. The biosensor exhibited low applied potential, high sensitivity and acceptable stability, thus providing a promising tool for analysis of pesticides.
ESTHER : Yang_2013_Biosens.Bioelectron_49C_25
PubMedSearch : Yang_2013_Biosens.Bioelectron_49C_25
PubMedID: 23708814

Title : An acetylcholinesterase biosensor based on platinum nanoparticles-carboxylic graphene-nafion-modified electrode for detection of pesticides - Yang_2013_Anal.Biochem_437_144
Author(s) : Yang L , Wang G , Liu Y
Ref : Analytical Biochemistry , 437 :144 , 2013
Abstract : A sensitive amperometric acetylcholinesterase (AChE) biosensor based on platinum nanoparticles (Pt NPs), carboxylic graphene (CGR), and nafion (NF)-modified glassy carbon electrode (GCE) has been developed. The Pt NPs-CGR-NF nanocomposites with excellent conductivity, catalysis, and biocompatibility offered an extremely hydrophilic surface for AChE adhesion. Chitosan (CS) was used as cross-linker to immobilize the AChE on Pt-CGR-NF-modified GCE. NF was used as a protective membrane of the AChE biosensors. The AChE biosensor showed favorable affinity to acetylthiocholine chloride (ATCl) and could catalyze the hydrolysis of ATCl with an apparent Michaelis-Menten constant value of 148muM. Under optimum conditions, the biosensor detected methyl parathion in the linear range from 1.0x10(-13) to 1x10(-10)M and from 1.0x10(-10) to 1x10(-8)M with a detection limit of 5x10(-14)M and detected carbofuran in the linear range from 1.0x10(-12) to 1x10(-10)M and from 1.0x10(-10) to 1x10(-8)M with a detection limit of 5x10(-13)M. The biosensor exhibited good sensitivity, acceptable stability, and reproducibility, thus providing a promising tool for analysis of enzyme inhibitors.
ESTHER : Yang_2013_Anal.Biochem_437_144
PubMedSearch : Yang_2013_Anal.Biochem_437_144
PubMedID: 23499967

Title : Development of a stable biosensor based on a SiO2 nanosheet-Nafion-modified glassy carbon electrode for sensitive detection of pesticides - Yang_2013_Anal.Bioanal.Chem_405_2545
Author(s) : Yang L , Wang GC , Liu YJ , An JJ , Wang M
Ref : Anal Bioanal Chem , 405 :2545 , 2013
Abstract : SiO(2) nanosheets (SNS) have been prepared by a chemical method using montmorillonite as raw material and were characterized by scanning electron microscopy and X-ray diffraction. SiO(2) nanosheet-Nafion nanocomposites with excellent conductivity, catalytic activity, and biocompatibility provided an extremely hydrophilic surface for biomolecule adhesion. Chitosan was used as a cross-linker to immobilize acetylcholinesterase (AChE), and Nafion was used as a protective membrane to efficiently improve the stability of the AChE biosensor. The AChE biosensor showed favorable affinity for acetylthiocholine chloride and catalyzed the hydrolysis of acetylthiocholine chloride with an apparent Michaelis-Menten constant of 134 muM to form thiocholine, which was then oxidized to produce a detectable and fast response. Based on the inhibition by pesticides of the enzymatic activity of AChE, detection of the amperometric response from thiocholine on the biosensor is a simple and effective way to biomonitor exposure to pesticides. Under optimum conditions, the biosensor detected methyl parathion, chlorpyrifos, and carbofuran at concentrations ranging from 1.0 x 10(-12) to 1 x 10(-10) M and from 1.0 x 10(-10) to 1 x 10(-8) M. The detection limits for methyl parathion, chlorpyrifos, and carbofuran were 5 x 10(-13) M. The biosensor developed exhibited good sensitivity, stability, reproducibility, and low cost, thus providing a new promising tool for analysis of enzyme inhibitors.
ESTHER : Yang_2013_Anal.Bioanal.Chem_405_2545
PubMedSearch : Yang_2013_Anal.Bioanal.Chem_405_2545
PubMedID: 23354570

Title : Comparative analysis of bat genomes provides insight into the evolution of flight and immunity - Zhang_2013_Science_339_456
Author(s) : Zhang G , Cowled C , Shi Z , Huang Z , Bishop-Lilly KA , Fang X , Wynne JW , Xiong Z , Baker ML , Zhao W , Tachedjian M , Zhu Y , Zhou P , Jiang X , Ng J , Yang L , Wu L , Xiao J , Feng Y , Chen Y , Sun X , Zhang Y , Marsh GA , Crameri G , Broder CC , Frey KG , Wang LF , Wang J
Ref : Science , 339 :456 , 2013
Abstract : Bats are the only mammals capable of sustained flight and are notorious reservoir hosts for some of the world's most highly pathogenic viruses, including Nipah, Hendra, Ebola, and severe acute respiratory syndrome (SARS). To identify genetic changes associated with the development of bat-specific traits, we performed whole-genome sequencing and comparative analyses of two distantly related species, fruit bat Pteropus alecto and insectivorous bat Myotis davidii. We discovered an unexpected concentration of positively selected genes in the DNA damage checkpoint and nuclear factor kappaB pathways that may be related to the origin of flight, as well as expansion and contraction of important gene families. Comparison of bat genomes with other mammalian species has provided new insights into bat biology and evolution.
ESTHER : Zhang_2013_Science_339_456
PubMedSearch : Zhang_2013_Science_339_456
PubMedID: 23258410
Gene_locus related to this paper: myods-l5mij9 , pteal-l5k8f5 , pteal-l5kjy3 , pteal-l5k6f0 , pteal-l5kxe2 , myods-l5m0a8 , myods-l5lvb4 , pteal-l5k7h7 , myods-l5lm42 , pteal-l5jz73 , pteal-l5kvh1.1 , pteal-l5kvh1.2 , pteal-l5kw21 , myods-l5lug5 , pteal-l5kv18 , myods-l5lbf8 , pteal-l5kwh0 , myods-l5lfh8 , myods-l5lfr7 , myods-l5lu20 , pteal-l5jzi4 , pteal-l5kib7 , pteal-l5kyq5 , myods-l5lf36 , myods-l5lnh7 , myods-l5lu25 , pteal-l5k0u1 , pteal-l5k2g6 , pteal-l5l3r3 , myods-l5mdx5 , pteal-l5k220 , myolu-g1pdp2 , pteal-l5l5n3 , pteal-l5k1s7 , myolu-g1nth4 , pteal-l5l7w7 , pteal-l5l537 , myods-l5lwe4 , pteal-l5klr9 , pteal-l5k670 , pteal-l5jr94 , pteal-l5kvb4 , myolu-g1q4e3 , pteal-l5jrl1

Title : Genome of the Chinese tree shrew - Fan_2013_Nat.Commun_4_1426
Author(s) : Fan Y , Huang ZY , Cao CC , Chen CS , Chen YX , Fan DD , He J , Hou HL , Hu L , Hu XT , Jiang XT , Lai R , Lang YS , Liang B , Liao SG , Mu D , Ma YY , Niu YY , Sun XQ , Xia JQ , Xiao J , Xiong ZQ , Xu L , Yang L , Zhang Y , Zhao W , Zhao XD , Zheng YT , Zhou JM , Zhu YB , Zhang GJ , Wang J , Yao YG
Ref : Nat Commun , 4 :1426 , 2013
Abstract : Chinese tree shrews (Tupaia belangeri chinensis) possess many features valuable in animals used as experimental models in biomedical research. Currently, there are numerous attempts to employ tree shrews as models for a variety of human disorders: depression, myopia, hepatitis B and C virus infections, and hepatocellular carcinoma, to name a few. Here we present a publicly available annotated genome sequence for the Chinese tree shrew. Phylogenomic analysis of the tree shrew and other mammalians highly support its close affinity to primates. By characterizing key factors and signalling pathways in nervous and immune systems, we demonstrate that tree shrews possess both shared common and unique features, and provide a genetic basis for the use of this animal as a potential model for biomedical research.
ESTHER : Fan_2013_Nat.Commun_4_1426
PubMedSearch : Fan_2013_Nat.Commun_4_1426
PubMedID: 23385571
Gene_locus related to this paper: tupch-l9l8p0 , tupch-l9l7d8.1 , tupch-l9l7d8.2 , tupch-l9l7d8.3 , tupch-l8y4e3 , tupch-l9jqg5 , tupch-l9l3m0 , tupch-l9kxg8 , tupch-l9knn8 , tupch-l9kf47 , tupch-l9ja32 , tupch-l9l5b1 , tupch-l9khv5

Title : Design, synthesis and anti-tuberculosis activity of 1-adamantyl-3-heteroaryl ureas with improved in vitro pharmacokinetic properties - North_2013_Bioorg.Med.Chem_21_2587
Author(s) : North EJ , Scherman MS , Bruhn DF , Scarborough JS , Maddox MM , Jones V , Grzegorzewicz A , Yang L , Hess T , Morisseau C , Jackson M , McNeil MR , Lee RE
Ref : Bioorganic & Medicinal Chemistry , 21 :2587 , 2013
Abstract : Out of the prominent global ailments, tuberculosis (TB) is still one of the leading causes of death worldwide due to infectious disease. Development of new drugs that shorten the current tuberculosis treatment time and have activity against drug resistant strains is of utmost importance. Towards these goals we have focused our efforts on developing novel anti-TB compounds with the general structure of 1-adamantyl-3-phenyl urea. This series is active against Mycobacteria and previous lead compounds were found to inhibit the membrane transporter MmpL3, the protein responsible for mycolic acid transport across the plasma membrane. However, these compounds suffered from poor in vitro pharmacokinetic (PK) profiles and they have a similar structure/SAR to inhibitors of human soluble epoxide hydrolase (sEH) enzymes. Therefore, in this study the further optimization of this compound class was driven by three factors: (1) to increase selectivity for anti-TB activity over human sEH activity, (2) to optimize PK profiles including solubility and (3) to maintain target inhibition. A new series of 1-adamantyl-3-heteroaryl ureas was designed and synthesized replacing the phenyl substituent of the original series with pyridines, pyrimidines, triazines, oxazoles, isoxazoles, oxadiazoles and pyrazoles. This study produced lead isoxazole, oxadiazole and pyrazole substituted adamantyl ureas with improved in vitro PK profiles, increased selectivity and good anti-TB potencies with sub mug/mL minimum inhibitory concentrations.
ESTHER : North_2013_Bioorg.Med.Chem_21_2587
PubMedSearch : North_2013_Bioorg.Med.Chem_21_2587
PubMedID: 23498915

Title : First case of E anophelis outbreak in an intensive-care unit -
Author(s) : Teo J , Tan SY , Tay M , Ding Y , Kjelleberg S , Givskov M , Lin RT , Yang L
Ref : Lancet , 382 :855 , 2013
PubMedID: 24012265
Gene_locus related to this paper: 9flao-h0kx79

Title : Cloning of a dibutyl phthalate hydrolase gene from Acinetobacter sp. strain M673 and functional analysis of its expression product in Escherichia coli - Wu_2013_Appl.Microbiol.Biotechnol_97_2483
Author(s) : Wu J , Liao X , Yu F , Wei Z , Yang L
Ref : Applied Microbiology & Biotechnology , 97 :2483 , 2013
Abstract : A dibutyl phthalate (DBP) transforming bacterium, strain M673, was isolated and identified as Acinetobacter sp. This strain could not grow on dialkyl phthalates, including dimethyl, diethyl, dipropyl, dibutyl, dipentyl, dihexyl, di(2-ethylhexyl), di-n-octyl, and dinonyl phthalate, but suspensions of cells could transform these compounds to phthalate via corresponding monoalkyl phthalates. During growth in Luria-Bertani medium, M673 produced the high amounts of non-DBP-induced intracellular hydrolase in the stationary phase. One DBP hydrolase gene containing an open reading frame of 1,095 bp was screened from a genomic library, and its expression product hydrolyzed various dialkyl phthalates to the corresponding monoalkyl phthalates.
ESTHER : Wu_2013_Appl.Microbiol.Biotechnol_97_2483
PubMedSearch : Wu_2013_Appl.Microbiol.Biotechnol_97_2483
PubMedID: 22729233
Gene_locus related to this paper: acilw-ESTA

Title : Identification and characterization of a cold-active phthalate esters hydrolase by screening a metagenomic library derived from biofilms of a wastewater treatment plant - Jiao_2013_PLoS.One_8_e75977
Author(s) : Jiao Y , Chen X , Wang X , Liao X , Xiao L , Miao A , Wu J , Yang L
Ref : PLoS ONE , 8 :e75977 , 2013
Abstract : A cold-active phthalate esters hydrolase gene (designated dphB) was identified through functional screening of a metagenomic library derived from biofilms of a wastewater treatment plant. The enzyme specifically catalyzed the hydrolysis of dipropyl phthalate, dibutyl phthalate, and dipentyl phthalate to the corresponding monoalkyl phthalate esters at low temperatures. The catalytic triad residues of DphB were proposed to be Ser159, Asp251, and His281.
ESTHER : Jiao_2013_PLoS.One_8_e75977
PubMedSearch : Jiao_2013_PLoS.One_8_e75977
PubMedID: 24116085
Gene_locus related to this paper: acilw-ESTA , 9bact-u5qec2

Title : Effects of Di-n-butyl Phthalate and Diethyl Phthalate on Acetylcholinesterase Activity and Neurotoxicity Related Gene Expression in Embryonic Zebrafish - Xu_2013_Bull.Environ.Contam.Toxicol_91_635
Author(s) : Xu H , Shao X , Zhang Z , Zou Y , Chen Y , Han S , Wang S , Wu X , Yang L , Chen Z
Ref : Bulletin of Environmental Contamination & Toxicology , 91 :635 , 2013
Abstract : In the present study, zebrafish embryos were used to assess the neurotoxicity of di-n-butyl phthalate (DBP), diethyl phthalate (DEP) and their mixture. Four-hour post-fertilization (hpf) zebrafish embryos were exposed to various concentrations of DBP, DEP and their mixture (DBP-DEP) until 96 hpf. The transcriptions levels of selected neuron-related genes reported as neurotoxicity biomarkers were analyzed. The results showed that transcripts of growth associated protein 43 (gap43), embryonic lethal abnormal vision-like 3 (elavl3), glial fibrillary acidic protein (gfap), myelin basic protein (mbp), alpha1-tubulin and neurogenin1 (ngn1) were significantly up-regulated after DBP, DEP and DBP-DEP mixture exposure. In addition, acetylcholinesterase activity was significantly inhibited in the embryos. These results indicate that DBP and DEP have the potential neurotoxicity in zebrafish embryos.
ESTHER : Xu_2013_Bull.Environ.Contam.Toxicol_91_635
PubMedSearch : Xu_2013_Bull.Environ.Contam.Toxicol_91_635
PubMedID: 24042840
Gene_locus related to this paper: danre-ACHE

Title : Two new triterpenoids from Gelsemium elegans and Aglaia odorata - Liu_2013_Nat.Prod.Commun_8_1373
Author(s) : Liu B , Yang L , Xu YK , Liao SG , Luo HR , Na Z
Ref : Nat Prod Commun , 8 :1373 , 2013
Abstract : Eleganoside A (1) and odoratanone A (15), a triterpenoid trisaccharide glycoside and a nortriterpenoid, together with twelve known compounds (2-13) and a mixture of cerebrosides (14) were isolated from Gelsemium elegans and Aglaia odorata. Their structures were elucidated by extensive spectroscopic and spectrometric analysis. Eleganoside A (1) features a 3-O-alpha-L-rhamnopyranosyl (1-->4)-beta-D-glucopyranosyl (1-->4)-beta-D-glucopyranoside of a peculiar 3,16-dihydroxyl-lanosta-8,24-dien-26-oic acid triterpenoid skeleton, and odoratanone A (15) is a 29-norcycloartane-type triterpenoid bearing an unusual five-membered methyl acetal ring. Anti-acetylcholinesterase/butyrylcholinesterase (AChE/BChE) assay indicated that at 50 microM, ethyl caffeate (5) was promising as a dual inhibitor of AChE and BChE, and paeonol (3) and 24-hydroperoxy-24-vinylcholesterol (9) exhibited BChE-selective inhibition.
ESTHER : Liu_2013_Nat.Prod.Commun_8_1373
PubMedSearch : Liu_2013_Nat.Prod.Commun_8_1373
PubMedID: 24354178

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 : Acetylcholinesterase is associated with apoptosis in beta cells and contributes to insulin-dependent diabetes mellitus pathogenesis - Zhang_2012_Acta.Biochim.Biophys.Sin.(Shanghai)_44_207
Author(s) : Zhang B , Yang L , Yu L , Lin B , Hou Y , Wu J , Huang Q , Han Y , Guo L , Ouyang Q , Lu L , Zhang X
Ref : Acta Biochim Biophys Sin (Shanghai) , 44 :207 , 2012
Abstract : Acetylcholinesterase (AChE) expression is pivotal during apoptosis. Indeed, AChE inhibitors partially protect cells from apoptosis. Insulin-dependent diabetes mellitus (IDDM) is characterized in part by pancreatic beta-cell apoptosis. Here, we investigated the role of AChE in the development of IDDM and analyzed protective effects of AChE inhibitors. Multiple low-dose streptozotocin (MLD-STZ) administration resulted in IDDM in a mouse model. Western blot analysis, cytochemical staining, and immunofluorescence staining were used to detect AChE expression in MIN6 cells, primary beta cells, and apoptotic pancreatic beta cells of MLD-STZ-treated mice. AChE inhibitors were administered intraperitoneally to the MLD-STZ mice for 30 days. Blood glucose, plasma insulin, and creatine levels were measured, and glucose tolerance tests were performed. The effects of AChE inhibitors on MIN6 cells were also evaluated. AChE expression was induced in the apoptotic MIN6 cells and primary beta cells in vitro and pancreatic islets in vivo when treated with STZ. Induction and progressive accumulation of AChE in the pancreatic islets were associated with apoptotic beta cells during IDDM development. The administration of AChE inhibitors effectively decreased hyperglycemia and incidence of diabetes, and restored plasma insulin levels and plasma creatine clearance in the MLD-STZ mice. AChE inhibitors partially protected MIN6 cells from the damage caused by STZ treatment. Induction and accumulation of AChE in pancreatic islets and the protective effects of AChE inhibitors on the onset and development of IDDM indicate a close relationship between AChE and IDDM.
ESTHER : Zhang_2012_Acta.Biochim.Biophys.Sin.(Shanghai)_44_207
PubMedSearch : Zhang_2012_Acta.Biochim.Biophys.Sin.(Shanghai)_44_207
PubMedID: 22236578

Title : Orally active metabotropic glutamate subtype 2 receptor positive allosteric modulators: structure-activity relationships and assessment in a rat model of nicotine dependence - Sidique_2012_J.Med.Chem_55_9434
Author(s) : Sidique S , Dhanya RP , Sheffler DJ , Nickols HH , Yang L , Dahl R , Mangravita-Novo A , Smith LH , D'Souza MS , Semenova S , Conn PJ , Markou A , Cosford ND
Ref : Journal of Medicinal Chemistry , 55 :9434 , 2012
Abstract : Compounds that modulate metabotropic glutamate subtype 2 (mGlu(2)) receptors have the potential to treat several disorders of the central nervous system (CNS) including drug dependence. Herein we describe the synthesis and structure-activity relationship (SAR) studies around a series of mGlu(2) receptor positive allosteric modulators (PAMs). The effects of N-substitution (R(1)) and substitutions on the aryl ring (R(2)) were identified as key areas for SAR exploration (Figure 3). Investigation of the effects of varying substituents in both the isoindolinone (2) and benzisothiazolone (3) series led to compounds with improved in vitro potency and/or efficacy. In addition, several analogues exhibited promising pharmacokinetic (PK) properties. Furthermore, compound 2 was shown to dose-dependently decrease nicotine self-administration in rats following oral administration. Our data, showing for the first time efficacy of an mGlu(2) receptor PAM in this in vivo model, suggest potential utility for the treatment of nicotine dependence in humans.
ESTHER : Sidique_2012_J.Med.Chem_55_9434
PubMedSearch : Sidique_2012_J.Med.Chem_55_9434
PubMedID: 23009245

Title : Expression of APP, BACE1, AChE and ChAT in an AD model in rats and the effect of donepezil hydrochloride treatment - Li_2012_Mol.Med.Rep_6_1450
Author(s) : Li Q , Chen M , Liu H , Yang L , Yang G
Ref : Mol Med Rep , 6 :1450 , 2012
Abstract : The aim of this study was to investigate the pathological changes in a rat model of Alzheimer's disease (AD) and the effect of donepezil hydrochloride (HCl) treatment. The rat model of AD was established by the bilateral injection of amyloid beta1-40 (Abeta1-40) into the hippocampus. Changes in spatial learning and memory functions were examined using the Morris water maze test and changes in catalase (CAT) and glutathione peroxidase (GSH-Px) activities were determined using chemical colorimetry. Moreover, the changes in acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) expression were analyzed using immunohistochemical staining. The mRNA expression levels of the amyloid precursor protein (APP) and beta-secreted enzyme 1 (BACE1) were evaluated using RT-PCR. The effects of donepezil HCl on the aforementioned indices were also observed. The rat memories of the platform quadrants in the blank, sham and donepezil HCl groups were improved compared with those of the rats in the model group. The ratio of swim distance in the fourth platform quadrant (l4) to the total swim distance (l total) for the model group rats (l4/l total) was significantly decreased compared with that for the blank and sham group rats. Following donepezil HCl treatment, the ratio of l4/l total significantly increased. AD modeling caused a significant decrease in the CAT and GSH-Px activities in the brain tissues of the rats. The CAT and GSH-Px activities in the AD model rats significantly increased following donepezil HCl treatment. Moreover, donepezil HCl treatment significantly decreased the AChE, APP and BACE1 mRNA expression levels and increased the ChAT expression levels. Therefore, donepezil HCl was able to significantly decrease learning and memory damage in a rat model of AD.
ESTHER : Li_2012_Mol.Med.Rep_6_1450
PubMedSearch : Li_2012_Mol.Med.Rep_6_1450
PubMedID: 23023803

Title : The oyster genome reveals stress adaptation and complexity of shell formation - Zhang_2012_Nature_490_49
Author(s) : Zhang G , Fang X , Guo X , Li L , Luo R , Xu F , Yang P , Zhang L , Wang X , Qi H , Xiong Z , Que H , Xie Y , Holland PW , Paps J , Zhu Y , Wu F , Chen Y , Wang J , Peng C , Meng J , Yang L , Liu J , Wen B , Zhang N , Huang Z , Zhu Q , Feng Y , Mount A , Hedgecock D , Xu Z , Liu Y , Domazet-Loso T , Du Y , Sun X , Zhang S , Liu B , Cheng P , Jiang X , Li J , Fan D , Wang W , Fu W , Wang T , Wang B , Zhang J , Peng Z , Li Y , Li N , Chen M , He Y , Tan F , Song X , Zheng Q , Huang R , Yang H , Du X , Chen L , Yang M , Gaffney PM , Wang S , Luo L , She Z , Ming Y , Huang W , Huang B , Zhang Y , Qu T , Ni P , Miao G , Wang Q , Steinberg CE , Wang H , Qian L , Liu X , Yin Y
Ref : Nature , 490 :49 , 2012
Abstract : The Pacific oyster Crassostrea gigas belongs to one of the most species-rich but genomically poorly explored phyla, the Mollusca. Here we report the sequencing and assembly of the oyster genome using short reads and a fosmid-pooling strategy, along with transcriptomes of development and stress response and the proteome of the shell. The oyster genome is highly polymorphic and rich in repetitive sequences, with some transposable elements still actively shaping variation. Transcriptome studies reveal an extensive set of genes responding to environmental stress. The expansion of genes coding for heat shock protein 70 and inhibitors of apoptosis is probably central to the oyster's adaptation to sessile life in the highly stressful intertidal zone. Our analyses also show that shell formation in molluscs is more complex than currently understood and involves extensive participation of cells and their exosomes. The oyster genome sequence fills a void in our understanding of the Lophotrochozoa.
ESTHER : Zhang_2012_Nature_490_49
PubMedSearch : Zhang_2012_Nature_490_49
PubMedID: 22992520
Gene_locus related to this paper: cragi-k1qzk7 , cragi-k1rad0 , cragi-k1p6v9 , cragi-k1pa46 , cragi-k1pga2 , cragi-k1pp63 , cragi-k1pwa8 , cragi-k1q0b1.1 , cragi-k1q0b1.2 , cragi-k1q1h2 , cragi-k1q2z6 , cragi-k1qaj8 , cragi-k1qaw5 , cragi-k1qhl5 , cragi-k1qly1 , cragi-k1qqb1.1 , cragi-k1qqb1.2 , cragi-k1qs61 , cragi-k1qs99 , cragi-k1qwl6 , cragi-k1r068 , cragi-k1r0n3.1 , cragi-k1r0n3.2 , cragi-k1r0r4 , cragi-k1r1i9 , cragi-k1r8q9 , cragi-k1rgi1 , cragi-k1rig4 , cragi-k1s0a7.1 , cragi-k1s0a7.2 , cragi-k1s0a7.3 , cragi-k1q6q0 , cragi-k1rru1 , cragi-k1qfi4 , cragi-k1qvm5 , cragi-k1qq58 , cragi-k1qdc0 , cragi-k1r754 , cragi-k1pje5 , cragi-k1qca6 , cragi-k1qdt5 , cragi-k1qkz7 , cragi-k1rgd2 , cragi-k1puh6 , cragi-k1raz4 , cragi-k1qqj4 , cragi-k1rbs1

Title : The genome of flax (Linum usitatissimum) assembled de novo from short shotgun sequence reads - Wang_2012_Plant.J_72_461
Author(s) : Wang Z , Hobson N , Galindo L , Zhu S , Shi D , McDill J , Yang L , Hawkins S , Neutelings G , Datla R , Lambert G , Galbraith DW , Grassa CJ , Geraldes A , Cronk QC , Cullis C , Dash PK , Kumar PA , Cloutier S , Sharpe AG , Wong GK , Wang J , Deyholos MK
Ref : Plant J , 72 :461 , 2012
Abstract : Flax (Linum usitatissimum) is an ancient crop that is widely cultivated as a source of fiber, oil and medicinally relevant compounds. To accelerate crop improvement, we performed whole-genome shotgun sequencing of the nuclear genome of flax. Seven paired-end libraries ranging in size from 300 bp to 10 kb were sequenced using an Illumina genome analyzer. A de novo assembly, comprised exclusively of deep-coverage (approximately 94x raw, approximately 69x filtered) short-sequence reads (44-100 bp), produced a set of scaffolds with N(50) =694 kb, including contigs with N(50)=20.1 kb. The contig assembly contained 302 Mb of non-redundant sequence representing an estimated 81% genome coverage. Up to 96% of published flax ESTs aligned to the whole-genome shotgun scaffolds. However, comparisons with independently sequenced BACs and fosmids showed some mis-assembly of regions at the genome scale. A total of 43384 protein-coding genes were predicted in the whole-genome shotgun assembly, and up to 93% of published flax ESTs, and 86% of A. thaliana genes aligned to these predicted genes, indicating excellent coverage and accuracy at the gene level. Analysis of the synonymous substitution rates (K(s) ) observed within duplicate gene pairs was consistent with a recent (5-9 MYA) whole-genome duplication in flax. Within the predicted proteome, we observed enrichment of many conserved domains (Pfam-A) that may contribute to the unique properties of this crop, including agglutinin proteins. Together these results show that de novo assembly, based solely on whole-genome shotgun short-sequence reads, is an efficient means of obtaining nearly complete genome sequence information for some plant species.
ESTHER : Wang_2012_Plant.J_72_461
PubMedSearch : Wang_2012_Plant.J_72_461
PubMedID: 22757964
Gene_locus related to this paper: linus-i6xnh8

Title : Acute exposure to DE-71: effects on locomotor behavior and developmental neurotoxicity in zebrafish larvae - Chen_2012_Environ.Toxicol.Chem_31_2338
Author(s) : Chen L , Huang C , Hu C , Yu K , Yang L , Zhou B
Ref : Environ Toxicol Chem , 31 :2338 , 2012
Abstract : The aim of the present study was to investigate the acute developmental neurotoxicity of polybrominated diphenyl ethers (PBDEs) in zebrafish larvae. From 2 to 120 h postfertilization zebrafish embryos were exposed to DE-71 (0, 31.0, 68.7, and 227.6 microg/L). The authors studied the locomotor behavior of larvae, involvement of the cholinergic system, and selected gene and protein expressions in the central nervous system. The results showed that low DE-71 concentration caused hyperactivity, whereas higher concentrations decreased activity during the dark period. During the light period, larval activity was significantly reduced in a concentration-dependent manner. In the cholinergic system, acetylcholinesterase activity significantly increased (10.7 and 12.4%) in the 68.7 and 227.6 microg/L exposure groups, respectively, and acetylcholine concentration accordingly decreased (60.5%) in the 227.6 microg/L exposure group. The mRNA expressions of genes encoding myelin basic protein, neuron microtubule protein (alpha1-tubulin), and sonic hedgehog a were significantly downregulated. Western blotting assay demonstrated that the protein concentration of alpha1-tubulin was also decreased. Overall, the present study demonstrated that acute exposure to PBDEs can disrupt the neurobehavior of zebrafish larvae and affect cholinergic neurotransmission and neuron development.
ESTHER : Chen_2012_Environ.Toxicol.Chem_31_2338
PubMedSearch : Chen_2012_Environ.Toxicol.Chem_31_2338
PubMedID: 22833361

Title : Novel pyrrolopyrimidine analogues as potent dipeptidyl peptidase IV inhibitors based on pharmacokinetic property-driven optimization - Xie_2012_Eur.J.Med.Chem_52_205
Author(s) : Xie H , Zeng L , Zeng S , Lu X , Zhang G , Zhao X , Cheng N , Tu Z , Li Z , Xu H , Yang L , Zhang X , Huang M , Zhao J , Hu W
Ref : Eur Journal of Medicinal Chemistry , 52 :205 , 2012
Abstract : We previously reported a highly potent DPP-IV inhibitor 6 with low in vivo efficacy. While trying to maintain consistent in vitro and in vivo biological activity, we initiated a pharmacokinetic property-driven optimization to improve the metabolic stability and permeability of inhibitor 6. A simple scaffold replacement of thienopyrimidine with pyrrolopyrimidine (21a) led to significantly improved metabolic stability (4% vs. 65% remaining). Further modification of the pyrrolopyrimidine scaffold to produce compound 21j resulted in much better oral bioavailability than 6. Importantly, compound 21j exhibits greater in vivo efficacy than does 6 and Alogliptin and is worthy of further development.
ESTHER : Xie_2012_Eur.J.Med.Chem_52_205
PubMedSearch : Xie_2012_Eur.J.Med.Chem_52_205
PubMedID: 22475866

Title : Whole-genome sequence of Schistosoma haematobium - Young_2012_Nat.Genet_44_221
Author(s) : Young ND , Jex AR , Li B , Liu S , Yang L , Xiong Z , Li Y , Cantacessi C , Hall RS , Xu X , Chen F , Wu X , Zerlotini A , Oliveira G , Hofmann A , Zhang G , Fang X , Kang Y , Campbell BE , Loukas A , Ranganathan S , Rollinson D , Rinaldi G , Brindley PJ , Yang H , Wang J , Gasser RB
Ref : Nat Genet , 44 :221 , 2012
Abstract : Schistosomiasis is a neglected tropical disease caused by blood flukes (genus Schistosoma; schistosomes) and affecting 200 million people worldwide. No vaccines are available, and treatment relies on one drug, praziquantel. Schistosoma haematobium has come into the spotlight as a major cause of urogenital disease, as an agent linked to bladder cancer and as a predisposing factor for HIV/AIDS. The parasite is transmitted to humans from freshwater snails. Worms dwell in blood vessels and release eggs that become embedded in the bladder wall to elicit chronic immune-mediated disease and induce squamous cell carcinoma. Here we sequenced the 385-Mb genome of S. haematobium using Illumina-based technology at 74-fold coverage and compared it to sequences from related parasites. We included genome annotation based on function, gene ontology, networking and pathway mapping. This genome now provides an unprecedented resource for many fundamental research areas and shows great promise for the design of new disease interventions.
ESTHER : Young_2012_Nat.Genet_44_221
PubMedSearch : Young_2012_Nat.Genet_44_221
PubMedID: 22246508
Gene_locus related to this paper: schha-ACHE , schha-a0a094zs51 , schha-a0a095agr4 , schha-a0a095ai61 , schha-a0a095ayl3 , schha-a0a095c2i3 , schha-a0a095ce64

Title : Genome sequence of Enterobacter sp. strain SP1, an endophytic nitrogen-fixing bacterium isolated from sugarcane - Zhu_2012_J.Bacteriol_194_6963
Author(s) : Zhu B , Chen M , Lin L , Yang L , Li Y , An Q
Ref : Journal of Bacteriology , 194 :6963 , 2012
Abstract : Enterobacter sp. strain SP1 is an endophytic nitrogen-fixing bacterium isolated from a sugarcane stem and can promote plant growth. The draft genome sequence of strain SP1 presented here will promote comparative genomic studies to determine the genetic background of interactions between endophytic enterobacteria and plants.
ESTHER : Zhu_2012_J.Bacteriol_194_6963
PubMedSearch : Zhu_2012_J.Bacteriol_194_6963
PubMedID: 23209221
Gene_locus related to this paper: 9entr-w6iyd9 , 9entr-w6j8b5 , 9entr-w6jbs2 , 9entr-w6j1u8

Title : The genome of melon (Cucumis melo L.) - Garcia-Mas_2012_Proc.Natl.Acad.Sci.U.S.A_109_11872
Author(s) : Garcia-Mas J , Benjak A , Sanseverino W , Bourgeois M , Mir G , Gonzalez VM , Henaff E , Camara F , Cozzuto L , Lowy E , Alioto T , Capella-Gutierrez S , Blanca J , Canizares J , Ziarsolo P , Gonzalez-Ibeas D , Rodriguez-Moreno L , Droege M , Du L , Alvarez-Tejado M , Lorente-Galdos B , Mele M , Yang L , Weng Y , Navarro A , Marques-Bonet T , Aranda MA , Nuez F , Pico B , Gabaldon T , Roma G , Guigo R , Casacuberta JM , Arus P , Puigdomenech P
Ref : Proc Natl Acad Sci U S A , 109 :11872 , 2012
Abstract : We report the genome sequence of melon, an important horticultural crop worldwide. We assembled 375 Mb of the double-haploid line DHL92, representing 83.3% of the estimated melon genome. We predicted 27,427 protein-coding genes, which we analyzed by reconstructing 22,218 phylogenetic trees, allowing mapping of the orthology and paralogy relationships of sequenced plant genomes. We observed the absence of recent whole-genome duplications in the melon lineage since the ancient eudicot triplication, and our data suggest that transposon amplification may in part explain the increased size of the melon genome compared with the close relative cucumber. A low number of nucleotide-binding site-leucine-rich repeat disease resistance genes were annotated, suggesting the existence of specific defense mechanisms in this species. The DHL92 genome was compared with that of its parental lines allowing the quantification of sequence variability in the species. The use of the genome sequence in future investigations will facilitate the understanding of evolution of cucurbits and the improvement of breeding strategies.
ESTHER : Garcia-Mas_2012_Proc.Natl.Acad.Sci.U.S.A_109_11872
PubMedSearch : Garcia-Mas_2012_Proc.Natl.Acad.Sci.U.S.A_109_11872
PubMedID: 22753475
Gene_locus related to this paper: cucme-a0a1s3cge4 , cucme-a0a1s3ct47 , cucme-a0a1s3bcl7 , cucsa-a0a0a0m228 , cucme-a0a1s3bnl4 , cucme-a0a1s3b1c9 , cucme-a0a1s3b1d4 , cucme-a0a1s3buy0 , cucme-a0a1s3bva9 , cucme-a0a1s3c6j4 , cucme-a0a1s3cky2 , cucme-a0a1s3clz8 , cucme-a0a1s3buy6 , cucme-a0a1s3bp26

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

Title : Genome sequencing reveals insights into physiology and longevity of the naked mole rat - Kim_2011_Nature_479_223
Author(s) : Kim EB , Fang X , Fushan AA , Huang Z , Lobanov AV , Han L , Marino SM , Sun X , Turanov AA , Yang P , Yim SH , Zhao X , Kasaikina MV , Stoletzki N , Peng C , Polak P , Xiong Z , Kiezun A , Zhu Y , Chen Y , Kryukov GV , Zhang Q , Peshkin L , Yang L , Bronson RT , Buffenstein R , Wang B , Han C , Li Q , Chen L , Zhao W , Sunyaev SR , Park TJ , Zhang G , Wang J , Gladyshev VN
Ref : Nature , 479 :223 , 2011
Abstract : The naked mole rat (Heterocephalus glaber) is a strictly subterranean, extraordinarily long-lived eusocial mammal. Although it is the size of a mouse, its maximum lifespan exceeds 30 years, making this animal the longest-living rodent. Naked mole rats show negligible senescence, no age-related increase in mortality, and high fecundity until death. In addition to delayed ageing, they are resistant to both spontaneous cancer and experimentally induced tumorigenesis. Naked mole rats pose a challenge to the theories that link ageing, cancer and redox homeostasis. Although characterized by significant oxidative stress, the naked mole rat proteome does not show age-related susceptibility to oxidative damage or increased ubiquitination. Naked mole rats naturally reside in large colonies with a single breeding female, the 'queen', who suppresses the sexual maturity of her subordinates. They also live in full darkness, at low oxygen and high carbon dioxide concentrations, and are unable to sustain thermogenesis nor feel certain types of pain. Here we report the sequencing and analysis of the naked mole rat genome, which reveals unique genome features and molecular adaptations consistent with cancer resistance, poikilothermy, hairlessness and insensitivity to low oxygen, and altered visual function, circadian rythms and taste sensing. This information provides insights into the naked mole rat's exceptional longevity and ability to live in hostile conditions, in the dark and at low oxygen. The extreme traits of the naked mole rat, together with the reported genome and transcriptome information, offer opportunities for understanding ageing and advancing other areas of biological and biomedical research.
ESTHER : Kim_2011_Nature_479_223
PubMedSearch : Kim_2011_Nature_479_223
PubMedID: 21993625
Gene_locus related to this paper: hetga-g5amh8 , hetga-g5an68 , hetga-g5anw7 , hetga-g5as32 , hetga-g5atg6 , hetga-g5b5b7 , hetga-g5b9m6 , hetga-g5bdh8 , hetga-g5bmv3 , hetga-g5bp66 , hetga-g5bp67 , hetga-g5bp68 , hetga-g5bpp3 , hetga-g5bsd4 , hetga-g5bul0 , hetga-g5bw29 , hetga-g5bze3 , hetga-g5c6q5 , hetga-g5bfw4 , hetga-g5b832 , hetga-g5c6q8 , hetga-g5bj87 , hetga-a0a0p6jix7 , hetga-g5c108 , hetga-g5c109 , hetga-g5c110 , hetga-g5arh0 , hetga-g5aua1 , hetga-g5are8 , hetga-g5ax31 , hetga-a0a0p6jud6 , hetga-g5b7v3 , hetga-a0a0p6jw61 , hetga-a0a0p6jdl4 , hetga-g5bg83 , hetga-g5bcu5 , hetga-g5bvp0 , hetga-g5b8m7 , hetga-g5b709 , hetga-g5bt99 , hetga-g5b4q4

Title : The Medicago genome provides insight into the evolution of rhizobial symbioses - Young_2011_Nature_480_520
Author(s) : Young ND , Debelle F , Oldroyd GE , Geurts R , Cannon SB , Udvardi MK , Benedito VA , Mayer KF , Gouzy J , Schoof H , Van de Peer Y , Proost S , Cook DR , Meyers BC , Spannagl M , Cheung F , De Mita S , Krishnakumar V , Gundlach H , Zhou S , Mudge J , Bharti AK , Murray JD , Naoumkina MA , Rosen B , Silverstein KA , Tang H , Rombauts S , Zhao PX , Zhou P , Barbe V , Bardou P , Bechner M , Bellec A , Berger A , Berges H , Bidwell S , Bisseling T , Choisne N , Couloux A , Denny R , Deshpande S , Dai X , Doyle JJ , Dudez AM , Farmer AD , Fouteau S , Franken C , Gibelin C , Gish J , Goldstein S , Gonzalez AJ , Green PJ , Hallab A , Hartog M , Hua A , Humphray SJ , Jeong DH , Jing Y , Jocker A , Kenton SM , Kim DJ , Klee K , Lai H , Lang C , Lin S , Macmil SL , Magdelenat G , Matthews L , McCorrison J , Monaghan EL , Mun JH , Najar FZ , Nicholson C , Noirot C , O'Bleness M , Paule CR , Poulain J , Prion F , Qin B , Qu C , Retzel EF , Riddle C , Sallet E , Samain S , Samson N , Sanders I , Saurat O , Scarpelli C , Schiex T , Segurens B , Severin AJ , Sherrier DJ , Shi R , Sims S , Singer SR , Sinharoy S , Sterck L , Viollet A , Wang BB , Wang K , Wang M , Wang X , Warfsmann J , Weissenbach J , White DD , White JD , Wiley GB , Wincker P , Xing Y , Yang L , Yao Z , Ying F , Zhai J , Zhou L , Zuber A , Denarie J , Dixon RA , May GD , Schwartz DC , Rogers J , Quetier F , Town CD , Roe BA
Ref : Nature , 480 :520 , 2011
Abstract : Legumes (Fabaceae or Leguminosae) are unique among cultivated plants for their ability to carry out endosymbiotic nitrogen fixation with rhizobial bacteria, a process that takes place in a specialized structure known as the nodule. Legumes belong to one of the two main groups of eurosids, the Fabidae, which includes most species capable of endosymbiotic nitrogen fixation. Legumes comprise several evolutionary lineages derived from a common ancestor 60 million years ago (Myr ago). Papilionoids are the largest clade, dating nearly to the origin of legumes and containing most cultivated species. Medicago truncatula is a long-established model for the study of legume biology. Here we describe the draft sequence of the M. truncatula euchromatin based on a recently completed BAC assembly supplemented with Illumina shotgun sequence, together capturing approximately 94% of all M. truncatula genes. A whole-genome duplication (WGD) approximately 58 Myr ago had a major role in shaping the M. truncatula genome and thereby contributed to the evolution of endosymbiotic nitrogen fixation. Subsequent to the WGD, the M. truncatula genome experienced higher levels of rearrangement than two other sequenced legumes, Glycine max and Lotus japonicus. M. truncatula is a close relative of alfalfa (Medicago sativa), a widely cultivated crop with limited genomics tools and complex autotetraploid genetics. As such, the M. truncatula genome sequence provides significant opportunities to expand alfalfa's genomic toolbox.
ESTHER : Young_2011_Nature_480_520
PubMedSearch : Young_2011_Nature_480_520
PubMedID: 22089132
Gene_locus related to this paper: medtr-b7fki4 , medtr-b7fmi1 , medtr-g7itl1 , medtr-g7iu67 , medtr-g7izm0 , medtr-g7j641 , medtr-g7jtf8 , medtr-g7jtg2 , medtr-g7jtg4 , medtr-g7kem3 , medtr-g7kml3 , medtr-g7ksx5 , medtr-g7leb3 , medtr-q1s5d8 , medtr-q1s9m3 , medtr-q1t171 , medtr-g7k9e1 , medtr-g7k9e3 , medtr-g7k9e5 , medtr-g7k9e8 , medtr-g7k9e9 , medtr-g7lbp2 , medtr-g7lch3 , medtr-g7ib94 , medtr-g7ljk8 , medtr-g7i6w5 , medtr-g7kvg4 , medtr-g7iam1 , medtr-g7iam3 , medtr-g7l754 , medtr-g7jr41 , medtr-g7l4f5 , medtr-g7l755 , medtr-a0a072vyl4 , medtr-g7jwk8 , medtr-a0a072vhg0 , medtr-a0a072vrv9 , medtr-g7kmk5 , medtr-a0a072uuf6 , medtr-a0a072urp3 , medtr-g7zzc3 , medtr-g7ie19 , medtr-g7kst7 , medtr-a0a072u5k5 , medtr-a0a072v056 , medtr-scp1 , medtr-g7kyn0 , medtr-g7inw6 , medtr-g7j3q3

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 : The Arabidopsis lyrata genome sequence and the basis of rapid genome size change - Hu_2011_Nat.Genet_43_476
Author(s) : Hu TT , Pattyn P , Bakker EG , Cao J , Cheng JF , Clark RM , Fahlgren N , Fawcett JA , Grimwood J , Gundlach H , Haberer G , Hollister JD , Ossowski S , Ottilar RP , Salamov AA , Schneeberger K , Spannagl M , Wang X , Yang L , Nasrallah ME , Bergelson J , Carrington JC , Gaut BS , Schmutz J , Mayer KF , Van de Peer Y , Grigoriev IV , Nordborg M , Weigel D , Guo YL
Ref : Nat Genet , 43 :476 , 2011
Abstract : We report the 207-Mb genome sequence of the North American Arabidopsis lyrata strain MN47 based on 8.3x dideoxy sequence coverage. We predict 32,670 genes in this outcrossing species compared to the 27,025 genes in the selfing species Arabidopsis thaliana. The much smaller 125-Mb genome of A. thaliana, which diverged from A. lyrata 10 million years ago, likely constitutes the derived state for the family. We found evidence for DNA loss from large-scale rearrangements, but most of the difference in genome size can be attributed to hundreds of thousands of small deletions, mostly in noncoding DNA and transposons. Analysis of deletions and insertions still segregating in A. thaliana indicates that the process of DNA loss is ongoing, suggesting pervasive selection for a smaller genome. The high-quality reference genome sequence for A. lyrata will be an important resource for functional, evolutionary and ecological studies in the genus Arabidopsis.
ESTHER : Hu_2011_Nat.Genet_43_476
PubMedSearch : Hu_2011_Nat.Genet_43_476
PubMedID: 21478890
Gene_locus related to this paper: arall-d7kc59 , arall-d7kfz1 , arall-d7kjk9 , arall-d7kk58 , arall-d7kuj1 , arall-d7kwx5 , arall-d7kzq8 , arall-d7laf7 , arall-D7LAK6 , arall-d7ltj2 , arall-d7lu11 , arall-d7ly06 , arall-d7lyn6 , arall-d7m1k0 , arall-d7m1k1 , arall-d7m1k3 , arall-d7m1l4 , arall-d7m814 , arall-d7mbk0 , arall-d7mbn8 , arall-d7mgs1 , arall-d7mi04 , arall-d7mld7 , arall-d7mpg7 , arall-d7mul9 , arath-At2g45610 , arath-At1g05790 , arath-At1g09980 , arath-At1g18360 , arath-AT1G29120 , arath-AT1G73920 , arath-AT1G76140 , arath-AT2G05260 , arath-At2g15230 , arath-At2g24280 , arath-AT2G42690 , arath-At2g47630 , arath-AT3G12150 , arath-At3g61680 , arath-AT3g62590 , arath-AT4G00500 , arath-AT4G25770 , arath-AT4g30610 , arath-At5g11650 , arath-At5g13640 , arath-AT5G19050 , arath-AT5G20060 , arath-AT5G20520 , arath-AT5G27320 , arath-At5g42930 , arath-At5g47330 , arath-CGEP , arath-clh1 , arath-clh2 , arath-F1N13.220 , arath-F2G14.100 , arath-F12A4.4 , arath-F14O10.2 , arath-SCP27 , arath-HNL , arath-GID1B , arath-LIP2 , arath-At5g17670 , arath-pip , arath-PLA11 , arath-PLA12 , arath-PLA13 , arath-PLA15 , arath-PLA17 , arath-Q8LPF5 , arath-Q9FFZ1 , arath-Q9FJ29 , arath-Q9FKP9 , arath-Q9FNF6 , arath-q9lhe8 , arath-Q9SFF6 , arath-q84w08 , arath-SCP7 , arath-SCP8 , arath-SCP26 , arath-SCP28 , arath-SCP33 , arath-SCP40 , arath-SCPL34 , arath-At4g12230 , arath-MES14 , arath-T19F11.2 , arath-MES10 , arath-At5g11790 , arath-T26B15.8 , arath-ZW18 , arall-d7l971 , arall-d7lfd3 , arall-d7lg04 , arall-d7lg05 , arall-d7lg06 , arall-d7lg07 , arall-d7mb17 , arall-d7mb18 , arall-d7l7v2 , arall-d7l7v3 , arall-d7lst0 , arall-d7lfw9 , arall-d7mgs6 , arall-d7mur3 , arall-d7kjr5 , arall-d7l7v1 , arall-d7ls88 , arall-d7kzg6 , arall-d7kcm6 , arall-d7krm0 , arall-d7kwe4 , arall-d7lri7 , arall-d7kq26

Title : The Selaginella genome identifies genetic changes associated with the evolution of vascular plants - Banks_2011_Science_332_960
Author(s) : Banks JA , Nishiyama T , Hasebe M , Bowman JL , Gribskov M , dePamphilis C , Albert VA , Aono N , Aoyama T , Ambrose BA , Ashton NW , Axtell MJ , Barker E , Barker MS , Bennetzen JL , Bonawitz ND , Chapple C , Cheng C , Correa LG , Dacre M , DeBarry J , Dreyer I , Elias M , Engstrom EM , Estelle M , Feng L , Finet C , Floyd SK , Frommer WB , Fujita T , Gramzow L , Gutensohn M , Harholt J , Hattori M , Heyl A , Hirai T , Hiwatashi Y , Ishikawa M , Iwata M , Karol KG , Koehler B , Kolukisaoglu U , Kubo M , Kurata T , Lalonde S , Li K , Li Y , Litt A , Lyons E , Manning G , Maruyama T , Michael TP , Mikami K , Miyazaki S , Morinaga S , Murata T , Mueller-Roeber B , Nelson DR , Obara M , Oguri Y , Olmstead RG , Onodera N , Petersen BL , Pils B , Prigge M , Rensing SA , Riano-Pachon DM , Roberts AW , Sato Y , Scheller HV , Schulz B , Schulz C , Shakirov EV , Shibagaki N , Shinohara N , Shippen DE , Sorensen I , Sotooka R , Sugimoto N , Sugita M , Sumikawa N , Tanurdzic M , Theissen G , Ulvskov P , Wakazuki S , Weng JK , Willats WW , Wipf D , Wolf PG , Yang L , Zimmer AD , Zhu Q , Mitros T , Hellsten U , Loque D , Otillar R , Salamov A , Schmutz J , Shapiro H , Lindquist E , Lucas S , Rokhsar D , Grigoriev IV
Ref : Science , 332 :960 , 2011
Abstract : Vascular plants appeared ~410 million years ago, then diverged into several lineages of which only two survive: the euphyllophytes (ferns and seed plants) and the lycophytes. We report here the genome sequence of the lycophyte Selaginella moellendorffii (Selaginella), the first nonseed vascular plant genome reported. By comparing gene content in evolutionarily diverse taxa, we found that the transition from a gametophyte- to a sporophyte-dominated life cycle required far fewer new genes than the transition from a nonseed vascular to a flowering plant, whereas secondary metabolic genes expanded extensively and in parallel in the lycophyte and angiosperm lineages. Selaginella differs in posttranscriptional gene regulation, including small RNA regulation of repetitive elements, an absence of the trans-acting small interfering RNA pathway, and extensive RNA editing of organellar genes.
ESTHER : Banks_2011_Science_332_960
PubMedSearch : Banks_2011_Science_332_960
PubMedID: 21551031
Gene_locus related to this paper: selml-d8qua5 , selml-d8qva1 , selml-d8qyh7 , selml-d8qza0 , selml-d8r5d4 , selml-d8r6d4 , selml-d8r504 , selml-d8r506 , selml-d8rbi1 , selml-d8rbs1 , selml-d8rck8 , selml-d8rf38 , selml-d8rkl6 , selml-d8rpr1 , selml-d8rpy0 , selml-d8ru47 , selml-d8ry54 , selml-d8rzp6 , selml-d8rzy7 , selml-d8s0c9 , selml-d8s0u3 , selml-d8s2t1 , selml-d8s3z8 , selml-d8s401 , selml-d8sba6 , selml-d8sch9 , selml-d8spq2 , selml-d8sq37 , selml-d8ssx7 , selml-d8swp2 , selml-d8t7a3 , selml-d8t8v4 , selml-d8taz4 , selml-d8tdq6 , selml-d8rai8 , selml-d8qt54 , selml-d8r2d8 , selml-d8rmd3 , selml-d8rra9 , selml-d8slg4 , selml-d8swp0 , selml-d8s7i0 , selml-d8qz37 , selml-d8sz00 , selml-d8s776 , selml-d8qw15 , selml-d8ska7 , selml-d8t0c4 , selml-d8r194 , selml-d8s5m8 , selml-d8s7r2 , selml-d8ta80 , selml-d8ru55

Title : Transcriptional response of zebrafish embryos exposed to neurotoxic compounds reveals a muscle activity dependent hspb11 expression - Kluver_2011_PLoS.One_6_e29063
Author(s) : Kluver N , Yang L , Busch W , Scheffler K , Renner P , Strahle U , Scholz S
Ref : PLoS ONE , 6 :e29063 , 2011
Abstract : Acetylcholinesterase (AChE) inhibitors are widely used as pesticides and drugs. Their primary effect is the overstimulation of cholinergic receptors which results in an improper muscular function. During vertebrate embryonic development nerve activity and intracellular downstream events are critical for the regulation of muscle fiber formation. Whether AChE inhibitors and related neurotoxic compounds also provoke specific changes in gene transcription patterns during vertebrate development that allow them to establish a mechanistic link useful for identification of developmental toxicity pathways has, however, yet not been investigated. Therefore we examined the transcriptomic response of a known AChE inhibitor, the organophosphate azinphos-methyl (APM), in zebrafish embryos and compared the response with two non-AChE inhibiting unspecific control compounds, 1,4-dimethoxybenzene (DMB) and 2,4-dinitrophenol (DNP). A highly specific cluster of APM induced gene transcripts was identified and a subset of strongly regulated genes was analyzed in more detail. The small heat shock protein hspb11 was found to be the most sensitive induced gene in response to AChE inhibitors. Comparison of expression in wildtype, ache and sop(fixe) mutant embryos revealed that hspb11 expression was dependent on the nicotinic acetylcholine receptor (nAChR) activity. Furthermore, modulators of intracellular calcium levels within the whole embryo led to a transcriptional up-regulation of hspb11 which suggests that elevated intracellular calcium levels may regulate the expression of this gene. During early zebrafish development, hspb11 was specifically expressed in muscle pioneer cells and Hspb11 morpholino-knockdown resulted in effects on slow muscle myosin organization. Our findings imply that a comparative toxicogenomic approach and functional analysis can lead to the identification of molecular mechanisms and specific marker genes for potential neurotoxic compounds.
ESTHER : Kluver_2011_PLoS.One_6_e29063
PubMedSearch : Kluver_2011_PLoS.One_6_e29063
PubMedID: 22205996
Gene_locus related to this paper: danre-ACHE

Title : Design and synthesis of prolylcarboxypeptidase (PrCP) inhibitors to validate PrCP as a potential target for obesity - Zhou_2010_J.Med.Chem_53_7251
Author(s) : Zhou C , Garcia-Calvo M , Pinto S , Lombardo M , Feng Z , Bender K , Pryor KD , Bhatt UR , Chabin RM , Geissler WM , Shen Z , Tong X , Zhang Z , Wong KK , Roy RS , Chapman KT , Yang L , Xiong Y
Ref : Journal of Medicinal Chemistry , 53 :7251 , 2010
Abstract : Prolylcarboxypeptidase (PrCP) is a serine protease that may have a role in metabolism regulation. A class of reversible, potent, and selective PrCP inhibitors was developed starting from a mechanism based design for inhibiting this serine protease. Compound 8o inhibits human and mouse PrCP at IC(50) values of 1 and 2 nM and is not active (IC(50) > 25 microM) against a panel of closely related proteases. It has lower serum binding than its close analogues and is bioavailable in mouse. Subchronic dosing of 8o in PrCP(-/-) and WT mice at 100 mg/kg for 5 days resulted in a 5% reduction in body weight in WT mice and a 1% reduction in PrCP KO mice.
ESTHER : Zhou_2010_J.Med.Chem_53_7251
PubMedSearch : Zhou_2010_J.Med.Chem_53_7251
PubMedID: 20857914
Gene_locus related to this paper: human-PRCP

Title : Synthesis and biological evaluation of 3,6-diaryl-7H-thiazolo[3,2-b] [1,2,4]triazin-7-one derivatives as acetylcholinesterase inhibitors - Jin_2010_Arch.Pharm.Res_33_1641
Author(s) : Jin Z , Yang L , Liu SJ , Wang J , Li S , Lin HQ , Wan DC , Hu C
Ref : Arch Pharm Res , 33 :1641 , 2010
Abstract : Acetylcholinesterase (AChE) inhibitors played an important role in developing a cure for Alzheimer' s disease. In order to study on the influence of modifications at different groups and side chains on the AChE inhibitory ability and the active sites of 7H-thiazolo[3,2-b][1,2,4]triazin-7-one derivatives, fourteen 3,6-diaryl-7H-thiazolo[3,2-b][1,2,4]triazin-7-one derivatives were designed and synthesized. The study of AChE inhibitory activity was carried out using the Ellman colorimetric assay with huperzine-A as the positive control drug. Most of the target compounds exhibited more than 50% inhibition at 10 muM. Some target compounds showed strong inhibition against AChE. The molecular fields analysis and preliminary structure-activity relationships are discussed.
ESTHER : Jin_2010_Arch.Pharm.Res_33_1641
PubMedSearch : Jin_2010_Arch.Pharm.Res_33_1641
PubMedID: 21052939

Title : Comparative study of properties of immobilized lipase onto glutaraldehyde-activated amino-silica gel via different methods - Yang_2010_Colloids.Surf.B.Biointerfaces_78_351
Author(s) : Yang G , Wu J , Xu G , Yang L
Ref : Colloids Surf B Biointerfaces , 78 :351 , 2010
Abstract : The enzyme-aggregate coating method was performed to immobilize Arthrobacter sp. lipase in order to achieve better catalytic properties comparable to the conventional covalent attachment and covalent attachment plus cross-linking. The glutaraldehyde-activated amino-silica gel which was synthesized by sol-gel technique was used as the support, and the catalytic characteristics of the lipase preparations were tested in the asymmetric acylation of 4-hydroxy-3-methyl-2-(2-propenyl)-2-cyclopenten-1-one (HMPC) in organic solvents. The results showed that the immobilized lipase by enzyme-aggregate coating possessed both higher activity and stability than those by other methods, e.g. it obtained an activity of 82.6 U/g and remained 42% and 93% of the original activity after incubation in vinyl acetate at 60 degrees C for 16 h and 9 times recycles, respectively, while the covalently attached lipase got an activity of 67.4 U/g and left 33% and 73% of the original under the same conditions, and the enzyme prepared by covalent attachment plus cross-linking exhibited the lowest activity yield. Moreover, excellent enantioselectivity (E > or =400) was achieved by all the three prepared lipases in our paper (E=85 for the free enzyme).
ESTHER : Yang_2010_Colloids.Surf.B.Biointerfaces_78_351
PubMedSearch : Yang_2010_Colloids.Surf.B.Biointerfaces_78_351
PubMedID: 20399626

Title : Identifying unexpected therapeutic targets via chemical-protein interactome - Yang_2010_PLoS.One_5_e9568
Author(s) : Yang L , Chen J , Shi L , Hudock MP , Wang K , He L
Ref : PLoS ONE , 5 :e9568 , 2010
Abstract : Drug medications inevitably affect not only their intended protein targets but also other proteins as well. In this study we examined the hypothesis that drugs that share the same therapeutic effect also share a common therapeutic mechanism by targeting not only known drug targets, but also by interacting unexpectedly on the same cryptic targets. By constructing and mining an Alzheimer's disease (AD) drug-oriented chemical-protein interactome (CPI) using a matrix of 10 drug molecules known to treat AD towards 401 human protein pockets, we found that such cryptic targets exist. We recovered from CPI the only validated therapeutic target of AD, acetylcholinesterase (ACHE), and highlighted several other putative targets. For example, we discovered that estrogen receptor (ER) and histone deacetylase (HDAC), which have recently been identified as two new therapeutic targets of AD, might already have been targeted by the marketed AD drugs. We further established that the CPI profile of a drug can reflect its interacting character towards multi-protein sets, and that drugs with the same therapeutic attribute will share a similar interacting profile. These findings indicate that the CPI could represent the landscape of chemical-protein interactions and uncover "behind-the-scenes" aspects of the therapeutic mechanisms of existing drugs, providing testable hypotheses of the key nodes for network pharmacology or brand new drug targets for one-target pharmacology paradigm.
ESTHER : Yang_2010_PLoS.One_5_e9568
PubMedSearch : Yang_2010_PLoS.One_5_e9568
PubMedID: 20221449

Title : Early postnatal parathion exposure in rats causes sex-selective cognitive impairment and neurotransmitter defects which emerge in aging - Levin_2010_Behav.Brain.Res_208_319
Author(s) : Levin ED , Timofeeva OA , Yang L , Petro A , Ryde IT , Wrench N , Seidler FJ , Slotkin TA
Ref : Behavioural Brain Research , 208 :319 , 2010
Abstract : Developmental exposure of rats to the organophosphate (OP) pesticides leads to altered neurobehavioral function in juvenile and young adult stages. The current study was conducted to determine whether effects of neonatal parathion exposure on cognitive performance persist in older adult and aged rats, and the relationship of behavioral changes to underlying cholinergic and serotonergic mechanisms. We administered parathion to rat pups on postnatal days 1-4, at doses spanning the threshold for the initial signs of systemic toxicity and for barely detectable cholinesterase inhibition (0.1 or 0.2 mg/kg/day). Beginning at 14 months of age and continuing until 19 months, the rats were trained in the 16-arm radial maze. Controls showed the normal sex difference in this spatial learning and memory task, with the males committing significantly fewer working memory errors than females. Neonatal parathion exposure eliminated the sex difference primarily by causing impairment in males. In association with the effects on cognitive performance, neonatal parathion exposure elicited widespread abnormalities in indices of serotonergic (5HT) and cholinergic synaptic function, characterized by upregulation of 5HT(2) receptors and the 5HT transporter, deficits in choline acetyltransferase activity and nicotinic cholinergic receptors, and increases in hemicholinium-3 binding to the presynaptic choline transporter. Within-animal correlations between behavior and neurochemistry indicated a specific correlation between working memory performance and hippocampal hemicholinium-3 binding; parathion exposure eliminated this relationship. Like the behavioral effects, males showed greater effects of parathion on neurochemical parameters. This study demonstrates the sex-selective, long-term behavioral alterations caused by otherwise nontoxic neonatal exposure to parathion, with effects increasingly expressed with aging.
ESTHER : Levin_2010_Behav.Brain.Res_208_319
PubMedSearch : Levin_2010_Behav.Brain.Res_208_319
PubMedID: 20015457

Title : The B73 maize genome: complexity, diversity, and dynamics - Schnable_2009_Science_326_1112
Author(s) : Schnable PS , Ware D , Fulton RS , Stein JC , Wei F , Pasternak S , Liang C , Zhang J , Fulton L , Graves TA , Minx P , Reily AD , Courtney L , Kruchowski SS , Tomlinson C , Strong C , Delehaunty K , Fronick C , Courtney B , Rock SM , Belter E , Du F , Kim K , Abbott RM , Cotton M , Levy A , Marchetto P , Ochoa K , Jackson SM , Gillam B , Chen W , Yan L , Higginbotham J , Cardenas M , Waligorski J , Applebaum E , Phelps L , Falcone J , Kanchi K , Thane T , Scimone A , Thane N , Henke J , Wang T , Ruppert J , Shah N , Rotter K , Hodges J , Ingenthron E , Cordes M , Kohlberg S , Sgro J , Delgado B , Mead K , Chinwalla A , Leonard S , Crouse K , Collura K , Kudrna D , Currie J , He R , Angelova A , Rajasekar S , Mueller T , Lomeli R , Scara G , Ko A , Delaney K , Wissotski M , Lopez G , Campos D , Braidotti M , Ashley E , Golser W , Kim H , Lee S , Lin J , Dujmic Z , Kim W , Talag J , Zuccolo A , Fan C , Sebastian A , Kramer M , Spiegel L , Nascimento L , Zutavern T , Miller B , Ambroise C , Muller S , Spooner W , Narechania A , Ren L , Wei S , Kumari S , Faga B , Levy MJ , McMahan L , Van Buren P , Vaughn MW , Ying K , Yeh CT , Emrich SJ , Jia Y , Kalyanaraman A , Hsia AP , Barbazuk WB , Baucom RS , Brutnell TP , Carpita NC , Chaparro C , Chia JM , Deragon JM , Estill JC , Fu Y , Jeddeloh JA , Han Y , Lee H , Li P , Lisch DR , Liu S , Liu Z , Nagel DH , McCann MC , SanMiguel P , Myers AM , Nettleton D , Nguyen J , Penning BW , Ponnala L , Schneider KL , Schwartz DC , Sharma A , Soderlund C , Springer NM , Sun Q , Wang H , Waterman M , Westerman R , Wolfgruber TK , Yang L , Yu Y , Zhang L , Zhou S , Zhu Q , Bennetzen JL , Dawe RK , Jiang J , Jiang N , Presting GG , Wessler SR , Aluru S , Martienssen RA , Clifton SW , McCombie WR , Wing RA , Wilson RK
Ref : Science , 326 :1112 , 2009
Abstract : We report an improved draft nucleotide sequence of the 2.3-gigabase genome of maize, an important crop plant and model for biological research. Over 32,000 genes were predicted, of which 99.8% were placed on reference chromosomes. Nearly 85% of the genome is composed of hundreds of families of transposable elements, dispersed nonuniformly across the genome. These were responsible for the capture and amplification of numerous gene fragments and affect the composition, sizes, and positions of centromeres. We also report on the correlation of methylation-poor regions with Mu transposon insertions and recombination, and copy number variants with insertions and/or deletions, as well as how uneven gene losses between duplicated regions were involved in returning an ancient allotetraploid to a genetically diploid state. These analyses inform and set the stage for further investigations to improve our understanding of the domestication and agricultural improvements of maize.
ESTHER : Schnable_2009_Science_326_1112
PubMedSearch : Schnable_2009_Science_326_1112
PubMedID: 19965430
Gene_locus related to this paper: maize-b4ffc7 , maize-b6u7e1 , maize-c0pcy5 , maize-c0pgf7 , maize-c0pgw1 , maize-c0pfl3 , maize-b4fpr7 , maize-k7vy73 , maize-a0a096swr3 , maize-k7v3i9 , maize-b6u9v9 , maize-a0a3l6e780 , maize-b4fv80 , maize-a0a1d6nse2 , maize-c4j9a1 , maize-k7uba1

Title : The selective alpha7 agonist GTS-21 attenuates cytokine production in human whole blood and human monocytes activated by ligands for TLR2, TLR3, TLR4, TLR9, and RAGE - Rosas-Ballina_2009_Mol.Med_15_195
Author(s) : Rosas-Ballina M , Goldstein RS , Gallowitsch-Puerta M , Yang L , Valdes-Ferrer SI , Patel NB , Chavan S , Al-Abed Y , Yang H , Tracey KJ
Ref : Mol Med , 15 :195 , 2009
Abstract : The cholinergic antiinflammatory pathway modulates inflammatory cytokine production through a mechanism dependent on the vagus nerve and the alpha7 subunit of the nicotinic acetylcholine receptor. GTS-21 [3-(2,4-dimethoxybenzylidene) anabaseine], a selective alpha7 agonist, inhibits inflammatory cytokine production in murine and human macrophages and in several models of inflammatory disease in vivo, but to date its antiinflammatory efficacy in human monocytes has not been characterized. We report here our findings that GTS-21 attenuates tumor necrosis factor (TNF) and interleukin 1beta levels in human whole blood activated by exposure to endotoxin. GTS-21 inhibited TNF production in endotoxin-stimulated primary human monocytes in vitro at the transcriptional level. The suppressive effect of GTS-21 was more potent than nicotine in whole blood and monocytes. Furthermore, GTS-21 attenuated TNF production in monocytes stimulated with peptidoglycan, polyinosinic-polycytidylic acid, CpG, HMGB1 (high-mobility group box 1 protein), and advanced glycation end product-modified albumin. GTS-21 decreased TNF levels in endotoxin-stimulated whole blood obtained from patients with severe sepsis. These findings establish the immunoregulatory effect of GTS-21 on human monocytes, and indicate the potential benefits of further exploration of GTS-21's therapeutic uses in human inflammatory disease.
ESTHER : Rosas-Ballina_2009_Mol.Med_15_195
PubMedSearch : Rosas-Ballina_2009_Mol.Med_15_195
PubMedID: 19593403

Title : Structural basis and enzymatic mechanism of the biosynthesis of C9- from C10-monoterpenoid indole alkaloids - Yang_2009_Angew.Chem.Int.Ed.Engl_48_5211
Author(s) : Yang L , Hill M , Wang M , Panjikar S , Stockigt J
Ref : Angew Chem Int Ed Engl , 48 :5211 , 2009
Abstract : Cutting carbons: The three-dimensional structure of polyneuridine aldehyde esterase (PNAE) gives insight into the enzymatic mechanism of the biosynthesis of C(9)- from C(10)-monoterpenoid indole alkaloids (see scheme). PNAE is a very substrate-specific serine esterase. It harbors the catalytic triad S87-D216-H244, and is a new member of the alpha/beta-fold hydrolase superfamily. Its novel function leads to the diversification of alkaloid structures.
ESTHER : Yang_2009_Angew.Chem.Int.Ed.Engl_48_5211
PubMedSearch : Yang_2009_Angew.Chem.Int.Ed.Engl_48_5211
PubMedID: 19496101
Gene_locus related to this paper: rause-pnae

Title : Characterization of the human CUTA isoform2 present in the stably transfected HeLa cells - Yang_2009_Mol.Biol.Rep_36_63
Author(s) : Yang J , Yang H , Yan L , Yang L , Yu L
Ref : Mol Biol Rep , 36 :63 , 2009
Abstract : CUTA, Homo sapiens divalent cation tolerance homolog, has been implicated in anchoring of acetylcholinesterase in neuronal cell membranes. However, a protein highly homologous to CUTA in Rattus norvegicus is structurally similar to the signal transduction protein PII, and this similarity suggests an intriguing role of CUTA in signal transduction. Recent researches indicated that CUTA was one of the 35 key genes responsible for lactation in mammary gland development. However, the physiological role of CUTA is still unclear, so more information of this gene is needed. In this study, the expression profile of CUTA gene in human tissues was examined, and our research revealed that CUTA gene was constitutively expressed in all of the 18 tissues tested. As reported, CUTA gene has five variant transcripts encoding three isoforms with different N terminals. CUTA isoform2 is encoded by three of the five variant transcripts as the common part of the three isoforms. So CUTA isoform2 was chose as representative to characterize the CUTA protein. We constructed a HeLa cell line stably transfected with the encoding sequence of CUTA isoform2 for further study. The subcellular location and oligomeric structure of the CUTA isoform2 was analyzed in the stable cell lines. It was found that the CUTA isoform2 was mainly located in mitochondria as a new potential mitochondrial protein. Furthermore, CUTA isoform2 formed trimers in cell lysate with the possible occurrence of heteropolymers. These findings would be helpful to the further study on the specific function of CUTA protein.
ESTHER : Yang_2009_Mol.Biol.Rep_36_63
PubMedSearch : Yang_2009_Mol.Biol.Rep_36_63
PubMedID: 17924204

Title : Protective effect of an endothelial lipase gene variant on coronary artery disease in a Chinese population - Tang_2008_J.Lipid.Res_49_369
Author(s) : Tang NP , Wang LS , Yang L , Zhou B , Gu HJ , Sun QM , Cong RH , Zhu HJ , Wang B
Ref : J Lipid Res , 49 :369 , 2008
Abstract : The aim of the present study was to assess the influence of the endothelial lipase (EL) gene 584C/T variant, which results in a change at codon 111 of the EL gene from threonine to isoleucine, on the risk of coronary artery disease (CAD) in a Chinese population. The study population consisted of 265 CAD patients and 265 age- and sex-matched control subjects. The T allele frequency was significantly lower among CAD patients than among control subjects (18.3% vs. 29.8%; P < 0.001). In both the CAD and control groups, the T allele carriers had higher high density lipoprotein cholesterol (HDL-C) levels than homozygote C allele carriers. In a multiple logistic regression model adjusted for age, sex, body mass index, smoking, hypertension, diabetes, hyperlipidemia, and low density lipoprotein cholesterol, a significantly decreased risk of developing CAD was found in subjects carrying a variant CT or TT genotype (odds ratio = 0.496, 95% confidence interval = 0.341-0.723; P < 0.001), and the significance persisted after further adjustment for HDL-C. In conclusion, our observation that the EL 584T allele was associated with protection from CAD in this Chinese population replicates the findings in a Japanese study, which found a similar association of this allele with acute myocardial infarction, independent of HDL-C levels.
ESTHER : Tang_2008_J.Lipid.Res_49_369
PubMedSearch : Tang_2008_J.Lipid.Res_49_369
PubMedID: 17986713
Gene_locus related to this paper: human-LIPG

Title : Characterization of ST-4821 complex, a unique Neisseria meningitidis clone - Peng_2008_Genomics_91_78
Author(s) : Peng J , Yang L , Yang F , Yang J , Yan Y , Nie H , Zhang X , Xiong Z , Jiang Y , Cheng F , Xu X , Chen S , Sun L , Li W , Shen Y , Shao Z , Liang X , Xu J , Jin Q
Ref : Genomics , 91 :78 , 2008
Abstract : Ten outbreaks of a new serogroup C meningococcal disease emerged during 2003-2005 in China. The multilocus sequence typing results indicated that unique sequence type 4821 clone meningococci were responsible for these outbreaks. Herein, we determined the entire genomic DNA sequence of serogroup C isolate 053442, which belongs to ST-4821. Comparison of 053442 gene contents with other meningococcal genomes shows that they have similar characteristics, including thousands of repetitive elements and simple sequence repeats, numerous phase-variable genes, and similar virulence-related factors. However, many strain-specific regions were found in each genome. We also present the results of a genomic comparison of 28 ST-4821 complex isolates that were isolated from different serogroups using comparative genomic hybridization analysis. Genome comparison between the newly emerged hyperinvasive isolates belonging to different serogroups will further our understanding of their respective pathogenetic mechanisms.
ESTHER : Peng_2008_Genomics_91_78
PubMedSearch : Peng_2008_Genomics_91_78
PubMedID: 18031983
Gene_locus related to this paper: neigo-pip , neima-metx , neimb-q9k0t9 , neime-ESD , neime-NMA2216 , neime-NMB0276 , neime-NMB1877

Title : The Physcomitrella genome reveals evolutionary insights into the conquest of land by plants - Rensing_2008_Science_319_64
Author(s) : Rensing SA , Lang D , Zimmer AD , Terry A , Salamov A , Shapiro H , Nishiyama T , Perroud PF , Lindquist EA , Kamisugi Y , Tanahashi T , Sakakibara K , Fujita T , Oishi K , Shin IT , Kuroki Y , Toyoda A , Suzuki Y , Hashimoto S , Yamaguchi K , Sugano S , Kohara Y , Fujiyama A , Anterola A , Aoki S , Ashton N , Barbazuk WB , Barker E , Bennetzen JL , Blankenship R , Cho SH , Dutcher SK , Estelle M , Fawcett JA , Gundlach H , Hanada K , Heyl A , Hicks KA , Hughes J , Lohr M , Mayer K , Melkozernov A , Murata T , Nelson DR , Pils B , Prigge M , Reiss B , Renner T , Rombauts S , Rushton PJ , Sanderfoot A , Schween G , Shiu SH , Stueber K , Theodoulou FL , Tu H , Van de Peer Y , Verrier PJ , Waters E , Wood A , Yang L , Cove D , Cuming AC , Hasebe M , Lucas S , Mishler BD , Reski R , Grigoriev IV , Quatrano RS , Boore JL
Ref : Science , 319 :64 , 2008
Abstract : We report the draft genome sequence of the model moss Physcomitrella patens and compare its features with those of flowering plants, from which it is separated by more than 400 million years, and unicellular aquatic algae. This comparison reveals genomic changes concomitant with the evolutionary movement to land, including a general increase in gene family complexity; loss of genes associated with aquatic environments (e.g., flagellar arms); acquisition of genes for tolerating terrestrial stresses (e.g., variation in temperature and water availability); and the development of the auxin and abscisic acid signaling pathways for coordinating multicellular growth and dehydration response. The Physcomitrella genome provides a resource for phylogenetic inferences about gene function and for experimental analysis of plant processes through this plant's unique facility for reverse genetics.
ESTHER : Rensing_2008_Science_319_64
PubMedSearch : Rensing_2008_Science_319_64
PubMedID: 18079367
Gene_locus related to this paper: phypa-a9rbi6 , phypa-a9rfh1 , phypa-a9rg19 , phypa-a9rgt9 , phypa-a9rhz9 , phypa-a9rkj1 , phypa-a9rns2 , phypa-a9rp52 , phypa-a9rq03 , phypa-a9ry17 , phypa-a9ry72 , phypa-a9s5n8 , phypa-a9s6w1 , phypa-a9s8c7 , phypa-a9s299 , phypa-a9san7 , phypa-a9sc75 , phypa-a9se75 , phypa-a9sg07 , phypa-a9skf7 , phypa-a9skr1 , phypa-a9skw1 , phypa-a9sl58 , phypa-a9slp7 , phypa-a9smq5 , phypa-a9sp13 , phypa-a9ssb0 , phypa-a9sse1 , phypa-a9ssf6 , phypa-a9st85 , phypa-a9sx74 , phypa-a9sy58 , phypa-a9syy4 , phypa-a9t0n4 , phypa-a9t0p4 , phypa-a9t1j2 , phypa-a9t5h1 , phypa-a9t7g6 , phypa-a9t8u8 , phypa-a9t9c9 , phypa-a9t9d9 , phypa-a0a7i4d2t7 , phypa-a9t498 , phypa-a9tbu4 , phypa-a9tc36 , phypa-a9tds0 , phypa-a9te64 , phypa-a9tfw2 , phypa-a9tin6 , phypa-a9tja4 , phypa-a9tmp3 , phypa-a9tmr4 , phypa-a9tql4 , phypa-a9tr83 , phypa-a9tsl1 , phypa-a9tsv6 , phypa-a9tu05 , phypa-a9tw81 , phypa-a9tyr8 , phypa-a9u0c9 , phypa-a9u0k3 , phypa-a9u0p4 , phypa-a9u2u7 , phypa-a9u3s0 , phypa-a9tfm7 , phypa-a9tfp6 , phypa-a9syg9 , phypa-a9tzk2 , phypa-a9tvg4 , phypa-a9t1y4 , phypa-a9tqt6 , phypa-a9st18 , phypa-a9tix9 , phypa-a0a2k1kfe3 , phypa-a9sqk3 , phypa-a0a2k1ie71 , phypa-a0a2k1kg29 , phypa-a0a2k1iji3

Title : A non-spatial, stimulus-comparison working memory task in rats and disruption by scopolamine - Shannon_2007_Neurosci_145_955
Author(s) : Shannon HE , Yang L
Ref : Neuroscience , 145 :955 , 2007
Abstract : Working memory is a theoretical concept referring to a set of cognitive processes that provide temporary maintenance and manipulation of the information necessary for complex cognitive tasks. The preponderance of working memory tasks emphasizes the maintenance of information, and, is spatially oriented. Working memory tasks which are not spatially oriented and which require not only the maintenance but also the manipulation of information are needed in order to further our understanding of working memory in animals. The present studies describe a non-spatial, stimulus-comparison procedure for evaluating working memory in rats which may also tap into the central executive component of working memory. The present procedure requires the animals to compare two stimuli (a light and a tone) and, after a delay, respond on one of two levers if the stimuli are the same and on the other lever if the stimuli are different. Thus, the rats must not only remember the stimuli, but must also operate on, i.e. compare, them in order to respond correctly. The rats relatively rapidly acquired the behavior in approximately 30 sessions and did not exhibit a response bias for response location or stimulus type. Moreover, the percent correct responding was dependent on the duration of the retention interval. The muscarinic cholinergic receptor antagonist scopolamine, but not by its quaternary analog N-methyl scopolamine, decreased the percentage of correct responding as well as the discriminability of the stimuli as measured by log d while having no effect on bias as measured by log b. The present findings are consistent with the hypothesis that the present non-spatial, stimulus-comparison procedure may be useful for evaluating working memory in a manner which may involve the central executive component.
ESTHER : Shannon_2007_Neurosci_145_955
PubMedSearch : Shannon_2007_Neurosci_145_955
PubMedID: 17303343

Title : Cholinergic regulation of the central nucleus of the amygdala in rats: Effects of local microinjections of cholinomimetics and cholinergic antagonists on arousal and sleep - Sanford_2006_Neurosci_141_2167
Author(s) : Sanford LD , Yang L , Tang X , Dong E , Ross RJ , Morrison AR
Ref : Neuroscience , 141 :2167 , 2006
Abstract : The amygdala has emerged as an important forebrain modulator of arousal. Acetylcholine plays a role in the regulation of sleep and wakefulness, particularly rapid eye movement sleep (REM). The major cholinergic input to the amygdala comes from the basal forebrain, a region primarily linked to wakefulness. We examined sleep and the encephalogram for 8 h following bilateral microinjections into the central nucleus of the amygdala (CNA) of the cholinergic agonist, carbachol (CARB(L): 0.3 microg; CARB(H): 3.0 microg), the acetylcholinesterase inhibitor, neostigmine (NEO(L): 0.3 microg; NEO(H): 3.0 microg), the muscarinic antagonist, scopolamine (SCO(L): 0.3 microg; SCO(H): 1.0 microg), the nicotinic antagonist, mecamylamine (MEC(L): 0.3 microg; MEC(H): 1.0 microg) and saline (SAL, 0.2 microl) alone. Both doses of CARB and NEO significantly reduced REM, but did not significantly alter non-rapid eye movement sleep (NREM). Both doses of SCO significantly increased NREM, and SCO(H) also produced an initial increase in REM followed by a significant decrease. CARB(H) and NEO(H) decreased REM electroencephalogram (EEG) power in the 5.5-10 Hz band, and NEO(L) and NEO(H) decreased NREM EEG power in the 0.5-5.0 Hz band. CARB(L) decreased waking EEG power in the 0.5-5.0 Hz band, and NEO(H) decreased waking EEG power in the 5.0-10.0 Hz band. Both doses of SCO significantly increased waking EEG power in the 5.5-10.0 Hz band. Compared with SAL, MEC did not significantly alter sleep or EEG power. The reduction of REM by CARB and NEO and the alteration of sleep by SCO indicate that cholinergic regulation of the amygdala is involved in the control of arousal in rodents. In contrast, CARB microinjections into CNA increase REM in cats, though the reasons for the species difference are not known. The results are discussed in the context of anatomical inputs and species differences in the cholinergic regulation of CNA.
ESTHER : Sanford_2006_Neurosci_141_2167
PubMedSearch : Sanford_2006_Neurosci_141_2167
PubMedID: 16843604

Title : Relationship between plasma HDL subclasses distribution and lipoprotein lipase gene HindIII polymorphism in hyperlipidemia - Long_2006_Clin.Chim.Acta_366_316
Author(s) : Long S , Tian Y , Zhang R , Yang L , Xu Y , Jia L , Fu M
Ref : Clinica Chimica Acta , 366 :316 , 2006
Abstract : BACKGROUND: Different high-density lipoprotein (HDL) subclasses have distinct but interrelated metabolic functions. HDL directly influences the atherogenic process, and changes in HDL subclasses distribution may be related to the incidence and prevalence of atherosclerosis. Lipoprotein lipase (LPL) is an important enzyme for hydrolysis of triglyceride-rich lipoproteins, and its activity is positively correlated with the plasma HDL cholesterol level. LPL gene HindIII polymorphism has been found associated with variations in lipid levels, but the impact on HDL subclasses distribution is less clearly established.
METHODS: The relative apolipoprotein (apo) A-I contents (% apoA-I) of plasma HDL subclasses were determined by two-dimensional gel electrophoresis coupled with immunodetection and LPL gene HindIII polymorphism was assayed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 173 hyperlipidemic and 155 normolipidemic subjects.
RESULTS: The frequencies of 495TT genotype and allele T were the highest both in the hyperlipidemic and control groups. Compared with the control group, the frequency of 495TT genotype was higher, while the frequencies of 495TG and 495GG genotypes were significantly lower (P<0.05) in the hyperlipidemic group. Two-dimensional gel electrophoresis and immunodetection showed that HDL subclasses distribution was altered in hyperlipidemia, and had a general shift toward smaller size. Compared with the control group, the hyperlipidemic group had significantly higher relative apoA-I contents of prebeta1-HDL, prebeta2-HDL, HDL3b and HDL3a (P<0.05) and lower HDL2a and HDL2b levels (P<0.001). In the hyperlipidemic group, allele T carriers' frequency was higher than that in the control group (P<0.05), and the genotype of 495TT showed higher levels of plasma TG, apoB100, TG/HDL-C ratio, relative apoA-I contents of prebeta1-HDL, HDL3b and lower HDL2a, HDL2b compared with that of the 495GG genotype subgroup (P<0.05). In the control group, the genotype of 495TT had higher plasma TG, HDL3c and lower HDL2a compared with that of 495GG subgroup (P<0.05).
CONCLUSIONS: The 495TT genotype of LPL gene HindIII polymorphism was associated with changes of HDL subclasses distribution in Chinese population with hyperlipidemia. The particle size of HDL shifted toward smaller, which, in turn, indicated that RCT might be weakened and HDL maturation might be abnormal in hyperlipidemic subjects with 495TT genotype.
ESTHER : Long_2006_Clin.Chim.Acta_366_316
PubMedSearch : Long_2006_Clin.Chim.Acta_366_316
PubMedID: 16364275

Title : Neurotransmitter level changes in domestic ducks (Shaoxing duck) growing up in typical mercury contaminated area in China - Ji_2005_J.Environ.Sci.(China)_17_256
Author(s) : Ji XL , Yang L , Shen ZM , Cheng JP , Jin GW , Qu LY , Wang WH
Ref : J Environ Sci (China) , 17 :256 , 2005
Abstract : The neurotransmitter level changes of ducks exposed 8-month in a mercury-polluted site (Wanshan, China) and a reference site (Shanghai, China) were examined. Chemical analyses showed both higher mercury and selenium concentrations in the organ of Wanshan ducks. An increased content of acetylcholine (ACh) in brain and blood and a decreased activity of acetylcholinesterase (AChE) in blood were observed. Moreover, there was an increasing trend for nitric oxide synthase (NOS) activity and nitric oxide(NO) production in duck brain, but a reduction of NOS activity in duck serum. The possible explanations were due to the interactive effect of selenium accumulation and the sublethal exposure level of mercury in Wanshan area. The present study showed that AChE and NOS were sensitive to mercury contamination of real circumstance, suggesting that these two indexes have the potential to be biomarkers in assessment of health effects by mercury contamination.
ESTHER : Ji_2005_J.Environ.Sci.(China)_17_256
PubMedSearch : Ji_2005_J.Environ.Sci.(China)_17_256
PubMedID: 16295900

Title : Specific inhibition of hormone-sensitive lipase improves lipid profile while reducing plasma glucose - Claus_2005_J.Pharmacol.Exp.Ther_315_1396
Author(s) : Claus TH , Lowe DB , Liang Y , Salhanick AI , Lubeski CK , Yang L , Lemoine L , Zhu J , Clairmont KB
Ref : Journal of Pharmacology & Experimental Therapeutics , 315 :1396 , 2005
Abstract : Elevation of plasma free fatty acids has been linked with insulin resistance and diabetes. Inhibition of lipolysis may provide a mechanism to decrease plasma fatty acids, thereby improving insulin sensitivity. Hormone-sensitive lipase (HSL) is a critical enzyme involved in the hormonally regulated release of fatty acids and glycerol from adipocyte lipid stores, and its inhibition may thus improve insulin sensitivity and blood glucose handling in type 2 diabetes. In rat adipocytes, forskolin-activated lipolysis was blocked by in vitro addition of a potent and selective HSL inhibitor or by prior treatment of the animals themselves. Antilipolytic effects also were demonstrated in overnight-fasted mice, rats, and dogs with species-dependent effects on plasma free fatty acid levels but with similar reductions in plasma glycerol being observed in all species. Inhibition of HSL also reduced hyperglycemia in streptozotocin-induced diabetic rats. The data support a connection between adipose tissue lipolysis and plasma glucose levels.
ESTHER : Claus_2005_J.Pharmacol.Exp.Ther_315_1396
PubMedSearch : Claus_2005_J.Pharmacol.Exp.Ther_315_1396
PubMedID: 16162821

Title : The Genomes of Oryza sativa: a history of duplications - Yu_2005_PLoS.Biol_3_e38
Author(s) : Yu J , Wang J , Lin W , Li S , Li H , Zhou J , Ni P , Dong W , Hu S , Zeng C , Zhang J , Zhang Y , Li R , Xu Z , Li X , Zheng H , Cong L , Lin L , Yin J , Geng J , Li G , Shi J , Liu J , Lv H , Li J , Deng Y , Ran L , Shi X , Wang X , Wu Q ,